CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012302
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Protein-tyrosine kinase 2-beta 
Protein Synonyms/Alias
 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 Name
 PTK2B 
Gene Synonyms/Alias
 FAK2; PYK2; RAFTK 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
188LELRRFFKDMPHNALubiquitination[1, 2]
295QLTSQDAKPTCLAEFubiquitination[3]
581IEDEDYYKASVTRLPubiquitination[3]
944TEIEGTQKLLNKDLAubiquitination[1, 2]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 39 359 FERM.
 DOMAIN 425 683 Protein kinase.
 NP_BIND 431 439 ATP.
 NP_BIND 503 509 ATP.
 REGION 801 1009 Interaction with TGFB1I1 (By similarity).
 REGION 868 1009 Focal adhesion targeting (FAT).
 ACT_SITE 549 549 Proton acceptor (By similarity).
 BINDING 457 457 ATP.
 MOD_RES 361 361 Phosphoserine.
 MOD_RES 375 375 Phosphoserine.
 MOD_RES 399 399 Phosphoserine.
 MOD_RES 402 402 Phosphotyrosine; by autocatalysis.
 MOD_RES 440 440 Phosphotyrosine (By similarity).
 MOD_RES 579 579 Phosphotyrosine; by SRC, LYN and LCK.
 MOD_RES 580 580 Phosphotyrosine; by SRC, LYN and LCK.
 MOD_RES 722 722 Phosphotyrosine.
 MOD_RES 762 762 Phosphoserine.
 MOD_RES 765 765 Phosphothreonine.
 MOD_RES 819 819 Phosphotyrosine.
 MOD_RES 834 834 Phosphotyrosine.
 MOD_RES 839 839 Phosphoserine.
 MOD_RES 842 842 Phosphothreonine.
 MOD_RES 849 849 Phosphotyrosine.
 MOD_RES 866 866 Phosphoserine.
 MOD_RES 881 881 Phosphotyrosine; by SRC.  
Keyword
 3D-structure; Adaptive immunity; Alternative splicing; Angiogenesis; ATP-binding; Cell junction; Cell membrane; Cell projection; Complete proteome; Cytoplasm; Immunity; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Transferase; Tyrosine-protein kinase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1009 AA 
Protein Sequence
MSGVSEPLSR VKLGTLRRPE GPAEPMVVVP VDVEKEDVRI LKVCFYSNSF NPGKNFKLVK 60
CTVQTEIREI ITSILLSGRI GPNIRLAECY GLRLKHMKSD EIHWLHPQMT VGEVQDKYEC 120
LHVEAEWRYD LQIRYLPEDF MESLKEDRTT LLYFYQQLRN DYMQRYASKV SEGMALQLGC 180
LELRRFFKDM PHNALDKKSN FELLEKEVGL DLFFPKQMQE NLKPKQFRKM IQQTFQQYAS 240
LREEECVMKF FNTLAGFANI DQETYRCELI QGWNITVDLV IGPKGIRQLT SQDAKPTCLA 300
EFKQIRSIRC LPLEEGQAVL QLGIEGAPQA LSIKTSSLAE AENMADLIDG YCRLQGEHQG 360
SLIIHPRKDG EKRNSLPQIP MLNLEARRSH LSESCSIESD IYAEIPDETL RRPGGPQYGI 420
AREDVVLNRI LGEGFFGEVY EGVYTNHKGE KINVAVKTCK KDCTLDNKEK FMSEAVIMKN 480
LDHPHIVKLI GIIEEEPTWI IMELYPYGEL GHYLERNKNS LKVLTLVLYS LQICKAMAYL 540
ESINCVHRDI AVRNILVASP ECVKLGDFGL SRYIEDEDYY KASVTRLPIK WMSPESINFR 600
RFTTASDVWM FAVCMWEILS FGKQPFFWLE NKDVIGVLEK GDRLPKPDLC PPVLYTLMTR 660
CWDYDPSDRP RFTELVCSLS DVYQMEKDIA MEQERNARYR TPKILEPTAF QEPPPKPSRP 720
KYRPPPQTNL LAPKLQFQVP EGLCASSPTL TSPMEYPSPV NSLHTPPLHR HNVFKRHSMR 780
EEDFIQPSSR EEAQQLWEAE KVKMRQILDK QQKQMVEDYQ WLRQEEKSLD PMVYMNDKSP 840
LTPEKEVGYL EFTGPPQKPP RLGAQSIQPT ANLDRTDDLV YLNVMELVRA VLELKNELCQ 900
LPPEGYVVVV KNVGLTLRKL IGSVDDLLPS LPSSSRTEIE GTQKLLNKDL AELINKMRLA 960
QQNAVTSLSE ECKRQMLTAS HTLAVDAKNL LDAVDQAKVL ANLAHPPAE 1009 
Gene Ontology
 GO:0030424; C:axon; IEA:Compara.
 GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005925; C:focal adhesion; IDA:UniProtKB.
 GO:0030426; C:growth cone; IEA:Compara.
 GO:0030027; C:lamellipodium; IDA:UniProtKB.
 GO:0045121; C:membrane raft; IEA:Compara.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
 GO:0014069; C:postsynaptic density; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
 GO:0004871; F:signal transducer activity; NAS:ProtInc.
 GO:0042976; P:activation of Janus kinase activity; IMP:UniProtKB.
 GO:0032863; P:activation of Rac GTPase activity; IEA:Compara.
 GO:0006915; P:apoptotic process; TAS:ProtInc.
 GO:0043534; P:blood vessel endothelial cell migration; IEA:Compara.
 GO:0045453; P:bone resorption; ISS:UniProtKB.
 GO:0071300; P:cellular response to retinoic acid; IMP:BHF-UCL.
 GO:0070098; P:chemokine-mediated signaling pathway; ISS:UniProtKB.
 GO:0007204; P:elevation of cytosolic calcium ion concentration; IEA:Compara.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; IEA:Compara.
 GO:0048041; P:focal adhesion assembly; IEA:Compara.
 GO:0014009; P:glial cell proliferation; IEA:Compara.
 GO:0007229; P:integrin-mediated signaling pathway; IMP:UniProtKB.
 GO:0000165; P:MAPK cascade; IEA:Compara.
 GO:0002315; P:marginal zone B cell differentiation; ISS:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
 GO:0030502; P:negative regulation of bone mineralization; ISS:UniProtKB.
 GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB.
 GO:0045638; P:negative regulation of myeloid cell differentiation; IMP:UniProtKB.
 GO:0043267; P:negative regulation of potassium ion transport; IDA:UniProtKB.
 GO:0031175; P:neuron projection development; IEA:Compara.
 GO:0001556; P:oocyte maturation; IEA:Compara.
 GO:0030838; P:positive regulation of actin filament polymerization; IMP:UniProtKB.
 GO:0045766; P:positive regulation of angiogenesis; IEA:Compara.
 GO:2000538; P:positive regulation of B cell chemotaxis; ISS:UniProtKB.
 GO:0030307; P:positive regulation of cell growth; IEA:Compara.
 GO:0008284; P:positive regulation of cell proliferation; IMP:UniProtKB.
 GO:0001954; P:positive regulation of cell-matrix adhesion; IMP:UniProtKB.
 GO:0010595; P:positive regulation of endothelial cell migration; IDA:BHF-UCL.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
 GO:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB.
 GO:0043507; P:positive regulation of JUN kinase activity; IEA:Compara.
 GO:0010976; P:positive regulation of neuron projection development; IMP:BHF-UCL.
 GO:0051000; P:positive regulation of nitric-oxide synthase activity; IEA:Compara.
 GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL.
 GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISS:UniProtKB.
 GO:2000060; P:positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IEA:Compara.
 GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IEA:Compara.
 GO:0045727; P:positive regulation of translation; IEA:Compara.
 GO:0046777; P:protein autophosphorylation; TAS:UniProtKB.
 GO:2000249; P:regulation of actin cytoskeleton reorganization; ISS:UniProtKB.
 GO:0050848; P:regulation of calcium-mediated signaling; IEA:Compara.
 GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
 GO:0030826; P:regulation of cGMP biosynthetic process; IEA:Compara.
 GO:0010752; P:regulation of cGMP-mediated signaling; IEA:Compara.
 GO:2000114; P:regulation of establishment of cell polarity; ISS:UniProtKB.
 GO:0032960; P:regulation of inositol trisphosphate biosynthetic process; ISS:UniProtKB.
 GO:0010758; P:regulation of macrophage chemotaxis; ISS:UniProtKB.
 GO:0045428; P:regulation of nitric oxide biosynthetic process; IEA:Compara.
 GO:2000058; P:regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
 GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; ISS:UniProtKB.
 GO:0051592; P:response to calcium ion; IEA:Compara.
 GO:0051591; P:response to cAMP; IEA:Compara.
 GO:0042220; P:response to cocaine; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0045471; P:response to ethanol; IEA:Compara.
 GO:0009749; P:response to glucose stimulus; IEA:Compara.
 GO:0009725; P:response to hormone stimulus; IEA:Compara.
 GO:0042542; P:response to hydrogen peroxide; IEA:Compara.
 GO:0001666; P:response to hypoxia; IEA:Compara.
 GO:0010226; P:response to lithium ion; IEA:Compara.
 GO:0009612; P:response to mechanical stimulus; IEA:Compara.
 GO:0006970; P:response to osmotic stress; IEA:Compara.
 GO:0006950; P:response to stress; TAS:ProtInc.
 GO:0007172; P:signal complex assembly; TAS:ProtInc.
 GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB.
 GO:0043149; P:stress fiber assembly; IEA:Compara.
 GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB.
 GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IMP:BHF-UCL. 
Interpro
 IPR019749; Band_41_domain.
 IPR014352; FERM/acyl-CoA-bd_prot_3-hlx.
 IPR019748; FERM_central.
 IPR000299; FERM_domain.
 IPR005189; Focal_adhesion_kin_target_dom.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom. 
Pfam
 PF00373; FERM_M
 PF03623; Focal_AT
 PF07714; Pkinase_Tyr 
SMART
 SM00295; B41
 SM00219; TyrKc 
PROSITE
 PS00660; FERM_1
 PS00661; FERM_2
 PS50057; FERM_3
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR 
PRINTS
 PR00109; TYRKINASE.