1M6B

Structure of the HER3 (ERBB3) Extracellular Domain

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d1m6ba1	Alpha and beta proteins (a/b)	Leucine-rich repeat, LRR (right-handed beta-alpha superhelix)	L domain-like	L domain	Receptor protein-tyrosine kinase Erbb-3 extracellular domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1m6ba3	Small proteins	Knottins (small inhibitors, toxins, lectins)	Growth factor receptor domain	Growth factor receptor domain	Receptor protein-tyrosine kinase Erbb-3 Cys-rich domains	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d1m6bb1	Alpha and beta proteins (a/b)	Leucine-rich repeat, LRR (right-handed beta-alpha superhelix)	L domain-like	L domain	Receptor protein-tyrosine kinase Erbb-3 extracellular domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d1m6bb3	Small proteins	Knottins (small inhibitors, toxins, lectins)	Growth factor receptor domain	Growth factor receptor domain	Receptor protein-tyrosine kinase Erbb-3 Cys-rich domains	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2 Family	L domain	8029260	4003546	SCOP2 (2022-06-29)
A	SCOP2 Family	L domain	8029262	4003546	SCOP2 (2022-06-29)
A	SCOP2 Family	Growth factor receptor domain	8029264	4003193	SCOP2 (2022-06-29)
A	SCOP2 Family	Growth factor receptor domain	8029265	4003193	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	L domain-like	8041639	3001010	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	L domain-like	8041641	3001010	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Growth factor receptor domain-like	8041643	3000398	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Growth factor receptor domain-like	8041644	3000398	SCOP2 (2022-06-29)
B	SCOP2B Superfamily	Growth factor receptor domain-like	8041644	3000398	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	L domain-like	8041641	3001010	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Growth factor receptor domain-like	8041643	3000398	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	L domain-like	8041639	3001010	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	Recep_L_domain	e1m6bA1	A: beta duplicates or obligate multimers	X: Single-stranded right-handed beta-helix	H: Leucine-rich repeats (From Topology)	T: Leucine-rich repeats	F: Recep_L_domain	ECOD (1.6)
A	GF_recep_IV	e1m6bA4	A: few secondary structure elements	X: EGF-like	H: Growth factor receptor domain (From Topology)	T: Growth factor receptor domain	F: GF_recep_IV	ECOD (1.6)
A	Furin-like	e1m6bA3	A: few secondary structure elements	X: EGF-like	H: Growth factor receptor domain (From Topology)	T: Growth factor receptor domain	F: Furin-like	ECOD (1.6)
B	Recep_L_domain	e1m6bB1	A: beta duplicates or obligate multimers	X: Single-stranded right-handed beta-helix	H: Leucine-rich repeats (From Topology)	T: Leucine-rich repeats	F: Recep_L_domain	ECOD (1.6)
B	GF_recep_IV	e1m6bB4	A: few secondary structure elements	X: EGF-like	H: Growth factor receptor domain (From Topology)	T: Growth factor receptor domain	F: GF_recep_IV	ECOD (1.6)
B	Furin-like	e1m6bB3	A: few secondary structure elements	X: EGF-like	H: Growth factor receptor domain (From Topology)	T: Growth factor receptor domain	F: Furin-like	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.80.20.20	Alpha Beta	Alpha-Beta Horseshoe	24 nucleotide stem-loop, u2 snrnp hairpin iv. U2 a'	Chain A	CATH (4.3.0)
A	2.10.220.10	Mainly Beta	Ribbon	Hormone Receptor, Insulin-like Growth Factor Receptor 1	Chain A domain 2	CATH (4.3.0)
B	3.80.20.20	Alpha Beta	Alpha-Beta Horseshoe	24 nucleotide stem-loop, u2 snrnp hairpin iv. U2 a'	Chain A	CATH (4.3.0)
B	2.10.220.10	Mainly Beta	Ribbon	Hormone Receptor, Insulin-like Growth Factor Receptor 1	Chain A domain 2	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF00757	Furin-like cysteine rich region (Furin-like)	Furin-like cysteine rich region	-	Domain
A, B	PF01030	Receptor L domain (Recep_L_domain)	Receptor L domain	-	Repeat
A, B	PF14843	Growth factor receptor domain IV (GF_recep_IV)	Growth factor receptor domain IV	This is the fourth extracellular domain of receptor tyrosine protein kinases. Interaction between this domain and the furin-like domain (Pfam:PF00757) regulates the binding of ligands to the receptor L domains (Pfam:PF01030) [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Receptor protein-tyrosine kinase erbB-3	protein tyrosine kinase activator activity enzyme regulator activity kinase activator activity enzyme activator activity molecular function activator activity molecular function regulator activity protein kinase activator activity protein kinase regulator activity kinase regulator activity neuregulin binding protein binding binding growth factor binding molecular transducer activity protein tyrosine kinase activator activity enzyme regulator activity kinase activator activity enzyme activator activity molecular function activator activity molecular function regulator activity protein kinase activator activity protein kinase regulator activity kinase regulator activity neuregulin binding protein binding binding growth factor binding molecular transducer activity transmembrane signaling receptor activity signaling receptor activity neuregulin receptor activity adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding ubiquitin protein ligase binding ubiquitin-like protein ligase binding enzyme binding identical protein binding protein heterodimerization activity protein dimerization activity signaling receptor binding ErbB-3 class receptor binding	cellular response to stimulus regulation of signaling regulation of biological process regulation of cellular process response to stimulus negative regulation of signaling signaling negative regulation of response to stimulus biological regulation negative regulation of biological process regulation of signal transduction negative regulation of signal transduction negative regulation of cell communication cell communication regulation of response to stimulus cellular response to stimulus regulation of signaling regulation of biological process regulation of cellular process response to stimulus negative regulation of signaling signaling negative regulation of response to stimulus biological regulation negative regulation of biological process regulation of signal transduction negative regulation of signal transduction negative regulation of cell communication cell communication regulation of response to stimulus negative regulation of cellular process regulation of cell communication cellular process signal transduction developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development cellular biosynthetic process positive regulation of biological process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process positive regulation of cellular process regulation of biosynthetic process cellular metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process positive regulation of gene expression regulation of macromolecule biosynthetic process metabolic process macromolecule metabolic process regulation of metabolic process positive regulation of cellular biosynthetic process regulation of localization regulation of transport transport secretion negative regulation of transport establishment of localization regulation of secretion localization negative regulation of secretion ERBB2 signaling pathway cell surface receptor signaling pathway ERBB2-ERBB3 signaling pathway cell surface receptor protein tyrosine kinase signaling pathway ERBB signaling pathway ERBB3 signaling pathway enzyme-linked receptor protein signaling pathway signal transduction in absence of ligand cell death extrinsic apoptotic signaling pathway apoptotic signaling pathway extrinsic apoptotic signaling pathway in absence of ligand apoptotic process programmed cell death mesenchyme development tissue development endocardial cushion development cell adhesion regulation of cell adhesion negative regulation of cell adhesion neurogenesis cellular developmental process cell differentiation nervous system development intracellular signal transduction intracellular signaling cassette phosphatidylinositol 3-kinase/protein kinase B signal transduction neuron apoptotic process motor neuron apoptotic process negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death negative regulation of apoptotic process regulation of muscle tissue development regulation of developmental process striated muscle tissue development muscle structure development positive regulation of developmental process positive regulation of muscle organ development regulation of cardiac muscle tissue development regulation of multicellular organismal process muscle tissue development muscle organ development positive regulation of cardiac muscle tissue development cardiac muscle tissue development positive regulation of striated muscle tissue development regulation of striated muscle tissue development positive regulation of muscle tissue development regulation of muscle organ development positive regulation of multicellular organismal process peripheral nervous system development cell development glial cell development Schwann cell development gliogenesis glial cell differentiation Schwann cell differentiation calcineurin-NFAT signaling cascade positive regulation of cell communication positive regulation of signal transduction positive regulation of response to stimulus regulation of intracellular signal transduction regulation of calcineurin-mediated signaling positive regulation of calcineurin-NFAT signaling cascade regulation of calcium-mediated signaling positive regulation of calcium-mediated signaling regulation of calcineurin-NFAT signaling cascade positive regulation of calcineurin-mediated signaling positive regulation of intracellular signal transduction calcium-mediated signaling calcineurin-mediated signaling positive regulation of signaling regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction negative regulation of neuron apoptotic process regulation of neuron apoptotic process cell population proliferation positive regulation of cell population proliferation regulation of cell population proliferation nerve development cranial nerve development wound healing response to stress response to wounding myelination axon ensheathment ensheathment of neurons regulation of motor neuron apoptotic process negative regulation of motor neuron apoptotic process	cell periphery protein-containing complex plasma membrane protein complex membrane plasma membrane plasma membrane signaling receptor complex membrane protein complex ERBB3:ERBB2 complex cellular anatomical entity receptor complex basal part of cell basal plasma membrane plasma membrane region basolateral plasma membrane cell periphery protein-containing complex plasma membrane protein complex membrane plasma membrane plasma membrane signaling receptor complex membrane protein complex ERBB3:ERBB2 complex cellular anatomical entity receptor complex basal part of cell basal plasma membrane plasma membrane region basolateral plasma membrane extracellular region extracellular space apical part of cell apical plasma membrane lateral plasma membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR016245	Tyrosine protein kinase, EGF/ERB/XmrK receptor	Family
A, B	IPR000719	Protein kinase domain	Domain
A, B	IPR036941	Receptor L-domain superfamily	Homologous Superfamily
A, B	IPR032778	Growth factor receptor domain 4	Domain
A, B	IPR006212	Furin-like repeat	Repeat
A, B	IPR000494	Receptor L-domain	Domain
A, B	IPR001245	Serine-threonine/tyrosine-protein kinase, catalytic domain	Domain
A, B	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A, B	IPR006211	Furin-like cysteine-rich domain	Domain
A, B	IPR009030	Growth factor receptor cysteine-rich domain superfamily	Homologous Superfamily
A, B	IPR050122	Receptor Tyrosine Kinase	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P21860	lethal congenital contracture syndrome 2 breast cancer nasopharyngeal carcinoma Neoplasm Metastasis prostate cancer gallbladder cancer breast carcinoma alopecia areata cutaneous lupus erythematosus urinary bladder neoplasm ductal breast carcinoma in situ gastric adenocarcinoma osteosarcoma acute erythroleukemia, familial glioblastoma lethal congenital contracture syndrome 2 breast cancer nasopharyngeal carcinoma Neoplasm Metastasis prostate cancer gallbladder cancer breast carcinoma alopecia areata cutaneous lupus erythematosus urinary bladder neoplasm ductal breast carcinoma in situ gastric adenocarcinoma osteosarcoma acute erythroleukemia, familial glioblastoma pancreatic ductal adenocarcinoma anorexia nervosa head and neck carcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia attention deficit hyperactivity disorder, inattentive type invasive ductal breast carcinoma pituitary cancer bipolar disorder lung adenocarcinoma rheumatoid arthritis skin neoplasm cancer malignant glioma subependymal giant cell astrocytoma cleft lip urinary bladder cancer cystic fibrosis vitiligo Down syndrome gastric carcinoma ovarian cancer allergic rhinitis Hashimoto thyroiditis pancreatic intraductal papillary-mucinous carcinoma arthrogryposis head and neck neoplasm Pick disease atypical teratoid rhabdoid tumor large cell medulloblastoma polycystic ovary syndrome bladder benign neoplasm lung benign neoplasm schizophrenia major depressive disorder spina bifida carcinoma ulcerative colitis colon carcinoma malignant pancreatic neoplasm urinary bladder carcinoma medulloblastoma Duchenne muscular dystrophy gallbladder neoplasm gastric neoplasm ovarian mucinous adenocarcinoma head and neck cancer pancreatic intraductal papillary-mucinous neoplasm asthma interstitial cystitis pilocytic astrocytoma benign neoplasm of stomach progressive supranuclear palsy bladder carcinoma in situ lung cancer skin cancer breast fibroadenoma malignant ependymoma stomach carcinoma in situ cholangiocarcinoma

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.