ERBB3
entrez
2065
canonical
uniprot
P21860
canonical
ensembl
ENSG00000065361
resolver
ensp
ENSP00000267101
resolver
ensp
ENSP00000415753
resolver
ensp
ENSP00000507402
resolver
ensp
ENSP00000508051
resolver
genesymbol
ERBB3
resolver
genesymbol_syn
HER3
resolver
hgnc
HGNC:3431
resolver
uniprot
A8K6L6
resolver
uniprot
B4DIK7
resolver
uniprot
B4DV32
resolver
uniprot
E9PDT8
resolver
uniprot
Q9BUD7
resolver
uniprot_entry
ERBB3_HUMAN
resolver
uniprot_sec
A8K6L6
resolver
uniprot_sec
B4DIK7
resolver
uniprot_sec
B4DV32
resolver
uniprot_sec
E9PDT8
resolver
uniprot_sec
Q9BUD7
resolver
amino_acid_sequence
MRANDALQVLGLLFSLARGSEVGNSQAVCPGTLNGLSVTGDAENQYQTLYKLYERCEVVMGNLEIVLTGHNADLSFLQWIREVTGYVLVAMNEFSTLPLPNLRVVRGTQVYDGKFAIFVMLNYNTNSSHALRQLRLTQLTEILSGGVYIEKNDKLCHMDTIDWRDIVRDRDAEIVVKDNGRSCPPCHEVCKGRCWGPGSEDCQTLTKTICAPQCNGHCFGPNPNQCCHDECAGGCSGPQDTDCFACRHFNDSGACVPRCPQPLVYNKLTFQLEPNPHTKYQYGGVCVASCPHNFVVDQTSCVRACPPDKMEVDKNGLKMCEPCGGLCPKACEGTGSGSRFQTVDSSNIDGFVNCTKILGNLDFLITGLNGDPWHKIPALDPEKLNVFRTVREITGYLNIQSWPPHMHNFSVFSNLTTIGGRSLYNRGFSLLIMKNLNVTSLGFRSLKEISAGRIYISANRQLCYHHSLNWTKVLRGPTEERLDIKHNRPRRDCVAEGKVCDPLCSSGGCWGPGPGQCLSCRNYSRGGVCVTHCNFLNGEPREFAHEAECFSCHPECQPMEGTATCNGSGSDTCAQCAHFRDGPHCVSSCPHGVLGAKGPIYKYPDVQNECRPCHENCTQGCKGPELQDCLGQTLVLIGKTHLTMALTVIAGLVVIFMMLGGTFLYWRGRRIQNKRAMRRYLERGESIEPLDPSEKANKVLARIFKETELRKLKVLGSGVFGTVHKGVWIPEGESIKIPVCIKVIEDKSGRQSFQAVTDHMLAIGSLDHAHIVRLLGLCPGSSLQLVTQYLPLGSLLDHVRQHRGALGPQLLLNWGVQIAKGMYYLEEHGMVHRNLAARNVLLKSPSQVQVADFGVADLLPPDDKQLLYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVTVWELMTFGAEPYAGLRLAEVPDLLEKGERLAQPQICTIDVYMVMVKCWMIDENIRPTFKELANEFTRMARDPPRYLVIKRESGPGIAPGPEPHGLTNKKLEEVELEPELDLDLDLEAEEDNLATTTLGSALSLPVGTLNRPRGSQSLLSPSSGYMPMNQGNLGESCQESAVSGSSERCPRPVSLHPMPRGCLASESSEGHVTGSEAELQEKVSMCRSRSRSRSPRPRGDSAYHSQRHSLLTPVTPLSPPGLEEEDVNGYVMPDTHLKGTPSSREGTLSSVGLSSVLGTEEEDEDEEYEYMNRRRRHSPPHPPRPSSLEELGYEYMDVGSDLSASLGSTQSCPLHPVPIMPTAGTTPDEDYEYMNRQRDGGGPGGDYAAMGACPASEQGYEEMRAFQGPGHQAPHVHYARLKTLRSLEATDSAFDNPDYWHSRLFPKANAQRT
uniprot
proteins
disease_involvement
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. {ECO:0000269|PubMed:17701904}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Erythroleukemia, familial (FERLK) [MIM:133180]: An autosomal dominant myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood. Disease penetrance is incomplete. {ECO:0000269|PubMed:27416908}. Note=Disease susceptibility may be associated with variants affecting the gene represented in this entry.; DISEASE: Visceral neuropathy, familial, 1, autosomal recessive (VSCN1) [MIM:243180]: An autosomal recessive disorder characterized by intestinal dysmotility due to aganglionosis (Hirschsprung disease), hypoganglionosis, and/or chronic intestinal pseudoobstruction. Additional variable features are progressive peripheral neuropathy, arthrogryposis, hypoplasia or aplasia of the olfactory bulb and of the external auditory canals, microtia or anotia, and facial dysmorphism. Some patients present structural cardiac anomalies and arthrogryposis with multiple pterygia. {ECO:0000269|PubMed:33497358}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.10.1
uniprot
proteins
function
FUNCTION: Tyrosine kinase receptor that, despite substitutions of key catalytic residues in the kinase domain, retains residual catalytic activity enabling autophosphorylation (PubMed:9148746, PubMed:20351256). Functions primarily as a heterodimer, preferentially partnering with ERBB2/HER2, which phosphorylates ERBB3 on specific tyrosine residues and provides the kinase activity required for downstream signaling (PubMed:22983903). Binds neuregulins NRG1 and NRG2 through its extracellular domain, which induces conformational change from a tethered autoinhibited state to an extended conformation competent for dimerization (PubMed:20682778). Upon heterodimerization and trans-phosphorylation, acts as the most efficient activator of the PI3K/AKT pathway within the ErbB family (PubMed:22983903). Also activates the RAS/MAPK/ERK cascade to promote cell proliferation (PubMed:22983903). Plays an essential role in cardiac development; required for normal formation of the endocardial cushion and ventricular trabeculation during embryogenesis (Potential). Critical for peripheral nervous system development, where neuregulin-1/ERBB3 signaling drives Schwann cell survival, proliferation, and differentiation, and is required for axonal myelination (By similarity). Involved in epithelial morphogenesis and mammary gland development (By similarity). Also involved in the regulation of myeloid cell differentiation (PubMed:27416908). Participates in a regulatory feedback loop whereby pathway activation induces transcriptional up-regulation of ERBB3 expression (PubMed:21368164). Participates in vesicular sorting by stabilizing the ARF6-GGA3-RABEP1 endosomal sorting complex, to promote early recycling of TFRC and ITGB1 (PubMed:41348103). May also be activated by additional ligands including CSPG5 and EGFL6; the latter triggers assembly of an ERBB2/ERBB3/ITGB3 signaling complex leading to ERK phosphorylation and cell proliferation (PubMed:15358134, PubMed:41151154). {ECO:0000250|UniProtKB:Q61526, ECO:0000269|PubMed:15358134, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:21368164, ECO:0000269|PubMed:22983903, ECO:0000269|PubMed:27416908, ECO:0000269|PubMed:41151154, ECO:0000269|PubMed:41348103, ECO:0000269|PubMed:9148746}.
uniprot
proteins
mass_dalton
148098
uniprot
proteins
mutagenesis
MUTAGEN 742; /note="K->M: Strongly reduced autophosphorylation."; /evidence="ECO:0000269|PubMed:20351256"; MUTAGEN 868; /note="Y->E: Strongly reduced tyrosine phosphorylation."; /evidence="ECO:0000269|PubMed:20351256
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated (PubMed:20351256). Ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778). {ECO:0000269|PubMed:20351256, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:33497358}.
uniprot
proteins
protein_family
EGF receptor subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
11325528
uniprot
proteins
pubmed
12154198
uniprot
proteins
pubmed
12939402
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15358134
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
16832058
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17701904
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
20007378
uniprot
proteins
pubmed
20351256
uniprot
proteins
pubmed
20682778
uniprot
proteins
pubmed
21368164
uniprot
proteins
pubmed
21575594
uniprot
proteins
pubmed
2164210
uniprot
proteins
pubmed
22983903
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
2687875
uniprot
proteins
pubmed
27416908
uniprot
proteins
pubmed
33497358
uniprot
proteins
pubmed
41151154
uniprot
proteins
pubmed
41348103
uniprot
proteins
pubmed
7685162
uniprot
proteins
pubmed
9148746
uniprot
proteins
pubmed
9516479
uniprot
proteins
sequence_length
1342
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:33497358}; Single-pass type I membrane protein.; SUBCELLULAR LOCATION: [Isoform 2]: Secreted.
uniprot
proteins
transmembrane_region
TRANSMEM 644..664; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins