Reviewed, UniProtKB/Swiss-Prot P00523 (SRC_CHICK)

Names and origin

Protein names

Recommended name:
    Proto-oncogene tyrosine-protein kinase Src
    EC=2.7.10.2
Alternative name(s):
    pp60c-src
      Short name=p60-Src
      Short name=c-Src

Gene names

Name:

SRC

Organism

Gallus gallus (Chicken)

Taxonomic identifier

9031 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Archosauria › Dinosauria › Saurischia › Theropoda › Coelurosauria › Aves › Neognathae › Galliformes › Phasianidae › Phasianinae › Gallus

Protein attributes

Sequence length	533 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	Unknown.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	Becomes activated when its major tyrosine phosphorylation site is not phosphorylated. It can also be activated by point mutations as well as by truncations at the C-terminal end or by other mutations.
Subunit structure	Forms a complex with polyoma virus middle T antigen. Interacts with AFAP-110. Interacts with IGF2BP1. Ref.12 Ref.13
Tissue specificity	Expressed to high levels, and with a high degree of kinase activity, in certain fully differentiated cells such as neurons, platelets and macrophages. Isoform 1 is widely expressed. Isoform 2 is expressed only in the muscle.
Post-translational modification	Phosphorylated on Tyr-527 by c-Src kinase (CSK). The phosphorylated form is termed pp60c-src. The phosphorylated tail interacts with the SH2 domain thereby repressing kinase activity By similarity.
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
Coding sequence diversity	Alternative splicing
Disease	Proto-oncogene
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase 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 physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ASAP1	O97902	1	EBI-848039,EBI-848008	From a different organism.
Asap1	Q9QWY8-1	1	EBI-848039,EBI-698517	From a different organism.
Asap1	Q9QWY8-2	3	EBI-848039,EBI-698524	From a different organism.
CSK	P41240	3	EBI-848039,EBI-1380630	From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P00523-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P00523-2)

The sequence of this isoform differs from the canonical sequence as follows:
     183-193: AYCLSVSDFDN → DPCIPLPSCLC
     194-533: Missing.

Note: Membrane-bound.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 533

532

Proto-oncogene tyrosine-protein kinase Src

PRO_0000088144

Regions

Domain

81 – 142

62

SH3

Domain

148 – 245

98

SH2

Domain

267 – 520

254

Protein kinase

Nucleotide binding

273 – 281

9

ATP By similarity

Sites

Active site

386

1

Proton acceptor By similarity

Binding site

295

1

ATP

Amino acid modifications

Modified residue

12

1

Phosphoserine; by PKC

Modified residue

34

1

Phosphothreonine Ref.11

Modified residue

46

1

Phosphothreonine Ref.11

Modified residue

72

1

Phosphoserine Ref.11

Modified residue

416

1

Phosphotyrosine; by autocatalysis Ref.4 Ref.9

Modified residue

436

1

Phosphotyrosine; by autocatalysis Ref.4

Modified residue

527

1

Phosphotyrosine; by CSK Ref.10

Lipidation

2

1

N-myristoyl glycine By similarity

Natural variations

Alternative sequence

183 – 193

11

AYCLSVSDFDN → DPCIPLPSCLC in isoform 2.

VSP_011844

Alternative sequence

194 – 533

340

Missing in isoform 2.

VSP_011845

Experimental info

Sequence conflict

301

1

T → N Ref.1

Sequence conflict

501

1

K → R Ref.1

Secondary structure

1

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533

Helix Strand Turn

Details...

Beta strand

85 – 90

6

Beta strand

96 – 99

4

Beta strand

107 – 109

3

Beta strand

117 – 123

7

Turn

124 – 126

3

Beta strand

129 – 133

5

Helix

134 – 136

3

Beta strand

137 – 139

3

Beta strand

149 – 152

4

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

212 – 215

4

Beta strand

220 – 222

3

Helix

223 – 230

8

Beta strand

237 – 239

3

Helix

264 – 266

3

Beta strand

267 – 272

6

Beta strand

281 – 286

6

Turn

287 – 289

3

Beta strand

290 – 295

6

Helix

312 – 316

5

Beta strand

325 – 329

5

Beta strand

335 – 339

5

Helix

346 – 351

6

Helix

353 – 355

3

Helix

360 – 379

20

Helix

389 – 391

3

Beta strand

392 – 394

3

Helix

396 – 398

3

Beta strand

400 – 402

3

Helix

426 – 428

3

Helix

431 – 434

4

Helix

441 – 456

16

Helix

468 – 476

9

Helix

489 – 498

10

Helix

503 – 505

3

Helix

509 – 517

9

Helix

519 – 522

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: ABDB036F7D63C30A	FASTA	533	60,010
	10 20 30 40 50 60 MGSSKSKPKD PSQRRRSLEP 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 VPYPGMVNRE VLDQVERGYR 490 500 510 520 530 MPCPPECPES LHDLMCQCWR KDPEERPTFE YLQAFLEDYF TSTEPQYQPG ENL
	Isoform 2. Checksum: 9D1BE54C33B02D98	FASTA	193	21,180
	10 20 30 40 50 60 MGSSKSKPKD PSQRRRSLEP 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 KGDPCIPLPS CLC

References

[1]	"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 [MRNA] (ISOFORM 1).
[2]	Erratum Takeya T., Hanafusa H. Cell 34:319-319(1983) Cited for: SEQUENCE REVISION TO 526.
[3]	"An alternative non-tyrosine protein kinase product of the c-src gene in chicken skeletal muscle." Dorai T., Wang L.-H. Mol. Cell. Biol. 10:4068-4079(1990) [PubMed: 2115117] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Pectoralis muscle.
[4]	"The purification and characterization of the catalytic domain of Src expressed in Schizosaccharomyces pombe. Comparison of unphosphorylated and tyrosine phosphorylated species." Weijland A., Neubauer G., Courtneidge S.A., Mann M., Wierenga R.K., Superti-Furga G. Eur. J. Biochem. 240:756-764(1996) [PubMed: 8856081] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PHOSPHORYLATION AT TYR-416 AND TYR-436.
[5]	"DNA sequence of the viral and cellular src gene of chickens. II. Comparison of the src genes of two strains of Avian sarcoma virus and of the cellular homolog." Takeya T., Hanafusa H. J. Virol. 44:12-18(1982) [PubMed: 6292480] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-7.
[6]	"Analysis of cDNAs of the proto-oncogene c-src: heterogeneity in 5' exons and possible mechanism for the genesis of the 3' end of v-src." Dorai T., Levy J.B., Kang L., Brugge J.S., Wang L.-H. Mol. Cell. Biol. 11:4165-4176(1991) [PubMed: 1712905] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-19 AND 485-534 (ISOFORM 1).
[7]	"Direct evidence that oncogenic tyrosine kinases and cyclic AMP-dependent protein kinase have homologous ATP-binding sites." Kamps M.P., Taylor S.S., Sefton B.M. Nature 310:589-592(1984) [PubMed: 6431300] [Abstract] Cited for: ATP-BINDING SITE.
[8]	"Protein kinase C phosphorylates pp60src at a novel site." Gould K.L., Woodgett J.R., Cooper J.A., Buss J.E., Shalloway D., Hunter T. Cell 42:849-857(1985) [PubMed: 2996780] [Abstract] Cited for: PHOSPHORYLATION.
[9]	"Characterization of sites for tyrosine phosphorylation in the transforming protein of Rous sarcoma virus (pp60v-src) and its normal cellular homologue (pp60c-src)." Smart J.E., Oppermann H., Czernilofsky A.P., Purchio A.F., Erikson R.L., Bishop J.M. Proc. Natl. Acad. Sci. U.S.A. 78:6013-6017(1981) [PubMed: 6273838] [Abstract] Cited for: PHOSPHORYLATION AT TYR-416.
[10]	"Tyr527 is phosphorylated in pp60c-src: implications for regulation." Cooper J.A., Gould K.L., Cartwright C.A., Hunter T. Science 231:1431-1434(1986) [PubMed: 2420005] [Abstract] Cited for: PHOSPHORYLATION AT TYR-527.
[11]	"Purified maturation promoting factor phosphorylates pp60c-src at the sites phosphorylated during fibroblast mitosis." Shenoy S., Choi J.K., Bagrodia S., Copeland T.D., Maller J.L., Shalloway D. Cell 57:763-774(1989) [PubMed: 2470512] [Abstract] Cited for: PHOSPHORYLATION AT THR-34; THR-46 AND SER-72.
[12]	"Formation of a stable src-AFAP-110 complex through either an amino-terminal or a carboxy-terminal SH2-binding motif." Guappone A.C., Weimer T., Flynn D.C. Mol. Carcinog. 22:110-119(1998) [PubMed: 9655255] [Abstract] Cited for: INTERACTION WITH AFAP-110.
[13]	"Spatial regulation of beta-actin translation by Src-dependent phosphorylation of ZBP1." Huttelmaier S., Zenklusen D., Lederer M., Dictenberg J., Lorenz M., Meng X., Bassell G.J., Condeelis J., Singer R.H. Nature 438:512-515(2005) [PubMed: 16306994] [Abstract] Cited for: INTERACTION WITH IGF2BP1.
[14]	"The 2.35 A crystal structure of the inactivated form of chicken Src: a dynamic molecule with multiple regulatory interactions." Williams J.C., Weijland A., Gonfloni S., Thompson A., Courtneidge S.A., Superti-Furga G., Wierenga R.K. J. Mol. Biol. 274:757-775(1997) [PubMed: 9405157] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 83-533.
[15]	"1H and 15N assignments and secondary structure of the Src SH3 domain." Yu H., Rosen M.K., Schreiber S.L. FEBS Lett. 324:87-92(1993) [PubMed: 8504863] [Abstract] Cited for: STRUCTURE BY NMR OF 81-140.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

V00402 Genomic DNA. Translation: CAA23696.1.
J00908 Genomic DNA. No translation available.
M57290 mRNA. Translation: AAA49078.1.
S43604 mRNA. Translation: AAD13831.1.
S43616 mRNA. Translation: AAD13835.1.
S43587 mRNA. Translation: AAD13830.1.
S43609 mRNA. Translation: AAD13832.1.
S43614 mRNA. Translation: AAD13834.1.
S43579 mRNA. Translation: AAB19353.2.

IPI

IPI00571705.
IPI00598719.

PIR

TVCHS. A00630.

RefSeq

XP_001232485.1.

UniGene

Gga.9406

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1F1W	X-ray	2.10	A	145-246	[»]
1F2F	X-ray	1.70	A	145-246	[»]
1NLO	NMR	-	C	81-140	[»]
1NLP	NMR	-	C	81-140	[»]
1P13	X-ray	1.63	A/B	145-245	[»]
1PRL	NMR	-	C	77-139	[»]
1PRM	NMR	-	C	77-139	[»]
1RLP	NMR	-	C	77-139	[»]
1RLQ	NMR	-	C	77-139	[»]
1SRL	NMR	-	A	77-140	[»]
1SRM	NMR	-	A	77-140	[»]
2HWO	X-ray	2.50	A/B	251-532	[»]
2HWP	X-ray	2.48	A/B	251-532	[»]
2OIQ	X-ray	2.07	A/B	251-532	[»]
2PTK	X-ray	2.35	A	81-533	[»]
2QI8	X-ray	2.32	A/B	251-533	[»]
2QLQ	X-ray	2.33	A/B	251-533	[»]
2QQ7	X-ray	2.38	A/B	251-533	[»]
3D7T	X-ray	2.90	B	258-533	[»]
3D7U	X-ray	4.11	B/D	260-523	[»]
3DQW	X-ray	2.02	A/B/C/D	251-533	[»]
3DQX	X-ray	2.30	A/B	251-533	[»]
3EL7	X-ray	2.80	A	251-533	[»]
3EL8	X-ray	2.30	A/B	251-533	[»]
3EN4	X-ray	2.55	A/B	251-533	[»]
3EN5	X-ray	2.66	A/B	251-533	[»]
3EN6	X-ray	2.39	A/B	251-533	[»]
3EN7	X-ray	2.81	A/B	251-533	[»]
3F3T	X-ray	2.50	A/B	251-533	[»]
3F3U	X-ray	2.50	A/B	251-533	[»]
3F6X	X-ray	2.35	A/B/C/D	251-533	[»]
3FJ5	X-ray	1.65	A/B	85-140	[»]
3G6G	X-ray	2.31	A/B	251-533	[»]
3G6H	X-ray	2.35	A/B	251-533	[»]
3GEQ	X-ray	2.20	A/B	251-533	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:449N.

IntAct

P00523. 4 interactions.

Genome annotation databases

Ensembl

ENSGALG00000003855. Gallus gallus. [Contig view]

GeneID

396442.

KEGG

gga:396442.

Phylogenomic databases

HOVERGEN

P00523.

OMA

P00523. KVDVREG.

Enzyme and pathway databases

BRENDA

2.7.10.2. 4.

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. 2 hits.
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...

Entry information

Entry name

SRC_CHICK

Accession

Primary (citable) accession number: P00523
Secondary accession number(s): Q90992 , Q90993, Q91343, Q91345, Q92013, Q98915

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 116 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)