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 13-FEB-2019, entry version 154. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA 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., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA 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., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164, AND IDENTIFICATION RP BY 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Involved in the maturation of Asn-linked CC oligosaccharides. Trim alpha-1,2-linked mannose residues from CC Man(9)GlcNAc(2) to produce first Man(8)GlcNAc(2) then Man(6)GlcNAc CC and a small amount of Man(5)GlcNAc. CC -!- CATALYTIC ACTIVITY: CC Reaction=Hydrolysis of the terminal (1->2)-linked alpha-D-mannose CC residues in the oligo-mannose oligosaccharide CC Man(9)(GlcNAc)(2).; EC=3.2.1.113; CC 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 CC II membrane protein. CC -!- TISSUE SPECIFICITY: Expressed in most tissues with the exception CC of lung, muscle and pancreas. Highly expressed in placenta. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 47 family. 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; 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 UniGene; Hs.197043; -. DR ProteinModelPortal; Q9NR34; -. 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 MaxQB; Q9NR34; -. DR PaxDb; Q9NR34; -. DR PeptideAtlas; Q9NR34; -. DR PRIDE; Q9NR34; -. DR ProteomicsDB; 82269; -. 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 EuPathDB; HostDB:ENSG00000117643.14; -. DR GeneCards; MAN1C1; -. DR HGNC; HGNC:19080; MAN1C1. DR HPA; HPA048352; -. DR neXtProt; NX_Q9NR34; -. DR OpenTargets; ENSG00000117643; -. DR PharmGKB; PA38788; -. DR eggNOG; KOG2431; Eukaryota. DR eggNOG; ENOG410XP04; LUCA. DR GeneTree; ENSGT00940000159312; -. DR HOGENOM; HOG000181988; -. DR HOVERGEN; HBG052389; -. 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 PRO; PR:Q9NR34; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000117643; Expressed in 212 organ(s), highest expression level in chorionic villus. 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; Complete proteome; Disulfide bond; Glycoprotein; Glycosidase; KW Golgi apparatus; Hydrolase; Membrane; Metal-binding; Phosphoprotein; KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix. FT CHAIN 1 630 Mannosyl-oligosaccharide 1,2-alpha- FT mannosidase IC. FT /FTId=PRO_0000210315. FT TOPO_DOM 1 22 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 23 43 Helical; Signal-anchor for type II FT membrane protein. {ECO:0000255}. FT TOPO_DOM 44 630 Lumenal. {ECO:0000255}. FT ACT_SITE 499 499 Proton donor. FT {ECO:0000250|UniProtKB:P31723}. FT METAL 610 610 Calcium. {ECO:0000250|UniProtKB:P32906}. FT MOD_RES 164 164 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT CARBOHYD 250 250 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 618 618 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 453 485 {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 //