MTAP information

MTAP
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1SD1, 3OZD, 3OZC, 3LN5, 3OZE, 1SD2, 1CB0, 1CG6, 1K27
Identifiers
Aliases	MTAP, BDMF, DMSFH, DMSMFH, HEL-249, LGMBF, MSAP, c86fus, methylthioadenosine phosphorylase
External IDs	OMIM: 156540; MGI: 1914152; HomoloGene: 1838; GeneCards: MTAP; OMA:MTAP - orthologs
Gene location (Human)
Chr.	Chromosome 9 (human)
End	21,937,651 bp
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)
End	89,099,318 bp
RNA expression pattern
	Top expressed in
	Achilles tendon; ; epithelium of colon; ; sural nerve; ; stromal cell of endometrium; ; islet of Langerhans; ; rectum; ; ganglionic eminence; ; ventricular zone; ; body of pancreas; ; gonad;
	Top expressed in
	primitive streak; ; endothelial cell of lymphatic vessel; ; condyle; ; epithelium of lens; ; facial motor nucleus; ; fossa; ; somite; ; maxillary prominence; ; mandibular prominence; ; external carotid artery;
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	transferase activity; glycosyltransferase activity; 1,4-alpha-oligoglucan phosphorylase activity; catalytic activity; protein binding; pentosyltransferase activity; S-methyl-5-thioadenosine phosphorylase activity;
Cellular component	extracellular exosome; nucleus; cytosol; cytoplasm;
Biological process	L-methionine salvage from methylthioadenosine; purine ribonucleoside salvage; nucleoside metabolic process; nicotinamide riboside catabolic process; nucleobase-containing compound metabolic process; interleukin-12-mediated signaling pathway; methylation; response to testosterone;
	Sources:Amigo / QuickGO
Orthologs
	4507
	66902
	ENSG00000099810
	ENSMUSG00000062937
	Q13126
	Q9CQ65
	NM_002451
	NM_024433
	NP_002442
	NP_077753
	Wikidata
View/Edit Human	View/Edit Mouse

S-methyl-5'-thioadenosine phosphorylase (MTAP) is an enzyme in humans responsible for polyamine metabolism. It is encoded by the methylthioadenosine phosphorylase (MTAP) gene on chromosome 9.^[5] Multiple alternatively spliced transcript variants have been described for this gene, but their full-length natures remain unknown.^[6]

This gene encodes an enzyme that plays a major role in polyamine metabolism and is important for the salvage of both adenine and methionine. It is responsible for the first step in this pathway, where it catalyzes the reversible phosphorylation of MTA to adenine and 5-methylthioribose-1-phosphate. This takes place after MTA is generated from S-adenosylmethionine.^[5]

MTAP was identified for the first time and characterized likely as a phosphorylase in 1969 by Pegg and Williams-Ashman.^[7] The first purification that allowed characterization was by a group in 1986.^[8] This purification allowed researchers to investigate why there is the lower expression of MTAP in some types of cancer.

Increased levels of MTA in tumor cells along with lower expression of MTAP.^[9] The enzyme is deficient in many cancers because this gene and the tumor-suppressive p16 gene are co-deleted.^[9]^[10]^[11]^[12]^[13]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000099810 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000062937 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b ^c "MTAP - S-methyl-5'-thioadenosine phosphorylase - Homo sapiens (Human) - MTAP gene & protein". www.uniprot.org. Retrieved 2021-12-03.
^ "MTAP methylthioadenosine phosphorylase [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-12-03.
^ Pegg AE, Williams-Ashman HG (November 1969). "Phosphate-stimulated breakdown of 5'-methylthioadenosine by rat ventral prostate". The Biochemical Journal. 115 (2): 241–247. doi:10.1042/bj1150241. PMC 1185095. PMID 5378381.
^ Della Ragione F, Cartenì-Farina M, Gragnaniello V, Schettino MI, Zappia V (September 1986). "Purification and characterization of 5'-deoxy-5'-methylthioadenosine phosphorylase from human placenta". The Journal of Biological Chemistry. 261 (26): 12324–12329. doi:10.1016/S0021-9258(18)67242-4. PMID 3091600.
^ ^a ^b Kirovski G, Stevens AP, Czech B, Dettmer K, Weiss TS, Wild P, et al. (March 2011). "Down-regulation of methylthioadenosine phosphorylase (MTAP) induces progression of hepatocellular carcinoma via accumulation of 5'-deoxy-5'-methylthioadenosine (MTA)". The American Journal of Pathology. 178 (3): 1145–1152. doi:10.1016/j.ajpath.2010.11.059. PMC 3069916. PMID 21356366.
^ Barekatain Y, Ackroyd JJ, Yan VC, Khadka S, Wang L, Chen KC, et al. (July 2021). "Homozygous MTAP deletion in primary human glioblastoma is not associated with elevation of methylthioadenosine". Nature Communications. 12 (1): 4228. Bibcode:2021NatCo..12.4228B. doi:10.1038/s41467-021-24240-3. PMC 8270912. PMID 34244484.
^ Menezes WP, Silva VA, Gomes IN, Rosa MN, Spina ML, Carloni AC, et al. (February 2020). "Loss of 5'-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness". Cells. 9 (2): 492. doi:10.3390/cells9020492. PMC 7072758. PMID 32093414.
^ Xu J, Chang WH, Fong LW, Weiss RH, Yu SL, Chen CH (2019-01-25). "Targeting the insulin-like growth factor-1 receptor in MTAP-deficient renal cell carcinoma". Signal Transduction and Targeted Therapy. 4: 2. doi:10.1038/s41392-019-0035-z. PMC 6345872. PMID 30701095.
^ Hansen LJ, Sun R, Yang R, Singh SX, Chen LH, Pirozzi CJ, et al. (July 2019). "MTAP Loss Promotes Stemness in Glioblastoma and Confers Unique Susceptibility to Purine Starvation". Cancer Research. 79 (13): 3383–3394. doi:10.1158/0008-5472.CAN-18-1010. PMC 6810595. PMID 31040154.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000099810 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000062937 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[MTAP_HUMAN-5] "MTAP - S-methyl-5'-thioadenosine phosphorylase - Homo sapiens (Human) - MTAP gene & protein". www.uniprot.org. Retrieved 2021-12-03.

[6] "MTAP methylthioadenosine phosphorylase [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-12-03.

[7] Pegg AE, Williams-Ashman HG (November 1969). "Phosphate-stimulated breakdown of 5'-methylthioadenosine by rat ventral prostate". The Biochemical Journal. 115 (2): 241–247. doi:10.1042/bj1150241. PMC 1185095. PMID 5378381.

[Della_Ragione_1986-8] Della Ragione F, Cartenì-Farina M, Gragnaniello V, Schettino MI, Zappia V (September 1986). "Purification and characterization of 5'-deoxy-5'-methylthioadenosine phosphorylase from human placenta". The Journal of Biological Chemistry. 261 (26): 12324–12329. doi:10.1016/S0021-9258(18)67242-4. PMID 3091600.

[Kirovski_2011-9] Kirovski G, Stevens AP, Czech B, Dettmer K, Weiss TS, Wild P, et al. (March 2011). "Down-regulation of methylthioadenosine phosphorylase (MTAP) induces progression of hepatocellular carcinoma via accumulation of 5'-deoxy-5'-methylthioadenosine (MTA)". The American Journal of Pathology. 178 (3): 1145–1152. doi:10.1016/j.ajpath.2010.11.059. PMC 3069916. PMID 21356366.

[Barekatain_2021-10] Barekatain Y, Ackroyd JJ, Yan VC, Khadka S, Wang L, Chen KC, et al. (July 2021). "Homozygous MTAP deletion in primary human glioblastoma is not associated with elevation of methylthioadenosine". Nature Communications. 12 (1): 4228. Bibcode:2021NatCo..12.4228B. doi:10.1038/s41467-021-24240-3. PMC 8270912. PMID 34244484.

[Menezes_2020-11] Menezes WP, Silva VA, Gomes IN, Rosa MN, Spina ML, Carloni AC, et al. (February 2020). "Loss of 5'-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness". Cells. 9 (2): 492. doi:10.3390/cells9020492. PMC 7072758. PMID 32093414.

[12] Xu J, Chang WH, Fong LW, Weiss RH, Yu SL, Chen CH (2019-01-25). "Targeting the insulin-like growth factor-1 receptor in MTAP-deficient renal cell carcinoma". Signal Transduction and Targeted Therapy. 4: 2. doi:10.1038/s41392-019-0035-z. PMC 6345872. PMID 30701095.

[13] Hansen LJ, Sun R, Yang R, Singh SX, Chen LH, Pirozzi CJ, et al. (July 2019). "MTAP Loss Promotes Stemness in Glioblastoma and Confers Unique Susceptibility to Purine Starvation". Cancer Research. 79 (13): 3383–3394. doi:10.1158/0008-5472.CAN-18-1010. PMC 6810595. PMID 31040154.

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