O88643
uniprot
O88643
canonical
activity_regulation
ACTIVITY REGULATION: Phosphorylation of Thr-84 by OXSR1 inhibits activation (By similarity). Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, and enables activation by phosphorylation of Thr-423 (By similarity). {ECO:0000250}.
uniprot
proteins
amino_acid_sequence
MSNNGVDIQDKPPAPPMRNTSTMIGAGSKDTGTLNHGSKPLPPNPEEKKKKDRFYRSILPGDKTNKKREKERPEISLPSDFEHTIHVGFDAVTGEFTGMPEQWARLLQTSNITKSEQKKNPQAVLDVLEFYNSKKTSNSKKYMSFTDKSAEDYNSSNTLNVKTVSETPAVPPVSEDDEDDDDDATPPPVIAPRPEHTKSVYTRSVIEPLPVTPTRDVATSPISPTENNTTPPDALTRNTEKQKKKPKMSDEEILEKLRSIVSVGDPKKKYTPFEKIGQGASGTVYTAMDVATGQEVAIKQMNLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPLRALYLIATNGTPELQNPEKLSAIFRDFLQCCLEMDVEKRGSAKELLQHQFLKIAKPLSSLTPLMHAAKEATKNNH
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: 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:10611223, PubMed:12165471, PubMed:12176334, PubMed:15800193, PubMed:22669945, PubMed:23633677). Can directly phosphorylate BAD and protects cells against apoptosis (PubMed:10611223). Activated by interaction with CDC42 and RAC1 (By similarity). Functions as a GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway (By similarity). Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases (By similarity). Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes (By similarity). Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton (PubMed:12176334). Plays a role in the regulation of insulin secretion in response to elevated glucose levels (PubMed:22669945). 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) (PubMed:12165471). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2 (By similarity). Phosphorylates MYL9/MLC2 (By similarity). 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 (By similarity). Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus (By similarity). In podocytes, promotes NR3C2 nuclear localization (By similarity). 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 (PubMed:23633677). In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation (By similarity). Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion (By similarity). 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). Phosphorylates FXR1, promoting its localization to stress granules and activity (By similarity). Phosphorylates ILK on 'Thr-173' and 'Ser-246', promoting nuclear export of ILK (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}.
uniprot
proteins
mass_dalton
60737
uniprot
proteins
mutagenesis
MUTAGEN 83; /note="H->L: When expressed in hippocampal neurons, strongly decreases the number of dendritic spines; when associated with L-86 and R-299."; /evidence="ECO:0000269|PubMed:15800193"; MUTAGEN 86; /note="H->L: When expressed in hippocampal neurons, strongly decreases the number of dendritic spines; when associated with L-83 and R-299."; /evidence="ECO:0000269|PubMed:15800193"; MUTAGEN 299; /note="K->R: When expressed in hippocampal neurons, decreases the number of dendritic spines. Strong decrease in the number of dendritic spines; when associated with L-83 and L-86."; /evidence="ECO:0000269|PubMed:15800193"; MUTAGEN 423; /note="T->E: When expressed in hippocampal neurons, increases the density of both spines and dendritic protrusions."; /evidence="ECO:0000269|PubMed:15800193
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated in trans, meaning that in a dimer, one kinase molecule phosphorylates the other one. Activated by autophosphorylation at Thr-423 in response to a conformation change, triggered by interaction with GTP-bound CDC42 or RAC1. Activated by phosphorylation at Thr-423 by BRSK2 and by PDPK1. Phosphorylated by JAK2 in response to PRL; this increases PAK1 kinase activity. Phosphorylated at Ser-21 by PKB/AKT; this reduces interaction with NCK1 and association with focal adhesion sites (By similarity). Upon DNA damage, phosphorylated at Thr-212 and translocates to the nucleoplasm (By similarity). Phosphorylated at tyrosine residues, which can be enhanced by NTN1 (PubMed:22685302). {ECO:0000250|UniProtKB:P35465, ECO:0000250|UniProtKB:Q13153, ECO:0000269|PubMed:22685302}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
STE Ser/Thr protein kinase family
uniprot
proteins
protein_family
STE20 subfamily
uniprot
proteins
pubmed
10352232
uniprot
proteins
pubmed
10611223
uniprot
proteins
pubmed
12165471
uniprot
proteins
pubmed
12176334
uniprot
proteins
pubmed
15169762
uniprot
proteins
pubmed
15229651
uniprot
proteins
pubmed
15345747
uniprot
proteins
pubmed
15800193
uniprot
proteins
pubmed
18716323
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22669945
uniprot
proteins
pubmed
22685302
uniprot
proteins
pubmed
22751929
uniprot
proteins
pubmed
23633677
uniprot
proteins
pubmed
26048998
uniprot
proteins
sequence_length
545
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q13153}. Cell junction, focal adhesion {ECO:0000250|UniProtKB:Q13153}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:Q13153}. Cell membrane {ECO:0000250|UniProtKB:Q13153}. Cell projection, ruffle membrane {ECO:0000250|UniProtKB:Q13153}. Cell projection, invadopodium {ECO:0000250|UniProtKB:Q13153}. Nucleus, nucleoplasm {ECO:0000250|UniProtKB:Q13153}. Chromosome {ECO:0000250|UniProtKB:Q13153}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:Q13153}. Note=Recruited to the cell membrane by interaction with CDC42 and RAC1 (By similarity). Recruited to focal adhesions upon activation. Colocalized with CIB1 within membrane ruffles during cell spreading upon readhesion to fibronectin. Colocalizes with RUFY3, F-actin and other core migration components in invadopodia at the cell periphery (By similarity). Upon DNA damage, translocates to the nucleoplasm when phosphorylated at Thr-212 where is co-recruited with MORC2 on damaged chromatin (By similarity). Localization to the centrosome does not depend upon the presence of gamma-tubulin (By similarity). Localization of the active, but not inactive, protein to the adhesions and edge of lamellipodia is mediated by interaction with GIT1 (By similarity). {ECO:0000250|UniProtKB:P35465, ECO:0000250|UniProtKB:Q13153}.
uniprot
proteins