Ask about this productRelated genes to: METAP1 antibody
- Gene:
- METAP1 NIH gene
- Name:
- methionyl aminopeptidase 1
- Previous symbol:
- -
- Synonyms:
- KIAA0094, MetAP1A, MAP1A
- Chromosome:
- 4q23
- Locus Type:
- gene with protein product
- Date approved:
- 2001-09-26
- Date modifiied:
- 2014-11-19
Related products to: METAP1 antibody
Related articles to: METAP1 antibody
- N-terminal acetylation is an abundant and predominantly co-translational modification in eukaryotes that profoundly affects folding, compartmentalization fidelity and turnover of target proteins. Unlike other N-acetyltransferases, human NatD is composed solely of the catalytic subunit NAA40 and exclusively modifies histone proteins H2A and H4. However, the molecular details of co-translational NAA40 activity have remained elusive. Here, we show biochemically and by cryo-EM how NAA40 activity is coordinated at the ribosomal peptide tunnel exit involving the NAC complex. We demonstrate that the NAA40-NAC interaction is required for efficient ribosome binding and histone acetylation. Furthermore, we provide insights on the potential coordination of methionine removal and subsequent NAA40-mediated acetylation by formation of a multienzyme complex on the ribosome involving METAP1. Therefore, our results illustrate the details of N-terminal histone acetylation by NAA40 and highlight the role of NAC as a general coordinator of nascent protein modification. - Source: PubMed
Publication date: 2026/03/12
Guan DandanDenk TimoKlavaris ArielThoms MatthiasBerninghausen OttoBeatrix BirgittaKirmizis AntonisBeckmann Roland - The replication-dependent histones H2A and H4 are among the most highly expressed proteins in eukaryotes during the S phase to ensure packaging of replicated chromosomes. Nearly all newly synthesized H2A and H4 are N-terminally acetylated by N-terminal acetyltransferase D (NatD) following excision of the initiator methionine by methionine aminopeptidases (MetAPs). These modifications influence chromatin function, but how they occur cotranslationally on these exceptionally abundant and small proteins was not understood. Here, we show that the nascent polypeptide-associated complex controls the cotranslational modification of histones H2A and H4 by recruiting NatD and the upstream enzyme MetAP1 to ribosomes. MetAP1 and NatD cooperate on the ribosome to create a confined environment for the efficient sequential modification of the nascent histone chain. Our work provides a mechanistic model for the early steps of histone maturation. - Source: PubMed
Publication date: 2025/12/19
Yudin DenisJaskolowski MateuszFan ZiyiBurg NicolasChandrasekar SowmyaLentzsch Alfred MScaiola AlainBothe AdrianDeuerling ElkeGamerdinger MartinShan Shu-OuBan Nenad - Methionine aminopeptidases (MetAPs) and N-terminal acetyltransferases (NATs) function co-translationally at the ribosome to enzymatically modify the emerging nascent chain. Eukaryotes express two types of MetAPs, namely MetAP1 and MetAP2, which can both carry out N-terminal methionine excision (NME) at the ribosome during translation. Following NME, the most abundant NAT, NatA, can acetylate the penultimate amino acid of the nascent chain, under regulation of the NatA inhibitor HypK. Alternatively, NatA can accommodate a second enzyme, called NAA50, to form the NatE complex capable of acetylating the initiator methionine. The abundant N-terminal modifications facilitated by MetAP1/2 and NatA/E-HypK impinge on protein function, interactions, lifetime and overall proteostasis. Robust and reliable methods for the expression and purification of MetAPs and NATs set the stage for targeted functional and structural studies of these enzymes. Established methods for the production of pure ribosome-associated enzymes and stochiometric complexes will be delineated in this chapter. - Source: PubMed
Publication date: 2025/07/05
Klein Marius AlexanderSinning Irmgard - Zinc plays a crucial role in the gut barrier function and are widely used for the prevention of bowel disease. However, the mechanism via which zinc supplementation exerts this regulatory effect is unclear. The present study identifies and characterizes the zinc-responsive activation of AKT and demonstrates its function in alleviating gut barrier dysfunction. Mechanistically, zinc increased intracellular SAM production, a methyl donor, by promoting the activation of the metallochaperone ZNG1-METAP1 complex. Subsequently, zinc facilitates methylation (symmetrical dimethylarginine, SDMA) of AKT at residues R391 and R15, which is facilitated by PRMT5. The AKT modification promotes AKT translocation from the cytoplasm to the plasma membrane and its interaction with mTORC2, ultimately promoting AKT activation and cell proliferation. Notably, histidine has an antagonistic effect on zinc-induced the AKT activation, cell proliferation, and gut barrier improvement by chelating zinc. These results demonstrate that zinc activates AKT and alleviates gut barrier dysfunction by inducing activation of the ZNG1-METAP1-PRMT5-AKT pathway, and highlight that limiting histidine intake may have effective therapeutic potential for bowel diseases such as Crohn's disease and Ulcerative colitis. - Source: PubMed
Publication date: 2025/07/11
Cai ChuanjiangZheng YiningSun BoWang GuoyanLi PengfeiGeng HuijunLi RongnuoZhu MiaomiaoZhu YuanyuanFeng DingpingChen LeiChu GuiyanDeng LuQiao Shiyan - N-myristoyltransferases (NMTs) cotranslationally transfer the fatty acid myristic acid to the N terminus of newly synthesized proteins, regulating their function and cellular localization. These enzymes are important drug targets for the treatment of cancer and viral infections. N-myristoylation of nascent proteins occurs specifically on N-terminal glycine residues after the excision of the initiator methionine by methionine aminopeptidases (METAPs). How NMTs interact with ribosomes and gain timely and specific access to their substrates remains unknown. Here, we show that human NMT1 exchanges with METAP1 at the ribosomal tunnel exit to form an active cotranslational complex together with the nascent polypeptide-associated complex (NAC). NMT1 binding is sequence selective and specifically triggered by methionine excision, which exposes the N-myristoylation motif in the nascent chain. The revealed mode of interaction of NMT1 with NAC and the methionine-cleaved nascent protein elucidates how a specific subset of proteins can be efficiently N-myristoylated in human cells. - Source: PubMed
Publication date: 2025/07/09
Gamerdinger MartinEcheverria BlancaLentzsch Alfred MBurg NicolasFan ZiyiJaskolowski MateuszScaiola AlainPiening SelinaShan Shu-OuBan NenadDeuerling Elke