METAP2

From Wikipedia, the free encyclopedia

Methionyl aminopeptidase 2

PDB rendering based on 1b59.

Available structures: 1b59, 1b6a, 1bn5, 1boa, 1kq0, 1kq9, 1qzy, 1r58, 1r5g, 1r5h, 1yw7, 1yw8, 1yw9, 2adu, 2ga2

Identifiers

Symbol(s)

METAP2; p67; MNPEP; p67eIF2

External IDs

OMIM: 601870 MGI: 1929701 HomoloGene: 4981

Gene ontology
Molecular Function:	• methionyl aminopeptidase activity • protein binding • peptidase activity • metal ion binding • cobalt ion binding
Cellular Component:	• cytoplasm
Biological Process:	• regulation of translation • protein modification process • proteolysis • peptidyl-methionine modification • N-terminal protein amino acid modification

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

n/a

n/a

Refseq

NM_006838 (mRNA)
NP_006829 (protein)

NM_019648 (mRNA)
NP_062622 (protein)

Location

Chr 12: 94.39 - 94.43 Mb

n/a

Pubmed search

[1]

[2]

Methionyl aminopeptidase 2, also known as METAP2, is a human gene.

This gene is a member of the methionyl aminopeptidase family and encodes a protein that binds 2 cobalt or manganese ions. This protein functions both by protecting the alpha subunit of eukaryotic initiation factor 2 from inhibitory phosphorylation and by removing the amino-terminal methionine residue from nascent protein. Increased expression of this gene is associated with various forms of cancer and the anti-cancer drugs fumagillin and ovalicin inhibit the protein by irreversibly binding to its active site. A pseudogene of this gene is located on chromosome 2.^[1]

[edit] References

^ Entrez Gene: METAP2 methionyl aminopeptidase 2.

[edit] Further reading

Arfin SM, Kendall RL, Hall L, et al. (1995). "Eukaryotic methionyl aminopeptidases: two classes of cobalt-dependent enzymes.". Proc. Natl. Acad. Sci. U.S.A. 92 (17): 7714–8. PMID 7644482.
Prigmore E, Ahmed S, Best A, et al. (1995). "A 68-kDa kinase and NADPH oxidase component p67phox are targets for Cdc42Hs and Rac1 in neutrophils.". J. Biol. Chem. 270 (18): 10717–22. PMID 7738010.
Li X, Chang YH (1995). "Molecular cloning of a human complementary DNA encoding an initiation factor 2-associated protein (p67).". Biochim. Biophys. Acta 1260 (3): 333–6. PMID 7873610.
Ray MK, Chakraborty A, Datta B, et al. (1993). "Characteristics of the eukaryotic initiation factor 2 associated 67-kDa polypeptide.". Biochemistry 32 (19): 5151–9. PMID 8098621.
Li X, Chang YH (1996). "Evidence that the human homologue of a rat initiation factor-2 associated protein (p67) is a methionine aminopeptidase.". Biochem. Biophys. Res. Commun. 227 (1): 152–9. doi:10.1006/bbrc.1996.1482. PMID 8858118.
Sin N, Meng L, Wang MQ, et al. (1997). "The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2.". Proc. Natl. Acad. Sci. U.S.A. 94 (12): 6099–103. PMID 9177176.
Liu S, Widom J, Kemp CW, et al. (1998). "Structure of human methionine aminopeptidase-2 complexed with fumagillin.". Science 282 (5392): 1324–7. PMID 9812898.
Griffith EC, Su Z, Niwayama S, et al. (1999). "Molecular recognition of angiogenesis inhibitors fumagillin and ovalicin by methionine aminopeptidase 2.". Proc. Natl. Acad. Sci. U.S.A. 95 (26): 15183–8. PMID 9860943.
Datta B, Datta R, Mukherjee S, Zhang Z (1999). "Increased phosphorylation of eukaryotic initiation factor 2alpha at the G2/M boundary in human osteosarcoma cells correlates with deglycosylation of p67 and a decreased rate of protein synthesis.". Exp. Cell Res. 250 (1): 223–30. doi:10.1006/excr.1999.4508. PMID 10388536.
Gil J, Esteban M, Roth D (2001). "In vivo regulation of the dsRNA-dependent protein kinase PKR by the cellular glycoprotein p67.". Biochemistry 39 (51): 16016–25. PMID 11123929.
Catalano A, Romano M, Robuffo I, et al. (2001). "Methionine aminopeptidase-2 regulates human mesothelioma cell survival: role of Bcl-2 expression and telomerase activity.". Am. J. Pathol. 159 (2): 721–31. PMID 11485930.
Endo H, Takenaga K, Kanno T, et al. (2002). "Methionine aminopeptidase 2 is a new target for the metastasis-associated protein, S100A4.". J. Biol. Chem. 277 (29): 26396–402. doi:10.1074/jbc.M202244200. PMID 11994292.
Kanno T, Endo H, Takeuchi K, et al. (2002). "High expression of methionine aminopeptidase type 2 in germinal center B cells and their neoplastic counterparts.". Lab. Invest. 82 (7): 893–901. PMID 12118091.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.
Datta R, Tammali R, Datta B (2003). "Negative regulation of the protection of eIF2alpha phosphorylation activity by a unique acidic domain present at the N-terminus of p67.". Exp. Cell Res. 283 (2): 237–46. PMID 12581743.
Wang J, Sheppard GS, Lou P, et al. (2003). "Physiologically relevant metal cofactor for methionine aminopeptidase-2 is manganese.". Biochemistry 42 (17): 5035–42. doi:10.1021/bi020670c. PMID 12718546.
Serero A, Giglione C, Sardini A, et al. (2004). "An unusual peptide deformylase features in the human mitochondrial N-terminal methionine excision pathway.". J. Biol. Chem. 278 (52): 52953–63. doi:10.1074/jbc.M309770200. PMID 14532271.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Selvakumar P, Lakshmikuttyamma A, Kanthan R, et al. (2004). "High expression of methionine aminopeptidase 2 in human colorectal adenocarcinomas.". Clin. Cancer Res. 10 (8): 2771–5. PMID 15102683.
Kim S, LaMontagne K, Sabio M, et al. (2004). "Depletion of methionine aminopeptidase 2 does not alter cell response to fumagillin or bengamides.". Cancer Res. 64 (9): 2984–7. PMID 15126329.