ID  Q9QVP9;
PN  Protein-tyrosine kinase 2-beta;
GN  Ptk2b;
OS  10090;
SL  Nucleus Position: SL-0198;
SL  Comments: Cytoplasm. Cytoplasm, perinuclear region {ECO:0000250}. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell junction, focal adhesion. Cell projection, lamellipodium {ECO:0000250}. Cytoplasm, cell cortex {ECO:0000250}. Nucleus {ECO:0000250}. Note=Colocalizes with integrins at the cell periphery (By similarity). Interaction with NPHP1 induces the membrane- association of the kinase. Colocalizes with PXN at the microtubule- organizing center. The tyrosine phosphorylated form is detected at cell-cell contacts. {ECO:0000250}.
DR  UNIPROT: Q9QVP9;
DR  UNIPROT: B2RQ16;
DR  UNIPROT: G3X8V1;
DR  Pfam: PF00373;
DR  Pfam: PF18038;
DR  Pfam: PF03623;
DR  Pfam: PF07714;
DR  PROSITE: PS50057;
DR  PROSITE: PS00107;
DR  PROSITE: PS50011;
DR  PROSITE: PS00109;
DE  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' (By similarity). 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 (By similarity). {ECO:0000250, ECO:0000269|PubMed:10881171, ECO:0000269|PubMed:11238453, ECO:0000269|PubMed:12960403, ECO:0000269|PubMed:14739300, ECO:0000269|PubMed:17537919, ECO:0000269|PubMed:17698736, ECO:0000269|PubMed:17846174, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:19561089, ECO:0000269|PubMed:19880522, ECO:0000269|PubMed:20688918, ECO:0000269|PubMed:21640103}.
DE  Reference Proteome: Yes;
DE  Interaction: P16054; IntAct: EBI-298523; Score: 0.35
DE  Interaction: P35438; IntAct: EBI-396959; Score: 0.46
DE  Interaction: Q9QWY8; IntAct: EBI-8651469; Score: 0.65
DE  Interaction: P59240; IntAct: EBI-11790541; Score: 0.40
DE  Interaction: Q9EPK7; IntAct: EBI-17171503; Score: 0.35
DE  Interaction: Q8BIZ1; IntAct: EBI-26595802; Score: 0.35
DE  Interaction: Q8VI24; IntAct: EBI-26885104; Score: 0.35
GO  GO:0097440;
GO  GO:0030424;
GO  GO:0044297;
GO  GO:0005938;
GO  GO:0042995;
GO  GO:0005856;
GO  GO:0030425;
GO  GO:0043197;
GO  GO:0031234;
GO  GO:0005925;
GO  GO:0098978;
GO  GO:0030426;
GO  GO:0030027;
GO  GO:0045121;
GO  GO:0043025;
GO  GO:0017146;
GO  GO:0005634;
GO  GO:0048471;
GO  GO:0098794;
GO  GO:0014069;
GO  GO:0043423;
GO  GO:0005524;
GO  GO:0004683;
GO  GO:0019899;
GO  GO:0004972;
GO  GO:0004715;
GO  GO:0008022;
GO  GO:0004672;
GO  GO:0043621;
GO  GO:0004713;
GO  GO:0044877;
GO  GO:0005102;
GO  GO:0031625;
GO  GO:0007015;
GO  GO:0090630;
GO  GO:0042976;
GO  GO:0002250;
GO  GO:0001525;
GO  GO:0043534;
GO  GO:0045453;
GO  GO:0007155;
GO  GO:0030154;
GO  GO:0007166;
GO  GO:0006968;
GO  GO:0071498;
GO  GO:0071300;
GO  GO:0070098;
GO  GO:0086100;
GO  GO:0007173;
GO  GO:0048041;
GO  GO:0014009;
GO  GO:0045087;
GO  GO:0007229;
GO  GO:0035235;
GO  GO:0060292;
GO  GO:0060291;
GO  GO:0000165;
GO  GO:0002315;
GO  GO:0043066;
GO  GO:0030502;
GO  GO:0008285;
GO  GO:0010656;
GO  GO:0045638;
GO  GO:0043524;
GO  GO:0030279;
GO  GO:0043267;
GO  GO:0031175;
GO  GO:0001556;
GO  GO:0038083;
GO  GO:0018108;
GO  GO:0030838;
GO  GO:0045766;
GO  GO:2000538;
GO  GO:0030307;
GO  GO:0030335;
GO  GO:0008284;
GO  GO:0001954;
GO  GO:0007204;
GO  GO:2000573;
GO  GO:0010595;
GO  GO:0070374;
GO  GO:2000463;
GO  GO:0046330;
GO  GO:0043507;
GO  GO:0010976;
GO  GO:0045429;
GO  GO:0051000;
GO  GO:0050731;
GO  GO:0043552;
GO  GO:0045860;
GO  GO:0051247;
GO  GO:2000379;
GO  GO:0051968;
GO  GO:0045727;
GO  GO:2000060;
GO  GO:0006468;
GO  GO:2000249;
GO  GO:0050848;
GO  GO:0030155;
GO  GO:0008360;
GO  GO:0010752;
GO  GO:2000114;
GO  GO:0032960;
GO  GO:0010758;
GO  GO:0045428;
GO  GO:2000310;
GO  GO:0051279;
GO  GO:2000058;
GO  GO:0051592;
GO  GO:0051591;
GO  GO:0043157;
GO  GO:0042220;
GO  GO:0045471;
GO  GO:0009749;
GO  GO:0009725;
GO  GO:0042542;
GO  GO:0001666;
GO  GO:0035902;
GO  GO:0002931;
GO  GO:0010226;
GO  GO:0009612;
GO  GO:0009410;
GO  GO:0007172;
GO  GO:0002040;
GO  GO:0043149;
GO  GO:0007169;
GO  GO:0033209;
GO  GO:0048010;
TP  Membrane Topology: Peripheral; Source: UniProt - Sequence Analysis;
SQ  MSGVSEPLSRVKVGTLRRPEGPPEPMVVVPVDVEKEDVRILKVCFYSNSFNPGKNFKLVKCTVQTEIQEIITSILLSGRI
SQ  GPNIQLAECYGLRLKHMKSDEIHWLHPQMTVGEVQDKYECLHVEAEWRYDLQIRYLPEDFMESLKEDRTTLLYFYQQLRN
SQ  DYMQRYASKVSEGMALQLGCLELRRFFKDMPHNALDKKSNFELLEKEVGLDLFFPKQMQENLKPKQFRKMIQQTFQQYAS
SQ  LREEECVMKFFNTLAGFANIDQETYRCELIQGWNITVDLVIGPKGIRQLTSQDTKPTCLAEFKQIKSIRCLPLEETQAVL
SQ  QLGIEGAPQSLSIKTSSLAEAENMADLIDGYCRLQGEHKGSLIMHAKKDGEKRNSLPQIPTLNLEARRSHLSESCSIESD
SQ  IYAEIPDETLRRPGGPQYGVAREEVVLNRILGEGFFGEVYEGVYTNHKGEKINVAVKTCKKDCTQDNKEKFMSEAVIMKN
SQ  LDHPHIVKLIGIIEEEPTWIIMELYPYGELGHYLERNKNSLKVPTLVLYTLQICKAMAYLESINCVHRDIAVRNILVASP
SQ  ECVKLGDFGLSRYIEDEDYYKASVTRLPIKWMSPESINFRRFTTASDVWMFAVCMWEILSFGKQPFFWLENKDVIGVLEK
SQ  GDRLPKPELCPPVLYTLMTRCWDYDPSDRPRFTELVCSLSDIYQMEKDIAIEQERNARYRPPKILEPTTFQEPPPKPSRP
SQ  KYRPPPQTNLLAPKLQFQVPEGLCASSPTLTSPMEYPSPVNSLHTPPLHRHNVFKRHSMREEDFIRPSSREEAQQLWEAE
SQ  KIKMKQVLERQQKQMVEDSQWLRREERCLDPMVYMNDKSPLTPEKEAGYTEFTGPPQKPPRLGAQSIQPTANLDRTDDLV
SQ  YHNVMTLVEAVLELKNKLGQLPPEDYVVVVKNVGLNLRKLIGSVDDLLPSLPASSRTEIEGTQKLLNKDLAELINKMKLA
SQ  QQNAVTSLSEDCKRQMLTASHTLAVDAKNLLDAVDQAKVVANLAHPPAE
//