MA2C1_HUMAN
ID MA2C1_HUMAN Reviewed; 1040 AA.
AC Q9NTJ4; H3BMX2; H3BQY8; H3BUT6; Q13358; Q68EM8; Q9UL64;
DT 27-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Alpha-mannosidase 2C1;
DE EC=3.2.1.24 {ECO:0000269|PubMed:16848760};
DE AltName: Full=Alpha mannosidase 6A8B;
DE AltName: Full=Alpha-D-mannoside mannohydrolase;
DE AltName: Full=Mannosidase alpha class 2C member 1;
GN Name=MAN2C1; Synonyms=MANA, MANA1;
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] (ISOFORM 1).
RA Li B., Ma F.-R., Shi G.-X., Zhao F.-T., Li J., Li L., Wang Y., Cai Y.-Y.,
RA Zhu L.-P.;
RT "Cloning of a human full-length cDNA encoding an alpha-mannosidase.";
RL Ji Chu Yi Xue Yu Lin Chuang 19:409-415(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT ILE-960.
RC TISSUE=Cerebellum;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP CYS-323.
RC TISSUE=Skin, and Uterus;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 630-1040 (ISOFORM 1).
RC TISSUE=Tonsil;
RA Zhang L.-X., Zhu L.-P., Shi W., Ma F.-R.;
RT "Cloning of a human cDNA homologous to the cDNA encoding a rat ER alpha-
RT mannosidase.";
RL Zhonghua Wei Sheng Wu Xue He Mian Yi Xue Za Zhi 17:34-39(1997).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=16848760; DOI=10.1042/bj20060945;
RA Suzuki T., Hara I., Nakano M., Shigeta M., Nakagawa T., Kondo A.,
RA Funakoshi Y., Taniguchi N.;
RT "Man2C1, an alpha-mannosidase, is involved in the trimming of free
RT oligosaccharides in the cytosol.";
RL Biochem. J. 400:33-41(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
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:16848760}.
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:16848760};
CC -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:16848760};
CC -!- ACTIVITY REGULATION: Strongly inhibited by swainsonine. Also inhibited
CC to a lesser extent by deoxymannojirimycin (DMM).
CC {ECO:0000269|PubMed:16848760}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16848760}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9NTJ4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NTJ4-2; Sequence=VSP_046375;
CC Name=3;
CC IsoId=Q9NTJ4-3; Sequence=VSP_046395;
CC Name=4;
CC IsoId=Q9NTJ4-4; Sequence=VSP_046895;
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 38 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC00190.2; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAC00568.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF044414; AAC00190.2; ALT_FRAME; mRNA.
DR EMBL; AL136876; CAB66810.1; -; mRNA.
DR EMBL; AK225145; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC068338; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471136; EAW99253.1; -; Genomic_DNA.
DR EMBL; BC050550; AAH50550.1; -; mRNA.
DR EMBL; BC080191; AAH80191.1; -; mRNA.
DR EMBL; U37248; AAC00568.1; ALT_SEQ; mRNA.
DR CCDS; CCDS32298.1; -. [Q9NTJ4-1]
DR CCDS; CCDS58389.1; -. [Q9NTJ4-3]
DR CCDS; CCDS58390.1; -. [Q9NTJ4-2]
DR CCDS; CCDS58391.1; -. [Q9NTJ4-4]
DR PIR; T46931; T46931.
DR RefSeq; NP_001243423.1; NM_001256494.1. [Q9NTJ4-4]
DR RefSeq; NP_001243424.1; NM_001256495.1. [Q9NTJ4-2]
DR RefSeq; NP_001243425.1; NM_001256496.1. [Q9NTJ4-3]
DR RefSeq; NP_006706.2; NM_006715.3. [Q9NTJ4-1]
DR AlphaFoldDB; Q9NTJ4; -.
DR SMR; Q9NTJ4; -.
DR BioGRID; 110296; 37.
DR IntAct; Q9NTJ4; 13.
DR MINT; Q9NTJ4; -.
DR STRING; 9606.ENSP00000457788; -.
DR CAZy; GH38; Glycoside Hydrolase Family 38.
DR iPTMnet; Q9NTJ4; -.
DR PhosphoSitePlus; Q9NTJ4; -.
DR BioMuta; MAN2C1; -.
DR DMDM; 27923805; -.
DR EPD; Q9NTJ4; -.
DR jPOST; Q9NTJ4; -.
DR MassIVE; Q9NTJ4; -.
DR MaxQB; Q9NTJ4; -.
DR PaxDb; Q9NTJ4; -.
DR PeptideAtlas; Q9NTJ4; -.
DR PRIDE; Q9NTJ4; -.
DR ProteomicsDB; 41029; -.
DR ProteomicsDB; 41922; -.
DR ProteomicsDB; 43020; -.
DR ProteomicsDB; 82619; -. [Q9NTJ4-1]
DR Antibodypedia; 27278; 112 antibodies from 19 providers.
DR DNASU; 4123; -.
DR Ensembl; ENST00000267978.10; ENSP00000267978.4; ENSG00000140400.18. [Q9NTJ4-1]
DR Ensembl; ENST00000563622.5; ENSP00000454589.1; ENSG00000140400.18. [Q9NTJ4-3]
DR Ensembl; ENST00000565683.5; ENSP00000457788.1; ENSG00000140400.18. [Q9NTJ4-4]
DR Ensembl; ENST00000569482.5; ENSP00000455998.1; ENSG00000140400.18. [Q9NTJ4-2]
DR GeneID; 4123; -.
DR KEGG; hsa:4123; -.
DR MANE-Select; ENST00000267978.10; ENSP00000267978.4; NM_006715.4; NP_006706.2.
DR UCSC; uc002baf.5; human. [Q9NTJ4-1]
DR CTD; 4123; -.
DR DisGeNET; 4123; -.
DR GeneCards; MAN2C1; -.
DR HGNC; HGNC:6827; MAN2C1.
DR HPA; ENSG00000140400; Low tissue specificity.
DR MIM; 154580; gene.
DR neXtProt; NX_Q9NTJ4; -.
DR OpenTargets; ENSG00000140400; -.
DR Orphanet; 528084; Non-specific syndromic intellectual disability.
DR PharmGKB; PA30576; -.
DR VEuPathDB; HostDB:ENSG00000140400; -.
DR eggNOG; KOG4342; Eukaryota.
DR GeneTree; ENSGT01030000234638; -.
DR HOGENOM; CLU_003442_0_1_1; -.
DR InParanoid; Q9NTJ4; -.
DR OMA; GQYWDAW; -.
DR OrthoDB; 85892at2759; -.
DR PhylomeDB; Q9NTJ4; -.
DR TreeFam; TF300335; -.
DR BRENDA; 3.2.1.24; 2681.
DR PathwayCommons; Q9NTJ4; -.
DR Reactome; R-HSA-8853383; Lysosomal oligosaccharide catabolism.
DR SignaLink; Q9NTJ4; -.
DR BioGRID-ORCS; 4123; 15 hits in 1080 CRISPR screens.
DR ChiTaRS; MAN2C1; human.
DR GenomeRNAi; 4123; -.
DR Pharos; Q9NTJ4; Tbio.
DR PRO; PR:Q9NTJ4; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9NTJ4; protein.
DR Bgee; ENSG00000140400; Expressed in right lobe of thyroid gland and 147 other tissues.
DR ExpressionAtlas; Q9NTJ4; baseline and differential.
DR Genevisible; Q9NTJ4; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0004559; F:alpha-mannosidase activity; IBA:GO_Central.
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 Alternative splicing; Cobalt; Cytoplasm; Glycosidase; Hydrolase;
KW Metal-binding; Reference proteome.
FT CHAIN 1..1040
FT /note="Alpha-mannosidase 2C1"
FT /id="PRO_0000206907"
FT ACT_SITE 372
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q29451"
FT BINDING 260
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000305"
FT BINDING 262
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000305"
FT BINDING 372
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000305"
FT BINDING 577
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000305"
FT VAR_SEQ 201..299
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_046395"
FT VAR_SEQ 650..682
FT /note="ALVTVPSMGYAPVPPPTSLQPLLPQQPVFVVQE -> GLTPSPGDSAQHGLC
FT SCSSPHLTAAPAAPAACVRSARAPTDSASRPPPTK (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_046895"
FT VAR_SEQ 913..935
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046375"
FT VARIANT 323
FT /note="R -> C (in dbSNP:rs200595616)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_069180"
FT VARIANT 818
FT /note="R -> H (in dbSNP:rs58557444)"
FT /id="VAR_061192"
FT VARIANT 950
FT /note="V -> M (in dbSNP:rs3803467)"
FT /id="VAR_049211"
FT VARIANT 960
FT /note="V -> I (in dbSNP:rs3803466)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021914"
FT VARIANT 975
FT /note="R -> K (in dbSNP:rs5745934)"
FT /id="VAR_049212"
FT CONFLICT 6
FT /note="A -> F (in Ref. 1; AAC00190)"
FT /evidence="ECO:0000305"
FT CONFLICT 14
FT /note="L -> F (in Ref. 1; AAC00190)"
FT /evidence="ECO:0000305"
FT CONFLICT 24
FT /note="L -> I (in Ref. 1; AAC00190)"
FT /evidence="ECO:0000305"
FT CONFLICT 170
FT /note="M -> I (in Ref. 1; AAC00190)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1040 AA; 115835 MW; 2B40AE6E03AC1E3C CRC64;
MAAAPALKHW RTTLERVEKF VSPLYFTDCN LRGRLFGASC PVAVLSSFLT PERLPYQEAV
QRDFRPAQVG DSFGPTWWTC WFRVELTIPE AWVGQEVHLC WESDGEGLVW RDGEPVQGLT
KEGEKTSYVL TDRLGERDPR SLTLYVEVAC NGLLGAGKGS MIAAPDPEKM FQLSRAELAV
FHRDVHMLLV DLELLLGIAK GLGKDNQRSF QALYTANQMV NVCDPAQPET FPVAQALASR
FFGQHGGESQ HTIHATGHCH IDTAWLWPFK ETVRKCARSW VTALQLMERN PEFIFACSQA
QQLEWVKSRY PGLYSRIQEF ACRGQFVPVG GTWVEMDGNL PSGEAMVRQF LQGQNFFLQE
FGKMCSEFWL PDTFGYSAQL PQIMHGCGIR RFLTQKLSWN LVNSFPHHTF FWEGLDGSRV
LVHFPPGDSY GMQGSVEEVL KTVANNRDKG RANHSAFLFG FGDGGGGPTQ TMLDRLKRLS
NTDGLPRVQL SSPRQLFSAL ESDSEQLCTW VGELFLELHN GTYTTHAQIK KGNRECERIL
HDVELLSSLA LARSAQFLYP AAQLQHLWRL LLLNQFHDVV TGSCIQMVAE EAMCHYEDIR
SHGNTLLSAA AAALCAGEPG PEGLLIVNTL PWKRIEVMAL PKPGGAHSLA LVTVPSMGYA
PVPPPTSLQP LLPQQPVFVV QETDGSVTLD NGIIRVKLDP TGRLTSLVLV ASGREAIAEG
AVGNQFVLFD DVPLYWDAWD VMDYHLETRK PVLGQAGTLA VGTEGGLRGS AWFLLQISPN
SRLSQEVVLD VGCPYVRFHT EVHWHEAHKF LKVEFPARVR SSQATYEIQF GHLQRPTHYN
TSWDWARFEV WAHRWMDLSE HGFGLALLND CKYGASVRGS ILSLSLLRAP KAPDATADTG
RHEFTYALMP HKGSFQDAGV IQAAYSLNFP LLALPAPSPA PATSWSAFSV SSPAVVLETV
KQAESSPQRR SLVLRLYEAH GSHVDCWLHL SLPVQEAILC DLLERPDPAG HLTLRDNRLK
LTFSPFQVLS LLLVLQPPPH
