SRC_RSVSA
ID SRC_RSVSA Reviewed; 526 AA.
AC P00524;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 5.
DT 03-AUG-2022, entry version 170.
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 Avian leukosis virus RSA (RSV-SRA) (Rous sarcoma virus (strain
OS Schmidt-Ruppin A)).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Alpharetrovirus.
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 NUCLEOTIDE SEQUENCE.
RC STRAIN=Isolate td mutant 1441;
RX PubMed=6299580; DOI=10.1016/0092-8674(83)90073-9;
RA Takeya T., Hanafusa H.;
RT "Structure and sequence of the cellular gene homologous to the RSV src gene
RT and the mechanism for generating the transforming virus.";
RL Cell 32:881-890(1983).
RN [4]
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 [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.
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 EMBL; K00928; AAA42565.1; -; 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 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 Gene3D; 3.30.505.10; -; 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 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; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 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 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"
FT CONFLICT 16
FT /note="C -> R (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 95..96
FT /note="RT -> WI (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 117
FT /note="D -> N (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 338
FT /note="T -> I (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
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; 58878 MW; 7DB3903F80233E49 CRC64;
MGSSKSKPKD PSQRRCSLEP PDSTHHGGFP ASQTPNKTAA PDTHRTPSRS FGTVATEPKL
FGGFNTSDTV TSPQRAGALA GGVTTFVALY DYESRTETDL SFKKGERLQI VNNTEGDWWL
AHSLTTGQTG YIPSNYVAPS DSIQAEEWYF GKITRRESER LLLNPENPRG TFLVRESETT
KGAYCLSVSD FDNAKGLNVK HYKIRKLDSG GFYITSRTQF SSLQQLVAYY SKHADGLCHR
LTNVCPTSKP QTQGLAKDAW EIPRESLRLE VKLGQGCFGE VWMGTWNGTT RVAIKTLKPG
TMSPEAFLQE AQVMKKLRHE KLVQLYAVVS EEPIYIVTEY MSKGSLLDFL KGEMGKYLRL
PQLVDMAAQI ASGMAYVERM NYVHRDLRAA NILVGENLVC KVADFGLARL IEDNEYTARQ
GAKFPIKWTA PEAALYGRFT IKSDVWSFGI LLTELTTKGR VPYPGMGNGE VLDRVERGYR
MPCPPECPES LHDLMCQCWR RDPEERPTFE YLQAQLLPAC VLEVAE
