Annotations: 4FYS

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	ARM repeat-like	8054111	3000116	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Leukotriene A4 hydrolase N-terminal domain	8054108	3000390	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Metalloproteases (zincins), catalytic domain	8054109	3001975	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	ERAP1, insert domain	8054110	3002272	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	ERAP1_C	e4fysA3	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: ERAP1_C	ECOD (1.6)
A	Peptidase_M1_2	e4fysA6	A: beta sandwiches	X: Baculovirus p35 protein-related (From Topology)	H: Baculovirus p35 protein-related (From Topology)	T: Baculovirus p35 protein-related	F: Peptidase_M1_2	ECOD (1.6)
A	ERAP1_C	e4fysA2	A: alpha superhelices	X: Repetitive alpha hairpins	H: ARM repeat (From Topology)	T: ARM repeat	F: ERAP1_C	ECOD (1.6)
A	Peptidase_M1	e4fysA4	A: mixed a+b and a/b	X: Zincin-like	H: Metalloproteases (zincins) catalytic domain (From Topology)	T: Metalloproteases (zincins) catalytic domain	F: Peptidase_M1	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.60.40.1730	Mainly Beta	Sandwich	Immunoglobulin-like	tricorn interacting facor f3 domain	CATH (4.3.0)
A	1.10.390.10	Mainly Alpha	Orthogonal Bundle	Neutral Protease	domain 2	CATH (4.3.0)
A	2.60.40.1910	Mainly Beta	Sandwich	Immunoglobulin-like		CATH (4.3.0)
A	1.25.50.20	Mainly Alpha	Alpha Horseshoe	Zincin-like fold		CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF11838	ERAP1-like C-terminal domain (ERAP1_C)	ERAP1-like C-terminal domain	This large domain is composed of 16 alpha helices organized as 8 HEAT-like repeats. This domain forms a concave face that faces towards the active site of the peptidase.	Domain
A	PF01433	Peptidase family M1 domain (Peptidase_M1)	Peptidase family M1 domain	Members of this family are aminopeptidases. The members differ widely in specificity, hydrolysing acidic, basic or neutral N-terminal residues. This family includes leukotriene-A4 hydrolase Swiss:P09960, this enzyme also has an aminopeptidase activ ...	Members of this family are aminopeptidases. The members differ widely in specificity, hydrolysing acidic, basic or neutral N-terminal residues. This family includes leukotriene-A4 hydrolase Swiss:P09960, this enzyme also has an aminopeptidase activity [1].	Domain
A	PF17900	Peptidase M1 N-terminal domain (Peptidase_M1_N)	Peptidase M1 N-terminal domain	This domain is found at the N-terminus of aminopeptidases from the M1 family.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
B [auth C]	Angiotensin IV	protein binding binding molecular function activator activity signaling receptor binding molecular function regulator activity signaling receptor regulator activity growth factor activity receptor ligand activity signaling receptor activator activity angiotensin receptor binding type 1 angiotensin receptor binding G protein-coupled receptor binding type 2 angiotensin receptor binding enzyme regulator activity protein binding binding molecular function activator activity signaling receptor binding molecular function regulator activity signaling receptor regulator activity growth factor activity receptor ligand activity signaling receptor activator activity angiotensin receptor binding type 1 angiotensin receptor binding G protein-coupled receptor binding type 2 angiotensin receptor binding enzyme regulator activity molecular function inhibitor activity peptidase regulator activity serine-type endopeptidase inhibitor activity enzyme inhibitor activity peptidase inhibitor activity endopeptidase regulator activity endopeptidase inhibitor activity hormone activity	heart process multicellular organismal process system process regulation of biological process regulation of cardiac conduction regulation of heart contraction regulation of system process biological regulation circulatory system process regulation of blood circulation cardiac conduction regulation of multicellular organismal process heart contraction blood circulation heart process multicellular organismal process system process regulation of biological process regulation of cardiac conduction regulation of heart contraction regulation of system process biological regulation circulatory system process regulation of blood circulation cardiac conduction regulation of multicellular organismal process heart contraction blood circulation regulation of blood pressure regulation of biological quality regulation of defense response response to stimulus regulation of response to external stimulus defense response positive regulation of biological process response to external stimulus regulation of inflammatory response positive regulation of response to stimulus positive regulation of response to external stimulus positive regulation of inflammatory response regulation of response to stimulus regulation of response to stress response to stress positive regulation of defense response inflammatory response renal system process positive regulation of cellular component organization regulation of cellular process regulation of cellular component organization gap junction assembly cellular component organization cellular component biogenesis cellular component assembly positive regulation of gap junction assembly cell junction assembly cellular component organization or biogenesis positive regulation of cellular process cell-cell junction assembly cell-cell junction organization positive regulation of cellular component biogenesis regulation of gap junction assembly regulation of cellular component biogenesis regulation of cell junction assembly positive regulation of cell junction assembly cell junction organization cellular process regulation of systemic arterial blood pressure by renin-angiotensin regulation of systemic arterial blood pressure by hormone regulation of blood volume by renin-angiotensin regulation of systemic arterial blood pressure mediated by a chemical signal regulation of systemic arterial blood pressure endocrine process regulation of renal output by angiotensin cellular response to stimulus regulation of catalytic activity negative regulation of biological process negative regulation of catalytic activity regulation of signal transduction regulation of transferase activity regulation of MAP kinase activity intracellular signal transduction regulation of primary metabolic process cell communication negative regulation of kinase activity negative regulation of transferase activity regulation of phosphate metabolic process phosphate-containing compound metabolic process intracellular signaling cassette negative regulation of protein modification process signal transduction phosphorus metabolic process protein modification process negative regulation of protein metabolic process protein phosphorylation phosphorylation regulation of protein metabolic process negative regulation of metabolic process primary metabolic process regulation of MAPK cascade regulation of molecular function regulation of kinase activity negative regulation of protein phosphorylation regulation of protein serine/threonine kinase activity macromolecule modification regulation of phosphorus metabolic process metabolic process macromolecule metabolic process regulation of metabolic process regulation of protein modification process regulation of protein phosphorylation signaling negative regulation of signaling negative regulation of intracellular signal transduction negative regulation of phosphate metabolic process negative regulation of cell communication regulation of intracellular signal transduction negative regulation of protein serine/threonine kinase activity negative regulation of cellular process protein metabolic process negative regulation of macromolecule metabolic process regulation of signaling negative regulation of response to stimulus negative regulation of molecular function negative regulation of MAP kinase activity regulation of protein kinase activity regulation of macromolecule metabolic process negative regulation of protein kinase activity negative regulation of signal transduction negative regulation of phosphorus metabolic process MAPK cascade regulation of cell communication regulation of phosphorylation negative regulation of phosphorylation negative regulation of MAPK cascade regulation of CoA-transferase activity positive regulation of molecular function positive regulation of transferase activity positive regulation of CoA-transferase activity positive regulation of catalytic activity regulation of localization renal sodium excretion inorganic ion homeostasis regulation of renal system process transport homeostatic process localization monoatomic ion homeostasis monoatomic cation homeostasis excretion sodium ion homeostasis regulation of transport secretion renal tubular secretion establishment of localization regulation of secretion regulation of renal sodium excretion chemical homeostasis regulation of excretion regulation of tube diameter regulation of tube size vascular process in circulatory system blood vessel diameter maintenance vasoconstriction regulation of anatomical structure size cellular response to growth factor stimulus negative regulation of cellular response to growth factor stimulus cell surface receptor protein tyrosine kinase signaling pathway cellular response to endogenous stimulus neurotrophin signaling pathway enzyme-linked receptor protein signaling pathway cell surface receptor signaling pathway response to endogenous stimulus regulation of cellular response to growth factor stimulus neurotrophin TRK receptor signaling pathway regulation of neurotrophin TRK receptor signaling pathway negative regulation of neurotrophin TRK receptor signaling pathway response to growth factor regulation of growth growth regulation of cell growth cell growth response to angiotensin response to hormone response to chemical response to peptide hormone response to oxygen-containing compound response to nitrogen compound cell-cell signaling regulation of apoptotic process apoptotic process regulation of programmed cell death cell death programmed cell death regulation of vasoconstriction cellular response to nitrogen compound angiotensin-activated signaling pathway cellular response to angiotensin cellular response to hormone stimulus cellular response to peptide hormone stimulus cellular response to oxygen-containing compound cellular response to chemical stimulus G protein-coupled receptor signaling pathway positive regulation of cell communication positive regulation of signal transduction positive regulation of ERBB signaling pathway regulation of epidermal growth factor receptor signaling pathway epidermal growth factor receptor signaling pathway positive regulation of epidermal growth factor receptor signaling pathway regulation of ERBB signaling pathway ERBB signaling pathway positive regulation of signaling positive regulation of DNA-templated transcription RNA metabolic process positive regulation of miRNA transcription positive regulation of miRNA metabolic process positive regulation of macromolecule biosynthetic process nucleobase-containing compound metabolic process RNA biosynthetic process DNA-templated transcription nucleic acid biosynthetic process positive regulation of metabolic process regulation of RNA metabolic process miRNA transcription positive regulation of biosynthetic process regulation of miRNA metabolic process positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process miRNA metabolic process regulation of RNA biosynthetic process regulation of biosynthetic process positive regulation of nucleobase-containing compound metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process positive regulation of RNA metabolic process regulation of gene expression biosynthetic process positive regulation of RNA biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription regulation of miRNA transcription regulation of aldosterone secretion regulation of steroid hormone secretion aldosterone secretion mineralocorticoid secretion regulation of hormone levels lipid transport regulation of corticosteroid hormone secretion endocrine hormone secretion lipid export from cell renin-angiotensin regulation of aldosterone production regulation of mineralocorticoid secretion regulation of endocrine process corticosteroid hormone secretion regulation of hormone secretion steroid hormone secretion regulation of lipid transport organic hydroxy compound transport hormone secretion secretion by cell regulation of secretion by cell signal release renal system process involved in regulation of systemic arterial blood pressure lipid localization export from cell regulation of lipid localization macromolecule localization hormone transport positive regulation of DNA-binding transcription factor activity positive regulation of NF-kappaB transcription factor activity regulation of DNA-binding transcription factor activity phospholipase C-activating G protein-coupled receptor signaling pathway muscle hypertrophy regulation of muscle adaptation positive regulation of cardiac muscle hypertrophy striated muscle hypertrophy regulation of muscle system process muscle system process regulation of cardiac muscle hypertrophy regulation of muscle hypertrophy muscle adaptation positive regulation of muscle hypertrophy cardiac muscle hypertrophy positive regulation of multicellular organismal process nitric oxide mediated signal transduction cGMP-mediated signaling nitric oxide-cGMP-mediated signaling developmental process multicellular organism development anatomical structure development animal organ development kidney development renal system development system development G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger positive regulation of protein metabolic process plasma lipoprotein particle organization low-density lipoprotein particle remodeling protein-containing complex organization protein-containing complex remodeling protein-lipid complex organization plasma lipoprotein particle remodeling regulation of plasma lipoprotein particle levels protein-lipid complex remodeling positive regulation of locomotion regulation of cell motility endothelial cell migration positive regulation of cell migration regulation of locomotion positive regulation of endothelial cell migration positive regulation of cell motility regulation of cell migration regulation of endothelial cell migration cell migration cell motility locomotion mesonephric epithelium development kidney epithelium development branching morphogenesis of an epithelial tube nephron tubule morphogenesis regulation of kidney development regulation of branching involved in ureteric bud morphogenesis positive regulation of developmental process tube morphogenesis animal organ morphogenesis nephron development regulation of morphogenesis of a branching structure epithelium development regulation of animal organ morphogenesis tissue development mesonephric tubule development renal tubule morphogenesis regulation of developmental process nephron morphogenesis nephron epithelium morphogenesis nephron tubule development ureteric bud morphogenesis positive regulation of morphogenesis of an epithelium branching involved in ureteric bud morphogenesis renal tubule development regulation of morphogenesis of an epithelium epithelial tube morphogenesis regulation of anatomical structure morphogenesis nephron epithelium development ureteric bud development tube development mesonephros development morphogenesis of an epithelium tissue morphogenesis anatomical structure morphogenesis kidney morphogenesis morphogenesis of a branching structure positive regulation of branching involved in ureteric bud morphogenesis mesonephric tubule morphogenesis morphogenesis of a branching epithelium response to muscle activity involved in regulation of muscle adaptation response to activity response to stimulus involved in regulation of muscle adaptation response to muscle activity regulation of epithelial to mesenchymal transition cellular developmental process positive regulation of epithelial to mesenchymal transition regulation of cell differentiation mesenchyme development positive regulation of cell differentiation cell differentiation epithelial to mesenchymal transition mesenchymal cell differentiation positive regulation of extracellular matrix organization extracellular matrix organization regulation of extracellular matrix assembly positive regulation of extracellular matrix assembly regulation of extracellular matrix organization extracellular matrix assembly extracellular structure organization external encapsulating structure organization fibroblast proliferation cell population proliferation positive regulation of cell population proliferation regulation of fibroblast proliferation regulation of cell population proliferation positive regulation of fibroblast proliferation extrinsic apoptotic signaling pathway positive regulation of apoptotic signaling pathway positive regulation of programmed cell death positive regulation of extrinsic apoptotic signaling pathway positive regulation of apoptotic process regulation of extrinsic apoptotic signaling pathway apoptotic signaling pathway regulation of apoptotic signaling pathway regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of intracellular signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction phosphatidylinositol 3-kinase/protein kinase B signal transduction macrophage derived foam cell differentiation foam cell differentiation regulation of macrophage derived foam cell differentiation positive regulation of macrophage derived foam cell differentiation reactive oxygen species metabolic process positive regulation of reactive oxygen species metabolic process regulation of reactive oxygen species metabolic process blood vessel remodeling tissue remodeling maintenance of blood vessel diameter homeostasis by renin-angiotensin renal control of peripheral vascular resistance involved in regulation of systemic arterial blood pressure cytokine production regulation of cytokine production positive regulation of gene expression positive regulation of cytokine production	extracellular exosome membrane-bounded organelle extracellular vesicle cellular anatomical structure extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix extracellular exosome membrane-bounded organelle extracellular vesicle cellular anatomical structure extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix blood microparticle
A	Aminopeptidase N	peptidase activity catalytic activity, acting on a protein metallopeptidase activity hydrolase activity catalytic activity protein binding binding virus receptor activity exogenous protein binding molecular transducer activity signaling receptor activity aminopeptidase activity metalloaminopeptidase activity exopeptidase activity peptidase activity catalytic activity, acting on a protein metallopeptidase activity hydrolase activity catalytic activity protein binding binding virus receptor activity exogenous protein binding molecular transducer activity signaling receptor activity aminopeptidase activity metalloaminopeptidase activity exopeptidase activity metalloexopeptidase activity peptide binding cation binding transition metal ion binding zinc ion binding ion binding metal ion binding small molecule binding	cellular catabolic process catabolic process metabolic process cellular process peptide metabolic process peptide catabolic process developmental process cellular developmental process cell differentiation multicellular organismal process blood vessel morphogenesis tube development angiogenesis vasculature development cellular catabolic process catabolic process metabolic process cellular process peptide metabolic process peptide catabolic process developmental process cellular developmental process cell differentiation multicellular organismal process blood vessel morphogenesis tube development angiogenesis vasculature development circulatory system development multicellular organism development anatomical structure morphogenesis tube morphogenesis anatomical structure development anatomical structure formation involved in morphogenesis blood vessel development system development proteolysis primary metabolic process protein metabolic process macromolecule metabolic process	cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm intracellular vesicle intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle membrane bounding membrane of organelle vesicle membrane cytoplasmic vesicle secretory granule secretory vesicle organelle membrane secretory granule membrane vacuolar membrane lytic vacuole vacuole lytic vacuole membrane lysosomal membrane lysosome endoplasmic reticulum-Golgi intermediate compartment

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
B [auth C]	IPR000215	Serpin family	Family
B [auth C]	IPR042178	Serpin superfamily, domain 1	Homologous Superfamily
B [auth C]	IPR023795	Serpin, conserved site	Conserved Site
B [auth C]	IPR033834	Angiotensinogen, serpin domain	Domain
B [auth C]	IPR036186	Serpin superfamily	Homologous Superfamily
B [auth C]	IPR000227	Angiotensinogen	Family
B [auth C]	IPR023796	Serpin domain	Domain
B [auth C]	IPR042185	Serpin superfamily, domain 2	Homologous Superfamily
A	IPR001930	Peptidase M1, alanine aminopeptidase/leukotriene A4 hydrolase	Family
A	IPR042097	Aminopeptidase N-like , N-terminal domain superfamliy	Homologous Superfamily
A	IPR024571	ERAP1-like C-terminal domain	Domain
A	IPR027268	Peptidase M4/M1, CTD superfamily	Homologous Superfamily
A	IPR034016	Aminopeptidase N-type	Family
A	IPR014782	Peptidase M1, membrane alanine aminopeptidase	Domain
A	IPR045357	Aminopeptidase N-like , N-terminal domain	Domain
A	IPR050344	Peptidase M1 family aminopeptidases	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B [auth C]	Pharos: P01019	hypertensive disorder endomyocardial fibrosis IgA glomerulonephritis abdominal aortic aneurysm aortic aneurysm retinopathy of prematurity essential hypertension kidney disease heart disease renal hypertension cardiomyopathy kidney failure glomerulonephritis diabetic retinopathy Hypertrophy hypertensive disorder endomyocardial fibrosis IgA glomerulonephritis abdominal aortic aneurysm aortic aneurysm retinopathy of prematurity essential hypertension kidney disease heart disease renal hypertension cardiomyopathy kidney failure glomerulonephritis diabetic retinopathy Hypertrophy anemia preeclampsia glucose intolerance visual epilepsy renal tubular dysgenesis of genetic origin myocardial infarction cardiovascular disease alcoholic cardiomyopathy cirrhosis of liver focal segmental glomerulosclerosis ureteral obstruction potassium deficiency disease nephrosis carotid artery disease cholestasis pneumonia congestive heart failure anuria proteinuria malignant hypertension pulmonary fibrosis atherosclerosis bipolar disorder esophageal adenocarcinoma ulcerative colitis large cell medulloblastoma pneumonitis lung cancer psoriasis arteriosclerosis disorder malignant pancreatic neoplasm diabetic kidney disease Down syndrome hypotensive disorder subependymal giant cell astrocytoma interstitial cystitis pancreatic ductal adenocarcinoma pituitary cancer congenital diaphragmatic hernia primitive neuroectodermal tumor lung carcinoma depressive disorder atypical teratoid rhabdoid tumor breast cancer myocardial ischemia idiopathic interstitial pneumonia essential hypertension, genetic intellectual disability fetal growth restriction thrombotic disease ischemia reperfusion injury pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia gastric carcinoma lung adenocarcinoma coronary artery disease heart failure medulloblastoma renal tubular dysgenesis
A	Pharos: P15144	urinary bladder cancer pancreatic intraductal papillary-mucinous neoplasm ulcerative colitis urinary bladder neoplasm ACUTE ALCOHOL WITHDRAWAL Barrett esophagus cancer ductal breast carcinoma in situ major depressive disorder malignant pancreatic neoplasm pancreatic ductal adenocarcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia acute myeloid leukemia breast cancer Crohn disease urinary bladder cancer pancreatic intraductal papillary-mucinous neoplasm ulcerative colitis urinary bladder neoplasm ACUTE ALCOHOL WITHDRAWAL Barrett esophagus cancer ductal breast carcinoma in situ major depressive disorder malignant pancreatic neoplasm pancreatic ductal adenocarcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia acute myeloid leukemia breast cancer Crohn disease gallbladder disease malignant colon neoplasm nephrosclerosis pancreatic intraductal papillary-mucinous carcinoma tuberculosis atypical teratoid rhabdoid tumor breast carcinoma cystic fibrosis lung carcinoma malignant mesothelioma non-small cell lung carcinoma

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.