SRC_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: SRC_MOUSE
• UniProt AC: P05480
• Protein Name: Neuronal proto-oncogene tyrosine-protein kinase Src
• Gene Name: Src
• Organism: Mus musculus (Mouse).
• Sequence Length: 541
• Subcellular Localization: Cell membrane . Mitochondrion inner membrane . Nucleus . Cytoplasm, cytoskeleton . Cytoplasm, perinuclear region . Localizes to focal adhesion sites following integrin engagement. Localization to focal adhesion sites requires myristoylation and the S
• Protein Description: Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN) (Probable). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) (By similarity). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1 (Probable). Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors. [PubMed: 9344858 Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated calcium-activated chloride channel activation (By similarity Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor (Probable Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus (By similarity Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function]
• Protein Sequence: MGSNKSKPKDASQRRRSLEPSENVHGAGGAFPASQTPSKPASADGHRGPSAAFVPPAAEPKLFGGFNSSDTVTSPQRAGPLAGGVTTFVALYDYESRTETDLSFKKGERLQIVNNTRKVDVREGDWWLAHSLSTGQTGYIPSNYVAPSDSIQAEEWYFGKITRRESERLLLNAENPRGTFLVRESETTKGAYCLSVSDFDNAKGLNVKHYKIRKLDSGGFYITSRTQFNSLQQLVAYYSKHADGLCHRLTTVCPTSKPQTQGLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTRVAIKTLKPGTMSPEAFLQEAQVMKKLRHEKLVQLYAVVSEEPIYIVTEYMNKGSLLDFLKGETGKYLRLPQLVDMSAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIEDNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPECPESLHDLMCQCWRKEPEERPTFEYLQAFLEDYFTSTEPQYQPGENL

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
2	Myristoylation	------MGSNKSKPK ------CCCCCCCCC	39.67	-
12	Phosphorylation	KSKPKDASQRRRSLE CCCCCCHHHHHHCCC	34.06	20469934
17	Phosphorylation	DASQRRRSLEPSENV CHHHHHHCCCCCCCC	34.96	26824392
21	Phosphorylation	RRRSLEPSENVHGAG HHHCCCCCCCCCCCC	32.21	27742792
34	Phosphorylation	AGGAFPASQTPSKPA CCCCCCCCCCCCCCC	34.52	25619855
36	Phosphorylation	GAFPASQTPSKPASA CCCCCCCCCCCCCCC	27.34	25619855
38	Phosphorylation	FPASQTPSKPASADG CCCCCCCCCCCCCCC	55.44	25619855
42	Phosphorylation	QTPSKPASADGHRGP CCCCCCCCCCCCCCC	35.11	25619855
68	Phosphorylation	KLFGGFNSSDTVTSP CCCCCCCCCCCCCCC	27.59	24925903
69	Phosphorylation	LFGGFNSSDTVTSPQ CCCCCCCCCCCCCCC	38.10	24925903
71	Phosphorylation	GGFNSSDTVTSPQRA CCCCCCCCCCCCCCC	27.86	24925903
73	Phosphorylation	FNSSDTVTSPQRAGP CCCCCCCCCCCCCCC	36.46	25263469
74	Phosphorylation	NSSDTVTSPQRAGPL CCCCCCCCCCCCCCC	18.07	25521595
92	Phosphorylation	VTTFVALYDYESRTE CEEEEEEEECCCCCC	13.52	22817900
98	Phosphorylation	LYDYESRTETDLSFK EEECCCCCCEECCCC	53.14	-
100	Phosphorylation	DYESRTETDLSFKKG ECCCCCCEECCCCCC	41.44	-
103	Phosphorylation	SRTETDLSFKKGERL CCCCEECCCCCCCCE	37.52	-
139	Phosphorylation	LSTGQTGYIPSNYVA CCCCCCCCCCCCCCC	17.04	-
144	Phosphorylation	TGYIPSNYVAPSDSI CCCCCCCCCCCCCCC	11.43	-
186	Phosphorylation	TFLVRESETTKGAYC CEEEECCCCCCCEEE	56.60	18034455
188	Phosphorylation	LVRESETTKGAYCLS EEECCCCCCCEEEEE	24.35	-
192	Phosphorylation	SETTKGAYCLSVSDF CCCCCCEEEEEHHHC	11.55	22817900
221	Phosphorylation	KLDSGGFYITSRTQF ECCCCCEEEEEHHHC	13.43	11572968
237	Phosphorylation	SLQQLVAYYSKHADG CHHHHHHHHHHCCCC	10.78	22817900
343	Phosphorylation	VVSEEPIYIVTEYMN EECCCCEEEEEECCC	10.47	22817900
418	Phosphorylation	ADFGLARLIEDNEYT HHHHHHHHHCCCCCC	4.12	25731159
424	Phosphorylation	RLIEDNEYTARQGAK HHHCCCCCCCCCCCC	16.38	11149930
425	Phosphorylation	LIEDNEYTARQGAKF HHCCCCCCCCCCCCC	14.80	23649490
431	Malonylation	YTARQGAKFPIKWTA CCCCCCCCCCCEECC	59.50	26320211
444	Phosphorylation	TAPEAALYGRFTIKS CCCCHHHHCCEEEEH	11.09	20116462
461	Phosphorylation	WSFGILLTELTTKGR HHEEEEEEECCCCCC	26.04	26160508
464	Phosphorylation	GILLTELTTKGRVPY EEEEEECCCCCCCCC	21.89	26160508
465	Phosphorylation	ILLTELTTKGRVPYP EEEEECCCCCCCCCC	44.09	26160508
516	Phosphorylation	KEPEERPTFEYLQAF CCCCCCCHHHHHHHH	35.01	-
527	Phosphorylation	LQAFLEDYFTSTEPQ HHHHHHHHHCCCCCC	10.20	21962514
529	Phosphorylation	AFLEDYFTSTEPQYQ HHHHHHHCCCCCCCC	28.63	25731159
535	Phosphorylation	FTSTEPQYQPGENL- HCCCCCCCCCCCCC-	27.65	11572968

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
74	S	Phosphorylation	Kinase	CDK1	P11440	PSP
144	Y	Phosphorylation	Kinase	PDGFRB	P05622	GPS
424	Y	Phosphorylation	Kinase	FAK2	Q9QVP9	Uniprot
424	Y	Phosphorylation	Kinase	SRC	P12931	PSP
424	Y	Phosphorylation	Kinase	SRC	P05480	PSP
527	Y	Phosphorylation	Kinase	SRC	P05480	GPS
535	Y	Phosphorylation	Kinase	CSK	P41240	PSP
535	Y	Phosphorylation	Kinase	CSK	P41241	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
2	G	Myristoylation	Myristoylated at Gly-2, and this is essential for targeting to membranes.	-
74	S	Phosphorylation	CDK5-mediated phosphorylation at Ser-74 targets SRC to ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization.	21183079
74	S	ubiquitylation	CDK5-mediated phosphorylation at Ser-74 targets SRC to ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization.	21183079

Disease-associated PTM Sites based on SAP

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

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

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
KPCE_MOUSE	Prkce	physical	11834516
DVL2_MOUSE	Dvl2	physical	19920076
S1PR1_MOUSE	S1pr1	physical	21102457
JAK2_MOUSE	Jak2	physical	21102457
KHDR1_MOUSE	Khdrbs1	physical	15890643
CBL_MOUSE	Cbl	physical	8849724
CBL_MOUSE	Cbl	physical	9013636
ENOA_MOUSE	Eno1	physical	9013636
ENOA_MOUSE	Eno1	physical	14739300
SHIP1_MOUSE	Inpp5d	physical	16601135
SRC_MOUSE	Src	physical	10684249
CASB_MOUSE	Csn2	physical	10684249
P3C2A_MOUSE	Pik3c2a	physical	10684249
KHDR1_MOUSE	Khdrbs1	physical	10844001
EFS_MOUSE	Efs	physical	8647432
DIAP1_MOUSE	Diap1	physical	18194650
EGFR_MOUSE	Egfr	physical	11274221
FAK2_MOUSE	Ptk2b	physical	11274221
CAV3_MOUSE	Cav3	physical	14600260
CSF1R_MOUSE	Csf1r	physical	17420256
CBL_MOUSE	Cbl	physical	17420256
CBL_MOUSE	Cbl	physical	8635998
PAXI_MOUSE	Pxn	physical	14636584
AKT1_MOUSE	Akt1	physical	19122674
ARRB2_MOUSE	Arrb2	physical	19122674
CBL_MOUSE	Cbl	physical	11804588
EP300_MOUSE	Ep300	physical	26695438

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Solid tumor proteome and phosphoproteome analysis by high resolutionmass spectrometry.";
Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J.,Faessler R., Mann M.;
J. Proteome Res. 7:5314-5326(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17, AND MASSSPECTROMETRY.
PubMed: 19367708

"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-192, AND MASSSPECTROMETRY.
PubMed: 18034455