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Angiogenin, ribonuclease, RNase A family, 5

Ribonuclease inhibitor-angiogenin complex. From PDB 1a4y
Available structures
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 OMIM105850 MGI88022 HomoloGene74385 GeneCards: ANG Gene
Orthologs
Species Human Mouse
Entrez 283 11727
Ensembl n/a ENSMUSG00000072115
UniProt n/a Q3TBG7
RefSeq (mRNA) NM_001145 NM_007447
RefSeq (protein) NP_001136 NP_031473
Location (UCSC) n/a Chr 14:
50.02 - 50.02 Mb
PubMed search [1] [2]

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 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.

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.[1]

References

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 (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.  
  • 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. 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. 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. PMID 2646638.  
  • 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. 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. 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. PMID 7679494.  
  • 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. 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. doi:10.1073/pnas.91.8.2915. PMID 8159679.  
  • 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. PMID 9122172.  
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