ERBB3_HUMAN » Receptor tyrosine-protein kinase erbB-3

ERBB3_HUMAN » Receptor tyrosine-protein kinase erbB-3
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
ERBB3_HUMAN » Receptor tyrosine-protein kinase erbB-3 » Proto-oncogene-like protein c-ErbB-3;Tyrosine kinase-type cell surface receptor HER3;
Hydrophobic Thickness 33.6 ± 1.8 Å
Tilt Angle 6 ± 5°
ΔGtransfer -45.4 kcal/mol
ΔGfold -23.1 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology Out
TM Segments 639-664 (639-669)
Pathways

Calcium signaling pathway (KEGG)

Endocytosis (KEGG)

ErbB signaling pathway (KEGG)

Immune System (Reactome)

Proteoglycans in cancer (KEGG)

Signal Transduction (Reactome)

PDB 1m6b (20-640), 3lmg (684-1020), 4otw (698-1020), 2l9u (A/B=639-670), 3kex (A/B=698-1019), 4rix (A/C=698-1020), 4riw (A/C=698-1020), 4riy (A/C=698-1020), 3p11 (A=20-532), 4p59 (A=20-640), 4leo (C=20-631)
OPM 1m6b, 2l9u
Complexes

EGFR:ERBB3_HUMAN

ERBB3:ERBB3_HUMAN

Interactions

1A29, Complex: 1A29:ERBB3, PubMed

1A31, Complex: 1A31:ERBB3, PubMed

1B44, Complex: 1B44:ERBB3, PubMed

1B45, Complex: 1B45:ERBB3, PubMed

CALX, Complex: CALX:ERBB3, PubMed

EGFR, Complex: ERBB3:EGFR, PDBID: 4riw, PubMed

EGF, Complex: EGF:ERBB3, PubMed

ERBB2, Complex: ERBB3:ERBB2:NRG1, PubMed

ERBB3, Complex: Transmembrane homodimer of ERBB3, PDBID: 2L9U

ERBB4, Complex: ERBB3:ERBB4, PubMed

FGFR1, Complex: FGFR1:ERBB3, PubMed

IL6RB, Complex: IL6RB:ERBB3, PubMed

LRIG1, Complex: LRIG1:ERBB3, PubMed

MUC1, Complex: ERBB3:MUC1, PubMed

NRG1, Complex: ERBB3:NRG1, PubMed

NRG2, Complex: NRG2:ERBB3, PubMed

ROR1, Complex: ERBB3:ROR1, PubMed

RPN1, Complex: RPN1:ERBB3, PubMed

SSRA, Complex: SSRA:ERBB3, PubMed

Domains

AA: 55-167, PDBID: 1M6B, Subunit B, Seq Identity:100%, Receptor L domain

AA: 169-332, PDBID: 1M6B, Subunit B, Seq Identity:100%, Furin-like cysteine rich region

AA: 353-474, PDBID: 1M6B, Subunit B, Seq Identity:100%, Receptor L domain

AA: 499-630, PDBID: 1M6B, Subunit B, Seq Identity:100%, Growth factor receptor domain IV

AA: 709-965, PDBID: 3KEX, Subunit A, Seq Identity:100%, Protein tyrosine kinase

UniProt annotation for ERBB3_HUMAN » Receptor tyrosine-protein kinase erbB-3
FUNCTION: Binds and is activated by neuregulins and NTAK. May also be activated by CSPG5.

CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

SUBUNIT: Monomer and homodimer. Heterodimer with each of the other ERBB receptors (Potential). Interacts with CSPG5, GRB7, and MUC1. Interacts with MYOC (By similarity). Interacts with isoform 2 of PA2G4.

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.

DISEASE: Lethal congenital contracture syndrome 2 (LCCS2) OMIM: 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. caused by mutations affecting the gene represented in this entry.

UniProt features for ERBB3_HUMAN » Receptor tyrosine-protein kinase erbB-3
SIGNAL 1 19 Potential.
CHAIN 20 1342 Receptor tyrosine-protein kinase erbB-3.
DOMAIN 709 966 Protein kinase.
ACT_SITE 834 834 Proton acceptor (By similarity).
DISULFID 29 56
DISULFID 156 183
DISULFID 186 194
DISULFID 190 202
DISULFID 210 218
DISULFID 214 226
DISULFID 227 235
DISULFID 231 243
DISULFID 246 255
DISULFID 259 286
DISULFID 290 301
DISULFID 305 320
DISULFID 323 327
DISULFID 500 509
DISULFID 504 517
DISULFID 520 529
DISULFID 533 549
DISULFID 552 565
DISULFID 556 573
DISULFID 576 585
DISULFID 589 610 By similarity.
DISULFID 613 621 By similarity.
DISULFID 617 629 By similarity.
Amino Acid Sequence for ERBB3_HUMAN » Receptor tyrosine-protein kinase erbB-3
MRANDALQVL GLLFSLARGS EVGNSQAVCP GTLNGLSVTG DAENQYQTLY KLYERCEVVM GNLEIVLTGH NADLSFLQWI REVTGYVLVA MNEFSTLPLP NLRVVRGTQV YDGKFAIFVM LNYNTNSSHA LRQLRLTQLT EILSGGVYIE KNDKLCHMDT IDWRDIVRDR DAEIVVKDNG RSCPPCHEVC KGRCWGPGSE DCQTLTKTIC APQCNGHCFG PNPNQCCHDE CAGGCSGPQD TDCFACRHFN DSGACVPRCP QPLVYNKLTF QLEPNPHTKY QYGGVCVASC PHNFVVDQTS CVRACPPDKM EVDKNGLKMC EPCGGLCPKA CEGTGSGSRF QTVDSSNIDG FVNCTKILGN LDFLITGLNG DPWHKIPALD PEKLNVFRTV REITGYLNIQ SWPPHMHNFS VFSNLTTIGG RSLYNRGFSL LIMKNLNVTS LGFRSLKEIS AGRIYISANR QLCYHHSLNW TKVLRGPTEE RLDIKHNRPR RDCVAEGKVC DPLCSSGGCW GPGPGQCLSC RNYSRGGVCV THCNFLNGEP REFAHEAECF SCHPECQPME GTATCNGSGS DTCAQCAHFR DGPHCVSSCP HGVLGAKGPI YKYPDVQNEC RPCHENCTQG CKGPELQDCL GQTLVLIGKT HLTMALTVIA GLVVIFMMLG GTFLYWRGRR IQNKRAMRRY LERGESIEPL DPSEKANKVL ARIFKETELR KLKVLGSGVF GTVHKGVWIP EGESIKIPVC IKVIEDKSGR QSFQAVTDHM LAIGSLDHAH IVRLLGLCPG SSLQLVTQYL PLGSLLDHVR QHRGALGPQL LLNWGVQIAK GMYYLEEHGM VHRNLAARNV LLKSPSQVQV ADFGVADLLP PDDKQLLYSE AKTPIKWMAL ESIHFGKYTH QSDVWSYGVT VWELMTFGAE PYAGLRLAEV PDLLEKGERL AQPQICTIDV YMVMVKCWMI DENIRPTFKE LANEFTRMAR DPPRYLVIKR ESGPGIAPGP EPHGLTNKKL EEVELEPELD LDLDLEAEED NLATTTLGSA LSLPVGTLNR PRGSQSLLSP SSGYMPMNQG NLGESCQESA VSGSSERCPR PVSLHPMPRG CLASESSEGH VTGSEAELQE KVSMCRSRSR SRSPRPRGDS AYHSQRHSLL TPVTPLSPPG LEEEDVNGYV MPDTHLKGTP SSREGTLSSV GLSSVLGTEE EDEDEEYEYM NRRRRHSPPH PPRPSSLEEL GYEYMDVGSD LSASLGSTQS CPLHPVPIMP TAGTTPDEDY EYMNRQRDGG GPGGDYAAMG ACPASEQGYE EMRAFQGPGH QAPHVHYARL KTLRSLEATD SAFDNPDYWH SRLFPKANAQ RT