ID   MA1A1_MOUSE             Reviewed;         655 AA.
AC   P45700;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   02-SEP-2026, entry version 190.
DE   RecName: Full=Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA;
DE            EC=3.2.1.113 {ECO:0000250|UniProtKB:P32906};
DE   AltName: Full=Man(9)-alpha-mannosidase;
DE            Short=Man9-mannosidase;
DE   AltName: Full=Mannosidase alpha class 1A member 1;
DE   AltName: Full=Processing alpha-1,2-mannosidase IA;
DE            Short=Alpha-1,2-mannosidase IA;
GN   Name=Man1a1; Synonyms=Man1a;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ;
RX   PubMed=8144580; DOI=10.1016/s0021-9258(17)36964-8;
RA   Lal A., Schutzbach J.S., Forsee W.T., Neame P.J., Moremen K.W.;
RT   "Isolation and expression of murine and rabbit cDNAs encoding an alpha 1,2-
RT   mannosidase involved in the processing of asparagine-linked
RT   oligosaccharides.";
RL   J. Biol. Chem. 269:9872-9881(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Kidney;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   PROTEIN SEQUENCE OF 424-437, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=OF1; TISSUE=Hippocampus;
RA   Lubec G., Sunyer B., Chen W.-Q.;
RL   Submitted (JAN-2009) to UniProtKB.
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver, Pancreas, and Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [5] {ECO:0007744|PDB:1NXC}
RP   X-RAY CRYSTALLOGRAPHY (1.51 ANGSTROMS) OF 178-655, DISULFIDE BOND,
RP   CALCIUM-BINDING SITE, AND GLYCOSYLATION AT ASN-515.
RX   PubMed=15102839; DOI=10.1074/jbc.m403065200;
RA   Tempel W., Karaveg K., Liu Z.-J., Rose J., Wang B.C., Moremen K.W.;
RT   "Structure of mouse Golgi alpha-mannosidase IA reveals the molecular basis
RT   for substrate specificity among class 1 (family 47 glycosylhydrolase)
RT   alpha1,2-mannosidases.";
RL   J. Biol. Chem. 279:29774-29786(2004).
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   -!- CATALYTIC ACTIVITY:
CC       Reaction=N(4)-(alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-
CC         (1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-
CC         alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-
CC         GlcNAc-(1->4)-beta-D-GlcNAc)-L-asparaginyl-[protein] (N-glucan
CC         mannose isomer 9A1,2,3B1,2,3) + 4 H2O = N(4)-(alpha-D-Man-(1->3)-
CC         [alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-
CC         Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc)-L-asparaginyl-
CC         [protein] (N-glucan mannose isomer 5A1,2) + 4 beta-D-mannose;
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:0000250|UniProtKB:P32906};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=N(4)-(alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-
CC         (1->3)-[alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->6)]-
CC         alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-
CC         GlcNAc)-L-asparaginyl-[protein] (N-glucan mannose isomer 8A1,2,3B1,3)
CC         + 3 H2O = N(4)-(alpha-D-Man-(1->3)-[alpha-D-Man-(1->3)-[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         5A1,2) + 3 beta-D-mannose; 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:0000250|UniProtKB:P32906};
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000269|PubMed:15102839};
CC   -!- ACTIVITY REGULATION: Inhibited by both 1-deoxymannojirimycin and
CC       kifunensine. {ECO:0000250}.
CC   -!- PATHWAY: Protein modification; protein glycosylation.
CC       {ECO:0000250|UniProtKB:P32906}.
CC   -!- SUBCELLULAR LOCATION: Golgi apparatus membrane; Single-pass type II
CC       membrane protein.
CC   -!- PTM: N-linked glycan at Asn-515 consists of Man(6)-GlcNAc(2).
CC       {ECO:0000269|PubMed:15102839}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 47 family. {ECO:0000305}.
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DR   EMBL; U04299; AAA17747.1; -; mRNA.
DR   EMBL; BC015265; AAH15265.1; -; mRNA.
DR   CCDS; CCDS23848.1; -.
DR   PIR; A54408; A54408.
DR   RefSeq; NP_032574.1; NM_008548.5.
DR   RefSeq; XP_006512632.1; XM_006512569.5.
DR   PDB; 1NXC; X-ray; 1.51 A; A=178-655.
DR   PDB; 5KKB; X-ray; 1.77 A; A/B=176-644.
DR   AlphaFoldDB; P45700; -.
DR   SMR; P45700; -.
DR   FunCoup; P45700; 3937.
DR   STRING; 10090.ENSMUSP00000003843; -.
DR   CAZy; GH47; Glycoside Hydrolase Family 47.
DR   GlyCosmos; P45700; 1 site, No reported glycans.
DR   GlyGen; P45700; 1 site, 1 N-linked glycan (1 site).
DR   iPTMnet; P45700; -.
DR   PhosphoSitePlus; P45700; -.
DR   jPOST; P45700; -.
DR   PaxDb; 10090-ENSMUSP00000003843; -.
DR   PeptideAtlas; P45700; -.
DR   ProteomicsDB; 291989; -.
DR   Pumba; P45700; -.
DR   Antibodypedia; 32605; 84 antibodies from 20 providers.
DR   DNASU; 17155; -.
DR   Ensembl; ENSMUST00000003843.16; ENSMUSP00000003843.9; ENSMUSG00000003746.17.
DR   Ensembl; ENSMUST00000105470.9; ENSMUSP00000101110.2; ENSMUSG00000003746.17.
DR   GeneID; 17155; -.
DR   KEGG; mmu:17155; -.
DR   UCSC; uc007fbw.1; mouse.
DR   AGR; MGI:104677; -.
DR   CTD; 17155; -.
DR   MGI; MGI:104677; Man1a.
DR   VEuPathDB; HostDB:ENSMUSG00000003746; -.
DR   eggNOG; KOG2204; Eukaryota.
DR   GeneTree; ENSGT00940000158188; -.
DR   HOGENOM; CLU_003818_3_2_1; -.
DR   InParanoid; P45700; -.
DR   OMA; WRMFKNI; -.
DR   OrthoDB; 8118055at2759; -.
DR   PhylomeDB; P45700; -.
DR   BRENDA; 3.2.1.113; 3474.
DR   BRENDA; 3.2.1.209; 3474.
DR   Reactome; R-MMU-964827; Progressive trimming of alpha-1,2-linked mannose residues from Man9/8/7GlcNAc2 to produce Man5GlcNAc2.
DR   UniPathway; UPA00378; -.
DR   BioGRID-ORCS; 17155; 3 hits in 77 CRISPR screens.
DR   EvolutionaryTrace; P45700; -.
DR   PRO; PR:P45700; -.
DR   Proteomes; UP000000589; Chromosome 10.
DR   RNAct; P45700; protein.
DR   Bgee; ENSMUSG00000003746; Expressed in parotid gland and 285 other cell types or tissues.
DR   ExpressionAtlas; P45700; baseline and differential.
DR   GO; GO:0031410; C:cytoplasmic vesicle; ISO:GO_Central.
DR   GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR   GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISO:GO_Central.
DR   GO; GO:0005794; C:Golgi apparatus; ISO:GO_Central.
DR   GO; GO:0000139; C:Golgi membrane; IDA:MGI.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0004571; F:mannosyl-oligosaccharide 1,2-alpha-mannosidase activity; ISS:UniProtKB.
DR   GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR   GO; GO:0036503; P:ERAD pathway; ISO:GO_Central.
DR   GO; GO:1904382; P:mannose trimming involved in glycoprotein ERAD pathway; ISO:GO_Central.
DR   GO; GO:0045047; P:protein targeting to ER; ISO:GO_Central.
DR   FunFam; 1.50.10.10:FF:000002; alpha-1,2-Mannosidase; 1.
DR   Gene3D; 1.50.10.10; -; 1.
DR   InterPro; IPR012341; 6hp_glycosidase-like_sf.
DR   InterPro; IPR001382; Glyco_hydro_47.
DR   InterPro; IPR050749; Glycosyl_Hydrolase_47.
DR   InterPro; IPR036026; Seven-hairpin_glycosidases.
DR   PANTHER; PTHR11742:SF31; MANNOSYL-OLIGOSACCHARIDE 1,2-ALPHA-MANNOSIDASE IA; 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.
DR   PDBsum; 1NXC; -.
DR   PDBsum; 5KKB; -.
PE   1: Evidence at protein level;
KW   3D-structure; Calcium; Direct protein sequencing; Disulfide bond;
KW   Glycoprotein; Glycosidase; Golgi apparatus; Hydrolase; Membrane;
KW   Metal-binding; Reference proteome; Signal-anchor; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..655
FT                   /note="Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA"
FT                   /id="PRO_0000210309"
FT   TOPO_DOM        1..43
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        44..64
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        65..655
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        524
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P31723"
FT   BINDING         635
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:15102839,
FT                   ECO:0007744|PDB:1NXC"
FT   CARBOHYD        515
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:15102839,
FT                   ECO:0007744|PDB:1NXC"
FT   DISULFID        478..510
FT                   /evidence="ECO:0000269|PubMed:15102839,
FT                   ECO:0007744|PDB:1NXC"
FT   HELIX           187..189
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           192..216
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          219..223
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   TURN            224..227
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          228..230
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           233..235
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           241..252
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           256..269
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          275..279
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           280..283
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           284..288
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           289..298
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           301..314
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           315..318
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          320..323
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           324..326
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          327..330
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   TURN            331..333
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          335..337
FT                   /evidence="ECO:0007829|PDB:5KKB"
FT   HELIX           343..345
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           349..352
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           356..366
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           370..384
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           388..390
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          394..396
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   TURN            398..400
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   TURN            412..414
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           415..427
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   TURN            428..430
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           433..449
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          451..453
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          459..461
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          463..465
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          468..470
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          472..474
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           476..479
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           480..486
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   TURN            487..490
FT                   /evidence="ECO:0007829|PDB:5KKB"
FT   HELIX           496..515
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          517..521
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          524..529
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          533..535
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           539..541
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           549..561
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           564..580
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          595..597
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           608..612
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   HELIX           613..619
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   TURN            628..630
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          631..633
FT                   /evidence="ECO:0007829|PDB:1NXC"
FT   STRAND          639..641
FT                   /evidence="ECO:0007829|PDB:1NXC"
SQ   SEQUENCE   655 AA;  73276 MW;  15AF658364930BF4 CRC64;
     MPVGGLLPLF SSPGGGGLGS GLGGGLGGGR KGSGPAAFRL TEKFVLLLVF SAFITLCFGA
     IFFLPDSSKL LSGVLFHSNP ALQPPAEHKP GLGARAEDAA EGRVRHREEG APGDPGAGLE
     DNLARIRENH ERALREAKET LQKLPEEIQR DILLEKEKVA QDQLRDKDLF RGLPKVDFLP
     PVGVENREPA DATIREKRAK IKEMMTHAWN NYKRYAWGLN ELKPISKEGH SSSLFGNIKG
     ATIVDALDTL FIMGMKTEFQ EAKSWIKKYL DFNVNAEVSV FEVNIRFVGG LLSAYYLSGE
     EIFRKKAVEL GVKLLPAFHT PSGIPWALLN MKSGIGRNWP WASGGSSILA EFGTLHLEFM
     HLSHLSGDPV FAEKVMKIRT VLNKLDKPEG LYPNYLNPSS GQWGQHHVSV GGLGDSFYEY
     LLKAWLMSDK TDLEAKKMYF DAVQAIETHL IRKSSGGLTY IAEWKGGLLE HKMGHLTCFA
     GGMFALGADG APEARAQHYL ELGAEIARTC HESYNRTYVK LGPEAFRFDG GVEAIATRQN
     EKYYILRPEV IETYMYMWRL THDPKYRTWA WEAVEALESH CRVNGGYSGL RDVYIARESY
     DDVQQSFFLA ETLKYLYLIF SDDDLLPLEH WIFNTEAHPF PILREQKKEI DGKEK
//