ID   SRC_RSVSA               Reviewed;         526 AA.
AC   P00524;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   22-FEB-2023, sequence version 6.
DT   24-JAN-2024, entry version 177.
DE   RecName: Full=Tyrosine-protein kinase transforming protein Src;
DE            EC=2.7.10.2;
DE   AltName: Full=pp60v-src;
DE            Short=p60-Src;
DE            Short=v-Src;
GN   Name=V-SRC;
OS   Rous sarcoma virus subgroup A (strain Schmidt-Ruppin) (RSV-SR-A).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Alpharetrovirus;
OC   Rous sarcoma virus.
OX   NCBI_TaxID=269446;
OH   NCBI_TaxID=9031; Gallus gallus (Chicken).
RN   [1]
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=6253794; DOI=10.1038/287198a0;
RA   Czernilofsky A.P., Levinson A.D., Varmus H.E., Bishop J.M., Tischer E.,
RA   Goodman H.M.;
RT   "Nucleotide sequence of an avian sarcoma virus oncogene (src) and proposed
RT   amino acid sequence for gene product.";
RL   Nature 287:198-203(1980).
RN   [2]
RP   SEQUENCE REVISION.
RX   PubMed=6298633; DOI=10.1038/301736b0;
RA   Czernilofsky A.P., Levinson A.D., Varmus H.E., Bishop J.M., Tischer E.,
RA   Goodman H.;
RT   "Corrections to the nucleotide sequence of the src gene of Rous sarcoma
RT   virus.";
RL   Nature 301:736-738(1983).
RN   [3]
RP   PHOSPHORYLATION AT TYR-416.
RX   PubMed=6264320; DOI=10.1038/291675a0;
RA   Neil J.C., Ghysdael J., Vogt P.K., Smart J.E.;
RT   "Homologous tyrosine phosphorylation sites in transformation-specific gene
RT   products of distinct avian sarcoma viruses.";
RL   Nature 291:675-677(1981).
RN   [4]
RP   FUNCTION.
RX   PubMed=30135207; DOI=10.1074/jbc.ra118.002784;
RA   Horiuchi M., Kuga T., Saito Y., Nagano M., Adachi J., Tomonaga T.,
RA   Yamaguchi N., Nakayama Y.;
RT   "The tyrosine kinase v-Src causes mitotic slippage by phosphorylating an
RT   inhibitory tyrosine residue of Cdk1.";
RL   J. Biol. Chem. 293:15524-15537(2018).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 148-245 (SH2 DOMAIN).
RX   PubMed=1379696; DOI=10.1038/358646a0;
RA   Waksman G., Kominos D., Robertson S.C., Pant N., Baltimore D., Birge R.B.,
RA   Cowburn D., Hanafusa H., Mayer B.J., Overduin M., Resh M.D., Rios C.B.,
RA   Silverman L., Kuriyan J.;
RT   "Crystal structure of the phosphotyrosine recognition domain SH2 of v-src
RT   complexed with tyrosine-phosphorylated peptides.";
RL   Nature 358:646-653(1992).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 146-247 (SH2 DOMAIN).
RX   PubMed=7680960; DOI=10.1016/0092-8674(93)90405-f;
RA   Waksman G., Shoelson S.E., Pant N., Cowburn D., Kuriyan J.;
RT   "Binding of a high affinity phosphotyrosyl peptide to the Src SH2 domain:
RT   crystal structures of the complexed and peptide-free forms.";
RL   Cell 72:779-790(1993).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 146-247 (SH2 DOMAIN).
RX   PubMed=9371236; DOI=10.1021/jm970402q;
RA   Plummer M.S., Holland D.R., Shahripour A., Lunney E.A., Fergus J.H.,
RA   Marks J.S., McConnell P., Mueller W.T., Sawyer T.K.;
RT   "Design, synthesis, and cocrystal structure of a nonpeptide Src SH2 domain
RT   ligand.";
RL   J. Med. Chem. 40:3719-3725(1997).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 145-247 (SH2 DOMAIN).
RX   PubMed=11851339; DOI=10.1006/jmbi.2001.5362;
RA   Lubman O.Y., Waksman G.;
RT   "Dissection of the energetic coupling across the Src SH2 domain-tyrosyl
RT   phosphopeptide interface.";
RL   J. Mol. Biol. 316:291-304(2002).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 146-248 (SH2 DOMAIN).
RX   PubMed=11782172; DOI=10.1021/ja011746f;
RA   Davidson J.P., Lubman O.Y., Rose T., Waksman G., Martin S.F.;
RT   "Calorimetric and structural studies of 1,2,3-trisubstituted cyclopropanes
RT   as conformationally constrained peptide inhibitors of Src SH2 domain
RT   binding.";
RL   J. Am. Chem. Soc. 124:205-215(2002).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 145-247 (SH2 DOMAIN).
RX   PubMed=12706723; DOI=10.1016/s0022-2836(03)00344-9;
RA   Lubman O.Y., Waksman G.;
RT   "Structural and thermodynamic basis for the interaction of the Src SH2
RT   domain with the activated form of the PDGF beta-receptor.";
RL   J. Mol. Biol. 328:655-668(2003).
CC   -!- FUNCTION: This phosphoprotein, required for both the initiation and the
CC       maintenance of neoplastic transformation, is a protein kinase that
CC       catalyzes the phosphorylation of tyrosine residues in vitro. Causes
CC       mitotic slippage in addition to cytokinesis failure in the host cell
CC       (PubMed:30135207). Phosphorylates and attenuates the activity of host
CC       CDK1, possibly causing the mitotic slippage (PubMed:30135207).
CC       {ECO:0000269|PubMed:30135207}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC         [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC         COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC         ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC   -!- SUBUNIT: Homodimer.
CC   -!- PTM: The phosphorylated form is termed pp60v-src.
CC       {ECO:0000269|PubMed:6264320}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC       kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR   EMBL; L29199; AAA42563.1; -; Genomic_DNA.
DR   EMBL; V01169; CAA24495.1; -; Genomic_RNA.
DR   PIR; A38017; TVFV60.
DR   PDB; 1BKL; X-ray; 2.10 A; A=145-249.
DR   PDB; 1BKM; X-ray; 2.00 A; A=145-249.
DR   PDB; 1IS0; X-ray; 1.90 A; A/B=144-249.
DR   PDB; 1KC2; X-ray; 2.10 A; A=145-247.
DR   PDB; 1NZL; X-ray; 1.90 A; A/B=145-247.
DR   PDB; 1NZV; X-ray; 2.10 A; A/B=145-247.
DR   PDB; 1SHA; X-ray; 1.50 A; A=144-247.
DR   PDB; 1SHB; X-ray; 2.00 A; A=144-247.
DR   PDB; 1SKJ; X-ray; 2.00 A; A=145-249.
DR   PDB; 1SPR; X-ray; 2.50 A; A/B/C/D=144-247.
DR   PDB; 1SPS; X-ray; 2.70 A; A/B/C=144-247.
DR   PDBsum; 1BKL; -.
DR   PDBsum; 1BKM; -.
DR   PDBsum; 1IS0; -.
DR   PDBsum; 1KC2; -.
DR   PDBsum; 1NZL; -.
DR   PDBsum; 1NZV; -.
DR   PDBsum; 1SHA; -.
DR   PDBsum; 1SHB; -.
DR   PDBsum; 1SKJ; -.
DR   PDBsum; 1SPR; -.
DR   PDBsum; 1SPS; -.
DR   BMRB; P00524; -.
DR   SMR; P00524; -.
DR   ELM; P00524; -.
DR   IntAct; P00524; 4.
DR   MINT; P00524; -.
DR   BindingDB; P00524; -.
DR   ChEMBL; CHEMBL4296300; -.
DR   DrugBank; DB08434; 2-METHYLCARBAMOYL-3-(4-PHOSPHONOOXY-PHENYL)-CYCLOPROPANECARBOXYLIC ACID.
DR   iPTMnet; P00524; -.
DR   EvolutionaryTrace; P00524; -.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   CDD; cd10365; SH2_Src_Src; 1.
DR   CDD; cd12008; SH3_Src; 1.
DR   Gene3D; 3.30.505.10; SH2 domain; 1.
DR   Gene3D; 2.30.30.40; SH3 Domains; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR   InterPro; IPR000980; SH2.
DR   InterPro; IPR036860; SH2_dom_sf.
DR   InterPro; IPR036028; SH3-like_dom_sf.
DR   InterPro; IPR001452; SH3_domain.
DR   InterPro; IPR008266; Tyr_kinase_AS.
DR   InterPro; IPR020635; Tyr_kinase_cat_dom.
DR   PANTHER; PTHR24418:SF53; PROTO-ONCOGENE TYROSINE-PROTEIN KINASE SRC; 1.
DR   PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1.
DR   Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR   Pfam; PF00017; SH2; 1.
DR   Pfam; PF00018; SH3_1; 1.
DR   PRINTS; PR00401; SH2DOMAIN.
DR   PRINTS; PR00452; SH3DOMAIN.
DR   PRINTS; PR00109; TYRKINASE.
DR   SMART; SM00252; SH2; 1.
DR   SMART; SM00326; SH3; 1.
DR   SMART; SM00219; TyrKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   SUPFAM; SSF55550; SH2 domain; 1.
DR   SUPFAM; SSF50044; SH3-domain; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR   PROSITE; PS50001; SH2; 1.
DR   PROSITE; PS50002; SH3; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Kinase; Lipoprotein; Myristate;
KW   Nucleotide-binding; Oncogene; Phosphoprotein; SH2 domain; SH3 domain;
KW   Transferase; Tyrosine-protein kinase.
FT   INIT_MET        1
FT                   /note="Removed; by host"
FT                   /evidence="ECO:0000250"
FT   CHAIN           2..526
FT                   /note="Tyrosine-protein kinase transforming protein Src"
FT                   /id="PRO_0000088153"
FT   DOMAIN          81..142
FT                   /note="SH3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT   DOMAIN          148..245
FT                   /note="SH2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT   DOMAIN          267..517
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1..57
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        8..22
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        27..53
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        386
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10028"
FT   BINDING         273..281
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         295
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         416
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:6264320"
FT   LIPID           2
FT                   /note="N-myristoyl glycine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P00526"
FT   STRAND          149..152
FT                   /evidence="ECO:0007829|PDB:1SHA"
FT   HELIX           155..162
FT                   /evidence="ECO:0007829|PDB:1SHA"
FT   STRAND          172..176
FT                   /evidence="ECO:0007829|PDB:1SHA"
FT   STRAND          178..180
FT                   /evidence="ECO:0007829|PDB:1SHA"
FT   STRAND          184..192
FT                   /evidence="ECO:0007829|PDB:1SHA"
FT   TURN            193..195
FT                   /evidence="ECO:0007829|PDB:1SHA"
FT   STRAND          196..206
FT                   /evidence="ECO:0007829|PDB:1SHA"
FT   STRAND          208..210
FT                   /evidence="ECO:0007829|PDB:1IS0"
FT   STRAND          212..215
FT                   /evidence="ECO:0007829|PDB:1SHA"
FT   STRAND          219..222
FT                   /evidence="ECO:0007829|PDB:1SHA"
FT   HELIX           223..230
FT                   /evidence="ECO:0007829|PDB:1SHA"
FT   STRAND          237..239
FT                   /evidence="ECO:0007829|PDB:1SHA"
SQ   SEQUENCE   526 AA;  58984 MW;  66FE67355203D7D0 CRC64;
     MGSSKSKPKD PSQRRRSLEP PDSTHHGGFP ASQTPNKTAA PDTHRTPSRS FGTVATEPKL
     FGGFNTSDTV TSPQRAGALA GGVTTFVALY DYESWIETDL SFKKGERLQI VNNTEGNWWL
     AHSLTTGQTG YIPSNYVAPS DSIQAEEWYF GKITRRESER LLLNPENPRG TFLVRESETT
     KGAYCLSVSD FDNAKGLNVK HYKIRKLDSG GFYITSRTQF SSLQQLVAYY SKHADGLCHR
     LTNVCPTSKP QTQGLAKDAW EIPRESLRLE VKLGQGCFGE VWMGTWNGTT RVAIKTLKPG
     TMSPEAFLQE AQVMKKLRHE KLVQLYAVVS EEPIYIVIEY MSKGSLLDFL KGEMGKYLRL
     PQLVDMAAQI ASGMAYVERM NYVHRDLRAA NILVGENLVC KVADFGLARL IEDNEYTARQ
     GAKFPIKWTA PEAALYGRFT IKSDVWSFGI LLTELTTKGR VPYPGMGNGE VLDRVERGYR
     MPCPPECPES LHDLMCQCWR RDPEERPTFE YLQAQLLPAC VLEVAE
//