Angiogenin

Angiogenin, ribonuclease, RNase A family, 5
Ribonuclease inhibitor-angiogenin complex. From PDB 1a4y
Available structures PDB 1A4Y, 1ANG, 1AWZ, 1B1E, 1B1I, 1B1J, 1GV7, 1H0D, 1H52, 1H53, 1HBY, 1K58, 1K59, 1K5A, 1K5B, 1UN3, 1UN4, 1UN5, 2ANG
Identifiers
Symbols	ANG; ALS9; HEL168; MGC22466; MGC71966; 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 • 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	Q3TBG7
RefSeq (mRNA)	NM_001097577.2	NM_007447
RefSeq (protein)	NP_001091046.1	NP_031473
Location (UCSC)	Chr 14: 21.15 – 21.16 Mb	Chr 14: 51.71 – 51.72 Mb
PubMed search	[1]	[2]

Angiogenin (Ang) also known as ribonuclease 5 is a protein that in humans is encoded by the ANG gene. 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.

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.

Further reading

• Saxena SK, Rybak SM, Davey RT et al (1992). "Angiogenin is a cytotoxic, tRNA-specific ribonuclease in the RNase A superfamily". J. Biol. Chem. 267 (30): 21982–6. PMID 1400510. 
• Weremowicz S, Fox EA, Morton CC, Vallee BL (1991). "The placental ribonuclease inhibitor (RNH) gene is located on chromosome subband 11p15.5". Genomics 8 (4): 717–21. doi:10.1016/0888-7543(90)90260-2. PMID 2276743. 
• Shapiro R, Riordan JF, Vallee BL (1986). "Characteristic ribonucleolytic activity of human angiogenin". Biochemistry 25 (12): 3527–32. doi:10.1021/bi00360a008. PMID 2424496. 
• Weiner HL, Weiner LH, Swain JL (1987). "Tissue distribution and developmental expression of the messenger RNA encoding angiogenin". Science 237 (4812): 280–2. doi:10.1126/science.2440105. PMID 2440105. 
• Bicknell R, Vallee BL (1988). "Angiogenin activates endothelial cell phospholipase C". Proc. Natl. Acad. Sci. U.S.A. 85 (16): 5961–5. doi:10.1073/pnas.85.16.5961. PMC 281885. PMID 2457905. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=281885. 
• Shapiro R, Vallee BL (1990). "Site-directed mutagenesis of histidine-13 and histidine-114 of human angiogenin. Alanine derivatives inhibit angiogenin-induced angiogenesis". Biochemistry 28 (18): 7401–8. doi:10.1021/bi00444a038. PMID 2479414. 
• Bicknell R, Vallee BL (1989). "Angiogenin stimulates endothelial cell prostacyclin secretion by activation of phospholipase A2". Proc. Natl. Acad. Sci. U.S.A. 86 (5): 1573–7. doi:10.1073/pnas.86.5.1573. PMC 286740. PMID 2646638. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=286740. 
• Lee FS, Vallee BL (1989). "Characterization of ribonucleolytic activity of angiogenin towards tRNA". Biochem. Biophys. Res. Commun. 161 (1): 121–6. doi:10.1016/0006-291X(89)91569-6. PMID 2730651. 
• Lee FS, Vallee BL (1989). "Binding of placental ribonuclease inhibitor to the active site of angiogenin". Biochemistry 28 (8): 3556–61. doi:10.1021/bi00434a061. PMID 2742853. 
• Strydom DJ, Fett JW, Lobb RR et al (1986). "Amino acid sequence of human tumor derived angiogenin". Biochemistry 24 (20): 5486–94. doi:10.1021/bi00341a031. PMID 2866794. 
• Kurachi K, Davie EW, Strydom DJ et al (1986). "Sequence of the cDNA and gene for angiogenin, a human angiogenesis factor". Biochemistry 24 (20): 5494–9. doi:10.1021/bi00341a032. PMID 2866795. 
• Shapiro R, Vallee BL (1987). "Human placental ribonuclease inhibitor abolishes both angiogenic and ribonucleolytic activities of angiogenin". Proc. Natl. Acad. Sci. U.S.A. 84 (8): 2238–41. doi:10.1073/pnas.84.8.2238. PMC 304624. PMID 3470787. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=304624. 
• Rybak SM, Fett JW, Yao QZ, Vallee BL (1987). "Angiogenin mRNA in human tumor and normal cells". Biochem. Biophys. Res. Commun. 146 (3): 1240–8. doi:10.1016/0006-291X(87)90781-9. PMID 3619929. 
• Shapiro R, Strydom DJ, Olson KA, Vallee BL (1987). "Isolation of angiogenin from normal human plasma". Biochemistry 26 (16): 5141–6. doi:10.1021/bi00390a037. PMID 3663649. 
• Hu GF, Strydom DJ, Fett JW et al (1993). "Actin is a binding protein for angiogenin". Proc. Natl. Acad. Sci. U.S.A. 90 (4): 1217–21. doi:10.1073/pnas.90.4.1217. PMC 45843. PMID 7679494. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=45843. 
• Moroianu J, Riordan JF (1994). "Identification of the nucleolar targeting signal of human angiogenin". Biochem. Biophys. Res. Commun. 203 (3): 1765–72. doi:10.1006/bbrc.1994.2391. PMID 7945327. 
• Moroianu J, Riordan JF (1994). "Nuclear translocation of angiogenin in proliferating endothelial cells is essential to its angiogenic activity". Proc. Natl. Acad. Sci. U.S.A. 91 (5): 1677–81. doi:10.1073/pnas.91.5.1677. PMC 43226. PMID 8127865. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=43226. 
• Acharya KR, Shapiro R, Allen SC et al (1994). "Crystal structure of human angiogenin reveals the structural basis for its functional divergence from ribonuclease". Proc. Natl. Acad. Sci. U.S.A. 91 (8): 2915–9. doi:10.1073/pnas.91.8.2915. PMC 43485. PMID 8159679. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=43485. 
• Hu GF, Riordan JF, Vallee BL (1997). "A putative angiogenin receptor in angiogenin-responsive human endothelial cells". Proc. Natl. Acad. Sci. U.S.A. 94 (6): 2204–9. doi:10.1073/pnas.94.6.2204. PMC 20065. PMID 9122172. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=20065.