dbPTM

FAK1_RAT - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	FAK1_RAT
UniProt AC	O35346
Protein Name	Focal adhesion kinase 1
Gene Name	Ptk2
Organism	Rattus norvegicus (Rat).
Sequence Length	1055
Subcellular Localization	Cell junction, focal adhesion. Cell membrane Peripheral membrane protein Cytoplasmic side. Cytoplasm, perinuclear region. Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Nucleus. Constituent of focal adh
Protein 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 2 (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 (By similarity)..
Protein Sequence	MAAAYLDPNLNHTPSSSTKTHLGTGTERSPGAMERVLKVFHYFESSNEPTTWASIIRHGDATDVRGIIQKIVDSHKVKHVACYGFRLSHLRSEEVHWLHVDMGVSSVREKYELAHPPEEWKYELRIRYLPKGFLNQFTEDKPTLNFFYQQVKSDYMLEIADQVDQDIALKLGCLEIRRSYWEMRGNALEKKSNYEVLEKDVGLKRFFPKSLLDSVKAKTLRKLIQQTFRQFANLNREESILKFFEILSPVYRFDKECFKCALGSSWIISVELAIGPEEGISYLTDKGCNPTHLADFNQVQTIQYSNSEDKDRKGMLQLKIAGAPEPLTVTAPSLTIAENMADLIDGYCRLVNGATQSFIIRPQKEGERALPSIPKLANNEKQGMRTHAVSVSETDDYAEIIDEEDTYTMPSTRDYEIQRERIELGRCIGEGQFGDVHQGVYLSPENPALAVAIKTCKNCTSDSVREKFLQEALTMRQFDHPHIVKLIGVITENPVWIIMELCTLGELRSFLQVRKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSNDCVKLGDFGLSRYMEDSTYYKASKGKLPIKWMAPESINFRRFTSASDVWMFGVCMWEILMHGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLYSLMTKCWAYDPSRRPRFTELKAQLSTILEEEKVQQEERMRMESRRQATVSWDSGGSDEAPPKPSRPGYPSPRSSEGFYPSPQHMVQTNHYQISGYPGSHGIPAMAGSIYPGQASLLDQTELWNHRPQEMSMWQPSVEDSAALDLRGMGQVLPPHLMEERLIRQQQEMEEDQRWLEKEERFLKPDVRLSRGSIDREDGSFQGPTGNQHIYQPVGKPDPAAPPKKPPRPGAPGHLSNLSSISSPAESYNEGVKPWRLQPQEISPPPTANLDRSNDKVYENVTGLVKAVIEMSSKIQPAPPEEYVPMVKEVGLALRTLLATVDETIPILPASTHREIEMAQKLLNSDLGELISKMKLAQQYVMTSLQQEYKKQMLTAAHALAVDAKNLLDVIDQARLKMLGQTRPH

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MAAAYLDPN ------CCCCCCCCC	16.47	-
5	Phosphorylation	---MAAAYLDPNLNH ---CCCCCCCCCCCC	13.60	27097102
13	Phosphorylation	LDPNLNHTPSSSTKT CCCCCCCCCCCCCCC	24.64	27097102
15	Phosphorylation	PNLNHTPSSSTKTHL CCCCCCCCCCCCCCC	37.77	27097102
16	Phosphorylation	NLNHTPSSSTKTHLG CCCCCCCCCCCCCCC	43.14	27097102
17	Phosphorylation	LNHTPSSSTKTHLGT CCCCCCCCCCCCCCC	37.96	27097102
18	Phosphorylation	NHTPSSSTKTHLGTG CCCCCCCCCCCCCCC	41.74	27097102
20	Phosphorylation	TPSSSTKTHLGTGTE CCCCCCCCCCCCCCC	23.56	28432305
24	Phosphorylation	STKTHLGTGTERSPG CCCCCCCCCCCCCCC	47.49	28432305
26	Phosphorylation	KTHLGTGTERSPGAM CCCCCCCCCCCCCHH	28.23	28432305
29	Phosphorylation	LGTGTERSPGAMERV CCCCCCCCCCHHHHH	22.81	27097102
54	Phosphorylation	NEPTTWASIIRHGDA CCCCCHHHHHHCCCC	15.31	-
152	Sumoylation	NFFYQQVKSDYMLEI HHHHHHHCCCHHHHH	33.02	14500712
152	Sumoylation	NFFYQQVKSDYMLEI HHHHHHHCCCHHHHH	33.02	-
210	Phosphorylation	LKRFFPKSLLDSVKA CHHHCCHHHHHHHHH	34.11	22673903
214	Phosphorylation	FPKSLLDSVKAKTLR CCHHHHHHHHHHHHH	26.03	22673903
386	Phosphorylation	NEKQGMRTHAVSVSE CCCCCCCCEEEEECC	12.80	25575281
390	Phosphorylation	GMRTHAVSVSETDDY CCCCEEEEECCCCCC	22.25	22108457
392	Phosphorylation	RTHAVSVSETDDYAE CCEEEEECCCCCCHH	27.54	25575281
394	Phosphorylation	HAVSVSETDDYAEII EEEEECCCCCCHHCC	27.02	25575281
397	Phosphorylation	SVSETDDYAEIIDEE EECCCCCCHHCCCCC	14.67	16407217
406	Phosphorylation	EIIDEEDTYTMPSTR HCCCCCCCCCCCCCC	24.95	25575281
407	Phosphorylation	IIDEEDTYTMPSTRD CCCCCCCCCCCCCCC	17.23	16769082
568	Phosphorylation	KLGDFGLSRYMEDST EECCCCHHHHHCCCC	23.03	27097102
570	Phosphorylation	GDFGLSRYMEDSTYY CCCCHHHHHCCCCEE	11.07	27097102
574	Phosphorylation	LSRYMEDSTYYKASK HHHHHCCCCEECCCC	12.66	27097102
575	Phosphorylation	SRYMEDSTYYKASKG HHHHCCCCEECCCCC	43.10	27097102
576	Phosphorylation	RYMEDSTYYKASKGK HHHCCCCEECCCCCC	13.61	12912913
577	Phosphorylation	YMEDSTYYKASKGKL HHCCCCEECCCCCCC	10.52	12805241
580	Phosphorylation	DSTYYKASKGKLPIK CCCEECCCCCCCCCE	37.48	25575281
677	Phosphorylation	TELKAQLSTILEEEK HHHHHHHHHHHHHHH	11.00	27097102
678	Phosphorylation	ELKAQLSTILEEEKV HHHHHHHHHHHHHHH	37.87	27097102
700	Phosphorylation	MESRRQATVSWDSGG HHHHHHCEECCCCCC	13.51	27097102
702	Phosphorylation	SRRQATVSWDSGGSD HHHHCEECCCCCCCC	22.32	27097102
705	Phosphorylation	QATVSWDSGGSDEAP HCEECCCCCCCCCCC	38.50	27097102
708	Phosphorylation	VSWDSGGSDEAPPKP ECCCCCCCCCCCCCC	35.48	28432305
716	Phosphorylation	DEAPPKPSRPGYPSP CCCCCCCCCCCCCCC	58.18	28432305
720	Phosphorylation	PKPSRPGYPSPRSSE CCCCCCCCCCCCCCC	11.83	25575281
722	Phosphorylation	PSRPGYPSPRSSEGF CCCCCCCCCCCCCCC	25.18	29779826
732	Phosphorylation	SSEGFYPSPQHMVQT CCCCCCCCCCCEEEE	26.30	-
834	Acetylation	EKEERFLKPDVRLSR HHHHHHCCCCCEECC	36.14	22902405
840	Phosphorylation	LKPDVRLSRGSIDRE CCCCCEECCCCCCCC	24.83	29779826
843	Phosphorylation	DVRLSRGSIDREDGS CCEECCCCCCCCCCC	21.87	27097102
850	Phosphorylation	SIDREDGSFQGPTGN CCCCCCCCEECCCCC	27.07	27097102
855	Phosphorylation	DGSFQGPTGNQHIYQ CCCEECCCCCCEEEC	56.44	28432305
861	Phosphorylation	PTGNQHIYQPVGKPD CCCCCEEECCCCCCC	12.49	15576648
913	Phosphorylation	RLQPQEISPPPTANL CCCCCCCCCCCCCCC	30.51	28689409
917	Phosphorylation	QEISPPPTANLDRSN CCCCCCCCCCCCCCC	33.67	27097102
928	Phosphorylation	DRSNDKVYENVTGLV CCCCCHHHHCHHHHH	13.92	18757826

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
397	Y	Phosphorylation	Kinase	PTK2	Q05397	GPS
397	Y	Phosphorylation	Kinase	FAK	O35346	PSP
397	Y	Phosphorylation	Kinase	SRC	P12931	PSP
576	Y	Phosphorylation	Kinase	LYN	Q07014	PSP
577	Y	Phosphorylation	Kinase	LYN	Q07014	PSP
577	Y	Phosphorylation	Kinase	RET	G3V9H8	Uniprot
577	Y	Phosphorylation	Kinase	SRC	Q9WUD9	Uniprot
732	S	Phosphorylation	Kinase	CDK5	Q03114	Uniprot
928	Y	Phosphorylation	Kinase	FYN	P06241	PSP
928	Y	Phosphorylation	Kinase	SRC	Q9WUD9	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
722	S	Phosphorylation		12732587
Tyr-397, Tyr-576 and Ser-722 are phosphorylated only when cells are adherent.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of FAK1_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
BCAR1_RAT	Bcar1	physical	9038154

Drug and Disease Associations

Kegg Drug
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of FAK1_RAT

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Subcellular redistribution of focal adhesion kinase and its relatednonkinase in hypertrophic myocardium."; Yi X.P., Wang X., Gerdes A.M., Li F.; Hypertension 41:1317-1323(2003). Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-722 AND SER-913, ANDCHARACTERIZATION OF ISOFORM 2.	12732587 [Abstract]
"PIAS1-mediated sumoylation of focal adhesion kinase activates itsautophosphorylation."; Kadare G., Toutant M., Formstecher E., Corvol J.C., Carnaud M.,Boutterin M.C., Girault J.A.; J. Biol. Chem. 278:47434-47440(2003). Cited for: SUMOYLATION AT LYS-152, MUTAGENESIS OF LYS-152, INTERACTION WITHPIAS1, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-397, ANDSUBCELLULAR LOCATION.	14500712 [Abstract]
Sumoylation
Reference	PubMed
"PIAS1-mediated sumoylation of focal adhesion kinase activates itsautophosphorylation."; Kadare G., Toutant M., Formstecher E., Corvol J.C., Carnaud M.,Boutterin M.C., Girault J.A.; J. Biol. Chem. 278:47434-47440(2003). Cited for: SUMOYLATION AT LYS-152, MUTAGENESIS OF LYS-152, INTERACTION WITHPIAS1, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-397, ANDSUBCELLULAR LOCATION.	14500712 [Abstract]

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