ID   MNS1_YEAST              Reviewed;         549 AA.
AC   P32906; D6VWU9;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1993, sequence version 1.
DT   27-MAR-2024, entry version 203.
DE   RecName: Full=Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase;
DE            EC=3.2.1.113 {ECO:0000269|PubMed:12090241};
DE   AltName: Full=ER alpha-1,2-mannosidase;
DE   AltName: Full=Man(9)-alpha-mannosidase;
GN   Name=MNS1; OrderedLocusNames=YJR131W; ORFNames=J2110;
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], PROTEIN SEQUENCE OF 29-51; 226-233;
RP   241-259; 314-323 AND 369-383, AND DISRUPTION PHENOTYPE.
RX   PubMed=1714453; DOI=10.1016/s0021-9258(18)98594-7;
RA   Camirand A., Heysen A., Grondin B., Herscovics A.;
RT   "Glycoprotein biosynthesis in Saccharomyces cerevisiae. Isolation and
RT   characterization of the gene encoding a specific processing alpha-
RT   mannosidase.";
RL   J. Biol. Chem. 266:15120-15127(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA   Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA   Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA   Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA   Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA   Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA   Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA   Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA   Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA   To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA   von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT   "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL   EMBO J. 15:2031-2049(1996).
RN   [3]
RP   GENOME REANNOTATION.
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   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND PATHWAY.
RX   PubMed=12090241;
RA   Herscovics A., Romero P.A., Tremblay L.O.;
RT   "The specificity of the yeast and human class I ER alpha 1,2-mannosidases
RT   involved in ER quality control is not as strict previously reported.";
RL   Glycobiology 12:14G-15G(2002).
RN   [5]
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   [6]
RP   X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 34-549, DISULFIDE BONDS,
RP   CALCIUM-BINDING, COFACTOR, AND SUBUNIT.
RX   PubMed=10675327; DOI=10.1093/emboj/19.4.581;
RA   Vallee F., Lipari F., Yip P., Sleno B., Herscovics A., Howell P.L.;
RT   "Crystal structure of a class I alpha1,2-mannosidase involved in N-glycan
RT   processing and endoplasmic reticulum quality control.";
RL   EMBO J. 19:581-588(2000).
RN   [7] {ECO:0007744|PDB:1G6I}
RP   X-RAY CRYSTALLOGRAPHY (1.59 ANGSTROMS) IN COMPLEX WITH MANNOSE, AND
RP   GLYCOSYLATION AT ASN-96; ASN-155 AND ASN-224.
RA   Herscovics A., Lipari F., Sleno B., Romera P.A., Vallee F., Yip P.,
RA   Howell P.A.;
RT   "Structure and function of Class I a1,2-mannosidases involved in
RT   glycoprotein biosynthesis.";
RL   Submitted (NOV-2000) to the PDB data bank.
CC   -!- FUNCTION: Involved in glycoprotein quality control as it is important
CC       for the targeting of misfolded glycoproteins for degradation. It
CC       primarily trims a single alpha-1,2-linked mannose residue from
CC       Man(9)GlcNAc(2) to produce Man(8)GlcNAc(2), but at high enzyme
CC       concentrations it further trims the carbohydrates to Man(5)GlcNAc(2).
CC       {ECO:0000269|PubMed:12090241}.
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:12090241};
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:12090241};
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000305|PubMed:10675327};
CC   -!- PATHWAY: Protein modification; protein glycosylation.
CC       {ECO:0000269|PubMed:12090241}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10675327}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type
CC       II membrane protein.
CC   -!- DISRUPTION PHENOTYPE: No visible phenotype.
CC       {ECO:0000269|PubMed:1714453}.
CC   -!- MISCELLANEOUS: Present with 8260 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 47 family. {ECO:0000305}.
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DR   EMBL; M63598; AAA34799.1; -; Genomic_DNA.
DR   EMBL; Z49631; CAA89662.1; -; Genomic_DNA.
DR   EMBL; BK006943; DAA08915.1; -; Genomic_DNA.
DR   PIR; A39345; A39345.
DR   RefSeq; NP_012665.3; NM_001181789.3.
DR   PDB; 1DL2; X-ray; 1.54 A; A=34-549.
DR   PDB; 1G6I; X-ray; 1.59 A; A=1-549.
DR   PDBsum; 1DL2; -.
DR   PDBsum; 1G6I; -.
DR   AlphaFoldDB; P32906; -.
DR   SMR; P32906; -.
DR   BioGRID; 33886; 155.
DR   DIP; DIP-1441N; -.
DR   IntAct; P32906; 6.
DR   MINT; P32906; -.
DR   STRING; 4932.YJR131W; -.
DR   CAZy; GH47; Glycoside Hydrolase Family 47.
DR   GlyCosmos; P32906; 3 sites, No reported glycans.
DR   GlyGen; P32906; 3 sites.
DR   MaxQB; P32906; -.
DR   PaxDb; 4932-YJR131W; -.
DR   PeptideAtlas; P32906; -.
DR   EnsemblFungi; YJR131W_mRNA; YJR131W; YJR131W.
DR   GeneID; 853595; -.
DR   KEGG; sce:YJR131W; -.
DR   AGR; SGD:S000003892; -.
DR   SGD; S000003892; MNS1.
DR   VEuPathDB; FungiDB:YJR131W; -.
DR   eggNOG; KOG2431; Eukaryota.
DR   GeneTree; ENSGT00940000155422; -.
DR   HOGENOM; CLU_003818_3_0_1; -.
DR   InParanoid; P32906; -.
DR   OMA; AAFKHSW; -.
DR   OrthoDB; 1331861at2759; -.
DR   BioCyc; MetaCyc:YJR131W-MONOMER; -.
DR   BioCyc; YEAST:YJR131W-MONOMER; -.
DR   BRENDA; 3.2.1.209; 984.
DR   UniPathway; UPA00378; -.
DR   BioGRID-ORCS; 853595; 0 hits in 10 CRISPR screens.
DR   EvolutionaryTrace; P32906; -.
DR   PRO; PR:P32906; -.
DR   Proteomes; UP000002311; Chromosome X.
DR   RNAct; P32906; Protein.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR   GO; GO:0004571; F:mannosyl-oligosaccharide 1,2-alpha-mannosidase activity; IDA:UniProtKB.
DR   GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR   GO; GO:0035977; P:protein deglycosylation involved in glycoprotein catabolic process; IMP:SGD.
DR   GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway.
DR   GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:SGD.
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:SF55; ENDOPLASMIC RETICULUM MANNOSYL-OLIGOSACCHARIDE 1,2-ALPHA-MANNOSIDASE; 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; Calcium; Direct protein sequencing; Disulfide bond;
KW   Endoplasmic reticulum; Glycoprotein; Glycosidase; Hydrolase; Membrane;
KW   Metal-binding; Reference proteome; Signal-anchor; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..549
FT                   /note="Endoplasmic reticulum mannosyl-oligosaccharide 1,2-
FT                   alpha-mannosidase"
FT                   /id="PRO_0000210319"
FT   TOPO_DOM        1..4
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        5..24
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        25..354
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        399
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P31723"
FT   BINDING         525
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:10675327"
FT   CARBOHYD        96
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|Ref.7, ECO:0007744|PDB:1G6I"
FT   CARBOHYD        155
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|Ref.7, ECO:0007744|PDB:1G6I"
FT   CARBOHYD        224
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|Ref.7, ECO:0007744|PDB:1G6I"
FT   DISULFID        340..385
FT                   /evidence="ECO:0000269|PubMed:10675327,
FT                   ECO:0007744|PDB:1DL2, ECO:0007744|PDB:1G6I"
FT   DISULFID        468..471
FT                   /evidence="ECO:0000269|PubMed:10675327,
FT                   ECO:0007744|PDB:1DL2, ECO:0007744|PDB:1G6I"
FT   VARIANT         40
FT                   /note="D -> Y"
FT   VARIANT         376
FT                   /note="D -> L"
FT   HELIX           35..56
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   STRAND          61..64
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   TURN            65..68
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   STRAND          69..71
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           84..97
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   STRAND          99..101
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           102..118
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   STRAND          125..129
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           130..151
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           156..171
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           172..175
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   STRAND          176..180
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   STRAND          184..187
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   TURN            188..190
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           199..201
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           205..208
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           212..222
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           225..232
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           235..242
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           244..248
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   STRAND          253..256
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   TURN            258..260
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   TURN            272..274
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           275..288
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           291..307
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   STRAND          309..311
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   TURN            313..315
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   STRAND          318..320
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   TURN            324..328
FT                   /evidence="ECO:0007829|PDB:1G6I"
FT   STRAND          334..336
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           337..341
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           342..351
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           356..359
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           372..390
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   STRAND          399..403
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   STRAND          417..423
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           425..427
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           435..447
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           451..467
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   STRAND          468..470
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   TURN            474..476
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   STRAND          482..489
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           498..502
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           504..511
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   STRAND          520..523
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   STRAND          529..531
FT                   /evidence="ECO:0007829|PDB:1DL2"
FT   HELIX           535..540
FT                   /evidence="ECO:0007829|PDB:1DL2"
SQ   SEQUENCE   549 AA;  63057 MW;  B85FF351900A9BB2 CRC64;
     MKNSVGISIA TIVAIIAAIY YVPWYEHFER KSPGAGEMRD RIESMFLESW RDYSKHGWGY
     DVYGPIEHTS HNMPRGNQPL GWIIVDSVDT LMLMYNSSTL YKSEFEAEIQ RSEHWINDVL
     DFDIDAEVNV FETTIRMLGG LLSAYHLSDV LEVGNKTVYL NKAIDLGDRL ALAFLSTQTG
     IPYSSINLHS GQAVKNHADG GASSTAEFTT LQMEFKYLAY LTGNRTYWEL VERVYEPLYK
     NNDLLNTYDG LVPIYTFPDT GKFGASTIRF GSRGDSFYEY LLKQYLLTHE TLYYDLYRKS
     MEGMKKHLLA QSKPSSLWYI GEREQGLHGQ LSPKMDHLVC FMGGLLASGS TEGLSIHEAR
     RRPFFSLSLE RKSDWDLAKG ITDTCYQMYK QSSSGLAPEI VVFNDGNIKQ DGWWRSSVGD
     FFVKPLDRHN LQRPETVESI MFMYHLSHDH KYREWGAEIA TSFFENTCVD CNDPKLRRFT
     SLSDCITLPT KKSNNMESFW LAETLKYLYI LFLDEFDLTK VVFNTEAHPF PVLDEEILKS
     QSLTTGWSL
//