MAP2_YEAST
ID MAP2_YEAST Reviewed; 421 AA.
AC P38174; D6VPR3; P89493;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 4.
DT 03-AUG-2022, entry version 193.
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=YBL091C;
GN ORFNames=YBL0701;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 76626 / YPH500;
RX PubMed=8618900; DOI=10.1073/pnas.92.26.12357;
RA Li X., Chang Y.-H.;
RT "Amino-terminal protein processing in Saccharomyces cerevisiae is an
RT essential function that requires two distinct methionine aminopeptidases.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:12357-12361(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7502586; DOI=10.1002/yea.320111112;
RA Obermaier B., Gassenhuber J., Piravandi E., Domdey H.;
RT "Sequence analysis of a 78.6 kb segment of the left end of Saccharomyces
RT cerevisiae chromosome II.";
RL Yeast 11:1103-1112(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7813418; DOI=10.1002/j.1460-2075.1994.tb06923.x;
RA Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C.,
RA Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M.,
RA Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M.,
RA Cziepluch C., Demolis N., Delaveau T., Doignon F., Domdey H.,
RA Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D.,
RA Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N.,
RA Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J.,
RA Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C.,
RA Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P.,
RA Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y.,
RA Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F.,
RA Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E.,
RA Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M.,
RA Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B.,
RA Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L.,
RA Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M.,
RA Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S.,
RA Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K.,
RA Mewes H.-W., Kleine K.;
RT "Complete DNA sequence of yeast chromosome II.";
RL EMBO J. 13:5795-5809(1994).
RN [4]
RP GENOME REANNOTATION, AND SEQUENCE REVISION TO 86.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [5]
RP IDENTIFICATION.
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 [6]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=9177176; DOI=10.1073/pnas.94.12.6099;
RA Sin N., Meng L., Wang M.Q., Wen J.J., Bornmann W.G., Crews C.M.;
RT "The anti-angiogenic agent fumagillin covalently binds and inhibits the
RT methionine aminopeptidase, MetAP-2.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:6099-6103(1997).
RN [7]
RP FUNCTION, AND SUBSTRATE SPECIFICITY.
RX PubMed=11811952; DOI=10.1006/abbi.2001.2675;
RA Chen S., Vetro J.A., Chang Y.H.;
RT "The specificity in vivo of two distinct methionine aminopeptidases in
RT Saccharomyces cerevisiae.";
RL Arch. Biochem. Biophys. 398:87-93(2002).
RN [8]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=12874831; DOI=10.1002/jcb.10566;
RA Dummitt B., Micka W.S., Chang Y.H.;
RT "N-terminal methionine removal and methionine metabolism in Saccharomyces
RT cerevisiae.";
RL J. Cell. Biochem. 89:964-974(2003).
RN [9]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [10]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF HIS-174.
RX PubMed=15547949; DOI=10.1002/jcb.20285;
RA Vetro J.A., Dummitt B., Micka W.S., Chang Y.H.;
RT "Evidence of a dominant negative mutant of yeast methionine aminopeptidase
RT type 2 in Saccharomyces cerevisiae.";
RL J. Cell. Biochem. 94:656-668(2005).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(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). Plays only a minor role in N-
CC terminal methionine removal. Less efficient when the second residue is
CC Val, Gly, Cys or Thr. {ECO:0000255|HAMAP-Rule:MF_03175,
CC ECO:0000269|PubMed:11811952, ECO:0000269|PubMed:12874831,
CC ECO:0000269|PubMed:15547949, ECO:0000269|PubMed:8618900,
CC ECO:0000269|PubMed:9177176}.
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 ECO:0000269|PubMed:8618900};
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 Also zinc has been proposed to be the physiological cofactor for yeast.
CC {ECO:0000255|HAMAP-Rule:MF_03175};
CC -!- ACTIVITY REGULATION: Irreversibly inhibited by the fungal metabolite
CC fumagillin, an antiangiogenic drug. Subject to product inhibition by
CC cytosolic methionine. {ECO:0000269|PubMed:12874831,
CC ECO:0000269|PubMed:9177176}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03175,
CC ECO:0000269|PubMed:14562095}.
CC -!- MISCELLANEOUS: Present with 1080 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the peptidase M24A family. Methionine
CC aminopeptidase eukaryotic type 2 subfamily. {ECO:0000255|HAMAP-
CC Rule:MF_03175}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA56011.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U17437; AAC49142.1; -; Genomic_DNA.
DR EMBL; X79489; CAA56011.1; ALT_INIT; Genomic_DNA.
DR EMBL; Z35851; CAA84912.1; -; Genomic_DNA.
DR EMBL; Z35852; CAA84913.1; -; Genomic_DNA.
DR EMBL; BK006936; DAA07033.2; -; Genomic_DNA.
DR RefSeq; NP_009462.2; NM_001178331.2.
DR AlphaFoldDB; P38174; -.
DR SMR; P38174; -.
DR BioGRID; 32613; 76.
DR DIP; DIP-6459N; -.
DR IntAct; P38174; 3.
DR STRING; 4932.YBL091C; -.
DR MEROPS; M24.002; -.
DR iPTMnet; P38174; -.
DR MaxQB; P38174; -.
DR PaxDb; P38174; -.
DR PRIDE; P38174; -.
DR EnsemblFungi; YBL091C_mRNA; YBL091C; YBL091C.
DR GeneID; 852187; -.
DR KEGG; sce:YBL091C; -.
DR SGD; S000000187; MAP2.
DR VEuPathDB; FungiDB:YBL091C; -.
DR eggNOG; KOG2775; Eukaryota.
DR GeneTree; ENSGT00940000172436; -.
DR HOGENOM; CLU_015857_7_1_1; -.
DR InParanoid; P38174; -.
DR OMA; NEIAAHY; -.
DR BioCyc; YEAST:YBL091C-MON; -.
DR Reactome; R-SCE-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR PRO; PR:P38174; -.
DR Proteomes; UP000002311; Chromosome II.
DR RNAct; P38174; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:0004177; F:aminopeptidase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IGI:SGD.
DR GO; GO:0008235; F:metalloexopeptidase activity; IBA:GO_Central.
DR GO; GO:0035551; P:protein initiator methionine removal involved in protein maturation; IMP:SGD.
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 Aminopeptidase; Cytoplasm; Hydrolase; Metal-binding; Phosphoprotein;
KW Protease; Reference proteome.
FT CHAIN 1..421
FT /note="Methionine aminopeptidase 2"
FT /id="PRO_0000148988"
FT REGION 1..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 18..41
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 174
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT BINDING 194
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 205
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 205
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 274
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 282
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT BINDING 307
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 402
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 402
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 35
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MUTAGEN 174
FT /note="H->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:15547949"
FT CONFLICT 86
FT /note="D -> V (in Ref. 2; CAA56011 and 3; CAA84912)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 421 AA; 47518 MW; 206E9651D88925A8 CRC64;
MTDAEIENSP ASDLKELNLE NEGVEQQDQA KADESDPVES KKKKNKKKKK KKSNVKKIEL
LFPDGKYPEG AWMDYHQDFN LQRTTDEESR YLKRDLERAE HWNDVRKGAE IHRRVRRAIK
DRIVPGMKLM DIADMIENTT RKYTGAENLL AMEDPKSQGI GFPTGLSLNH CAAHFTPNAG
DKTVLKYEDV MKVDYGVQVN GNIIDSAFTV SFDPQYDNLL AAVKDATYTG IKEAGIDVRL
TDIGEAIQEV MESYEVEING ETYQVKPCRN LCGHSIAPYR IHGGKSVPIV KNGDTTKMEE
GEHFAIETFG STGRGYVTAG GEVSHYARSA EDHQVMPTLD SAKNLLKTID RNFGTLPFCR
RYLDRLGQEK YLFALNNLVR HGLVQDYPPL NDIPGSYTAQ FEHTILLHAH KKEVVSKGDD
Y
