Methylthioadenosine Phosphorylase (MTAP)

MSAP; S-methyl-5'-thioadenosine phosphorylase

SPN	Q791
HGNC	7413
MGI	1914152
PubMed	19567676
UniProt	Q13126
Wiki	MTAP

Methylthioadenosine phosphorylase (EC 24.2.28) plays a major role in polyamine metabolism and is important for the salvage of both adenine and methionine. For example, as much as 97% of the endogenous adenine produced by human lymphoblasts in culture is formed by catabolism of methylthioadenosine (MeSAdo) by the phosphorylase. MeSAdo, a by-product of the synthesis of the polyamines spermidine and spermine, potently inhibits polyamine aminopropyltransferase reactions if not removed by the above phosphorylase reaction. The encoded enzyme is deficient in many cancers because this gene and the tumor suppressor p16 gene are co-deleted. Multiple alternatively spliced transcript variants have been described for this gene, but their full-length natures remain unknown.

Reference

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Proc. Natl. Acad. Sci. U.S.A. 92:6489-6493(1995) [PubMed] [Europe PMC] [Abstract]

"Genomic cloning of methylthioadenosine phosphorylase: a purine metabolic enzyme deficient in multiple different cancers."
Proc. Natl. Acad. Sci. U.S.A. 93:6203-6208(1996) [PubMed] [Europe PMC] [Abstract]

"Primate genome gain and loss: a bone dysplasia, muscular dystrophy, and bone cancer syndrome resulting from mutated retroviral-derived MTAP transcripts."
Am. J. Hum. Genet. 90:614-627(2012) [PubMed] [Europe PMC] [Abstract]

"DNA sequence and analysis of human chromosome 9."
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Purification and characterization of 5'-deoxy-5'-methylthioadenosine phosphorylase from human placenta."
J. Biol. Chem. 261:12324-12329(1986) [PubMed] [Europe PMC] [Abstract]

"Purification and characterization of recombinant human 5'-methylthioadenosine phosphorylase: definite identification of coding cDNA."
Biochem. Biophys. Res. Commun. 223:514-519(1996) [PubMed] [Europe PMC] [Abstract]

"Methylthioadenosine phosphorylase gene deletions are common in osteosarcoma."
Clin. Cancer Res. 8:782-787(2002) [PubMed] [Europe PMC] [Abstract]

"Methylthioadenosine phosphorylase deficiency in Japanese osteosarcoma patients."
Int. J. Oncol. 31:1069-1076(2007) [PubMed] [Europe PMC] [Abstract]

"Direct and tumor microenvironment mediated influences of 5'-deoxy-5'-(methylthio)adenosine on tumor progression of malignant melanoma."
J. Cell. Biochem. 106:210-219(2009) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Downregulation of methylthioadenosine phosphorylase by homozygous deletion in gastric carcinoma."
Genes Chromosomes Cancer 50:421-433(2011) [PubMed] [Europe PMC] [Abstract]

"The structure of human 5'-deoxy-5'-methylthioadenosine phosphorylase at 1.7-A resolution provides insights into substrate binding and catalysis."
Structure 7:629-641(1999) [PubMed] [Europe PMC] [Abstract]

"Structural comparison of MTA phosphorylase and MTA/AdoHcy nucleosidase explains substrate preferences and identifies regions exploitable for inhibitor design."
Biochemistry 43:5159-5169(2004) [PubMed] [Europe PMC] [Abstract]

"Picomolar transition state analogue inhibitors of human 5'-methylthioadenosine phosphorylase and X-ray structure with MT-immucillin-A."
Biochemistry 43:9-18(2004) [PubMed] [Europe PMC] [Abstract]

"The impact of human leukocyte antigen (HLA) micropolymorphism on ligand specificity within the HLA-B*41 allotypic family."
Haematologica 96:110-118(2011) [PubMed] [Europe PMC] [Abstract]