MA1A1_MOUSE
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 03-AUG-2022, entry version 173.
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=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:0000250|UniProtKB:P32906};
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: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_008548.4.
DR RefSeq; XP_006512632.1; XM_006512569.3.
DR PDB; 1NXC; X-ray; 1.51 A; A=178-655.
DR PDB; 5KKB; X-ray; 1.77 A; A/B=176-644.
DR PDBsum; 1NXC; -.
DR PDBsum; 5KKB; -.
DR AlphaFoldDB; P45700; -.
DR SMR; P45700; -.
DR STRING; 10090.ENSMUSP00000003843; -.
DR CAZy; GH47; Glycoside Hydrolase Family 47.
DR GlyGen; P45700; 1 site.
DR iPTMnet; P45700; -.
DR PhosphoSitePlus; P45700; -.
DR EPD; P45700; -.
DR jPOST; P45700; -.
DR PaxDb; P45700; -.
DR PeptideAtlas; P45700; -.
DR PRIDE; P45700; -.
DR ProteomicsDB; 291989; -.
DR Antibodypedia; 32605; 80 antibodies from 18 providers.
DR DNASU; 17155; -.
DR Ensembl; ENSMUST00000003843; ENSMUSP00000003843; ENSMUSG00000003746.
DR Ensembl; ENSMUST00000105470; ENSMUSP00000101110; ENSMUSG00000003746.
DR GeneID; 17155; -.
DR KEGG; mmu:17155; -.
DR UCSC; uc007fbw.1; mouse.
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; MEMKHEF; -.
DR OrthoDB; 693882at2759; -.
DR PhylomeDB; P45700; -.
DR TreeFam; TF313420; -.
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 72 CRISPR screens.
DR ChiTaRS; Man1a; mouse.
DR EvolutionaryTrace; P45700; -.
DR PRO; PR:P45700; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P45700; protein.
DR Bgee; ENSMUSG00000003746; Expressed in parotid gland and 284 other tissues.
DR ExpressionAtlas; P45700; baseline and differential.
DR Genevisible; P45700; MM.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004571; F:mannosyl-oligosaccharide 1,2-alpha-mannosidase activity; ISO:MGI.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:1904382; P:mannose trimming involved in glycoprotein ERAD pathway; ISO:MGI.
DR GO; GO:0006491; P:N-glycan processing; IBA:GO_Central.
DR GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway.
DR GO; GO:0045047; P:protein targeting to ER; ISO:MGI.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISO:MGI.
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 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 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..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 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 606..610
FT /evidence="ECO:0007829|PDB:1NXC"
FT HELIX 612..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
