MAP2_ENCCU
ID MAP2_ENCCU Reviewed; 358 AA.
AC Q8SR45; Q6VH17; Q6VH18;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 142.
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=Peptidase M {ECO:0000255|HAMAP-Rule:MF_03175};
GN Name=MAP2 {ECO:0000255|HAMAP-Rule:MF_03175}; OrderedLocusNames=ECU10_0750;
OS Encephalitozoon cuniculi (strain GB-M1) (Microsporidian parasite).
OC Eukaryota; Fungi; Fungi incertae sedis; Microsporidia; Unikaryonidae;
OC Encephalitozoon.
OX NCBI_TaxID=284813;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=16004378; DOI=10.14411/fp.2005.023;
RA Zhang H., Huang H., Cali A., Takvorian P.M., Feng X., Zhou G., Weiss L.M.;
RT "Investigations into microsporidian methionine aminopeptidase type 2: a
RT therapeutic target for microsporidiosis.";
RL Folia Parasitol. 52:182-192(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=GB-M1;
RX PubMed=11719806; DOI=10.1038/35106579;
RA Katinka M.D., Duprat S., Cornillot E., Metenier G., Thomarat F.,
RA Prensier G., Barbe V., Peyretaillade E., Brottier P., Wincker P.,
RA Delbac F., El Alaoui H., Peyret P., Saurin W., Gouy M., Weissenbach J.,
RA Vivares C.P.;
RT "Genome sequence and gene compaction of the eukaryote parasite
RT Encephalitozoon cuniculi.";
RL Nature 414:450-453(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 13-349.
RC STRAIN=ATCC 50502 / ECIII, ATCC 50503 / ECI, and ECII;
RX PubMed=15760654; DOI=10.1016/j.molbiopara.2004.12.006;
RA Pandrea I., Mittleider D., Brindley P.J., Didier E.S., Robertson D.L.;
RT "Phylogenetic relationships of methionine aminopeptidase 2 among
RT Encephalitozoon species and genotypes of microsporidia.";
RL Mol. Biochem. Parasitol. 140:141-152(2005).
RN [4]
RP FUNCTION.
RX PubMed=14736176; DOI=10.1111/j.1550-7408.2003.tb00643.x;
RA Weiss L.M., Zhou G.C., Zhang H.;
RT "Characterization of recombinant microsporidian methionine aminopeptidase
RT type 2.";
RL J. Eukaryot. Microbiol. 50:597-599(2003).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF ALA-241.
RX PubMed=16917013; DOI=10.1128/aac.00726-06;
RA Upadhya R., Zhang H.S., Weiss L.M.;
RT "System for expression of microsporidian methionine amino peptidase type 2
RT (MetAP2) in the yeast Saccharomyces cerevisiae.";
RL Antimicrob. Agents Chemother. 50:3389-3395(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], AND
RP DEVELOPMENTAL STAGE.
RX PubMed=16691553; DOI=10.1002/pmic.200500796;
RA Brosson D., Kuhn L., Delbac F., Garin J., Vivares C.P., Texier C.;
RT "Proteomic analysis of the eukaryotic parasite Encephalitozoon cuniculi
RT (microsporidia): a reference map for proteins expressed in late sporogonial
RT stages.";
RL Proteomics 6:3625-3635(2006).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.18 ANGSTROMS) IN COMPLEX WITH IRON AND INHIBITOR,
RP AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19660503; DOI=10.1016/j.molbiopara.2009.07.008;
RA Alvarado J.J., Nemkal A., Sauder J.M., Russell M., Akiyoshi D.E., Shi W.,
RA Almo S.C., Weiss L.M.;
RT "Structure of a microsporidian methionine aminopeptidase type 2 complexed
RT with fumagillin and TNP-470.";
RL Mol. Biochem. Parasitol. 168:158-167(2009).
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, ECO:0000269|PubMed:14736176,
CC ECO:0000269|PubMed:16004378, ECO:0000269|PubMed:16917013}.
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.95 mM for a Met-Ala-Ser peptide {ECO:0000269|PubMed:19660503};
CC Vmax=7.3 nmol/min/mg enzyme {ECO:0000269|PubMed:19660503};
CC pH dependence:
CC Optimum pH is 8.5. {ECO:0000269|PubMed:19660503};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius.
CC {ECO:0000269|PubMed:19660503};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03175}.
CC -!- DEVELOPMENTAL STAGE: Expressed in late sporogonial stages.
CC {ECO:0000269|PubMed:16691553}.
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; AF440270; AAM49625.1; -; Genomic_DNA.
DR EMBL; AL590449; CAD25794.1; -; Genomic_DNA.
DR EMBL; AY339777; AAR04551.1; -; Genomic_DNA.
DR EMBL; AY339778; AAR04552.1; -; Genomic_DNA.
DR EMBL; AY339779; AAR04553.1; -; Genomic_DNA.
DR RefSeq; NP_586190.1; NM_001042023.1.
DR PDB; 3FM3; X-ray; 2.18 A; A/B=1-358.
DR PDB; 3FMQ; X-ray; 2.50 A; A/B=1-358.
DR PDB; 3FMR; X-ray; 2.89 A; A/B=1-358.
DR PDBsum; 3FM3; -.
DR PDBsum; 3FMQ; -.
DR PDBsum; 3FMR; -.
DR AlphaFoldDB; Q8SR45; -.
DR SMR; Q8SR45; -.
DR STRING; 284813.Q8SR45; -.
DR DNASU; 859839; -.
DR GeneID; 859839; -.
DR KEGG; ecu:ECU10_0750; -.
DR VEuPathDB; MicrosporidiaDB:ECU10_0750; -.
DR HOGENOM; CLU_015857_7_0_1; -.
DR InParanoid; Q8SR45; -.
DR OMA; HGDKQVP; -.
DR OrthoDB; 601484at2759; -.
DR BRENDA; 3.4.11.18; 7412.
DR EvolutionaryTrace; Q8SR45; -.
DR PRO; PR:Q8SR45; -.
DR Proteomes; UP000000819; Chromosome X.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0070084; P:protein initiator methionine removal; IEA:UniProtKB-UniRule.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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; 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 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 3D-structure; Aminopeptidase; Cytoplasm; Hydrolase; Metal-binding;
KW Protease; Reference proteome.
FT CHAIN 1..358
FT /note="Methionine aminopeptidase 2"
FT /id="PRO_0000148985"
FT BINDING 109
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175,
FT ECO:0000269|PubMed:19660503"
FT BINDING 130
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 ECO:0000269|PubMed:19660503"
FT BINDING 141
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 ECO:0000269|PubMed:19660503"
FT BINDING 141
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 ECO:0000269|PubMed:19660503"
FT BINDING 210
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 ECO:0000269|PubMed:19660503"
FT BINDING 218
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175,
FT ECO:0000269|PubMed:19660503"
FT BINDING 243
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 ECO:0000269|PubMed:19660503"
FT BINDING 339
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 ECO:0000269|PubMed:19660503"
FT BINDING 339
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 ECO:0000269|PubMed:19660503"
FT VARIANT 288
FT /note="L -> F (in strain: ATCC 50502 / ECIII)"
FT MUTAGEN 241
FT /note="A->T: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:16917013"
FT HELIX 43..65
FT /evidence="ECO:0007829|PDB:3FM3"
FT HELIX 72..86
FT /evidence="ECO:0007829|PDB:3FM3"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:3FM3"
FT HELIX 91..94
FT /evidence="ECO:0007829|PDB:3FM3"
FT STRAND 95..103
FT /evidence="ECO:0007829|PDB:3FM3"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:3FM3"
FT STRAND 126..135
FT /evidence="ECO:0007829|PDB:3FM3"
FT STRAND 138..147
FT /evidence="ECO:0007829|PDB:3FM3"
FT HELIX 150..152
FT /evidence="ECO:0007829|PDB:3FM3"
FT HELIX 153..169
FT /evidence="ECO:0007829|PDB:3FM3"
FT HELIX 176..187
FT /evidence="ECO:0007829|PDB:3FM3"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:3FM3"
FT STRAND 195..200
FT /evidence="ECO:0007829|PDB:3FM3"
FT STRAND 209..213
FT /evidence="ECO:0007829|PDB:3FM3"
FT STRAND 236..249
FT /evidence="ECO:0007829|PDB:3FM3"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:3FM3"
FT HELIX 275..287
FT /evidence="ECO:0007829|PDB:3FM3"
FT TURN 288..290
FT /evidence="ECO:0007829|PDB:3FM3"
FT HELIX 295..300
FT /evidence="ECO:0007829|PDB:3FM3"
FT HELIX 309..317
FT /evidence="ECO:0007829|PDB:3FM3"
FT STRAND 320..323
FT /evidence="ECO:0007829|PDB:3FM3"
FT STRAND 335..345
FT /evidence="ECO:0007829|PDB:3FM3"
FT STRAND 348..353
FT /evidence="ECO:0007829|PDB:3FM3"
SQ SEQUENCE 358 AA; 39975 MW; 058A8AB457EC258F CRC64;
MKCILLNQAE ELPIEFLPKD GVYGKGKLFD SRNMEIENFT ESDILQDARR AAEAHRRARY
RVQSIVRPGI TLLEIVRSIE DSTRTLLKGE RNNGIGFPAG MSMNSCAAHY TVNPGEQDIV
LKEDDVLKID FGTHSDGRIM DSAFTVAFKE NLEPLLVAAR EGTETGIKSL GVDVRVCDIG
RDINEVISSY EVEIGGRMWP IRPISDLHGH SISQFRIHGG ISIPAVNNRD TTRIKGDSFY
AVETFATTGK GSIDDRPPCS HFVLNTYKSR KLFNKDLIKV YEFVKDSLGT LPFSPRHLDY
YGLVKGGSLK SVNLLTMMGL LTPYPPLNDI DGCKVAQFEH TVYLSEHGKE VLTRGDDY
