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 29-MAY-2024, entry version 226. 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"; 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; 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; 101. 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 GlyCosmos; O00754; 11 sites, 16 glycans. DR GlyGen; O00754; 14 sites, 21 N-linked glycans (8 sites), 1 O-linked glycan (2 sites). DR iPTMnet; O00754; -. DR PhosphoSitePlus; O00754; -. DR SwissPalm; O00754; -. DR BioMuta; MAN2B1; -. DR CPTAC; CPTAC-2225; -. DR EPD; O00754; -. DR jPOST; O00754; -. DR MassIVE; O00754; -. DR MaxQB; O00754; -. DR PaxDb; 9606-ENSP00000395473; -. DR PeptideAtlas; O00754; -. DR ProteomicsDB; 33811; -. DR ProteomicsDB; 48018; -. [O00754-1] DR Pumba; O00754; -. DR Antibodypedia; 26063; 69 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 AGR; HGNC:6826; -. 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; 5474711at2759; -. 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 1160 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 96 other cell types or tissues. DR ExpressionAtlas; O00754; baseline and differential. 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:0000139; C:Golgi membrane; IEA:TreeGrafter. 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:0006491; P:N-glycan processing; IEA:TreeGrafter. DR GO; GO:0009313; P:oligosaccharide catabolic process; IEA:Ensembl. DR GO; GO:0006517; P:protein deglycosylation; TAS:ProtInc. DR GO; GO:0036211; P:protein modification process; IDA:UniProtKB. DR CDD; cd10810; GH38N_AMII_LAM_like; 1. DR Gene3D; 2.60.40.1360; -; 1. DR Gene3D; 3.20.110.10; Glycoside hydrolase 38, N terminal domain; 1. DR Gene3D; 1.20.1270.50; Glycoside hydrolase family 38, central domain; 2. DR Gene3D; 2.60.40.1180; Golgi alpha-mannosidase II; 1. DR InterPro; IPR011013; Gal_mutarotase_sf_dom. 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 InterPro; IPR048534; Man2a1-like_dom. DR PANTHER; PTHR11607; ALPHA-MANNOSIDASE; 1. DR PANTHER; PTHR11607:SF3; LYSOSOMAL ALPHA-MANNOSIDASE; 1. DR Pfam; PF09261; Alpha-mann_mid; 1. DR Pfam; PF07748; Glyco_hydro_38C; 1. DR Pfam; PF01074; Glyco_hydro_38N; 1. DR Pfam; PF21260; Laman-like_dom; 1. DR SMART; SM00872; Alpha-mann_mid; 1. DR SUPFAM; SSF88688; Families 57/38 glycoside transferase middle domain; 1. DR SUPFAM; SSF74650; Galactose mutarotase-like; 1. DR SUPFAM; SSF88713; Glycoside hydrolase/deacetylase; 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; uncertain 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 //