ID   MNS4_ARATH              Reviewed;         624 AA.
AC   Q9FG93;
DT   05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   03-AUG-2022, entry version 121.
DE   RecName: Full=Alpha-mannosidase I MNS4;
DE            EC=3.2.1.- {ECO:0000269|PubMed:24737672};
GN   Name=MNS4; OrderedLocusNames=At5g43710; ORFNames=MQD19.4, MQO24.4;
OS   Arabidopsis thaliana (Mouse-ear cress).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX   NCBI_TaxID=3702;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=cv. Columbia;
RA   Kaneko T., Katoh T., Asamizu E., Sato S., Nakamura Y., Kotani H.,
RA   Tabata S.;
RT   "Structural analysis of Arabidopsis thaliana chromosome 5. XI.";
RL   Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=cv. Columbia;
RX   PubMed=27862469; DOI=10.1111/tpj.13415;
RA   Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA   Town C.D.;
RT   "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT   genome.";
RL   Plant J. 89:789-804(2017).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=cv. Columbia;
RX   PubMed=14593172; DOI=10.1126/science.1088305;
RA   Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M.,
RA   Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G.,
RA   Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L.,
RA   Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C.,
RA   Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J.,
RA   Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A.,
RA   Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C.,
RA   Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X.,
RA   Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M.,
RA   Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K.,
RA   Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A.,
RA   Ecker J.R.;
RT   "Empirical analysis of transcriptional activity in the Arabidopsis
RT   genome.";
RL   Science 302:842-846(2003).
RN   [4]
RP   IDENTIFICATION.
RX   PubMed=20023195; DOI=10.1105/tpc.109.072363;
RA   Liebminger E., Huttner S., Vavra U., Fischl R., Schoberer J., Grass J.,
RA   Blaukopf C., Seifert G.J., Altmann F., Mach L., Strasser R.;
RT   "Class I alpha-mannosidases are required for N-glycan processing and root
RT   development in Arabidopsis thaliana.";
RL   Plant Cell 21:3850-3867(2009).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLU-376.
RX   PubMed=24737672; DOI=10.1105/tpc.114.123216;
RA   Huettner S., Veit C., Vavra U., Schoberer J., Liebminger E., Maresch D.,
RA   Grass J., Altmann F., Mach L., Strasser R.;
RT   "Arabidopsis class I alpha-mannosidases MNS4 and MNS5 are involved in
RT   endoplasmic reticulum-associated degradation of misfolded glycoproteins.";
RL   Plant Cell 26:1712-1728(2014).
CC   -!- FUNCTION: Can convert Man(9)GlcNAc(2) and Man(8)GlcNAc(2) into N-
CC       glycans with a terminal alpha-1,6-linked Man residue in the C-branch.
CC       Functions in the formation of unique N-glycan structures that are
CC       specifically recognized by components of the endoplasmic reticulum-
CC       associated degradation (ERAD) machinery, which leads to the degradation
CC       of misfolded glycoproteins. Most likely generates N-glycan signal on
CC       misfolded glycoproteins that is subsequently recognized by OS9.
CC       Required for ERAD of the heavily glycosylated and misfolded BRI1
CC       variants BRI1-5 and BRI1-9. Does not seem to play role in N-glycan
CC       processing of correctly folded proteins destined for secretion.
CC       {ECO:0000269|PubMed:24737672}.
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000250|UniProtKB:P45700};
CC   -!- PATHWAY: Protein modification; protein glycosylation. {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:24737672}; Single-pass type II membrane protein
CC       {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 47 family. {ECO:0000305}.
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DR   EMBL; AB026651; BAB11298.1; -; Genomic_DNA.
DR   EMBL; CP002688; AED94999.1; -; Genomic_DNA.
DR   EMBL; AF370128; AAK43943.1; -; mRNA.
DR   EMBL; AY040044; AAK64102.1; -; mRNA.
DR   RefSeq; NP_199184.1; NM_123737.3.
DR   AlphaFoldDB; Q9FG93; -.
DR   SMR; Q9FG93; -.
DR   STRING; 3702.AT5G43710.1; -.
DR   CAZy; GH47; Glycoside Hydrolase Family 47.
DR   TCDB; 3.A.16.1.5; the endoplasmic reticular retrotranslocon (er-rt) family.
DR   PaxDb; Q9FG93; -.
DR   PRIDE; Q9FG93; -.
DR   ProteomicsDB; 238295; -.
DR   EnsemblPlants; AT5G43710.1; AT5G43710.1; AT5G43710.
DR   GeneID; 834391; -.
DR   Gramene; AT5G43710.1; AT5G43710.1; AT5G43710.
DR   KEGG; ath:AT5G43710; -.
DR   Araport; AT5G43710; -.
DR   TAIR; locus:2170872; AT5G43710.
DR   eggNOG; KOG2429; Eukaryota.
DR   HOGENOM; CLU_003818_5_5_1; -.
DR   InParanoid; Q9FG93; -.
DR   OrthoDB; 434316at2759; -.
DR   PhylomeDB; Q9FG93; -.
DR   UniPathway; UPA00378; -.
DR   PRO; PR:Q9FG93; -.
DR   Proteomes; UP000006548; Chromosome 5.
DR   ExpressionAtlas; Q9FG93; baseline and differential.
DR   Genevisible; Q9FG93; AT.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:TAIR.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IEA:GOC.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0004559; F:alpha-mannosidase activity; IMP:TAIR.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0004571; F:mannosyl-oligosaccharide 1,2-alpha-mannosidase activity; IEA:InterPro.
DR   GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR   GO; GO:1904380; P:endoplasmic reticulum mannose trimming; IBA:GO_Central.
DR   GO; GO:1904382; P:mannose trimming involved in glycoprotein ERAD pathway; IBA:GO_Central.
DR   GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway.
DR   GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:TAIR.
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; Hydrolase; Membrane; Metal-binding;
KW   Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT   CHAIN           1..624
FT                   /note="Alpha-mannosidase I MNS4"
FT                   /id="PRO_0000397936"
FT   TOPO_DOM        1..7
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        8..28
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        29..624
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   REGION          574..624
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        586..624
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        122
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        262
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        355
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P31723"
FT   ACT_SITE        376
FT                   /evidence="ECO:0000250"
FT   BINDING         466
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P32906"
FT   CARBOHYD        115
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        494
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   MUTAGEN         376
FT                   /note="E->Q: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:24737672"
SQ   SEQUENCE   624 AA;  70096 MW;  07BF24D5BB347CA9 CRC64;
     MDSNFKWLLF AILISLTFSG FVLHHGVLAE SVKPDEAKQL RDEVRGMFYH AFDGYMNNAF
     PLDELRPLSC QGEDTLGGYA LTLIDSLDTL ALLGDRERFT SSVEWIGKNL QFNINKTVSV
     FETTIRVLGG LLSAHLIASD YATGMRIPSY NNELLVLAEN LARRMLPAFD TPTGIPFGSV
     NLMYGVDKHE SKITSTAGGG TLSLEFGVLS RLTNDPVFEQ VAKNAVRGLW ARRSNLDLVG
     AHINVFTGEW TQKDAGIGTS IDSFYEYLLK AYILFGDEEY LYIFQEAYRS AMQYLHKDPW
     YVEVNMDSAA IVWPVFNSLQ AFWPGLQVLA GDVDPAIRTH TAFFSVWKRY GFTPEGFNLA
     TLSVQYGQKS YPLRPELIES TYWLYKATRD PRYLDAGRDF VASLQYGAKC PCGYCHITDV
     ELHKQEDHME SFFLAETVKY LWLLFDLAVD SDNLVDNGPY KYIFSTEGHL LPITPQISLA
     REHCSYFGGY CPSNSTKLEQ EVLGEDSSND DHSNDYPYHE SFPVTGLIKG LCPGLTHAQK
     YGFSYVLPEK TDREDVNQPK PVVTSSSIVL ISDQTVEKRP QEEEGFTSQS EPIMTISGGS
     SNDQTGQELT LLESETDDQR SYSS