ID   MAN12_PENCI             Reviewed;         511 AA.
AC   P31723;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 2.
DT   24-JAN-2024, entry version 124.
DE   RecName: Full=Mannosyl-oligosaccharide alpha-1,2-mannosidase;
DE            EC=3.2.1.113 {ECO:0000269|PubMed:8452520};
DE   AltName: Full=Man(9)-alpha-mannosidase;
DE   Flags: Precursor;
GN   Name=MSDC;
OS   Penicillium citrinum.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=5077;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE.
RX   PubMed=7640307; DOI=10.1016/0167-4781(95)00101-l;
RA   Yoshida T., Ichishima E.;
RT   "Molecular cloning and nucleotide sequence of the genomic DNA for 1,2-
RT   alpha-D-mannosidase gene, msdC from Penicillium citrinum.";
RL   Biochim. Biophys. Acta 1263:159-162(1995).
RN   [2]
RP   PROTEIN SEQUENCE OF 36-49; 77-94 AND 405-415, BIOPHYSICOCHEMICAL
RP   PROPERTIES, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=8452520; DOI=10.1042/bj2900349;
RA   Yoshida T., Inoue T., Ichishima E.;
RT   "1,2-alpha-D-mannosidase from Penicillium citrinum: molecular and enzymic
RT   properties of two isoenzymes.";
RL   Biochem. J. 290:349-354(1993).
RN   [3]
RP   X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH SUBSTRATE,
RP   GLYCOSYLATION AT ASN-182; ASN-366 AND ASN-438, ACTIVE SITE, SUBUNIT, AND
RP   DISULFIDE BONDS.
RX   PubMed=11714724; DOI=10.1074/jbc.m110243200;
RA   Lobsanov Y.D., Vallee F., Imberty A., Yoshida T., Yip P., Herscovics A.,
RA   Howell P.L.;
RT   "Structure of Penicillium citrinum alpha 1,2-mannosidase reveals the basis
RT   for differences in specificity of the endoplasmic reticulum and Golgi class
RT   I enzymes.";
RL   J. Biol. Chem. 277:5620-5630(2002).
CC   -!- FUNCTION: Involved in the maturation of Asn-linked oligosaccharides.
CC       Progressively trim alpha-1,2-linked mannose residues from
CC       Man(9)GlcNAc(2) to produce Man(5)GlcNAc(2).
CC       {ECO:0000269|PubMed:8452520}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4 H2O + N(4)-(alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-
CC         Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-
CC         (1->2)-alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-
CC         beta-D-GlcNAc-(1->4)-beta-D-GlcNAc)-L-asparaginyl-[protein] (N-glucan
CC         mannose isomer 9A1,2,3B1,2,3) = 4 beta-D-mannose + N(4)-(alpha-D-Man-
CC         (1->3)-[alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-
CC         beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc)-L-asparaginyl-
CC         [protein] (N-glucan mannose isomer 5A1,2); Xref=Rhea:RHEA:56008,
CC         Rhea:RHEA-COMP:14356, Rhea:RHEA-COMP:14367, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:28563, ChEBI:CHEBI:59087, ChEBI:CHEBI:139493;
CC         EC=3.2.1.113; Evidence={ECO:0000269|PubMed:8452520};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3 H2O + N(4)-(alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-
CC         Man-(1->3)-[alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-
CC         (1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-
CC         beta-D-GlcNAc)-L-asparaginyl-[protein] (N-glucan mannose isomer
CC         8A1,2,3B1,3) = 3 beta-D-mannose + N(4)-(alpha-D-Man-(1->3)-[alpha-D-
CC         Man-(1->3)-[alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-
CC         (1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc)-L-asparaginyl-[protein]
CC         (N-glucan mannose isomer 5A1,2); Xref=Rhea:RHEA:56028, Rhea:RHEA-
CC         COMP:14358, Rhea:RHEA-COMP:14367, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:28563, ChEBI:CHEBI:59087, ChEBI:CHEBI:60628;
CC         EC=3.2.1.113; Evidence={ECO:0000269|PubMed:8452520};
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000250|UniProtKB:P32906};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 5.0. {ECO:0000269|PubMed:8452520};
CC   -!- PATHWAY: Protein modification; protein glycosylation.
CC       {ECO:0000269|PubMed:8452520}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11714724}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:8452520}.
CC   -!- MISCELLANEOUS: The enzyme is inactivated by reaction of carbodiimide
CC       reagents with Asp-375. Since the antibiotic 1-deoxymannojirimycin (DMM)
CC       acts as a competitive inhibitor, and it blocks the reaction with
CC       carbodiimides, Asp-375 is established as an active site. High activity
CC       in presence of EDTA. {ECO:0000269|PubMed:11714724}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 47 family. {ECO:0000305}.
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DR   EMBL; D45839; BAA08275.1; -; Genomic_DNA.
DR   PIR; S30362; S30362.
DR   PIR; S58766; S58766.
DR   PDB; 1KKT; X-ray; 2.20 A; A/B=1-511.
DR   PDB; 1KRE; X-ray; 2.20 A; A/B=1-511.
DR   PDB; 1KRF; X-ray; 2.20 A; A/B=1-511.
DR   PDB; 2RI8; X-ray; 2.16 A; A/B=36-510.
DR   PDB; 2RI9; X-ray; 1.95 A; A/B=36-510.
DR   PDBsum; 1KKT; -.
DR   PDBsum; 1KRE; -.
DR   PDBsum; 1KRF; -.
DR   PDBsum; 2RI8; -.
DR   PDBsum; 2RI9; -.
DR   AlphaFoldDB; P31723; -.
DR   SMR; P31723; -.
DR   DrugBank; DB03206; Duvoglustat.
DR   DrugBank; DB02742; Kifunensine.
DR   CAZy; GH47; Glycoside Hydrolase Family 47.
DR   CLAE; MSD47C1_PENCI; -.
DR   CLAE; MSD47C2_PENCI; -.
DR   GlyCosmos; P31723; 3 sites, No reported glycans.
DR   iPTMnet; P31723; -.
DR   BRENDA; 3.2.1.113; 4608.
DR   UniPathway; UPA00378; -.
DR   EvolutionaryTrace; P31723; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:InterPro.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0004571; F:mannosyl-oligosaccharide 1,2-alpha-mannosidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR   GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway.
DR   GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IEA:UniProt.
DR   Gene3D; 1.50.10.10; -; 1.
DR   InterPro; IPR012341; 6hp_glycosidase-like_sf.
DR   InterPro; IPR001382; Glyco_hydro_47.
DR   InterPro; IPR036026; Seven-hairpin_glycosidases.
DR   PANTHER; PTHR11742:SF101; MANNOSYL-OLIGOSACCHARIDE ALPHA-1,2-MANNOSIDASE 1B; 1.
DR   PANTHER; PTHR11742; MANNOSYL-OLIGOSACCHARIDE ALPHA-1,2-MANNOSIDASE-RELATED; 1.
DR   Pfam; PF01532; Glyco_hydro_47; 1.
DR   PRINTS; PR00747; GLYHDRLASE47.
DR   SUPFAM; SSF48225; Seven-hairpin glycosidases; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Glycosidase; Hydrolase; Metal-binding; Secreted; Signal.
FT   SIGNAL          1..35
FT                   /evidence="ECO:0000269|PubMed:8452520"
FT   CHAIN           36..511
FT                   /note="Mannosyl-oligosaccharide alpha-1,2-mannosidase"
FT                   /id="PRO_0000012085"
FT   ACT_SITE        375
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000269|PubMed:11714724"
FT   BINDING         501
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P45700"
FT   CARBOHYD        182
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11714724,
FT                   ECO:0007744|PDB:1KKT, ECO:0007744|PDB:1KRE,
FT                   ECO:0007744|PDB:1KRF, ECO:0007744|PDB:2RI8,
FT                   ECO:0007744|PDB:2RI9"
FT   CARBOHYD        366
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11714724,
FT                   ECO:0007744|PDB:1KKT, ECO:0007744|PDB:1KRE,
FT                   ECO:0007744|PDB:1KRF, ECO:0007744|PDB:2RI8,
FT                   ECO:0007744|PDB:2RI9"
FT   CARBOHYD        438
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11714724,
FT                   ECO:0007744|PDB:1KKT, ECO:0007744|PDB:1KRE,
FT                   ECO:0007744|PDB:1KRF, ECO:0007744|PDB:2RI8,
FT                   ECO:0007744|PDB:2RI9"
FT   DISULFID        332..361
FT                   /evidence="ECO:0000269|PubMed:11714724,
FT                   ECO:0007744|PDB:1KKT, ECO:0007744|PDB:1KRE,
FT                   ECO:0007744|PDB:1KRF, ECO:0007744|PDB:2RI8,
FT                   ECO:0007744|PDB:2RI9"
FT   CONFLICT        407
FT                   /note="R -> H (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   HELIX           37..58
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   TURN            59..61
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          62..66
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   TURN            67..70
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          71..73
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   TURN            75..78
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           81..93
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           96..108
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           120..139
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   TURN            140..144
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           149..166
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           167..170
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          172..175
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          179..181
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   TURN            183..185
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          192..195
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           196..200
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           203..213
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           217..230
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           235..237
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          246..249
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   TURN            250..252
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   TURN            264..266
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           267..279
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   TURN            281..284
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           285..301
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          317..319
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          322..324
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          326..328
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           330..333
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           334..345
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           348..366
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          368..371
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          375..378
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   TURN            381..383
FT                   /evidence="ECO:0007829|PDB:2RI8"
FT   HELIX           386..388
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           389..395
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          398..401
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           409..421
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           424..440
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          444..447
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           456..458
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          459..463
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           468..471
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   HELIX           473..479
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          496..499
FT                   /evidence="ECO:0007829|PDB:2RI9"
FT   STRAND          505..507
FT                   /evidence="ECO:0007829|PDB:2RI9"
SQ   SEQUENCE   511 AA;  56570 MW;  DCBDEBA5768E7596 CRC64;
     MRLPVSFPLT VLSLLGSTIA HPYGETEAVL RSEPKSNQAK ADAVKEAFQH AWNGYMKYAF
     PHDELTPVSN GHADSRNGWG ASAVDALSTA VIMGKADVVN AILEHVADID FSKTSDTVSL
     FETTIRYLAG MLSGYDLLQG PAKNLVDNQD LIDGLLDQSR NLADVLKFAF DTPSGVPYNN
     INITSHGNDG ATTNGLAVTG TLVLEWTRLS DLTGDEEYAK LSQKAESYLL KPQPSSSEPF
     PGLVGSSINI NDGQFADSRV SWNGGDDSFY EYLIKMYVYD PKRFETYKDR WVLAAESTIK
     HLKSHPKSRP DLTFLSSYSN RNYDLSSQHL TCFDGGSFLL GGTVLDRQDF IDFGLELVDG
     CEATYNSTLT KIGPDSWGWD PKKVPSDQKE FYEKAGFYIS SGSYVLRPEV IESFYYAHRV
     TGKEIYRDWV WNAFVAINST CRTDSGFAAV SDVNKANGGS KYDNQESFLF AEVMKYSYLA
     HSEDAAWQVQ KGGKNTFVYN TEAHPISVAR N
//