PTK2B
entrez
2185
canonical
uniprot
Q14289
canonical
ensembl
ENSG00000120899
resolver
ensp
ENSP00000332816
resolver
ensp
ENSP00000380638
resolver
ensp
ENSP00000391995
resolver
ensp
ENSP00000564195
resolver
ensp
ENSP00000564196
resolver
ensp
ENSP00000564197
resolver
ensp
ENSP00000564199
resolver
ensp
ENSP00000564200
resolver
ensp
ENSP00000564202
resolver
ensp
ENSP00000564206
resolver
ensp
ENSP00000564208
resolver
ensp
ENSP00000564210
resolver
ensp
ENSP00000564211
resolver
ensp
ENSP00000564213
resolver
ensp
ENSP00000583807
resolver
ensp
ENSP00000626580
resolver
ensp
ENSP00000626584
resolver
genesymbol
PTK2B
resolver
genesymbol_syn
FAK2
resolver
genesymbol_syn
PYK2
resolver
genesymbol_syn
RAFTK
resolver
hgnc
HGNC:9612
resolver
uniprot
D3DST0
resolver
uniprot
Q13475
resolver
uniprot
Q14290
resolver
uniprot
Q16709
resolver
uniprot
Q6PID4
resolver
uniprot_entry
FAK2_HUMAN
resolver
uniprot_sec
D3DST0
resolver
uniprot_sec
Q13475
resolver
uniprot_sec
Q14290
resolver
uniprot_sec
Q16709
resolver
uniprot_sec
Q6PID4
resolver
activity_regulation
ACTIVITY 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. {ECO:0000269|PubMed:18339875, ECO:0000269|PubMed:18951788, ECO:0000269|PubMed:19428251, ECO:0000269|PubMed:19648005}.
uniprot
proteins
amino_acid_sequence
MSGVSEPLSRVKLGTLRRPEGPAEPMVVVPVDVEKEDVRILKVCFYSNSFNPGKNFKLVKCTVQTEIREIITSILLSGRIGPNIRLAECYGLRLKHMKSDEIHWLHPQMTVGEVQDKYECLHVEAEWRYDLQIRYLPEDFMESLKEDRTTLLYFYQQLRNDYMQRYASKVSEGMALQLGCLELRRFFKDMPHNALDKKSNFELLEKEVGLDLFFPKQMQENLKPKQFRKMIQQTFQQYASLREEECVMKFFNTLAGFANIDQETYRCELIQGWNITVDLVIGPKGIRQLTSQDAKPTCLAEFKQIRSIRCLPLEEGQAVLQLGIEGAPQALSIKTSSLAEAENMADLIDGYCRLQGEHQGSLIIHPRKDGEKRNSLPQIPMLNLEARRSHLSESCSIESDIYAEIPDETLRRPGGPQYGIAREDVVLNRILGEGFFGEVYEGVYTNHKGEKINVAVKTCKKDCTLDNKEKFMSEAVIMKNLDHPHIVKLIGIIEEEPTWIIMELYPYGELGHYLERNKNSLKVLTLVLYSLQICKAMAYLESINCVHRDIAVRNILVASPECVKLGDFGLSRYIEDEDYYKASVTRLPIKWMSPESINFRRFTTASDVWMFAVCMWEILSFGKQPFFWLENKDVIGVLEKGDRLPKPDLCPPVLYTLMTRCWDYDPSDRPRFTELVCSLSDVYQMEKDIAMEQERNARYRTPKILEPTAFQEPPPKPSRPKYRPPPQTNLLAPKLQFQVPEGLCASSPTLTSPMEYPSPVNSLHTPPLHRHNVFKRHSMREEDFIQPSSREEAQQLWEAEKVKMRQILDKQQKQMVEDYQWLRQEEKSLDPMVYMNDKSPLTPEKEVGYLEFTGPPQKPPRLGAQSIQPTANLDRTDDLVYLNVMELVRAVLELKNELCQLPPEGYVVVVKNVGLTLRKLIGSVDDLLPSLPSSSRTEIEGTQKLLNKDLAELINKMRLAQQNAVTSLSEECKRQMLTASHTLAVDAKNLLDAVDQAKVLANLAHPPAE
uniprot
proteins
disease_involvement
DISEASE: 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.
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
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. {ECO:0000269|PubMed:10022920, ECO:0000269|PubMed:12771146, ECO:0000269|PubMed:12893833, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:15050747, ECO:0000269|PubMed:15166227, ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:18086875, ECO:0000269|PubMed:18339875, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18765415, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:19244237, ECO:0000269|PubMed:19428251, ECO:0000269|PubMed:19648005, ECO:0000269|PubMed:19880522, ECO:0000269|PubMed:20001213, ECO:0000269|PubMed:20381867, ECO:0000269|PubMed:20521079, ECO:0000269|PubMed:21357692, ECO:0000269|PubMed:21533080, ECO:0000269|PubMed:7544443, ECO:0000269|PubMed:8670418, ECO:0000269|PubMed:8849729}.
uniprot
proteins
mass_dalton
115875
uniprot
proteins
mutagenesis
MUTAGEN 402; /note="Y->F: Abolishes autophosphorylation. Abolishes interaction with SRC."; /evidence="ECO:0000269|PubMed:8849729"; MUTAGEN 457; /note="K->A: Abolishes kinase activity."; /evidence="ECO:0000269|PubMed:15166227"; MUTAGEN 859; /note="P->A: Loss of interaction with NPHP1."; /evidence="ECO:0000269|PubMed:11493697"; MUTAGEN 881; /note="Y->F: Loss of phosphorylation site. Strongly reduced interaction with GRB2."; /evidence="ECO:0000269|PubMed:20521079
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on tyrosine residues in response to various stimuli that elevate the intracellular calcium concentration; this activation is indirect and may be mediated by production of reactive oxygen species (ROS). Tyr-402 is the major autophosphorylation site, but other kinases can also phosphorylate Tyr-402. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-402 promotes interaction with SRC and SRC family members, leading to phosphorylation at Tyr-579; Tyr-580 and Tyr-881. Phosphorylation at Tyr-881 is important for interaction with GRB2. Phosphorylated on tyrosine residues upon activation of FGR and PKC. Recruitment by NPHP1 to cell matrix adhesions initiates Tyr-402 phosphorylation. In monocytes, adherence to substrata is required for tyrosine phosphorylation and kinase activation. Angiotensin II, thapsigargin and L-alpha-lysophosphatidic acid (LPA) also induce autophosphorylation and increase kinase activity. Phosphorylation by MYLK promotes ITGB2 activation and is thus essential to trigger neutrophil transmigration during lung injury. Dephosphorylated by PTPN12. {ECO:0000269|PubMed:11493697, ECO:0000269|PubMed:15166227, ECO:0000269|PubMed:17329398, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20381867, ECO:0000269|PubMed:20521079, ECO:0000269|PubMed:9545257}.
uniprot
proteins
protein_family
FAK subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10022920
uniprot
proteins
pubmed
10769033
uniprot
proteins
pubmed
11493697
uniprot
proteins
pubmed
12522270
uniprot
proteins
pubmed
12771146
uniprot
proteins
pubmed
12893833
uniprot
proteins
pubmed
14585963
uniprot
proteins
pubmed
15050747
uniprot
proteins
pubmed
15166227
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15888917
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
17329398
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17634955
uniprot
proteins
pubmed
18086875
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
18339875
uniprot
proteins
pubmed
18587400
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18765415
uniprot
proteins
pubmed
18951788
uniprot
proteins
pubmed
19086031
uniprot
proteins
pubmed
19207108
uniprot
proteins
pubmed
19244237
uniprot
proteins
pubmed
19358827
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19428251
uniprot
proteins
pubmed
19648005
uniprot
proteins
pubmed
19880522
uniprot
proteins
pubmed
20001213
uniprot
proteins
pubmed
20028775
uniprot
proteins
pubmed
20332118
uniprot
proteins
pubmed
20381867
uniprot
proteins
pubmed
20521079
uniprot
proteins
pubmed
21196189
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21357692
uniprot
proteins
pubmed
21533080
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
7499242
uniprot
proteins
pubmed
7544443
uniprot
proteins
pubmed
7673154
uniprot
proteins
pubmed
8670418
uniprot
proteins
pubmed
8838818
uniprot
proteins
pubmed
8849729
uniprot
proteins
pubmed
9422762
uniprot
proteins
pubmed
9545257
uniprot
proteins
sequence_length
1009
uniprot
proteins
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.
uniprot
proteins