Methionine aminopeptidase 2 (METAP2)
The protein contains 478 amino acids for an estimated molecular weight of 52892 Da.
Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). The catalytic activity of human METAP2 toward Met-Val peptides is consistently two orders of magnitude higher than that of METAP1, suggesting that it is responsible for processing proteins containing N-terminal Met-Val and Met-Thr sequences in vivo.', 'Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis. (updated: March 4, 2015)
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.
- 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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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.
This protein is annotated as membranous in Gene Ontology.
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The reference OMIM entry for this protein is 601870
Methionine aminopeptidase 2; metap2
Eukaryotic initiation factor 2-associated protein, 67-kd
P67
CLONING
Wu et al. (1993) cloned a rat cDNA encoding a 67-kD protein from a tumor hepatoma cDNA library. The deduced 480-amino acid protein has a molecular mass of 53 kD. Northern blot analysis showed a single 2-kb transcript. The protein exhibits significant sequence identity in the N-terminal region with the human eIF-2 beta subunit. Based on the sequence of rat p67, Li and Chang (1995) cloned the human p67 homolog. Sequence analysis showed that the human gene encodes a 478-amino acid polypeptide that shares 92% identity with rat p67. Northern blot analysis revealed that human p67 is expressed as a 2.1-kb transcript in all tissues tested. Li and Chang (1995) noted that human p67 shares approximately 22% identity with yeast and bacterial methionine aminopeptidases (MetAPs; EC 3.4.11.18).GENE FUNCTION
Datta et al. (1988) isolated a 67-kD protein, termed p67, from rabbit reticulocyte lysates, which bound to eukaryotic initiation factor-2 (eIF-2). They demonstrated that p67 protects eIF-2-alpha from phosphorylation by eIF-2 kinases and thus promotes protein synthesis in the cell. During heme or serum deprivation, p67 is degraded and protein synthesis is inhibited; on the other hand, after addition of a mitogen to serum-starved cells, p67 appears at a high level with an accompanying increase in protein synthesis. The authors suggested that p67 may play a critical role in the regulation of protein synthesis. Li and Chang (1996) purified human p67 and demonstrated that it has methionine aminopeptidase activity. Furthermore, they showed that its kinetic parameters, substrate specificity, and cobalt dependence are similar to those of other MetAPs. The authors suggested that human p67 may have dual functions: regulation of protein synthesis via interaction with eIF-2, and N-terminal protein processing. The inhibition of new blood vessel formation (angiogenesis) is an effective means of limiting both the size and metastasis of solid tumors. One of the leading angiogenic compounds, fumagillin and its derivative TNP-470, inhibits neovascularization via endothelial cell cycle arrest in the late G1 phase. Because TNP-470 proved to be effective in in vitro and animal model studies, phase III antitumor clinical trials were initiated. To investigate the molecular mode of action of TNP-470, Sin et al. (1997) used a derivative of the TNP-470 parent compound, the fungal metabolite fumagillin, and purified a mammalian protein from bovine brain lysate that is selectively and covalently bound by this natural product. This fumagillin binding protein was found to be a metalloprotease, methionine aminopeptidase-2 (MetAP2), which is highly conserved between human and Saccharomyces cerevisiae. In the absence of MetAP1, a distantly related methionine aminopeptidase, MetAP2 function is essential for vegetative growth in yeast. Sin et al. (1997) demonstrated that fumagillin selectively inhibits the S. cerevisiae MetAP2 protein in vivo. The binding is highly specific as judged by the failure of fumagillin to inhibit MetAP1 in vivo. Sin et al. (1997) recognized the identity of the methionine aminopeptidase-2, which selectively binds fumagillin, to the p67 cloned and characterized by Wu et al. (1993). Fumagillin and ovalicin are structurally related natural products that potently inhibit angiogenesis by blocking endothelial cell proliferation. To determine the structural elements of these inhibitors and methionine aminopeptidase-2 that are involve ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601870 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed