MA2C1_MOUSE
ID MA2C1_MOUSE Reviewed; 1039 AA.
AC Q91W89; Q3ZCX9;
DT 27-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Alpha-mannosidase 2C1;
DE EC=3.2.1.24 {ECO:0000269|PubMed:16904268, ECO:0000269|PubMed:24550399};
DE AltName: Full=Alpha-D-mannoside mannohydrolase;
DE AltName: Full=Mannosidase alpha class 2C member 1;
DE AltName: Full=Neutral/cytosolic alpha-mannosidase {ECO:0000303|PubMed:16904268};
GN Name=Man2c1 {ECO:0000303|PubMed:16904268};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=129 {ECO:0000312|EMBL:AAY53557.1};
RC TISSUE=Liver {ECO:0000312|EMBL:AAY53557.1};
RX PubMed=16904268; DOI=10.1016/j.bbagen.2006.06.011;
RA Costanzi E., Balducci C., Cacan R., Duvet S., Orlacchio A., Beccari T.;
RT "Cloning and expression of mouse cytosolic alpha-mannosidase (Man2c1).";
RL Biochim. Biophys. Acta 1760:1580-1586(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD {ECO:0000312|EMBL:BAE32264.1};
RC TISSUE=Thymus {ECO:0000312|EMBL:BAE32264.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Salivary gland;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=24550399; DOI=10.1074/jbc.m114.550509;
RA Paciotti S., Persichetti E., Klein K., Tasegian A., Duvet S., Hartmann D.,
RA Gieselmann V., Beccari T.;
RT "Accumulation of free oligosaccharides and tissue damage in cytosolic
RT alpha-mannosidase (Man2c1)-deficient mice.";
RL J. Biol. Chem. 289:9611-9622(2014).
CC -!- FUNCTION: Cleaves alpha 1,2-, alpha 1,3-, and alpha 1,6-linked mannose
CC residues from glycoproteins. Involved in the degradation of free
CC oligosaccharides in the cytoplasm. {ECO:0000269|PubMed:16904268,
CC ECO:0000269|PubMed:24550399}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of terminal, non-reducing alpha-D-mannose residues
CC in alpha-D-mannosides.; EC=3.2.1.24;
CC Evidence={ECO:0000269|PubMed:16904268, ECO:0000269|PubMed:24550399};
CC -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:16904268};
CC -!- ACTIVITY REGULATION: Inhibited by 1,4-dideoxy-1,4-imino-d-mannitol
CC (DIM) and EDTA. {ECO:0000269|PubMed:16904268}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16904268}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney and liver (at protein level)
CC (PubMed:24550399). Widely expressed, with highest levels in lung, ovary
CC and testis (PubMed:16904268). Also detected at lower levels in heart,
CC brain, liver, spleen, kidney and thymus (PubMed:16904268).
CC {ECO:0000269|PubMed:16904268, ECO:0000269|PubMed:24550399}.
CC -!- DISRUPTION PHENOTYPE: Viable and fertile with no gross defects. Loss of
CC neutral mannosidase activity leading to accumulation of free higher-
CC order oligosaccharides such as Man(8-9)GlcNAc(1) in many organs,
CC particularly liver and heart. Tissues show histopathological changes
CC with strongest defects observed in liver, small intestine, kidney and
CC central nervous system (CNS). In liver, hepatocytes appear swollen with
CC increased levels of glycogen and accumulation of lipid droplets. In the
CC small intestine, enterocytes accumulate glycogen apically and also
CC develop vacuoles in the basal cell region. In the CNS, neurons in
CC isocortex lamina V show signs of degeneration with formation of
CC vacuoles in basal cell regions. Vacuolation is also found in glial
CC cells of white matter tracts. In kidney, there are signs of fibrosis
CC along Bowman's capsule and a small number of glomeruli appear to be
CC collapsed. {ECO:0000269|PubMed:24550399}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 38 family. {ECO:0000305}.
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DR EMBL; AH014888; AAY53557.1; -; Genomic_DNA.
DR EMBL; AY996589; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996590; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996591; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996592; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996593; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996594; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996595; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996597; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996598; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996599; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996600; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996601; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996602; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996603; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996604; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996605; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996606; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996607; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996608; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996609; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996610; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996611; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996612; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AY996613; AAY53557.1; JOINED; Genomic_DNA.
DR EMBL; AK153935; BAE32264.1; -; mRNA.
DR EMBL; CH466522; EDL25887.1; -; Genomic_DNA.
DR EMBL; BC016253; AAH16253.1; -; mRNA.
DR CCDS; CCDS40646.1; -.
DR RefSeq; NP_082912.1; NM_028636.2.
DR AlphaFoldDB; Q91W89; -.
DR SMR; Q91W89; -.
DR BioGRID; 216226; 7.
DR STRING; 10090.ENSMUSP00000125478; -.
DR CAZy; GH38; Glycoside Hydrolase Family 38.
DR iPTMnet; Q91W89; -.
DR PhosphoSitePlus; Q91W89; -.
DR EPD; Q91W89; -.
DR MaxQB; Q91W89; -.
DR PaxDb; Q91W89; -.
DR PRIDE; Q91W89; -.
DR ProteomicsDB; 292141; -.
DR Antibodypedia; 27278; 112 antibodies from 19 providers.
DR DNASU; 73744; -.
DR Ensembl; ENSMUST00000160147; ENSMUSP00000125478; ENSMUSG00000032295.
DR GeneID; 73744; -.
DR KEGG; mmu:73744; -.
DR UCSC; uc009pud.1; mouse.
DR CTD; 4123; -.
DR MGI; MGI:1920994; Man2c1.
DR VEuPathDB; HostDB:ENSMUSG00000032295; -.
DR eggNOG; KOG4342; Eukaryota.
DR GeneTree; ENSGT01030000234638; -.
DR InParanoid; Q91W89; -.
DR OMA; GQYWDAW; -.
DR OrthoDB; 85892at2759; -.
DR PhylomeDB; Q91W89; -.
DR TreeFam; TF300335; -.
DR Reactome; R-MMU-8853383; Lysosomal oligosaccharide catabolism.
DR BioGRID-ORCS; 73744; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Man2c1; mouse.
DR PRO; PR:Q91W89; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q91W89; protein.
DR Bgee; ENSMUSG00000032295; Expressed in internal carotid artery and 257 other tissues.
DR ExpressionAtlas; Q91W89; baseline and differential.
DR Genevisible; Q91W89; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0004559; F:alpha-mannosidase activity; ISO:MGI.
DR GO; GO:0030246; F:carbohydrate binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006013; P:mannose metabolic process; IEA:InterPro.
DR GO; GO:0009313; P:oligosaccharide catabolic process; IBA:GO_Central.
DR Gene3D; 1.20.1270.50; -; 1.
DR Gene3D; 3.20.110.10; -; 1.
DR InterPro; IPR011013; Gal_mutarotase_sf_dom.
DR InterPro; IPR041147; GH38_C.
DR InterPro; IPR011330; Glyco_hydro/deAcase_b/a-brl.
DR InterPro; IPR011682; Glyco_hydro_38_C.
DR InterPro; IPR015341; Glyco_hydro_38_cen.
DR InterPro; IPR037094; Glyco_hydro_38_cen_sf.
DR InterPro; IPR000602; Glyco_hydro_38_N.
DR InterPro; IPR027291; Glyco_hydro_38_N_sf.
DR InterPro; IPR028995; Glyco_hydro_57/38_cen_sf.
DR Pfam; PF09261; Alpha-mann_mid; 1.
DR Pfam; PF17677; Glyco_hydro38C2; 1.
DR Pfam; PF07748; Glyco_hydro_38C; 1.
DR Pfam; PF01074; Glyco_hydro_38N; 1.
DR SMART; SM00872; Alpha-mann_mid; 1.
DR SUPFAM; SSF74650; SSF74650; 1.
DR SUPFAM; SSF88688; SSF88688; 1.
DR SUPFAM; SSF88713; SSF88713; 1.
PE 1: Evidence at protein level;
KW Cobalt; Cytoplasm; Glycosidase; Hydrolase; Metal-binding;
KW Reference proteome.
FT CHAIN 1..1039
FT /note="Alpha-mannosidase 2C1"
FT /id="PRO_0000206908"
FT ACT_SITE 371
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q29451"
FT BINDING 259
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000305"
FT BINDING 261
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000305"
FT BINDING 371
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000305"
FT BINDING 576
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1039 AA; 115688 MW; 308F2F841590F9E8 CRC64;
MAAAPFLKHW RTTFERVEKF VSPIYFTDCN LRGRLFGDSC SVTLSSFLTP ERLPYEKAVQ
QNFSPAQVGD SFGPTWWTCW FRVELVIPEV WVGQEVHLCW ESDGESLVWR DGEPVQGLTK
EGEKTSYVLS ERLRASDPRS LTLYVEVACN GLLGAGKGSM IAAPDPEKMF QLSQAKLAVF
HRDVHSLLVD LELLLGVAKG LGEDSQRSFQ ALHTANQMVN ICDPAQPETY PAAKALASKF
FGQHGGESQH TIHAMGHCHI DTAWLWPFKE TVRKCARSWS TAVTLMEQNT DFIFACSQAQ
QLEWVKSQYP GLHARLQEFA CRGQFVPVGG TWVEMDGNLP SGEAMVRQFL QGQNFFLQEF
GKMCSEFWLP DTFGYSAQLP QIMQGCGIKR FLTQKLSWNL VNSFPHHTFF WEGLDGSRVL
VHFPPGDSYG MQGSVEEVLK TVTNNRDKGR TNHSGFLFGF GDGGGGPTQT MLDRLKRLSN
TDGLPRVQLS SPGQLFTALE RDSGQLCTWV GELFLELHNG TYTTHAQLKK GNRECEQILH
DVEVLSSLAL ARSAQFLYPA AQLQHLWRLL LLNQFHDVVT GSCIQLVAED AMNYYEDIRS
HGNPLLSAAA AALCAGEPGP KGLLIINTLP WKRTEVLALP KPCGAHSLAL VTVPSIGYAP
APTPTSLQPL LPQQPVFVMQ ETDGSVTLDN GIIRVRLDPT GCLTSLVLVA SGREAIAEGA
LGNQFVLFDD VPLYWDAWDV MDYHLETRKP VLGQAGTLAV GTEGGLRGSA WFLLQISPNS
RLSQEVVLDV GCPYVRFHTE VHWHEAHKFL KVEFPARIRS PQATYEIQFG HLQRPTHNNT
SWDWARYEVW AHRWIDLSEC DFGLALLNNC KYGASVRGNV LSLSLLRAPK APDATADMGR
HEFTYALMPH KGSFQEAGVI HAAYNLNFPL LALPAPGPAP DTTWSAFSVS SPAVVLETIK
QAERCHQHRT LVLRLYEAHG SHVDCWLHTS LPVQEATLCD LLEQRDPTGH LSLQDNRLKL
TFSPFQVRSL LLVLQSPPN
