S-adenosylmethionine synthase isoform type-2 (MAT2A)
The protein contains 395 amino acids for an estimated molecular weight of 43661 Da.
Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The reaction comprises two steps that are both catalyzed by the same enzyme: formation of S-adenosylmethionine (AdoMet) and triphosphate, and subsequent hydrolysis of the triphosphate. (updated: Dec. 20, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
The reference OMIM entry for this protein is 601468
Methionine adenosyltransferase ii, alpha; mat2a
Mata2
Mat ii, kidney-specific
S-adenosylmethionine synthetase 2; sams2
DESCRIPTION
The MAT2A gene encodes the catalytic subunit of extrahepatic methionine adenosyltransferase (EC 2.5.1.6) (MAT II), which catalyzes the biosynthesis of S-adenosylmethionine (AdoMet, or SAM) from methionine and ATP (summary by Mao et al., 1998).CLONING
AdoMet is the major methyl donor for many of the transmethylation reactions in the body. Chamberlin et al. (1996) noted that AdoMet also participates in the transsulfuration pathway and, after decarboxylation, serves as a propylamine group donor in the biosynthesis of polyamines. Three forms of MAT have been identified in mammalian tissues. MAT I and MAT III, which are encoded by the single-copy MAT1A gene (610550), represent tetramers and dimers, respectively, formed from identical alpha-1 subunits and are synthesized primarily in the liver. MAT II, encoded by a separate gene, which was cloned by Horikawa and Tsukada (1992), is found in fetal liver (and to a lesser extent in adult liver) as well as in kidney, brain, testis, and lymphocytes. Horikawa and Tsukada (1992) showed that the 395-amino acid MAT II shares 84% amino acid similarity with the human liver MAT I/III protein. Mao et al. (1998) cloned the 5-prime flanking region of the MAT2A gene. They identified 2 major transcriptional start sites, one located within 10 nucleotides downstream and the other 158 nucleotides upstream from the TATA box. The MAT2A promoter is highly GC rich, especially in the first 300 bp. The promoter contains several potential SP1-, v-myb-, and GATA-binding sites, as well as potential binding sites for C/EBP, HSF2, c-myb, and STATx. Mao et al. (1998) showed that the MAT2A promoter can efficiently drive expression from a reporter gene in both Jurkat and 293 cells. The authors identified regions of the promoter that are important for cell-specific MAT2A expression.GENE FUNCTION
Using Northern blot analysis and in situ hybridization, O'Leary et al. (2015) found that low-dose (0.25 Gy) gamma irradiation of several human cell lines led to an early increase in expression of MAT2A, followed by increased expression of the long noncoding RNA PARTICLE (PARTICL; 616350). Low-dose irradiation of human breast cancer cells also led to secretion of MAT2A, PARTICLE, and SAM into the culture medium. Higher doses of radiation (2.50 Gy) had a weaker effect in all assays. In vitro irradiation of whole normal donor blood, as well as radiation therapy in head and neck cancer patients, caused a similar increase in circulating PARTICLE and MAT2A RNA. Knockdown of PARTICLE via short hairpin RNA enhanced expression of MAT2A mRNA and protein, increased MAT2A reporter gene activity, and increased intracellular and extracellular SAM concentration following low-dose irradiation. O'Leary et al. (2015) determined that the PARTICLE gene partly overlaps a CpG island in the promoter region of the MAT2A gene. Low-dose irradiation induced methylation of this CpG island, and this methylation was abrogated by knockdown of PARTICLE. PARTICLE formed an RNA-DNA triple helix with the promoter region of the MAT2A gene 456 bp upstream of the CpG island. Chromatin immunoprecipitation analysis and EMSA showed that PARTICLE interacted with gene-silencing factors, including the lysine methyltransferase G9A (EHMT2; 604599) and the transcription factor MYB (189990), and that it interacted directly with the polycomb repressor complex (PRC) subunit SUZ12 (606245). O'Leary et al. (2015) concluded that PARTICLE recr ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601468 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed