Annotations: 1CN4

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d1cn4a1	All beta proteins	Immunoglobulin-like beta-sandwich	Fibronectin type III	Fibronectin type III	Erythropoietin (EPO) receptor	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d1cn4b1	All beta proteins	Immunoglobulin-like beta-sandwich	Fibronectin type III	Fibronectin type III	Erythropoietin (EPO) receptor	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d1cn4c_	All alpha proteins	4-helical cytokines	4-helical cytokines	Short-chain cytokines	Erythropoietin	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	Fibronectin type III	8055513	3002063	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Fibronectin type III	8055127	3002063	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Fibronectin type III	8055127	3002063	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Fibronectin type III	8055513	3002063	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	4-helical cytokines	8037086	3001717	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	EpoR_lig-bind	e1cn4A1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: EpoR_lig-bind	ECOD (1.6)
A	fn3_6	e1cn4A2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: fn3_6	ECOD (1.6)
B	EpoR_lig-bind	e1cn4B1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: EpoR_lig-bind	ECOD (1.6)
B	fn3_6	e1cn4B2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: fn3_6	ECOD (1.6)
C	EPO_TPO	e1cn4C1	A: alpha bundles	X: Ferritin/Heme oxygenase/4-helical cytokines	H: 4-helical cytokines (From Topology)	T: 4-helical cytokines	F: EPO_TPO	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
B	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
C	1.20.1250.10	Mainly Alpha	Up-down Bundle	Growth Hormone	Chain: A	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF09067	Erythropoietin receptor, ligand binding (EpoR_lig-bind)	Erythropoietin receptor, ligand binding	Members of this family interact with erythropoietin (EPO), with subsequent initiation of the downstream chain of events associated with binding of EPO to the receptor, including EPO-induced erythroblast proliferation and differentiation through induc ...	Members of this family interact with erythropoietin (EPO), with subsequent initiation of the downstream chain of events associated with binding of EPO to the receptor, including EPO-induced erythroblast proliferation and differentiation through induction of the JAK2/STAT5 signaling cascade. The domain adopts a secondary structure composed of a short amino-terminal helix, followed by two beta-sandwich regions [1].	Domain
A, B	PF00041	Fibronectin type III domain (fn3)	Fibronectin type III domain		Domain
C	PF00758	Erythropoietin/thrombopoietin (EPO_TPO)	Erythropoietin/thrombopoietin		Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	PROTEIN (ERYTHROPOIETIN RECEPTOR)	molecular transducer activity erythropoietin receptor activity transmembrane signaling receptor activity signaling receptor activity cytokine receptor activity immune receptor activity identical protein binding protein binding binding	regulation of biological process cell population proliferation regulation of cellular process positive regulation of cell population proliferation regulation of cell population proliferation biological regulation positive regulation of biological process cellular process positive regulation of cellular process developmental process multicellular organism development multicellular organismal process head development central nervous system development regulation of biological process cell population proliferation regulation of cellular process positive regulation of cell population proliferation regulation of cell population proliferation biological regulation positive regulation of biological process cellular process positive regulation of cellular process developmental process multicellular organism development multicellular organismal process head development central nervous system development anatomical structure development animal organ development brain development nervous system development system development cellular response to stimulus cell surface receptor signaling pathway response to stimulus signaling response to cytokine cytokine-mediated signaling pathway cell communication response to peptide response to chemical cellular response to cytokine stimulus signal transduction heart development circulatory system development multi-multicellular organism process placenta development reproductive process maternal process involved in female pregnancy multicellular organismal reproductive process developmental process involved in reproduction tissue development maternal placenta development female pregnancy multi-organism reproductive process decidualization erythropoietin-mediated signaling pathway response to erythropoietin cellular response to erythropoietin cellular developmental process hemopoiesis cell differentiation cell development	cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck nuclear body intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen extracellular region
C	PROTEIN (ERYTHROPOIETIN)	protein binding binding signaling receptor binding cytokine receptor binding erythropoietin receptor binding enzyme regulator activity kinase activator activity enzyme activator activity molecular function activator activity molecular function regulator activity protein kinase activator activity protein kinase regulator activity kinase regulator activity cytokine activity protein binding binding signaling receptor binding cytokine receptor binding erythropoietin receptor binding enzyme regulator activity kinase activator activity enzyme activator activity molecular function activator activity molecular function regulator activity protein kinase activator activity protein kinase regulator activity kinase regulator activity cytokine activity signaling receptor regulator activity receptor ligand activity signaling receptor activator activity hormone activity	response to stimulus response to stress response to wounding response to axon injury response to hormone response to endogenous stimulus response to chemical response to estrogen cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction signaling positive regulation of biological process response to stimulus response to stress response to wounding response to axon injury response to hormone response to endogenous stimulus response to chemical response to estrogen cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction signaling positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus positive regulation of ERK1 and ERK2 cascade regulation of intracellular signal transduction intracellular signaling cassette signal transduction positive regulation of cellular process regulation of biological process regulation of signaling positive regulation of MAPK cascade biological regulation positive regulation of intracellular signal transduction regulation of MAPK cascade regulation of response to stimulus MAPK cascade regulation of cell communication cellular process ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade positive regulation of signaling erythropoietin-mediated signaling pathway cell surface receptor signaling pathway response to cytokine response to erythropoietin cytokine-mediated signaling pathway response to peptide cellular response to erythropoietin cellular response to cytokine stimulus response to ketone response to lipid response to oxygen-containing compound response to testosterone cell surface receptor signaling pathway via STAT response to interleukin-1 response to nutrient levels response to nutrient response to vitamin A response to vitamin regulation of localization negative regulation of ion transmembrane transporter activity negative regulation of cation channel activity transport monoatomic ion transmembrane transport negative regulation of monoatomic ion transport negative regulation of biological process regulation of transmembrane transporter activity negative regulation of transport regulation of monoatomic ion transmembrane transport negative regulation of transmembrane transport regulation of transporter activity monoatomic cation transmembrane transport localization negative regulation of monoatomic ion transmembrane transport negative regulation of cellular process negative regulation of cation transmembrane transport monoatomic ion transport monoatomic cation transport regulation of monoatomic ion transmembrane transporter activity regulation of transport regulation of monoatomic ion transport negative regulation of transporter activity negative regulation of molecular function establishment of localization regulation of cation channel activity transmembrane transport regulation of molecular function regulation of transmembrane transport regulation of monoatomic cation transmembrane transport myeloid cell apoptotic process negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process erythrocyte apoptotic process negative regulation of myeloid cell apoptotic process apoptotic process regulation of myeloid cell apoptotic process programmed cell death negative regulation of erythrocyte apoptotic process regulation of erythrocyte apoptotic process response to osmotic stress cellular response to chemical stress cellular response to osmotic stress cellular response to environmental stimulus cellular response to chemical stimulus hyperosmotic response cellular hyperosmotic response cellular response to stress response to abiotic stimulus cellular response to abiotic stimulus developmental process multicellular organism development multicellular organismal process multi-multicellular organism process reproductive process anatomical structure development female pregnancy embryo implantation multi-organism reproductive process regulation of neuron projection development regulation of cellular component organization positive regulation of cellular component organization cellular developmental process cell projection organization cell development neuron projection development cellular component organization neurogenesis neuron differentiation positive regulation of neuron projection development cell differentiation positive regulation of cell projection organization cellular component organization or biogenesis system development plasma membrane bounded cell projection organization regulation of cell projection organization nervous system development generation of neurons neuron development regulation of plasma membrane bounded cell projection organization response to electrical stimulus cell population proliferation positive regulation of cell population proliferation regulation of cell population proliferation regulation of leukocyte activation regulation of cell activation positive regulation of cell activation T cell activation lymphocyte proliferation positive regulation of leukocyte activation regulation of immune system process positive regulation of immune system process regulation of leukocyte proliferation positive regulation of T cell activation positive regulation of lymphocyte proliferation positive regulation of T cell proliferation positive regulation of activated T cell proliferation mononuclear cell proliferation regulation of leukocyte cell-cell adhesion positive regulation of leukocyte proliferation positive regulation of multicellular organismal process regulation of activated T cell proliferation positive regulation of leukocyte cell-cell adhesion lymphocyte activation leukocyte proliferation leukocyte cell-cell adhesion leukocyte activation activated T cell proliferation positive regulation of cell-cell adhesion positive regulation of lymphocyte activation cell adhesion cell-cell adhesion positive regulation of mononuclear cell proliferation regulation of multicellular organismal process regulation of cell-cell adhesion T cell proliferation regulation of lymphocyte proliferation positive regulation of cell adhesion regulation of cell adhesion cell activation regulation of T cell activation regulation of T cell proliferation immune system process regulation of mononuclear cell proliferation regulation of lymphocyte activation response to glucocorticoid response to corticosteroid response to steroid hormone response to dexamethasone regulation of developmental process regulation of cell differentiation positive regulation of neuron differentiation positive regulation of developmental process positive regulation of cell differentiation regulation of neuron differentiation acute-phase response defense response inflammatory response acute inflammatory response hemoglobin biosynthetic process biosynthetic process metabolic process primary metabolic process macromolecule metabolic process protein metabolic process macromolecule biosynthetic process hemoglobin metabolic process regulation of cellular response to stress regulation of response to osmotic stress regulation of cellular response to osmotic stress negative regulation of apoptotic signaling pathway intrinsic apoptotic signaling pathway regulation of intrinsic apoptotic signaling pathway in response to osmotic stress intrinsic apoptotic signaling pathway in response to osmotic stress regulation of apoptotic signaling pathway negative regulation of signaling negative regulation of intracellular signal transduction regulation of intrinsic apoptotic signaling pathway negative regulation of cell communication regulation of response to stress negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress negative regulation of response to stimulus negative regulation of signal transduction apoptotic signaling pathway negative regulation of intrinsic apoptotic signaling pathway response to decreased oxygen levels response to hypoxia response to oxygen levels positive regulation of DNA-templated transcription RNA metabolic process positive regulation of macromolecule biosynthetic process regulation of primary metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process nucleic acid biosynthetic process positive regulation of metabolic process DNA-templated transcription regulation of RNA metabolic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of biosynthetic process positive regulation of nucleobase-containing compound metabolic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression nucleic acid metabolic process positive regulation of RNA metabolic process regulation of gene expression positive regulation of RNA biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription regulation of metabolic process homeostatic process hemopoiesis erythrocyte differentiation multicellular organismal-level homeostasis myeloid cell differentiation homeostasis of number of cells myeloid cell homeostasis erythrocyte homeostasis negative regulation of RNA biosynthetic process transcription by RNA polymerase II negative regulation of nucleobase-containing compound metabolic process negative regulation of macromolecule metabolic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II negative regulation of metabolic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of RNA metabolic process regulation of calcium ion transport cellular localization regulation of calcium ion transport into cytosol calcium ion transport metal ion transport regulation of calcium ion transmembrane transport regulation of biological quality negative regulation of calcium ion transport into cytosol regulation of metal ion transport calcium ion transmembrane import into cytosol positive regulation of cytosolic calcium ion concentration inorganic ion transmembrane transport inorganic cation transmembrane transport negative regulation of calcium ion transport regulation of cellular localization negative regulation of calcium ion transmembrane transport negative regulation of cytosolic calcium ion concentration calcium ion transmembrane transport calcium ion transport into cytosol erythrocyte development erythrocyte maturation developmental maturation anatomical structure maturation myeloid cell development cell maturation biological process involved in interspecies interaction between organisms response to other organism response to external stimulus response to lipopolysaccharide response to biotic stimulus response to bacterium response to external biotic stimulus response to molecule of bacterial origin small GTPase-mediated signal transduction regulation of small GTPase mediated signal transduction regulation of Ras protein signal transduction positive regulation of Ras protein signal transduction Ras protein signal transduction positive regulation of small GTPase mediated signal transduction response to salt stress system process circulatory system process blood circulation response to hyperoxia response to increased oxygen levels	cell surface cellular anatomical structure extracellular region cell body extracellular space

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR015152	Growth hormone/erythropoietin receptor, ligand binding	Domain
A, B	IPR009167	Erythropoietin receptor	Family
A, B	IPR003961	Fibronectin type III	Domain
A, B	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
A, B	IPR003528	Long hematopoietin receptor, single chain, conserved site	Conserved Site
A, B	IPR036116	Fibronectin type III superfamily	Homologous Superfamily
C	IPR003013	Erythropoietin	Family
C	IPR019767	Erythropoietin/thrombopoeitin, conserved site	Conserved Site
C	IPR001323	Erythropoietin/thrombopoietin	Family
C	IPR009079	Four-helical cytokine-like, core	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P19235	polycythemia familial polycythemia melanoma breast carcinoma Neoplasm Metastasis primary familial polycythemia due to EPO receptor mutation thyroid adenoma breast cancer thyroid gland carcinoma large cell medulloblastoma medulloblastoma ovarian cancer acquired polycythemia vera pancreatic intraductal papillary-mucinous neoplasm anemia polycythemia familial polycythemia melanoma breast carcinoma Neoplasm Metastasis primary familial polycythemia due to EPO receptor mutation thyroid adenoma breast cancer thyroid gland carcinoma large cell medulloblastoma medulloblastoma ovarian cancer acquired polycythemia vera pancreatic intraductal papillary-mucinous neoplasm anemia atypical teratoid rhabdoid tumor cutaneous melanoma erythropoietin polycythemia glioblastoma lung cancer pancreatic ductal adenocarcinoma acute erythroid leukemia pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia psoriasis thyroid cancer dermatomyositis hypertensive disorder malignant glioma osteosarcoma pancreatic intraductal papillary-mucinous carcinoma acute erythroleukemia, familial rheumatoid arthritis
C	Pharos: P01588	thrombocytopenia myelodysplastic syndrome beta thalassemia hemolytic-uremic syndrome hypertensive disorder melanoma anemia pancytopenia kidney failure status epilepticus cardiomyopathy Inflammation chronic kidney disease critical illness polyneuropathy thyroid gland carcinoma thrombocytopenia myelodysplastic syndrome beta thalassemia hemolytic-uremic syndrome hypertensive disorder melanoma anemia pancytopenia kidney failure status epilepticus cardiomyopathy Inflammation chronic kidney disease critical illness polyneuropathy thyroid gland carcinoma uremia heart disease ventricular fibrillation ventricular tachycardia polyneuropathy central nervous system disease pulmonary embolism kidney disease microvascular complications of diabetes, susceptibility to, 2 thyroid adenoma vascular disease ventricular septal defect poisoning coronary artery disease myocardial infarction experimental autoimmune encephalomyelitis gastric ulcer hemolytic anemia paraneoplastic syndrome calcinosis iron deficiency anemia congenital diaphragmatic hernia familial polycythemia glioblastoma neurodegenerative disease ovarian cancer brain injury cancer inflammatory bowel disease large cell medulloblastoma cutaneous melanoma acute kidney failure erythrocytosis, familial, 5 hereditary persistence of fetal hemoglobin inborn carbohydrate metabolic disorder cerebrovascular disorder thalassemia minor thrombotic disease Diamond-Blackfan anemia-like thyroid cancer atypical teratoid rhabdoid tumor Hashimoto thyroiditis polycythemia

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