P21860 (ERBB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Receptor tyrosine-protein kinase erbB-3
EC=2.7.10.1

Alternative name(s):
Proto-oncogene-like protein c-ErbB-3
Tyrosine kinase-type cell surface receptor HER3

Gene names

Name:	ERBB3
Synonyms:	HER3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1342 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	Binds and is activated by neuregulins and NTAK. Ref.11
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.16
Subunit structure	Monomer and homodimer. Heterodimer with each of the other ERBB receptors Potential. Interacts with CSPG5, PA2G4, GRB7 and MUC1. Ref.8 Ref.9 Ref.10 Ref.11 Ref.15 Ref.16 Ref.17
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted.
Tissue specificity	Epithelial tissues and brain.
Developmental stage	Overexpressed in a subset of human mammary tumors.
Domain	The cytoplasmic part of the receptor may interact with the SH2 or SH3 domains of many signal-transducing proteins.
Post-translational modification	Ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase By similarity. Subject to autophosphorylation.
Involvement in disease	Lethal congenital contracture syndrome 2 (LCCS2) [MIM:607598]: A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy, and congenital non-progressive joint contractures (arthrogryposis). The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS2 patients manifest craniofacial/ocular findings, lack of hydrops, multiple pterygia, and fractures, as well as a normal duration of pregnancy and a unique feature of a markedly distended urinary bladder (neurogenic bladder defect). The phenotype suggests a spinal cord neuropathic etiology. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Schwann cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL cranial nerve development Inferred from sequence or structural similarity. Source: BHF-UCL endocardial cushion development Inferred from electronic annotation. Source: Compara heart development Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of cell adhesion Inferred from direct assay PubMed 7556068. Source: BHF-UCL negative regulation of neuron apoptotic process Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of secretion Inferred from direct assay PubMed 10559227. Source: BHF-UCL negative regulation of signal transduction Inferred from direct assay PubMed 11389077. Source: BHF-UCL neuron apoptotic process Inferred from mutant phenotype Ref.12. Source: BHF-UCL phosphatidylinositol 3-kinase cascade Inferred from direct assay PubMed 7556068. Source: BHF-UCL positive regulation of phosphatidylinositol 3-kinase cascade Traceable author statement Ref.12. Source: BHF-UCL regulation of cell proliferation Inferred from direct assay PubMed 11389077. Source: BHF-UCL transmembrane receptor protein tyrosine kinase signaling pathway Inferred from sequence or structural similarity PubMed 7514177. Source: BHF-UCL wound healing Non-traceable author statement PubMed 12646923. Source: BHF-UCL
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Compara basolateral plasma membrane Inferred from direct assay PubMed 12646923. Source: BHF-UCL extracellular space Inferred from direct assay PubMed 11389077. Source: BHF-UCL integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc lateral plasma membrane Inferred from electronic annotation. Source: Compara receptor complex Inferred from sequence or structural similarity PubMed 7514177. Source: BHF-UCL
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW growth factor binding Inferred from sequence or structural similarity PubMed 7514177. Source: BHF-UCL protein heterodimerization activity Inferred from direct assay PubMed 10572067. Source: UniProtKB protein homodimerization activity Non-traceable author statement PubMed 11389077. Source: BHF-UCL protein kinase activity Inferred from electronic annotation. Source: InterPro protein tyrosine kinase activator activity Inferred from direct assay PubMed 7556068. Source: BHF-UCL transmembrane signaling receptor activity Inferred from sequence or structural similarity PubMed 7514177. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EGFR	P00533	6	EBI-720706,EBI-297353
ERBB2	P04626	15	EBI-720706,EBI-641062
ERBB4	Q15303	4	EBI-720706,EBI-80371
NRG1	Q02297-7	3	EBI-720706,EBI-2460927
PIK3R1	P27986	23	EBI-720706,EBI-79464

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P21860-1)

Also known as: long form;

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: P21860-2)

Also known as: short form;

The sequence of this isoform differs from the canonical sequence as follows:
     141-183: EILSGGVYIE...IVVKDNGRSC → GQFPMVPSGL...SKVPVTLAAV
     184-1342: Missing.

Isoform 3 (identifier: P21860-3)

The sequence of this isoform differs from the canonical sequence as follows:
     331-331: C → F
     332-1342: Missing.

Isoform 4 (identifier: P21860-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: Missing.

Isoform 5 (identifier: P21860-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-643: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Potential

Chain

20 – 1342

1323

Receptor tyrosine-protein kinase erbB-3

PRO_0000016672

Regions

Topological domain

20 – 643

624

Extracellular Potential

Transmembrane

644 – 664

21

Helical; Potential

Topological domain

665 – 1342

678

Cytoplasmic Potential

Domain

709 – 966

258

Protein kinase

Nucleotide binding

715 – 723

9

ATP

Nucleotide binding

788 – 790

3

ATP

Nucleotide binding

834 – 839

6

ATP

Sites

Active site

834

1

Proton acceptor By similarity

Binding site

742

1

ATP

Amino acid modifications

Glycosylation

126

1

N-linked (GlcNAc...) Potential

Glycosylation

250

1

N-linked (GlcNAc...) Ref.14

Glycosylation

353

1

N-linked (GlcNAc...) Ref.14

Glycosylation

408

1

N-linked (GlcNAc...) Ref.14

Glycosylation

414

1

N-linked (GlcNAc...) Ref.14

Glycosylation

437

1

N-linked (GlcNAc...) Ref.14

Glycosylation

469

1

N-linked (GlcNAc...) Ref.14

Glycosylation

522

1

N-linked (GlcNAc...) Ref.14

Glycosylation

566

1

N-linked (GlcNAc...) Ref.14

Glycosylation

616

1

N-linked (GlcNAc...) Potential

Disulfide bond

29 ↔ 56

Ref.14

Disulfide bond

156 ↔ 183

Ref.14

Disulfide bond

186 ↔ 194

Ref.14

Disulfide bond

190 ↔ 202

Ref.14

Disulfide bond

210 ↔ 218

Ref.14

Disulfide bond

214 ↔ 226

Ref.14

Disulfide bond

227 ↔ 235

Ref.14

Disulfide bond

231 ↔ 243

Ref.14

Disulfide bond

246 ↔ 255

Ref.14

Disulfide bond

259 ↔ 286

Ref.14

Disulfide bond

290 ↔ 301

Ref.14

Disulfide bond

305 ↔ 320

Ref.14

Disulfide bond

323 ↔ 327

Ref.14

Disulfide bond

500 ↔ 509

Ref.14

Disulfide bond

504 ↔ 517

Ref.14

Disulfide bond

520 ↔ 529

Ref.14

Disulfide bond

533 ↔ 549

Ref.14

Disulfide bond

552 ↔ 565

Ref.14

Disulfide bond

556 ↔ 573

Ref.14

Disulfide bond

576 ↔ 585

Ref.14

Disulfide bond

589 ↔ 610

By similarity

Disulfide bond

613 ↔ 621

By similarity

Disulfide bond

617 ↔ 629

By similarity

Natural variations

Alternative sequence

1 – 643

643

Missing in isoform 5.

VSP_041661

Alternative sequence

1 – 59

59

Missing in isoform 4.

VSP_041662

Alternative sequence

141 – 183

43

EILSG…NGRSC → GQFPMVPSGLTPQPAQDWYL LDDDPRLLTLSASSKVPVTL AAV in isoform 2.

VSP_002893

Alternative sequence

184 – 1342

1159

Missing in isoform 2.

VSP_002894

Alternative sequence

331

1

C → F in isoform 3.

VSP_041663

Alternative sequence

332 – 1342

1011

Missing in isoform 3.

VSP_041664

Natural variant

20

1

S → Y. Ref.18
Corresponds to variant rs34379766 [ dbSNP | Ensembl ].

VAR_042101

Natural variant

30

1

P → L. Ref.18
Corresponds to variant rs56017157 [ dbSNP | Ensembl ].

VAR_042102

Natural variant

104

1

V → M in an ovarian mucinous carcinoma sample; somatic mutation. Ref.18

VAR_042103

Natural variant

204

1

T → I. Ref.18
Corresponds to variant rs56107455 [ dbSNP | Ensembl ].

VAR_042104

Natural variant

385

1

N → S.
Corresponds to variant rs12320176 [ dbSNP | Ensembl ].

VAR_049710

Natural variant

683

1

R → W. Ref.18
Corresponds to variant rs56387488 [ dbSNP | Ensembl ].

VAR_042105

Natural variant

717

1

S → L. Ref.18
Corresponds to variant rs35961836 [ dbSNP | Ensembl ].

VAR_042106

Natural variant

744

1

I → T. Ref.18
Corresponds to variant rs55787439 [ dbSNP | Ensembl ].

VAR_042107

Natural variant

998

1

K → R. Ref.18
Corresponds to variant rs56259600 [ dbSNP | Ensembl ].

VAR_042108

Natural variant

1119

1

S → C. Ref.18
Corresponds to variant rs773123 [ dbSNP | Ensembl ].

VAR_042109

Natural variant

1127

1

R → H. Ref.18
Corresponds to variant rs2271188 [ dbSNP | Ensembl ].

VAR_042110

Natural variant

1177

1

L → I. Ref.18
Corresponds to variant rs55699040 [ dbSNP | Ensembl ].

VAR_042111

Natural variant

1254

1

T → K. Ref.18
Corresponds to variant rs55709407 [ dbSNP | Ensembl ].

VAR_042112

Natural variant

1271

1

G → S.
Corresponds to variant rs11171743 [ dbSNP | Ensembl ].

VAR_049711

Experimental info

Mutagenesis

742

1

K → M: Strongly reduced autophosphorylation. Ref.16

Mutagenesis

868

1

Y → E: Strongly reduced tyrosine phosphorylation. Ref.16

Sequence conflict

560

1

E → G in AAA35979. Ref.2

Sequence conflict

684

1

G → S in BAF84370. Ref.5

Sequence conflict

1064

1

E → G in AAA35979. Ref.2

Sequence conflict

1078

1

C → S in BAG62544. Ref.5

Sequence conflict

1163

1

D → G in BAF84370. Ref.5

Secondary structure

1

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1342

Helix Strand Turn

Details...

Beta strand

58 – 61

4

Beta strand

63 – 67

5

Helix

75 – 79

5

Beta strand

82 – 85

4

Beta strand

87 – 91

5

Beta strand

95 – 98

4

Turn

112 – 114

3

Beta strand

115 – 120

6

Beta strand

133 – 135

3

Beta strand

146 – 150

5

Turn

158 – 160

3

Helix

163 – 166

4

Beta strand

174 – 178

5

Beta strand

194 – 198

5

Beta strand

214 – 216

3

Beta strand

218 – 222

5

Beta strand

231 – 233

3

Beta strand

235 – 239

5

Helix

240 – 242

3

Beta strand

243 – 251

9

Beta strand

254 – 258

5

Beta strand

262 – 265

4

Turn

267 – 269

3

Beta strand

270 – 274

5

Beta strand

280 – 282

3

Beta strand

285 – 289

5

Beta strand

295 – 297

3

Beta strand

300 – 304

5

Beta strand

309 – 314

6

Beta strand

317 – 322

6

Beta strand

330 – 332

3

Turn

345 – 347

3

Helix

348 – 351

4

Beta strand

356 – 363

8

Helix

365 – 369

5

Turn

372 – 375

4

Helix

381 – 389

9

Beta strand

392 – 395

4

Beta strand

397 – 400

4

Helix

410 – 412

3

Beta strand

425 – 433

9

Beta strand

451 – 457

7

Helix

470 – 473

4

Beta strand

482 – 488

7

Helix

490 – 493

4

Turn

494 – 497

4

Beta strand

509 – 513

5

Helix

514 – 516

3

Beta strand

517 – 527

11

Beta strand

529 – 531

3

Beta strand

534 – 536

3

Beta strand

538 – 540

3

Beta strand

542 – 545

4

Beta strand

548 – 551

4

Beta strand

564 – 570

7

Beta strand

573 – 581

9

Beta strand

584 – 588

5

Helix

641 – 670

30

Turn

706 – 708

3

Beta strand

709 – 716

8

Beta strand

722 – 728

7

Beta strand

731 – 733

3

Beta strand

737 – 744

8

Helix

758 – 764

7

Beta strand

774 – 778

5

Beta strand

780 – 788

9

Helix

796 – 800

5

Helix

803 – 805

3

Helix

810 – 827

18

Turn

837 – 839

3

Beta strand

840 – 846

7

Beta strand

848 – 850

3

Helix

855 – 858

4

Turn

875 – 877

3

Helix

880 – 885

6

Helix

890 – 905

16

Turn

911 – 914

4

Helix

919 – 925

7

Turn

938 – 941

4

Helix

942 – 947

6

Turn

952 – 954

3

Helix

958 – 968

11

Helix

972 – 975

4

Beta strand

980 – 983

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (long form) [UniParc]. Last modified May 1, 1991. Version 1. Checksum: 7201E7F66CA374BD	FASTA	1,342	148,098
	10 20 30 40 50 60 MRANDALQVL GLLFSLARGS EVGNSQAVCP GTLNGLSVTG DAENQYQTLY KLYERCEVVM 70 80 90 100 110 120 GNLEIVLTGH NADLSFLQWI REVTGYVLVA MNEFSTLPLP NLRVVRGTQV YDGKFAIFVM 130 140 150 160 170 180 LNYNTNSSHA LRQLRLTQLT EILSGGVYIE KNDKLCHMDT IDWRDIVRDR DAEIVVKDNG 190 200 210 220 230 240 RSCPPCHEVC KGRCWGPGSE DCQTLTKTIC APQCNGHCFG PNPNQCCHDE CAGGCSGPQD 250 260 270 280 290 300 TDCFACRHFN DSGACVPRCP QPLVYNKLTF QLEPNPHTKY QYGGVCVASC PHNFVVDQTS 310 320 330 340 350 360 CVRACPPDKM EVDKNGLKMC EPCGGLCPKA CEGTGSGSRF QTVDSSNIDG FVNCTKILGN 370 380 390 400 410 420 LDFLITGLNG DPWHKIPALD PEKLNVFRTV REITGYLNIQ SWPPHMHNFS VFSNLTTIGG 430 440 450 460 470 480 RSLYNRGFSL LIMKNLNVTS LGFRSLKEIS AGRIYISANR QLCYHHSLNW TKVLRGPTEE 490 500 510 520 530 540 RLDIKHNRPR RDCVAEGKVC DPLCSSGGCW GPGPGQCLSC RNYSRGGVCV THCNFLNGEP 550 560 570 580 590 600 REFAHEAECF SCHPECQPME GTATCNGSGS DTCAQCAHFR DGPHCVSSCP HGVLGAKGPI 610 620 630 640 650 660 YKYPDVQNEC RPCHENCTQG CKGPELQDCL GQTLVLIGKT HLTMALTVIA GLVVIFMMLG 670 680 690 700 710 720 GTFLYWRGRR IQNKRAMRRY LERGESIEPL DPSEKANKVL ARIFKETELR KLKVLGSGVF 730 740 750 760 770 780 GTVHKGVWIP EGESIKIPVC IKVIEDKSGR QSFQAVTDHM LAIGSLDHAH IVRLLGLCPG 790 800 810 820 830 840 SSLQLVTQYL PLGSLLDHVR QHRGALGPQL LLNWGVQIAK GMYYLEEHGM VHRNLAARNV 850 860 870 880 890 900 LLKSPSQVQV ADFGVADLLP PDDKQLLYSE AKTPIKWMAL ESIHFGKYTH QSDVWSYGVT 910 920 930 940 950 960 VWELMTFGAE PYAGLRLAEV PDLLEKGERL AQPQICTIDV YMVMVKCWMI DENIRPTFKE 970 980 990 1000 1010 1020 LANEFTRMAR DPPRYLVIKR ESGPGIAPGP EPHGLTNKKL EEVELEPELD LDLDLEAEED 1030 1040 1050 1060 1070 1080 NLATTTLGSA LSLPVGTLNR PRGSQSLLSP SSGYMPMNQG NLGESCQESA VSGSSERCPR 1090 1100 1110 1120 1130 1140 PVSLHPMPRG CLASESSEGH VTGSEAELQE KVSMCRSRSR SRSPRPRGDS AYHSQRHSLL 1150 1160 1170 1180 1190 1200 TPVTPLSPPG LEEEDVNGYV MPDTHLKGTP SSREGTLSSV GLSSVLGTEE EDEDEEYEYM 1210 1220 1230 1240 1250 1260 NRRRRHSPPH PPRPSSLEEL GYEYMDVGSD LSASLGSTQS CPLHPVPIMP TAGTTPDEDY 1270 1280 1290 1300 1310 1320 EYMNRQRDGG GPGGDYAAMG ACPASEQGYE EMRAFQGPGH QAPHVHYARL KTLRSLEATD 1330 1340 SAFDNPDYWH SRLFPKANAQ RT
	Isoform 2 (short form) [UniParc]. Checksum: DA25DD25D34DE5E3	FASTA	183	20,136
	10 20 30 40 50 60 MRANDALQVL GLLFSLARGS EVGNSQAVCP GTLNGLSVTG DAENQYQTLY KLYERCEVVM 70 80 90 100 110 120 GNLEIVLTGH NADLSFLQWI REVTGYVLVA MNEFSTLPLP NLRVVRGTQV YDGKFAIFVM 130 140 150 160 170 180 LNYNTNSSHA LRQLRLTQLT GQFPMVPSGL TPQPAQDWYL LDDDPRLLTL SASSKVPVTL AAV
	Isoform 3 [UniParc]. Checksum: 45B8EBEE683FE7E8	FASTA	331	36,490
	10 20 30 40 50 60 MRANDALQVL GLLFSLARGS EVGNSQAVCP GTLNGLSVTG DAENQYQTLY KLYERCEVVM 70 80 90 100 110 120 GNLEIVLTGH NADLSFLQWI REVTGYVLVA MNEFSTLPLP NLRVVRGTQV YDGKFAIFVM 130 140 150 160 170 180 LNYNTNSSHA LRQLRLTQLT EILSGGVYIE KNDKLCHMDT IDWRDIVRDR DAEIVVKDNG 190 200 210 220 230 240 RSCPPCHEVC KGRCWGPGSE DCQTLTKTIC APQCNGHCFG PNPNQCCHDE CAGGCSGPQD 250 260 270 280 290 300 TDCFACRHFN DSGACVPRCP QPLVYNKLTF QLEPNPHTKY QYGGVCVASC PHNFVVDQTS 310 320 330 CVRACPPDKM EVDKNGLKMC EPCGGLCPKA F
	Isoform 4 [UniParc]. Checksum: D40BB4459539D894	FASTA	1,283	141,752
	10 20 30 40 50 60 MGNLEIVLTG HNADLSFLQW IREVTGYVLV AMNEFSTLPL PNLRVVRGTQ VYDGKFAIFV 70 80 90 100 110 120 MLNYNTNSSH ALRQLRLTQL TEILSGGVYI EKNDKLCHMD TIDWRDIVRD RDAEIVVKDN 130 140 150 160 170 180 GRSCPPCHEV CKGRCWGPGS EDCQTLTKTI CAPQCNGHCF GPNPNQCCHD ECAGGCSGPQ 190 200 210 220 230 240 DTDCFACRHF NDSGACVPRC PQPLVYNKLT FQLEPNPHTK YQYGGVCVAS CPHNFVVDQT 250 260 270 280 290 300 SCVRACPPDK MEVDKNGLKM CEPCGGLCPK ACEGTGSGSR FQTVDSSNID GFVNCTKILG 310 320 330 340 350 360 NLDFLITGLN GDPWHKIPAL DPEKLNVFRT VREITGYLNI QSWPPHMHNF SVFSNLTTIG 370 380 390 400 410 420 GRSLYNRGFS LLIMKNLNVT SLGFRSLKEI SAGRIYISAN RQLCYHHSLN WTKVLRGPTE 430 440 450 460 470 480 ERLDIKHNRP RRDCVAEGKV CDPLCSSGGC WGPGPGQCLS CRNYSRGGVC VTHCNFLNGE 490 500 510 520 530 540 PREFAHEAEC FSCHPECQPM EGTATCNGSG SDTCAQCAHF RDGPHCVSSC PHGVLGAKGP 550 560 570 580 590 600 IYKYPDVQNE CRPCHENCTQ GCKGPELQDC LGQTLVLIGK THLTMALTVI AGLVVIFMML 610 620 630 640 650 660 GGTFLYWRGR RIQNKRAMRR YLERGESIEP LDPSEKANKV LARIFKETEL RKLKVLGSGV 670 680 690 700 710 720 FGTVHKGVWI PEGESIKIPV CIKVIEDKSG RQSFQAVTDH MLAIGSLDHA HIVRLLGLCP 730 740 750 760 770 780 GSSLQLVTQY LPLGSLLDHV RQHRGALGPQ LLLNWGVQIA KGMYYLEEHG MVHRNLAARN 790 800 810 820 830 840 VLLKSPSQVQ VADFGVADLL PPDDKQLLYS EAKTPIKWMA LESIHFGKYT HQSDVWSYGV 850 860 870 880 890 900 TVWELMTFGA EPYAGLRLAE VPDLLEKGER LAQPQICTID VYMVMVKCWM IDENIRPTFK 910 920 930 940 950 960 ELANEFTRMA RDPPRYLVIK RESGPGIAPG PEPHGLTNKK LEEVELEPEL DLDLDLEAEE 970 980 990 1000 1010 1020 DNLATTTLGS ALSLPVGTLN RPRGSQSLLS PSSGYMPMNQ GNLGESCQES AVSGSSERCP 1030 1040 1050 1060 1070 1080 RPVSLHPMPR GCLASESSEG HVTGSEAELQ EKVSMCRSRS RSRSPRPRGD SAYHSQRHSL 1090 1100 1110 1120 1130 1140 LTPVTPLSPP GLEEEDVNGY VMPDTHLKGT PSSREGTLSS VGLSSVLGTE EEDEDEEYEY 1150 1160 1170 1180 1190 1200 MNRRRRHSPP HPPRPSSLEE LGYEYMDVGS DLSASLGSTQ SCPLHPVPIM PTAGTTPDED 1210 1220 1230 1240 1250 1260 YEYMNRQRDG GGPGGDYAAM GACPASEQGY EEMRAFQGPG HQAPHVHYAR LKTLRSLEAT 1270 1280 DSAFDNPDYW HSRLFPKANA QRT
	Isoform 5 [UniParc]. Checksum: C7C94A8F051DCE15	FASTA	699	77,426
	10 20 30 40 50 60 MALTVIAGLV VIFMMLGGTF LYWRGRRIQN KRAMRRYLER GESIEPLDPS EKANKVLARI 70 80 90 100 110 120 FKETELRKLK VLGSGVFGTV HKGVWIPEGE SIKIPVCIKV IEDKSGRQSF QAVTDHMLAI 130 140 150 160 170 180 GSLDHAHIVR LLGLCPGSSL QLVTQYLPLG SLLDHVRQHR GALGPQLLLN WGVQIAKGMY 190 200 210 220 230 240 YLEEHGMVHR NLAARNVLLK SPSQVQVADF GVADLLPPDD KQLLYSEAKT PIKWMALESI 250 260 270 280 290 300 HFGKYTHQSD VWSYGVTVWE LMTFGAEPYA GLRLAEVPDL LEKGERLAQP QICTIDVYMV 310 320 330 340 350 360 MVKCWMIDEN IRPTFKELAN EFTRMARDPP RYLVIKRESG PGIAPGPEPH GLTNKKLEEV 370 380 390 400 410 420 ELEPELDLDL DLEAEEDNLA TTTLGSALSL PVGTLNRPRG SQSLLSPSSG YMPMNQGNLG 430 440 450 460 470 480 ESCQESAVSG SSERCPRPVS LHPMPRGCLA SESSEGHVTG SEAELQEKVS MCRSRSRSRS 490 500 510 520 530 540 PRPRGDSAYH SQRHSLLTPV TPLSPPGLEE EDVNGYVMPD THLKGTPSSR EGTLSSVGLS 550 560 570 580 590 600 SVLGTEEEDE DEEYEYMNRR RRHSPPHPPR PSSLEELGYE YMDVGSDLSA SLGSTQSCPL 610 620 630 640 650 660 HPVPIMPTAG TTPDEDYEYM NRQRDGGGPG GDYAAMGACP ASEQGYEEMR AFQGPGHQAP 670 680 690 HVHYARLKTL RSLEATDSAF DNPDYWHSRL FPKANAQRT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors." Kraus M.H., Issing W., Miki T., Popescu N.C., Aaronson S.A. Proc. Natl. Acad. Sci. U.S.A. 86:9193-9197(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Molecular cloning and expression of an additional epidermal growth factor receptor-related gene." Plowman G.D., Whitney G.S., Neubauer M.G., Green J.M., McDonald V.L., Todaro G.J., Shoyab M. Proc. Natl. Acad. Sci. U.S.A. 87:4905-4909(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"c-erbB3 gene encodes secreted as well as transmembrane receptor tyrosine kinase." Katoh M., Yazaki Y., Sugimura T., Terada M. Biochem. Biophys. Res. Commun. 192:1189-1197(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Placenta.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 4 AND 5). Tissue: Hippocampus, Placenta and Small intestine.
[6]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Tissue: Skin.
[8]	"Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals a novel target selectivity for erbB3." Fiddes R.J., Campbell D.H., Janes P.W., Sivertsen S.P., Sasaki H., Wallasch C., Daly R.J. J. Biol. Chem. 273:7717-7724(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRB7.
[9]	"Regulation of the ErbB3 binding protein Ebp1 by protein kinase C." Lessor T.J., Hamburger A.W. Mol. Cell. Endocrinol. 175:185-191(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PA2G4.
[10]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MUC1.
[11]	"Neuroglycan C, a novel member of the neuregulin family." Kinugasa Y., Ishiguro H., Tokita Y., Oohira A., Ohmoto H., Higashiyama S. Biochem. Biophys. Res. Commun. 321:1045-1049(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CSPG5, FUNCTION.
[12]	"Lethal congenital contractural syndrome type 2 (LCCS2) is caused by a mutation in ERBB3 (Her3), a modulator of the phosphatidylinositol-3-kinase/Akt pathway." Narkis G., Ofir R., Manor E., Landau D., Elbedour K., Birk O.S. Am. J. Hum. Genet. 81:589-595(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN LCCS2.
[13]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"Structure of the extracellular region of HER3 reveals an interdomain tether." Cho H.S., Leahy D.J. Science 297:1330-1333(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 20-640, DISULFIDE BONDS, GLYCOSYLATION AT ASN-250; ASN-353; ASN-408; ASN-414; ASN-437; ASN-469; ASN-522 AND ASN-566.
[15]	"Structural analysis of the catalytically inactive kinase domain of the human EGF receptor 3." Jura N., Shan Y., Cao X., Shaw D.E., Kuriyan J. Proc. Natl. Acad. Sci. U.S.A. 106:21608-21613(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 698-1019 IN COMPLEX WITH AMP-PNP, SUBUNIT.
[16]	"ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation." Shi F., Telesco S.E., Liu Y., Radhakrishnan R., Lemmon M.A. Proc. Natl. Acad. Sci. U.S.A. 107:7692-7697(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 684-1020 IN COMPLEX WITH AMP-PNP, CATALYTIC ACTIVITY, MUTAGENESIS OF LYS-742 AND TYR-868, AUTOPHOSPHORYLATION, SUBUNIT.
[17]	"Spatial structure and dimer-monomer equilibrium of the ErbB3 transmembrane domain in DPC micelles." Mineev K.S., Khabibullina N.F., Lyukmanova E.N., Dolgikh D.A., Kirpichnikov M.P., Arseniev A.S. Biochim. Biophys. Acta 1808:2081-2088(2011) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 640-670, SUBUNIT.
[18]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] TYR-20; LEU-30; MET-104; ILE-204; TRP-683; LEU-717; THR-744; ARG-998; CYS-1119; HIS-1127; ILE-1177 AND LYS-1254.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M29366 mRNA. Translation: AAA35790.1.
M34309 mRNA. Translation: AAA35979.1.
S61953 mRNA. Translation: AAB26935.1.
BT007226 mRNA. Translation: AAP35890.1.
AK291681 mRNA. Translation: BAF84370.1.
AK295650 mRNA. Translation: BAG58519.1.
AK300909 mRNA. Translation: BAG62544.1.
AC034102 Genomic DNA. No translation available.
BC002706 mRNA. Translation: AAH02706.1.
BC082992 mRNA. Translation: AAH82992.1.

IPI

IPI00219206.
IPI00298285.
IPI00794366.
IPI01010940.
IPI01022989.

PIR

A36223.
JH0803.

RefSeq

NP_001005915.1. NM_001005915.1.
NP_001973.2. NM_001982.3.

UniGene

Hs.118681.
Hs.622058.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M6B	X-ray	2.60	A/B	20-640	[»]
2L9U	NMR	-	A/B	640-670	[»]
3KEX	X-ray	2.80	A/B	698-1019	[»]
3LMG	X-ray	2.80	A/B	684-1020	[»]
3P11	X-ray	3.70	A	20-532	[»]

ProteinModelPortal

P21860.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-36441N.

IntAct

P21860. 14 interactions.

MINT

MINT-158484.

STRING

9606.ENSP00000267101.

PTM databases

PhosphoSite

P21860.

Polymorphism databases

DMDM

119534.

Proteomic databases

PaxDb

P21860.

PRIDE

P21860.

Protocols and materials databases

DNASU

2065.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000267101; ENSP00000267101; ENSG00000065361.
ENST00000411731; ENSP00000415753; ENSG00000065361.
ENST00000415288; ENSP00000408340; ENSG00000065361.
ENST00000450146; ENSP00000399178; ENSG00000065361.
ENST00000551242; ENSP00000447510; ENSG00000065361.

GeneID

2065.

KEGG

hsa:2065.

UCSC

uc001sjg.3. human.
uc001sjh.3. human.

Organism-specific databases

CTD

2065.

GeneCards

GC12P056473.

HGNC

HGNC:3431. ERBB3.

HPA

CAB025331.

MIM

190151. gene.
607598. phenotype.

neXtProt

NX_P21860.

Orphanet

137776. Lethal congenital contracture syndrome type 2.

PharmGKB

PA27846.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000230982.

HOVERGEN

HBG000490.

InParanoid

P21860.

KO

K05084.

OMA

VTDHMLA.

OrthoDB

EOG42BX7Q.

PhylomeDB

P21860.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

Pathway_Interaction_DB

a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P21860.

Bgee

P21860.

CleanEx

HS_ERBB3.

Genevestigator

P21860.

GermOnline

ENSG00000065361. Homo sapiens.

Family and domain databases

InterPro

IPR000494. EGF_rcpt_L.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR020635. Tyr_kinase_cat_dom.
IPR016245. Tyr_kinase_EGF/ERB/XmrK_rcpt.
[Graphical view]

Pfam

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

PIRSF

PIRSF000619. TyrPK_EGF-R. 1 hit.

PRINTS

PR00109. TYRKINASE.

SMART

SM00261. FU. 5 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF57184. Grow_fac_recept. 2 hits.
SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. False negative.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P21860.

ChEMBL

CHEMBL5838.

ChiTaRS

ERBB3. human.

EvolutionaryTrace

P21860.

GenomeRNAi

2065.

NextBio

8391.

SOURCE

Search...

Entry information

Entry name

ERBB3_HUMAN

Accession

Primary (citable) accession number: P21860
Secondary accession number(s): A8K6L6 , B4DIK7, B4DV32, E9PDT8, Q9BUD7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	May 1, 1991
Last modified:	May 1, 2013
This is version 156 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.