FAK2_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: FAK2_RAT
• UniProt AC: P70600
• Protein Name: Protein-tyrosine kinase 2-beta
• Gene Name: Ptk2b
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 1009
• Subcellular Localization: Cytoplasm . Cytoplasm, perinuclear region. Cell membrane ; Peripheral membrane protein ; Cytoplasmic side . Cell projection, lamellipodium. Cytoplasm, cell cortex. Nucleus. Colocalizes with integrins at the cell periphery. Interaction with NPHP1 indu
• Protein 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' (By similarity). 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 (By similarity)..
• Protein Sequence: MSGVSEPLSRVKVGTLRPPEGPPEPMVVVPVDVEKEDVRILKVCFYSNSFNPGKNFKLVKCTVQTEIQEIITSILLSGRIGPNIQLAECYGLRLKHMKSDEIHWLHPQMTVGEVQDKYECLHVEAEWRYDLQIRYLPEDFMESLKEDRTTLLYFYQQLRNDYMQRYASKVSEGMALQLGCLELRRFFKDMPHNALDKKSNFELLEKEVGLDLFFPKQMQENLKPKQFRKMIQQTFQQYASLREEECVMKFFNTLAGFANIDQETYRCELIQGWNITVDLVIGPKGIRQLTSQDTKPTCLAEFKQIRSIRCLPLEETQAVLQLGIEGAPQSLSIKTSSLAEAENMADLIDGYCRLQGEHKGSLIIHAKKDGEKRNSLPQIPTLNLESRRSHLSESCSIESDIYAEIPDETLRRPGGPQYGVAREDVVLNRILGEGFFGEVYEGVYTNHKGEKINVAVKTCKKDCTLDNKEKFMSEAVIMKNLDHPHIVKLIGIIEEEPTWIVMELYPYGELGHYLERNKNSLKVPTLVLYALQICKAMAYLESINCVHRDIAVRNILVASPECVKLGDFGLSRYIEDEDYYKASVTRLPIKWMSPESINFRRFTTASDVWMFAVCMWEILSFGKQPFFWLENKDVIGVLEKGDRLPKPELCPPVLYTLMTRCWDYDPSDRPRFTELVCSLSDIYQMERDIAIEQERNARYRPPKILEPTAFQEPPPKPSRPKYKHPPQTNLLAPKLQFQVPEGLCASSPTLTSPMEYPSPVNSLHTPPLHRHNVFKRHSMREEDFIRPSSREEAQQLWEAEKIKMRQVLDRQQKQMVEDSQWLRREERCLDPMVYMNDKSPLTPEKEAGYTEFTGPPQKPPRLGAQSIQPTANLDRTDDLVYHNVMTLVEAVLELKNKLSQLPPEEYVVVVKNVGLNLRKLIGSVDDLLPSLPASSRTEIEGTQKLLNKDLAELINKMRLAQQNAVTSLSEDCKRQMLTASHTLAVDAKNLLDAVDQAKVVANLAHPPAE

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
46	Phosphorylation	RILKVCFYSNSFNPG EEEEEEEECCCCCCC	11.21	-
47	Phosphorylation	ILKVCFYSNSFNPGK EEEEEEECCCCCCCC	13.02	-
150	Phosphorylation	SLKEDRTTLLYFYQQ HHHCCHHHHHHHHHH	18.69	22817900
153	Phosphorylation	EDRTTLLYFYQQLRN CCHHHHHHHHHHHHH	11.89	-
307	Phosphorylation	AEFKQIRSIRCLPLE HHHHHHCEEEEEEHH	18.93	22673903
351	Phosphorylation	MADLIDGYCRLQGEH HHHHHHHHHHCCCCC	3.17	-
361	Phosphorylation	LQGEHKGSLIIHAKK CCCCCCCEEEEEECC	22.62	-
375	Phosphorylation	KDGEKRNSLPQIPTL CCCCCCCCCCCCCCC	45.52	23712012
381	Phosphorylation	NSLPQIPTLNLESRR CCCCCCCCCCHHHHH	29.88	23984901
399	Phosphorylation	SESCSIESDIYAEIP CCCCCCCCCEEEECC	27.86	-
402	Phosphorylation	CSIESDIYAEIPDET CCCCCCEEEECCCHH	11.81	16574377
418	Phosphorylation	RRPGGPQYGVAREDV CCCCCCCCCCCHHHH	19.39	-
440	Phosphorylation	EGFFGEVYEGVYTNH CCCCCEEEEEEEECC	11.58	-
444	Phosphorylation	GEVYEGVYTNHKGEK CEEEEEEEECCCCCE	16.81	-
571	Phosphorylation	KLGDFGLSRYIEDED ECCCCCCCCCCCCCC	24.34	27097102
579	Phosphorylation	RYIEDEDYYKASVTR CCCCCCCCHHEECEE	12.57	22817900
580	Phosphorylation	YIEDEDYYKASVTRL CCCCCCCHHEECEEC	16.64	16574377
722	Phosphorylation	PKPSRPKYKHPPQTN CCCCCCCCCCCCCCC	19.74	22276854
746	Phosphorylation	VPEGLCASSPTLTSP CCCCCCCCCCCCCCC	35.53	27097102
747	Phosphorylation	PEGLCASSPTLTSPM CCCCCCCCCCCCCCC	11.90	27097102
749	Phosphorylation	GLCASSPTLTSPMEY CCCCCCCCCCCCCCC	44.61	27097102
751	Phosphorylation	CASSPTLTSPMEYPS CCCCCCCCCCCCCCC	33.01	27097102
752	Phosphorylation	ASSPTLTSPMEYPSP CCCCCCCCCCCCCCC	25.92	27097102
756	Phosphorylation	TLTSPMEYPSPVNSL CCCCCCCCCCCCCCC	11.62	27097102
758	Phosphorylation	TSPMEYPSPVNSLHT CCCCCCCCCCCCCCC	40.35	27097102
762	Phosphorylation	EYPSPVNSLHTPPLH CCCCCCCCCCCCCCC	23.05	27097102
765	Phosphorylation	SPVNSLHTPPLHRHN CCCCCCCCCCCCCCC	31.71	27097102
778	Phosphorylation	HNVFKRHSMREEDFI CCCHHHHCCCHHHCC	24.46	28432305
834	Phosphorylation	RCLDPMVYMNDKSPL HHCCCEEECCCCCCC	5.50	-
839	Phosphorylation	MVYMNDKSPLTPEKE EEECCCCCCCCCCHH	28.18	-
842	Phosphorylation	MNDKSPLTPEKEAGY CCCCCCCCCCHHCCC	32.55	28432305
849	Phosphorylation	TPEKEAGYTEFTGPP CCCHHCCCCCCCCCC	15.33	-
866	Phosphorylation	PPRLGAQSIQPTANL CCCCCCCCCCCCCCC	23.74	-
881	Phosphorylation	DRTDDLVYHNVMTLV CCCCCHHHHHHHHHH	8.58	22817900

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
402	Y	Phosphorylation	Kinase	PTK2B	P70600	GPS
579	Y	Phosphorylation	Kinase	LCK	Q01621	GPS
579	Y	Phosphorylation	Kinase	LYN	Q07014	GPS
579	Y	Phosphorylation	Kinase	SRC	Q9WUD9	GPS
580	Y	Phosphorylation	Kinase	LCK	Q01621	GPS
580	Y	Phosphorylation	Kinase	LYN	Q07014	GPS
580	Y	Phosphorylation	Kinase	SRC	Q9WUD9	GPS

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of FAK2_RAT !!

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of FAK2_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
EFS_MOUSE	Efs	physical	9750131
EFS_HUMAN	EFS	physical	9750131
PLD2_RAT	Pld2	physical	15705590

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"The Pyk2 FERM regulates Pyk2 complex formation and phosphorylation.";
Riggs D., Yang Z., Kloss J., Loftus J.C.;
Cell. Signal. 23:288-296(2011).
Cited for: PHOSPHORYLATION AT TYR-402; TYR-579 AND TYR-580, AND SUBUNIT.
PubMed: 20849950

"Differential regulation of Pyk2 phosphorylation at Tyr-402 and Tyr-580 in intestinal epithelial cells: roles of calcium, Src, Rho kinase,and the cytoskeleton.";
Wu S.S., Jacamo R.O., Vong S.K., Rozengurt E.;
Cell. Signal. 18:1932-1940(2006).
Cited for: FUNCTION, PHOSPHORYLATION AT TYR-402 AND TYR-580, AND CATALYTICACTIVITY.
PubMed: 16574377