Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A

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MGAT4A
Identifiers
AliasesMGAT4A, GNT-IV, GNT-IVA, GnT-4a, Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A, mannosyl (alpha-1,3-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase, isozyme A
External IDsOMIM: 604623 MGI: 2662992 HomoloGene: 8153 GeneCards: MGAT4A
Gene location (Human)
Chromosome 2 (human)
Chr.Chromosome 2 (human)[1]
Chromosome 2 (human)
Genomic location for MGAT4A
Genomic location for MGAT4A
Band2q11.2Start98,619,106 bp[1]
End98,731,132 bp[1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_012214
NM_001160154

NM_001290801
NM_173870

RefSeq (protein)

NP_001153626
NP_036346

NP_001277730
NP_776295

Location (UCSC)Chr 2: 98.62 – 98.73 MbChr 1: 37.44 – 37.54 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A is a type II membrane protein and an enzyme – particularly a glycosyltransferase – that, in addition to the related isoenzyme B (MGAT4B),[5] takes part in the transfer of N-acetylglucosamine (GlcNAc) to the core mannose residues of N-linked glycans in Golgi apparatus. Therefore, it is essential for the formation of tri- and tetra-antennary sugar chains. Furthermore, it is involved in glucose transport by mediating SLC2A2/GLUT2 glycosylation with controlling cell-surface expression of SLC2A2 in pancreatic beta cells [6][7] and, as it is suggested, in regulating the availability of serum glycoproteins, oncogenesis, and differentiation.[5]

Cloning and expression[edit]

In humans the enzyme is encoded by the MGAT4A gene.[7] The related cDNA was first isolated by Yoshida and others. Equipped with three potential N-glycosylation sites and a length of 535 amino acids the structure of the MGAT4A gene product is similar to other known Golgi glycosyltransferases. The amino acid sequence of humans and of bovines are identical to 95%. Up to now MGAT4A was found in all human tissues and cell lines tested, whether they are normal tissues or cancer cell lines. The expression levels of MGAT4A relative to one another are similar among all tissues, but the expression levels of the correlating mRNA are quite different: Of the normal tissues, spleen, thymus, peripheral blood leukocyte, lymph node, prostate, pancreas, and small intestine showed the highest mRNA level; of the cancer cell lines the promyelocytic leukemia cell line HL-60 and the lymphoblastic leukemia cell line MOLT-4 exhibited the highest expression.[6][8]

Animal studies[edit]

It has been proposed that the MGAT4A isoenzyme acts as a toggle for developing of type 2 diabetes. Mice that lack MGAT4A are hyperglycemic and hypoinsulinemic and have impaired glucose tolerance.[9] Moreover, MGAT4A normally protects mice from developing diabetes but is suppressed by high-fat diet.[10] If this mechanism also operates in human islets, MGAT4A may represent a link between type 2 diabetes and high-fat diet.[6]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000071073 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026110 - 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.
  5. ^ a b "Entrez Gene: MGAT4B mannosyl (alpha-1,3-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase, isozyme A". Retrieved 2015-09-08.
  6. ^ a b c Online Mendelian Inheritance in Man (OMIM) 604623
  7. ^ a b Q9UM21
  8. ^ Yoshida A, Minowa MT, Takamatsu S, Hara T, Oguri S, Ikenaga H, Takeuchi M (Mar 1999). "Tissue specific expression and chromosomal mapping of a human UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1, 4-N-acetylglucosaminyltransferase". Glycobiology. 9 (3): 303–10. doi:10.1093/glycob/9.3.303. PMID 10024668.
  9. ^ Ohtsubo K, Takamatsu S, Minowa MT, Yoshida A, Takeuchi M, Marth JD (Dec 2005). "Dietary and genetic control of glucose transporter 2 glycosylation promotes insulin secretion in suppressing diabetes". Cell. 123 (7): 1307–21. doi:10.1016/j.cell.2005.09.041. PMID 16377570.
  10. ^ Thorens B (Apr 2006). "A toggle for type 2 diabetes?". The New England Journal of Medicine. 354 (15): 1636–8. doi:10.1056/NEJMcibr060422. PMID 16611957.

External links[edit]