Names & Taxonomy

Uniprot ID:
Q14289
Entry Name:
FAK2_HUMAN
Status:
reviewed
Protein Names:
Protein-tyrosine kinase 2-beta (EC 2.7.10.2) (Calcium-dependent tyrosine kinase) (CADTK) (Calcium-regulated non-receptor proline-rich tyrosine kinase) (Cell adhesion kinase beta) (CAK-beta) (CAKB) (Focal adhesion kinase 2) (FADK 2) (Proline-rich tyrosine kinase 2) (Related adhesion focal tyrosine kinase) (RAFTK)
Gene Names:
PTK2B FAK2 PYK2 RAFTK
Gene Names Primary:
PTK2B
Organism:
Homo sapiens (Human)

Structure

Length:
1009
Sequence:
MSGVSEPLSRVKLGTLRRPEGPAEPMVVVPVDVEKEDVRILKVCFYSNSFNPGKNFKLVKCTVQTEIREIITSILLSGRIGPNIRLAECYGLRLKHMKSDEIHWLHPQMTVGEVQDKYECLHVEAEWRYDLQIRYLPEDFMESLKEDRTTLLYFYQQLRNDYMQRYASKVSEGMALQLGCLELRRFFKDMPHNALDKKSNFELLEKEVGLDLFFPKQMQENLKPKQFRKMIQQTFQQYASLREEECVMKFFNTLAGFANIDQETYRCELIQGWNITVDLVIGPKGIRQLTSQDAKPTCLAEFKQIRSIRCLPLEEGQAVLQLGIEGAPQALSIKTSSLAEAENMADLIDGYCRLQGEHQGSLIIHPRKDGEKRNSLPQIPMLNLEARRSHLSESCSIESDIYAEIPDETLRRPGGPQYGIAREDVVLNRILGEGFFGEVYEGVYTNHKGEKINVAVKTCKKDCTLDNKEKFMSEAVIMKNLDHPHIVKLIGIIEEEPTWIIMELYPYGELGHYLERNKNSLKVLTLVLYSLQICKAMAYLESINCVHRDIAVRNILVASPECVKLGDFGLSRYIEDEDYYKASVTRLPIKWMSPESINFRRFTTASDVWMFAVCMWEILSFGKQPFFWLENKDVIGVLEKGDRLPKPDLCPPVLYTLMTRCWDYDPSDRPRFTELVCSLSDVYQMEKDIAMEQERNARYRTPKILEPTAFQEPPPKPSRPKYRPPPQTNLLAPKLQFQVPEGLCASSPTLTSPMEYPSPVNSLHTPPLHRHNVFKRHSMREEDFIQPSSREEAQQLWEAEKVKMRQILDKQQKQMVEDYQWLRQEEKSLDPMVYMNDKSPLTPEKEVGYLEFTGPPQKPPRLGAQSIQPTANLDRTDDLVYLNVMELVRAVLELKNELCQLPPEGYVVVVKNVGLTLRKLIGSVDDLLPSLPSSSRTEIEGTQKLLNKDLAELINKMRLAQQNAVTSLSEECKRQMLTASHTLAVDAKNLLDAVDQAKVLANLAHPPAE
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm. Cytoplasm, perinuclear region. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell junction, focal adhesion. Cell projection, lamellipodium. Cytoplasm, cell cortex. Nucleus. Note=Interaction with NPHP1 induces the membrane-association of the kinase. Colocalizes with integrins at the cell periphery.

Function

Function:
Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2.
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:
ENZYME REGULATION: Activated in response to stimuli that lead to increased intracellular Ca(2+) levels; this activation is indirect and may be mediated by calcium-mediated production of reactive oxygen species (ROS). Activated by autophosphorylation at Tyr-402; this creates a binding site for SRC family kinases and leads to phosphorylation at additional tyrosine residues. Phosphorylation at Tyr-402, Tyr-579 and Tyr-580 is required for optimal kinase activity. Inhibited by PF-562,271, BIRB796, PF-4618433 and by PF-431396, PF-2318841 and their derivatives. Inhibited by sulfoximine-substituted trifluoromethylpyrimidines. Inhibited by 4-amino and 5-aryl substituted pyridinone compounds.
Active Site:
ACT_SITE 549 549 Proton acceptor.
Cross Reference Drug Bank:
DB01097
Gene Ontology Go:
apical dendrite
axon
cell body
cell cortex
cytoplasm
cytoskeleton
cytosol
dendrite
extrinsic component of cytoplasmic side of plasma membrane
focal adhesion
growth cone
lamellipodium
membrane raft
neuronal cell body
NMDA selective glutamate receptor complex
nucleoplasm
nucleus
perinuclear region of cytoplasm
postsynaptic density
ATP binding
calmodulin-dependent protein kinase activity
NMDA glutamate receptor activity
non-membrane spanning protein tyrosine kinase activity
protein tyrosine kinase activity
receptor binding
signal transducer activity
activation of GTPase activity
activation of Janus kinase activity
adaptive immune response
angiogenesis
apoptotic process
blood vessel endothelial cell migration
bone resorption
cell adhesion
cell surface receptor signaling pathway
cellular defense response
cellular response to fluid shear stress
cellular response to retinoic acid
chemokine-mediated signaling pathway
cytoskeleton organization
epidermal growth factor receptor signaling pathway
focal adhesion assembly
glial cell proliferation
innate immune response
integrin-mediated signaling pathway
ionotropic glutamate receptor signaling pathway
long term synaptic depression
long-term synaptic potentiation
MAPK cascade
marginal zone B cell differentiation
negative regulation of apoptotic process
negative regulation of bone mineralization
negative regulation of cell proliferation
negative regulation of muscle cell apoptotic process
negative regulation of myeloid cell differentiation
negative regulation of neuron apoptotic process
negative regulation of potassium ion transport
neuron projection development
oocyte maturation
peptidyl-tyrosine autophosphorylation
peptidyl-tyrosine phosphorylation
positive regulation of actin filament polymerization
positive regulation of angiogenesis
positive regulation of B cell chemotaxis
positive regulation of cell growth
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of cell-matrix adhesion
positive regulation of cytosolic calcium ion concentration
positive regulation of DNA biosynthetic process
positive regulation of endothelial cell migration
positive regulation of ERK1 and ERK2 cascade
positive regulation of excitatory postsynaptic potential
positive regulation of JNK cascade
positive regulation of JUN kinase activity
positive regulation of neuron projection development
positive regulation of nitric oxide biosynthetic process
positive regulation of nitric-oxide synthase activity
positive regulation of peptidyl-tyrosine phosphorylation
positive regulation of phosphatidylinositol 3-kinase activity
positive regulation of protein kinase activity
positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
positive regulation of synaptic transmission, glutamatergic
positive regulation of translation
protein autophosphorylation
protein complex assembly
protein phosphorylation
regulation of actin cytoskeleton reorganization
regulation of calcium-mediated signaling
regulation of cell adhesion
regulation of cell shape
regulation of cGMP biosynthetic process
regulation of cGMP-mediated signaling
regulation of establishment of cell polarity
regulation of inositol trisphosphate biosynthetic process
regulation of macrophage chemotaxis
regulation of N-methyl-D-aspartate selective glutamate receptor activity
regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
regulation of release of sequestered calcium ion into cytosol
response to calcium ion
response to cAMP
response to cocaine
response to drug
response to ethanol
response to glucose
response to hormone
response to hydrogen peroxide
response to hypoxia
response to immobilization stress
response to lithium ion
response to mechanical stimulus
response to osmotic stress
response to stress
signal complex assembly
signal transduction
sprouting angiogenesis
stress fiber assembly
tumor necrosis factor-mediated signaling pathway
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Biological Process:
activation of GTPase activity
activation of Janus kinase activity
adaptive immune response
angiogenesis
apoptotic process
blood vessel endothelial cell migration
bone resorption
cell adhesion
cell surface receptor signaling pathway
cellular defense response
cellular response to fluid shear stress
cellular response to retinoic acid
chemokine-mediated signaling pathway
cytoskeleton organization
epidermal growth factor receptor signaling pathway
focal adhesion assembly
glial cell proliferation
innate immune response
integrin-mediated signaling pathway
ionotropic glutamate receptor signaling pathway
long term synaptic depression
long-term synaptic potentiation
MAPK cascade
marginal zone B cell differentiation
negative regulation of apoptotic process
negative regulation of bone mineralization
negative regulation of cell proliferation
negative regulation of muscle cell apoptotic process
negative regulation of myeloid cell differentiation
negative regulation of neuron apoptotic process
negative regulation of potassium ion transport
neuron projection development
oocyte maturation
peptidyl-tyrosine autophosphorylation
peptidyl-tyrosine phosphorylation
positive regulation of actin filament polymerization
positive regulation of angiogenesis
positive regulation of B cell chemotaxis
positive regulation of cell growth
positive regulation of cell-matrix adhesion
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of cytosolic calcium ion concentration
positive regulation of DNA biosynthetic process
positive regulation of endothelial cell migration
positive regulation of ERK1 and ERK2 cascade
positive regulation of excitatory postsynaptic potential
positive regulation of JNK cascade
positive regulation of JUN kinase activity
positive regulation of neuron projection development
positive regulation of nitric oxide biosynthetic process
positive regulation of nitric-oxide synthase activity
positive regulation of peptidyl-tyrosine phosphorylation
positive regulation of phosphatidylinositol 3-kinase activity
positive regulation of protein kinase activity
positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
positive regulation of synaptic transmission, glutamatergic
positive regulation of translation
protein autophosphorylation
protein complex assembly
protein phosphorylation
regulation of actin cytoskeleton reorganization
regulation of calcium-mediated signaling
regulation of cell adhesion
regulation of cell shape
regulation of cGMP biosynthetic process
regulation of cGMP-mediated signaling
regulation of establishment of cell polarity
regulation of inositol trisphosphate biosynthetic process
regulation of macrophage chemotaxis
regulation of N-methyl-D-aspartate selective glutamate receptor activity
regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
regulation of release of sequestered calcium ion into cytosol
response to calcium ion
response to cAMP
response to cocaine
response to drug
response to ethanol
response to glucose
response to hormone
response to hydrogen peroxide
response to hypoxia
response to immobilization stress
response to lithium ion
response to mechanical stimulus
response to osmotic stress
response to stress
signal complex assembly
signal transduction
sprouting angiogenesis
stress fiber assembly
tumor necrosis factor-mediated signaling pathway
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Molecular Function:
ATP binding
calmodulin-dependent protein kinase activity
NMDA glutamate receptor activity
non-membrane spanning protein tyrosine kinase activity
protein tyrosine kinase activity
receptor binding
signal transducer activity
Gene Ontology Cellular Component:
apical dendrite
axon
cell body
cell cortex
cytoplasm
cytoskeleton
cytosol
dendrite
extrinsic component of cytoplasmic side of plasma membrane
focal adhesion
growth cone
lamellipodium
membrane raft
neuronal cell body
NMDA selective glutamate receptor complex
nucleoplasm
nucleus
perinuclear region of cytoplasm
postsynaptic density
Keywords:
3D-structure
ATP-binding
Adaptive immunity
Alternative splicing
Angiogenesis
Cell junction
Cell membrane
Cell projection
Complete proteome
Cytoplasm
Immunity
Kinase
Membrane
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Transferase
Tyrosine-protein kinase
Interacts With:
Q7L0Q8; P12931

Publication

PubMed ID:
7544443 8838818 7673154 7499242 9545257 16421571 15489334 8849729 8670418 9422762 10022920 10769033 11493697 12771146 12893833 14585963 12522270 15050747 15166227 17329398 17634955 18339875 18765415 18088087 18691976 18086875 18587400 19207108 19648005 19086031 19369195 20521079 19880522 20028775 20381867 21269460 21357692 21533080 15888917 20001213 20332118 21196189 18951788 19358827 19428251 19244237 17344846