MAP2_RAT
ID MAP2_RAT Reviewed; 478 AA.
AC P38062;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 161.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Reuber H35; TISSUE=Liver;
RX PubMed=8496145; DOI=10.1016/s0021-9258(18)82055-5;
RA Wu S., Gupta S., Chatterjee N., Hileman R.E., Kinzy T.G., Denslow N.D.,
RA Merrick W.C., Chakrabarti D., Osterman J.C., Gupta N.K.;
RT "Cloning and characterization of complementary DNA encoding the eukaryotic
RT initiation factor 2-associated 67-kDa protein (p67).";
RL J. Biol. Chem. 268:10796-10801(1993).
RN [2]
RP SEQUENCE REVISION TO C-TERMINUS.
RX PubMed=7644482; DOI=10.1073/pnas.92.17.7714;
RA Arfin S.M., Kendall R.L., Hall L., Weaver L.H., Stewart A.E.,
RA Matthews B.W., Bradshaw R.A.;
RT "Eukaryotic methionyl aminopeptidases: two classes of cobalt-dependent
RT enzymes.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:7714-7718(1995).
RN [3]
RP INDUCTION BY HEAT SHOCK.
RX PubMed=9705841; DOI=10.1006/bbrc.1998.9056;
RA Chatterjee M., Chatterjee N., Datta R., Datta B., Gupta N.K.;
RT "Expression and activity of p67 are induced during heat shock.";
RL Biochem. Biophys. Res. Commun. 249:113-117(1998).
RN [4]
RP GLYCOSYLATION AT SER-60 AND SER-63.
RX PubMed=12731887; DOI=10.1021/bi020699g;
RA Datta R., Choudhury P., Ghosh A., Datta B.;
RT "A glycosylation site, 60SGTS63, of p67 is required for its ability to
RT regulate the phosphorylation and activity of eukaryotic initiation factor
RT 2alpha.";
RL Biochemistry 42:5453-5460(2003).
RN [5]
RP INTERACTION WITH EIF2S3.
RX PubMed=16857189; DOI=10.1016/j.yexcr.2006.03.034;
RA Ghosh A., Datta R., Majumdar A., Bhattacharya M., Datta B.;
RT "The N-terminal lysine residue-rich domain II and the 340-430 amino acid
RT segment of eukaryotic initiation factor 2-associated glycoprotein p67 are
RT the binding sites for the gamma-subunit of eIF2.";
RL Exp. Cell Res. 312:3184-3203(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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).
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.
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 (By similarity).
CC Interacts strongly with the eIF-2 gamma-subunit EIF2S3.
CC {ECO:0000255|HAMAP-Rule:MF_03175, ECO:0000269|PubMed:16857189}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Note=About 30% of expressed METAP2
CC associates with polysomes. {ECO:0000255|HAMAP-Rule:MF_03175}.
CC -!- INDUCTION: Heat shock increases expression by more than 36-fold.
CC {ECO:0000269|PubMed:9705841}.
CC -!- PTM: O-glycosylated; contains 12 O-linked GlcNAc.
CC {ECO:0000269|PubMed:12731887}.
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; L10652; AAA41111.1; -; mRNA.
DR PIR; A46702; A46702.
DR RefSeq; NP_071984.1; NM_022539.1.
DR AlphaFoldDB; P38062; -.
DR SMR; P38062; -.
DR STRING; 10116.ENSRNOP00000032680; -.
DR MEROPS; M24.002; -.
DR GlyGen; P38062; 2 sites.
DR iPTMnet; P38062; -.
DR PhosphoSitePlus; P38062; -.
DR jPOST; P38062; -.
DR PaxDb; P38062; -.
DR PeptideAtlas; P38062; -.
DR PRIDE; P38062; -.
DR GeneID; 64370; -.
DR KEGG; rno:64370; -.
DR UCSC; RGD:70995; rat.
DR CTD; 10988; -.
DR RGD; 70995; Metap2.
DR eggNOG; KOG2775; Eukaryota.
DR InParanoid; P38062; -.
DR OrthoDB; 601484at2759; -.
DR PhylomeDB; P38062; -.
DR BRENDA; 3.4.11.18; 5301.
DR Reactome; R-RNO-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR PRO; PR:P38062; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:HGNC-UCL.
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; Glycoprotein; Hydrolase;
KW Metal-binding; Phosphoprotein; Protease; 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_0000148984"
FT REGION 1..123
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 15..35
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 59..78
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 MOD_RES 63
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50579"
FT CARBOHYD 60
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000305|PubMed:12731887"
FT CARBOHYD 63
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000305|PubMed:12731887"
FT CONFLICT 464..478
FT /note="LRPTCKEVVSRGDDY -> CAQPVKKLSAEEMTIKT (in Ref. 1;
FT AAA41111)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 478 AA; 53052 MW; BE1C0E91E0CB3D74 CRC64;
MAGVEEASSF GGHLNRDLDP DDREEGTSST AEEAAKKKRR KKKKGKGAVS AGQQELDKES
GTSVDEVAKQ LERQALEEKE KDDDDEDGDG DGDGAAGKKK KKKKKKRGPR VQTDPPSVPI
CDLYPNGVFP KGQECEYPPT QDGRTAAWRT TSEEKKALDQ ASEEIWNDFR EAAEAHRQVR
KYVMSWIKPG MTMIEICEKL EDCSRKLIKE NGLNAGLAFP TGCSLNNCAA HYTPNAGDTT
VLQYDDICKI DFGTHISGRI IDCAFTVTFN PKYDILLKAV KDATNTGIKC AGIDVRLCDV
GEAIQEVMES YEVEIDGKTY QVKPIRNLNG HSIGPYRIHA GKTVPIVKGG EATRMEEGEV
YAIETFGSTG KGVVHDDMEC SHYMKNFDVG HVPIRLPRTK HLLNVINENF GTLAFCRRWL
DRLGESKYLM ALKNLCDLGI VDPYPPLCDI KGSYTAQFEH TILLRPTCKE VVSRGDDY
