GeneID: 433



Names

Common Name: METAP2 Type: Gene
Chromosome: 12 (NC_000012.12) Locus: NM_006838.4 (METAP2)
HUGO Symbol: METAP2 Full Name: methionyl aminopeptidase 2
Exons: 11 Introns: 10

Description:
The protein encoded by this gene is a member of the methionyl aminopeptidase family. The encoded 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 proteins when the second residue is Gly, Ala, Ser, Thr, Cys, Pro, or Val. With respect to the latter, exposing these stabilizing residues may contribute to increasing protein lifeltime, while the stabilized residues can be further modified. The most extensive of these modifications is N-terminal acetylation, which is thought to exert a protective effect against spurious aminopeptidase cleavages. MetAP2 is responsible for removing the initiator methionine (iMet) from Val1 of both α- and β-globins, including the sickle β-globin. Functional studies with erythroid cells and transgenic mouse models showed that MetAP2 inhibition irreversibly modifies sickle haemoglobin (HbS) by N-terminal retention of iMet and subsequent acetylation to acetylated iMet (acetyl-iMet). These N-terminal modifications of HbS stabilize the high O2–affinity R2 state of modified HbS, increase its oxygen affinity to delay polymerization, and prevent red blood cell sickling under low oxygen tension.

Synonyms: MAP2 , MNPEP , p67eIF2

Comments:
N/A

Number of entries/variants: 0

IthaScore

Sequence Viewer

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Publications / Origin

  1. Bonissone S, Gupta N, Romine M, Bradshaw RA, Pevzner PA, N-terminal protein processing: a comparative proteogenomic analysis., Mol Cell Proteomics, 12(1), 14-28, 2013 PubMed
  2. Demers M, Sturtevant S, Guertin KR, Gupta D, Desai K, Vieira BF, Li W, Hicks A, Ismail A, Gonçalves BP, Di Caprio G, Schonbrun E, Hansen S, Musayev FN, Safo MK, Wood DK, Higgins JM, Light DR, MetAP2 inhibition modifies hemoglobin S to delay polymerization and improves blood flow in sickle cell disease., Blood Adv, 5(5), 1388-1402, 2021 PubMed
Created on 2021-07-16 13:49:04, Last reviewed on (Show full history)


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