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Protein

Receptor tyrosine-protein kinase erbB-3

Gene

ERBB3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778). May also be activated by CSPG5 (PubMed:15358134).2 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei742ATP1
Active sitei834Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi715 – 723ATP9
Nucleotide bindingi788 – 790ATP3
Nucleotide bindingi834 – 839ATP6

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • growth factor binding Source: BHF-UCL
  • neuregulin binding Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: Reactome
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: BHF-UCL
  • protein tyrosine kinase activator activity Source: BHF-UCL
  • protein tyrosine kinase activity Source: Reactome
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • transmembrane signaling receptor activity Source: BHF-UCL

GO - Biological processi

  • cranial nerve development Source: BHF-UCL
  • endocardial cushion development Source: Ensembl
  • ERBB2 signaling pathway Source: Reactome
  • extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
  • heart development Source: BHF-UCL
  • MAPK cascade Source: Reactome
  • negative regulation of cell adhesion Source: BHF-UCL
  • negative regulation of neuron apoptotic process Source: BHF-UCL
  • negative regulation of secretion Source: BHF-UCL
  • negative regulation of signal transduction Source: BHF-UCL
  • neuron apoptotic process Source: BHF-UCL
  • peripheral nervous system development Source: BHF-UCL
  • phosphatidylinositol 3-kinase signaling Source: BHF-UCL
  • phosphatidylinositol-mediated signaling Source: Reactome
  • positive regulation of calcineurin-NFAT signaling cascade Source: Ensembl
  • positive regulation of cardiac muscle tissue development Source: Ensembl
  • positive regulation of gene expression Source: Ensembl
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
  • positive regulation of protein tyrosine kinase activity Source: BHF-UCL
  • regulation of cell motility Source: Reactome
  • regulation of cell proliferation Source: BHF-UCL
  • regulation of phosphatidylinositol 3-kinase signaling Source: Reactome
  • Schwann cell differentiation Source: BHF-UCL
  • signal transduction Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: BHF-UCL
  • wound healing Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS00838-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-1227986. Signaling by ERBB2.
R-HSA-1236394. Signaling by ERBB4.
R-HSA-1250196. SHC1 events in ERBB2 signaling.
R-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1306955. GRB7 events in ERBB2 signaling.
R-HSA-1358803. Downregulation of ERBB2:ERBB3 signaling.
R-HSA-1963642. PI3K events in ERBB2 signaling.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6785631. ERBB2 Regulates Cell Motility.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-HSA-8847993. ERBB2 Activates PTK6 Signaling.
R-HSA-8863795. Downregulation of ERBB2 signaling.
SignaLinkiP21860.
SIGNORiP21860.

Names & Taxonomyi

Protein namesi
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 namesi
Name:ERBB3
Synonyms:HER3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:3431. ERBB3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 643ExtracellularSequence analysisAdd BLAST624
Transmembranei644 – 664HelicalSequence analysisAdd BLAST21
Topological domaini665 – 1342CytoplasmicSequence analysisAdd BLAST678

GO - Cellular componenti

  • apical plasma membrane Source: Ensembl
  • basolateral plasma membrane Source: BHF-UCL
  • extracellular space Source: BHF-UCL
  • integral component of plasma membrane Source: ProtInc
  • intracellular Source: GOC
  • lateral plasma membrane Source: Ensembl
  • plasma membrane Source: BHF-UCL
  • receptor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Lethal congenital contracture syndrome 2 (LCCS2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:607598

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi742K → M: Strongly reduced autophosphorylation. 1 Publication1
Mutagenesisi868Y → E: Strongly reduced tyrosine phosphorylation. 1 Publication1

Organism-specific databases

DisGeNETi2065.
MalaCardsiERBB3.
MIMi607598. phenotype.
OpenTargetsiENSG00000065361.
Orphaneti137776. Lethal congenital contracture syndrome type 2.
PharmGKBiPA27846.

Chemistry databases

ChEMBLiCHEMBL5838.
GuidetoPHARMACOLOGYi1798.

Polymorphism and mutation databases

BioMutaiERBB3.
DMDMi119534.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000001667220 – 1342Receptor tyrosine-protein kinase erbB-3Add BLAST1323

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi29 ↔ 561 Publication
Glycosylationi126N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi156 ↔ 1831 Publication
Disulfide bondi186 ↔ 1941 Publication
Disulfide bondi190 ↔ 2021 Publication
Disulfide bondi210 ↔ 2181 Publication
Disulfide bondi214 ↔ 2261 Publication
Disulfide bondi227 ↔ 2351 Publication
Disulfide bondi231 ↔ 2431 Publication
Disulfide bondi246 ↔ 2551 Publication
Glycosylationi250N-linked (GlcNAc...)1 Publication1
Disulfide bondi259 ↔ 2861 Publication
Disulfide bondi290 ↔ 3011 Publication
Disulfide bondi305 ↔ 3201 Publication
Disulfide bondi323 ↔ 3271 Publication
Glycosylationi353N-linked (GlcNAc...)1 Publication1
Glycosylationi408N-linked (GlcNAc...)1 Publication1
Glycosylationi414N-linked (GlcNAc...)1 Publication1
Glycosylationi437N-linked (GlcNAc...)1 Publication1
Glycosylationi469N-linked (GlcNAc...)1 Publication1
Disulfide bondi500 ↔ 5091 Publication
Disulfide bondi504 ↔ 5171 Publication
Disulfide bondi520 ↔ 5291 Publication
Glycosylationi522N-linked (GlcNAc...)1 Publication1
Disulfide bondi533 ↔ 5491 Publication
Disulfide bondi552 ↔ 5651 Publication
Disulfide bondi556 ↔ 5731 Publication
Glycosylationi566N-linked (GlcNAc...)1 Publication1
Disulfide bondi576 ↔ 5851 Publication
Disulfide bondi589 ↔ 610By similarity
Disulfide bondi613 ↔ 621By similarity
Glycosylationi616N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi617 ↔ 629By similarity
Modified residuei686PhosphoserineCombined sources1
Modified residuei982PhosphoserineCombined sources1

Post-translational modificationi

Autophosphorylated (PubMed:20351256). Ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778).2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP21860.
PaxDbiP21860.
PeptideAtlasiP21860.
PRIDEiP21860.

PTM databases

iPTMnetiP21860.
PhosphoSitePlusiP21860.

Expressioni

Tissue specificityi

Epithelial tissues and brain.

Developmental stagei

Overexpressed in a subset of human mammary tumors.

Gene expression databases

BgeeiENSG00000065361.
CleanExiHS_ERBB3.
ExpressionAtlasiP21860. baseline and differential.
GenevisibleiP21860. HS.

Organism-specific databases

HPAiCAB025331.
HPA045396.

Interactioni

Subunit structurei

Monomer and homodimer. Heterodimer with each of the other ERBB receptors (Potential). Interacts with CSPG5 (PubMed:15358134). Interacts with GRB7 (PubMed:9516479). Interacts with MUC1 (PubMed:12939402). Interacts with MYOC (By similarity). Interacts with isoform 2 of PA2G4 (PubMed:11325528, PubMed:16832058). Found in a ternary complex with NRG1 and ITGAV:ITGB3 or ITGA6:ITGB4 (PubMed:20682778).By similarityCurated6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-720706,EBI-720706
ABL2P4268410EBI-720706,EBI-1102694
CRKP461082EBI-720706,EBI-886
CRKLP461093EBI-720706,EBI-910
EGFRP0053312EBI-720706,EBI-297353
ERBB2P0462625EBI-720706,EBI-641062
ERBB4Q153034EBI-720706,EBI-80371
GRB2P629933EBI-720706,EBI-401755
GRB7Q144517EBI-720706,EBI-970191
HCKP086312EBI-720706,EBI-346340
HSP90AB1P082383EBI-720706,EBI-352572
NCK2O436392EBI-720706,EBI-713635
NRG1Q02297-73EBI-720706,EBI-2460927
PIK3CAP423363EBI-720706,EBI-2116585
PIK3R1P2798640EBI-720706,EBI-79464
PIK3R2O0045916EBI-720706,EBI-346930
PIK3R3Q9256922EBI-720706,EBI-79893
PLCG1P191744EBI-720706,EBI-79387
RASA1P209366EBI-720706,EBI-1026476
SH2B3Q9UQQ22EBI-720706,EBI-7879749
SHC1P293535EBI-720706,EBI-78835
SHC3Q925292EBI-720706,EBI-79084
SRCP129312EBI-720706,EBI-621482
SYKP434056EBI-720706,EBI-78302
TNS2Q63HR23EBI-720706,EBI-949753
TNS3Q68CZ22EBI-720706,EBI-1220488

GO - Molecular functioni

  • growth factor binding Source: BHF-UCL
  • neuregulin binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi108377. 148 interactors.
DIPiDIP-36441N.
IntActiP21860. 93 interactors.
MINTiMINT-158484.
STRINGi9606.ENSP00000267101.

Chemistry databases

BindingDBiP21860.

Structurei

Secondary structure

11342
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 30Combined sources3
Helixi43 – 53Combined sources11
Beta strandi58 – 61Combined sources4
Beta strandi63 – 67Combined sources5
Helixi75 – 79Combined sources5
Beta strandi82 – 85Combined sources4
Beta strandi87 – 91Combined sources5
Beta strandi95 – 98Combined sources4
Turni112 – 114Combined sources3
Beta strandi115 – 120Combined sources6
Beta strandi125 – 128Combined sources4
Beta strandi133 – 135Combined sources3
Beta strandi141 – 144Combined sources4
Beta strandi146 – 150Combined sources5
Turni158 – 160Combined sources3
Helixi163 – 166Combined sources4
Beta strandi174 – 178Combined sources5
Helixi188 – 190Combined sources3
Beta strandi194 – 198Combined sources5
Beta strandi214 – 216Combined sources3
Beta strandi218 – 222Combined sources5
Helixi223 – 225Combined sources3
Beta strandi231 – 233Combined sources3
Beta strandi235 – 239Combined sources5
Helixi240 – 242Combined sources3
Beta strandi243 – 251Combined sources9
Beta strandi254 – 258Combined sources5
Beta strandi262 – 265Combined sources4
Turni267 – 269Combined sources3
Beta strandi270 – 274Combined sources5
Beta strandi280 – 282Combined sources3
Beta strandi285 – 289Combined sources5
Beta strandi295 – 297Combined sources3
Beta strandi300 – 304Combined sources5
Beta strandi309 – 314Combined sources6
Beta strandi317 – 322Combined sources6
Beta strandi324 – 326Combined sources3
Beta strandi330 – 332Combined sources3
Beta strandi338 – 342Combined sources5
Turni345 – 347Combined sources3
Helixi348 – 351Combined sources4
Beta strandi356 – 363Combined sources8
Helixi365 – 369Combined sources5
Turni372 – 375Combined sources4
Helixi381 – 389Combined sources9
Beta strandi392 – 395Combined sources4
Beta strandi397 – 400Combined sources4
Helixi410 – 412Combined sources3
Beta strandi425 – 433Combined sources9
Beta strandi451 – 457Combined sources7
Helixi465 – 467Combined sources3
Helixi470 – 473Combined sources4
Beta strandi482 – 488Combined sources7
Helixi490 – 493Combined sources4
Turni494 – 497Combined sources4
Beta strandi509 – 513Combined sources5
Helixi514 – 516Combined sources3
Beta strandi517 – 527Combined sources11
Beta strandi529 – 531Combined sources3
Beta strandi534 – 536Combined sources3
Beta strandi538 – 540Combined sources3
Beta strandi542 – 545Combined sources4
Beta strandi548 – 551Combined sources4
Beta strandi560 – 562Combined sources3
Beta strandi564 – 570Combined sources7
Beta strandi573 – 581Combined sources9
Beta strandi584 – 588Combined sources5
Beta strandi591 – 594Combined sources4
Beta strandi600 – 604Combined sources5
Beta strandi608 – 612Combined sources5
Beta strandi622 – 625Combined sources4
Helixi626 – 628Combined sources3
Helixi641 – 670Combined sources30
Helixi706 – 708Combined sources3
Beta strandi709 – 716Combined sources8
Beta strandi722 – 728Combined sources7
Beta strandi731 – 733Combined sources3
Beta strandi737 – 744Combined sources8
Turni747 – 749Combined sources3
Beta strandi753 – 755Combined sources3
Helixi758 – 764Combined sources7
Beta strandi774 – 778Combined sources5
Beta strandi780 – 788Combined sources9
Helixi795 – 802Combined sources8
Helixi803 – 805Combined sources3
Helixi808 – 827Combined sources20
Helixi837 – 839Combined sources3
Beta strandi840 – 846Combined sources7
Beta strandi848 – 850Combined sources3
Helixi855 – 858Combined sources4
Helixi865 – 868Combined sources4
Turni870 – 872Combined sources3
Helixi875 – 877Combined sources3
Helixi880 – 885Combined sources6
Helixi890 – 905Combined sources16
Turni911 – 914Combined sources4
Helixi917 – 919Combined sources3
Helixi920 – 925Combined sources6
Helixi938 – 947Combined sources10
Turni952 – 954Combined sources3
Helixi958 – 968Combined sources11
Helixi972 – 975Combined sources4
Beta strandi980 – 983Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1M6BX-ray2.60A/B20-640[»]
2L9UNMR-A/B639-670[»]
3KEXX-ray2.80A/B698-1019[»]
3LMGX-ray2.80A/B684-1020[»]
3P11X-ray3.70A20-532[»]
4LEOX-ray2.64C20-631[»]
4OTWX-ray2.51A698-1020[»]
4P59X-ray3.40A20-640[»]
4RIWX-ray3.10A/C698-1020[»]
4RIXX-ray3.10A/C698-1020[»]
4RIYX-ray2.98A/C698-1020[»]
5CUSX-ray3.20A/B/C/D20-641[»]
ProteinModelPortaliP21860.
SMRiP21860.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21860.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini709 – 966Protein kinasePROSITE-ProRule annotationAdd BLAST258

Domaini

The cytoplasmic part of the receptor may interact with the SH2 or SH3 domains of many signal-transducing proteins.

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1025. Eukaryota.
ENOG410XNSR. LUCA.
GeneTreeiENSGT00760000118799.
HOGENOMiHOG000230982.
HOVERGENiHBG000490.
InParanoidiP21860.
KOiK05084.
OMAiCYHHSLN.
OrthoDBiEOG091G00IX.
PhylomeDBiP21860.
TreeFamiTF106002.

Family and domain databases

Gene3Di3.80.20.20. 2 hits.
InterProiIPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR032778. GF_recep_IV.
IPR009030. Growth_fac_rcpt_.
IPR011009. Kinase-like_dom.
IPR032675. L_dom-like.
IPR000719. Prot_kinase_dom.
IPR000494. Rcpt_L-dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR016245. Tyr_kinase_EGF/ERB/XmrK_rcpt.
[Graphical view]
PfamiPF00757. Furin-like. 1 hit.
PF14843. GF_recep_IV. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PIRSFiPIRSF000619. TyrPK_EGF-R. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00261. FU. 5 hits.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P21860-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MRANDALQVL GLLFSLARGS EVGNSQAVCP GTLNGLSVTG DAENQYQTLY
60 70 80 90 100
KLYERCEVVM GNLEIVLTGH NADLSFLQWI REVTGYVLVA MNEFSTLPLP
110 120 130 140 150
NLRVVRGTQV YDGKFAIFVM LNYNTNSSHA LRQLRLTQLT EILSGGVYIE
160 170 180 190 200
KNDKLCHMDT IDWRDIVRDR DAEIVVKDNG RSCPPCHEVC KGRCWGPGSE
210 220 230 240 250
DCQTLTKTIC APQCNGHCFG PNPNQCCHDE CAGGCSGPQD TDCFACRHFN
260 270 280 290 300
DSGACVPRCP QPLVYNKLTF QLEPNPHTKY QYGGVCVASC PHNFVVDQTS
310 320 330 340 350
CVRACPPDKM EVDKNGLKMC EPCGGLCPKA CEGTGSGSRF QTVDSSNIDG
360 370 380 390 400
FVNCTKILGN LDFLITGLNG DPWHKIPALD PEKLNVFRTV REITGYLNIQ
410 420 430 440 450
SWPPHMHNFS VFSNLTTIGG RSLYNRGFSL LIMKNLNVTS LGFRSLKEIS
460 470 480 490 500
AGRIYISANR QLCYHHSLNW TKVLRGPTEE RLDIKHNRPR RDCVAEGKVC
510 520 530 540 550
DPLCSSGGCW GPGPGQCLSC RNYSRGGVCV THCNFLNGEP REFAHEAECF
560 570 580 590 600
SCHPECQPME GTATCNGSGS DTCAQCAHFR DGPHCVSSCP HGVLGAKGPI
610 620 630 640 650
YKYPDVQNEC RPCHENCTQG CKGPELQDCL GQTLVLIGKT HLTMALTVIA
660 670 680 690 700
GLVVIFMMLG GTFLYWRGRR IQNKRAMRRY LERGESIEPL DPSEKANKVL
710 720 730 740 750
ARIFKETELR KLKVLGSGVF GTVHKGVWIP EGESIKIPVC IKVIEDKSGR
760 770 780 790 800
QSFQAVTDHM LAIGSLDHAH IVRLLGLCPG SSLQLVTQYL PLGSLLDHVR
810 820 830 840 850
QHRGALGPQL LLNWGVQIAK GMYYLEEHGM VHRNLAARNV LLKSPSQVQV
860 870 880 890 900
ADFGVADLLP PDDKQLLYSE AKTPIKWMAL ESIHFGKYTH QSDVWSYGVT
910 920 930 940 950
VWELMTFGAE PYAGLRLAEV PDLLEKGERL AQPQICTIDV YMVMVKCWMI
960 970 980 990 1000
DENIRPTFKE LANEFTRMAR DPPRYLVIKR ESGPGIAPGP EPHGLTNKKL
1010 1020 1030 1040 1050
EEVELEPELD LDLDLEAEED NLATTTLGSA LSLPVGTLNR PRGSQSLLSP
1060 1070 1080 1090 1100
SSGYMPMNQG NLGESCQESA VSGSSERCPR PVSLHPMPRG CLASESSEGH
1110 1120 1130 1140 1150
VTGSEAELQE KVSMCRSRSR SRSPRPRGDS AYHSQRHSLL TPVTPLSPPG
1160 1170 1180 1190 1200
LEEEDVNGYV MPDTHLKGTP SSREGTLSSV GLSSVLGTEE EDEDEEYEYM
1210 1220 1230 1240 1250
NRRRRHSPPH PPRPSSLEEL GYEYMDVGSD LSASLGSTQS CPLHPVPIMP
1260 1270 1280 1290 1300
TAGTTPDEDY EYMNRQRDGG GPGGDYAAMG ACPASEQGYE EMRAFQGPGH
1310 1320 1330 1340
QAPHVHYARL KTLRSLEATD SAFDNPDYWH SRLFPKANAQ RT
Length:1,342
Mass (Da):148,098
Last modified:May 1, 1991 - v1
Checksum:i7201E7F66CA374BD
GO
Isoform 2 (identifier: P21860-2) [UniParc]FASTAAdd to basket
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.

Show »
Length:183
Mass (Da):20,136
Checksum:iDA25DD25D34DE5E3
GO
Isoform 3 (identifier: P21860-3) [UniParc]FASTAAdd to basket

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

Show »
Length:331
Mass (Da):36,490
Checksum:i45B8EBEE683FE7E8
GO
Isoform 4 (identifier: P21860-4) [UniParc]FASTAAdd to basket

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

Show »
Length:1,283
Mass (Da):141,752
Checksum:iD40BB4459539D894
GO
Isoform 5 (identifier: P21860-5) [UniParc]FASTAAdd to basket

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

Show »
Length:699
Mass (Da):77,426
Checksum:iC7C94A8F051DCE15
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti560E → G in AAA35979 (PubMed:2164210).Curated1
Sequence conflicti684G → S in BAF84370 (PubMed:14702039).Curated1
Sequence conflicti1064E → G in AAA35979 (PubMed:2164210).Curated1
Sequence conflicti1078C → S in BAG62544 (PubMed:14702039).Curated1
Sequence conflicti1163D → G in BAF84370 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04210120S → Y.1 PublicationCorresponds to variant rs34379766dbSNPEnsembl.1
Natural variantiVAR_04210230P → L.1 PublicationCorresponds to variant rs56017157dbSNPEnsembl.1
Natural variantiVAR_042103104V → M in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_042104204T → I.1 PublicationCorresponds to variant rs56107455dbSNPEnsembl.1
Natural variantiVAR_049710385N → S.Corresponds to variant rs12320176dbSNPEnsembl.1
Natural variantiVAR_042105683R → W.1 PublicationCorresponds to variant rs56387488dbSNPEnsembl.1
Natural variantiVAR_042106717S → L.1 PublicationCorresponds to variant rs35961836dbSNPEnsembl.1
Natural variantiVAR_042107744I → T.1 PublicationCorresponds to variant rs55787439dbSNPEnsembl.1
Natural variantiVAR_042108998K → R.1 PublicationCorresponds to variant rs56259600dbSNPEnsembl.1
Natural variantiVAR_0421091119S → C.1 PublicationCorresponds to variant rs773123dbSNPEnsembl.1
Natural variantiVAR_0421101127R → H.1 PublicationCorresponds to variant rs2271188dbSNPEnsembl.1
Natural variantiVAR_0421111177L → I.1 PublicationCorresponds to variant rs55699040dbSNPEnsembl.1
Natural variantiVAR_0421121254T → K.1 PublicationCorresponds to variant rs55709407dbSNPEnsembl.1
Natural variantiVAR_0497111271G → S.Corresponds to variant rs11171743dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0416611 – 643Missing in isoform 5. 1 PublicationAdd BLAST643
Alternative sequenceiVSP_0416621 – 59Missing in isoform 4. 1 PublicationAdd BLAST59
Alternative sequenceiVSP_002893141 – 183EILSG…NGRSC → GQFPMVPSGLTPQPAQDWYL LDDDPRLLTLSASSKVPVTL AAV in isoform 2. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_002894184 – 1342Missing in isoform 2. 1 PublicationAdd BLAST1159
Alternative sequenceiVSP_041663331C → F in isoform 3. 2 Publications1
Alternative sequenceiVSP_041664332 – 1342Missing in isoform 3. 2 PublicationsAdd BLAST1011

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS31833.1. [P21860-1]
CCDS44918.1. [P21860-2]
PIRiA36223.
JH0803.
RefSeqiNP_001005915.1. NM_001005915.1. [P21860-2]
NP_001973.2. NM_001982.3. [P21860-1]
UniGeneiHs.118681.
Hs.622058.

Genome annotation databases

EnsembliENST00000267101; ENSP00000267101; ENSG00000065361. [P21860-1]
ENST00000411731; ENSP00000415753; ENSG00000065361. [P21860-2]
ENST00000415288; ENSP00000408340; ENSG00000065361. [P21860-4]
ENST00000551242; ENSP00000447510; ENSG00000065361. [P21860-3]
GeneIDi2065.
KEGGihsa:2065.
UCSCiuc001sjg.4. human. [P21860-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS31833.1. [P21860-1]
CCDS44918.1. [P21860-2]
PIRiA36223.
JH0803.
RefSeqiNP_001005915.1. NM_001005915.1. [P21860-2]
NP_001973.2. NM_001982.3. [P21860-1]
UniGeneiHs.118681.
Hs.622058.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1M6BX-ray2.60A/B20-640[»]
2L9UNMR-A/B639-670[»]
3KEXX-ray2.80A/B698-1019[»]
3LMGX-ray2.80A/B684-1020[»]
3P11X-ray3.70A20-532[»]
4LEOX-ray2.64C20-631[»]
4OTWX-ray2.51A698-1020[»]
4P59X-ray3.40A20-640[»]
4RIWX-ray3.10A/C698-1020[»]
4RIXX-ray3.10A/C698-1020[»]
4RIYX-ray2.98A/C698-1020[»]
5CUSX-ray3.20A/B/C/D20-641[»]
ProteinModelPortaliP21860.
SMRiP21860.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108377. 148 interactors.
DIPiDIP-36441N.
IntActiP21860. 93 interactors.
MINTiMINT-158484.
STRINGi9606.ENSP00000267101.

Chemistry databases

BindingDBiP21860.
ChEMBLiCHEMBL5838.
GuidetoPHARMACOLOGYi1798.

PTM databases

iPTMnetiP21860.
PhosphoSitePlusiP21860.

Polymorphism and mutation databases

BioMutaiERBB3.
DMDMi119534.

Proteomic databases

MaxQBiP21860.
PaxDbiP21860.
PeptideAtlasiP21860.
PRIDEiP21860.

Protocols and materials databases

DNASUi2065.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000267101; ENSP00000267101; ENSG00000065361. [P21860-1]
ENST00000411731; ENSP00000415753; ENSG00000065361. [P21860-2]
ENST00000415288; ENSP00000408340; ENSG00000065361. [P21860-4]
ENST00000551242; ENSP00000447510; ENSG00000065361. [P21860-3]
GeneIDi2065.
KEGGihsa:2065.
UCSCiuc001sjg.4. human. [P21860-1]

Organism-specific databases

CTDi2065.
DisGeNETi2065.
GeneCardsiERBB3.
HGNCiHGNC:3431. ERBB3.
HPAiCAB025331.
HPA045396.
MalaCardsiERBB3.
MIMi190151. gene.
607598. phenotype.
neXtProtiNX_P21860.
OpenTargetsiENSG00000065361.
Orphaneti137776. Lethal congenital contracture syndrome type 2.
PharmGKBiPA27846.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1025. Eukaryota.
ENOG410XNSR. LUCA.
GeneTreeiENSGT00760000118799.
HOGENOMiHOG000230982.
HOVERGENiHBG000490.
InParanoidiP21860.
KOiK05084.
OMAiCYHHSLN.
OrthoDBiEOG091G00IX.
PhylomeDBiP21860.
TreeFamiTF106002.

Enzyme and pathway databases

BioCyciZFISH:HS00838-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-1227986. Signaling by ERBB2.
R-HSA-1236394. Signaling by ERBB4.
R-HSA-1250196. SHC1 events in ERBB2 signaling.
R-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1306955. GRB7 events in ERBB2 signaling.
R-HSA-1358803. Downregulation of ERBB2:ERBB3 signaling.
R-HSA-1963642. PI3K events in ERBB2 signaling.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6785631. ERBB2 Regulates Cell Motility.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-HSA-8847993. ERBB2 Activates PTK6 Signaling.
R-HSA-8863795. Downregulation of ERBB2 signaling.
SignaLinkiP21860.
SIGNORiP21860.

Miscellaneous databases

ChiTaRSiERBB3. human.
EvolutionaryTraceiP21860.
GeneWikiiERBB3.
GenomeRNAii2065.
PROiP21860.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000065361.
CleanExiHS_ERBB3.
ExpressionAtlasiP21860. baseline and differential.
GenevisibleiP21860. HS.

Family and domain databases

Gene3Di3.80.20.20. 2 hits.
InterProiIPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR032778. GF_recep_IV.
IPR009030. Growth_fac_rcpt_.
IPR011009. Kinase-like_dom.
IPR032675. L_dom-like.
IPR000719. Prot_kinase_dom.
IPR000494. Rcpt_L-dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR016245. Tyr_kinase_EGF/ERB/XmrK_rcpt.
[Graphical view]
PfamiPF00757. Furin-like. 1 hit.
PF14843. GF_recep_IV. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PIRSFiPIRSF000619. TyrPK_EGF-R. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00261. FU. 5 hits.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiERBB3_HUMAN
AccessioniPrimary (citable) accession number: P21860
Secondary accession number(s): A8K6L6
, B4DIK7, B4DV32, E9PDT8, Q9BUD7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: May 1, 1991
Last modified: November 30, 2016
This is version 194 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.