Reviewed, UniProtKB/Swiss-Prot P04626 (ERBB2_HUMAN)

Names and origin

Protein names

Recommended name:
    Receptor tyrosine-protein kinase erbB-2
    EC=2.7.10.1
Alternative name(s):
    p185erbB2
    C-erbB-2
    NEU proto-oncogene
    Tyrosine kinase-type cell surface receptor HER2
    MLN 19
    CD_antigen=CD340

Gene names

Name:	ERBB2
Synonyms:	HER2, NEU, NGL

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1255 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	Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Not activated by EGF, TGF-alpha and amphiregulin.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Heterodimer with each of the other ERBB receptors Potential. Interacts with PRKCABP and PLXNB1. Part of a complex with EGFR and either PIK3C2A or PIK3C2B. May interact with PIK3C2B when phosphorylated on Tyr-1196. Interacts with MEMO when phosphorylated on Tyr-1248. Interacts with MUC1. Stimulation by heregulin (HRG) in breast cancer cell lines induces binding of MUC1 with gamma-catenin.
Subcellular location	Membrane; Single-pass type I membrane protein.
Post-translational modification	Ligand-binding increases phosphorylation on tyrosine residues By similarity.
Polymorphism	There are fours alleles due to the variations in positions 654 and 655. Allele B1 (Ile-654/Ile-655) has a frequency of 0.782; allele B2 (Ile-654/Val-655) has a frequency of 0.206; allele B3 (Val-654/Val-655) has a frequency of 0.012.
Involvement in disease	Defects in ERBB2 are associated with gastric cancer [MIM:137215]; also known as hereditary familial diffuse gastric cancer (HDGC). Defects in ERBB2 are associated with familial glioma of brain [MIM:137800]; also called glioblastoma multiforme. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Defects in ERBB2 are associated with ovarian cancer [MIM:167000]. Ovarian cancer is the leading cause of death from gynecologic malignancy. It is characterized by advanced presentation with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases. These typical features relate to the biology of the disease, which is a principal determinant of outcome. Defects in ERBB2 are associated with lung cancer [MIM:211980]; also called adenocarcinoma of lung.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cell proliferation Traceable author statement. Source: ProtInc heart development Traceable author statement. Source: UniProtKB mammary gland development Traceable author statement. Source: UniProtKB phosphoinositide 3-kinase cascade Inferred from direct assay. Source: UniProtKB phosphoinositide-mediated signaling Non-traceable author statement. Source: UniProtKB positive regulation of MAP kinase activity Inferred from direct assay. Source: UniProtKB positive regulation of cell adhesion Inferred from direct assay. Source: UniProtKB positive regulation of epithelial cell proliferation Inferred from direct assay. Source: UniProtKB protein amino acid autophosphorylation Inferred from direct assay. Source: UniProtKB regulation of angiogenesis Non-traceable author statement. Source: UniProtKB transmembrane receptor protein tyrosine kinase signaling pathway Inferred from direct assay. Source: UniProtKB wound healing Inferred from direct assay. Source: UniProtKB
Cellular component	basolateral plasma membrane Inferred from direct assay. Source: UniProtKB integral to membrane Non-traceable author statement. Source: UniProtKB receptor complex Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ErbB-3 class receptor binding Traceable author statement. Source: ProtInc epidermal growth factor receptor activity Non-traceable author statement. Source: UniProtKB identical protein binding Inferred from physical interaction. Source: IntAct protein C-terminus binding Inferred from physical interaction. Source: UniProtKB protein heterodimerization activity Inferred from direct assay. Source: UniProtKB protein phosphatase binding Inferred from physical interaction. Source: UniProtKB receptor signaling protein tyrosine kinase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-641062,EBI-641062
CALM	P62157	1	EBI-641062,EBI-397403	From a different organism.
Calm1	P62161	1	EBI-641062,EBI-397530	From a different organism.
EGFR	P00533	2	EBI-641062,EBI-297353
ERBB3	P21860	4	EBI-641062,EBI-720706
ERBB4	Q15303	2	EBI-641062,EBI-80371
PTPN12	Q05209	1	EBI-641062,EBI-2266035
PTPN22	Q9Y2R2	1	EBI-641062,EBI-1211241
PTPN3	P26045	1	EBI-641062,EBI-1047946
PTPRB	P23467	1	EBI-641062,EBI-1265766
PTPRC	P08575	1	EBI-641062,EBI-1341
PTPRG	P23470	1	EBI-641062,EBI-2258115
PTPRJ	Q12913	1	EBI-641062,EBI-2264500
PTPRK	Q15262	1	EBI-641062,EBI-474052
PTPRO	Q16827	1	EBI-641062,EBI-723739
PTPRZ1	P23471	1	EBI-641062,EBI-2263175

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Chain

23 – 1255

1233

Receptor tyrosine-protein kinase erbB-2

PRO_0000016669

Regions

Topological domain

23 – 652

630

Extracellular Potential

Transmembrane

653 – 675

23

Potential

Topological domain

676 – 1255

580

Cytoplasmic Potential

Domain

720 – 987

268

Protein kinase

Nucleotide binding

726 – 734

9

ATP By similarity

Region

1195 – 1197

3

Interaction with PIK3C2B Probable

Sites

Active site

845

1

Proton acceptor By similarity

Binding site

753

1

ATP By similarity

Amino acid modifications

Modified residue

735

1

Phosphotyrosine Ref.13

Modified residue

1054

1

Phosphoserine Ref.14 Ref.15

Modified residue

1139

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

1196

1

Phosphotyrosine Potential

Modified residue

1248

1

Phosphotyrosine; by autocatalysis By similarity

Glycosylation

68

1

N-linked (GlcNAc...) Potential

Glycosylation

124

1

N-linked (GlcNAc...) Potential

Glycosylation

187

1

N-linked (GlcNAc...) Potential

Glycosylation

259

1

N-linked (GlcNAc...) Potential

Glycosylation

530

1

N-linked (GlcNAc...) Potential

Glycosylation

571

1

N-linked (GlcNAc...) Potential

Glycosylation

629

1

N-linked (GlcNAc...) Potential

Disulfide bond

195 ↔ 204

By similarity

Disulfide bond

199 ↔ 212

By similarity

Disulfide bond

220 ↔ 227

By similarity

Disulfide bond

224 ↔ 235

By similarity

Disulfide bond

236 ↔ 244

By similarity

Disulfide bond

240 ↔ 252

By similarity

Disulfide bond

255 ↔ 264

By similarity

Disulfide bond

268 ↔ 295

By similarity

Disulfide bond

299 ↔ 311

By similarity

Disulfide bond

315 ↔ 331

By similarity

Disulfide bond

334 ↔ 338

By similarity

Disulfide bond

511 ↔ 520

By similarity

Disulfide bond

515 ↔ 528

By similarity

Disulfide bond

531 ↔ 540

By similarity

Disulfide bond

544 ↔ 560

By similarity

Disulfide bond

563 ↔ 576

By similarity

Disulfide bond

567 ↔ 584

By similarity

Disulfide bond

587 ↔ 596

By similarity

Disulfide bond

600 ↔ 623

By similarity

Disulfide bond

626 ↔ 634

By similarity

Disulfide bond

630 ↔ 642

By similarity

Natural variations

Natural variant

452

1

W → C: dbSNP rs4252633. Ref.3

VAR_016317

Natural variant

654

1

I → V in allele B3. dbSNP rs1801201. Ref.18 Ref.20

VAR_004077

Natural variant

655

1

I → V in allele B2 and allele B3. dbSNP rs1136201. Ref.3 Ref.18 Ref.20

VAR_004078

Natural variant

755

1

L → P in adenocarcinoma of lung; somatic mutation. Ref.19

VAR_055432

Natural variant

768

1

L → S: dbSNP rs56366519. Ref.20

VAR_042097

Natural variant

774

1

M → MAYVM in adenocarcinoma of lung; somatic mutationa.

VAR_055433

Natural variant

776

1

G → S in a gastric adenocarcinoma sample; somatic mutation. Ref.20 Ref.19

VAR_042098

Natural variant

779

1

S → SVGS in adenocarcinoma of lung; somatic mutation.

VAR_055434

Natural variant

857

1

N → S in ovarian cancer; somatic mutation. dbSNP rs28933370. Ref.20 Ref.19

VAR_042099

Natural variant

914

1

E → K in glioblastoma; somatic mutation. Ref.19

VAR_055435

Natural variant

1170

1

P → A: dbSNP rs1058808 and dbSNP rs61552325. Ref.3 Ref.20 Ref.2 Ref.7

VAR_016318

Natural variant

1216

1

A → D: dbSNP rs55943169. Ref.20

VAR_042100

Secondary structure

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1255

Helix Strand Turn

Details...

Beta strand

25 – 27

3

Helix

39 – 50

12

Beta strand

55 – 64

10

Helix

72 – 74

3

Beta strand

79 – 82

4

Beta strand

84 – 88

5

Turn

109 – 111

3

Beta strand

112 – 117

6

Beta strand

152 – 157

6

Turn

164 – 166

3

Helix

169 – 172

4

Helix

175 – 177

3

Beta strand

182 – 184

3

Beta strand

199 – 202

4

Beta strand

204 – 208

5

Beta strand

217 – 219

3

Beta strand

221 – 223

3

Beta strand

227 – 231

5

Helix

232 – 234

3

Beta strand

240 – 242

3

Beta strand

244 – 248

5

Beta strand

251 – 260

10

Beta strand

263 – 267

5

Beta strand

271 – 274

4

Turn

276 – 278

3

Beta strand

281 – 283

3

Beta strand

289 – 291

3

Beta strand

294 – 298

5

Beta strand

303 – 305

3

Beta strand

309 – 314

6

Beta strand

319 – 323

5

Beta strand

329 – 333

5

Beta strand

335 – 337

3

Helix

348 – 350

3

Turn

358 – 360

3

Helix

361 – 364

4

Beta strand

368 – 376

9

Helix

378 – 380

3

Helix

396 – 402

7

Beta strand

405 – 408

4

Beta strand

410 – 413

4

Helix

423 – 425

3

Turn

438 – 440

3

Beta strand

441 – 447

7

Beta strand

463 – 469

7

Helix

482 – 485

4

Beta strand

493 – 498

6

Helix

501 – 506

6

Helix

516 – 518

3

Beta strand

520 – 524

5

Beta strand

528 – 536

9

Beta strand

539 – 542

4

Beta strand

545 – 551

7

Beta strand

553 – 556

4

Beta strand

559 – 562

4

Beta strand

571 – 573

3

Beta strand

575 – 580

6

Beta strand

583 – 592

10

Beta strand

595 – 599

5

Beta strand

615 – 617

3

Beta strand

621 – 625

5

Helix

651 – 678

28

Sequences

	Sequence		Length	Mass (Da)
	P04626-1 [UniParc]. Last modified August 13, 1987. Version 1. Checksum: 39E9DFDA04DCF962	FASTA	1,255	137,910
	10 20 30 40 50 60 MELAALCRWG LLLALLPPGA ASTQVCTGTD MKLRLPASPE THLDMLRHLY QGCQVVQGNL 70 80 90 100 110 120 ELTYLPTNAS LSFLQDIQEV QGYVLIAHNQ VRQVPLQRLR IVRGTQLFED NYALAVLDNG 130 140 150 160 170 180 DPLNNTTPVT GASPGGLREL QLRSLTEILK GGVLIQRNPQ LCYQDTILWK DIFHKNNQLA 190 200 210 220 230 240 LTLIDTNRSR ACHPCSPMCK GSRCWGESSE DCQSLTRTVC AGGCARCKGP LPTDCCHEQC 250 260 270 280 290 300 AAGCTGPKHS DCLACLHFNH SGICELHCPA LVTYNTDTFE SMPNPEGRYT FGASCVTACP 310 320 330 340 350 360 YNYLSTDVGS CTLVCPLHNQ EVTAEDGTQR CEKCSKPCAR VCYGLGMEHL REVRAVTSAN 370 380 390 400 410 420 IQEFAGCKKI FGSLAFLPES FDGDPASNTA PLQPEQLQVF ETLEEITGYL YISAWPDSLP 430 440 450 460 470 480 DLSVFQNLQV IRGRILHNGA YSLTLQGLGI SWLGLRSLRE LGSGLALIHH NTHLCFVHTV 490 500 510 520 530 540 PWDQLFRNPH QALLHTANRP EDECVGEGLA CHQLCARGHC WGPGPTQCVN CSQFLRGQEC 550 560 570 580 590 600 VEECRVLQGL PREYVNARHC LPCHPECQPQ NGSVTCFGPE ADQCVACAHY KDPPFCVARC 610 620 630 640 650 660 PSGVKPDLSY MPIWKFPDEE GACQPCPINC THSCVDLDDK GCPAEQRASP LTSIISAVVG 670 680 690 700 710 720 ILLVVVLGVV FGILIKRRQQ KIRKYTMRRL LQETELVEPL TPSGAMPNQA QMRILKETEL 730 740 750 760 770 780 RKVKVLGSGA FGTVYKGIWI PDGENVKIPV AIKVLRENTS PKANKEILDE AYVMAGVGSP 790 800 810 820 830 840 YVSRLLGICL TSTVQLVTQL MPYGCLLDHV RENRGRLGSQ DLLNWCMQIA KGMSYLEDVR 850 860 870 880 890 900 LVHRDLAARN VLVKSPNHVK ITDFGLARLL DIDETEYHAD GGKVPIKWMA LESILRRRFT 910 920 930 940 950 960 HQSDVWSYGV TVWELMTFGA KPYDGIPARE IPDLLEKGER LPQPPICTID VYMIMVKCWM 970 980 990 1000 1010 1020 IDSECRPRFR ELVSEFSRMA RDPQRFVVIQ NEDLGPASPL DSTFYRSLLE DDDMGDLVDA 1030 1040 1050 1060 1070 1080 EEYLVPQQGF FCPDPAPGAG GMVHHRHRSS STRSGGGDLT LGLEPSEEEA PRSPLAPSEG 1090 1100 1110 1120 1130 1140 AGSDVFDGDL GMGAAKGLQS LPTHDPSPLQ RYSEDPTVPL PSETDGYVAP LTCSPQPEYV 1150 1160 1170 1180 1190 1200 NQPDVRPQPP SPREGPLPAA RPAGATLERP KTLSPGKNGV VKDVFAFGGA VENPEYLTPQ 1210 1220 1230 1240 1250 GGAAPQPHPP PAFSPAFDNL YYWDQDPPER GAPPSTFKGT PTAENPEYLG LDVPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor." Yamamoto T., Ikawa S., Akiyama T., Semba K., Nomura N., Miyajima N., Saito T., Toyoshima K. Nature 319:230-234(1986) [PubMed: 3003577] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene." Coussens L., Yang-Feng T.L., Liao Y.C., Chen E., Gray A., McGrath J., Seeburg P.H., Libermann T.A., Schlessinger J., Francke U., Levinson A., Ullrich A. Science 230:1132-1139(1985) [PubMed: 2999974] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT ALA-1170.
[3]	NIEHS SNPs program Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-452; VAL-655 AND ALA-1170.
[4]	"Human HER2 (neu) promoter: evidence for multiple mechanisms for transcriptional initiation." Tal M., King C.R., Kraus M.H., Ullrich A., Schlessinger J., Givol D. Mol. Cell. Biol. 7:2597-2601(1987) [PubMed: 3039351] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-191.
[5]	"A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma." Semba K., Kamata N., Toyoshima K., Yamamoto T. Proc. Natl. Acad. Sci. U.S.A. 82:6497-6501(1985) [PubMed: 2995967] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 737-1031.
[6]	"Amplification of a novel v-erbB-related gene in a human mammary carcinoma." King C.R., Kraus M.H., Aaronson S.A. Science 229:974-976(1985) [PubMed: 2992089] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 832-909. Tissue: Mammary carcinoma.
[7]	"Molecular cloning and sequencing of an intron of Her-2/neu (ERBB2) gene." Sarkar F.H., Ball D.E., Li Y.W., Crissman J.D. DNA Cell Biol. 12:611-615(1993) [PubMed: 8104414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1081-1245, VARIANT ALA-1170.
[8]	"Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors." Arcaro A., Zvelebil M.J., Wallasch C., Ullrich A., Waterfield M.D., Domin J. Mol. Cell. Biol. 20:3817-3830(2000) [PubMed: 10805725] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH PIK3C2A AND EGFR, IDENTIFICATION IN A COMPLEX WITH PIK3C2B AND EGFR, INTERACTION WITH PIK3C2B.
[9]	"Heregulin targets gamma-catenin to the nucleolus by a mechanism dependent on the DF3/MUC1 oncoprotein." Li Y., Yu W.-H., Ren J., Chen W., Huang L., Kharbanda S., Loda M., Kufe D. Mol. Cancer Res. 1:765-775(2003) [PubMed: 12939402] [Abstract] Cited for: INTERACTION WITH MUC1.
[10]	"Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2." Swiercz J.M., Kuner R., Offermanns S. J. Cell Biol. 165:869-880(2004) [PubMed: 15210733] [Abstract] Cited for: INTERACTION WITH PLXNB1.
[11]	"Memo mediates ErbB2-driven cell motility." Marone R., Hess D., Dankort D., Muller W.J., Hynes N.E., Badache A. Nat. Cell Biol. 6:515-522(2004) [PubMed: 15156151] [Abstract] Cited for: INTERACTION WITH MEMO.
[12]	"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-1248, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	"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-735, MASS SPECTROMETRY. Tissue: Lung.
[14]	"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-1054, MASS SPECTROMETRY.
[15]	"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 SER-1054, MASS SPECTROMETRY.
[16]	"Poor binding of a HER-2/neu epitope (GP2) to HLA-A2.1 is due to a lack of interactions with the center of the peptide." Kuhns J.J., Batalia M.A., Yan S., Collins E.J. J. Biol. Chem. 274:36422-36427(1999) [PubMed: 10593938] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 654-662 IN COMPLEX WITH HLA AND BETA-2 MICROGLOBULIN.
[17]	"Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab." Cho H.-S., Mason K., Ramyar K.X., Stanley A.M., Gabelli S.B., Denney D.W. Jr., Leahy D.J. Nature 421:756-760(2003) [PubMed: 12610629] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) OF 23-629 IN COMPLEX WITH FAB.
[18]	"Characterization of a new allele of the human ERBB2 gene by allele-specific competition hybridization." Ehsani A., Low J., Wallace R.B., Wu A.M. Genomics 15:426-429(1993) [PubMed: 8095488] [Abstract] Cited for: VARIANTS VAL-654 AND VAL-655.
[19]	"Intragenic ERBB2 kinase mutations in tumours." Cancer genome project and collaborative group Stephens P., Hunter C., Bignell G., Edkins S., Davies H., Teague J., Stevens C., O'Meara S., Smith R., Parker A., Barthorpe A., Blow M., Brackenbury L., Butler A., Clarke O., Cole J., Dicks E., Dike A. , Drozd A., Edwards K., Forbes S., Foster R., Gray K., Greenman C., Halliday K., Hills K., Kosmidou V., Lugg R., Menzies A., Perry J., Petty R., Raine K., Ratford L., Shepherd R., Small A., Stephens Y., Tofts C., Varian J., West S., Widaa S., Yates A., Brasseur F., Cooper C.S., Flanagan A.M., Knowles M., Leung S.Y., Louis D.N., Looijenga L.H.J., Malkowicz B., Pierotti M.A., Teh B., Chenevix-Trench G., Weber B.L., Yuen S.T., Harris G., Goldstraw P., Nicholson A.G., Futreal P.A., Wooster R., Stratton M.R. Nature 431:525-526(2004) Cited for: VARIANTS ADENOCARCINOMA OF LUNG PRO-755; ALA-TYR-VAL-MET-774 INS AND VAL-GLY-SER-779 INS, VARIANT GASTRIC CANCER SER-776, VARIANT OVARIAN CANCER SER-857, VARIANT GLIOBLASTOMA LYS-914.
[20]	"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-654; VAL-655; SER-768; SER-776; SER-857; ALA-1170 AND ASP-1216.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Wikipedia

ERBB2 entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

M11767 , M11761, M11762, M11763, M11764, M11765, M11766 Genomic DNA. Translation: AAA35808.1.
M11730 mRNA. Translation: AAA75493.1.
M12036 Genomic DNA. Translation: AAA35978.1.
AY208911 Genomic DNA. Translation: AAO18082.1.
X03363 mRNA. Translation: CAA27060.1.
M16792 , M16789, M16790, M16791 Genomic DNA. Translation: AAA58637.1.
L29395 Genomic DNA. Translation: AAA35809.1.
M95667 Unassigned DNA. Translation: AAC37531.1.

IPI

IPI00300384.

PIR

A24571.

RefSeq

NP_001005862.1.
NP_004439.2.

UniGene

Hs.446352

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MFG	X-ray	1.25	B	1247-1255	[»]
1MFL	X-ray	1.88	B	1247-1255	[»]
1MW4	NMR	-	B	1135-1144	[»]
1N8Z	X-ray	2.52	C	23-629	[»]
1OVC	model	-	A	737-1031	[»]
1QR1	X-ray	2.40	C/F	654-662	[»]
1S78	X-ray	3.25	A/B	23-646	[»]
2A91	X-ray	2.50	A	22-530	[»]
2JWA	NMR	-	A/B	641-684	[»]
3BE1	X-ray	2.90	A	23-646	[»]

SMR

P04626. Positions 704-1026.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:8N.

IntAct

P04626. 21 interactions.

STRING

P04626.

PTM databases

PhosphoSite

P04626.

Proteomic databases

PRIDE

P04626.

Genome annotation databases

Ensembl

ENST00000269571; ENSP00000269571; ENSG00000141736; Homo sapiens. [Genome view]
ENST00000406381; ENSP00000385185; ENSG00000141736; Homo sapiens. [Genome view]
ENST00000445658; ENSP00000404047; ENSG00000141736; Homo sapiens. [Genome view]

GeneID

2064.

KEGG

hsa:2064.

UCSC

uc002hso.1. human.

Organism-specific databases

CTD

2064.

GeneCards

GC17P035109.

H-InvDB

HIX0039027.

HGNC

HGNC:3430. ERBB2.

HPA

CAB000043.
CAB020416.
HPA001383.

MIM

137215. phenotype.
137800. phenotype.
164870. gene.
167000. phenotype.
211980. phenotype.

PharmGKB

PA27844.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P04626.

HOVERGEN

P04626.

OMA

ACYPLCA.

Enzyme and pathway databases

BRENDA

2.7.10.1. 247.

Pathway_Interaction_DB

a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.

Reactome

REACT_18266. Axon guidance.

Gene expression databases

ArrayExpress

P04626.

Bgee

P04626.

CleanEx

HS_ERBB2.

Genevestigator

P04626.

GermOnline

ENSG00000141736. Homo sapiens.

Family and domain databases

InterPro

IPR000494. EGF_rcpt_L.
IPR006211. Furin-like.
IPR006212. Furin_repeat.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR016245. Tyr_kinase_rcpt_EGF/ERB/XmrK.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
IPR004019. YLP_motif.
[Graphical view]

Pfam

PF00757. Furin-like. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
PF02757. YLP. 2 hits.
[Graphical view]

PIRSF

PIRSF000619. TyrPK_EGF-R. 1 hit.

PRINTS

PR00109. TYRKINASE.

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00261. FU. 3 hits.
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.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB01259. Lapatinib.
DB01006. Letrozole.
DB00072. Trastuzumab.

NextBio

8385.

PMAP-CutDB

P04626.

SOURCE

Search...

Entry information

Entry name

ERBB2_HUMAN

Accession

Primary (citable) accession number: P04626
Secondary accession number(s): Q14256, Q6LDV1, Q9UMK4

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	August 13, 1987
Last modified:	November 3, 2009
This is version 136 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.