MA1C1_HUMAN
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 03-AUG-2022, entry version 170.
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; O95363: FARS2; NbExp=3; IntAct=EBI-7260764, EBI-2513774;
CC Q9NR34; Q9HB07: MYG1; NbExp=3; IntAct=EBI-7260764, EBI-709754;
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}.
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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 AlphaFoldDB; Q9NR34; -.
DR SMR; Q9NR34; -.
DR BioGRID; 121395; 5.
DR IntAct; Q9NR34; 3.
DR MINT; Q9NR34; -.
DR STRING; 9606.ENSP00000363452; -.
DR CAZy; GH47; Glycoside Hydrolase Family 47.
DR GlyGen; Q9NR34; 6 sites, 2 O-linked glycans (4 sites).
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; 59 antibodies from 16 providers.
DR DNASU; 57134; -.
DR Ensembl; ENST00000374332.9; ENSP00000363452.4; ENSG00000117643.15.
DR GeneID; 57134; -.
DR KEGG; hsa:57134; -.
DR MANE-Select; ENST00000374332.9; ENSP00000363452.4; NM_020379.4; NP_065112.1.
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 VEuPathDB; HostDB:ENSG00000117643; -.
DR eggNOG; KOG2204; Eukaryota.
DR GeneTree; ENSGT00940000159312; -.
DR InParanoid; Q9NR34; -.
DR OMA; CESFWMA; -.
DR OrthoDB; 693882at2759; -.
DR PhylomeDB; Q9NR34; -.
DR TreeFam; TF313420; -.
DR BioCyc; MetaCyc:HS04162-MON; -.
DR BRENDA; 3.2.1.113; 2681.
DR PathwayCommons; Q9NR34; -.
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; Q9NR34; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 57134; 18 hits in 1070 CRISPR screens.
DR ChiTaRS; MAN1C1; human.
DR GenomeRNAi; 57134; -.
DR Pharos; Q9NR34; Tbio.
DR PRO; PR:Q9NR34; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9NR34; protein.
DR Bgee; ENSG00000117643; Expressed in pigmented layer of retina and 185 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:0005975; P:carbohydrate metabolic process; IEA:InterPro.
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 REGION 74..140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 77..91
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 499
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P31723"
FT BINDING 610
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P32906"
FT MOD_RES 164
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|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
