ID MA1A2_HUMAN Reviewed; 641 AA. AC O60476; Q9H510; DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 27-MAR-2024, entry version 191. DE RecName: Full=Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB; DE EC=3.2.1.113 {ECO:0000250|UniProtKB:P32906}; DE AltName: Full=Mannosidase alpha class 1A member 2; DE AltName: Full=Processing alpha-1,2-mannosidase IB; DE Short=Alpha-1,2-mannosidase IB; GN Name=MAN1A2; Synonyms=MAN1B; 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 [GENOMIC DNA]. RC TISSUE=Brain, and Placenta; RX PubMed=9592125; DOI=10.1093/glycob/8.6.585; RA Tremblay L.O., Campbell-Dyke N., Herscovics A.; RT "Molecular cloning, chromosomal mapping and tissue-specific expression of a RT novel human alpha-1,2-mannosidase gene involved in N-glycan maturation."; RL Glycobiology 8:585-595(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [4] RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). 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)-beta-D-GlcNAc)-L-asparaginyl-[protein] (N-glucan CC mannose isomer 9A1,2,3B1,2,3) = 4 beta-D-mannose + N(4)-(alpha-D-Man- CC (1->3)-[alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]- CC beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc)-L-asparaginyl- CC [protein] (N-glucan mannose isomer 5A1,2); Xref=Rhea:RHEA:56008, CC Rhea:RHEA-COMP:14356, Rhea:RHEA-COMP:14367, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:28563, ChEBI:CHEBI:59087, ChEBI:CHEBI:139493; CC EC=3.2.1.113; 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 beta-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:0000250|UniProtKB:P45700}; CC -!- ACTIVITY REGULATION: Inhibited by both 1-deoxymannojirimycin and CC kifunensine. 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 -!- TISSUE SPECIFICITY: Highest levels of expression in placenta and CC testis. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 47 family. {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; AF053626; AAC26201.1; -; Genomic_DNA. DR EMBL; AF053622; AAC26201.1; JOINED; Genomic_DNA. DR EMBL; AF053623; AAC26201.1; JOINED; Genomic_DNA. DR EMBL; AF053624; AAC26201.1; JOINED; Genomic_DNA. DR EMBL; AF053625; AAC26201.1; JOINED; Genomic_DNA. DR EMBL; AF027156; AAC26169.1; -; mRNA. DR EMBL; AF053621; AAC26200.1; -; Genomic_DNA. DR EMBL; AF053619; AAC26200.1; JOINED; Genomic_DNA. DR EMBL; AF053620; AAC26200.1; JOINED; Genomic_DNA. DR EMBL; AF053615; AAC26200.1; JOINED; Genomic_DNA. DR EMBL; AF053616; AAC26200.1; JOINED; Genomic_DNA. DR EMBL; AF053617; AAC26200.1; JOINED; Genomic_DNA. DR EMBL; AF053618; AAC26200.1; JOINED; Genomic_DNA. DR EMBL; AL157902; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL358072; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC063300; AAH63300.1; -; mRNA. DR CCDS; CCDS895.1; -. DR RefSeq; NP_006690.1; NM_006699.3. DR AlphaFoldDB; O60476; -. DR SMR; O60476; -. DR BioGRID; 116111; 50. DR IntAct; O60476; 20. DR MINT; O60476; -. DR STRING; 9606.ENSP00000348959; -. DR CAZy; GH47; Glycoside Hydrolase Family 47. DR GlyCosmos; O60476; 1 site, No reported glycans. DR GlyGen; O60476; 1 site. DR iPTMnet; O60476; -. DR PhosphoSitePlus; O60476; -. DR SwissPalm; O60476; -. DR BioMuta; MAN1A2; -. DR EPD; O60476; -. DR jPOST; O60476; -. DR MassIVE; O60476; -. DR MaxQB; O60476; -. DR PaxDb; 9606-ENSP00000348959; -. DR PeptideAtlas; O60476; -. DR ProteomicsDB; 49416; -. DR Pumba; O60476; -. DR Antibodypedia; 33890; 104 antibodies from 25 providers. DR DNASU; 10905; -. DR Ensembl; ENST00000356554.7; ENSP00000348959.3; ENSG00000198162.12. DR GeneID; 10905; -. DR KEGG; hsa:10905; -. DR MANE-Select; ENST00000356554.7; ENSP00000348959.3; NM_006699.5; NP_006690.1. DR UCSC; uc001ehd.2; human. DR AGR; HGNC:6822; -. DR CTD; 10905; -. DR DisGeNET; 10905; -. DR GeneCards; MAN1A2; -. DR HGNC; HGNC:6822; MAN1A2. DR HPA; ENSG00000198162; Low tissue specificity. DR MIM; 604345; gene. DR neXtProt; NX_O60476; -. DR OpenTargets; ENSG00000198162; -. DR PharmGKB; PA30571; -. DR VEuPathDB; HostDB:ENSG00000198162; -. DR eggNOG; KOG2204; Eukaryota. DR GeneTree; ENSGT00940000157498; -. DR HOGENOM; CLU_003818_3_2_1; -. DR InParanoid; O60476; -. DR OMA; PESFGWD; -. DR OrthoDB; 942598at2759; -. DR PhylomeDB; O60476; -. DR TreeFam; TF313420; -. DR BioCyc; MetaCyc:HS05846-MONOMER; -. DR BRENDA; 3.2.1.113; 2681. DR PathwayCommons; O60476; -. DR Reactome; R-HSA-6811438; Intra-Golgi traffic. DR Reactome; R-HSA-964827; Progressive trimming of alpha-1,2-linked mannose residues from Man9/8/7GlcNAc2 to produce Man5GlcNAc2. DR SignaLink; O60476; -. DR UniPathway; UPA00378; -. DR BioGRID-ORCS; 10905; 25 hits in 1157 CRISPR screens. DR ChiTaRS; MAN1A2; human. DR GeneWiki; MAN1A2; -. DR GenomeRNAi; 10905; -. DR Pharos; O60476; Tbio. DR PRO; PR:O60476; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; O60476; Protein. DR Bgee; ENSG00000198162; Expressed in middle temporal gyrus and 207 other cell types or tissues. DR ExpressionAtlas; O60476; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0000139; C:Golgi membrane; IBA:GO_Central. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0004571; F:mannosyl-oligosaccharide 1,2-alpha-mannosidase activity; IBA:GO_Central. DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro. DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl. DR GO; GO:0006491; P:N-glycan processing; TAS:ProtInc. DR GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway. DR GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; IEA:Ensembl. 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 PANTHER; PTHR11742:SF40; MANNOSYL-OLIGOSACCHARIDE 1,2-ALPHA-MANNOSIDASE IB; 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 Genevisible; O60476; HS. PE 1: Evidence at protein level; KW Acetylation; Calcium; Disulfide bond; Glycoprotein; Glycosidase; KW Golgi apparatus; Hydrolase; Membrane; Metal-binding; Reference proteome; KW Signal-anchor; Transmembrane; Transmembrane helix. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22223895" FT CHAIN 2..641 FT /note="Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB" FT /id="PRO_0000210312" FT TOPO_DOM 2..36 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 37..57 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 58..641 FT /note="Lumenal" FT /evidence="ECO:0000255" FT REGION 153..175 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 508 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:P31723" FT BINDING 619 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P32906" FT MOD_RES 2 FT /note="N-acetylthreonine" FT /evidence="ECO:0007744|PubMed:22223895" FT CARBOHYD 631 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 462..494 FT /evidence="ECO:0000250|UniProtKB:P32906" SQ SEQUENCE 641 AA; 73004 MW; 19DA691A9C4B0ED3 CRC64; MTTPALLPLS GRRIPPLNLG PPSFPHHRAT LRLSEKFILL LILSAFITLC FGAFFFLPDS SKHKRFDLGL EDVLIPHVDA GKGAKNPGVF LIHGPDEHRH REEEERLRNK IRADHEKALE EAKEKLRKSR EEIRAEIQTE KNKVVQEMKI KENKPLPPVP IPNLVGIRGG DPEDNDIREK REKIKEMMKH AWDNYRTYGW GHNELRPIAR KGHSPNIFGS SQMGATIVDA LDTLYIMGLH DEFLDGQRWI EDNLDFSVNS EVSVFEVNIR FIGGLLAAYY LSGEEIFKIK AVQLAEKLLP AFNTPTGIPW AMVNLKSGVG RNWGWASAGS SILAEFGTLH MEFIHLSYLT GDLTYYKKVM HIRKLLQKMD RPNGLYPNYL NPRTGRWGQY HTSVGGLGDS FYEYLLKAWL MSDKTDHEAR KMYDDAIEAI EKHLIKKSRG GLTFIGEWKN GHLEKKMGHL ACFAGGMFAL GADGSRADKA GHYLELGAEI ARTCHESYDR TALKLGPESF KFDGAVEAVA VRQAEKYYIL RPEVIETYWY LWRFTHDPRY RQWGWEAALA IEKYCRVNGG FSGVKDVYSS TPTHDDVQQS FFLAETLKYL YLLFSGDDLL PLDHWVFNTE AHPLPVLHLA NTTLSGNPAV R //