2KS1

Heterodimeric association of Transmembrane domains of ErbB1 and ErbB2 receptors Enabling Kinase Activation

External Resource: Annotation

Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Membrane Protein Annotation: OPM
Membrane Protein Annotation: PDBTM
Membrane Protein Annotation: MemProtMD
Membrane Protein Annotation: mpstruc

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.20.5.100	Mainly Alpha	Up-down Bundle	Single alpha-helices involved in coiled-coils or other helix-helix interfaces	Cytochrome c1, transmembrane anchor, C-terminal	CATH (4.3.0)
B	1.20.5.420	Mainly Alpha	Up-down Bundle	Single alpha-helices involved in coiled-coils or other helix-helix interfaces	Immunoglobulin FC, subunit C	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF21314	Epidermal growth factor receptor transmembrane-juxtamembrane segment (TM_ErbB1)	Epidermal growth factor receptor transmembrane-juxtamembrane segment	Epidermal growth factor receptor (ErbB) family is a class of receptor tyrosine kinases (RTKs) that have a pivotal role in the processes of cell growth, proliferation, and differentiation [1-5]. They exist on the cell surface as dimers in both active ...	Epidermal growth factor receptor (ErbB) family is a class of receptor tyrosine kinases (RTKs) that have a pivotal role in the processes of cell growth, proliferation, and differentiation [1-5]. They exist on the cell surface as dimers in both active and inactive states, which switch between them through conformational changes upon ligand binding. They suffer a strong lateral dimerization that leads to proper assembly of their extracellular ligand-binding, single-span transmembrane, and cytoplasmic kinase domains which is key for ErbB activation. The transmembrane (TM) and juxtamembrane region of these receptors are essential for dimerization and activation [1-5]. This entry represents the TM and juxtamembrane segment of EGFR, ErbB2 and ErbB4.	Domain
A	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
B	PF21314	Epidermal growth factor receptor transmembrane-juxtamembrane segment (TM_ErbB1)	Epidermal growth factor receptor transmembrane-juxtamembrane segment	Epidermal growth factor receptor (ErbB) family is a class of receptor tyrosine kinases (RTKs) that have a pivotal role in the processes of cell growth, proliferation, and differentiation [1-5]. They exist on the cell surface as dimers in both active ...	Epidermal growth factor receptor (ErbB) family is a class of receptor tyrosine kinases (RTKs) that have a pivotal role in the processes of cell growth, proliferation, and differentiation [1-5]. They exist on the cell surface as dimers in both active and inactive states, which switch between them through conformational changes upon ligand binding. They suffer a strong lateral dimerization that leads to proper assembly of their extracellular ligand-binding, single-span transmembrane, and cytoplasmic kinase domains which is key for ErbB activation. The transmembrane (TM) and juxtamembrane region of these receptors are essential for dimerization and activation [1-5]. This entry represents the TM and juxtamembrane segment of EGFR, ErbB2 and ErbB4.	Domain
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	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
B	Epidermal growth factor receptor	cytoskeletal protein binding actin binding protein-containing complex binding protein binding binding actin filament binding protein phosphatase binding phosphatase binding enzyme binding protein tyrosine kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity cytoskeletal protein binding actin binding protein-containing complex binding protein binding binding actin filament binding protein phosphatase binding phosphatase binding enzyme binding protein tyrosine kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups 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 cell adhesion molecule binding cadherin binding calmodulin binding ubiquitin protein ligase binding ubiquitin-like protein ligase binding growth factor binding epidermal growth factor binding hormone binding molecular transducer activity transmembrane signaling receptor activity signaling receptor activity protein tyrosine kinase activator activity enzyme regulator activity transmembrane receptor protein tyrosine kinase activator activity molecular function activator activity protein kinase regulator activity signaling receptor activator activity kinase activator activity enzyme activator activity molecular function regulator activity signaling receptor regulator activity protein kinase activator activity kinase regulator activity kinase binding protein kinase binding protein serine/threonine kinase activity MAP kinase kinase kinase activity transmembrane receptor protein tyrosine kinase activity transmembrane receptor protein kinase activity ATPase binding identical protein binding virus receptor activity exogenous protein binding epidermal growth factor receptor activity chromatin binding integrin binding signaling receptor binding DNA binding double-stranded DNA binding nucleic acid binding	developmental process multicellular organismal process gland development animal organ development salivary gland development anatomical structure morphogenesis multicellular organism development gland morphogenesis salivary gland morphogenesis anatomical structure development animal organ morphogenesis exocrine system development system development regulation of biological process developmental process multicellular organismal process gland development animal organ development salivary gland development anatomical structure morphogenesis multicellular organism development gland morphogenesis salivary gland morphogenesis anatomical structure development animal organ morphogenesis exocrine system development system development regulation of biological process regulation of cellular process cellular metabolic process reactive oxygen species metabolic process biological regulation positive regulation of biological process regulation of superoxide metabolic process regulation of cellular metabolic process positive regulation of cellular metabolic process positive regulation of reactive oxygen species metabolic process superoxide metabolic process positive regulation of metabolic process superoxide anion generation metabolic process cellular process positive regulation of superoxide anion generation regulation of superoxide anion generation regulation of metabolic process regulation of reactive oxygen species metabolic process positive regulation of cellular process regulation of tube diameter system process regulation of tube size regulation of system process positive regulation of vasoconstriction circulatory system process regulation of blood circulation vascular process in circulatory system regulation of vasoconstriction positive regulation of multicellular organismal process regulation of multicellular organismal process blood vessel diameter maintenance regulation of biological quality vasoconstriction blood circulation regulation of anatomical structure size tongue development sensory organ development positive regulation of protein localization to plasma membrane protein localization regulation of localization cellular localization regulation of protein localization localization cellular macromolecule localization regulation of protein localization to membrane positive regulation of protein localization to cell periphery protein localization to cell periphery protein localization to plasma membrane positive regulation of protein localization to membrane localization within membrane regulation of protein localization to cell periphery protein localization to membrane regulation of cellular localization macromolecule localization positive regulation of protein localization regulation of protein localization to plasma membrane positive regulation of phosphorylation regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process regulation of peptidyl-serine phosphorylation positive regulation of phosphate metabolic process peptidyl-serine modification regulation of primary metabolic process positive regulation of protein modification process organic substance metabolic process peptidyl-serine phosphorylation regulation of phosphate metabolic process phosphate-containing compound metabolic process peptidyl-amino acid modification positive regulation of macromolecule metabolic process protein metabolic process positive regulation of protein phosphorylation phosphorus metabolic process protein modification process organonitrogen compound metabolic process protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process primary metabolic process regulation of macromolecule metabolic process positive regulation of peptidyl-serine phosphorylation macromolecule modification regulation of phosphorus metabolic process regulation of phosphorylation macromolecule metabolic process cerebral cortex cell migration head development forebrain development brain development nervous system development pallium development cerebral cortex development telencephalon cell migration central nervous system development forebrain cell migration cell migration telencephalon development cell motility cellular response to stimulus response to stimulus signaling negative regulation of signaling negative regulation of ERBB signaling pathway negative regulation of biological process regulation of signal transduction cell surface receptor protein tyrosine kinase signaling pathway negative regulation of cell communication cell communication regulation of epidermal growth factor receptor signaling pathway negative regulation of cellular process epidermal growth factor receptor signaling pathway signal transduction enzyme-linked receptor protein signaling pathway regulation of signaling regulation of ERBB signaling pathway cell surface receptor signaling pathway negative regulation of response to stimulus negative regulation of signal transduction regulation of response to stimulus negative regulation of epidermal growth factor receptor signaling pathway ERBB signaling pathway regulation of cell communication regulation of cellular response to stress positive regulation of response to stimulus nucleobase-containing compound metabolic process positive regulation of DNA repair cellular response to stress response to stress regulation of response to stress regulation of nucleobase-containing compound metabolic process DNA repair positive regulation of nucleobase-containing compound metabolic process DNA metabolic process nucleic acid metabolic process regulation of DNA repair organic cyclic compound metabolic process positive regulation of DNA metabolic process DNA damage response regulation of DNA metabolic process positive regulation of macromolecule biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of miRNA metabolic process organic substance biosynthetic process miRNA metabolic process positive regulation of RNA metabolic process regulation of gene expression biosynthetic process organic cyclic compound biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription cellular biosynthetic process positive regulation of DNA-templated transcription RNA metabolic process positive regulation of miRNA transcription positive regulation of miRNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process miRNA transcription positive regulation of biosynthetic process regulation of RNA biosynthetic process regulation of biosynthetic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process positive regulation of RNA biosynthetic process ncRNA metabolic process positive regulation of cellular biosynthetic process regulation of miRNA transcription response to nutrient levels response to organic substance response to organonitrogen compound response to nutrient response to oxygen-containing compound response to nitrogen compound response to vitamin response to cobalamin response to chemical response to organic cyclic compound cellular developmental process astrocyte differentiation cell development astrocyte activation glial cell development neurogenesis astrocyte development gliogenesis cell differentiation defense response cell activation glial cell differentiation glial cell activation inflammatory response neuroinflammatory response ossification cell population proliferation regulation of smooth muscle cell proliferation positive regulation of cell population proliferation smooth muscle cell proliferation positive regulation of smooth muscle cell proliferation regulation of cell population proliferation muscle cell proliferation digestive system development tube development digestive tract development tube morphogenesis digestive tract morphogenesis positive regulation of cell communication establishment of protein localization nitrogen compound transport positive regulation of establishment of protein localization regulation of peptide hormone secretion positive regulation of prolactin secretion regulation of hormone levels positive regulation of peptide hormone secretion organic substance transport establishment of protein localization to extracellular region protein secretion establishment of localization regulation of secretion regulation of protein secretion regulation of hormone secretion regulation of peptide secretion transport positive regulation of secretion by cell hormone secretion protein localization to extracellular region positive regulation of protein transport peptide secretion secretion by cell regulation of secretion by cell positive regulation of hormone secretion positive regulation of secretion amide transport signal release positive regulation of peptide secretion secretion regulation of transport regulation of peptide transport regulation of establishment of protein localization prolactin secretion cell-cell signaling export from cell regulation of protein transport positive regulation of protein secretion peptide transport positive regulation of transport protein transport peptide hormone secretion hormone transport positive regulation of signaling cellular response to chemical stimulus cellular response to xenobiotic stimulus response to xenobiotic stimulus ERBB2 signaling pathway ERBB2-EGFR signaling pathway ovulation cycle rhythmic process reproductive process multicellular organismal reproductive process 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 circadian rhythm hydrogen peroxide metabolic process positive regulation of signal transduction intracellular signal transduction positive regulation of ERK1 and ERK2 cascade regulation of intracellular signal transduction intracellular signaling cassette positive regulation of MAPK cascade positive regulation of intracellular signal transduction regulation of MAPK cascade MAPK cascade ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade modulation of chemical synaptic transmission synaptic transmission, glutamatergic regulation of synaptic transmission, glutamatergic synaptic signaling trans-synaptic signaling positive regulation of synaptic transmission positive regulation of synaptic transmission, glutamatergic chemical synaptic transmission regulation of trans-synaptic signaling anterograde trans-synaptic signaling nitric oxide mediated signal transduction regulation of nitric oxide mediated signal transduction positive regulation of nitric oxide mediated 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 epithelium development epidermis development molting cycle process hair cycle tissue development skin development skin epidermis development hair follicle development molting cycle hair cycle process morphogenesis of an epithelial fold tissue morphogenesis morphogenesis of an epithelium animal organ regeneration liver development regeneration hepaticobiliary system development liver regeneration regulation of catalytic activity regulation of cyclin-dependent protein kinase activity regulation of transferase activity positive regulation of protein serine/threonine kinase activity positive regulation of cyclin-dependent protein serine/threonine kinase activity regulation of cyclin-dependent protein serine/threonine kinase activity cell cycle regulation of molecular function positive regulation of kinase activity regulation of kinase activity regulation of protein serine/threonine kinase activity positive regulation of cyclin-dependent protein kinase activity positive regulation of molecular function positive regulation of protein kinase activity regulation of cell cycle positive regulation of transferase activity positive regulation of catalytic activity regulation of protein kinase activity positive regulation of cell cycle placenta development chordate embryonic development embryo development in utero embryonic development embryonic placenta development embryo development ending in birth or egg hatching embryonic organ development regulation of MAP kinase activity positive regulation of MAP kinase activity epithelial cell proliferation response to mechanical stimulus response to external stimulus response to abiotic stimulus cellular response to mechanical stimulus cellular response to abiotic stimulus cellular response to external stimulus cellular response to environmental stimulus positive regulation of locomotion regulation of cell motility positive regulation of cell migration regulation of locomotion positive regulation of cell motility regulation of cell migration locomotion regulation of non-canonical NF-kappaB signal transduction non-canonical NF-kappaB signal transduction positive regulation of non-canonical NF-kappaB signal transduction regulation of body fluid levels secretion by tissue regulation of mucus secretion mucus secretion body fluid secretion positive regulation of mucus secretion response to lipid cellular response to organic cyclic compound cellular response to oxygen-containing compound cellular response to lipid response to estradiol cellular response to estradiol stimulus cellular response to organic substance membrane organization establishment of protein localization to membrane protein insertion into membrane regulation of canonical Wnt signaling pathway canonical Wnt signaling pathway positive regulation of Wnt signaling pathway Wnt signaling pathway positive regulation of canonical Wnt signaling pathway regulation of Wnt signaling pathway eyelid development in camera-type eye eye development visual system development camera-type eye development sensory system development 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 positive regulation of nervous system development regulation of developmental process regulation of neurogenesis regulation of cell differentiation regulation of gliogenesis positive regulation of glial cell proliferation positive regulation of gliogenesis regulation of cell development regulation of nervous system development positive regulation of developmental process regulation of glial cell proliferation positive regulation of cell differentiation positive regulation of neurogenesis regulation of multicellular organismal development positive regulation of cell development glial cell proliferation regulation of monooxygenase activity regulation of nitric-oxide synthase activity regulation of oxidoreductase activity regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction phosphatidylinositol 3-kinase/protein kinase B signal transduction protein autophosphorylation peptidyl-tyrosine modification peptidyl-tyrosine autophosphorylation peptidyl-tyrosine phosphorylation midgut development regulation of JNK cascade JNK cascade response to metal ion response to calcium ion response to inorganic substance regulation of peptidyl-tyrosine phosphorylation positive regulation of DNA replication DNA replication regulation of DNA replication response to ketone response to hormone response to steroid hormone cellular response to ketone cellular response to steroid hormone stimulus cellular response to hormone stimulus cellular response to dexamethasone stimulus response to glucocorticoid cellular response to glucocorticoid stimulus cellular response to corticosteroid stimulus response to corticosteroid response to dexamethasone regulation of cell cycle phase transition cell cycle phase transition regulation of cell cycle G1/S phase transition cell cycle G1/S phase transition mitotic cell cycle regulation of mitotic cell cycle positive regulation of mitotic cell cycle phase transition positive regulation of cell cycle process positive regulation of mitotic cell cycle cell cycle process positive regulation of G1/S transition of mitotic cell cycle regulation of cell cycle process regulation of mitotic cell cycle phase transition positive regulation of cell cycle G1/S phase transition mitotic cell cycle process regulation of G1/S transition of mitotic cell cycle positive regulation of cell cycle phase transition G1/S transition of mitotic cell cycle mitotic cell cycle phase transition response to light stimulus response to radiation response to UV response to UV-A cellular response to acid chemical cellular response to amino acid stimulus response to acid chemical response to amino acid regulation of phospholipase activity positive regulation of phospholipase activity positive regulation of phospholipase C activity positive regulation of lipase activity positive regulation of hydrolase activity regulation of phospholipase C activity regulation of hydrolase activity regulation of lipase activity activation of phospholipase C activity homeostatic process regulation of bone remodeling tissue homeostasis regulation of tissue remodeling regulation of bone resorption bone resorption multicellular organismal-level homeostasis tissue remodeling bone remodeling anatomical structure homeostasis positive regulation of bone resorption catabolic process macromolecule catabolic process negative regulation of protein catabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process organonitrogen compound catabolic process negative regulation of catabolic process negative regulation of metabolic process protein catabolic process regulation of catabolic process organic substance catabolic process regulation of protein catabolic process cellular response to inorganic substance cellular response to metal ion response to cadmium ion cellular response to cadmium ion transcription by RNA polymerase II regulation of transcription by RNA polymerase II positive regulation of transcription by RNA polymerase II response to phenylpropanoid response to hydroxyisoflavone organonitrogen compound biosynthetic process translation negative regulation of cell differentiation negative regulation of cardiocyte differentiation heart development negative regulation of developmental process cardiocyte differentiation circulatory system development regulation of cardiocyte differentiation negative regulation of multicellular organismal process fibroblast proliferation regulation of fibroblast proliferation positive regulation of fibroblast proliferation respiratory tube development lung development respiratory system development positive regulation of epithelial cell proliferation regulation of epithelial cell proliferation positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction diterpenoid metabolic process cellular lipid metabolic process terpenoid metabolic process isoprenoid metabolic process lipid metabolic process cell projection organization 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 generation of neurons neuron development vasodilation cellular response to oxidative stress cellular response to chemical stress response to reactive oxygen species cellular response to reactive oxygen species response to oxidative stress behavior learning or memory nervous system process cognition cell adhesion cell-cell adhesion positive regulation of protein kinase C activity regulation of protein kinase C activity negative regulation of cell cycle negative regulation of mitotic cell cycle	membrane-bounded organelle intracellular anatomical structure nuclear membrane membrane nucleus cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle organelle envelope organelle nuclear envelope organelle membrane intracellular vesicle membrane-bounded organelle intracellular anatomical structure nuclear membrane membrane nucleus cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle organelle envelope organelle nuclear envelope organelle membrane intracellular vesicle bounding membrane of organelle cytoplasmic vesicle vesicle membrane clathrin-coated vesicle endocytic vesicle membrane coated vesicle vesicle endocytic vesicle clathrin-coated vesicle membrane clathrin-coated endocytic vesicle membrane clathrin-coated endocytic vesicle cytoplasmic vesicle membrane coated vesicle membrane cytoplasm protein-containing complex receptor complex Golgi membrane Golgi apparatus endosome membrane endosome extracellular region extracellular space anchoring junction cell junction focal adhesion cell-substrate junction cell periphery apical part of cell plasma membrane plasma membrane region apical plasma membrane ruffle cell leading edge leading edge membrane plasma membrane bounded cell projection cell projection ruffle membrane cell projection membrane basal part of cell basal plasma membrane cell surface membrane microdomain membrane raft organelle subcompartment endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum endoplasmic reticulum membrane basolateral plasma membrane perinuclear region of cytoplasm Shc-EGFR complex plasma membrane protein complex membrane protein complex multivesicular body, internal vesicle vesicle lumen multivesicular body, internal vesicle lumen membrane-enclosed lumen intracellular organelle lumen organelle lumen late endosome multivesicular body early endosome early endosome membrane

InterPro: Protein Family Classification InterPro Database Homepage

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

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	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
B	Pharos: P00533	non-small cell lung carcinoma glioblastoma inflammatory skin and bowel disease, neonatal, 2 giant cell glioblastoma osteosarcoma lung cancer cholangiocarcinoma squamous cell carcinoma autosomal recessive polycystic kidney disease dilated cardiomyopathy breast cancer cancer esophageal squamous cell carcinoma classic familial adenomatous polyposis gliosarcoma non-small cell lung carcinoma glioblastoma inflammatory skin and bowel disease, neonatal, 2 giant cell glioblastoma osteosarcoma lung cancer cholangiocarcinoma squamous cell carcinoma autosomal recessive polycystic kidney disease dilated cardiomyopathy breast cancer cancer esophageal squamous cell carcinoma classic familial adenomatous polyposis gliosarcoma breast carcinoma malignant colon neoplasm ovarian cancer papilloma urinary bladder cancer adrenal cortex carcinoma head and neck cancer squamous papilloma head and neck squamous cell carcinoma tubular adenocarcinoma dermatitis prostate cancer Mammary Neoplasms, Experimental adenocarcinoma rectal cancer cervical cancer small cell lung carcinoma colorectal cancer malignant mesothelioma bile duct cancer type 2 diabetes mellitus intrahepatic cholangiocarcinoma gallbladder cancer granular cell carcinoma bile duct carcinoma endometriosis esophageal cancer rectal neoplasm carcinoma sarcomatoid carcinoma nasopharyngeal carcinoma malignant glioma ovarian disease cribriform carcinoma pancreatic ductal adenocarcinoma benign neoplasm of esophagus papillomatosis hepatocellular carcinoma bile duct neoplasm malignant pancreatic neoplasm pituitary cancer brain disease urinary bladder disease acute kidney failure interstitial cystitis uterine disease endometrial carcinoma endometrium adenocarcinoma kidney disease maturity-onset diabetes of the young rheumatoid arthritis laryngeal squamous cell carcinoma carcinoma of esophagus lung benign neoplasm nasopharyngeal neoplasm gastric cancer lung disease neoplasm of esophagus major depressive disorder atypical teratoid rhabdoid tumor squamous cell lung carcinoma Cowden syndrome 1 ovarian neoplasm head and neck carcinoma benign colon neoplasm subependymal giant cell astrocytoma cribriform carcinoma of breast pancreatic neoplasm Pick disease bone disease malignant tumor of nasopharynx dilated cardiomyopathy 1A brain glioma urinary bladder neoplasm ductal breast carcinoma in situ prostate disease endometrium carcinoma in situ rectal carcinoma medulloblastoma esophagus carcinoma in situ adrenal carcinoma sarcoidosis myopathy alcohol abuse small cell carcinoma gastric neoplasm spina bifida colonic neoplasm neoplasm of neck colorectal carcinoma autosomal dominant polycystic kidney disease pancreatic adenocarcinoma head and neck neoplasm benign mesothelioma tongue squamous cell carcinoma cutaneous lupus erythematosus hematologic disease undifferentiated carcinoma digestive system disease pilocytic astrocytoma hereditary diffuse gastric adenocarcinoma bone osteosarcoma malignant tumor of neck prostate adenocarcinoma mammary neoplasms, animal invasive ductal breast carcinoma breast disease large cell medulloblastoma mesothelioma exanthem lung adenocarcinoma gallbladder neoplasm lung carcinoma genetic intestinal polyposis lymphatic system disease colorectal adenocarcinoma oligodendroglioma glioma astrocytic tumor

Membrane Protein Annotation: OPM OPM Database Homepage

Chains	External Link	Type	Class	Superfamily	Family
A, B	OPM	Transmembrane	Bitopic proteins	Receptor-type kinases	Protein tyrosine kinases

Membrane Protein Annotation: PDBTM PDBTM Database Homepage

Chains	External Link	Comment
A, B	PDBTM	Annotated as membrane protein by PDBTM

Membrane Protein Annotation: MemProtMD MemProtMD Database Homepage

Chains	External Link	Comment
A, B	MemProtMD	Annotated as membrane protein by MemProtMD

Membrane Protein Annotation: mpstruc mpstruc Database Homepage

Chains	Resource Link	Group	Subgroup	Protein
A, B	mpstruc	TRANSMEMBRANE PROTEINS: ALPHA-HELICAL	Epidermal Growth Factor Receptors (EGFRs)	ErbB1/ErbB2 transmembrane segment heterodimer

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.

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2KS1

Heterodimeric association of Transmembrane domains of ErbB1 and ErbB2 receptors Enabling Kinase Activation

External Resource: Annotation

Domain Annotation: CATH CATH Database Homepage

Protein Family Annotation Pfam Database Homepage

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

InterPro: Protein Family Classification InterPro Database Homepage

Pharos: Disease Associations Pharos Homepage Annotation

Membrane Protein Annotation: OPM OPM Database Homepage

Membrane Protein Annotation: PDBTM PDBTM Database Homepage

Membrane Protein Annotation: MemProtMD MemProtMD Database Homepage

Membrane Protein Annotation: mpstruc mpstruc Database Homepage