Angiogenin

Angiogenin, ribonuclease, RNase A family, 5
Ribonuclease inhibitor-angiogenin complex. From PDB: 1a4y​
Available structures PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB List of PDB id codes 1a4y​, 1ang​, 1awz​, 1b1e​, 1b1i​, 1b1j​, 1h0d​, 1h52​, 1h53​, 1hby​, 1k58​, 1k59​, 1k5a​, 1k5b​, 1un3​, 1un4​, 1un5​, 2ang​
Identifiers
Symbols	ANG ; MGC71966; RNASE4; RNASE5
External IDs	Template:OMIM5 Template:MGI HomoloGene: 74385
Gene ontology Molecular function Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Cellular component Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Biological process Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

Angiogenin (Ang) is a small polypeptide 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 RNase 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.

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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Weremowicz S, Fox EA, Morton CC, Vallee BL (1990). "Localization of the human angiogenin gene to chromosome band 14q11, proximal to the T cell receptor alpha/delta locus". Am. J. Hum. Genet. 47 (6): 973–81. PMID 1978563.CS1 maint: Multiple names: authors list (link)
• 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. PMID 2276743.CS1 maint: Multiple names: authors list (link)
• Shapiro R, Riordan JF, Vallee BL (1986). "Characteristic ribonucleolytic activity of human angiogenin". Biochemistry. 25 (12): 3527–32. PMID 2424496.CS1 maint: Multiple names: authors list (link)
• Weiner HL, Weiner LH, Swain JL (1987). "Tissue distribution and developmental expression of the messenger RNA encoding angiogenin". Science. 237 (4812): 280–2. PMID 2440105.CS1 maint: Multiple names: authors list (link)
• Bicknell R, Vallee BL (1988). "Angiogenin activates endothelial cell phospholipase C.". Proc. Natl. Acad. Sci. U.S.A. 85 (16): 5961–5. PMID 2457905.
• 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. 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. PMID 2646638.
• Lee FS, Vallee BL (1989). "Characterization of ribonucleolytic activity of angiogenin towards tRNA". Biochem. Biophys. Res. Commun. 161 (1): 121–6. PMID 2730651.
• Lee FS, Vallee BL (1989). "Binding of placental ribonuclease inhibitor to the active site of angiogenin". Biochemistry. 28 (8): 3556–61. PMID 2742853.
• Strydom DJ, Fett JW, Lobb RR; et al. (1986). "Amino acid sequence of human tumor derived angiogenin". Biochemistry. 24 (20): 5486–94. PMID 2866794.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. PMID 2866795.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. PMID 3470787.
• 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. PMID 3619929.CS1 maint: Multiple names: authors list (link)
• Shapiro R, Strydom DJ, Olson KA, Vallee BL (1987). "Isolation of angiogenin from normal human plasma". Biochemistry. 26 (16): 5141–6. PMID 3663649.CS1 maint: Multiple names: authors list (link)
• 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. PMID 7679494.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. PMID 8127865.
• 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. PMID 8159679.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. PMID 9122172.CS1 maint: Multiple names: authors list (link)