2AHX

Crystal structure of ErbB4/HER4 extracellular domain

External Resource: Annotation

Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

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	e2ahxA4	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	e2ahxA1	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	e2ahxA5	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	e2ahxB4	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	e2ahxB5	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	e2ahxB3	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 tyrosine-protein kinase erbB-4	DNA binding sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding binding double-stranded DNA binding organic cyclic compound binding nucleic acid binding transcription regulatory region nucleic acid binding molecular transducer activity transmembrane signaling receptor activity signaling receptor activity neuregulin receptor activity catalytic activity, acting on a protein DNA binding sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding binding double-stranded DNA binding organic cyclic compound binding nucleic acid binding transcription regulatory region nucleic acid binding molecular transducer activity transmembrane signaling receptor activity signaling receptor activity neuregulin receptor activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups protein tyrosine kinase activity transmembrane receptor protein tyrosine kinase activity transmembrane receptor protein kinase activity catalytic activity adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding epidermal growth factor receptor activity protein binding signaling receptor binding GABA receptor binding identical protein binding protein homodimerization activity protein dimerization activity epidermal growth factor receptor binding growth factor receptor binding	protein localization protein localization to postsynaptic specialization membrane cellular localization protein localization to postsynaptic membrane protein localization to cell periphery protein localization to synapse biological regulation localization within membrane protein localization to membrane protein-containing complex localization neurotransmitter receptor localization to postsynaptic specialization membrane localization regulation of postsynaptic membrane neurotransmitter receptor levels protein localization to organelle cellular macromolecule localization protein localization protein localization to postsynaptic specialization membrane cellular localization protein localization to postsynaptic membrane protein localization to cell periphery protein localization to synapse biological regulation localization within membrane protein localization to membrane protein-containing complex localization neurotransmitter receptor localization to postsynaptic specialization membrane localization regulation of postsynaptic membrane neurotransmitter receptor levels protein localization to organelle cellular macromolecule localization macromolecule localization cellular process protein localization to postsynapse regulation of biological quality protein localization to cell junction receptor localization to synapse developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development olfactory bulb interneuron differentiation head development cellular developmental process olfactory lobe development forebrain development brain development nervous system development generation of neurons neurogenesis neuron differentiation central nervous system development cell differentiation olfactory bulb development telencephalon development mammary gland epithelial cell differentiation epithelium development mammary gland development gland development tissue development epithelial cell differentiation mammary gland epithelium development cellular response to stimulus ERBB2 signaling pathway regulation of biological process ERBB4 signaling pathway regulation of cellular process cell surface receptor signaling pathway response to stimulus signaling cell surface receptor protein tyrosine kinase signaling pathway cell communication ERBB signaling pathway signal transduction enzyme-linked receptor protein signaling pathway ERBB2-ERBB4 signaling pathway regulation of growth positive regulation of cell population proliferation regulation of cardiac muscle tissue growth regulation of developmental process developmental growth cardiac muscle cell proliferation positive regulation of biological process organ growth striated muscle tissue development positive regulation of developmental process positive regulation of cardiac muscle cell proliferation regulation of organ growth regulation of heart growth regulation of cardiac muscle cell proliferation muscle cell proliferation regulation of multicellular organismal process cardiac muscle tissue growth muscle tissue development positive regulation of developmental growth positive regulation of cellular process striated muscle cell proliferation positive regulation of heart growth heart growth regulation of multicellular organismal development cell population proliferation regulation of developmental growth cardiac muscle tissue development positive regulation of organ growth growth positive regulation of growth regulation of cell population proliferation positive regulation of cardiac muscle tissue growth positive regulation of multicellular organismal process cell migration cell motility regulation of cell motility regulation of locomotion regulation of cell migration locomotion protein phosphorylation organonitrogen compound metabolic process protein autophosphorylation phosphorylation cellular metabolic process primary metabolic process organic substance metabolic process macromolecule modification phosphate-containing compound metabolic process metabolic process protein metabolic process macromolecule metabolic process protein modification process phosphorus metabolic process tissue regeneration cardiac muscle tissue regeneration regeneration cell fate commitment regulation of localization regulation of protein localization positive regulation of protein localization to cell surface protein localization to cell surface regulation of cellular localization positive regulation of protein localization regulation of protein localization to cell surface regulation of body fluid levels secretion transport establishment of localization body fluid secretion lactation cellular component organization cellular component biogenesis cell junction organization cellular component assembly cell junction assembly synapse organization cellular component organization or biogenesis synapse assembly positive regulation of cell communication positive regulation of signal transduction regulation of signal transduction intracellular signal transduction positive regulation of response to stimulus positive regulation of ERK1 and ERK2 cascade regulation of intracellular signal transduction intracellular signaling cassette regulation of signaling positive regulation of MAPK cascade positive regulation of intracellular signal transduction regulation of MAPK cascade regulation of response to stimulus MAPK cascade regulation of cell communication ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade positive regulation of signaling negative regulation of programmed cell death regulation of apoptotic process negative regulation of biological process regulation of programmed cell death cell death negative regulation of apoptotic process negative regulation of cellular process apoptotic process programmed cell death regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction phosphatidylinositol 3-kinase/protein kinase B signal transduction stem cell development neural crest cell differentiation neural crest cell development cell development mesenchyme development mesenchymal cell migration stem cell differentiation ameboidal-type cell migration mesenchymal cell differentiation neural crest cell migration organelle organization mitochondrial fragmentation involved in apoptotic process apoptotic mitochondrial changes mitochondrion organization peptidyl-tyrosine modification peptidyl-amino acid modification peptidyl-tyrosine phosphorylation establishment of planar polarity involved in nephron morphogenesis establishment of planar polarity nephron morphogenesis morphogenesis of an epithelium renal system development anatomical structure morphogenesis tissue morphogenesis kidney morphogenesis establishment of tissue polarity morphogenesis of a polarized epithelium animal organ morphogenesis nephron development kidney development negative regulation of cell population proliferation positive regulation of phosphorylation positive regulation of phosphate metabolic process regulation of primary metabolic process positive regulation of metabolic process regulation of phosphate metabolic process positive regulation of macromolecule metabolic process positive regulation of protein phosphorylation tyrosine phosphorylation of STAT protein positive regulation of phosphorus metabolic process regulation of protein metabolic process regulation of cellular metabolic process regulation of phosphorus metabolic process regulation of metabolic process cell surface receptor signaling pathway via STAT regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of cellular metabolic process positive regulation of peptidyl-tyrosine phosphorylation positive regulation of protein modification process regulation of tyrosine phosphorylation of STAT protein regulation of peptidyl-tyrosine phosphorylation regulation of macromolecule metabolic process positive regulation of tyrosine phosphorylation of STAT protein regulation of phosphorylation cell surface receptor signaling pathway via JAK-STAT positive regulation of receptor signaling pathway via STAT positive regulation of receptor signaling pathway via JAK-STAT regulation of receptor signaling pathway via JAK-STAT regulation of receptor signaling pathway via STAT central nervous system morphogenesis positive regulation of macromolecule biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process organic substance biosynthetic process regulation of nucleobase-containing compound metabolic process positive regulation of nucleobase-containing compound metabolic process positive regulation of RNA metabolic process organic cyclic compound metabolic process regulation of gene expression biosynthetic process organic cyclic compound biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription positive regulation of DNA-templated transcription cellular biosynthetic process RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process positive regulation of biosynthetic process regulation of RNA biosynthetic process regulation of biosynthetic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process positive regulation of RNA biosynthetic process positive regulation of cellular biosynthetic process cellular response to endogenous stimulus cellular response to growth factor stimulus response to endogenous stimulus cellular response to epidermal growth factor stimulus response to epidermal growth factor response to growth factor embryonic pattern specification pattern specification process embryo development mammary gland lobule development mammary gland alveolus development ERBB4-ERBB4 signaling pathway	postsynaptic specialization membrane postsynaptic specialization synapse membrane plasma membrane cellular anatomical entity postsynaptic density membrane synaptic membrane cell periphery postsynaptic density postsynapse neuron to neuron synapse organelle cell junction postsynaptic specialization membrane postsynaptic specialization synapse membrane plasma membrane cellular anatomical entity postsynaptic density membrane synaptic membrane cell periphery postsynaptic density postsynapse neuron to neuron synapse organelle cell junction postsynaptic membrane asymmetric synapse plasma membrane region intracellular anatomical structure cytoplasm cytosol presynapse presynaptic membrane basal part of cell basal plasma membrane basolateral plasma membrane glutamatergic synapse protein-containing complex receptor complex neuromuscular junction membrane-bounded organelle intracellular organelle mitochondrion intracellular membrane-bounded organelle nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen GABA-ergic synapse extracellular region mitochondrial matrix

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR016245	Tyrosine protein kinase, EGF/ERB/XmrK receptor	Family
A, B	IPR008266	Tyrosine-protein kinase, active site	Active Site
A, B	IPR020635	Tyrosine-protein kinase, catalytic domain	Domain
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	IPR049328	Epidermal growth factor receptor-like, transmembrane-juxtamembrane segment	Domain
A, B	IPR006212	Furin-like repeat	Repeat
A, B	IPR000494	Receptor L-domain	Domain
A, B	IPR017441	Protein kinase, ATP binding site	Binding Site
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

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: Q15303	amyotrophic lateral sclerosis amyotrophic lateral sclerosis type 19 melanoma gallbladder cancer skin cancer breast carcinoma skin neoplasm cutaneous melanoma atrial fibrillation polycystic ovary syndrome gastroesophageal reflux disease large cell medulloblastoma lung carcinoma Malignant neoplasm of breast neurodegenerative disease amyotrophic lateral sclerosis amyotrophic lateral sclerosis type 19 melanoma gallbladder cancer skin cancer breast carcinoma skin neoplasm cutaneous melanoma atrial fibrillation polycystic ovary syndrome gastroesophageal reflux disease large cell medulloblastoma lung carcinoma Malignant neoplasm of breast neurodegenerative disease attention deficit hyperactivity disorder, inattentive type pancreatic intraductal papillary-mucinous neoplasm breast cancer psoriasis breast fibroadenoma cutaneous lupus erythematosus subependymal giant cell astrocytoma diabetes mellitus endometriosis gallbladder neoplasm glioblastoma lung adenocarcinoma malignant ependymoma bipolar disorder pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia schizophrenia cancer facioscapulohumeral muscular dystrophy gastric carcinoma lung cancer malignant glioma non-small cell lung carcinoma breast adenocarcinoma breast disease sinusitis colorectal adenocarcinoma squamous cell lung carcinoma cystic fibrosis endogenous depression

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), 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 R01GM133198.