| IED ID | IndEnz0002002533 |
| Enzyme Type ID | protease002533 |
| Protein Name |
Methionine aminopeptidase 2 MAP 2 MetAP 2 EC 3.4.11.18 Initiation factor 2-associated 67 kDa glycoprotein p67 p67eIF2 Peptidase M |
| Gene Name | METAP2 MNPEP P67EIF2 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MAGVEEVAASGSHLNGDLDPDDREEGAASTAEEAAKKKRRKKKKSKGPSAAGEQEPDKESGASVDEVARQLERSALEDKERDEDDEDGDGDGDGATGKKKKKKKKKRGPKVQTDPPSVPICDLYPNGVFPKGQECEYPPTQDGRTAAWRTTSEEKKALDQASEEIWNDFREAAEAHRQVRKYVMSWIKPGMTMIEICEKLEDCSRKLIKENGLNAGLAFPTGCSLNNCAAHYTPNAGDTTVLQYDDICKIDFGTHISGRIIDCAFTVTFNPKYDTLLKAVKDATNTGIKCAGIDVRLCDVGEAIQEVMESYEVEIDGKTYQVKPIRNLNGHSIGQYRIHAGKTVPIVKGGEATRMEEGEVYAIETFGSTGKGVVHDDMECSHYMKNFDVGHVPIRLPRTKHLLNVINENFGTLAFCRRWLDRLGESKYLMALKNLCDLGIVDPYPPLCDIKGSYTAQFEHTILLRPTCKEVVSRGDDY |
| Enzyme Length | 478 |
| Uniprot Accession Number | P50579 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | BINDING 231; /note="Substrate"; /evidence="ECO:0000255|HAMAP-Rule:MF_03175, ECO:0000269|PubMed:16540317"; BINDING 339; /note="Substrate"; /evidence="ECO:0000255|HAMAP-Rule:MF_03175, ECO:0000269|PubMed:16540317" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Release of N-terminal amino acids, preferentially methionine, from peptides and arylamides.; EC=3.4.11.18; Evidence={ECO:0000255|HAMAP-Rule:MF_03175, ECO:0000269|PubMed:20521764}; |
| DNA Binding | |
| EC Number | 3.4.11.18 |
| Enzyme Function | FUNCTION: 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.; FUNCTION: 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. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (3); Beta strand (17); Binding site (2); Chain (1); Compositional bias (2); Glycosylation (2); Helix (12); Initiator methionine (1); Metal binding (7); Modified residue (5); Region (1); Sequence conflict (1); Turn (2) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Aminopeptidase;Cytoplasm;Direct protein sequencing;Glycoprotein;Hydrolase;Metal-binding;Phosphoprotein;Protease;Reference proteome |
| Interact With | P21917 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03175, ECO:0000269|PubMed:21537465}. Note=About 30% of expressed METAP2 associates with polysomes. |
| Modified Residue | MOD_RES 2; /note="N-acetylalanine"; /evidence="ECO:0007744|PubMed:19413330"; MOD_RES 45; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 60; /note="Phosphoserine; alternate"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 63; /note="Phosphoserine; alternate"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"; MOD_RES 74; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" |
| Post Translational Modification | PTM: Contains approximately 12 O-linked N-acetylglucosamine (GlcNAc) residues. O-glycosylation is required for EIF2S1 binding. {ECO:0000255|HAMAP-Rule:MF_03175, ECO:0000269|PubMed:2511207}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (37) |
| Cross Reference PDB | 1B59; 1B6A; 1BN5; 1BOA; 1KQ0; 1KQ9; 1QZY; 1R58; 1R5G; 1R5H; 1YW7; 1YW8; 1YW9; 2ADU; 2EA2; 2EA4; 2GA2; 2OAZ; 5CLS; 5D6E; 5D6F; 5JFR; 5JHU; 5JI6; 5LYW; 5LYX; 6QED; 6QEF; 6QEG; 6QEH; 6QEI; 6QEJ; 7A12; 7A13; 7A14; 7A15; 7A16; |
| Mapped Pubmed ID | 11994292; 12118091; 15102683; 15336565; 15962312; 16274222; 16632353; 16789740; 17114291; 17446530; 18264137; 18337751; 18828628; 18850631; 19703310; 20689807; 21937698; 23161775; 24041691; 24700462; 25886145; 26686773; 26935506; 27136719; 27155900; 27542228; 27998678; 29116484; 30939017; 32919012; 32922205; 33637565; 9177176; |
| Motif | |
| Gene Encoded By | |
| Mass | 52,892 |
| Kinetics | |
| Metal Binding | METAL 251; /note="Divalent metal cation 1"; /evidence="ECO:0000255|HAMAP-Rule:MF_03175, ECO:0000269|PubMed:14534293, ECO:0000269|PubMed:16134930, ECO:0000269|PubMed:16540317, ECO:0000269|PubMed:17350258, ECO:0000269|PubMed:17636946"; METAL 262; /note="Divalent metal cation 1"; /evidence="ECO:0000255|HAMAP-Rule:MF_03175, ECO:0000269|PubMed:14534293, ECO:0000269|PubMed:16134930, ECO:0000269|PubMed:16540317, ECO:0000269|PubMed:17350258, ECO:0000269|PubMed:17636946"; METAL 262; /note="Divalent metal cation 2; catalytic"; /evidence="ECO:0000255|HAMAP-Rule:MF_03175, ECO:0000269|PubMed:14534293, ECO:0000269|PubMed:16134930, ECO:0000269|PubMed:16540317, ECO:0000269|PubMed:17350258, ECO:0000269|PubMed:17636946"; METAL 331; /note="Divalent metal cation 2; catalytic; via tele nitrogen"; /evidence="ECO:0000255|HAMAP-Rule:MF_03175, ECO:0000269|PubMed:14534293, ECO:0000269|PubMed:16134930, ECO:0000269|PubMed:16540317, ECO:0000269|PubMed:17350258, ECO:0000269|PubMed:17636946"; METAL 364; /note="Divalent metal cation 2; catalytic"; /evidence="ECO:0000255|HAMAP-Rule:MF_03175, ECO:0000269|PubMed:14534293, ECO:0000269|PubMed:16134930, ECO:0000269|PubMed:16540317, ECO:0000269|PubMed:17350258, ECO:0000269|PubMed:17636946"; METAL 459; /note="Divalent metal cation 1"; /evidence="ECO:0000255|HAMAP-Rule:MF_03175, ECO:0000269|PubMed:14534293, ECO:0000269|PubMed:16134930, ECO:0000269|PubMed:16540317, ECO:0000269|PubMed:17350258, ECO:0000269|PubMed:17636946"; METAL 459; /note="Divalent metal cation 2; catalytic"; /evidence="ECO:0000255|HAMAP-Rule:MF_03175, ECO:0000269|PubMed:14534293, ECO:0000269|PubMed:16134930, ECO:0000269|PubMed:16540317, ECO:0000269|PubMed:17350258, ECO:0000269|PubMed:17636946" |
| Rhea ID | |
| Cross Reference Brenda | 3.4.11.18; |