MA2B1_HUMAN
ID MA2B1_HUMAN Reviewed; 1011 AA.
AC O00754; G5E928; O15330; Q16680; Q93094; Q9BW13;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Lysosomal alpha-mannosidase;
DE Short=Laman;
DE EC=3.2.1.24;
DE AltName: Full=Lysosomal acid alpha-mannosidase;
DE AltName: Full=Mannosidase alpha class 2B member 1;
DE AltName: Full=Mannosidase alpha-B;
DE Contains:
DE RecName: Full=Lysosomal alpha-mannosidase A peptide;
DE Contains:
DE RecName: Full=Lysosomal alpha-mannosidase B peptide;
DE Contains:
DE RecName: Full=Lysosomal alpha-mannosidase C peptide;
DE Contains:
DE RecName: Full=Lysosomal alpha-mannosidase D peptide;
DE Contains:
DE RecName: Full=Lysosomal alpha-mannosidase E peptide;
DE Flags: Precursor;
GN Name=MAN2B1; Synonyms=LAMAN, MANB;
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).
RX PubMed=8166692; DOI=10.1006/bbrc.1994.1440;
RA Nebes V.L., Schmidt M.C.;
RT "Human lysosomal alpha-mannosidase: isolation and nucleotide sequence of
RT the full-length cDNA.";
RL Biochem. Biophys. Res. Commun. 200:239-245(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, AND
RP VARIANT MANSA LEU-72.
RC TISSUE=Lung, and Skin;
RX PubMed=9158146; DOI=10.1093/hmg/6.5.717;
RA Nilssen O., Berg T., Riise H.M.F., Ramachandran U., Evjen G., Hansen G.M.,
RA Malm D., Tranebjaerg L., Tollersrud O.-K.;
RT "Alpha-mannosidosis: functional cloning of the lysosomal alpha-mannosidase
RT cDNA and identification of a mutation in two affected siblings.";
RL Hum. Mol. Genet. 6:717-726(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=9192839; DOI=10.1006/geno.1997.4668;
RA Riise H.M.F., Berg T., Nilssen O., Romeo G., Tollersrud O.-K.,
RA Ceccherini I.;
RT "Genomic structure of the human lysosomal alpha-mannosidase gene (MANB).";
RL Genomics 42:200-207(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
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] (ISOFORM 1).
RC TISSUE=Placenta;
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 9-1010 (ISOFORM 1).
RC TISSUE=Spleen;
RX PubMed=8910458; DOI=10.1074/jbc.271.45.28348;
RA Liao Y.-F., Lal A., Moremen K.W.;
RT "Cloning, expression, purification, and characterization of the human broad
RT specificity lysosomal acid alpha-mannosidase.";
RL J. Biol. Chem. 271:28348-28358(1996).
RN [8]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=7832746; DOI=10.1042/bj3050363;
RA Emiliani C., Martino S., Stirling J.L., Maras B., Orlacchio A.;
RT "Partial sequence of the purified protein confirms the identity of cDNA
RT coding for human lysosomal alpha-mannosidase B.";
RL Biochem. J. 305:363-366(1995).
RN [9]
RP GLYCOSYLATION AT ASN-930.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-367 AND ASN-766.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [11]
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).
RN [12]
RP IDENTIFICATION 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., 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).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [14]
RP VARIANTS MANSA LEU-72; ARG-356 AND TRP-750.
RX PubMed=9758606; DOI=10.1086/302048;
RA Gotoda Y., Wakamatsu N., Kawai H., Nishida Y., Matsumoto T.;
RT "Missense and nonsense mutations in the lysosomal alpha-mannosidase gene
RT (MANB) in severe and mild forms of alpha-mannosidosis.";
RL Am. J. Hum. Genet. 63:1015-1024(1998).
RN [15]
RP VARIANTS MANSA PRO-355; LYS-402; ARG-714 AND PRO-809, AND VARIANTS VAL-278;
RP ILE-312; GLN-337 AND SER-413.
RX PubMed=9915946; DOI=10.1086/302183;
RA Berg T., Riise H.M.F., Hansen G.M., Malm D., Tranebjaerg L.,
RA Tollersrud O.-K., Nilssen O.;
RT "Spectrum of mutations in alpha-mannosidosis.";
RL Am. J. Hum. Genet. 64:77-88(1999).
RN [16]
RP VARIANT MANSA TYR-453.
RX PubMed=12718372;
RA Oelmez A., Nilssen O., Coskun T., Klenow H.;
RT "Alpha-mannosidosis and mutational analysis in a Turkish patient.";
RL Turk. J. Pediatr. 45:46-50(2003).
RN [17]
RP VARIANTS MANSA LEU-200 AND ASP-801, AND CHARACTERIZATION OF VARIANTS MANSA
RP LEU-200 AND ASP-801.
RX PubMed=15712269; DOI=10.1002/humu.9310;
RA Sbaragli M., Bibi L., Pittis M.G., Balducci C., Heikinheimo P., Ricci R.,
RA Antuzzi D., Parini R., Spaccini L., Bembi B., Beccari T.;
RT "Identification and characterization of five novel MAN2B1 mutations in
RT Italian patients with alpha-mannosidosis.";
RL Hum. Mutat. 25:320-320(2005).
RN [18]
RP VARIANTS MANSA PHE-55; GLU-74; PRO-95; HIS-99; ASN-159; ARG-197; ASN-200;
RP LEU-200; PRO-202; TRP-229; LEU-263; LEU-318; 339-VAL--GLN-342 DEL; PRO-352;
RP LEU-379; CYS-390; LYS-402; VAL-420; TYR-445; CYS-451; TYR-453; PHE-453;
RP GLU-457; SER-501; PRO-565; ARG-745; ARG-800; TRP-800; HIS-ARG-815 INS;
RP ARG-891; PRO-892; CYS-916; HIS-916; PRO-950; ARG-956 AND SER-1000, VARIANTS
RP LEU-248; VAL-278; SER-282; ILE-312; GLN-337; SER-413; SER-481 AND LEU-669,
RP AND CHARACTERIZATION OF VARIANTS MANSA PHE-55; GLU-74; PRO-95; HIS-99;
RP ASN-159; ARG-197; ASN-200; LEU-200; PRO-202; TRP-229; LEU-263; LEU-318;
RP PRO-352; LEU-379; CYS-390; LYS-402; VAL-420; TYR-445; CYS-451; TYR-453;
RP PHE-453; GLU-457; SER-501; PRO-565; ARG-745; ARG-800; TRP-800; HIS-ARG-815
RP INS; ARG-891; PRO-892; CYS-916; HIS-916; PRO-950; ARG-956 AND SER-1000.
RX PubMed=22161967; DOI=10.1002/humu.22005;
RA Riise Stensland H.M., Klenow H.B., Van Nguyen L., Hansen G.M., Malm D.,
RA Nilssen O.;
RT "Identification of 83 novel alpha-mannosidosis-associated sequence
RT variants: functional analysis of MAN2B1 missense mutations.";
RL Hum. Mutat. 33:511-520(2012).
CC -!- FUNCTION: Necessary for the catabolism of N-linked carbohydrates
CC released during glycoprotein turnover. Cleaves all known types of
CC alpha-mannosidic linkages.
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 -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Lysosome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O00754-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00754-2; Sequence=VSP_047391;
CC -!- PTM: First processed into 3 peptides of 70 kDa, 42 kDa (D) and 13/15
CC kDa (E). The 70 kDa peptide is further processed into three peptides
CC (A, B and C). The A, B and C peptides are disulfide-linked.
CC -!- PTM: Heavily glycosylated. {ECO:0000269|PubMed:12754519,
CC ECO:0000269|PubMed:19159218}.
CC -!- DISEASE: Mannosidosis, alpha B, lysosomal (MANSA) [MIM:248500]: A
CC lysosomal storage disease characterized by accumulation of unbranched
CC oligosaccharide chains. This accumulation is expressed histologically
CC as cytoplasmic vacuolation predominantly in the CNS and parenchymatous
CC organs. Depending on the clinical findings at the age of onset, a
CC severe infantile (type I) and a mild juvenile (type II) form of alpha-
CC mannosidosis are recognized. There is considerable variation in the
CC clinical expression with intellectual disability, recurrent infections,
CC impaired hearing and Hurler-like skeletal changes being the most
CC consistent abnormalities. {ECO:0000269|PubMed:12718372,
CC ECO:0000269|PubMed:15712269, ECO:0000269|PubMed:22161967,
CC ECO:0000269|PubMed:9158146, ECO:0000269|PubMed:9758606,
CC ECO:0000269|PubMed:9915946}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 38 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB03816.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAC50812.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Mendelian genes mannosidase, alpha, class 2B, member
CC 1 (MAN2B1); Note=Leiden Open Variation Database (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/MAN2B1";
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DR EMBL; U05572; AAB03816.1; ALT_INIT; mRNA.
DR EMBL; U60266; AAC34130.1; -; mRNA.
DR EMBL; U60899; AAC51362.1; -; Genomic_DNA.
DR EMBL; U60885; AAC51362.1; JOINED; Genomic_DNA.
DR EMBL; U60886; AAC51362.1; JOINED; Genomic_DNA.
DR EMBL; U60887; AAC51362.1; JOINED; Genomic_DNA.
DR EMBL; U60888; AAC51362.1; JOINED; Genomic_DNA.
DR EMBL; U60889; AAC51362.1; JOINED; Genomic_DNA.
DR EMBL; U60890; AAC51362.1; JOINED; Genomic_DNA.
DR EMBL; U60891; AAC51362.1; JOINED; Genomic_DNA.
DR EMBL; U60892; AAC51362.1; JOINED; Genomic_DNA.
DR EMBL; U60893; AAC51362.1; JOINED; Genomic_DNA.
DR EMBL; U60894; AAC51362.1; JOINED; Genomic_DNA.
DR EMBL; U60895; AAC51362.1; JOINED; Genomic_DNA.
DR EMBL; U60896; AAC51362.1; JOINED; Genomic_DNA.
DR EMBL; U60897; AAC51362.1; JOINED; Genomic_DNA.
DR EMBL; U60898; AAC51362.1; JOINED; Genomic_DNA.
DR EMBL; AC010422; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84279.1; -; Genomic_DNA.
DR EMBL; BC000736; AAH00736.1; -; mRNA.
DR EMBL; U68567; AAC50812.1; ALT_INIT; mRNA.
DR CCDS; CCDS32919.1; -. [O00754-1]
DR CCDS; CCDS54224.1; -. [O00754-2]
DR RefSeq; NP_000519.2; NM_000528.3. [O00754-1]
DR RefSeq; NP_001166969.1; NM_001173498.1. [O00754-2]
DR AlphaFoldDB; O00754; -.
DR SMR; O00754; -.
DR BioGRID; 110298; 85.
DR IntAct; O00754; 5.
DR MINT; O00754; -.
DR STRING; 9606.ENSP00000395473; -.
DR BindingDB; O00754; -.
DR ChEMBL; CHEMBL4059; -.
DR CAZy; GH38; Glycoside Hydrolase Family 38.
DR GlyConnect; 775; 16 N-Linked glycans (6 sites).
DR GlyGen; O00754; 13 sites, 17 N-linked glycans (6 sites), 1 O-linked glycan (1 site).
DR iPTMnet; O00754; -.
DR PhosphoSitePlus; O00754; -.
DR BioMuta; MAN2B1; -.
DR CPTAC; CPTAC-2225; -.
DR EPD; O00754; -.
DR jPOST; O00754; -.
DR MassIVE; O00754; -.
DR MaxQB; O00754; -.
DR PaxDb; O00754; -.
DR PeptideAtlas; O00754; -.
DR PRIDE; O00754; -.
DR ProteomicsDB; 33811; -.
DR ProteomicsDB; 48018; -. [O00754-1]
DR Antibodypedia; 26063; 56 antibodies from 11 providers.
DR DNASU; 4125; -.
DR Ensembl; ENST00000221363.8; ENSP00000221363.4; ENSG00000104774.13. [O00754-2]
DR Ensembl; ENST00000456935.7; ENSP00000395473.2; ENSG00000104774.13. [O00754-1]
DR GeneID; 4125; -.
DR KEGG; hsa:4125; -.
DR MANE-Select; ENST00000456935.7; ENSP00000395473.2; NM_000528.4; NP_000519.2.
DR UCSC; uc002mub.3; human. [O00754-1]
DR CTD; 4125; -.
DR DisGeNET; 4125; -.
DR GeneCards; MAN2B1; -.
DR GeneReviews; MAN2B1; -.
DR HGNC; HGNC:6826; MAN2B1.
DR HPA; ENSG00000104774; Low tissue specificity.
DR MalaCards; MAN2B1; -.
DR MIM; 248500; phenotype.
DR MIM; 609458; gene.
DR neXtProt; NX_O00754; -.
DR OpenTargets; ENSG00000104774; -.
DR Orphanet; 309288; Alpha-mannosidosis, adult form.
DR Orphanet; 309282; Alpha-mannosidosis, infantile form.
DR PharmGKB; PA30575; -.
DR VEuPathDB; HostDB:ENSG00000104774; -.
DR eggNOG; KOG1959; Eukaryota.
DR GeneTree; ENSGT01030000234638; -.
DR HOGENOM; CLU_004690_2_0_1; -.
DR InParanoid; O00754; -.
DR OMA; LEFIWRP; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; O00754; -.
DR TreeFam; TF313840; -.
DR BRENDA; 3.2.1.24; 2681.
DR PathwayCommons; O00754; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-8853383; Lysosomal oligosaccharide catabolism.
DR SignaLink; O00754; -.
DR BioGRID-ORCS; 4125; 13 hits in 1078 CRISPR screens.
DR ChiTaRS; MAN2B1; human.
DR GenomeRNAi; 4125; -.
DR Pharos; O00754; Tchem.
DR PRO; PR:O00754; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O00754; protein.
DR Bgee; ENSG00000104774; Expressed in bone marrow cell and 95 other tissues.
DR ExpressionAtlas; O00754; baseline and differential.
DR Genevisible; O00754; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
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:0007611; P:learning or memory; IEA:Ensembl.
DR GO; GO:0006013; P:mannose metabolic process; IEA:Ensembl.
DR GO; GO:0006517; P:protein deglycosylation; TAS:ProtInc.
DR GO; GO:0036211; P:protein modification process; IDA:UniProtKB.
DR Gene3D; 1.20.1270.50; -; 2.
DR Gene3D; 2.60.40.1180; -; 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 InterPro; IPR013780; Glyco_hydro_b.
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; Direct protein sequencing; Disease variant;
KW Disulfide bond; Glycoprotein; Glycosidase; Hydrolase; Lysosome;
KW Metal-binding; Reference proteome; Signal; Zinc; Zymogen.
FT SIGNAL 1..49
FT CHAIN 50..1011
FT /note="Lysosomal alpha-mannosidase"
FT /id="PRO_0000012069"
FT CHAIN 50..345
FT /note="Lysosomal alpha-mannosidase A peptide"
FT /id="PRO_0000012070"
FT CHAIN 346..429
FT /note="Lysosomal alpha-mannosidase B peptide"
FT /id="PRO_0000012071"
FT CHAIN 430..601
FT /note="Lysosomal alpha-mannosidase C peptide"
FT /id="PRO_0000012072"
FT CHAIN 602..882
FT /note="Lysosomal alpha-mannosidase D peptide"
FT /id="PRO_0000012073"
FT CHAIN 883..1011
FT /note="Lysosomal alpha-mannosidase E peptide"
FT /id="PRO_0000012074"
FT ACT_SITE 196
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 72
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 74
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 196
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 446
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 367
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 497
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 645
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 651
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 692
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 766
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 832
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 930
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519"
FT CARBOHYD 989
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 55..358
FT /evidence="ECO:0000250"
FT DISULFID 268..273
FT /evidence="ECO:0000250"
FT DISULFID 412..472
FT /evidence="ECO:0000250"
FT DISULFID 493..501
FT /evidence="ECO:0000250"
FT VAR_SEQ 343
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_047391"
FT VARIANT 55
FT /note="C -> F (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs864621975)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068034"
FT VARIANT 72
FT /note="H -> L (in MANSA; type II; dbSNP:rs387906261)"
FT /evidence="ECO:0000269|PubMed:9158146,
FT ECO:0000269|PubMed:9758606"
FT /id="VAR_003338"
FT VARIANT 74
FT /note="D -> E (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs746702002)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068035"
FT VARIANT 95
FT /note="A -> P (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs754036398)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068036"
FT VARIANT 99
FT /note="Y -> H (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs794727484)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068037"
FT VARIANT 159
FT /note="D -> N (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs864621976)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068038"
FT VARIANT 197
FT /note="P -> R (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs864621977)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068039"
FT VARIANT 200
FT /note="H -> L (in MANSA; no residual enzyme activity;
FT dbSNP:rs864621978)"
FT /evidence="ECO:0000269|PubMed:15712269,
FT ECO:0000269|PubMed:22161967"
FT /id="VAR_026412"
FT VARIANT 200
FT /note="H -> N (in MANSA; reduced enzyme activity;
FT dbSNP:rs772108001)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068040"
FT VARIANT 202
FT /note="R -> P (in MANSA; reduced enzyme activity;
FT dbSNP:rs864621979)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068041"
FT VARIANT 229
FT /note="R -> W (in MANSA; reduced enzyme activity;
FT dbSNP:rs763257568)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068042"
FT VARIANT 248
FT /note="P -> L (in dbSNP:rs117843968)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068043"
FT VARIANT 250
FT /note="A -> S (in dbSNP:rs3745650)"
FT /id="VAR_049209"
FT VARIANT 263
FT /note="P -> L (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs746808159)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068044"
FT VARIANT 278
FT /note="L -> V (in dbSNP:rs1054486)"
FT /evidence="ECO:0000269|PubMed:22161967,
FT ECO:0000269|PubMed:9915946"
FT /id="VAR_003339"
FT VARIANT 282
FT /note="P -> S (in dbSNP:rs45576136)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068045"
FT VARIANT 312
FT /note="T -> I (in dbSNP:rs1054487)"
FT /evidence="ECO:0000269|PubMed:22161967,
FT ECO:0000269|PubMed:9915946"
FT /id="VAR_003340"
FT VARIANT 318
FT /note="S -> L (in MANSA; reduced enzyme activity;
FT dbSNP:rs774034389)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068046"
FT VARIANT 337
FT /note="R -> Q (in dbSNP:rs1133330)"
FT /evidence="ECO:0000269|PubMed:22161967,
FT ECO:0000269|PubMed:9915946"
FT /id="VAR_003341"
FT VARIANT 339..342
FT /note="Missing (in MANSA)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068047"
FT VARIANT 352
FT /note="L -> P (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs864621980)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068048"
FT VARIANT 355
FT /note="T -> P (in MANSA; dbSNP:rs864621992)"
FT /evidence="ECO:0000269|PubMed:9915946"
FT /id="VAR_003342"
FT VARIANT 356
FT /note="P -> R (in MANSA; type I; dbSNP:rs121434333)"
FT /evidence="ECO:0000269|PubMed:9758606"
FT /id="VAR_003343"
FT VARIANT 379
FT /note="P -> L (in MANSA; reduced enzyme activity;
FT dbSNP:rs864621981)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068049"
FT VARIANT 390
FT /note="G -> C (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs864621982)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068050"
FT VARIANT 402
FT /note="E -> K (in MANSA; unknown pathological significance;
FT dbSNP:rs370760999)"
FT /evidence="ECO:0000269|PubMed:22161967,
FT ECO:0000269|PubMed:9915946"
FT /id="VAR_003344"
FT VARIANT 413
FT /note="N -> S (in dbSNP:rs35836657)"
FT /evidence="ECO:0000269|PubMed:22161967,
FT ECO:0000269|PubMed:9915946"
FT /id="VAR_003345"
FT VARIANT 420
FT /note="G -> V (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs772853856)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068051"
FT VARIANT 445
FT /note="H -> Y (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs864621983)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068052"
FT VARIANT 451
FT /note="G -> C (in MANSA; reduced enzyme activity;
FT dbSNP:rs368899357)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068053"
FT VARIANT 453
FT /note="S -> F (in MANSA; reduced enzyme activity;
FT dbSNP:rs864621984)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068054"
FT VARIANT 453
FT /note="S -> Y (in MANSA; dbSNP:rs864621984)"
FT /evidence="ECO:0000269|PubMed:12718372,
FT ECO:0000269|PubMed:22161967"
FT /id="VAR_026413"
FT VARIANT 457
FT /note="V -> E (in MANSA; reduced enzyme activity;
FT dbSNP:rs864621985)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068055"
FT VARIANT 481
FT /note="A -> S (in dbSNP:rs34544747)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_049210"
FT VARIANT 501
FT /note="C -> S (in MANSA; reduced enzyme activity;
FT dbSNP:rs747721968)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068056"
FT VARIANT 565
FT /note="L -> P (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs864621986)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068057"
FT VARIANT 669
FT /note="P -> L (in dbSNP:rs75029862)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068058"
FT VARIANT 714
FT /note="W -> R (in MANSA; dbSNP:rs864621993)"
FT /evidence="ECO:0000269|PubMed:9915946"
FT /id="VAR_003346"
FT VARIANT 745
FT /note="T -> R (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs864621987)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068059"
FT VARIANT 750
FT /note="R -> W (in MANSA; type II; dbSNP:rs80338680)"
FT /evidence="ECO:0000269|PubMed:9758606"
FT /id="VAR_003347"
FT VARIANT 800
FT /note="G -> R (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs398123456)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068060"
FT VARIANT 800
FT /note="G -> W (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs398123456)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068061"
FT VARIANT 801
FT /note="G -> D (in MANSA; no residual enzyme activity;
FT dbSNP:rs864621994)"
FT /evidence="ECO:0000269|PubMed:15712269"
FT /id="VAR_026414"
FT VARIANT 809
FT /note="L -> P (in MANSA; dbSNP:rs80338681)"
FT /evidence="ECO:0000269|PubMed:9915946"
FT /id="VAR_003348"
FT VARIANT 815
FT /note="R -> RHR (in MANSA; results in less than 20% of
FT wild-type enzyme activity)"
FT /id="VAR_068062"
FT VARIANT 891
FT /note="G -> R (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs864621988)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068063"
FT VARIANT 892
FT /note="L -> P (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs864621989)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068064"
FT VARIANT 916
FT /note="R -> C (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs864621990)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068065"
FT VARIANT 916
FT /note="R -> H (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs758765126)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068066"
FT VARIANT 950
FT /note="R -> P (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs139041112)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068067"
FT VARIANT 956
FT /note="L -> R (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs768233248)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068068"
FT VARIANT 1000
FT /note="F -> S (in MANSA; results in less than 20% of wild-
FT type enzyme activity; dbSNP:rs864621991)"
FT /evidence="ECO:0000269|PubMed:22161967"
FT /id="VAR_068069"
FT CONFLICT 3
FT /note="Missing (in Ref. 3; AAC51362)"
FT /evidence="ECO:0000305"
FT CONFLICT 186
FT /note="D -> V (in Ref. 2; AAC34130)"
FT /evidence="ECO:0000305"
FT CONFLICT 384
FT /note="P -> H (in Ref. 7; AAC50812)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1011 AA; 113744 MW; E11C77C19D8BD88C CRC64;
MGAYARASGV CARGCLDSAG PWTMSRALRP PLPPLCFFLL LLAAAGARAG GYETCPTVQP
NMLNVHLLPH THDDVGWLKT VDQYFYGIKN DIQHAGVQYI LDSVISALLA DPTRRFIYVE
IAFFSRWWHQ QTNATQEVVR DLVRQGRLEF ANGGWVMNDE AATHYGAIVD QMTLGLRFLE
DTFGNDGRPR VAWHIDPFGH SREQASLFAQ MGFDGFFFGR LDYQDKWVRM QKLEMEQVWR
ASTSLKPPTA DLFTGVLPNG YNPPRNLCWD VLCVDQPLVE DPRSPEYNAK ELVDYFLNVA
TAQGRYYRTN HTVMTMGSDF QYENANMWFK NLDKLIRLVN AQQAKGSSVH VLYSTPACYL
WELNKANLTW SVKHDDFFPY ADGPHQFWTG YFSSRPALKR YERLSYNFLQ VCNQLEALVG
LAANVGPYGS GDSAPLNEAM AVLQHHDAVS GTSRQHVAND YARQLAAGWG PCEVLLSNAL
ARLRGFKDHF TFCQQLNISI CPLSQTAARF QVIVYNPLGR KVNWMVRLPV SEGVFVVKDP
NGRTVPSDVV IFPSSDSQAH PPELLFSASL PALGFSTYSV AQVPRWKPQA RAPQPIPRRS
WSPALTIENE HIRATFDPDT GLLMEIMNMN QQLLLPVRQT FFWYNASIGD NESDQASGAY
IFRPNQQKPL PVSRWAQIHL VKTPLVQEVH QNFSAWCSQV VRLYPGQRHL ELEWSVGPIP
VGDTWGKEVI SRFDTPLETK GRFYTDSNGR EILERRRDYR PTWKLNQTEP VAGNYYPVNT
RIYITDGNMQ LTVLTDRSQG GSSLRDGSLE LMVHRRLLKD DGRGVSEPLM ENGSGAWVRG
RHLVLLDTAQ AAAAGHRLLA EQEVLAPQVV LAPGGGAAYN LGAPPRTQFS GLRRDLPPSV
HLLTLASWGP EMVLLRLEHQ FAVGEDSGRN LSAPVTLNLR DLFSTFTITR LQETTLVANQ
LREAASRLKW TTNTGPTPHQ TPYQLDPANI TLEPMEIRTF LASVQWKEVD G
