MNS1_YEAST
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 03-AUG-2022, entry version 196.
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)-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: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 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: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; 148.
DR DIP; DIP-1441N; -.
DR IntAct; P32906; 6.
DR MINT; P32906; -.
DR STRING; 4932.YJR131W; -.
DR CAZy; GH47; Glycoside Hydrolase Family 47.
DR MaxQB; P32906; -.
DR PaxDb; P32906; -.
DR PRIDE; P32906; -.
DR EnsemblFungi; YJR131W_mRNA; YJR131W; YJR131W.
DR GeneID; 853595; -.
DR KEGG; sce:YJR131W; -.
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 BioCyc; MetaCyc:YJR131W-MON; -.
DR BioCyc; YEAST:YJR131W-MON; -.
DR BRENDA; 3.2.1.209; 984.
DR UniPathway; UPA00378; -.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0006491; P:N-glycan processing; IBA:GO_Central.
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 Pfam; PF01532; Glyco_hydro_47; 1.
DR PRINTS; PR00747; GLYHDRLASE47.
DR SUPFAM; SSF48225; SSF48225; 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
