MA1B1_HUMAN
ID MA1B1_HUMAN Reviewed; 699 AA.
AC Q9UKM7; Q5VSG3; Q9BRS9; Q9Y5K7;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase;
DE EC=3.2.1.113 {ECO:0000269|PubMed:10409699, ECO:0000269|PubMed:12090241, ECO:0000269|PubMed:15713668};
DE AltName: Full=ER alpha-1,2-mannosidase;
DE AltName: Full=ER mannosidase 1;
DE Short=ERMan1;
DE AltName: Full=Man9GlcNAc2-specific-processing alpha-mannosidase;
DE AltName: Full=Mannosidase alpha class 1B member 1;
GN Name=MAN1B1; ORFNames=UNQ747/PRO1477;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP SPECIFICITY, AND VARIANT SER-59.
RC TISSUE=Fetal brain, Liver, Placenta, and Testis;
RX PubMed=10521544; DOI=10.1093/glycob/9.10.1073;
RA Tremblay L.O., Herscovics A.;
RT "Cloning and expression of a specific human alpha1,2-mannosidase that trims
RT Man9GlcNAc2 to Man8GlcNAc2 isomer B during N-glycan biosynthesis.";
RL Glycobiology 9:1073-1078(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 37-699, TISSUE SPECIFICITY, ENZYME ACTIVITY,
RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND VARIANT SER-59.
RX PubMed=10409699; DOI=10.1074/jbc.274.30.21375;
RA Gonzalez D.S., Karaveg K., Vandersall-Nairn A.S., Lal A., Moremen K.W.;
RT "Identification, expression, and characterization of a cDNA encoding human
RT endoplasmic reticulum mannosidase I, the enzyme that catalyzes the first
RT mannose trimming step in mammalian Asn-linked oligosaccharide
RT biosynthesis.";
RL J. Biol. Chem. 274:21375-21386(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-59.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-59.
RC TISSUE=Lung, and Placenta;
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
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 [7]
RP FUNCTION.
RX PubMed=18003979; DOI=10.1091/mbc.e07-05-0505;
RA Avezov E., Frenkel Z., Ehrlich M., Herscovics A., Lederkremer G.Z.;
RT "Endoplasmic reticulum (ER) mannosidase I is compartmentalized and required
RT for N-glycan trimming to Man5-6GlcNAc2 in glycoprotein ER-associated
RT degradation.";
RL Mol. Biol. Cell 19:216-225(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 243-699, AND DISULFIDE BOND.
RX PubMed=10995765; DOI=10.1074/jbc.m006927200;
RA Vallee F., Karaveg K., Herscovics A., Moremen K.W., Howell P.L.;
RT "Structural basis for catalysis and inhibition of N-glycan processing class
RT I alpha 1,2-mannosidases.";
RL J. Biol. Chem. 275:41287-41298(2000).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.41 ANGSTROMS) OF 172-699 IN COMPLEX WITH A
RP THIO-DISACCHARIDE SUBSTRATE ANALOG, ENZYME ACTIVITY, AND MUTAGENESIS OF
RP GLU-330; ASP-463; HIS-524 AND GLU-599.
RX PubMed=15713668; DOI=10.1074/jbc.m500119200;
RA Karaveg K., Siriwardena A., Tempel W., Liu Z.J., Glushka J., Wang B.C.,
RA Moremen K.W.;
RT "Mechanism of class 1 (glycosylhydrolase family 47) {alpha}-mannosidases
RT involved in N-glycan processing and endoplasmic reticulum quality
RT control.";
RL J. Biol. Chem. 280:16197-16207(2005).
RN [11]
RP VARIANTS RAFQS CYS-334 AND LYS-397, AND CHARACTERIZATION OF VARIANTS RAFQS
RP CYS-334 AND LYS-397.
RX PubMed=21763484; DOI=10.1016/j.ajhg.2011.06.006;
RA Rafiq M.A., Kuss A.W., Puettmann L., Noor A., Ramiah A., Ali G., Hu H.,
RA Kerio N.A., Xiang Y., Garshasbi M., Khan M.A., Ishak G.E., Weksberg R.,
RA Ullmann R., Tzschach A., Kahrizi K., Mahmood K., Naeem F., Ayub M.,
RA Moremen K.W., Vincent J.B., Ropers H.H., Ansar M., Najmabadi H.;
RT "Mutations in the alpha 1,2-mannosidase gene, MAN1B1, cause autosomal-
RT recessive intellectual disability.";
RL Am. J. Hum. Genet. 89:176-182(2011).
CC -!- FUNCTION: Involved in glycoprotein quality control targeting of
CC misfolded glycoproteins for degradation. It primarily trims a single
CC alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce
CC Man(8)GlcNAc(2), but at high enzyme concentrations, as found in the ER
CC quality control compartment (ERQC), it further trims the carbohydrates
CC to Man(5-6)GlcNAc(2). {ECO:0000269|PubMed:12090241,
CC ECO:0000269|PubMed:18003979}.
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:10409699, ECO:0000269|PubMed:12090241,
CC ECO:0000269|PubMed:15713668};
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:10409699,
CC ECO:0000269|PubMed:12090241, ECO:0000269|PubMed:15713668};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P45700};
CC -!- ACTIVITY REGULATION: Inhibited by both 1-deoxymannojirimycin (dMNJ) and
CC kifunensine. {ECO:0000269|PubMed:10409699}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.4 mM for Man9GlcNAc2 {ECO:0000269|PubMed:10521544};
CC pH dependence:
CC Optimum pH is between 6.5 and 6.9. {ECO:0000269|PubMed:10521544};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000250|UniProtKB:P32906}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10409699}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:10409699}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10409699,
CC ECO:0000269|PubMed:10521544}.
CC -!- DISEASE: Rafiq syndrome (RAFQS) [MIM:614202]: An autosomal recessive
CC disorder characterized by variably impaired intellectual and motor
CC development, a characteristic facial dysmorphism, truncal obesity, and
CC hypotonia. The facial dysmorphism comprises prominent eyebrows with
CC lateral thinning, downward-slanting palpebral fissures, bulbous tip of
CC the nose, large ears, and a thin upper lip. Behavioral problems,
CC including overeating, verbal and physical aggression, have been
CC reported in some cases. Serum transferrin isoelectric focusing shows a
CC type 2 pattern. {ECO:0000269|PubMed:21763484}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 47 family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-37 is the initiator.
CC {ECO:0000305}.
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DR EMBL; AF148509; AAF03215.1; -; mRNA.
DR EMBL; AF145732; AAD45504.1; -; mRNA.
DR EMBL; AY358465; AAQ88830.1; -; mRNA.
DR EMBL; AL929554; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL807752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002953; AAH02953.1; -; mRNA.
DR EMBL; BC006079; AAH06079.1; -; mRNA.
DR CCDS; CCDS7029.1; -.
DR RefSeq; NP_057303.2; NM_016219.4.
DR PDB; 1FMI; X-ray; 1.90 A; A=243-697.
DR PDB; 1FO2; X-ray; 2.38 A; A=243-699.
DR PDB; 1FO3; X-ray; 1.75 A; A=243-699.
DR PDB; 1X9D; X-ray; 1.41 A; A=172-699.
DR PDB; 5KIJ; X-ray; 1.65 A; A=245-696.
DR PDB; 5KK7; X-ray; 1.73 A; A/B=245-699.
DR PDBsum; 1FMI; -.
DR PDBsum; 1FO2; -.
DR PDBsum; 1FO3; -.
DR PDBsum; 1X9D; -.
DR PDBsum; 5KIJ; -.
DR PDBsum; 5KK7; -.
DR AlphaFoldDB; Q9UKM7; -.
DR SMR; Q9UKM7; -.
DR BioGRID; 116414; 106.
DR IntAct; Q9UKM7; 11.
DR MINT; Q9UKM7; -.
DR STRING; 9606.ENSP00000360645; -.
DR BindingDB; Q9UKM7; -.
DR ChEMBL; CHEMBL2308; -.
DR DrugBank; DB01955; 1,4-Butanediol.
DR DrugBank; DB03206; Duvoglustat.
DR DrugBank; DB02742; Kifunensine.
DR DrugBank; DB02422; Methyl-2-S-(Alpha-D-Mannopyranosyl)-2-Thio-Alpha-D-Mannopyranoside.
DR CAZy; GH47; Glycoside Hydrolase Family 47.
DR GlyGen; Q9UKM7; 4 sites, 2 O-linked glycans (3 sites).
DR iPTMnet; Q9UKM7; -.
DR PhosphoSitePlus; Q9UKM7; -.
DR SwissPalm; Q9UKM7; -.
DR BioMuta; MAN1B1; -.
DR DMDM; 93195043; -.
DR EPD; Q9UKM7; -.
DR jPOST; Q9UKM7; -.
DR MassIVE; Q9UKM7; -.
DR MaxQB; Q9UKM7; -.
DR PaxDb; Q9UKM7; -.
DR PeptideAtlas; Q9UKM7; -.
DR PRIDE; Q9UKM7; -.
DR ProteomicsDB; 84820; -.
DR Antibodypedia; 32359; 145 antibodies from 24 providers.
DR DNASU; 11253; -.
DR Ensembl; ENST00000371589.9; ENSP00000360645.4; ENSG00000177239.16.
DR GeneID; 11253; -.
DR KEGG; hsa:11253; -.
DR MANE-Select; ENST00000371589.9; ENSP00000360645.4; NM_016219.5; NP_057303.2.
DR UCSC; uc004cld.3; human.
DR CTD; 11253; -.
DR DisGeNET; 11253; -.
DR GeneCards; MAN1B1; -.
DR HGNC; HGNC:6823; MAN1B1.
DR HPA; ENSG00000177239; Low tissue specificity.
DR MalaCards; MAN1B1; -.
DR MIM; 604346; gene.
DR MIM; 614202; phenotype.
DR neXtProt; NX_Q9UKM7; -.
DR OpenTargets; ENSG00000177239; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR Orphanet; 397941; MAN1B1-CDG.
DR PharmGKB; PA30572; -.
DR VEuPathDB; HostDB:ENSG00000177239; -.
DR eggNOG; KOG2431; Eukaryota.
DR GeneTree; ENSGT00940000155422; -.
DR HOGENOM; CLU_003818_3_3_1; -.
DR InParanoid; Q9UKM7; -.
DR OMA; AAFKHSW; -.
DR OrthoDB; 693882at2759; -.
DR PhylomeDB; Q9UKM7; -.
DR TreeFam; TF354274; -.
DR BioCyc; MetaCyc:HS11144-MON; -.
DR BRENDA; 3.2.1.113; 2681.
DR BRENDA; 3.2.1.209; 2681.
DR PathwayCommons; Q9UKM7; -.
DR Reactome; R-HSA-4793950; Defective MAN1B1 causes MRT15.
DR Reactome; R-HSA-901032; ER Quality Control Compartment (ERQC).
DR Reactome; R-HSA-9694548; Maturation of spike protein.
DR SABIO-RK; Q9UKM7; -.
DR SignaLink; Q9UKM7; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 11253; 16 hits in 1080 CRISPR screens.
DR ChiTaRS; MAN1B1; human.
DR EvolutionaryTrace; Q9UKM7; -.
DR GeneWiki; MAN1B1; -.
DR GenomeRNAi; 11253; -.
DR Pharos; Q9UKM7; Tchem.
DR PRO; PR:Q9UKM7; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9UKM7; protein.
DR Bgee; ENSG00000177239; Expressed in stromal cell of endometrium and 186 other tissues.
DR ExpressionAtlas; Q9UKM7; baseline and differential.
DR Genevisible; Q9UKM7; HS.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IDA:ParkinsonsUK-UCL.
DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; TAS:ParkinsonsUK-UCL.
DR GO; GO:0016021; C:integral component of membrane; TAS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; TAS:UniProtKB.
DR GO; GO:0004571; F:mannosyl-oligosaccharide 1,2-alpha-mannosidase activity; IDA:UniProtKB.
DR GO; GO:1904380; P:endoplasmic reticulum mannose trimming; IMP:ParkinsonsUK-UCL.
DR GO; GO:1904382; P:mannose trimming involved in glycoprotein ERAD pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006491; P:N-glycan processing; IBA:GO_Central.
DR GO; GO:0009311; P:oligosaccharide metabolic process; TAS:ProtInc.
DR GO; GO:0036508; P:protein alpha-1,2-demannosylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway.
DR GO; GO:0036511; P:trimming of first mannose on A branch; TAS:Reactome.
DR GO; GO:0036512; P:trimming of second mannose on A branch; TAS:Reactome.
DR GO; GO:0036509; P:trimming of terminal mannose on B branch; IDA:ParkinsonsUK-UCL.
DR GO; GO:0036510; P:trimming of terminal mannose on C branch; TAS:Reactome.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:UniProtKB.
DR GO; GO:0019082; P:viral protein processing; TAS:Reactome.
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; Disease variant; Disulfide bond;
KW Endoplasmic reticulum; Glycosidase; Hydrolase; Intellectual disability;
KW Membrane; Metal-binding; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..699
FT /note="Endoplasmic reticulum mannosyl-oligosaccharide 1,2-
FT alpha-mannosidase"
FT /id="PRO_0000210314"
FT TOPO_DOM 1..84
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 85..105
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 106..699
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 125..243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 147..162
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..197
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 330
FT /note="Proton donor"
FT /evidence="ECO:0000305"
FT ACT_SITE 463
FT /evidence="ECO:0000305"
FT ACT_SITE 570
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P31723"
FT ACT_SITE 599
FT /evidence="ECO:0000305"
FT BINDING 688
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P32906"
FT DISULFID 527..556
FT /evidence="ECO:0000269|PubMed:10995765"
FT VARIANT 59
FT /note="N -> S (in dbSNP:rs968733)"
FT /evidence="ECO:0000269|PubMed:10409699,
FT ECO:0000269|PubMed:10521544, ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_055841"
FT VARIANT 334
FT /note="R -> C (in RAFQS; results in about 1300-fold
FT decrease in activity; dbSNP:rs387906886)"
FT /evidence="ECO:0000269|PubMed:21763484"
FT /id="VAR_066592"
FT VARIANT 397
FT /note="E -> K (in RAFQS; disrupts stable protein
FT expression; dbSNP:rs387906885)"
FT /evidence="ECO:0000269|PubMed:21763484"
FT /id="VAR_066593"
FT MUTAGEN 330
FT /note="E->Q: About 44-fold reduction in K(cat), slight
FT reduction in K(m), about 100-fold increase in binding
FT affinity for Man(9)GlcnAc(2) but no change in binding
FT affinity for the inhibitor, dMNJ. Even further greater
FT reduction in K(cat) and increase in K(m); when associated
FT with Q-599."
FT /evidence="ECO:0000269|PubMed:15713668"
FT MUTAGEN 463
FT /note="D->N: Some reduction in K(cat) but no change in
FT K(m), abolishes almost all binding to Man(9)GlcnAc(2) but
FT reduced binding to the inhibitor dMNJ by about 73-fold.
FT Further reduction in K(m) but slight increase in K(m); when
FT associated with Q-599."
FT /evidence="ECO:0000269|PubMed:15713668"
FT MUTAGEN 524
FT /note="H->A: About 4-fold reduction in K(cat)."
FT /evidence="ECO:0000269|PubMed:15713668"
FT MUTAGEN 599
FT /note="E->Q: Very significant reduction in K(cat), 4-fold
FT weaker binding affinity for Man(9)GlcnAc(2) but about 1000-
FT fold reduction in binding affinity for the inhibitor, dMNJ.
FT Significant reductions in K(cat) and slight increase in
FT K(m); when associated with E-330 or N-463."
FT /evidence="ECO:0000269|PubMed:15713668"
FT CONFLICT 204
FT /note="T -> A (in Ref. 2; AAD45504)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="S -> P (in Ref. 2; AAD45504)"
FT /evidence="ECO:0000305"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:1FO3"
FT HELIX 248..267
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 271..275
FT /evidence="ECO:0007829|PDB:1X9D"
FT TURN 276..279
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 284..287
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 289..300
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 304..317
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 328..346
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 349..362
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 363..366
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 368..370
FT /evidence="ECO:0007829|PDB:1FO3"
FT STRAND 375..378
FT /evidence="ECO:0007829|PDB:1X9D"
FT TURN 379..381
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 391..394
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 395..399
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 402..412
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 416..429
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 441..444
FT /evidence="ECO:0007829|PDB:1X9D"
FT TURN 445..447
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 450..452
FT /evidence="ECO:0007829|PDB:1X9D"
FT TURN 460..462
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 463..475
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 481..497
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 499..501
FT /evidence="ECO:0007829|PDB:1X9D"
FT TURN 503..505
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 508..510
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 512..514
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 517..519
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 521..523
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 524..527
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 528..538
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 543..561
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 563..566
FT /evidence="ECO:0007829|PDB:1FO2"
FT STRAND 570..573
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 584..586
FT /evidence="ECO:0007829|PDB:5KIJ"
FT HELIX 589..591
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 599..611
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 615..630
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 659..662
FT /evidence="ECO:0007829|PDB:1X9D"
FT HELIX 664..672
FT /evidence="ECO:0007829|PDB:1X9D"
FT TURN 676..679
FT /evidence="ECO:0007829|PDB:5KIJ"
FT TURN 681..683
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 684..686
FT /evidence="ECO:0007829|PDB:1X9D"
FT STRAND 692..694
FT /evidence="ECO:0007829|PDB:1X9D"
SQ SEQUENCE 699 AA; 79580 MW; B8BF3BE333D90261 CRC64;
MAACEGRRSG ALGSSQSDFL TPPVGGAPWA VATTVVMYPP PPPPPHRDFI SVTLSFGENY
DNSKSWRRRS CWRKWKQLSR LQRNMILFLL AFLLFCGLLF YINLADHWKA LAFRLEEEQK
MRPEIAGLKP ANPPVLPAPQ KADTDPENLP EISSQKTQRH IQRGPPHLQI RPPSQDLKDG
TQEEATKRQE APVDPRPEGD PQRTVISWRG AVIEPEQGTE LPSRRAEVPT KPPLPPARTQ
GTPVHLNYRQ KGVIDVFLHA WKGYRKFAWG HDELKPVSRS FSEWFGLGLT LIDALDTMWI
LGLRKEFEEA RKWVSKKLHF EKDVDVNLFE STIRILGGLL SAYHLSGDSL FLRKAEDFGN
RLMPAFRTPS KIPYSDVNIG TGVAHPPRWT SDSTVAEVTS IQLEFRELSR LTGDKKFQEA
VEKVTQHIHG LSGKKDGLVP MFINTHSGLF THLGVFTLGA RADSYYEYLL KQWIQGGKQE
TQLLEDYVEA IEGVRTHLLR HSEPSKLTFV GELAHGRFSA KMDHLVCFLP GTLALGVYHG
LPASHMELAQ ELMETCYQMN RQMETGLSPE IVHFNLYPQP GRRDVEVKPA DRHNLLRPET
VESLFYLYRV TGDRKYQDWG WEILQSFSRF TRVPSGGYSS INNVQDPQKP EPRDKMESFF
LGETLKYLFL LFSDDPNLLS LDAYVFNTEA HPLPIWTPA
