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Overview

Uniprot ID	Q14289
Protein Name	Protein-tyrosine kinase 2-beta
Gene Name	PTK2B
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
721	PPKPSRPKYRPPPQT

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

Protein Sequence

10 MSGVSEPLSR 20 VKLGTLRRPE 30 GPAEPMVVVP 40 VDVEKEDVRI 50 LKVCFYSNSF 60 NPGKNFKLVK 70 CTVQTEIREI 80 ITSILLSGRI 90 GPNIRLAECY 100 GLRLKHMKSD 110 EIHWLHPQMT 120 VGEVQDKYEC 130 LHVEAEWRYD 140 LQIRYLPEDF 150 MESLKEDRTT 160 LLYFYQQLRN 170 DYMQRYASKV 180 SEGMALQLGC 190 LELRRFFKDM 200 PHNALDKKSN 210 FELLEKEVGL 220 DLFFPKQMQE 230 NLKPKQFRKM 240 IQQTFQQYAS 250 LREEECVMKF 260 FNTLAGFANI 270 DQETYRCELI 280 QGWNITVDLV 290 IGPKGIRQLT 300 SQDAKPTCLA 310 EFKQIRSIRC 320 LPLEEGQAVL 330 QLGIEGAPQA 340 LSIKTSSLAE 350 AENMADLIDG 360 YCRLQGEHQG 370 SLIIHPRKDG 380 EKRNSLPQIP 390 MLNLEARRSH 400 LSESCSIESD 410 IYAEIPDETL 420 RRPGGPQYGI 430 AREDVVLNRI 440 LGEGFFGEVY 450 EGVYTNHKGE 460 KINVAVKTCK 470 KDCTLDNKEK 480 FMSEAVIMKN 490 LDHPHIVKLI 500 GIIEEEPTWI 510 IMELYPYGEL 520 GHYLERNKNS 530 LKVLTLVLYS 540 LQICKAMAYL 550 ESINCVHRDI 560 AVRNILVASP 570 ECVKLGDFGL 580 SRYIEDEDYY 590 KASVTRLPIK 600 WMSPESINFR 610 RFTTASDVWM 620 FAVCMWEILS 630 FGKQPFFWLE 640 NKDVIGVLEK 650 GDRLPKPDLC 660 PPVLYTLMTR 670 CWDYDPSDRP 680 RFTELVCSLS 690 DVYQMEKDIA 700 MEQERNARYR 710 TPKILEPTAF 720 QEPPPKPSRP 730 KYRPPPQTNL 740 LAPKLQFQVP 750 EGLCASSPTL 760 TSPMEYPSPV 770 NSLHTPPLHR 780 HNVFKRHSMR 790 EEDFIQPSSR 800 EEAQQLWEAE 810 KVKMRQILDK 820 QQKQMVEDYQ 830 WLRQEEKSLD 840 PMVYMNDKSP 850 LTPEKEVGYL 860 EFTGPPQKPP 870 RLGAQSIQPT 880 ANLDRTDDLV 890 YLNVMELVRA 900 VLELKNELCQ 910 LPPEGYVVVV 920 KNVGLTLRKL 930 IGSVDDLLPS 940 LPSSSRTEIE 950 GTQKLLNKDL 960 AELINKMRLA 970 QQNAVTSLSE 980 ECKRQMLTAS 990 HTLAVDAKNL 1000 LDAVDQAKVL ANLAHPPAE

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0097440	apical dendrite
Cellular Component	GO:0044297	cell body
Cellular Component	GO:0005938	cell cortex
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0030425	dendrite
Cellular Component	GO:0005925	focal adhesion
Cellular Component	GO:0098978	glutamatergic synapse
Cellular Component	GO:0030426	growth cone
Cellular Component	GO:0030027	lamellipodium
Cellular Component	GO:0043025	neuronal cell body
Cellular Component	GO:0017146	NMDA selective glutamate receptor complex
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0048471	perinuclear region of cytoplasm
Cellular Component	GO:0005886	plasma membrane
Cellular Component	GO:0014069	postsynaptic density
Cellular Component	GO:0099092	postsynaptic density, intracellular component
Cellular Component	GO:0098793	presynapse
Molecular Function	GO:0005524	ATP binding
Molecular Function	GO:0004683	calcium/calmodulin-dependent protein kinase activity
Molecular Function	GO:0035255	ionotropic glutamate receptor binding
Molecular Function	GO:0099602	neurotransmitter receptor regulator activity
Molecular Function	GO:0004715	non-membrane spanning protein tyrosine kinase activity
Molecular Function	GO:0004713	protein tyrosine kinase activity
Molecular Function	GO:0030546	signaling receptor activator activity
Biological Process	GO:0042976	activation of Janus kinase activity
Biological Process	GO:0002250	adaptive immune response
Biological Process	GO:0006915	apoptotic process
Biological Process	GO:0045453	bone resorption
Biological Process	GO:0007166	cell surface receptor signaling pathway
Biological Process	GO:0006968	cellular defense response
Biological Process	GO:0071300	cellular response to retinoic acid
Biological Process	GO:0070098	chemokine-mediated signaling pathway
Biological Process	GO:0030865	cortical cytoskeleton organization
Biological Process	GO:0086100	endothelin receptor signaling pathway
Biological Process	GO:0007173	epidermal growth factor receptor signaling pathway
Biological Process	GO:0007229	integrin-mediated signaling pathway
Biological Process	GO:0035235	ionotropic glutamate receptor signaling pathway
Biological Process	GO:0060291	long-term synaptic potentiation
Biological Process	GO:0002315	marginal zone B cell differentiation
Biological Process	GO:0043066	negative regulation of apoptotic process
Biological Process	GO:0030502	negative regulation of bone mineralization
Biological Process	GO:0008285	negative regulation of cell population proliferation
Biological Process	GO:0045638	negative regulation of myeloid cell differentiation
Biological Process	GO:0043524	negative regulation of neuron apoptotic process
Biological Process	GO:0043267	negative regulation of potassium ion transport
Biological Process	GO:0038083	peptidyl-tyrosine autophosphorylation
Biological Process	GO:0018108	peptidyl-tyrosine phosphorylation
Biological Process	GO:0030838	positive regulation of actin filament polymerization
Biological Process	GO:0045766	positive regulation of angiogenesis
Biological Process	GO:2000538	positive regulation of B cell chemotaxis
Biological Process	GO:0030335	positive regulation of cell migration
Biological Process	GO:0008284	positive regulation of cell population proliferation
Biological Process	GO:0001954	positive regulation of cell-matrix adhesion
Biological Process	GO:0010595	positive regulation of endothelial cell migration
Biological Process	GO:0070374	positive regulation of ERK1 and ERK2 cascade
Biological Process	GO:2000463	positive regulation of excitatory postsynaptic potential
Biological Process	GO:0046330	positive regulation of JNK cascade
Biological Process	GO:0010976	positive regulation of neuron projection development
Biological Process	GO:0051897	positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Process	GO:0045860	positive regulation of protein kinase activity
Biological Process	GO:0051968	positive regulation of synaptic transmission, glutamatergic
Biological Process	GO:2000060	positive regulation of ubiquitin-dependent protein catabolic process
Biological Process	GO:0046777	protein autophosphorylation
Biological Process	GO:0065003	protein-containing complex assembly
Biological Process	GO:0032956	regulation of actin cytoskeleton organization
Biological Process	GO:0030155	regulation of cell adhesion
Biological Process	GO:0008360	regulation of cell shape
Biological Process	GO:0010758	regulation of macrophage chemotaxis
Biological Process	GO:0099151	regulation of postsynaptic density assembly
Biological Process	GO:0051279	regulation of release of sequestered calcium ion into cytosol
Biological Process	GO:0048167	regulation of synaptic plasticity
Biological Process	GO:2000058	regulation of ubiquitin-dependent protein catabolic process
Biological Process	GO:0007172	signal complex assembly
Biological Process	GO:0007165	signal transduction
Biological Process	GO:0002040	sprouting angiogenesis
Biological Process	GO:0033209	tumor necrosis factor-mediated signaling pathway
Biological Process	GO:0048010	vascular endothelial growth factor receptor signaling pathway

Reference

[1] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.