MA1A2_HUMAN
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 03-AUG-2022, entry version 182.
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)-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: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}.
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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; 45.
DR IntAct; O60476; 19.
DR MINT; O60476; -.
DR STRING; 9606.ENSP00000348959; -.
DR CAZy; GH47; Glycoside Hydrolase Family 47.
DR GlyGen; O60476; 1 site.
DR iPTMnet; O60476; -.
DR PhosphoSitePlus; O60476; -.
DR BioMuta; MAN1A2; -.
DR EPD; O60476; -.
DR jPOST; O60476; -.
DR MassIVE; O60476; -.
DR MaxQB; O60476; -.
DR PaxDb; O60476; -.
DR PeptideAtlas; O60476; -.
DR PRIDE; O60476; -.
DR ProteomicsDB; 49416; -.
DR Antibodypedia; 33890; 96 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 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; LIKMYLY; -.
DR OrthoDB; 693882at2759; -.
DR PhylomeDB; O60476; -.
DR TreeFam; TF313420; -.
DR BioCyc; MetaCyc:HS05846-MON; -.
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; 24 hits in 1077 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 205 other tissues.
DR ExpressionAtlas; O60476; baseline and differential.
DR Genevisible; O60476; HS.
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:0016021; C:integral component of membrane; TAS:ProtInc.
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:1904381; P:Golgi apparatus mannose trimming; TAS:Reactome.
DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl.
DR GO; GO:0006491; P:N-glycan processing; IBA:GO_Central.
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 Pfam; PF01532; Glyco_hydro_47; 1.
DR PRINTS; PR00747; GLYHDRLASE47.
DR SUPFAM; SSF48225; SSF48225; 1.
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
