MNL1_YEAST
ID MNL1_YEAST Reviewed; 796 AA.
AC P38888; D3DLF3;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=ER degradation-enhancing alpha-mannosidase-like protein 1;
DE EC=3.2.1.24 {ECO:0000269|PubMed:19124653, ECO:0000269|PubMed:21700223};
DE Flags: Precursor;
GN Name=MNL1; Synonyms=HTM1; OrderedLocusNames=YHR204W;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8091229; DOI=10.1126/science.8091229;
RA Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z.,
RA Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., Kucaba T.,
RA Hillier L.W., Jier M., Johnston L., Langston Y., Latreille P., Louis E.J.,
RA Macri C., Mardis E., Menezes S., Mouser L., Nhan M., Rifkin L., Riles L.,
RA St Peter H., Trevaskis E., Vaughan K., Vignati D., Wilcox L., Wohldman P.,
RA Waterston R., Wilson R., Vaudin M.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome
RT VIII.";
RL Science 265:2077-2082(1994).
RN [2]
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 [3]
RP FUNCTION.
RX PubMed=11375935; DOI=10.1093/embo-reports/kve089;
RA Jakob C.A., Bodmer D., Spirig U., Baettig P., Marcil A., Dignard D.,
RA Bergeron J.J.M., Thomas D.Y., Aebi M.;
RT "Htm1p, a mannosidase-like protein, is involved in glycoprotein degradation
RT in yeast.";
RL EMBO Rep. 2:423-430(2001).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11254655; DOI=10.1074/jbc.c100023200;
RA Nakatsukasa K., Nishikawa S., Hosokawa N., Nagata K., Endo T.;
RT "Mnl1p, an alpha -mannosidase-like protein in yeast Saccharomyces
RT cerevisiae, is required for endoplasmic reticulum-associated degradation of
RT glycoproteins.";
RL J. Biol. Chem. 276:8635-8638(2001).
RN [5]
RP FUNCTION.
RX PubMed=15078901; DOI=10.1083/jcb.200309132;
RA Vashist S., Ng D.T.W.;
RT "Misfolded proteins are sorted by a sequential checkpoint mechanism of ER
RT quality control.";
RL J. Cell Biol. 165:41-52(2004).
RN [6]
RP FUNCTION.
RX PubMed=15215312; DOI=10.1091/mbc.e04-01-0024;
RA Gnann A., Riordan J.R., Wolf D.H.;
RT "Cystic fibrosis transmembrane conductance regulator degradation depends on
RT the lectins Htm1p/EDEM and the Cdc48 protein complex in yeast.";
RL Mol. Biol. Cell 15:4125-4135(2004).
RN [7]
RP FUNCTION.
RX PubMed=15809311; DOI=10.1083/jcb.200411136;
RA Spear E.D., Ng D.T.W.;
RT "Single, context-specific glycans can target misfolded glycoproteins for
RT ER-associated degradation.";
RL J. Cell Biol. 169:73-82(2005).
RN [8]
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 [9]
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 [10]
RP FUNCTION, INTERACTION WITH PDI1, AND CATALYTIC ACTIVITY.
RX PubMed=19124653; DOI=10.1083/jcb.200809198;
RA Clerc S., Hirsch C., Oggier D.M., Deprez P., Jakob C., Sommer T., Aebi M.;
RT "Htm1 protein generates the N-glycan signal for glycoprotein degradation in
RT the endoplasmic reticulum.";
RL J. Cell Biol. 184:159-172(2009).
RN [11]
RP FUNCTION, INTERACTION WITH PDI1, AND CATALYTIC ACTIVITY.
RX PubMed=21700223; DOI=10.1016/j.molcel.2011.04.027;
RA Gauss R., Kanehara K., Carvalho P., Ng D.T., Aebi M.;
RT "A complex of Pdi1p and the mannosidase Htm1p initiates clearance of
RT unfolded glycoproteins from the endoplasmic reticulum.";
RL Mol. Cell 42:782-793(2011).
CC -!- FUNCTION: Alpha-1,2-specific exomannosidase involved in endoplasmic
CC reticulum-associated degradation (ERAD). Delivers misfolded
CC glycoproteins to proteasomes. Forms a complex with PDI1 to process
CC unfolded protein-bound Man8GlcNAc2 oligosaccharides to Man7GlcNAc2,
CC promoting degradation in unfolded protein response.
CC {ECO:0000269|PubMed:11254655, ECO:0000269|PubMed:11375935,
CC ECO:0000269|PubMed:15078901, ECO:0000269|PubMed:15215312,
CC ECO:0000269|PubMed:15809311, ECO:0000269|PubMed:19124653,
CC ECO:0000269|PubMed:21700223}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of terminal, non-reducing alpha-D-mannose residues
CC in alpha-D-mannosides.; EC=3.2.1.24;
CC Evidence={ECO:0000269|PubMed:19124653, ECO:0000269|PubMed:21700223};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P45700};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000250|UniProtKB:P32906}.
CC -!- SUBUNIT: Interacts with PDI1. {ECO:0000269|PubMed:19124653,
CC ECO:0000269|PubMed:21700223}.
CC -!- INTERACTION:
CC P38888; P17967: PDI1; NbExp=4; IntAct=EBI-24256, EBI-13012;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:11254655, ECO:0000269|PubMed:14562095}.
CC -!- MISCELLANEOUS: Present with 656 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; U00030; AAB68370.1; -; Genomic_DNA.
DR EMBL; BK006934; DAA06897.1; -; Genomic_DNA.
DR PIR; S46693; S46693.
DR RefSeq; NP_012074.3; NM_001179335.3.
DR AlphaFoldDB; P38888; -.
DR SMR; P38888; -.
DR BioGRID; 36638; 37.
DR ComplexPortal; CPX-1283; HTM1-PDI1 exomannosidase complex.
DR DIP; DIP-1890N; -.
DR IntAct; P38888; 3.
DR MINT; P38888; -.
DR STRING; 4932.YHR204W; -.
DR CAZy; GH47; Glycoside Hydrolase Family 47.
DR MaxQB; P38888; -.
DR PaxDb; P38888; -.
DR PRIDE; P38888; -.
DR EnsemblFungi; YHR204W_mRNA; YHR204W; YHR204W.
DR GeneID; 856611; -.
DR KEGG; sce:YHR204W; -.
DR SGD; S000001247; MNL1.
DR VEuPathDB; FungiDB:YHR204W; -.
DR eggNOG; KOG2429; Eukaryota.
DR GeneTree; ENSGT00940000157717; -.
DR HOGENOM; CLU_003818_5_3_1; -.
DR InParanoid; P38888; -.
DR OMA; EIDYRYN; -.
DR BioCyc; MetaCyc:YHR204W-MON; -.
DR BioCyc; YEAST:YHR204W-MON; -.
DR UniPathway; UPA00378; -.
DR PRO; PR:P38888; -.
DR Proteomes; UP000002311; Chromosome VIII.
DR RNAct; P38888; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:SGD.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IEA:GOC.
DR GO; GO:0106055; C:mannosyl-oligosaccharide 1,2-alpha-mannosidase complex; IPI:ComplexPortal.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0030246; F:carbohydrate binding; IMP:SGD.
DR GO; GO:0004571; F:mannosyl-oligosaccharide 1,2-alpha-mannosidase activity; IDA:SGD.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:1904380; P:endoplasmic reticulum mannose trimming; IDA:ComplexPortal.
DR GO; GO:1904382; P:mannose trimming involved in glycoprotein ERAD pathway; IDA:SGD.
DR GO; GO:1900103; P:positive regulation of endoplasmic reticulum unfolded protein response; IDA:ComplexPortal.
DR GO; GO:0036508; P:protein alpha-1,2-demannosylation; IDA:SGD.
DR GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR GO; GO:0097466; P:ubiquitin-dependent glycoprotein ERAD pathway; IMP:SGD.
DR Gene3D; 1.50.10.10; -; 1.
DR InterPro; IPR012341; 6hp_glycosidase-like_sf.
DR InterPro; IPR044674; EDEM1/2/3.
DR InterPro; IPR001382; Glyco_hydro_47.
DR InterPro; IPR036026; Seven-hairpin_glycosidases.
DR PANTHER; PTHR45679; PTHR45679; 1.
DR Pfam; PF01532; Glyco_hydro_47; 1.
DR PRINTS; PR00747; GLYHDRLASE47.
DR SUPFAM; SSF48225; SSF48225; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Glycosidase; Hydrolase; Metal-binding;
KW Reference proteome; Signal; Unfolded protein response.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..796
FT /note="ER degradation-enhancing alpha-mannosidase-like
FT protein 1"
FT /id="PRO_0000210324"
FT ACT_SITE 372
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P31723"
FT BINDING 495
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P32906"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 517
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 672
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 762
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 796 AA; 91246 MW; D538E6F28D35BE80 CRC64;
MVCCLWVLLA LLLHLDHVAC EDDAYSFTSK ELKAYKQEVK ELFYFGFDNY LEHGYPYDEV
KPISCVPKKR NFEDPTDQGT NDILGNFTIT LIDSLTTIAI LEDRPQFLKA VRLVERTFPD
GNFDIDSTIQ VFEITIRVIG SLLSSHLYAT DPTKAVYLGD DYDGSLLRLA QNMADRLLPA
YLTSTGLPMP RRNIKRKWDV SEFPEFLETE NNVAAMASPM FEFTILSYLT GDPKYEKVTR
YAFDKTWSLR TGLDLLPMSF HPEKLTPYTP MTGIGASIDS LFEYALKGAI LFDDSELMEV
WNVAYEALKT NCKNDWFFAN VMADTGHLFV PWIDSLSAFF SGLQVLAGDL DDAIANHLMF
LKMWNTFGGI PERWNFSPPE FPPLSPLERS GAVALDNILP LEWYPLRPEF FESTYFLYRA
TKDPFYLNIG VHLLKDLKQR FKSNCGFAGF QNVITGELQD RMETFVLSET LKYLYLLFDE
ENELHNSASD VIFSTEAHPM WLPQEVRSNY KRNAKFNNSV YSSHLEICQK KDREQAGENT
LSQRIVGFAK SIFHKGPPDE EATDPIIDYT IDTELPGTCS IKPHHVIGDE FWYSPMLSNF
DRLFEIDSRF AATLIKPSHM HNYNAIELEP GFYNRWSNPQ FSTCLIPPTT EIFELLFDLP
GYHQLNPLML ENKTITFETF GGRSRLKIEK LQIYQIDYYG DLITASTFQD VSRKDIFSNA
CDAVASLYSP TYLYRVVAIN GRILPRHGSV QIKKHSPVLT SNGTREEDEF KMDGIGINDH
SQLMLECTPI INLFIV
