Reviewed, UniProtKB/Swiss-Prot P00524 (SRC_RSVSA)

Names and origin

Protein names

Recommended name:
    Tyrosine-protein kinase transforming protein Src
    EC=2.7.10.2
Alternative name(s):
    pp60v-src
      Short name=p60-Src
      Short name=v-Src

Gene names

Name:

V-SRC

Organism

Avian leukosis virus RSA (RSV-SRA) (Rous sarcoma virus (strain Schmidt-Ruppin A))

Taxonomic identifier

269446 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Alpharetrovirus

Virus host

Gallus gallus (Chicken) [TaxID: 9031]

Protein attributes

Sequence length	526 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This phosphoprotein, required for both the initiation and the maintenance of neoplastic transformation, is a protein kinase that catalyzes the phosphorylation of tyrosine residues in vitro.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Homodimer.
Post-translational modification	The phosphorylated form is termed pp60v-src. Ref.4
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. Contains 1 protein kinase domain. Contains 1 SH2 domain. Contains 1 SH3 domain.

Ontologies

Keywords
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Oncogene Transferase Tyrosine-protein kinase
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed; by host By similarity

Chain

2 – 526

525

Tyrosine-protein kinase transforming protein Src

PRO_0000088153

Regions

Domain

81 – 142

62

SH3

Domain

148 – 245

98

SH2

Domain

267 – 517

251

Protein kinase

Nucleotide binding

273 – 281

9

ATP By similarity

Sites

Active site

386

1

Proton acceptor By similarity

Binding site

295

1

ATP By similarity

Amino acid modifications

Modified residue

416

1

Phosphotyrosine; by autocatalysis Ref.4

Lipidation

2

1

N-myristoyl glycine; by host By similarity

Experimental info

Sequence conflict

16

1

C → R Ref.1

Sequence conflict

16

1

C → R Ref.2

Sequence conflict

95 – 96

2

RT → WI Ref.1

Sequence conflict

95 – 96

2

RT → WI Ref.2

Sequence conflict

117

1

D → N Ref.1

Sequence conflict

117

1

D → N Ref.2

Sequence conflict

338

1

T → I Ref.1

Sequence conflict

338

1

T → I Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

526

Helix Strand Turn

Details...

Helix

155 – 162

8

Beta strand

171 – 176

6

Beta strand

178 – 180

3

Beta strand

184 – 192

9

Turn

193 – 195

3

Beta strand

196 – 206

11

Beta strand

208 – 210

3

Beta strand

212 – 215

4

Beta strand

218 – 222

5

Helix

223 – 232

10

Beta strand

237 – 239

3

Sequences

	Sequence		Length	Mass (Da)
	P00524-1 [UniParc]. Last modified January 23, 2007. Version 5. Checksum: 7DB3903F80233E49	FASTA	526	58,878
	10 20 30 40 50 60 MGSSKSKPKD PSQRRCSLEP PDSTHHGGFP ASQTPNKTAA PDTHRTPSRS FGTVATEPKL 70 80 90 100 110 120 FGGFNTSDTV TSPQRAGALA GGVTTFVALY DYESRTETDL SFKKGERLQI VNNTEGDWWL 130 140 150 160 170 180 AHSLTTGQTG YIPSNYVAPS DSIQAEEWYF GKITRRESER LLLNPENPRG TFLVRESETT 190 200 210 220 230 240 KGAYCLSVSD FDNAKGLNVK HYKIRKLDSG GFYITSRTQF SSLQQLVAYY SKHADGLCHR 250 260 270 280 290 300 LTNVCPTSKP QTQGLAKDAW EIPRESLRLE VKLGQGCFGE VWMGTWNGTT RVAIKTLKPG 310 320 330 340 350 360 TMSPEAFLQE AQVMKKLRHE KLVQLYAVVS EEPIYIVTEY MSKGSLLDFL KGEMGKYLRL 370 380 390 400 410 420 PQLVDMAAQI ASGMAYVERM NYVHRDLRAA NILVGENLVC KVADFGLARL IEDNEYTARQ 430 440 450 460 470 480 GAKFPIKWTA PEAALYGRFT IKSDVWSFGI LLTELTTKGR VPYPGMGNGE VLDRVERGYR 490 500 510 520 MPCPPECPES LHDLMCQCWR RDPEERPTFE YLQAQLLPAC VLEVAE

References

[1]	"Nucleotide sequence of an avian sarcoma virus oncogene (src) and proposed amino acid sequence for gene product." Czernilofsky A.P., Levinson A.D., Varmus H.E., Bishop J.M., Tischer E., Goodman H.M. Nature 287:198-203(1980) [PubMed: 6253794] [Abstract] Cited for: NUCLEOTIDE SEQUENCE.
[2]	"Corrections to the nucleotide sequence of the src gene of Rous sarcoma virus." Czernilofsky A.P., Levinson A.D., Varmus H.E., Bishop J.M., Tischer E., Goodman H. Nature 301:736-738(1983) [PubMed: 6298633] [Abstract] Cited for: SEQUENCE REVISION.
[3]	"Structure and sequence of the cellular gene homologous to the RSV src gene and the mechanism for generating the transforming virus." Takeya T., Hanafusa H. Cell 32:881-890(1983) [PubMed: 6299580] [Abstract] Cited for: NUCLEOTIDE SEQUENCE. Strain: Isolate td mutant 1441.
[4]	"Homologous tyrosine phosphorylation sites in transformation-specific gene products of distinct avian sarcoma viruses." Neil J.C., Ghysdael J., Vogt P.K., Smart J.E. Nature 291:675-677(1981) [PubMed: 6264320] [Abstract] Cited for: PHOSPHORYLATION AT TYR-416.
[5]	"Crystal structure of the phosphotyrosine recognition domain SH2 of v-src complexed with tyrosine-phosphorylated peptides." Waksman G., Kominos D., Robertson S.C., Pant N., Baltimore D., Birge R.B., Cowburn D., Hanafusa H., Mayer B.J., Overduin M., Resh M.D., Rios C.B., Silverman L., Kuriyan J. Nature 358:646-653(1992) [PubMed: 1379696] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 148-245 (SH2 DOMAIN).
[6]	"Binding of a high affinity phosphotyrosyl peptide to the Src SH2 domain: crystal structures of the complexed and peptide-free forms." Waksman G., Shoelson S.E., Pant N., Cowburn D., Kuriyan J. Cell 72:779-790(1993) [PubMed: 7680960] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 146-247 (SH2 DOMAIN).
[7]	"Design, synthesis, and cocrystal structure of a nonpeptide Src SH2 domain ligand." Plummer M.S., Holland D.R., Shahripour A., Lunney E.A., Fergus J.H., Marks J.S., McConnell P., Mueller W.T., Sawyer T.K. J. Med. Chem. 40:3719-3725(1997) [PubMed: 9371236] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 146-247 (SH2 DOMAIN).
[8]	"Dissection of the energetic coupling across the Src SH2 domain-tyrosyl phosphopeptide interface." Lubman O.Y., Waksman G. J. Mol. Biol. 316:291-304(2002) [PubMed: 11851339] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 145-247 (SH2 DOMAIN).
[9]	"Calorimetric and structural studies of 1,2,3-trisubstituted cyclopropanes as conformationally constrained peptide inhibitors of Src SH2 domain binding." Davidson J.P., Lubman O.Y., Rose T., Waksman G., Martin S.F. J. Am. Chem. Soc. 124:205-215(2002) [PubMed: 11782172] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 146-248 (SH2 DOMAIN).
[10]	"Structural and thermodynamic basis for the interaction of the Src SH2 domain with the activated form of the PDGF beta-receptor." Lubman O.Y., Waksman G. J. Mol. Biol. 328:655-668(2003) [PubMed: 12706723] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 145-247 (SH2 DOMAIN).

Cross-references

Sequence databases

EMBLGenBankDDBJ

L29199 Genomic DNA. Translation: AAA42563.1.
V01169 Genomic RNA. Translation: CAA24495.1.
K00928 Genomic RNA. Translation: AAA42565.1.

PIR

TVFV60. A38017.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BKL	X-ray	2.10	A	145-249	[»]
1BKM	X-ray	2.00	A	145-249	[»]
1IS0	X-ray	1.90	A/B	144-249	[»]
1KC2	X-ray	2.10	A	145-247	[»]
1NZL	X-ray	1.90	A/B	145-247	[»]
1NZV	X-ray	2.10	A/B	145-247	[»]
1SHA	X-ray	1.50	A	144-247	[»]
1SHB	X-ray	2.00	A	144-247	[»]
1SKJ	X-ray	2.00	A	145-249	[»]
1SPR	X-ray	2.50	A/B/C/D	144-247	[»]
1SPS	X-ray	2.70	A/B/C	144-247	[»]

SMR

P00524. Positions 83-515, 84-516.

ModBase

Search...

Enzyme and pathway databases

BRENDA

2.7.10.2. 96036.

Family and domain databases

InterPro

IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
[Graphical view]

Gene3D

G3DSA:3.30.505.10. SH2. 1 hit.

Pfam

PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.
PR00109. TYRKINASE.

ProDom

PD000001. Prot_kinase. 1 hit.
PD000093. SH2. 1 hit.
PD000066. SH3. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

BindingDB

P00524.

Entry information

Entry name

SRC_RSVSA

Accession

Primary (citable) accession number: P00524

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 106 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)