Angiogenin

Angiogenin, ribonuclease, RNase A family, 5
Ribonuclease inhibitor-angiogenin complex. From PDB 1a4y
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1A4Y, 1ANG, 1AWZ, 1B1E, 1B1I, 1B1J, 1GV7, 1H0D, 1H52, 1H53, 1HBY, 1K58, 1K59, 1K5A, 1K5B, 1UN3, 1UN4, 1UN5, 2ANG
Identifiers
Symbols	ANG; ALS9; HEL168; RNASE4; RNASE5
External IDs	OMIM: 105850 MGI: 88022 HomoloGene: 74385 GeneCards: ANG Gene
EC number	3.1.27.-
Gene Ontology Molecular function • DNA binding • actin binding • endonuclease activity • pancreatic ribonuclease activity • ribonuclease activity • receptor binding • copper ion binding • protein binding • heparin binding • hydrolase activity • rRNA binding • peptide binding Cellular component • extracellular region • basal lamina • extracellular space • nucleus • nucleolus • growth cone • angiogenin-PRI complex • neuronal cell body Biological process • angiogenesis • angiogenesis • angiogenesis • ovarian follicle development • oocyte maturation • response to hypoxia • response to hypoxia • placenta development • positive regulation of endothelial cell proliferation • diacylglycerol biosynthetic process • cell communication • activation of phospholipase C activity • multicellular organismal development • metabolic process • cell death • rRNA transcription • response to hormone stimulus • cell migration • negative regulation of translation • actin filament polymerization • cell differentiation • activation of protein kinase B activity • activation of phospholipase A2 activity • positive regulation of phosphorylation • homeostatic process • negative regulation of smooth muscle cell proliferation • positive regulation of protein secretion • positive regulation of protein secretion Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	283	11727
Ensembl	ENSG00000214274	ENSMUSG00000072115
UniProt	P03950	P21570
RefSeq (mRNA)	NM_001097577.2	NM_001161731.2
RefSeq (protein)	NP_001091046.1	NP_001155203.1
Location (UCSC)	Chr 14: 21.15 – 21.17 Mb	Chr 14: 51.71 – 51.72 Mb
PubMed search	[1]	[2]
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Angiogenin (Ang) also known as ribonuclease 5 is a protein that in humans is encoded by the ANG gene.^[1] Angiogenin is a potent stimulator of new blood vessel formation. It hydrolyzes cellular tRNAs resulting in decreased protein synthesis and is similar to pancreatic ribonuclease.^[2]

Function

Angiogenin is a small protein that is implicated in angiogenesis (formation of new blood vessels) in tumor growth. However, angiogenin is unique among the many proteins that are involved in angiogenesis in that it is also an enzyme with an amino acid sequence 33% identical to that of bovine pancreatic ribonuclease (RNase) A. Moreover, although Ang has the same general catalytic properties as RNase A – it cleaves preferentially on the 3' side of pyrimidines and follows a transphosphorylation/hydrolysis mechanism – its activity differs markedly both in magnitude and in specificity.

Although angiogenin contains counterparts for the key catalytic residues of bovine pancreatic RNase A, it cleaves standard RNA substrates 10⁵–10⁶ times less efficiently than does RNase A. Despite this apparent weakness, the enzymatic activity of Ang appears to be essential for biological activity: replacements of important active site residues invariably diminish ribonuclease and angiogenesis activities in parallel, and a substitution that increases enzymatic activity also enhances angiogenic potency.

Angiogenin may function as a tRNA-specific ribonuclease that binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus, thereby promoting the endothelial invasiveness necessary for blood vessel formation. Angiogenin induces vascularization of normal and malignant tissues, and abolishes protein synthesis by specifically hydrolyzing cellular tRNAs.

Gene

Alternative splicing results in two transcript variants encoding the same protein. This gene and the gene that encodes ribonuclease, RNase A family, 4 share promoters and 5' exons. Each gene splices to a unique downstream exon that contains its complete coding region.^[2]

References

Further reading

v t e PDB gallery 1a4y: RIBONUCLEASE INHIBITOR-ANGIOGENIN COMPLEX   1ang: CRYSTAL STRUCTURE OF HUMAN ANGIOGENIN REVEALS THE STRUCTURAL BASIS FOR ITS FUNCTIONAL DIVERGENCE FROM RIBONUCLEASE   1awz: 3D SOLUTION STRUCTURE OF HUMAN ANGIOGENIN DETERMINED BY 1H, 15N NMR SPECTROSCOPY, 30 STRUCTURES   1b1e: CRYSTAL STRUCTURE OF HUMAN ANGIOGENIN VARIANT K40Q   1b1i: CRYSTAL STRUCTURE OF HUMAN ANGIOGENIN   1b1j: CRYSTAL STRUCTURE OF HUMAN ANGIOGENIN VARIANT H13A.   1h0d: CRYSTAL STRUCTURE OF HUMAN ANGIOGENIN IN COMPLEX WITH FAB FRAGMENT OF ITS MONOCLONAL ANTIBODY MAB 26-2F   1h52: BINDING OF PHOSPHATE AND PYROPHOSPHATE IONS AT THE ACTIVE SITE OF HUMAN ANGIOGENIN AS REVEALED BY X-RAY CRYSTALLOGRAPHY   1h53: BINDING OF PHOSPHATE AND PYROPHOSPHATE IONS AT THE ACTIVE SITE OF HUMAN ANGIOGENIN AS REVEALED BY X-RAY CRYSTALLOGRAPHY   1hby: BINDING OF PHOSPHATE AND PYROPHOSPHATE IONS AT THE ACTIVE SITE OF HUMAN ANGIOGENIN AS REVEALED BY X-RAY CRYSTALLOGRAPHY   1k58: Crystal Structure of Human Angiogenin Variant D116H   1k59: Crystal Structure of Human Angiogenin Variant Q117G   1k5a: Crystal structure of human angiogenin double variant I119A/F120A   1k5b: Crystal Structure of Human Angiogenin Variant des(121-123)   1un3: CRYSTAL STRUCTURE OF HUMAN ANGIOGENIN VARIANT T44D   1un4: CRYSTAL STRUCTURE OF HUMAN ANGIOGENIN VARIANT T80A   1un5: ARH-II, AN ANGIOGENIN/RNASE A CHIMERA   2ang: CRYSTAL STRUCTURE OF HUMAN ANGIOGENIN OF THE MET(-1) FORM

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