MAN12_PENCI
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 03-AUG-2022, entry version 119.
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)-alpha-D-GlcNAc)-L-asparaginyl-[protein] (N-
CC glucan mannose isomer 9A1,2,3B1,2,3) = 4 beta-D-mannose + N(4)-
CC (alpha-D-Man-(1->3)-[alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-alpha-D-
CC Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc)-L-
CC asparaginyl-[protein] (N-glucan mannose isomer 5A1,2);
CC Xref=Rhea:RHEA:56008, Rhea:RHEA-COMP:14356, Rhea:RHEA-COMP:14367,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:28563, ChEBI:CHEBI:59087,
CC ChEBI:CHEBI:139493; EC=3.2.1.113;
CC 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 alpha-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 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 Pfam; PF01532; Glyco_hydro_47; 1.
DR PRINTS; PR00747; GLYHDRLASE47.
DR SUPFAM; SSF48225; SSF48225; 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
