Search Results (25 substrates found)
Gene name
Organism
Protein name
BRSK1
Human
Serine/threonine-protein kinase BRSK1
- Organism
- Human (Homo sapiens)
- Uniprot ID
- BRSK1_HUMAN
- Accession #
- Q8TDC3
- Protein names
-
- Serine/threonine-protein kinase BRSK1
- EC 2.7.11.1
- Brain-selective kinase 1
- EC 2.7.11.26
- Brain-specific serine/threonine-protein kinase 1
- BR serine/threonine-protein kinase 1
- Serine/threonine-protein kinase SAD-B
- Synapses of Amphids Defective homolog 1
- SAD1 homolog
- hSAD1
- Gene names
-
- BRSK1
- KIAA1811
- SAD1
- SADB
- Description
-
Serine/threonine-protein kinase that plays a key role in polarization of neurons and centrosome duplication. Phosphorylates CDC25B, CDC25C, MAPT/TAU, RIMS1, TUBG1, TUBG2 and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at 'Thr-529' and 'Ser-579'. Also regulates neuron polarization by mediating phosphorylation of WEE1 at 'Ser-642' in postmitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. In neurons, localizes to synaptic vesicles and plays a role in neurotransmitter release, possibly by phosphorylating RIMS1. Also acts as a positive regulator of centrosome duplication by mediating phosphorylation of gamma-tubulin (TUBG1 and TUBG2) at 'Ser-131', leading to translocation of gamma-tubulin and its associated proteins to the centrosome. Involved in the UV-induced DNA damage checkpoint response, probably by inhibiting CDK1 activity through phosphorylation and activation of WEE1, and inhibition of CDC25B and CDC25C. {ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15150265, ECO:0000269|PubMed:20026642, ECO:0000269|PubMed:21985311}.
- Links
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Search Kinases of BRSK1 (Human)
N/A
- ATP binding
- G2/M transition of mitotic cell cycle
- associative learning
- axonogenesis
- cell junction
- cellular response to DNA damage stimulus
- cellular response to glucose starvation
- centrosome
- centrosome duplication
- cytoplasm
- distal axon
- establishment of cell polarity
- gamma-tubulin binding
- intracellular signal transduction
- magnesium ion binding
- microtubule cytoskeleton organization involved in establishment of planar polarity
- mitotic G2 DNA damage checkpoint signaling
- neuron differentiation
- neurotransmitter secretion
- nucleoplasm
- nucleus
- peptidyl-serine phosphorylation
- presynaptic active zone
- protein kinase binding
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- regulation of axonogenesis
- regulation of neuron projection development
- regulation of synaptic plasticity
- regulation of synaptic vesicle clustering
- response to UV
- synaptic vesicle
- synaptic vesicle cycle
- tau protein binding
- tau-protein kinase activity
BRSK2
Human
Serine/threonine-protein kinase BRSK2
- Organism
- Human (Homo sapiens)
- Uniprot ID
- BRSK2_HUMAN
- Accession #
- Q8IWQ3
- Protein names
-
- Serine/threonine-protein kinase BRSK2
- EC 2.7.11.1
- Brain-selective kinase 2
- EC 2.7.11.26
- Brain-specific serine/threonine-protein kinase 2
- BR serine/threonine-protein kinase 2
- Serine/threonine-protein kinase 29
- Serine/threonine-protein kinase SAD-A
- Gene names
-
- BRSK2
- C11orf7
- PEN11B
- SADA
- STK29
- HUSSY-12
- Description
-
Serine/threonine-protein kinase that plays a key role in polarization of neurons and axonogenesis, cell cycle progress and insulin secretion. Phosphorylates CDK16, CDC25C, MAPT/TAU, PAK1 and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at 'Thr-529' and 'Ser-579'. Also regulates neuron polarization by mediating phosphorylation of WEE1 at 'Ser-642' in postmitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. Plays a role in the regulation of the mitotic cell cycle progress and the onset of mitosis. Plays a role in the regulation of insulin secretion in response to elevated glucose levels, probably via phosphorylation of CDK16 and PAK1. While BRSK2 phosphorylated at Thr-174 can inhibit insulin secretion (PubMed:22798068), BRSK2 phosphorylated at Thr-260 can promote insulin secretion (PubMed:22669945). Regulates reorganization of the actin cytoskeleton. May play a role in the apoptotic response triggered by endoplasmic reticulum (ER) stress. {ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:20026642, ECO:0000269|PubMed:21985311, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:22798068, ECO:0000269|PubMed:23029325}.
- Links
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Search Kinases of BRSK2 (Human)
N/A
- ATP binding
- ATPase binding
- ATPase regulator activity
- ERAD pathway
- G2/M transition of mitotic cell cycle
- actin cytoskeleton reorganization
- axonogenesis
- cell division
- cellular response to glucose starvation
- centrosome
- cytoplasm
- distal axon
- endoplasmic reticulum
- establishment of cell polarity
- exocytosis
- intracellular signal transduction
- intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
- magnesium ion binding
- microtubule cytoskeleton organization involved in establishment of planar polarity
- neuron differentiation
- nucleus
- peptidyl-serine phosphorylation
- perinuclear region of cytoplasm
- protein kinase binding
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- regulation of ATPase activity
- regulation of axonogenesis
- regulation of insulin secretion involved in cellular response to glucose stimulus
- regulation of neuron projection development
- regulation of retrograde protein transport, ER to cytosol
- regulation of synaptic vesicle clustering
- tau protein binding
- tau-protein kinase activity
MARK1
Human
Serine/threonine-protein kinase MARK1
- Organism
- Human (Homo sapiens)
- Uniprot ID
- MARK1_HUMAN
- Accession #
- Q9P0L2
- Protein names
-
- Serine/threonine-protein kinase MARK1
- EC 2.7.11.1
- EC 2.7.11.26
- MAP/microtubule affinity-regulating kinase 1
- PAR1 homolog c
- Par-1c
- Par1c
- Gene names
-
- MARK1
- KIAA1477
- MARK
- Description
-
Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:17573348, ECO:0000269|PubMed:23666762}.
- Links
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Search Kinases of MARK1 (Human)
N/A
- ATP binding
- Wnt signaling pathway
- cytoplasm
- cytoskeleton
- cytoskeleton organization
- dendrite
- establishment of mitochondrion localization
- intracellular signal transduction
- magnesium ion binding
- microtubule cytoskeleton
- microtubule cytoskeleton organization
- neuron migration
- peptidyl-serine phosphorylation
- phosphatidic acid binding
- phosphatidylinositol-4,5-bisphosphate binding
- phosphatidylserine binding
- plasma membrane
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- regulation of dendrite development
- regulation of neuron projection development
- tau protein binding
- tau-protein kinase activity
MARK2
Human
Serine/threonine-protein kinase MARK2
- Organism
- Human (Homo sapiens)
- Uniprot ID
- MARK2_HUMAN
- Accession #
- Q7KZI7
- Protein names
-
- Serine/threonine-protein kinase MARK2
- EC 2.7.11.1
- EC 2.7.11.26
- ELKL motif kinase 1
- EMK-1
- MAP/microtubule affinity-regulating kinase 2
- PAR1 homolog
- PAR1 homolog b
- Par-1b
- Par1b
- Gene names
-
- MARK2
- EMK1
- Description
-
Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:12429843, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15158914, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:15365179, ECO:0000269|PubMed:16775013, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:18626018, ECO:0000269|PubMed:20194617, ECO:0000269|PubMed:23666762}.
- Links
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Search Kinases of MARK2 (Human)
N/A
- ATP binding
- RNA binding
- Wnt signaling pathway
- actin filament
- activation of protein kinase activity
- autophagy of mitochondrion
- axon development
- cadherin binding
- cytoplasm
- dendrite
- establishment of cell polarity
- establishment or maintenance of cell polarity regulating cell shape
- establishment or maintenance of epithelial cell apical/basal polarity
- intracellular signal transduction
- lateral plasma membrane
- lipid binding
- magnesium ion binding
- membrane
- microtubule bundle
- microtubule cytoskeleton organization
- mitochondrion
- mitochondrion localization
- neuron migration
- nucleoplasm
- peptidyl-serine phosphorylation
- peptidyl-threonine phosphorylation
- plasma membrane
- positive regulation of neuron projection development
- protein autophosphorylation
- protein kinase activator activity
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- regulation of axonogenesis
- regulation of cytoskeleton organization
- regulation of microtubule binding
- regulation of microtubule cytoskeleton organization
- tau protein binding
- tau-protein kinase activity
MARK3
Human
MAP/microtubule affinity-regulating kinase 3
- Organism
- Human (Homo sapiens)
- Uniprot ID
- MARK3_HUMAN
- Accession #
- P27448
- Protein names
-
- MAP/microtubule affinity-regulating kinase 3
- EC 2.7.11.1
- C-TAK1
- cTAK1
- Cdc25C-associated protein kinase 1
- ELKL motif kinase 2
- EMK-2
- Protein kinase STK10
- Ser/Thr protein kinase PAR-1
- Par-1a
- Serine/threonine-protein kinase p78
- Gene names
-
- MARK3
- CTAK1
- EMK2
- Description
-
Serine/threonine-protein kinase (PubMed:23666762). Involved in the specific phosphorylation of microtubule-associated proteins for MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Phosphorylates CDC25C on 'Ser-216'. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus (PubMed:16980613). Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1 (PubMed:28087714). {ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:28087714}.
- Links
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Search Kinases of MARK3 (Human)
N/A
- ATP binding
- MAPK cascade
- cytoplasm
- cytosol
- dendrite
- extracellular exosome
- intracellular signal transduction
- microtubule cytoskeleton organization
- negative regulation of hippo signaling
- peptidyl-serine autophosphorylation
- peptidyl-serine phosphorylation
- plasma membrane
- positive regulation of protein binding
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- tau protein binding
- tau-protein kinase activity
MARK4
Human
MAP/microtubule affinity-regulating kinase 4
- Organism
- Human (Homo sapiens)
- Uniprot ID
- MARK4_HUMAN
- Accession #
- Q96L34
- Protein names
-
- MAP/microtubule affinity-regulating kinase 4
- EC 2.7.11.1
- MAP/microtubule affinity-regulating kinase-like 1
- Gene names
-
- MARK4
- KIAA1860
- MARKL1
- Description
-
Serine/threonine-protein kinase (PubMed:15009667, PubMed:14594945, PubMed:23666762, PubMed:23184942). Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:14594945, PubMed:23666762). Also phosphorylates the microtubule-associated proteins MAP2 and MAP4 (PubMed:14594945). Involved in regulation of the microtubule network, causing reorganization of microtubules into bundles (PubMed:14594945, PubMed:25123532). Required for the initiation of axoneme extension during cilium assembly (PubMed:23400999). Regulates the centrosomal location of ODF2 and phosphorylates ODF2 in vitro (PubMed:23400999). Plays a role in cell cycle progression, specifically in the G1/S checkpoint (PubMed:25123532). Reduces neuronal cell survival (PubMed:15009667). Plays a role in energy homeostasis by regulating satiety and metabolic rate (By similarity). Promotes adipogenesis by activating JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway (By similarity). Phosphorylates mTORC1 complex member RPTOR and acts as a negative regulator of the mTORC1 complex, probably due to disruption of the interaction between phosphorylated RPTOR and the RRAGA/RRAGC heterodimer which is required for mTORC1 activation (PubMed:23184942). {ECO:0000250|UniProtKB:Q8CIP4, ECO:0000269|PubMed:14594945, ECO:0000269|PubMed:15009667, ECO:0000269|PubMed:23184942, ECO:0000269|PubMed:23400999, ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:25123532}.
- Links
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Search Kinases of MARK4 (Human)
N/A
- ATP binding
- cell cycle
- cell division
- centrosome
- ciliary basal body
- ciliary basal body-plasma membrane docking
- cilium organization
- cytoplasm
- cytosol
- dendrite
- gamma-tubulin binding
- gamma-tubulin complex
- intracellular signal transduction
- microtubule binding
- microtubule bundle formation
- microtubule cytoskeleton
- microtubule cytoskeleton organization
- microtubule organizing center
- midbody
- nervous system development
- neuron projection
- positive regulation of cilium assembly
- positive regulation of programmed cell death
- positive regulation of protein localization to centrosome
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- regulation of centrosome cycle
- tau protein binding
- tau-protein kinase activity
- ubiquitin binding
MELK
Human
Maternal embryonic leucine zipper kinase
- Organism
- Human (Homo sapiens)
- Uniprot ID
- MELK_HUMAN
- Accession #
- Q14680
- Protein names
-
- Maternal embryonic leucine zipper kinase
- hMELK
- EC 2.7.11.1
- Protein kinase Eg3
- pEg3 kinase
- Protein kinase PK38
- hPK38
- Tyrosine-protein kinase MELK
- EC 2.7.10.2
- Gene names
-
- MELK
- KIAA0175
- Description
-
Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis. {ECO:0000269|PubMed:11802789, ECO:0000269|PubMed:12400006, ECO:0000269|PubMed:14699119, ECO:0000269|PubMed:15908796, ECO:0000269|PubMed:16216881, ECO:0000269|PubMed:17280616}.
- Links
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Search Kinases of MELK (Human)
N/A
- ATP binding
- G2/M transition of mitotic cell cycle
- apoptotic process
- calcium ion binding
- cell cortex
- cell population proliferation
- cytoplasm
- hemopoiesis
- intracellular signal transduction
- intrinsic apoptotic signaling pathway in response to oxidative stress
- lipid binding
- membrane
- neural precursor cell proliferation
- non-membrane spanning protein tyrosine kinase activity
- nucleus
- plasma membrane
- positive regulation of apoptotic process
- protein autophosphorylation
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- transmembrane receptor protein tyrosine kinase activity
NUAK1
Human
NUAK family SNF1-like kinase 1
- Organism
- Human (Homo sapiens)
- Uniprot ID
- NUAK1_HUMAN
- Accession #
- O60285
- Protein names
-
- NUAK family SNF1-like kinase 1
- EC 2.7.11.1
- AMPK-related protein kinase 5
- ARK5
- Omphalocele kinase 1
- Gene names
-
- NUAK1
- ARK5
- KIAA0537
- OMPHK1
- Description
-
Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS1, PPP1R12A and p53/TP53. Acts as a regulator of cellular senescence and cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1, thereby controlling its stability. Controls cell adhesion by regulating activity of the myosin protein phosphatase 1 (PP1) complex. Acts by mediating phosphorylation of PPP1R12A subunit of myosin PP1: phosphorylated PPP1R12A then interacts with 14-3-3, leading to reduced dephosphorylation of myosin MLC2 by myosin PP1. May be involved in DNA damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser-392' and is recruited to the CDKN1A/WAF1 promoter to participate in transcription activation by p53/TP53. May also act as a tumor malignancy-associated factor by promoting tumor invasion and metastasis under regulation and phosphorylation by AKT1. Suppresses Fas-induced apoptosis by mediating phosphorylation of CASP6, thereby suppressing the activation of the caspase and the subsequent cleavage of CFLAR. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with STK11, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316). {ECO:0000269|PubMed:12409306, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15060171, ECO:0000269|PubMed:15273717, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:20354225, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:25329316}.
- Links
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Search Kinases of NUAK1 (Human)
N/A
- ATP binding
- cell adhesion
- cellular response to DNA damage stimulus
- cellular response to glucose starvation
- cytoplasm
- fibrillar center
- intracellular signal transduction
- metal ion binding
- microtubule cytoskeleton
- nucleoplasm
- nucleus
- p53 binding
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- regulation of cell adhesion
- regulation of cell population proliferation
- regulation of cellular senescence
- regulation of myosin-light-chain-phosphatase activity
- regulation of signal transduction by p53 class mediator
NUAK2
Human
NUAK family SNF1-like kinase 2
- Organism
- Human (Homo sapiens)
- Uniprot ID
- NUAK2_HUMAN
- Accession #
- Q9H093
- Protein names
-
- NUAK family SNF1-like kinase 2
- EC 2.7.11.1
- Omphalocele kinase 2
- SNF1/AMP kinase-related kinase
- SNARK
- Gene names
-
- NUAK2
- OMPHK2
- SNARK
- Description
-
Stress-activated kinase involved in tolerance to glucose starvation. Induces cell-cell detachment by increasing F-actin conversion to G-actin. Expression is induced by CD95 or TNF-alpha, via NF-kappa-B. Protects cells from CD95-mediated apoptosis and is required for the increased motility and invasiveness of CD95-activated tumor cells. Able to phosphorylate 'Ser-464' of LATS1. {ECO:0000269|PubMed:14575707, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15345718, ECO:0000269|PubMed:19927127}.
- Links
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Search Kinases of NUAK2 (Human)
N/A
- ATP binding
- actin cytoskeleton organization
- apoptotic process
- cellular response to glucose starvation
- cytoplasm
- intracellular signal transduction
- magnesium ion binding
- negative regulation of apoptotic process
- nucleus
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
Pak1
Mouse
Serine/threonine-protein kinase PAK 1
- Organism
- Mouse (Mus musculus)
- Uniprot ID
- PAK1_MOUSE
- Accession #
- O88643
- Protein names
-
- Serine/threonine-protein kinase PAK 1
- EC 2.7.11.1
- Alpha-PAK
- CDC42/RAC effector kinase PAK-A
- p21-activated kinase 1
- PAK-1
- p65-PAK
- Gene names
-
- Pak1
- Paka
- Description
-
Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2. Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus. In podocytes, promotes NR3C2 nuclear localization. Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation. Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion. In response to DNA damage, phosphorylates MORC2 which activates its ATPase activity and facilitates chromatin remodeling (By similarity). In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in F-actin stabilization (By similarity). In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (PubMed:15800193). Along with GIT1, positively regulates microtubule nucleation during interphase (By similarity). {ECO:0000250|UniProtKB:P35465, ECO:0000250|UniProtKB:Q13153, ECO:0000269|PubMed:10611223, ECO:0000269|PubMed:12165471, ECO:0000269|PubMed:12176334, ECO:0000269|PubMed:15800193, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:23633677}.
- Links
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Search Kinases of Pak1 (Mouse)
N/A
- ATP binding
- GABA-ergic synapse
- Z disc
- actin cytoskeleton reorganization
- actin filament
- activation of protein kinase activity
- amygdala development
- apoptotic process
- axon
- branching morphogenesis of an epithelial tube
- cell migration
- cell-cell junction
- cellular response to DNA damage stimulus
- cellular response to insulin stimulus
- cellular response to organic cyclic compound
- chromatin remodeling
- chromosome
- collagen binding
- cytoplasm
- cytosol
- dendrite
- dendrite development
- dendritic spine development
- establishment of cell polarity
- exocytosis
- focal adhesion
- gamma-aminobutyric acid secretion, neurotransmission
- gamma-tubulin binding
- glutamate secretion, neurotransmission
- glutamatergic synapse
- growth cone
- hepatocyte growth factor receptor signaling pathway
- identical protein binding
- intercalated disc
- lamellipodium
- membrane
- negative regulation of cell growth involved in cardiac muscle cell development
- negative regulation of cell proliferation involved in contact inhibition
- neuromuscular junction development
- neuron projection morphogenesis
- nuclear membrane
- nucleoplasm
- nucleus
- observational learning
- plasma membrane
- positive regulation of JUN kinase activity
- positive regulation of axon extension
- positive regulation of cell migration
- positive regulation of cell population proliferation
- positive regulation of fibroblast migration
- positive regulation of insulin receptor signaling pathway
- positive regulation of intracellular estrogen receptor signaling pathway
- positive regulation of microtubule nucleation
- positive regulation of microtubule polymerization
- positive regulation of peptidyl-serine phosphorylation
- positive regulation of protein phosphorylation
- positive regulation of protein targeting to membrane
- positive regulation of stress fiber assembly
- positive regulation of vascular associated smooth muscle cell migration
- positive regulation of vascular associated smooth muscle cell proliferation
- postsynaptic density
- presynapse
- protein autophosphorylation
- protein kinase activity
- protein kinase binding
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- protein-containing complex
- receptor clustering
- regulation of MAPK cascade
- regulation of actin cytoskeleton organization
- regulation of axonogenesis
- regulation of gene expression
- regulation of long-term synaptic potentiation
- response to hypoxia
- response to organic substance
- ruffle
- ruffle membrane
- stress-activated protein kinase signaling cascade
- trans-synaptic signaling by endocannabinoid, modulating synaptic transmission
- transmission of nerve impulse
- wound healing
PAK1
Human
Serine/threonine-protein kinase PAK 1
- Organism
- Human (Homo sapiens)
- Uniprot ID
- PAK1_HUMAN
- Accession #
- Q13153
- Protein names
-
- Serine/threonine-protein kinase PAK 1
- EC 2.7.11.1
- Alpha-PAK
- p21-activated kinase 1
- PAK-1
- p65-PAK
- Gene names
-
- PAK1
- Description
-
Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes (PubMed:11896197, PubMed:30290153). Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2. Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus. In podocytes, promotes NR3C2 nuclear localization. Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation. Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion (PubMed:25766321). In response to DNA damage, phosphorylates MORC2 which activates its ATPase activity and facilitates chromatin remodeling (PubMed:23260667). In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in F-actin stabilization (By similarity). In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (By similarity). Along with GIT1, positively regulates microtubule nucleation during interphase (PubMed:27012601). {ECO:0000250|UniProtKB:O88643, ECO:0000250|UniProtKB:P35465, ECO:0000269|PubMed:10551809, ECO:0000269|PubMed:11733498, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:12876277, ECO:0000269|PubMed:14585966, ECO:0000269|PubMed:15611088, ECO:0000269|PubMed:15831477, ECO:0000269|PubMed:15833848, ECO:0000269|PubMed:16278681, ECO:0000269|PubMed:17726028, ECO:0000269|PubMed:17989089, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:23633677, ECO:0000269|PubMed:25766321, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:30290153, ECO:0000269|PubMed:8805275, ECO:0000269|PubMed:9032240, ECO:0000269|PubMed:9395435, ECO:0000269|PubMed:9528787}.
- Links
-
Search Kinases of PAK1 (Human)
- Axon guidance
- C
- Chemokine signaling pathway
- Epithelial cell signaling in Helicobacter pylori infection
- ErbB signaling pathway
- Fc gamma R
- Focal adhesion
- Hippo signaling pathway
- Human immunodeficiency virus 1 infection
- MAPK signaling pathway
- Natural killer cell mediated cytotoxicity
- Pathogenic Escherichia coli infection
- Proteoglycans in cancer
- Ras signaling pathway
- Regulation of actin cytoskeleton
- Renal cell carcinoma
- Salmonella infection
- T cell receptor signaling pathway
- cAMP signaling pathway
- ATP binding
- Fc-epsilon receptor signaling pathway
- Fc-gamma receptor signaling pathway involved in phagocytosis
- T cell costimulation
- T cell receptor signaling pathway
- Z disc
- actin cytoskeleton reorganization
- actin filament
- activation of protein kinase activity
- apoptotic process
- axon
- branching morphogenesis of an epithelial tube
- cell migration
- cell-cell junction
- cellular response to DNA damage stimulus
- cellular response to insulin stimulus
- cerebellum development
- chromatin remodeling
- chromosome
- collagen binding
- cytoplasm
- cytosol
- dendrite
- ephrin receptor signaling pathway
- establishment of cell polarity
- exocytosis
- focal adhesion
- gamma-tubulin binding
- hepatocyte growth factor receptor signaling pathway
- identical protein binding
- intercalated disc
- lamellipodium
- negative regulation of cell growth involved in cardiac muscle cell development
- negative regulation of cell proliferation involved in contact inhibition
- neuron projection morphogenesis
- nuclear membrane
- nucleoplasm
- phosphorylation
- plasma membrane
- positive regulation of JUN kinase activity
- positive regulation of axon extension
- positive regulation of cell migration
- positive regulation of cell population proliferation
- positive regulation of fibroblast migration
- positive regulation of insulin receptor signaling pathway
- positive regulation of intracellular estrogen receptor signaling pathway
- positive regulation of microtubule nucleation
- positive regulation of microtubule polymerization
- positive regulation of peptidyl-serine phosphorylation
- positive regulation of protein phosphorylation
- positive regulation of protein targeting to membrane
- positive regulation of stress fiber assembly
- positive regulation of vascular associated smooth muscle cell migration
- positive regulation of vascular associated smooth muscle cell proliferation
- protein autophosphorylation
- protein kinase activity
- protein kinase binding
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- protein-containing complex
- regulation of axonogenesis
- response to hypoxia
- ruffle
- ruffle membrane
- stimulatory C-type lectin receptor signaling pathway
- stress-activated protein kinase signaling cascade
- wound healing
Prkaa1
Rat
5'-AMP-activated protein kinase catalytic subunit alpha-1
- Organism
- Rat (Rattus norvegicus)
- Uniprot ID
- AAPK1_RAT
- Accession #
- P54645
- Protein names
-
- 5'-AMP-activated protein kinase catalytic subunit alpha-1
- AMPK subunit alpha-1
- EC 2.7.11.1
- Acetyl-CoA carboxylase kinase
- ACACA kinase
- EC 2.7.11.27
- Hydroxymethylglutaryl-CoA reductase kinase
- HMGCR kinase
- EC 2.7.11.31
- Tau-protein kinase PRKAA1
- EC 2.7.11.26
- Gene names
-
- Prkaa1
- Ampk1
- Description
-
Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. In that process also activates WDR45. In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. {ECO:0000250|UniProtKB:Q5EG47, ECO:0000269|PubMed:10025949, ECO:0000269|PubMed:11069105, ECO:0000269|PubMed:11598104, ECO:0000269|PubMed:11724780, ECO:0000269|PubMed:12065600, ECO:0000269|PubMed:12740371, ECO:0000269|PubMed:14511394, ECO:0000269|PubMed:14709557, ECO:0000269|PubMed:17341212, ECO:0000269|PubMed:21204788, ECO:0000269|PubMed:2369897, ECO:0000269|PubMed:9029219}.
- Links
-
Search Kinases of Prkaa1 (Rat)
- AMPK signaling pathway
- Adipocytokine signaling pathway
- Apelin signaling pathway
- Autophagy
- Circadian rhythm
- Fluid shear stress and atherosclerosis
- FoxO signaling pathway
- Glucagon signaling pathway
- Hypertrophic cardiomyopathy
- Insulin resistance
- Insulin signaling pathway
- Longevity regulating pathway
- Non
- Oxytocin signaling pathway
- PI3K
- Thermogenesis
- Tight junction
- mTOR signaling pathway
- AMP-activated protein kinase activity
- ATP binding
- CAMKK-AMPK signaling cascade
- Wnt signaling pathway
- [acetyl-CoA carboxylase] kinase activity
- [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity
- apical plasma membrane
- autophagy
- axon
- bile acid and bile salt transport
- bile acid signaling pathway
- cellular response to calcium ion
- cellular response to ethanol
- cellular response to glucose starvation
- cellular response to glucose stimulus
- cellular response to hydrogen peroxide
- cellular response to hypoxia
- cellular response to nutrient levels
- cellular response to organonitrogen compound
- cellular response to oxidative stress
- cellular response to prostaglandin E stimulus
- cholesterol biosynthetic process
- chromatin binding
- cold acclimation
- cytoplasm
- cytosol
- dendrite
- energy homeostasis
- eukaryotic elongation factor-2 kinase activator activity
- fatty acid biosynthetic process
- fatty acid homeostasis
- fatty acid oxidation
- glucose homeostasis
- glucose metabolic process
- histone serine kinase activity
- intracellular signal transduction
- lipid biosynthetic process
- metal ion binding
- motor behavior
- negative regulation of TOR signaling
- negative regulation of apoptotic process
- negative regulation of gene expression
- negative regulation of insulin receptor signaling pathway
- negative regulation of lipid catabolic process
- negative regulation of translation
- negative regulation of tubulin deacetylation
- neuron cellular homeostasis
- neuronal cell body
- nuclear speck
- nucleotide-activated protein kinase complex
- nucleus
- positive regulation of autophagy
- positive regulation of cell population proliferation
- positive regulation of fatty acid oxidation
- positive regulation of gene expression
- positive regulation of gluconeogenesis
- positive regulation of glucose import
- positive regulation of glycolytic process
- positive regulation of mitochondrial transcription
- positive regulation of peptidyl-lysine acetylation
- positive regulation of protein localization
- positive regulation of protein targeting to mitochondrion
- positive regulation of skeletal muscle tissue development
- protein C-terminus binding
- protein kinase activity
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- protein-containing complex
- protein-containing complex binding
- regulation of bile acid secretion
- regulation of circadian rhythm
- regulation of gene expression
- regulation of microtubule cytoskeleton organization
- regulation of peptidyl-serine phosphorylation
- regulation of stress granule assembly
- regulation of vesicle-mediated transport
- response to 17alpha-ethynylestradiol
- response to UV
- response to activity
- response to caffeine
- response to camptothecin
- response to gamma radiation
- response to hydrogen peroxide
- rhythmic process
- tau-protein kinase activity
PRKAA1
Human
5'-AMP-activated protein kinase catalytic subunit alpha-1
- Organism
- Human (Homo sapiens)
- Uniprot ID
- AAPK1_HUMAN
- Accession #
- Q13131
- Protein names
-
- 5'-AMP-activated protein kinase catalytic subunit alpha-1
- AMPK subunit alpha-1
- EC 2.7.11.1
- Acetyl-CoA carboxylase kinase
- ACACA kinase
- EC 2.7.11.27
- Hydroxymethylglutaryl-CoA reductase kinase
- HMGCR kinase
- EC 2.7.11.31
- Tau-protein kinase PRKAA1
- EC 2.7.11.26
- Gene names
-
- PRKAA1
- AMPK1
- Description
-
Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. In that process also activates WDR45 (PubMed:28561066). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. {ECO:0000250|UniProtKB:Q5EG47, ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:28561066}.
- Links
-
Search Kinases of PRKAA1 (Human)
- AMPK signaling pathway
- Adipocytokine signaling pathway
- Apelin signaling pathway
- Autophagy
- Circadian rhythm
- Fluid shear stress and atherosclerosis
- FoxO signaling pathway
- Glucagon signaling pathway
- Hypertrophic cardiomyopathy
- Insulin resistance
- Insulin signaling pathway
- Longevity regulating pathway
- Non
- Oxytocin signaling pathway
- PI3K
- Thermogenesis
- Tight junction
- mTOR signaling pathway
- AMP-activated protein kinase activity
- ATP binding
- CAMKK-AMPK signaling cascade
- Wnt signaling pathway
- [acetyl-CoA carboxylase] kinase activity
- [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity
- apical plasma membrane
- axon
- bile acid and bile salt transport
- bile acid signaling pathway
- cAMP-dependent protein kinase activity
- cellular response to calcium ion
- cellular response to ethanol
- cellular response to glucose starvation
- cellular response to glucose stimulus
- cellular response to hydrogen peroxide
- cellular response to hypoxia
- cellular response to nutrient levels
- cellular response to organonitrogen compound
- cellular response to oxidative stress
- cellular response to prostaglandin E stimulus
- cholesterol biosynthetic process
- chromatin binding
- cold acclimation
- cytoplasm
- cytosol
- dendrite
- energy homeostasis
- fatty acid biosynthetic process
- fatty acid homeostasis
- fatty acid oxidation
- glucose homeostasis
- glucose metabolic process
- histone serine kinase activity
- intracellular signal transduction
- lipid biosynthetic process
- macroautophagy
- metal ion binding
- motor behavior
- negative regulation of TOR signaling
- negative regulation of apoptotic process
- negative regulation of gene expression
- negative regulation of glucosylceramide biosynthetic process
- negative regulation of insulin receptor signaling pathway
- negative regulation of lipid catabolic process
- negative regulation of tubulin deacetylation
- neuron cellular homeostasis
- neuronal cell body
- nuclear speck
- nucleoplasm
- nucleotide-activated protein kinase complex
- nucleus
- obsolete activation of MAPK activity
- positive regulation of autophagy
- positive regulation of cell population proliferation
- positive regulation of cholesterol biosynthetic process
- positive regulation of gene expression
- positive regulation of glycolytic process
- positive regulation of mitochondrial transcription
- positive regulation of peptidyl-lysine acetylation
- positive regulation of protein localization
- positive regulation of protein targeting to mitochondrion
- positive regulation of skeletal muscle tissue development
- protein C-terminus binding
- protein kinase activity
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- protein-containing complex binding
- regulation of bile acid secretion
- regulation of circadian rhythm
- regulation of macroautophagy
- regulation of microtubule cytoskeleton organization
- regulation of peptidyl-serine phosphorylation
- regulation of signal transduction by p53 class mediator
- regulation of stress granule assembly
- regulation of vesicle-mediated transport
- response to 17alpha-ethynylestradiol
- response to UV
- response to activity
- response to caffeine
- response to camptothecin
- response to gamma radiation
- response to hypoxia
- rhythmic process
- signal transduction
- tau protein binding
- tau-protein kinase activity
Prkaa1
Mouse
5'-AMP-activated protein kinase catalytic subunit alpha-1
- Organism
- Mouse (Mus musculus)
- Uniprot ID
- AAPK1_MOUSE
- Accession #
- Q5EG47
- Protein names
-
- 5'-AMP-activated protein kinase catalytic subunit alpha-1
- AMPK subunit alpha-1
- EC 2.7.11.1
- Acetyl-CoA carboxylase kinase
- ACACA kinase
- EC 2.7.11.27
- Hydroxymethylglutaryl-CoA reductase kinase
- HMGCR kinase
- EC 2.7.11.31
- Tau-protein kinase PRKAA1
- EC 2.7.11.26
- Gene names
-
- Prkaa1
- Description
-
Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. In that process also activates WDR45. In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (PubMed:23283301). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. {ECO:0000269|PubMed:15878856, ECO:0000269|PubMed:16148943, ECO:0000269|PubMed:16308421, ECO:0000269|PubMed:16804075, ECO:0000269|PubMed:16804077, ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:19833968, ECO:0000269|PubMed:20361929, ECO:0000269|PubMed:20647423, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:21258367, ECO:0000269|PubMed:21459323, ECO:0000269|PubMed:23283301}.
- Links
-
Search Kinases of Prkaa1 (Mouse)
- AMPK signaling pathway
- Adipocytokine signaling pathway
- Apelin signaling pathway
- Autophagy
- Circadian rhythm
- Fluid shear stress and atherosclerosis
- FoxO signaling pathway
- Glucagon signaling pathway
- Hypertrophic cardiomyopathy
- Insulin resistance
- Insulin signaling pathway
- Longevity regulating pathway
- Non
- Oxytocin signaling pathway
- PI3K
- Thermogenesis
- Tight junction
- mTOR signaling pathway
- AMP-activated protein kinase activity
- ATP binding
- CAMKK-AMPK signaling cascade
- Wnt signaling pathway
- [acetyl-CoA carboxylase] kinase activity
- [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity
- apical plasma membrane
- autophagy
- axon
- bile acid and bile salt transport
- bile acid signaling pathway
- cellular response to calcium ion
- cellular response to ethanol
- cellular response to glucose starvation
- cellular response to glucose stimulus
- cellular response to hydrogen peroxide
- cellular response to hypoxia
- cellular response to nutrient levels
- cellular response to organonitrogen compound
- cellular response to oxidative stress
- cellular response to prostaglandin E stimulus
- cholesterol biosynthetic process
- chromatin binding
- cold acclimation
- cytoplasm
- cytosol
- dendrite
- energy homeostasis
- fatty acid biosynthetic process
- fatty acid homeostasis
- fatty acid oxidation
- glucose homeostasis
- glucose metabolic process
- histone serine kinase activity
- intracellular signal transduction
- kinase binding
- lipid biosynthetic process
- metal ion binding
- motor behavior
- negative regulation of TOR signaling
- negative regulation of apoptotic process
- negative regulation of gene expression
- negative regulation of insulin receptor signaling pathway
- negative regulation of lipid catabolic process
- negative regulation of tubulin deacetylation
- neuron cellular homeostasis
- neuronal cell body
- nuclear speck
- nucleotide-activated protein kinase complex
- nucleus
- positive regulation of autophagy
- positive regulation of cell population proliferation
- positive regulation of gene expression
- positive regulation of glycolytic process
- positive regulation of mitochondrial transcription
- positive regulation of peptidyl-lysine acetylation
- positive regulation of protein localization
- positive regulation of protein targeting to mitochondrion
- positive regulation of skeletal muscle tissue development
- protein C-terminus binding
- protein kinase activity
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- protein-containing complex
- protein-containing complex binding
- regulation of bile acid secretion
- regulation of circadian rhythm
- regulation of microtubule cytoskeleton organization
- regulation of peptidyl-serine phosphorylation
- regulation of stress granule assembly
- regulation of vesicle-mediated transport
- response to 17alpha-ethynylestradiol
- response to UV
- response to activity
- response to caffeine
- response to camptothecin
- response to gamma radiation
- response to hydrogen peroxide
- rhythmic process
- tau-protein kinase activity
Prkaa2
Rat
5'-AMP-activated protein kinase catalytic subunit alpha-2
- Organism
- Rat (Rattus norvegicus)
- Uniprot ID
- AAPK2_RAT
- Accession #
- Q09137
- Protein names
-
- 5'-AMP-activated protein kinase catalytic subunit alpha-2
- AMPK subunit alpha-2
- EC 2.7.11.1
- Acetyl-CoA carboxylase kinase
- ACACA kinase
- EC 2.7.11.27
- Hydroxymethylglutaryl-CoA reductase kinase
- HMGCR kinase
- EC 2.7.11.31
- Gene names
-
- Prkaa2
- Ampk
- Ampk2
- Description
-
Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. Involved in insulin receptor/INSR internalization. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. In that process also activates WDR45. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. Plays an important role in the differential regulation of pro-autophagy (composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed of PIK3C3, BECN1 and PIK3R4) complexes, in response to glucose starvation. Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (By similarity). {ECO:0000250|UniProtKB:P54646, ECO:0000250|UniProtKB:Q8BRK8, ECO:0000269|PubMed:10025949, ECO:0000269|PubMed:11069105, ECO:0000269|PubMed:11598104, ECO:0000269|PubMed:11724780, ECO:0000269|PubMed:12065600, ECO:0000269|PubMed:12740371, ECO:0000269|PubMed:14511394, ECO:0000269|PubMed:14709557, ECO:0000269|PubMed:17341212, ECO:0000269|PubMed:2369897, ECO:0000269|PubMed:9029219}.
- Links
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Search Kinases of Prkaa2 (Rat)
- AMPK signaling pathway
- Adipocytokine signaling pathway
- Apelin signaling pathway
- Autophagy
- Circadian rhythm
- Fluid shear stress and atherosclerosis
- FoxO signaling pathway
- Glucagon signaling pathway
- Hypertrophic cardiomyopathy
- Insulin resistance
- Insulin signaling pathway
- Longevity regulating pathway
- Non
- Oxytocin signaling pathway
- PI3K
- Thermogenesis
- Tight junction
- mTOR signaling pathway
- AMP-activated protein kinase activity
- ATP binding
- Wnt signaling pathway
- [acetyl-CoA carboxylase] kinase activity
- [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity
- apical plasma membrane
- autophagy
- axon
- cellular response to calcium ion
- cellular response to glucose starvation
- cellular response to glucose stimulus
- cellular response to nutrient levels
- cellular response to organonitrogen compound
- cellular response to oxidative stress
- cellular response to prostaglandin E stimulus
- cholesterol biosynthetic process
- chromatin binding
- cytoplasm
- cytoplasmic stress granule
- dendrite
- energy homeostasis
- fatty acid biosynthetic process
- fatty acid homeostasis
- glucose homeostasis
- histone serine kinase activity
- intracellular signal transduction
- lipid biosynthetic process
- metal ion binding
- negative regulation of TOR signaling
- negative regulation of apoptotic process
- negative regulation of gene expression
- negative regulation of tubulin deacetylation
- neuronal cell body
- nucleoplasm
- nucleotide-activated protein kinase complex
- nucleus
- positive regulation of autophagy
- positive regulation of glycolytic process
- positive regulation of peptidyl-lysine acetylation
- positive regulation of protein localization
- protein kinase activity
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- protein serine/threonine/tyrosine kinase activity
- protein-containing complex
- protein-containing complex binding
- protein-macromolecule adaptor activity
- regulation of circadian rhythm
- regulation of gene expression
- regulation of lipid metabolic process
- regulation of macroautophagy
- regulation of microtubule cytoskeleton organization
- regulation of stress granule assembly
- response to activity
- response to caffeine
- response to muscle activity
- rhythmic process
PTEN
Human
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
- Organism
- Human (Homo sapiens)
- Uniprot ID
- PTEN_HUMAN
- Accession #
- P60484
- Protein names
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- Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
- EC 3.1.3.16
- EC 3.1.3.48
- EC 3.1.3.67
- Mutated in multiple advanced cancers 1
- Phosphatase and tensin homolog
- Gene names
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- PTEN
- MMAC1
- TEP1
- Description
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Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4 (PubMed:26504226, PubMed:16824732). The lipid phosphatase activity is critical for its tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with MAGI2 to suppress AKT1 activation. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement. {ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:26504226}.; [Isoform alpha]: Functional kinase, like isoform 1 it antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in mitochondrial energetic metabolism by promoting COX activity and ATP production, via collaboration with isoform 1 in increasing protein levels of PINK1.
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Search Kinases of PTEN (Human)
- Autophagy
- Breast cancer
- Cellular senescence
- Central carbon metabolism in cancer
- Chemical carcinogenesis
- Diabetic cardiomyopathy
- EGFR tyrosine kinase inhibitor resistance
- Endometrial cancer
- Focal adhesion
- FoxO signaling pathway
- Glioma
- Hepatocellular carcinoma
- Human T
- Human papillomavirus infection
- Inositol phosphate metabolism
- Insulin resistance
- Melanoma
- Metabolic pathways
- MicroRNAs in cancer
- PD
- PI3K
- Pathways in cancer
- Phosphatidylinositol signaling system
- Prostate cancer
- Small cell lung cancer
- Sphingolipid signaling pathway
- mTOR signaling pathway
- p53 signaling pathway
- PDZ domain binding
- PML body
- Schmidt-Lanterman incisure
- adult behavior
- aging
- anaphase-promoting complex binding
- angiogenesis
- apical plasma membrane
- apoptotic process
- brain morphogenesis
- canonical Wnt signaling pathway
- cardiac muscle tissue development
- cell migration
- cell motility
- cell projection
- cellular response to electrical stimulus
- cellular response to ethanol
- cellular response to hypoxia
- cellular response to insulin stimulus
- cellular response to insulin-like growth factor stimulus
- cellular response to leptin stimulus
- cellular response to nerve growth factor stimulus
- central nervous system development
- central nervous system myelin maintenance
- central nervous system neuron axonogenesis
- cytoplasm
- cytoplasmic side of plasma membrane
- cytosol
- dendritic spine
- dendritic spine morphogenesis
- dentate gyrus development
- dephosphorylation
- endothelial cell migration
- enzyme binding
- extracellular region
- forebrain morphogenesis
- heart development
- identical protein binding
- inositol phosphate dephosphorylation
- inositol phosphate metabolic process
- inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
- ionotropic glutamate receptor binding
- learning or memory
- lipid binding
- locomotor rhythm
- locomotory behavior
- long-term synaptic depression
- long-term synaptic potentiation
- male mating behavior
- maternal behavior
- memory
- mitochondrion
- multicellular organismal response to stress
- myelin sheath adaxonal region
- negative regulation of ERK1 and ERK2 cascade
- negative regulation of G1/S transition of mitotic cell cycle
- negative regulation of apoptotic process
- negative regulation of axon regeneration
- negative regulation of axonogenesis
- negative regulation of cardiac muscle cell proliferation
- negative regulation of cell aging
- negative regulation of cell cycle G1/S phase transition
- negative regulation of cell migration
- negative regulation of cell population proliferation
- negative regulation of cell size
- negative regulation of cyclin-dependent protein serine/threonine kinase activity
- negative regulation of dendritic spine morphogenesis
- negative regulation of epithelial cell proliferation
- negative regulation of epithelial to mesenchymal transition
- negative regulation of excitatory postsynaptic potential
- negative regulation of focal adhesion assembly
- negative regulation of keratinocyte migration
- negative regulation of myelination
- negative regulation of neuron projection development
- negative regulation of organ growth
- negative regulation of peptidyl-serine phosphorylation
- negative regulation of phagocytosis
- negative regulation of phosphatidylinositol 3-kinase signaling
- negative regulation of potassium ion transmembrane transporter activity
- negative regulation of protein kinase B signaling
- negative regulation of protein phosphorylation
- negative regulation of ribosome biogenesis
- negative regulation of signaling receptor activity
- negative regulation of synaptic vesicle clustering
- negative regulation of vascular associated smooth muscle cell proliferation
- negative regulation of wound healing, spreading of epidermal cells
- neuron projection
- neuron-neuron synaptic transmission
- nucleoplasm
- nucleus
- phosphatidylinositol 3-kinase signaling
- phosphatidylinositol biosynthetic process
- phosphatidylinositol dephosphorylation
- phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
- phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity
- phosphatidylinositol-3-phosphatase activity
- phosphoprotein phosphatase activity
- plasma membrane
- platelet-derived growth factor receptor binding
- platelet-derived growth factor receptor signaling pathway
- positive regulation of DNA-binding transcription factor activity
- positive regulation of ERK1 and ERK2 cascade
- positive regulation of TRAIL-activated apoptotic signaling pathway
- positive regulation of cardiac muscle cell apoptotic process
- positive regulation of cell population proliferation
- positive regulation of excitatory postsynaptic potential
- positive regulation of gene expression
- positive regulation of neuron differentiation
- positive regulation of ubiquitin protein ligase activity
- positive regulation of ubiquitin-dependent protein catabolic process
- postsynaptic cytosol
- postsynaptic density assembly
- postsynaptic membrane
- prepulse inhibition
- presynaptic membrane assembly
- prostate gland growth
- protein dephosphorylation
- protein deubiquitination
- protein kinase B signaling
- protein serine phosphatase activity
- protein serine/threonine phosphatase activity
- protein stabilization
- protein threonine phosphatase activity
- protein tyrosine kinase binding
- protein tyrosine phosphatase activity
- regulation of B cell apoptotic process
- regulation of cellular component size
- regulation of myeloid cell apoptotic process
- regulation of neuron projection development
- regulation of protein kinase B signaling
- regulation of protein stability
- regulation of synaptic transmission, GABAergic
- regulation of transcription initiation from RNA polymerase II promoter
- response to ATP
- response to activity
- response to arsenic-containing substance
- response to estradiol
- response to glucose
- response to nutrient
- response to zinc ion
- rhythmic synaptic transmission
- social behavior
- synapse assembly
- synapse maturation
- ubiquitin-specific protease binding
SIK1
Human
Serine/threonine-protein kinase SIK1
- Organism
- Human (Homo sapiens)
- Uniprot ID
- SIK1_HUMAN
- Accession #
- P57059
- Protein names
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- Serine/threonine-protein kinase SIK1
- EC 2.7.11.1
- Salt-inducible kinase 1
- SIK-1
- Serine/threonine-protein kinase SNF1-like kinase 1
- Serine/threonine-protein kinase SNF1LK
- Gene names
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- SIK1
- SIK
- SNF1LK
- Description
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Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression. Phosphorylates HDAC4, HDAC5, PPME1, SREBF1, CRTC1/TORC1. Inhibits CREB activity by phosphorylating and inhibiting activity of TORCs, the CREB-specific coactivators, like CRTC2/TORC2 and CRTC3/TORC3 in response to cAMP signaling (PubMed:29211348). Acts as a tumor suppressor and plays a key role in p53/TP53-dependent anoikis, a type of apoptosis triggered by cell detachment: required for phosphorylation of p53/TP53 in response to loss of adhesion and is able to suppress metastasis. Part of a sodium-sensing signaling network, probably by mediating phosphorylation of PPME1: following increases in intracellular sodium, SIK1 is activated by CaMK1 and phosphorylates PPME1 subunit of protein phosphatase 2A (PP2A), leading to dephosphorylation of sodium/potassium-transporting ATPase ATP1A1 and subsequent increase activity of ATP1A1. Acts as a regulator of muscle cells by phosphorylating and inhibiting class II histone deacetylases HDAC4 and HDAC5, leading to promote expression of MEF2 target genes in myocytes. Also required during cardiomyogenesis by regulating the exit of cardiomyoblasts from the cell cycle via down-regulation of CDKN1C/p57Kip2. Acts as a regulator of hepatic gluconeogenesis by phosphorylating and repressing the CREB-specific coactivators CRTC1/TORC1 and CRTC2/TORC2, leading to inhibit CREB activity. Also regulates hepatic lipogenesis by phosphorylating and inhibiting SREBF1. In concert with CRTC1/TORC1, regulates the light-induced entrainment of the circadian clock by attenuating PER1 induction; represses CREB-mediated transcription of PER1 by phosphorylating and deactivating CRTC1/TORC1 (By similarity). {ECO:0000250|UniProtKB:Q60670, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:16306228, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:19622832, ECO:0000269|PubMed:29211348}.
- Links
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Search Kinases of SIK1 (Human)
- 14-3-3 protein binding
- ATP binding
- cAMP response element binding protein binding
- cardiac muscle cell differentiation
- cell cycle
- cellular response to glucose starvation
- cytoplasm
- entrainment of circadian clock by photoperiod
- intracellular signal transduction
- magnesium ion binding
- negative regulation of CREB transcription factor activity
- negative regulation of gluconeogenesis
- negative regulation of triglyceride biosynthetic process
- nucleus
- positive regulation of anoikis
- protein autophosphorylation
- protein kinase binding
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- regulation of cell differentiation
- regulation of mitotic cell cycle
- regulation of myotube differentiation
- regulation of sodium ion transport
- rhythmic process
Sik1
Rat
Serine/threonine-protein kinase SIK1
- Organism
- Rat (Rattus norvegicus)
- Uniprot ID
- SIK1_RAT
- Accession #
- Q9R1U5
- Protein names
-
- Serine/threonine-protein kinase SIK1
- EC 2.7.11.1
- Protein kinase KID2
- Salt-inducible kinase 1
- SIK-1
- Serine/threonine-protein kinase SNF1-like kinase 1
- Serine/threonine-protein kinase SNF1LK
- Gene names
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- Sik1
- Kid2
- Sik
- Snf1lk
- Description
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Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression. Phosphorylates HDAC4, HDAC5, PPME1, SREBF1, CRTC1/TORC1 and CRTC2/TORC2. Acts as a tumor suppressor and plays a key role in p53/TP53-dependent anoikis, a type of apoptosis triggered by cell detachment: required for phosphorylation of p53/TP53 in response to loss of adhesion and is able to suppress metastasis. Part of a sodium-sensing signaling network, probably by mediating phosphorylation of PPME1: following increases in intracellular sodium, SIK1 is activated by CaMK1 and phosphorylates PPME1 subunit of protein phosphatase 2A (PP2A), leading to dephosphorylation of sodium/potassium-transporting ATPase ATP1A1 and subsequent increase activity of ATP1A1. Acts as a regulator of muscle cells by phosphorylating and inhibiting class II histone deacetylases HDAC4 and HDAC5, leading to promote expression of MEF2 target genes in myocytes. Also required during cardiomyogenesis by regulating the exit of cardiomyoblasts from the cell cycle via down-regulation of CDKN1C/p57Kip2. Acts as a regulator of hepatic gluconeogenesis by phosphorylating and repressing the CREB-specific coactivators CRTC1/TORC1 and CRTC2/TORC2, leading to inhibit CREB activity. Also regulates hepatic lipogenesis by phosphorylating and inhibiting SREBF1. In concert with CRTC1/TORC1, regulates the light-induced entrainment of the circadian clock by attenuating PER1 induction; represses CREB-mediated transcription of PER1 by phosphorylating and deactivating CRTC1/TORC1 (By similarity). {ECO:0000250|UniProtKB:Q60670, ECO:0000269|PubMed:10820182, ECO:0000269|PubMed:17939993, ECO:0000269|PubMed:18946175, ECO:0000269|PubMed:19244510}.
- Links
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Search Kinases of Sik1 (Rat)
- 14-3-3 protein binding
- ATP binding
- anoikis
- cAMP response element binding protein binding
- cardiac muscle cell differentiation
- cell cycle
- cellular response to glucose starvation
- cytoplasm
- cytosol
- entrainment of circadian clock by photoperiod
- histone deacetylase binding
- intracellular signal transduction
- magnesium ion binding
- negative regulation of CREB transcription factor activity
- negative regulation of gluconeogenesis
- negative regulation of transcription by RNA polymerase II
- negative regulation of triglyceride biosynthetic process
- nucleus
- positive regulation of anoikis
- protein autophosphorylation
- protein kinase binding
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- regulation of cell differentiation
- regulation of mitotic cell cycle
- regulation of myotube differentiation
- regulation of sodium ion transport
- rhythmic process
SIK2
Human
Serine/threonine-protein kinase SIK2
- Organism
- Human (Homo sapiens)
- Uniprot ID
- SIK2_HUMAN
- Accession #
- Q9H0K1
- Protein names
-
- Serine/threonine-protein kinase SIK2
- EC 2.7.11.1
- Qin-induced kinase
- Salt-inducible kinase 2
- SIK-2
- Serine/threonine-protein kinase SNF1-like kinase 2
- Gene names
-
- SIK2
- KIAA0781
- QIK
- SNF1LK2
- Description
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Phosphorylates 'Ser-794' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators. {ECO:0000269|PubMed:15454081}.
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Search Kinases of SIK2 (Human)
SMAD4
Human
Mothers against decapentaplegic homolog 4
- Organism
- Human (Homo sapiens)
- Uniprot ID
- SMAD4_HUMAN
- Accession #
- Q13485
- Protein names
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- Mothers against decapentaplegic homolog 4
- MAD homolog 4
- Mothers against DPP homolog 4
- Deletion target in pancreatic carcinoma 4
- SMAD family member 4
- SMAD 4
- Smad4
- hSMAD4
- Gene names
-
- SMAD4
- DPC4
- MADH4
- Description
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In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (By similarity). Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling (PubMed:25514493). Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. {ECO:0000250, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:25514493, ECO:0000269|PubMed:9389648}.
- Links
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Search Kinases of SMAD4 (Human)
- AGE
- Adherens junction
- Apelin signaling pathway
- Cell cycle
- Chronic myeloid leukemia
- Colorectal cancer
- FoxO signaling pathway
- Gastric cancer
- Hepatitis B
- Hepatocellular carcinoma
- Hippo signaling pathway
- Human T
- Pancreatic cancer
- Pathways in cancer
- Signaling pathways regulating pluripotency of stem cells
- TGF
- Th17 cell differentiation
- Wnt signaling pathway
- BMP signaling pathway
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity, RNA polymerase II-specific
- I-SMAD binding
- R-SMAD binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- SMAD protein complex
- SMAD protein complex assembly
- SMAD protein signal transduction
- activin responsive factor complex
- anatomical structure morphogenesis
- atrioventricular canal development
- atrioventricular valve formation
- axon guidance
- brainstem development
- branching involved in ureteric bud morphogenesis
- cardiac conduction system development
- cell differentiation
- cell population proliferation
- cellular iron ion homeostasis
- cellular response to BMP stimulus
- centrosome
- chromatin
- chromatin binding
- collagen binding
- cytoplasm
- cytosol
- developmental growth
- embryonic digit morphogenesis
- endocardial cell differentiation
- endothelial cell activation
- epithelial to mesenchymal transition involved in endocardial cushion formation
- female gonad morphogenesis
- formation of anatomical boundary
- gastrulation with mouth forming second
- heteromeric SMAD protein complex
- identical protein binding
- in utero embryonic development
- interleukin-6-mediated signaling pathway
- intracellular signal transduction
- left ventricular cardiac muscle tissue morphogenesis
- mesendoderm development
- metal ion binding
- metanephric mesenchyme morphogenesis
- negative regulation of BMP signaling pathway
- negative regulation of ERK1 and ERK2 cascade
- negative regulation of cardiac muscle hypertrophy
- negative regulation of cardiac myofibril assembly
- negative regulation of cell death
- negative regulation of cell growth
- negative regulation of cell population proliferation
- negative regulation of transcription by RNA polymerase II
- negative regulation of transcription, DNA-templated
- nephrogenic mesenchyme morphogenesis
- neural crest cell differentiation
- neuron fate commitment
- nucleoplasm
- nucleus
- outflow tract septum morphogenesis
- ovarian follicle development
- positive regulation of BMP signaling pathway
- positive regulation of SMAD protein signal transduction
- positive regulation of cell proliferation involved in heart valve morphogenesis
- positive regulation of epithelial to mesenchymal transition
- positive regulation of follicle-stimulating hormone secretion
- positive regulation of histone H3-K4 methylation
- positive regulation of histone H3-K9 acetylation
- positive regulation of luteinizing hormone secretion
- positive regulation of pathway-restricted SMAD protein phosphorylation
- positive regulation of pri-miRNA transcription by RNA polymerase II
- positive regulation of transcription by RNA polymerase II
- positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus
- positive regulation of transcription, DNA-templated
- positive regulation of transforming growth factor beta receptor signaling pathway
- protein deubiquitination
- protein homodimerization activity
- regulation of binding
- regulation of hair follicle development
- regulation of transforming growth factor beta receptor signaling pathway
- regulation of transforming growth factor beta2 production
- response to hypoxia
- response to transforming growth factor beta
- sebaceous gland development
- secondary palate development
- seminiferous tubule development
- single fertilization
- somatic stem cell population maintenance
- somite rostral/caudal axis specification
- spermatogenesis
- sulfate binding
- transcription cis-regulatory region binding
- transcription coactivator binding
- transcription regulator complex
- transforming growth factor beta receptor signaling pathway
- uterus development
- ventricular septum morphogenesis