MAP2_MOUSE
ID MAP2_MOUSE Reviewed; 478 AA.
AC O08663;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Methionine aminopeptidase 2 {ECO:0000255|HAMAP-Rule:MF_03175};
DE Short=MAP 2 {ECO:0000255|HAMAP-Rule:MF_03175};
DE Short=MetAP 2 {ECO:0000255|HAMAP-Rule:MF_03175};
DE EC=3.4.11.18 {ECO:0000255|HAMAP-Rule:MF_03175};
DE AltName: Full=Initiation factor 2-associated 67 kDa glycoprotein {ECO:0000255|HAMAP-Rule:MF_03175};
DE Short=p67 {ECO:0000255|HAMAP-Rule:MF_03175};
DE Short=p67eIF2 {ECO:0000255|HAMAP-Rule:MF_03175};
DE AltName: Full=Peptidase M {ECO:0000255|HAMAP-Rule:MF_03175};
GN Name=Metap2; Synonyms=Mnpep, P67eif2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6 X CBA; TISSUE=Liver;
RA Sekiguchi S., Suzuki E.;
RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 260-281; 297-318; 355-371 AND 386-395, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Cotranslationally removes the N-terminal methionine from
CC nascent proteins. The N-terminal methionine is often cleaved when the
CC second residue in the primary sequence is small and uncharged (Met-
CC Ala-, Cys, Gly, Pro, Ser, Thr, or Val). {ECO:0000255|HAMAP-
CC Rule:MF_03175}.
CC -!- FUNCTION: Protects eukaryotic initiation factor EIF2S1 from
CC translation-inhibiting phosphorylation by inhibitory kinases such as
CC EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of
CC protein synthesis. {ECO:0000255|HAMAP-Rule:MF_03175}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of N-terminal amino acids, preferentially methionine,
CC from peptides and arylamides.; EC=3.4.11.18;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03175};
CC -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03175};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03175};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03175};
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03175};
CC Note=Binds 2 divalent metal cations per subunit. Has a high-affinity
CC and a low affinity metal-binding site. The true nature of the
CC physiological cofactor is under debate. The enzyme is active with
CC cobalt, zinc, manganese or divalent iron ions. Most likely, methionine
CC aminopeptidases function as mononuclear Fe(2+)-metalloproteases under
CC physiological conditions, and the catalytically relevant metal-binding
CC site has been assigned to the histidine-containing high-affinity site.
CC {ECO:0000255|HAMAP-Rule:MF_03175};
CC -!- SUBUNIT: Binds EIF2S1 at low magnesium concentrations. Interacts
CC strongly with the eIF-2 gamma-subunit EIF2S3. {ECO:0000255|HAMAP-
CC Rule:MF_03175}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Note=About 30% of expressed METAP2
CC associates with polysomes. {ECO:0000255|HAMAP-Rule:MF_03175}.
CC -!- PTM: Contains approximately 12 O-linked N-acetylglucosamine (GlcNAc)
CC residues. O-glycosylation is required for EIF2S1 binding.
CC {ECO:0000255|HAMAP-Rule:MF_03175}.
CC -!- SIMILARITY: Belongs to the peptidase M24A family. Methionine
CC aminopeptidase eukaryotic type 2 subfamily. {ECO:0000255|HAMAP-
CC Rule:MF_03175}.
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DR EMBL; AB003144; BAA19789.1; -; mRNA.
DR EMBL; AK076804; BAC36488.1; -; mRNA.
DR EMBL; BC002213; AAH02213.1; -; mRNA.
DR CCDS; CCDS48673.1; -.
DR RefSeq; NP_062622.1; NM_019648.3.
DR RefSeq; XP_006513959.1; XM_006513896.3.
DR RefSeq; XP_006513960.1; XM_006513897.3.
DR AlphaFoldDB; O08663; -.
DR SMR; O08663; -.
DR BioGRID; 207891; 15.
DR STRING; 10090.ENSMUSP00000138006; -.
DR BindingDB; O08663; -.
DR ChEMBL; CHEMBL1075272; -.
DR MEROPS; M24.002; -.
DR GlyGen; O08663; 1 site.
DR iPTMnet; O08663; -.
DR PhosphoSitePlus; O08663; -.
DR SwissPalm; O08663; -.
DR EPD; O08663; -.
DR jPOST; O08663; -.
DR PaxDb; O08663; -.
DR PeptideAtlas; O08663; -.
DR PRIDE; O08663; -.
DR ProteomicsDB; 295816; -.
DR Antibodypedia; 4578; 311 antibodies from 34 providers.
DR DNASU; 56307; -.
DR Ensembl; ENSMUST00000047910; ENSMUSP00000048285; ENSMUSG00000036112.
DR Ensembl; ENSMUST00000180840; ENSMUSP00000138006; ENSMUSG00000036112.
DR GeneID; 56307; -.
DR KEGG; mmu:56307; -.
DR UCSC; uc007gve.1; mouse.
DR CTD; 10988; -.
DR MGI; MGI:1929701; Metap2.
DR VEuPathDB; HostDB:ENSMUSG00000036112; -.
DR eggNOG; KOG2775; Eukaryota.
DR GeneTree; ENSGT00940000155016; -.
DR HOGENOM; CLU_015857_7_2_1; -.
DR InParanoid; O08663; -.
DR OMA; NEIAAHY; -.
DR OrthoDB; 601484at2759; -.
DR PhylomeDB; O08663; -.
DR TreeFam; TF300426; -.
DR BRENDA; 3.4.11.18; 3474.
DR Reactome; R-MMU-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR BioGRID-ORCS; 56307; 25 hits in 74 CRISPR screens.
DR ChiTaRS; Metap2; mouse.
DR PRO; PR:O08663; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; O08663; protein.
DR Bgee; ENSMUSG00000036112; Expressed in retinal neural layer and 229 other tissues.
DR ExpressionAtlas; O08663; baseline and differential.
DR Genevisible; O08663; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:HGNC-UCL.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0004177; F:aminopeptidase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008235; F:metalloexopeptidase activity; ISS:HGNC.
DR GO; GO:0031365; P:N-terminal protein amino acid modification; ISS:HGNC-UCL.
DR GO; GO:0018206; P:peptidyl-methionine modification; ISS:HGNC-UCL.
DR GO; GO:0035551; P:protein initiator methionine removal involved in protein maturation; IBA:GO_Central.
DR GO; GO:0016485; P:protein processing; ISS:HGNC-UCL.
DR CDD; cd01088; MetAP2; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.90.230.10; -; 1.
DR HAMAP; MF_03175; MetAP_2_euk; 1.
DR InterPro; IPR036005; Creatinase/aminopeptidase-like.
DR InterPro; IPR000994; Pept_M24.
DR InterPro; IPR001714; Pept_M24_MAP.
DR InterPro; IPR002468; Pept_M24A_MAP2.
DR InterPro; IPR018349; Pept_M24A_MAP2_BS.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00557; Peptidase_M24; 1.
DR PRINTS; PR00599; MAPEPTIDASE.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF55920; SSF55920; 1.
DR TIGRFAMs; TIGR00501; met_pdase_II; 1.
DR PROSITE; PS01202; MAP_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Aminopeptidase; Cytoplasm; Direct protein sequencing;
KW Glycoprotein; Hydrolase; Metal-binding; Phosphoprotein; Protease;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P50579"
FT CHAIN 2..478
FT /note="Methionine aminopeptidase 2"
FT /id="PRO_0000148983"
FT REGION 1..123
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 16..35
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 59..77
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 231
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT BINDING 251
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT BINDING 262
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT BINDING 262
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT BINDING 331
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT BINDING 339
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT BINDING 364
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT BINDING 459
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT BINDING 459
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P50579"
FT MOD_RES 60
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50579"
FT CARBOHYD 60
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 478 AA; 52922 MW; BBB9A2AFC19952E8 CRC64;
MAGVEQAASF GGHLNGDLDP DDREEGTSST AEEAAKKKRR KKKKGKGAVS AVQQELDKES
GALVDEVAKQ LESQALEEKE RDDDDEDGDG DADGATGKKK KKKKKKRGPK VQTDPPSVPI
CDLYPNGVFP KGQECEYPPT QDGRTAAWRT TSEEKKALDQ ASEEIWNDFR EAAEAHRQVR
KYVMSWIKPG MTMIEICEKL EDCSRKLIKE NGLNAGLAFP TGCSLNNCAA HYTPNAGDTT
VLQYDDICKI DFGTHISGRI IDCAFTVTFN PKYDILLTAV KDATNTGIKC AGIDVRLCDV
GEAIQEVMES YEVEIDGKTY QVKPIRNLNG HSIGPYRIHA GKTVPIVKGG EATRMEEGEV
YAIETFGSTG KGVVHDDMEC SHYMKNFDVG HVPIRLPRTK HLLNVINENF GTLAFCRRWL
DRLGESKYLM ALKNLCDLGI VDPYPPLCDI KGSYTAQFEH TILLRPTCKE VVSRGDDY
