Reviewed, UniProtKB/Swiss-Prot P07947 (YES_HUMAN)

Names and origin

Protein names

Recommended name:
    Proto-oncogene tyrosine-protein kinase Yes
    EC=2.7.10.2
Alternative name(s):
    p61-Yes
    c-Yes

Gene names

Name:	YES1
Synonyms:	YES

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	543 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	Promotes infectivity of Neisseria gonorrhoeae in epithelial cells by phosphorylating MCP/CD46. Ref.5
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subcellular location	Cytoplasm › cytosol. Note: In epithelial cells infected with Neisseria gonorrhoeae, forms aggregates beneath bacterial microcolonies. Ref.5
Post-translational modification	Autophosphorylated. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
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
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
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)
Cellular component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell
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
CDKN1B	P46527	1	EBI-515331,EBI-519280
FAS	P25445	1	EBI-515331,EBI-494743
GP6	Q9HCN6	1	EBI-515331,EBI-515278

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 543

542

Proto-oncogene tyrosine-protein kinase Yes

PRO_0000088181

Regions

Domain

91 – 152

62

SH3

Domain

158 – 255

98

SH2

Domain

277 – 530

254

Protein kinase

Nucleotide binding

283 – 291

9

ATP By similarity

Sites

Active site

396

1

Proton acceptor By similarity

Binding site

305

1

ATP By similarity

Amino acid modifications

Modified residue

11

1

Phosphoserine Ref.13

Modified residue

21

1

Phosphothreonine Ref.14

Modified residue

32

1

Phosphotyrosine Ref.10

Modified residue

40

1

Phosphoserine Ref.13 Ref.14

Modified residue

111

1

Phosphoserine Ref.13

Modified residue

194

1

Phosphotyrosine Ref.14

Modified residue

195

1

Phosphoserine Ref.13

Modified residue

222

1

Phosphotyrosine Ref.10

Modified residue

223

1

Phosphotyrosine Ref.10

Modified residue

426

1

Phosphotyrosine; by autocatalysis Ref.6 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14

Modified residue

446

1

Phosphotyrosine Ref.10

Modified residue

537

1

Phosphotyrosine Ref.7 Ref.10 Ref.13

Lipidation

2

1

N-myristoyl glycine By similarity

Natural variations

Natural variant

198

1

I → V: dbSNP rs34580680. Ref.16

VAR_041879

Natural variant

282

1

K → R Ref.16

VAR_041880

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

543

Helix Strand Turn

Details...

Beta strand

93 – 100

8

Beta strand

117 – 121

5

Beta strand

126 – 133

8

Turn

134 – 136

3

Beta strand

139 – 143

5

Helix

144 – 146

3

Beta strand

147 – 149

3

Sequences

	Sequence		Length	Mass (Da)
	P07947-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: A2B376084686BBCD	FASTA	543	60,801
	10 20 30 40 50 60 MGCIKSKENK SPAIKYRPEN TPEPVSTSVS HYGAEPTTVS PCPSSSAKGT AVNFSSLSMT 70 80 90 100 110 120 PFGGSSGVTP FGGASSSFSV VPSSYPAGLT GGVTIFVALY DYEARTTEDL SFKKGERFQI 130 140 150 160 170 180 INNTEGDWWE ARSIATGKNG YIPSNYVAPA DSIQAEEWYF GKMGRKDAER LLLNPGNQRG 190 200 210 220 230 240 IFLVRESETT KGAYSLSIRD WDEIRGDNVK HYKIRKLDNG GYYITTRAQF DTLQKLVKHY 250 260 270 280 290 300 TEHADGLCHK LTTVCPTVKP QTQGLAKDAW EIPRESLRLE VKLGQGCFGE VWMGTWNGTT 310 320 330 340 350 360 KVAIKTLKPG TMMPEAFLQE AQIMKKLRHD KLVPLYAVVS EEPIYIVTEF MSKGSLLDFL 370 380 390 400 410 420 KEGDGKYLKL PQLVDMAAQI ADGMAYIERM NYIHRDLRAA NILVGENLVC KIADFGLARL 430 440 450 460 470 480 IEDNEYTARQ GAKFPIKWTA PEAALYGRFT IKSDVWSFGI LQTELVTKGR VPYPGMVNRE 490 500 510 520 530 540 VLEQVERGYR MPCPQGCPES LHELMNLCWK KDPDERPTFE YIQSFLEDYF TATEPQYQPG ENL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of cDNA clones for the human c-yes gene." Sukegawa J., Semba K., Yamanashi Y., Nishizawa M., Miyajima N., Yamamoto T., Toyoshima K. Mol. Cell. Biol. 7:41-47(1987) [PubMed: 2436037] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"DNA sequence and analysis of human chromosome 18." Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S. Nature 437:551-555(2005) [PubMed: 16177791] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	"CD46 is phosphorylated at tyrosine 354 upon infection of epithelial cells by Neisseria gonorrhoeae." Lee S.W., Bonnah R.A., Higashi D.L., Atkinson J.P., Milgram S.L., So M. J. Cell Biol. 156:951-957(2002) [PubMed: 11901164] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION, FUNCTION.
[6]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-426, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-537, MASS SPECTROMETRY.
[8]	"Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry." Tao W.A., Wollscheid B., O'Brien R., Eng J.K., Li X.-J., Bodenmiller B., Watts J.D., Hood L., Aebersold R. Nat. Methods 2:591-598(2005) [PubMed: 16094384] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-426, MASS SPECTROMETRY. Tissue: T-cell.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-426, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-32; TYR-222; TYR-223; TYR-426; TYR-446 AND TYR-537, MASS SPECTROMETRY.
[11]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-426, MASS SPECTROMETRY.
[12]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-426, MASS SPECTROMETRY. Tissue: Platelet.
[13]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11; SER-40; SER-111; SER-195; TYR-426 AND TYR-537, MASS SPECTROMETRY.
[14]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-21; SER-40; TYR-194 AND TYR-426, MASS SPECTROMETRY.
[15]	"Crystallographic structure of the SH3 domain of the human c-Yes tyrosine kinase: loop flexibility and amyloid aggregation." Martin-Garcia J.M., Luque I., Mateo P.L., Ruiz-Sanz J., Camara-Artigas A. FEBS Lett. 581:1701-1706(2007) [PubMed: 17418139] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 91-152.
[16]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-198 AND ARG-282.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M15990 mRNA. Translation: AAA35735.1.
AP001178 Genomic DNA. No translation available.
CH471113 Genomic DNA. Translation: EAX01709.1.
BC048960 mRNA. Translation: AAH48960.1.

IPI

IPI00013981.

PIR

TVHUYS. A26714.

RefSeq

NP_005424.1.

UniGene

Hs.194148

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2HDA	X-ray	1.90	A	91-152	[»]

SMR

P07947. Positions 93-542, 94-543.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07947. 14 interactions.

PTM databases

PhosphoSite

P07947.

Proteomic databases

PRIDE

P07947.

Genome annotation databases

Ensembl

ENSG00000176105. Homo sapiens. [Contig view]

GeneID

7525.

KEGG

hsa:7525.

Organism-specific databases

GeneCards

GC18M000711.

HGNC

HGNC:12841. YES1.

HPA

CAB004370.

MIM

164880. gene.

PharmGKB

PA37432.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P07947.

HOVERGEN

P07947.

OMA

P07947. EHTAVAP.

Enzyme and pathway databases

BRENDA

2.7.10.2. 247.

Pathway_Interaction_DB

alphasynuclein_pathway. Alpha-synuclein signaling.
amb2_neutrophils_pathway. amb2 Integrin signaling.
pi3kcipathway. Class I PI3K signaling events.
epha_fwdpathway. EPHA forward signaling.
ephrinbrevpathway. Ephrin B reverse signaling.
glypican_1pathway. Glypican 1 network.
wnt_calcium_pathway. Noncanonical Wnt signaling pathway.
pdgfrbpathway. PDGFR-beta signaling pathway.
p38alphabetapathway. Regulation of p38-alpha and p38-beta.
ptp1bpathway. Signaling events mediated by PTP1B.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
txa2pathway. Thromboxane A2 receptor signaling.

Gene expression databases

ArrayExpress

P07947.

Bgee

P07947.

CleanEx

HS_YES1.

GermOnline

ENSG00000176105. Homo sapiens.

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

DrugBank

DB01254. Dasatinib.

NextBio

29441.

SOURCE

Search...

Entry information

Entry name

YES_HUMAN

Accession

Primary (citable) accession number: P07947
Secondary accession number(s): A6NLB3

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 115 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)