ID G3HBJ9_CRIGR Unreviewed; 478 AA.
AC G3HBJ9;
DT 16-NOV-2011, integrated into UniProtKB/TrEMBL.
DT 16-NOV-2011, sequence version 1.
DT 27-MAR-2024, entry version 83.
DE RecName: Full=Methionine aminopeptidase 2 {ECO:0000256|HAMAP-Rule:MF_03175};
DE Short=MAP 2 {ECO:0000256|HAMAP-Rule:MF_03175};
DE Short=MetAP 2 {ECO:0000256|HAMAP-Rule:MF_03175};
DE EC=3.4.11.18 {ECO:0000256|HAMAP-Rule:MF_03175};
DE AltName: Full=Initiation factor 2-associated 67 kDa glycoprotein {ECO:0000256|HAMAP-Rule:MF_03175};
DE AltName: Full=Peptidase M {ECO:0000256|HAMAP-Rule:MF_03175};
DE Short=p67 {ECO:0000256|HAMAP-Rule:MF_03175};
DE Short=p67eIF2 {ECO:0000256|HAMAP-Rule:MF_03175};
GN Name=Metap2 {ECO:0000313|Ensembl:ENSCGRP00001002631.1,
GN ECO:0000313|RefSeq:XP_027248443.1};
GN Synonyms=METAP2 {ECO:0000256|HAMAP-Rule:MF_03175};
GN ORFNames=I79_007830 {ECO:0000313|EMBL:EGW08391.1};
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029 {ECO:0000313|EMBL:EGW08391.1, ECO:0000313|Proteomes:UP000001075};
RN [1] {ECO:0000313|Proteomes:UP000001075}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CHO K1 cell line {ECO:0000313|Proteomes:UP000001075};
RX PubMed=21804562; DOI=10.1038/nbt.1932;
RA Xu X., Nagarajan H., Lewis N.E., Pan S., Cai Z., Liu X., Chen W., Xie M.,
RA Wang W., Hammond S., Andersen M.R., Neff N., Passarelli B., Koh W.,
RA Fan H.C., Wang J., Gui Y., Lee K.H., Betenbaugh M.J., Quake S.R.,
RA Famili I., Palsson B.O., Wang J.;
RT "The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line.";
RL Nat. Biotechnol. 29:735-741(2011).
RN [2] {ECO:0000313|EMBL:EGW08391.1}
RP NUCLEOTIDE SEQUENCE.
RA Xu X., Nagarajan H., Lewis N.E., Pan S., Cai Z., Liu X., Chen W., Xie M.,
RA Wang W., Hammond S., Andersen M.R., Neff N., Passarelli B., Koh W.,
RA Fan C.H., Wang J., Gui Y., Lee K.H., Betenbaugh M.J., Quake S.R.,
RA Famili I., Palsson B.O., Wang J.;
RT "The genomic sequence of the Chinese hamster ovary CHO-K1 cell line.";
RL Submitted (AUG-2011) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000313|Ensembl:ENSCGRP00001002631.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-2023) to UniProtKB.
RN [4] {ECO:0000313|RefSeq:XP_027248443.1}
RP IDENTIFICATION.
RC STRAIN=17A/GY {ECO:0000313|RefSeq:XP_027248443.1};
RC TISSUE=Liver {ECO:0000313|RefSeq:XP_027248443.1};
RG RefSeq;
RL Submitted (NOV-2023) to UniProtKB.
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:0000256|HAMAP-
CC Rule:MF_03175, ECO:0000256|RuleBase:RU003653}.
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:0000256|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:0000256|ARBA:ARBA00000294, ECO:0000256|HAMAP-
CC Rule:MF_03175, ECO:0000256|RuleBase:RU003653};
CC -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_03175};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_03175};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_03175};
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000256|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:0000256|HAMAP-Rule:MF_03175};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000256|ARBA:ARBA00001954};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000256|ARBA:ARBA00001936};
CC -!- SUBUNIT: Binds EIF2S1 at low magnesium concentrations. Interacts
CC strongly with the eIF-2 gamma-subunit EIF2S3. {ECO:0000256|HAMAP-
CC Rule:MF_03175}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|HAMAP-Rule:MF_03175}.
CC Note=About 30% of expressed METAP2 associates with polysomes.
CC {ECO:0000256|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:0000256|HAMAP-Rule:MF_03175}.
CC -!- SIMILARITY: Belongs to the peptidase M24A family. Methionine
CC aminopeptidase eukaryotic type 2 subfamily. {ECO:0000256|HAMAP-
CC Rule:MF_03175}.
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DR EMBL; JH000270; EGW08391.1; -; Genomic_DNA.
DR RefSeq; XP_003501469.1; XM_003501421.3.
DR RefSeq; XP_007633308.1; XM_007635118.2.
DR RefSeq; XP_027248443.1; XM_027392642.2.
DR STRING; 10029.G3HBJ9; -.
DR MEROPS; M24.002; -.
DR PaxDb; 10029-XP_007633308-1; -.
DR Ensembl; ENSCGRT00001003564.1; ENSCGRP00001002631.1; ENSCGRG00001002959.1.
DR GeneID; 100755552; -.
DR KEGG; cge:100755552; -.
DR CTD; 10988; -.
DR eggNOG; KOG2775; Eukaryota.
DR GeneTree; ENSGT00940000155016; -.
DR OMA; WQDYRRS; -.
DR OrthoDB; 5473250at2759; -.
DR Proteomes; UP000001075; Unassembled WGS sequence.
DR Proteomes; UP000694386; Unplaced.
DR Proteomes; UP001108280; Chromosome 1.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0004239; F:initiator methionyl aminopeptidase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0016485; P:protein processing; IEA:Ensembl.
DR CDD; cd01088; MetAP2; 1.
DR Gene3D; 3.90.230.10; Creatinase/methionine aminopeptidase superfamily; 1.
DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 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 NCBIfam; TIGR00501; met_pdase_II; 1.
DR PANTHER; PTHR45777; METHIONINE AMINOPEPTIDASE 2; 1.
DR PANTHER; PTHR45777:SF2; METHIONINE AMINOPEPTIDASE 2; 1.
DR Pfam; PF00557; Peptidase_M24; 1.
DR PRINTS; PR00599; MAPEPTIDASE.
DR SUPFAM; SSF55920; Creatinase/aminopeptidase; 1.
DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1.
DR PROSITE; PS01202; MAP_2; 1.
PE 3: Inferred from homology;
KW Aminopeptidase {ECO:0000256|ARBA:ARBA00022438, ECO:0000256|HAMAP-
KW Rule:MF_03175}; Cytoplasm {ECO:0000256|HAMAP-Rule:MF_03175};
KW Glycoprotein {ECO:0000256|HAMAP-Rule:MF_03175};
KW Hydrolase {ECO:0000256|HAMAP-Rule:MF_03175};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, ECO:0000256|HAMAP-
KW Rule:MF_03175};
KW Protease {ECO:0000256|ARBA:ARBA00022670, ECO:0000256|HAMAP-Rule:MF_03175};
KW Reference proteome {ECO:0000313|Proteomes:UP000001075}.
FT DOMAIN 169..372
FT /note="Peptidase M24"
FT /evidence="ECO:0000259|Pfam:PF00557"
FT REGION 1..122
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 BINDING 231
FT /ligand="substrate"
FT /evidence="ECO:0000256|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:0000256|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:0000256|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:0000256|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:0000256|HAMAP-Rule:MF_03175"
FT BINDING 339
FT /ligand="substrate"
FT /evidence="ECO:0000256|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:0000256|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:0000256|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:0000256|HAMAP-Rule:MF_03175"
SQ SEQUENCE 478 AA; 52892 MW; E99C5F9E2918663D CRC64;
MAGVEEAASF GSHLNGDLDP DDREEGTSST AEEAAKKKRR KKKKGKGAVS AVQQEPDKES
GASVDEIAGQ LERQALDEKE RDDDDEDGDG DGDGAAGKKK KKKKKKRGPK 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
//
