CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011284
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Focal adhesion kinase 1 
Protein Synonyms/Alias
 FADK 1; Focal adhesion kinase-related nonkinase; FRNK; Protein phosphatase 1 regulatory subunit 71; PPP1R71; Protein-tyrosine kinase 2; p125FAK; pp125FAK 
Gene Name
 PTK2 
Gene Synonyms/Alias
 FAK; FAK1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
152NFFYQQVKSDYMLEIsumoylation[1]
Reference
 [1] PIAS1-mediated sumoylation of focal adhesion kinase activates its autophosphorylation.
 Kadaré G, Toutant M, Formstecher E, Corvol JC, Carnaud M, Boutterin MC, Girault JA.
 J Biol Chem. 2003 Nov 28;278(48):47434-40. [PMID: 14500712] 
Functional Description
 Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. 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 the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. 
Sequence Annotation
 DOMAIN 35 355 FERM.
 DOMAIN 422 680 Protein kinase.
 NP_BIND 428 434 ATP.
 NP_BIND 500 502 ATP.
 REGION 707 1052 Interaction with TGFB1I1.
 REGION 912 1052 Interaction with ARHGEF28 (By
 ACT_SITE 546 546 Proton acceptor (By similarity).
 BINDING 454 454 ATP.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 5 5 Phosphotyrosine.
 MOD_RES 13 13 Phosphothreonine.
 MOD_RES 29 29 Phosphoserine.
 MOD_RES 397 397 Phosphotyrosine; by autocatalysis.
 MOD_RES 407 407 Phosphotyrosine.
 MOD_RES 570 570 Phosphotyrosine.
 MOD_RES 576 576 Phosphotyrosine; by RET and SRC.
 MOD_RES 577 577 Phosphotyrosine; by RET and SRC.
 MOD_RES 580 580 Phosphoserine.
 MOD_RES 722 722 Phosphoserine.
 MOD_RES 732 732 Phosphoserine; by CDK5.
 MOD_RES 861 861 Phosphotyrosine.
 MOD_RES 887 887 Phosphoserine.
 MOD_RES 910 910 Phosphoserine.
 MOD_RES 914 914 Phosphothreonine.
 MOD_RES 925 925 Phosphotyrosine.
 CROSSLNK 152 152 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Acetylation; Alternative promoter usage; Alternative splicing; Angiogenesis; ATP-binding; Cell junction; Cell membrane; Complete proteome; Cytoplasm; Cytoskeleton; Developmental protein; Direct protein sequencing; Isopeptide bond; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Transferase; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1052 AA 
Protein Sequence
MAAAYLDPNL NHTPNSSTKT HLGTGMERSP GAMERVLKVF HYFESNSEPT TWASIIRHGD 60
ATDVRGIIQK IVDSHKVKHV ACYGFRLSHL RSEEVHWLHV DMGVSSVREK YELAHPPEEW 120
KYELRIRYLP KGFLNQFTED KPTLNFFYQQ VKSDYMLEIA DQVDQEIALK LGCLEIRRSY 180
WEMRGNALEK KSNYEVLEKD VGLKRFFPKS LLDSVKAKTL RKLIQQTFRQ FANLNREESI 240
LKFFEILSPV YRFDKECFKC ALGSSWIISV ELAIGPEEGI SYLTDKGCNP THLADFTQVQ 300
TIQYSNSEDK DRKGMLQLKI AGAPEPLTVT APSLTIAENM ADLIDGYCRL VNGTSQSFII 360
RPQKEGERAL PSIPKLANSE KQGMRTHAVS VSETDDYAEI IDEEDTYTMP STRDYEIQRE 420
RIELGRCIGE GQFGDVHQGI YMSPENPALA VAIKTCKNCT SDSVREKFLQ EALTMRQFDH 480
PHIVKLIGVI TENPVWIIME LCTLGELRSF LQVRKYSLDL ASLILYAYQL STALAYLESK 540
RFVHRDIAAR NVLVSSNDCV KLGDFGLSRY MEDSTYYKAS KGKLPIKWMA PESINFRRFT 600
SASDVWMFGV CMWEILMHGV KPFQGVKNND VIGRIENGER LPMPPNCPPT LYSLMTKCWA 660
YDPSRRPRFT ELKAQLSTIL EEEKAQQEER MRMESRRQAT VSWDSGGSDE APPKPSRPGY 720
PSPRSSEGFY PSPQHMVQTN HYQVSGYPGS HGITAMAGSI YPGQASLLDQ TDSWNHRPQE 780
IAMWQPNVED STVLDLRGIG QVLPTHLMEE RLIRQQQEME EDQRWLEKEE RFLKPDVRLS 840
RGSIDREDGS LQGPIGNQHI YQPVGKPDPA APPKKPPRPG APGHLGSLAS LSSPADSYNE 900
GVKLQPQEIS PPPTANLDRS NDKVYENVTG LVKAVIEMSS KIQPAPPEEY VPMVKEVGLA 960
LRTLLATVDE TIPLLPASTH REIEMAQKLL NSDLGELINK MKLAQQYVMT SLQQEYKKQM 1020
LTAAHALAVD AKNLLDVIDQ ARLKMLGQTR PH 1052 
Gene Ontology
 GO:0016324; C:apical plasma membrane; IEA:Compara.
 GO:0016323; C:basolateral plasma membrane; IEA:Compara.
 GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
 GO:0005856; C:cytoskeleton; TAS:ProtInc.
 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0005925; C:focal adhesion; IDA:UniProtKB.
 GO:0014704; C:intercalated disc; IEA:Compara.
 GO:0030027; C:lamellipodium; IEA:Compara.
 GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
 GO:0016604; C:nuclear body; IEA:Compara.
 GO:0005730; C:nucleolus; IEA:Compara.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0042383; C:sarcolemma; IEA:Compara.
 GO:0003779; F:actin binding; IDA:BHF-UCL.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0008432; F:JUN kinase binding; IDA:BHF-UCL.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
 GO:0004871; F:signal transducer activity; IEA:InterPro.
 GO:0001525; P:angiogenesis; TAS:UniProtKB.
 GO:0007411; P:axon guidance; TAS:UniProtKB.
 GO:0048870; P:cell motility; TAS:UniProtKB.
 GO:0030644; P:cellular chloride ion homeostasis; IEA:Compara.
 GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; TAS:Reactome.
 GO:0021955; P:central nervous system neuron axonogenesis; IEA:Compara.
 GO:0009790; P:embryo development; TAS:UniProtKB.
 GO:0043542; P:endothelial cell migration; IEA:Compara.
 GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB.
 GO:0030010; P:establishment of cell polarity; TAS:UniProtKB.
 GO:0040023; P:establishment of nucleus localization; IEA:Compara.
 GO:0030198; P:extracellular matrix organization; IEA:Compara.
 GO:0045444; P:fat cell differentiation; IEA:Compara.
 GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
 GO:0060396; P:growth hormone receptor signaling pathway; IDA:BHF-UCL.
 GO:0003007; P:heart morphogenesis; TAS:UniProtKB.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0007229; P:integrin-mediated signaling pathway; IMP:UniProtKB.
 GO:0007254; P:JNK cascade; IEA:Compara.
 GO:0000226; P:microtubule cytoskeleton organization; IEA:Compara.
 GO:2000811; P:negative regulation of anoikis; IMP:UniProtKB.
 GO:0050771; P:negative regulation of axonogenesis; IEA:Compara.
 GO:0030336; P:negative regulation of cell migration; IEA:Compara.
 GO:0022408; P:negative regulation of cell-cell adhesion; IDA:BHF-UCL.
 GO:0046621; P:negative regulation of organ growth; IEA:Compara.
 GO:0051964; P:negative regulation of synapse assembly; IEA:Compara.
 GO:0038007; P:netrin-activated signaling pathway; TAS:UniProtKB.
 GO:0001764; P:neuron migration; IEA:Compara.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
 GO:0001890; P:placenta development; TAS:UniProtKB.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0045785; P:positive regulation of cell adhesion; IEA:Compara.
 GO:0030307; P:positive regulation of cell growth; IEA:Compara.
 GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
 GO:0008284; P:positive regulation of cell proliferation; ISS:UniProtKB.
 GO:0060252; P:positive regulation of glial cell proliferation; IEA:Compara.
 GO:0050766; P:positive regulation of phagocytosis; IEA:Compara.
 GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; TAS:UniProtKB.
 GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase cascade; IMP:UniProtKB.
 GO:0045860; P:positive regulation of protein kinase activity; IMP:UniProtKB.
 GO:0051897; P:positive regulation of protein kinase B signaling cascade; IMP:UniProtKB.
 GO:2000060; P:positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
 GO:0014911; P:positive regulation of smooth muscle cell migration; IEA:Compara.
 GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Compara.
 GO:0050806; P:positive regulation of synaptic transmission; IEA:Compara.
 GO:0045909; P:positive regulation of vasodilation; IEA:Compara.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:0033628; P:regulation of cell adhesion mediated by integrin; IDA:UniProtKB.
 GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
 GO:0051493; P:regulation of cytoskeleton organization; TAS:UniProtKB.
 GO:0010594; P:regulation of endothelial cell migration; TAS:UniProtKB.
 GO:0051893; P:regulation of focal adhesion assembly; TAS:UniProtKB.
 GO:0045667; P:regulation of osteoblast differentiation; IMP:UniProtKB.
 GO:0032319; P:regulation of Rho GTPase activity; TAS:UniProtKB.
 GO:0046685; P:response to arsenic-containing substance; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0032355; P:response to estradiol stimulus; IEA:Compara.
 GO:0009749; P:response to glucose stimulus; IEA:Compara.
 GO:0009612; P:response to mechanical stimulus; IEA:Compara.
 GO:0007172; P:signal complex assembly; IEA:InterPro.
 GO:0001570; P:vasculogenesis; IEA:Compara. 
Interpro
 IPR019749; Band_41_domain.
 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.