InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PTK2B

Summary

InnateDB Protein

IDBP-235165.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PTK2B

Protein Name

PTK2B protein tyrosine kinase 2 beta

Synonyms

CADTK; CAKB; FADK2; FAK2; PKB; PTK; PYK2; RAFTK;

Species

Homo sapiens

Ensembl Protein

ENSP00000380638

InnateDB Gene

IDBG-13899 (PTK2B)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10022920, ECO:0000269PubMed:12771146, ECO:0000269PubMed:12893833, ECO:0000269PubMed:14585963, ECO:0000269PubMed:15050747, ECO:0000269PubMed:15166227, ECO:0000269PubMed:17634955, ECO:0000269PubMed:18086875, ECO:0000269PubMed:18339875, ECO:0000269PubMed:18587400, ECO:0000269PubMed:18765415, ECO:0000269PubMed:19086031, ECO:0000269PubMed:19207108, ECO:0000269PubMed:19244237, ECO:0000269PubMed:19428251, ECO:0000269PubMed:19648005, ECO:0000269PubMed:19880522, ECO:0000269PubMed:20001213, ECO:0000269PubMed:20381867, ECO:0000269PubMed:20521079, ECO:0000269PubMed:21357692, ECO:0000269PubMed:21533080, ECO:0000269PubMed:7544443, ECO:0000269PubMed:8670418, ECO:0000269PubMed:8849729}.

Subcellular Localization

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.

Disease Associations

Note=Aberrant PTK2B/PYK2 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. Elevated PTK2B/PYK2 expression is seen in gliomas, hepatocellular carcinoma, lung cancer and breast cancer.

Tissue Specificity

Most abundant in the brain, with highest levels in amygdala and hippocampus. Low levels in kidney (at protein level). Also expressed in spleen and lymphocytes. {ECO:0000269PubMed:7544443, ECO:0000269PubMed:9545257}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 97 experimentally validated interaction(s) in this database.
They are also associated with 13 interaction(s) predicted by orthology.

Experimentally validated
Total	97 [view]
Protein-Protein	96 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	13 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004683	calmodulin-dependent protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0004871	signal transducer activity
GO:0004972	N-methyl-D-aspartate selective glutamate receptor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0032403	protein complex binding
GO:0043423	3-phosphoinositide-dependent protein kinase binding

Biological Process

GO:0000165	MAPK cascade
GO:0000302	response to reactive oxygen species
GO:0001525	angiogenesis
GO:0001556	oocyte maturation
GO:0001666	response to hypoxia
GO:0001954	positive regulation of cell-matrix adhesion
GO:0002040	sprouting angiogenesis
GO:0002315	marginal zone B cell differentiation
GO:0006461	protein complex assembly
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0006950	response to stress
GO:0006968	cellular defense response
GO:0006970	response to osmotic stress
GO:0007015	actin filament organization
GO:0007155	cell adhesion
GO:0007165	signal transduction
GO:0007166	cell surface receptor signaling pathway
GO:0007172	signal complex assembly
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007204	positive regulation of cytosolic calcium ion concentration
GO:0007229	integrin-mediated signaling pathway
GO:0008284	positive regulation of cell proliferation
GO:0008285	negative regulation of cell proliferation
GO:0008360	regulation of cell shape
GO:0009612	response to mechanical stimulus
GO:0009725	response to hormone
GO:0009749	response to glucose
GO:0010226	response to lithium ion
GO:0010243	response to organonitrogen compound
GO:0010595	positive regulation of endothelial cell migration
GO:0010656	negative regulation of muscle cell apoptotic process
GO:0010758	regulation of macrophage chemotaxis
GO:0010976	positive regulation of neuron projection development
GO:0014009	glial cell proliferation
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030154	cell differentiation
GO:0030155	regulation of cell adhesion
GO:0030279	negative regulation of ossification
GO:0030307	positive regulation of cell growth
GO:0030335	positive regulation of cell migration
GO:0030502	negative regulation of bone mineralization
GO:0030838	positive regulation of actin filament polymerization
GO:0031175	neuron projection development
GO:0032863	activation of Rac GTPase activity
GO:0032960	regulation of inositol trisphosphate biosynthetic process
GO:0033209	tumor necrosis factor-mediated signaling pathway
GO:0035235	ionotropic glutamate receptor signaling pathway
GO:0035902	response to immobilization stress
GO:0038083	peptidyl-tyrosine autophosphorylation
GO:0042220	response to cocaine
GO:0042493	response to drug
GO:0042542	response to hydrogen peroxide
GO:0042976	activation of Janus kinase activity
GO:0043066	negative regulation of apoptotic process
GO:0043149	stress fiber assembly
GO:0043267	negative regulation of potassium ion transport
GO:0043507	positive regulation of JUN kinase activity
GO:0043524	negative regulation of neuron apoptotic process
GO:0043534	blood vessel endothelial cell migration
GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity
GO:0045087	innate immune response (InnateDB)
GO:0045453	bone resorption
GO:0045471	response to ethanol
GO:0045638	negative regulation of myeloid cell differentiation
GO:0045727	positive regulation of translation
GO:0045860	positive regulation of protein kinase activity
GO:0046330	positive regulation of JNK cascade
GO:0046777	protein autophosphorylation
GO:0048010	vascular endothelial growth factor receptor signaling pathway
GO:0048041	focal adhesion assembly
GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation
GO:0051279	regulation of release of sequestered calcium ion into cytosol
GO:0051591	response to cAMP
GO:0051592	response to calcium ion
GO:0051968	positive regulation of synaptic transmission, glutamatergic
GO:0060291	long-term synaptic potentiation
GO:0070098	chemokine-mediated signaling pathway
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0071300	cellular response to retinoic acid
GO:2000058	regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:2000114	regulation of establishment of cell polarity
GO:2000249	regulation of actin cytoskeleton reorganization
GO:2000310	regulation of N-methyl-D-aspartate selective glutamate receptor activity
GO:2000379	positive regulation of reactive oxygen species metabolic process
GO:2000463	positive regulation of excitatory postsynaptic membrane potential
GO:2000538	positive regulation of B cell chemotaxis

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005856	cytoskeleton
GO:0005925	focal adhesion
GO:0005938	cell cortex
GO:0014069	postsynaptic density
GO:0017146	N-methyl-D-aspartate selective glutamate receptor complex
GO:0030027	lamellipodium
GO:0030424	axon
GO:0030425	dendrite
GO:0030426	growth cone
GO:0043025	neuronal cell body
GO:0044297	cell body
GO:0045121	membrane raft
GO:0048471	perinuclear region of cytoplasm
GO:0097440	apical dendrite

Protein Structure and Domains

PDB ID

InterPro

IPR000299 FERM domain
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR005189 Focal adhesion kinase, targeting (FAT) domain
IPR011009 Protein kinase-like domain
IPR019748 FERM central domain
IPR019749 Band 4.1 domain
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR029071 Ubiquitin-related domain

PFAM

PF00069
PF07714
PF03623
PF00373

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00295
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt