4HRN

Structural Basis for Eliciting a Cytotoxic Effect in HER2-Overexpressing Cancer Cells via Binding to the Extracellular Domain of HER2

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	PF13637	e4hrnA1	A: alpha superhelices	X: Repetitive alpha hairpins	H: Ankyrin repeat (From Topology)	T: Ankyrin repeat	F: PF13637	ECOD (1.6)
B	PF13637	e4hrnB1	A: alpha superhelices	X: Repetitive alpha hairpins	H: Ankyrin repeat (From Topology)	T: Ankyrin repeat	F: PF13637	ECOD (1.6)
C	PF14843	e4hrnC1	A: few secondary structure elements	X: EGF-like	H: Growth factor receptor domain (From Topology)	T: Growth factor receptor domain	F: PF14843	ECOD (1.6)
D	PF14843	e4hrnD1	A: few secondary structure elements	X: EGF-like	H: Growth factor receptor domain (From Topology)	T: Growth factor receptor domain	F: PF14843	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.25.40.20	Mainly Alpha	Alpha Horseshoe	Serine Threonine Protein Phosphatase 5, Tetratricopeptide repeat	Ankyrin repeat-containing domain	CATH (4.3.0)
B	1.25.40.20	Mainly Alpha	Alpha Horseshoe	Serine Threonine Protein Phosphatase 5, Tetratricopeptide repeat	Ankyrin repeat-containing domain	CATH (4.3.0)
C	2.10.220.10	Mainly Beta	Ribbon	Hormone Receptor, Insulin-like Growth Factor Receptor 1	Chain A domain 2	CATH (4.3.0)
D	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
C, D	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	Designed Ankyrin Repeat Protein H10-2-G	-	-	-
C, D	Receptor tyrosine-protein kinase erbB-2	molecular transducer activity coreceptor activity signaling receptor activity RNA polymerase I core binding RNA polymerase binding protein binding binding RNA polymerase core enzyme binding enzyme binding catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity phosphotransferase activity, alcohol group as acceptor molecular transducer activity coreceptor activity signaling receptor activity RNA polymerase I core binding RNA polymerase binding protein binding binding RNA polymerase core enzyme binding enzyme binding 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 transmembrane signaling receptor activity catalytic 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 protein tyrosine kinase binding kinase binding signaling receptor binding receptor tyrosine kinase binding protein kinase binding identical protein binding protein heterodimerization activity protein dimerization activity ErbB-3 class 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 multicellular organismal process regulation of multicellular organismal development regulation of biological process regulation of developmental process blood vessel morphogenesis tube development angiogenesis vasculature development regulation of vasculature development circulatory system development multicellular organism development anatomical structure morphogenesis tube morphogenesis regulation of angiogenesis anatomical structure development anatomical structure formation involved in morphogenesis regulation of multicellular organismal process regulation of anatomical structure morphogenesis blood vessel development system development heart development animal organ development cellular response to stimulus ERBB2 signaling pathway 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 cellular developmental process immature T cell proliferation in thymus cell development mononuclear cell differentiation lymphocyte activation lymphocyte differentiation leukocyte proliferation leukocyte activation T cell differentiation in thymus T cell activation cell differentiation lymphocyte proliferation T cell differentiation T cell proliferation cell population proliferation hemopoiesis cell activation immature T cell proliferation immune system process mononuclear cell proliferation leukocyte differentiation ERBB2-ERBB3 signaling pathway ERBB3 signaling pathway negative regulation of lymphocyte proliferation regulation of leukocyte differentiation regulation of leukocyte activation negative regulation of biological process regulation of cell activation negative regulation of T cell differentiation in thymus regulation of cell differentiation negative regulation of T cell proliferation regulation of cell development negative regulation of cell adhesion negative regulation of T cell differentiation negative regulation of leukocyte proliferation regulation of immune system process regulation of immature T cell proliferation negative regulation of hemopoiesis regulation of leukocyte proliferation negative regulation of immature T cell proliferation negative regulation of leukocyte differentiation regulation of immature T cell proliferation in thymus negative regulation of T cell activation negative regulation of leukocyte cell-cell adhesion regulation of cell population proliferation negative regulation of cell-cell adhesion regulation of leukocyte cell-cell adhesion negative regulation of lymphocyte differentiation negative regulation of multicellular organismal process negative regulation of leukocyte activation regulation of T cell differentiation in thymus negative regulation of lymphocyte activation leukocyte cell-cell adhesion regulation of T cell differentiation negative regulation of mononuclear cell proliferation cell adhesion cell-cell adhesion negative regulation of cellular process regulation of cell-cell adhesion negative regulation of cell differentiation negative regulation of immature T cell proliferation in thymus regulation of lymphocyte proliferation regulation of lymphocyte differentiation negative regulation of cell population proliferation negative regulation of developmental process regulation of cell adhesion regulation of T cell activation negative regulation of cell activation negative regulation of cell development regulation of T cell proliferation negative regulation of immune system process regulation of hemopoiesis regulation of mononuclear cell proliferation regulation of lymphocyte activation protein phosphorylation organonitrogen compound metabolic process 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 regulation of signaling regulation of signal transduction regulation of MAPK cascade intracellular signal transduction regulation of intracellular signal transduction regulation of response to stimulus intracellular signaling cassette MAPK cascade regulation of cell communication ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade epidermal growth factor receptor signaling pathway ERBB2-EGFR signaling pathway regulation of localization establishment of protein localization regulation of protein localization protein targeting positive regulation of biological process positive regulation of establishment of protein localization regulation of protein targeting to membrane regulation of protein localization to membrane positive regulation of cellular process establishment of protein localization to membrane regulation of establishment of protein localization positive regulation of protein localization to membrane establishment of localization protein targeting to membrane regulation of cellular localization regulation of protein targeting positive regulation of protein localization positive regulation of protein targeting to membrane regulation of growth regulation of cellular component organization growth positive regulation of cell growth regulation of cell growth cell growth cellular component organization positive regulation of growth cellular component organization or biogenesis neurogenesis nervous system development central nervous system development gliogenesis oligodendrocyte differentiation glial cell differentiation phosphatidylinositol 3-kinase/protein kinase B signal transduction negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process apoptotic process programmed cell death peripheral nervous system development glial cell development Schwann cell development Schwann cell differentiation cell junction organization neuromuscular junction development synapse organization axonogenesis cell projection organization motor neuron axon guidance plasma membrane bounded cell projection morphogenesis neuron projection development cell morphogenesis cell projection morphogenesis neuron differentiation neuron projection morphogenesis plasma membrane bounded cell projection organization axon guidance axon development cell morphogenesis involved in neuron differentiation generation of neurons neuron projection guidance neuron development positive regulation of cell communication small GTPase-mediated signal transduction positive regulation of signal transduction regulation of small GTPase mediated signal transduction Rho protein signal transduction positive regulation of response to stimulus positive regulation of intracellular signal transduction regulation of Rho protein signal transduction positive regulation of Rho protein signal transduction positive regulation of small GTPase mediated signal transduction positive regulation of signaling positive regulation of cell population proliferation positive regulation of epithelial cell proliferation regulation of epithelial cell proliferation epithelial cell proliferation positive regulation of cell adhesion cellular biosynthetic process positive regulation of protein metabolic process organonitrogen compound biosynthetic process positive regulation of translation positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process regulation of primary metabolic process post-transcriptional regulation of gene expression positive regulation of metabolic process positive regulation of biosynthetic process organic substance biosynthetic process positive regulation of macromolecule metabolic process regulation of biosynthetic process regulation of protein metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression translation macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process positive regulation of gene expression regulation of translation regulation of macromolecule biosynthetic process regulation of metabolic process positive regulation of cellular biosynthetic process peptidyl-tyrosine modification peptidyl-amino acid modification peptidyl-tyrosine phosphorylation positive regulation of phosphorylation regulation of catalytic activity regulation of transferase activity positive regulation of phosphate metabolic process regulation of MAP kinase activity positive regulation of protein serine/threonine kinase activity regulation of phosphate metabolic process positive regulation of protein phosphorylation positive regulation of MAP kinase activity positive regulation of phosphorus metabolic process positive regulation of MAPK cascade regulation of molecular function positive regulation of kinase activity regulation of kinase activity regulation of protein serine/threonine kinase activity regulation of phosphorus metabolic process regulation of protein modification process regulation of protein phosphorylation positive regulation of molecular function positive regulation of protein modification process positive regulation of protein kinase activity positive regulation of transferase activity positive regulation of catalytic activity regulation of protein kinase activity regulation of phosphorylation semaphorin-plexin signaling pathway cellular response to endogenous stimulus cellular response to growth factor stimulus response to endogenous stimulus response to growth factor wound healing response to stress response to wounding nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase I regulation of nucleobase-containing compound metabolic process positive regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase I positive regulation of RNA metabolic process organic cyclic compound metabolic process organic cyclic compound biosynthetic process regulation of DNA-templated transcription positive regulation of DNA-templated transcription RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process positive regulation of transcription by RNA polymerase I regulation of RNA biosynthetic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process positive regulation of RNA biosynthetic process myelination axon ensheathment ensheathment of neurons cellular response to epidermal growth factor stimulus response to epidermal growth factor regulation of microtubule-based process microtubule-based process	membrane cellular anatomical entity intracellular anatomical structure cytoplasm cytosol cell periphery protein-containing complex plasma membrane protein complex plasma membrane plasma membrane signaling receptor complex membrane protein complex ERBB3:ERBB2 complex receptor complex presynapse membrane cellular anatomical entity intracellular anatomical structure cytoplasm cytosol cell periphery protein-containing complex plasma membrane protein complex plasma membrane plasma membrane signaling receptor complex membrane protein complex ERBB3:ERBB2 complex receptor complex presynapse synapse cell junction presynaptic membrane plasma membrane region synaptic membrane basal part of cell basal plasma membrane basolateral plasma membrane semaphorin receptor complex neuromuscular junction perinuclear region of cytoplasm endosome membrane membrane-bounded organelle endosome intracellular vesicle intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle membrane bounding membrane of organelle vesicle membrane cytoplasmic vesicle organelle vesicle organelle membrane myelin sheath apical part of cell apical plasma membrane ruffle cell leading edge leading edge membrane plasma membrane bounded cell projection cell projection ruffle membrane cell projection membrane nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen early endosome

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
C, D	IPR016245	Tyrosine protein kinase, EGF/ERB/XmrK receptor	Family
C, D	IPR008266	Tyrosine-protein kinase, active site	Active Site
C, D	IPR020635	Tyrosine-protein kinase, catalytic domain	Domain
C, D	IPR000719	Protein kinase domain	Domain
C, D	IPR036941	Receptor L-domain superfamily	Homologous Superfamily
C, D	IPR032778	Growth factor receptor domain 4	Domain
C, D	IPR049328	Epidermal growth factor receptor-like, transmembrane-juxtamembrane segment	Domain
C, D	IPR006212	Furin-like repeat	Repeat
C, D	IPR000494	Receptor L-domain	Domain
C, D	IPR017441	Protein kinase, ATP binding site	Binding Site
C, D	IPR001245	Serine-threonine/tyrosine-protein kinase, catalytic domain	Domain
C, D	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
C, D	IPR006211	Furin-like cysteine-rich domain	Domain
C, D	IPR009030	Growth factor receptor cysteine-rich domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
C, D	Pharos: P04626	lung cancer gastric cancer ovarian cancer Lymphatic Metastasis cholangiocarcinoma prostate cancer medulloblastoma invasive ductal breast carcinoma nasopharyngeal carcinoma breast carcinoma malignant glioma papilloma renal cell carcinoma childhood medulloblastoma head and neck cancer lung cancer gastric cancer ovarian cancer Lymphatic Metastasis cholangiocarcinoma prostate cancer medulloblastoma invasive ductal breast carcinoma nasopharyngeal carcinoma breast carcinoma malignant glioma papilloma renal cell carcinoma childhood medulloblastoma head and neck cancer adenocarcinoma adult medulloblastoma intrahepatic cholangiocarcinoma mixed glioma ductal breast carcinoma in situ ulcerative colitis breast cancer neuroblastoma glioblastoma papillary renal cell carcinoma glioma susceptibility 1 collecting duct carcinoma sarcomatoid renal cell carcinoma melanotic medulloblastoma skin basal cell carcinoma squamous papilloma lung carcinoma urinary bladder cancer gallbladder cancer glioma malignant pancreatic neoplasm chromophobe renal cell carcinoma granular cell carcinoma hereditary diffuse gastric adenocarcinoma medullomyoblastoma with myogenic differentiation tubular adenocarcinoma esophageal cancer malignant colon neoplasm ovarian carcinoma gastric carcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia clear cell renal carcinoma papillomatosis mammary neoplasms, animal colonic neoplasm primary biliary cholangitis marginal zone lymphoma sarcoma melanoma Crohn disease astrocytoma (excluding glioblastoma) skin pigmented basal cell carcinoma liver disease benign colon neoplasm neoplasm of esophagus subependymoma biliary tract neoplasm ependymoma malignant ependymoma non-small cell lung carcinoma gastric neoplasm carcinoma ovarian neoplasm peripheral nervous system disease head and neck carcinoma colorectal adenocarcinoma cribriform carcinoma renal carcinoma inflammatory bowel disease desmoplastic/nodular medulloblastoma atopic eczema lung adenocarcinoma benign neoplasm of stomach systemic lupus erythematosus bipolar disorder lymphoma neutropenia cancer pancreatic ductal adenocarcinoma colonic disease peripheral neuropathy head and neck neoplasm colorectal cancer cribriform carcinoma of breast interstitial cystitis digestive system cancer skin disease leukemia atypical teratoid rhabdoid tumor stomach carcinoma in situ lung benign neoplasm bile duct cancer endometriosis breast adenocarcinoma breast fibroadenoma gallbladder neoplasm

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 R01GM133198.