ID MA1C1_HUMAN Reviewed; 630 AA. AC Q9NR34; A6NNE2; B2RNP2; Q9Y545; DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 22-APR-2020, entry version 159. DE RecName: Full=Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC; DE EC=3.2.1.113 {ECO:0000250|UniProtKB:P32906}; DE AltName: Full=HMIC; DE AltName: Full=Mannosidase alpha class 1C member 1; DE AltName: Full=Processing alpha-1,2-mannosidase IC; DE Short=Alpha-1,2-mannosidase IC; GN Name=MAN1C1; Synonyms=MAN1A3, MAN1C; 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]. RC TISSUE=Brain, and Eye; RX PubMed=10915796; DOI=10.1074/jbc.m004935200; RA Tremblay L.O., Herscovics A.; RT "Characterization of a cDNA encoding a novel human Golgi alpha 1,2- RT mannosidase involved in N-glycan biosynthesis."; RL J. Biol. Chem. 275:31655-31660(2000). 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Involved in the maturation of Asn-linked oligosaccharides. CC Trim alpha-1,2-linked mannose residues from Man(9)GlcNAc(2) to produce CC first Man(8)GlcNAc(2) then Man(6)GlcNAc and a small amount of CC Man(5)GlcNAc. 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 -!- INTERACTION: CC Q9NR34; Q9HB07: C12orf10; NbExp=3; IntAct=EBI-7260764, EBI-709754; CC Q9NR34; O95363: FARS2; NbExp=3; IntAct=EBI-7260764, EBI-2513774; CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane; Single-pass type II CC membrane protein. CC -!- TISSUE SPECIFICITY: Expressed in most tissues with the exception of CC lung, muscle and pancreas. Highly expressed in placenta. 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; AF261655; AAF97058.1; -; mRNA. DR EMBL; AL020996; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL031280; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC137017; AAI37018.1; -; mRNA. DR CCDS; CCDS265.1; -. DR RefSeq; NP_001275939.1; NM_001289010.1. DR RefSeq; NP_065112.1; NM_020379.3. DR SMR; Q9NR34; -. DR BioGrid; 121395; 3. DR IntAct; Q9NR34; 3. DR MINT; Q9NR34; -. DR STRING; 9606.ENSP00000363452; -. DR CAZy; GH47; Glycoside Hydrolase Family 47. DR iPTMnet; Q9NR34; -. DR PhosphoSitePlus; Q9NR34; -. DR BioMuta; MAN1C1; -. DR DMDM; 17369308; -. DR EPD; Q9NR34; -. DR jPOST; Q9NR34; -. DR MassIVE; Q9NR34; -. DR MaxQB; Q9NR34; -. DR PaxDb; Q9NR34; -. DR PeptideAtlas; Q9NR34; -. DR PRIDE; Q9NR34; -. DR ProteomicsDB; 82269; -. DR Antibodypedia; 30480; 54 antibodies. DR DNASU; 57134; -. DR Ensembl; ENST00000374332; ENSP00000363452; ENSG00000117643. DR GeneID; 57134; -. DR KEGG; hsa:57134; -. DR UCSC; uc001bkm.3; human. DR CTD; 57134; -. DR DisGeNET; 57134; -. DR GeneCards; MAN1C1; -. DR HGNC; HGNC:19080; MAN1C1. DR HPA; ENSG00000117643; Low tissue specificity. DR neXtProt; NX_Q9NR34; -. DR OpenTargets; ENSG00000117643; -. DR PharmGKB; PA38788; -. DR eggNOG; KOG2431; Eukaryota. DR eggNOG; ENOG410XP04; LUCA. DR GeneTree; ENSGT00940000159312; -. DR InParanoid; Q9NR34; -. DR KO; K01230; -. DR OMA; QITRTCH; -. DR OrthoDB; 693882at2759; -. DR PhylomeDB; Q9NR34; -. DR TreeFam; TF313420; -. DR BioCyc; MetaCyc:HS04162-MONOMER; -. DR BRENDA; 3.2.1.113; 2681. 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 UniPathway; UPA00378; -. DR ChiTaRS; MAN1C1; human. DR GenomeRNAi; 57134; -. DR Pharos; Q9NR34; Tdark. DR PRO; PR:Q9NR34; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9NR34; protein. DR Bgee; ENSG00000117643; Expressed in chorionic villus and 211 other tissues. DR ExpressionAtlas; Q9NR34; baseline and differential. DR Genevisible; Q9NR34; HS. DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IBA:GO_Central. DR GO; GO:0030173; C:integral component of Golgi membrane; TAS:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; TAS:UniProtKB. DR GO; GO:0004571; F:mannosyl-oligosaccharide 1,2-alpha-mannosidase activity; IBA:GO_Central. DR GO; GO:1904381; P:Golgi apparatus mannose trimming; TAS:Reactome. DR GO; GO:0006491; P:N-glycan processing; IBA:GO_Central. DR GO; GO:0006487; P:protein N-linked glycosylation; TAS:UniProtKB. 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 Calcium; Disulfide bond; Glycoprotein; Glycosidase; Golgi apparatus; KW Hydrolase; Membrane; Metal-binding; Phosphoprotein; Reference proteome; KW Signal-anchor; Transmembrane; Transmembrane helix. FT CHAIN 1..630 FT /note="Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC" FT /id="PRO_0000210315" FT TOPO_DOM 1..22 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 23..43 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 44..630 FT /note="Lumenal" FT /evidence="ECO:0000255" FT ACT_SITE 499 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:P31723" FT METAL 610 FT /note="Calcium" FT /evidence="ECO:0000250|UniProtKB:P32906" FT MOD_RES 164 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:24275569" FT CARBOHYD 250 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 618 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 453..485 FT /evidence="ECO:0000250|UniProtKB:P32906" SQ SEQUENCE 630 AA; 70911 MW; 80FFC71EFB36552A CRC64; MLMRKVPGFV PASPWGLRLP QKFLFLLFLS GLVTLCFGAL FLLPHSSRLK RLFLAPRTQQ PGLEVVAEIA GHAPAREQEP PPNPAPAAPA PGEDDPSSWA SPRRRKGGLR RTRPTGPREE ATAARGNSIP ASRPGDEGVP FRFDFNAFRS RLRHPVLGTR ADESQEPQSQ VRAQREKIKE MMQFAWQSYK RYAMGKNELR PLTKDGYEGN MFGGLSGATV IDSLDTLYLM ELKEEFQEAK AWVGESFHLN VSGEASLFEV NIRYIGGLLS AFYLTGEEVF RIKAIRLGEK LLPAFNTPTG IPKGVVSFKS GNWGWATAGS SSILAEFGSL HLEFLHLTEL SGNQVFAEKV RNIRKVLRKI EKPFGLYPNF LSPVSGNWVQ HHVSVGGLGD SFYEYLIKSW LMSGKTDMEA KNMYYEALEA IETYLLNVSP GGLTYIAEWR GGILDHKMGH LACFSGGMIA LGAEDAKEEK RAHYRELAAQ ITKTCHESYA RSDTKLGPEA FWFNSGREAV ATQLSESYYI LRPEVVESYM YLWRQTHNPI YREWGWEVVL ALEKYCRTEA GFSGIQDVYS STPNHDNKQQ SFFLAETLKY LYLLFSEDDL LSLEDWVFNT EAHPLPVNHS DSSGRAWGRH //