Annotations: 1A4Y

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d1a4yb_	Alpha and beta proteins (a+b)	RNase A-like	RNase A-like	Ribonuclease A-like	Angiogenin	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D [auth E]	d1a4ye_	Alpha and beta proteins (a+b)	RNase A-like	RNase A-like	Ribonuclease A-like	Angiogenin	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C [auth D]	d1a4yd_	Alpha and beta proteins (a/b)	Leucine-rich repeat, LRR (right-handed beta-alpha superhelix)	RNI-like	28-residue LRR	Ribonuclease inhibitor	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1a4ya_	Alpha and beta proteins (a/b)	Leucine-rich repeat, LRR (right-handed beta-alpha superhelix)	RNI-like	28-residue LRR	Ribonuclease inhibitor	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)
B	SCOP2B Superfamily	RNase A-like	8040055	3001918	SCOP2B (2022-06-29)
D [auth E]	SCOP2B Superfamily	RNase A-like	8040055	3001918	SCOP2B (2022-06-29)
C [auth D]	SCOP2B Superfamily	RNI-like	8035352	3000990	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	RNI-like	8035352	3000990	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)
B	RnaseA	e1a4yB1	A: a+b complex topology	X: RNase A-like	H: RNase A-like (From Topology)	T: RNase A-like	F: RnaseA	ECOD (1.6)
D [auth E]	RnaseA	e1a4yE1	A: a+b complex topology	X: RNase A-like	H: RNase A-like (From Topology)	T: RNase A-like	F: RnaseA	ECOD (1.6)
C [auth D]	LRR_8_4	e1a4yD1	A: beta duplicates or obligate multimers	X: Single-stranded right-handed beta-helix	H: Leucine-rich repeats (From Topology)	T: Leucine-rich repeats	F: LRR_8_4	ECOD (1.6)
A	LRR_8_4	e1a4yA1	A: beta duplicates or obligate multimers	X: Single-stranded right-handed beta-helix	H: Leucine-rich repeats (From Topology)	T: Leucine-rich repeats	F: LRR_8_4	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	3.10.130.10	Alpha Beta	Roll	P-30 Protein	Ribonuclease A-like domain	CATH (4.3.0)
D [auth E]	3.10.130.10	Alpha Beta	Roll	P-30 Protein	Ribonuclease A-like domain	CATH (4.3.0)
C [auth D]	3.80.10.10	Alpha Beta	Alpha-Beta Horseshoe	Leucine-rich repeat, LRR (right-handed beta-alpha superhelix)	Ribonuclease Inhibitor	CATH (4.3.0)
A	3.80.10.10	Alpha Beta	Alpha-Beta Horseshoe	Leucine-rich repeat, LRR (right-handed beta-alpha superhelix)	Ribonuclease Inhibitor	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
B, D [auth E]	PF00074	Pancreatic ribonuclease (RnaseA)	Pancreatic ribonuclease	Ribonucleases. Members include pancreatic RNAase A and angiogenins. Structure is an alpha+beta fold -- long curved beta sheet and three helices.	Domain
A, C [auth D]	PF13516	Leucine Rich repeat (LRR_6)	Leucine Rich repeat	-	Repeat
A, C [auth D]	PF18779	Capping Ribonuclease inhibitor Leucine Rich Repeat (LRR_RI_capping)	Capping Ribonuclease inhibitor Leucine Rich Repeat	-	Repeat

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
B, D [auth E]	ANGIOGENIN	RNA binding binding rRNA binding nucleic acid binding cation binding transition metal ion binding copper ion binding ion binding metal ion binding small molecule binding tRNA-specific ribonuclease activity nuclease activity catalytic activity, acting on RNA catalytic activity, acting on a nucleic acid RNA binding binding rRNA binding nucleic acid binding cation binding transition metal ion binding copper ion binding ion binding metal ion binding small molecule binding tRNA-specific ribonuclease activity nuclease activity catalytic activity, acting on RNA catalytic activity, acting on a nucleic acid RNA nuclease activity catalytic activity, acting on a tRNA catalytic activity DNA binding endonuclease activity RNA endonuclease activity protein binding signaling receptor binding molecular function activator activity molecular function regulator activity signaling receptor regulator activity receptor ligand activity signaling receptor activator activity identical protein binding protein homodimerization activity protein dimerization activity cytoskeletal protein binding actin binding ribonucleoprotein complex binding protein-containing complex binding ribosome binding peptide binding heparin binding glycosaminoglycan binding carbohydrate derivative binding sulfur compound binding	developmental process stem cell proliferation cell population proliferation cellular developmental process hemopoiesis cell differentiation anatomical structure development hematopoietic stem cell proliferation cell development cellular process catabolic process RNA metabolic process primary metabolic process nucleic acid metabolic process developmental process stem cell proliferation cell population proliferation cellular developmental process hemopoiesis cell differentiation anatomical structure development hematopoietic stem cell proliferation cell development cellular process catabolic process RNA metabolic process primary metabolic process nucleic acid metabolic process macromolecule catabolic process nucleobase-containing compound catabolic process tRNA metabolic process nucleobase-containing compound metabolic process nucleic acid catabolic process metabolic process macromolecule metabolic process tRNA decay RNA catabolic process placenta development animal organ development humoral immune response biological process involved in interspecies interaction between organisms response to stimulus response to other organism defense response immune response antibacterial humoral response defense response to symbiont response to external stimulus antimicrobial humoral response response to biotic stimulus defense response to bacterium defense response to other organism response to stress immune system process response to bacterium response to external biotic stimulus innate immune response cell migration cell motility sexual reproduction reproductive process multicellular organismal reproductive process oogenesis cellular process involved in reproduction in multicellular organism developmental maturation developmental process involved in reproduction female gamete generation gamete generation oocyte development anatomical structure maturation germ cell development oocyte maturation oocyte differentiation cell maturation multicellular organismal process gonad development reproductive system development female gonad development sex differentiation female sex differentiation development of primary female sexual characteristics multicellular organism development development of primary sexual characteristics reproductive structure development ovarian follicle development system development nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process RNA biosynthetic process DNA-templated transcription nucleic acid biosynthetic process biosynthetic process rRNA transcription rRNA metabolic process response to decreased oxygen levels response to hypoxia response to oxygen levels response to abiotic stimulus cellular component biogenesis cellular component organization organelle organization cellular component assembly stress granule assembly organelle assembly membraneless organelle assembly cellular component organization or biogenesis response to hormone response to endogenous stimulus response to chemical blood vessel morphogenesis tube development angiogenesis vasculature development circulatory system development anatomical structure morphogenesis tube morphogenesis anatomical structure formation involved in morphogenesis blood vessel development regulation of biological process regulation of cellular process negative regulation of programmed cell death regulation of apoptotic process biological regulation negative regulation of biological process regulation of programmed cell death cell death negative regulation of apoptotic process negative regulation of cellular process apoptotic process programmed cell death protein polymerization actin polymerization or depolymerization actin filament polymerization actin cytoskeleton organization protein-containing complex organization actin filament organization protein-containing complex assembly actin filament-based process supramolecular fiber organization cytoskeleton organization negative regulation of cell population proliferation regulation of smooth muscle cell proliferation smooth muscle cell proliferation negative regulation of smooth muscle cell proliferation regulation of cell population proliferation muscle cell proliferation cellular response to stimulus negative regulation of translation in response to stress protein biosynthetic process regulation of primary metabolic process post-transcriptional regulation of gene expression negative regulation of translation regulation of translation in response to stress cellular response to stress protein metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process regulation of biosynthetic process regulation of protein metabolic process negative regulation of metabolic process regulation of macromolecule metabolic process translation regulation of gene expression negative regulation of gene expression negative regulation of biosynthetic process regulation of translation negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process regulation of metabolic process signaling signal transduction cell communication regulation of localization establishment of protein localization nitrogen compound transport regulation of protein localization transport positive regulation of biological process positive regulation of establishment of protein localization positive regulation of secretion by cell protein localization to extracellular region positive regulation of protein transport localization regulation of secretion by cell secretion by cell positive regulation of secretion intracellular protein localization positive regulation of cellular process regulation of transport secretion regulation of establishment of protein localization establishment of protein localization to extracellular region export from cell regulation of protein transport protein secretion establishment of localization positive regulation of protein secretion regulation of protein secretion regulation of secretion positive regulation of transport protein transport macromolecule localization positive regulation of protein localization antimicrobial humoral immune response mediated by antimicrobial peptide positive regulation of phosphorylation positive regulation of phosphorus metabolic process phosphorylation positive regulation of phosphate metabolic process positive regulation of metabolic process phosphate-containing compound metabolic process regulation of phosphorus metabolic process regulation of phosphorylation phosphorus metabolic process positive regulation of cell population proliferation endothelial cell proliferation positive regulation of epithelial cell proliferation regulation of endothelial cell proliferation positive regulation of endothelial cell proliferation regulation of epithelial cell proliferation epithelial cell proliferation homeostatic process defense response to Gram-positive bacterium	basement membrane cell periphery extracellular matrix cellular anatomical structure external encapsulating structure intracellular organelle intracellular anatomical structure cytoskeleton organelle membraneless organelle intracellular membraneless organelle actin cytoskeleton cytoplasm cytosol basement membrane cell periphery extracellular matrix cellular anatomical structure external encapsulating structure intracellular organelle intracellular anatomical structure cytoskeleton organelle membraneless organelle intracellular membraneless organelle actin cytoskeleton cytoplasm cytosol membrane-bounded organelle intracellular vesicle intracellular membrane-bounded organelle cytoplasmic vesicle vesicle endocytic vesicle chromosome somatodendritic compartment cell body neuronal cell body extracellular region extracellular space nucleus membrane-enclosed lumen nucleolus intracellular organelle lumen organelle lumen nuclear lumen cytoplasmic ribonucleoprotein granule ribonucleoprotein granule supramolecular complex cytoplasmic stress granule protein-containing complex angiogenin-PRI complex growth cone axon cell projection distal axon neuron projection plasma membrane bounded cell projection site of polarized growth
A, C [auth D]	RIBONUCLEASE INHIBITOR	enzyme regulator activity molecular function inhibitor activity molecular function regulator activity nuclease inhibitor activity enzyme inhibitor activity ribonuclease inhibitor activity	developmental process multicellular organismal process regulation of multicellular organismal development regulation of biological process regulation of developmental process blood vessel morphogenesis tube development biological regulation angiogenesis vasculature development regulation of vasculature development circulatory system development anatomical structure morphogenesis multicellular organism development tube morphogenesis developmental process multicellular organismal process regulation of multicellular organismal development regulation of biological process regulation of developmental process blood vessel morphogenesis tube development biological regulation angiogenesis vasculature development regulation of vasculature development circulatory system development anatomical structure morphogenesis multicellular organism development tube morphogenesis regulation of angiogenesis anatomical structure formation involved in morphogenesis anatomical structure development regulation of multicellular organismal process regulation of anatomical structure morphogenesis blood vessel development system development regulation of cellular process catabolic process negative regulation of biological process RNA metabolic process macromolecule catabolic process nucleobase-containing compound metabolic process negative regulation of cellular process RNA catabolic process negative regulation of macromolecule metabolic process regulation of biosynthetic process mRNA catabolic process negative regulation of metabolic process primary metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process mRNA metabolic process nucleic acid metabolic process nucleobase-containing compound catabolic process regulation of gene expression negative regulation of gene expression biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process nucleic acid catabolic process regulation of macromolecule biosynthetic process metabolic process cellular process macromolecule metabolic process regulation of metabolic process regulation of Arp2/3 complex-mediated actin nucleation regulation of cytoskeleton organization regulation of cellular component organization regulation of actin filament-based process cellular component organization regulation of actin nucleation actin filament-based process cellular component organization or biogenesis regulation of actin filament organization actin cytoskeleton organization actin filament organization Arp2/3 complex-mediated actin nucleation regulation of organelle organization organelle organization regulation of actin cytoskeleton organization regulation of supramolecular fiber organization actin nucleation supramolecular fiber organization cytoskeleton organization cell migration cell motility negative regulation of tRNA metabolic process regulation of primary metabolic process post-transcriptional regulation of gene expression regulation of RNA metabolic process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of biological quality tRNA decay tRNA metabolic process tRNA stabilization regulation of tRNA metabolic process negative regulation of RNA metabolic process negative regulation of tRNA catabolic process regulation of tRNA stability negative regulation of catabolic process negative regulation of RNA catabolic process regulation of catabolic process RNA stabilization regulation of tRNA catabolic process regulation of RNA stability	cell projection cellular anatomical structure cell leading edge plasma membrane bounded cell projection lamellipodium extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cell projection cellular anatomical structure cell leading edge plasma membrane bounded cell projection lamellipodium extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle protein-containing complex angiogenin-PRI complex intracellular anatomical structure cytoplasm cytosol cell periphery plasma membrane membrane nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen nuclear lumen

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
B, D [auth E]	IPR036816	Ribonuclease A-like domain superfamily	Homologous Superfamily
B, D [auth E]	IPR001427	Pancreatic ribonuclease	Family
B, D [auth E]	IPR023411	Ribonuclease A, active site	Active Site
B, D [auth E]	IPR023412	Ribonuclease A-domain	Domain
A, C [auth D]	IPR001611	Leucine-rich repeat	Repeat
A, C [auth D]	IPR032675	Leucine-rich repeat domain superfamily	Homologous Superfamily
A, C [auth D]	IPR041302	Ribonuclease inhibitor, leucine rich repeat cap	Repeat
A, C [auth D]	IPR050637	NLRP family, innate immunity and inflammation regulators	Family
A, C [auth D]	IPR006553	Leucine-rich repeat, cysteine-containing subtype	Repeat

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B, D [auth E]	Pharos: P03950	amyotrophic lateral sclerosis type 9 amyotrophic lateral sclerosis Acute-Phase Reaction amyotrophic lateral sclerosis type 1 non-small cell lung carcinoma ovarian cyst pancreatic intraductal papillary-mucinous carcinoma psoriasis breast carcinoma cutaneous lupus erythematosus invasive ductal breast carcinoma malignant colon neoplasm malignant mesothelioma osteosarcoma pancreatic intraductal papillary-mucinous neoplasm amyotrophic lateral sclerosis type 9 amyotrophic lateral sclerosis Acute-Phase Reaction amyotrophic lateral sclerosis type 1 non-small cell lung carcinoma ovarian cyst pancreatic intraductal papillary-mucinous carcinoma psoriasis breast carcinoma cutaneous lupus erythematosus invasive ductal breast carcinoma malignant colon neoplasm malignant mesothelioma osteosarcoma pancreatic intraductal papillary-mucinous neoplasm Sjogren syndrome atypical teratoid rhabdoid tumor breast fibroadenoma ductal breast carcinoma in situ lung adenocarcinoma malignant ependymoma neurodegenerative disease ovarian cancer pancreatic ductal adenocarcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia breast cancer corpus luteum cyst glioblastoma lung cancer malignant glioma
A, C [auth D]	Pharos: P13489	diabetes mellitus ovarian cancer lung cancer psoriasis malignant mesothelioma systemic lupus erythematosus

Structure Motif Annotation: Mechanism and Catalytic Site Atlas M-CSA Database Homepage

Chains	Enzyme Name	Description	Catalytic Residues
B	ribonuclease V M-CSA #564	Angiogenin is a ribonuclease which induces neovascularisation. It binds specifically to endothelial cells in culture and elicits second-messenger responses. It also binds heparin and can serve as a substratum for endothelial cell adhesion. Its amino acid sequence is 33% identical to that of bovine pancreatic ribonuclease RNase A and it has the same general catalytic properties as RNase A, however, it differs markedly both in magnitude and in specificity with RNase A. Angiogenin was first isolated from culture medium conditioned by adenocarcinoma cells, and has since been shown to be critical for the establishment and/or metastatic spread of a wide variety of human tumours in athymic mice, most likely by supporting the growth of tumour vasculature. Moreover, clinical studies have revealed increased Angiogenin expression to be associated with progression of several human cancers. These findings identify Angiogenin as a promising target for new anticancer drugs.	Defined by 3 residues: HIS:B-13LYS:B-40HIS:B-114 \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 3.1.27 (PDB Primary Data) Search M-CSA Motif + EC 3.1.27

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.