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 10-JUN-2026, entry version 222. 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=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:0000269|PubMed:10409699, ECO:0000269|PubMed:12090241, CC ECO:0000269|PubMed:15713668}; 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: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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_016219.5. 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; 138. DR FunCoup; Q9UKM7; 3134. DR IntAct; Q9UKM7; 58. DR MINT; Q9UKM7; -. DR NDEx; IQUERY-CP-MAN1B1; 1 NDEx IQuery Curated Pathway. 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 GlyCosmos; Q9UKM7; 3 sites, 2 glycans. DR GlyGen; Q9UKM7; 16 sites, 4 O-linked glycans (15 sites). DR iPTMnet; Q9UKM7; -. DR PhosphoSitePlus; Q9UKM7; -. DR SwissPalm; Q9UKM7; -. DR BioMuta; MAN1B1; -. DR DMDM; 93195043; -. DR jPOST; Q9UKM7; -. DR MassIVE; Q9UKM7; -. DR PaxDb; 9606-ENSP00000360645; -. DR PeptideAtlas; Q9UKM7; -. DR ProteomicsDB; 84820; -. DR Pumba; Q9UKM7; -. DR Antibodypedia; 32359; 137 antibodies from 24 providers. DR DNASU; 11253; -. DR Ensembl; ENST00000371589.9; ENSP00000360645.4; ENSG00000177239.17. 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 AGR; HGNC:6823; -. DR ClinPGx; PA30572; -. 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 OpenTargets; ENSG00000177239; -. DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability. DR Orphanet; 397941; MAN1B1-CDG. 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; 8118055at2759; -. DR PAN-GO; Q9UKM7; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q9UKM7; -. DR BioCyc; MetaCyc:HS11144-MONOMER; -. 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 Agora; ENSG00000177239; -. DR BioGRID-ORCS; 11253; 28 hits in 1158 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 188 other cell types or tissues. DR ExpressionAtlas; Q9UKM7; baseline and differential. 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; IDA:FlyBase. 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: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; IDA:ParkinsonsUK-UCL. DR GO; GO:0140277; P:endoplasmic reticulum N-glycan trimming; IMP:FlyBase. DR GO; GO:0036503; P:ERAD pathway; IDA:ParkinsonsUK-UCL. DR GO; GO:0009311; P:oligosaccharide metabolic process; TAS:ProtInc. DR GO; GO:0036510; P:trimming of terminal mannose on C branch; TAS:Reactome. DR GO; GO:0019082; P:viral protein processing; TAS:Reactome. DR FunFam; 1.50.10.10:FF:000010; 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:SF55; ENDOPLASMIC RETICULUM MANNOSYL-OLIGOSACCHARIDE 1,2-ALPHA-MANNOSIDASE; 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. 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; Proteomics identification; Reference proteome; KW Signal-anchor; Transmembrane; 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 176..201 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 FT 1000-fold reduction in binding affinity for the inhibitor, FT dMNJ. Significant reductions in K(cat) and slight increase FT in 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..331 FT /evidence="ECO:0007829|PDB:1X9D" FT HELIX 332..336 FT /evidence="ECO:0007829|PDB:1X9D" FT HELIX 337..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 HELIX 372..374 FT /evidence="ECO:0007829|PDB:1X9D" 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 660..664 FT /evidence="ECO:0007829|PDB:1X9D" FT HELIX 665..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 //