dbPTM

FAK1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	FAK1_MOUSE
UniProt AC	P34152
Protein Name	Focal adhesion kinase 1
Gene Name	Ptk2
Organism	Mus musculus (Mouse).
Sequence Length	1090
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 9 (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	MAAAYLDPNLNHTPSSSTKTHLGTGMERSPGAMERVLKVFHYFESSSEPTTWASIIRHGDATDVRGIIQKIVDSHKVKHVACYGFRLSHLRSEEVHWLHVDMGVSSVREKYELAHPPEEWKYELRIRYLPKGFLNQFTEDKPTLNFFYQQVKSDYMQEIADQVDQEIALKLGCLEIRRSYWEMRGNALEKKSNYEVLEKDVGLKRFFPKSLLDSVKAKTLRKLIQQTFRQFANLNREESILKFFEILSPVYRFDKECFKCALGSSWIISVELAIGPEEGISYLTDKGCNPTHLADFNQVQTIQYSNSEDKDRKGMLQLKIAGAPEPLTVTAPSLTIAENMADLIDGYCRLVNGATQSFIIRPQKEGERALPSIPKLANSEKQGMRTHAVSVSHCQHKVKKARRFLPLVFCSLEPPPTDEISGDETDDYAEIIDEEDTYTMPSKSYGIDEARDYEIQRERIELGRCIGEGQFGDVHQGVYLSPENPALAVAIKTCKNCTSDSVREKFLQEALTMRQFDHPHIVKLIGVITENPVWIIMELCTLGELRSFLQVRKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSNDCVKLGDFGLSRYMEDSTYYKASKGKLPIKWMAPESINFRRFTSASDVWMFGVCMWEILMHGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLYSLMTKCWAYDPSRRPRFTELKAQLSTILEEEKVQQEERMRMESRRQATVSWDSGGSDEAPPKPSRPGYPSPRSSEGFYPSPQHMVQTNHYQVSGYPGSHGIPAMAGSIYQGQASLLDQTELWNHRPQEMSMWQPSVEDSAALDLRGMGQVLPPHLMEERLIRQQQEMEEDQRWLEKEERFLKPDVRLSRGSIDREDGSFQGPTGNQHIYQPVGKPDPAAPPKKPPRPGAPGHLSNLSSISSPADSYNEGVKLQPQEISPPPTANLDRSNDKVYENVTGLVKAVIEMSSKIQPAPPEEYVPMVKEVGLALRTLLATVDETIPALPASTHREIEMAQKLLNSDLGELISKMKLAQQYVMTSLQQEYKKQMLTAAHALAVDAKNLLDVIDQARLKMLGQTRPH

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	22499769
13	Phosphorylation	LDPNLNHTPSSSTKT CCCCCCCCCCCCCCC	24.64	22499769
15	Phosphorylation	PNLNHTPSSSTKTHL CCCCCCCCCCCCCCC	37.77	28066266
16	Phosphorylation	NLNHTPSSSTKTHLG CCCCCCCCCCCCCCC	43.14	28066266
17	Phosphorylation	LNHTPSSSTKTHLGT CCCCCCCCCCCCCCC	37.96	28066266
18	Phosphorylation	NHTPSSSTKTHLGTG CCCCCCCCCCCCCCC	41.74	22499769
20	Phosphorylation	TPSSSTKTHLGTGME CCCCCCCCCCCCCCC	23.56	26643407
24	Phosphorylation	STKTHLGTGMERSPG CCCCCCCCCCCCCCC	39.45	26643407
29	Phosphorylation	LGTGMERSPGAMERV CCCCCCCCCCHHHHH	17.87	26643407
45	Phosphorylation	KVFHYFESSSEPTTW HHHHHHCCCCCCCCH	29.30	-
51	Phosphorylation	ESSSEPTTWASIIRH CCCCCCCCHHHHHHC	29.74	21183079
54	Phosphorylation	SEPTTWASIIRHGDA CCCCCHHHHHHCCCC	15.31	19060867
83	Phosphorylation	KVKHVACYGFRLSHL CCCEEEEECEEHHHH	15.01	-
192	Phosphorylation	GNALEKKSNYEVLEK CCHHHHHCCHHHHHH	56.57	-
194	Phosphorylation	ALEKKSNYEVLEKDV HHHHHCCHHHHHHHH	17.95	29514104
313	Acetylation	NSEDKDRKGMLQLKI CCCCCCCCCCEEEEE	59.82	19867421
347	Phosphorylation	MADLIDGYCRLVNGA HHHHHHHHHHHHCCC	3.17	16512673
386 (in isoform 4)	Phosphorylation	-	12.80	26239621
386 (in isoform 6)	Phosphorylation	-	12.80	26239621
386 (in isoform 3)	Phosphorylation	-	12.80	26239621
390 (in isoform 5)	Phosphorylation	-	20.77	28285833
390 (in isoform 4)	Phosphorylation	-	20.77	26239621
390 (in isoform 6)	Phosphorylation	-	20.77	26239621
390 (in isoform 3)	Phosphorylation	-	20.77	26239621
392 (in isoform 4)	Phosphorylation	-	15.84	26239621
392 (in isoform 6)	Phosphorylation	-	15.84	26239621
392 (in isoform 3)	Phosphorylation	-	15.84	26239621
394 (in isoform 4)	Phosphorylation	-	3.36	26239621
394 (in isoform 6)	Phosphorylation	-	3.36	26239621
394 (in isoform 3)	Phosphorylation	-	3.36	26239621
395 (in isoform 5)	Phosphorylation	-	33.73	28285833
397 (in isoform 6)	Phosphorylation	-	29.85	25521595
397 (in isoform 4)	Phosphorylation	-	29.85	25521595
397	Phosphorylation	SVSHCQHKVKKARRF EHHHHHHHHHHHHHH	29.85	11420674
397 (in isoform 3)	Phosphorylation	-	29.85	25521595
406 (in isoform 3)	Phosphorylation	-	24.62	22499769
406 (in isoform 6)	Phosphorylation	-	24.62	22499769
406 (in isoform 4)	Phosphorylation	-	24.62	22499769
407	Phosphorylation	KARRFLPLVFCSLEP HHHHHHCEEEECCCC	5.12	7529876
407 (in isoform 3)	Phosphorylation	-	5.12	22499769
407 (in isoform 4)	Phosphorylation	-	5.12	22499769
407 (in isoform 6)	Phosphorylation	-	5.12	22499769
408 (in isoform 6)	Phosphorylation	-	4.25	22499769
408 (in isoform 4)	Phosphorylation	-	4.25	22499769
408 (in isoform 3)	Phosphorylation	-	4.25	22499769
428	Phosphorylation	SGDETDDYAEIIDEE CCCCCCCHHHHCCCC	14.67	20442405
437 (in isoform 2)	Phosphorylation	-	24.95	-
438	Phosphorylation	IIDEEDTYTMPSKSY HCCCCCCEECCCHHC	17.23	10430888
438 (in isoform 2)	Phosphorylation	-	17.23	11420674
439 (in isoform 2)	Phosphorylation	-	25.38	-
570	Phosphorylation	LYAYQLSTALAYLES HHHHHHHHHHHHHHH	33.99	-
576	Phosphorylation	STALAYLESKRFVHR HHHHHHHHHCCCCCH	41.35	17242355
577	Phosphorylation	TALAYLESKRFVHRD HHHHHHHHCCCCCHH	26.91	17242355
580	Phosphorylation	AYLESKRFVHRDIAA HHHHHCCCCCHHHHH	6.62	-
606	Phosphorylation	KLGDFGLSRYMEDST EECCCCHHHHHCCCC	23.03	26643407
608	Phosphorylation	GDFGLSRYMEDSTYY CCCCHHHHHCCCCEE	11.07	25521595
609	Oxidation	DFGLSRYMEDSTYYK CCCHHHHHCCCCEEC	4.48	17242355
612	Phosphorylation	LSRYMEDSTYYKASK HHHHHCCCCEECCCC	12.66	25521595
613	Phosphorylation	SRYMEDSTYYKASKG HHHHCCCCEECCCCC	43.10	25521595
614	Phosphorylation	RYMEDSTYYKASKGK HHHCCCCEECCCCCC	13.61	25521595
615	Phosphorylation	YMEDSTYYKASKGKL HHCCCCEECCCCCCC	10.52	25521595
618	Phosphorylation	DSTYYKASKGKLPIK CCCEECCCCCCCCCE	37.48	22499769
715	Phosphorylation	TELKAQLSTILEEEK HHHHHHHHHHHHHHH	11.00	29899451
716	Phosphorylation	ELKAQLSTILEEEKV HHHHHHHHHHHHHHH	37.87	29899451
722	Phosphorylation	STILEEEKVQQEERM HHHHHHHHHHHHHHH	48.93	-
732	Phosphorylation	QEERMRMESRRQATV HHHHHHHHHHHHCEE	30.63	12941275
740	Phosphorylation	SRRQATVSWDSGGSD HHHHCEECCCCCCCC	22.32	29514104
743	Phosphorylation	QATVSWDSGGSDEAP HCEECCCCCCCCCCC	38.50	21659605
746	Phosphorylation	VSWDSGGSDEAPPKP ECCCCCCCCCCCCCC	35.48	21659605
754	Phosphorylation	DEAPPKPSRPGYPSP CCCCCCCCCCCCCCC	58.18	26160508
758	Phosphorylation	PKPSRPGYPSPRSSE CCCCCCCCCCCCCCC	11.83	26160508
760	Phosphorylation	PSRPGYPSPRSSEGF CCCCCCCCCCCCCCC	25.18	27087446
770	Phosphorylation	SSEGFYPSPQHMVQT CCCCCCCCCCCEEEE	26.30	12941275
797	Phosphorylation	GIPAMAGSIYQGQAS CCCCCCCCEECCCCH	14.48	-
799	Phosphorylation	PAMAGSIYQGQASLL CCCCCCEECCCCHHC	14.32	-
843	Phosphorylation	GMGQVLPPHLMEERL CCCCCCCHHHHHHHH	29.14	-
861	Phosphorylation	QQEMEEDQRWLEKEE HHHHHHHHHHHHHHH	41.55	11420674
878	Phosphorylation	LKPDVRLSRGSIDRE CCCCCEECCCCCCCC	24.83	26824392
881	Phosphorylation	DVRLSRGSIDREDGS CCEECCCCCCCCCCC	21.87	26824392
888	Phosphorylation	SIDREDGSFQGPTGN CCCCCCCCEECCCCC	27.07	28066266
893	Phosphorylation	DGSFQGPTGNQHIYQ CCCEECCCCCCEEEC	56.44	26643407
899	Phosphorylation	PTGNQHIYQPVGKPD CCCCCEEECCCCCCC	12.49	26824392
910	Phosphorylation	GKPDPAAPPKKPPRP CCCCCCCCCCCCCCC	43.26	-
913 (in isoform 4)	Phosphorylation	-	67.06	26643407
914	Phosphorylation	PAAPPKKPPRPGAPG CCCCCCCCCCCCCCC	35.94	-
917 (in isoform 4)	Phosphorylation	-	49.42	26643407
923 (in isoform 4)	Phosphorylation	-	4.50	26643407
925	Phosphorylation	GAPGHLSNLSSISSP CCCCCHHCHHHCCCC	50.75	7997267
930	Phosphorylation	LSNLSSISSPADSYN HHCHHHCCCCCCCCC	32.02	25338131
948	Phosphorylation	KLQPQEISPPPTANL CCCCCCCCCCCCCCC	30.51	25521595
952	Phosphorylation	QEISPPPTANLDRSN CCCCCCCCCCCCCCC	33.67	22942356
958	Phosphorylation	PTANLDRSNDKVYEN CCCCCCCCCCHHHHC	49.39	23984901
963	Phosphorylation	DRSNDKVYENVTGLV CCCCCHHHHCHHHHH	13.92	10373530
967	Phosphorylation	DKVYENVTGLVKAVI CHHHHCHHHHHHHHH	36.06	25367039
1049	Phosphorylation	AQQYVMTSLQQEYKK HHHHHHHHHHHHHHH	13.19	29899451

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 ISOFORM 3	-	GPS
397	Y	Phosphorylation	Kinase	PTK2	P34152-2	GPS
397	Y	Phosphorylation	Kinase	SRC	P05480	PSP
407	Y	Phosphorylation	Kinase	SRC	P05480	GPS
407	Y	Phosphorylation	Kinase	SRC	P05480	PSP
407	Y	Phosphorylation	Kinase	SRC	P12931	PSP
428	Y	Phosphorylation	Kinase	PTK2	P34152	GPS
428	Y	Phosphorylation	Kinase	PTK2	P34152-2	GPS
576	Y	Phosphorylation	Kinase	RET	P35546	Uniprot
576	Y	Phosphorylation	Kinase	SRC	P05480	GPS
576	Y	Phosphorylation	Kinase	SRC	P05480	Uniprot
576	Y	Phosphorylation	Kinase	SRC	P12931	PSP
577	Y	Phosphorylation	Kinase	SRC	P12931	PSP
577	Y	Phosphorylation	Kinase	SRC	P05480	Uniprot
577	Y	Phosphorylation	Kinase	SRC	P05480	GPS
577	Y	Phosphorylation	Kinase	RET	P35546	Uniprot
614	Y	Phosphorylation	Kinase	RET	P35546	GPS
615	Y	Phosphorylation	Kinase	RET	P35546	GPS
732	S	Phosphorylation	Kinase	CDK5	P49615	Uniprot
843	S	Phosphorylation	Kinase	CAMK2A	P11798	PSP
843	S	Phosphorylation	Kinase	CAMK2A	Q9UQM7	PSP
861	Y	Phosphorylation	Kinase	SRC	P12931	PSP
861	Y	Phosphorylation	Kinase	SRC	P05480	GPS
910	S	Phosphorylation	Kinase	MAPK1	P63085	GPS
910	S	Phosphorylation	Kinase	MAPK3	Q63844	GPS
925	Y	Phosphorylation	Kinase	SRC	P12931	PSP
925	Y	Phosphorylation	Kinase	SRC	P05480	Uniprot
925	Y	Phosphorylation	Kinase	SRC	P05480	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
722	S	Phosphorylation		10373530
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_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PAXI_HUMAN	PXN	physical	10417825
EFS_MOUSE	Efs	physical	9750131
EFS_HUMAN	EFS	physical	9750131
BCAR1_MOUSE	Bcar1	physical	9038154
EFS_MOUSE	Efs	physical	9038154
SRBS1_MOUSE	Sorbs1	physical	9461600
FAK1_MOUSE	Ptk2	physical	10431817
SRC_MOUSE	Src	physical	16966330
NMDE1_RAT	Grin2a	physical	12764094
NMDE2_RAT	Grin2b	physical	12764094
NMDZ1_RAT	Grin1	physical	12764094

Drug and Disease Associations

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

Regulatory Network of FAK1_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Qualitative and quantitative analyses of protein phosphorylation innaive and stimulated mouse synaptosomal preparations."; Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D.,Gerrits B., Panse C., Schlapbach R., Mansuy I.M.; Mol. Cell. Proteomics 6:283-293(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-948, AND MASSSPECTROMETRY.	17114649 [Abstract]
"Serine 732 phosphorylation of FAK by Cdk5 is important formicrotubule organization, nuclear movement, and neuronal migration."; Xie Z., Sanada K., Samuels B.A., Shih H., Tsai L.H.; Cell 114:469-482(2003). Cited for: FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-770.	12941275 [Abstract]
"Large-scale identification and evolution indexing of tyrosinephosphorylation sites from murine brain."; Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.; J. Proteome Res. 7:311-318(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-614; TYR-615 ANDTYR-963, AND MASS SPECTROMETRY.	18034455 [Abstract]
"Large-scale phosphorylation analysis of mouse liver."; Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-614 AND TYR-615, ANDMASS SPECTROMETRY.	17242355 [Abstract]
"Different modes and qualities of tyrosine phosphorylation of Fak andPyk2 during epithelial-mesenchymal transdifferentiation and cellmigration: analysis of specific phosphorylation events using site-directed antibodies."; Nakamura K., Yano H., Schaefer E., Sabe H.; Oncogene 20:2626-2635(2001). Cited for: PHOSPHORYLATION AT TYR-428; TYR-438; TYR-614; TYR-615; TYR-899 ANDTYR-963.	11420674 [Abstract]
"FAK integrates growth-factor and integrin signals to promote cellmigration."; Sieg D.J., Hauck C.R., Ilic D., Klingbeil C.K., Schaefer E.,Damsky C.H., Schlaepfer D.D.; Nat. Cell Biol. 2:249-256(2000). Cited for: FUNCTION, AND PHOSPHORYLATION AT TYR-428.	10806474 [Abstract]
"Induced focal adhesion kinase (FAK) expression in FAK-null cellsenhances cell spreading and migration requiring both auto- andactivation loop phosphorylation sites and inhibits adhesion-dependenttyrosine phosphorylation of Pyk2."; Owen J.D., Ruest P.J., Fry D.W., Hanks S.K.; Mol. Cell. Biol. 19:4806-4818(1999). Cited for: FUNCTION IN CELL SPREADING; MIGRATION AND PHOSPHORYLATION OF BCAR1,CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-428 AND614-TYR-TYR-615, AND PHOSPHORYLATION AT TYR-428; TYR-614 AND TYR-615.	10373530 [Abstract]
"Focal adhesion kinase overexpression enhances ras-dependent integrinsignaling to ERK2/mitogen-activated protein kinase throughinteractions with and activation of c-Src."; Schlaepfer D.D., Hunter T.; J. Biol. Chem. 272:13189-13195(1997). Cited for: FUNCTION IN PHOSPHORYLATION OF SHC1 AND ACTIVATION OF MAPK1/ERK2,PHOSPHORYLATION AT TYR-963, AND INTERACTION WITH GRB2.	9148935 [Abstract]
"Evidence for in vivo phosphorylation of the Grb2 SH2-domain bindingsite on focal adhesion kinase by Src-family protein-tyrosinekinases."; Schlaepfer D.D., Hunter T.; Mol. Cell. Biol. 16:5623-5633(1996). Cited for: PHOSPHORYLATION AT TYR-963, MUTAGENESIS OF TYR-963, AND INTERACTIONWITH GRB2.	8816475 [Abstract]
"Phosphorylation of tyrosine 397 in focal adhesion kinase is requiredfor binding phosphatidylinositol 3-kinase."; Chen H.C., Appeddu P.A., Isoda H., Guan J.L.; J. Biol. Chem. 271:26329-26334(1996). Cited for: INTERACTION WITH PIK3R1, MUTAGENESIS OF TYR-428, AND PHOSPHORYLATIONAT TYR-428.	8824286 [Abstract]
"Tyrosine phosphorylation of focal adhesion kinase at sites in thecatalytic domain regulates kinase activity: a role for Src familykinases."; Calalb M.B., Polte T.R., Hanks S.K.; Mol. Cell. Biol. 15:954-963(1995). Cited for: PHOSPHORYLATION AT TYR-428; TYR-438; TYR-614 AND TYR-615,AUTOPHOSPHORYLATION, CATALYTIC ACTIVITY, MUTAGENESIS OF TYR-428 AND614-TYR-615, AND ENZYME REGULATION.	7529876 [Abstract]
"Integrin-mediated signal transduction linked to Ras pathway by GRB2binding to focal adhesion kinase."; Schlaepfer D.D., Hanks S.K., Hunter T., van der Geer P.; Nature 372:786-791(1994). Cited for: FUNCTION IN INTEGRIN SIGNALING AND ACTIVATION OF MAP KINASES,INTERACTION WITH GRB2; BCAR1; SHC1 AND SRC, PHOSPHORYLATION ATTYR-963, AND MUTAGENESIS OF TYR-963.	7997267 [Abstract]

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