MANBA_HUMAN
ID MANBA_HUMAN Reviewed; 879 AA.
AC O00462; Q96BC3; Q9NYX9;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 3.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Beta-mannosidase;
DE EC=3.2.1.25 {ECO:0000305|PubMed:12890191, ECO:0000305|PubMed:16904924, ECO:0000305|PubMed:18565776};
DE AltName: Full=Lysosomal beta A mannosidase;
DE AltName: Full=Mannanase;
DE Short=Mannase;
DE Flags: Precursor;
GN Name=MANBA; Synonyms=MANB1;
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], INVOLVEMENT IN MANSB, VARIANT ILE-253, AND
RP TISSUE SPECIFICITY.
RX PubMed=9384606; DOI=10.1093/hmg/7.1.75;
RA Alkhayat A.H., Kraemer S.A., Leipprandt J.R., Macek M., Kleijer W.J.,
RA Friderici K.H.;
RT "Human beta-mannosidase cDNA characterization and first identification of a
RT mutation associated with human beta-mannosidosis.";
RL Hum. Mol. Genet. 7:75-83(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Chang H.-M., Tsai S.-F.;
RT "Genome sequencing of the chromosome 4q region implicated in human
RT hepatocellular carcinoma pathogenesis.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-701.
RC TISSUE=Muscle;
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 FUNCTION, INVOLVEMENT IN MANSB, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=12890191; DOI=10.1046/j.1365-2133.2003.05365.x;
RA Uchino Y., Fukushige T., Yotsumoto S., Hashiguchi T., Taguchi H.,
RA Suzuki N., Konohana I., Kanzaki T.;
RT "Morphological and biochemical studies of human beta-mannosidosis:
RT identification of a novel beta-mannosidase gene mutation.";
RL Br. J. Dermatol. 149:23-29(2003).
RN [5]
RP VARIANTS MANSB TRP-182; GLU-392 AND 466-TRP--TYR-879 DEL, AND CATALYTIC
RP ACTIVITY.
RX PubMed=16904924; DOI=10.1016/j.ymgme.2006.07.001;
RA Gort L., Duque J., Fabeiro J.M., Zulaica A., Coll M.J., Chabas A.;
RT "Molecular analysis in two beta-mannosidosis patients: description of a new
RT adult case.";
RL Mol. Genet. Metab. 89:398-400(2006).
RN [6]
RP VARIANT MANSB PRO-505, CHARACTERIZATION OF VARIANTS MANSB TRP-182; GLU-392
RP AND PRO-505, CHARACTERIZATION OF VARIANT ILE-253, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF ARG-638; ARG-641 AND LEU-749.
RX PubMed=18565776; DOI=10.1016/j.ymgme.2008.04.010;
RA Riise Stensland H.M., Persichetti E., Sorriso C., Hansen G.M., Bibi L.,
RA Paciotti S., Balducci C., Beccari T.;
RT "Identification of two novel beta-mannosidosis-associated sequence
RT variants: biochemical analysis of beta-mannosidase (MANBA) missense
RT mutations.";
RL Mol. Genet. Metab. 94:476-480(2008).
RN [7]
RP CHARACTERIZATION OF VARIANTS MANSB TRP-182; GLU-392; 466-TRP--TYR-879 DEL
RP AND PRO-505, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=30552791; DOI=10.1111/febs.14731;
RA Gytz H., Liang J., Liang Y., Gorelik A., Illes K., Nagar B.;
RT "The structure of mammalian beta-mannosidase provides insight into beta-
RT mannosidosis and nystagmus.";
RL FEBS J. 286:1319-1331(2019).
CC -!- FUNCTION: Exoglycosidase that cleaves the single beta-linked mannose
CC residue from the non-reducing end of all N-linked glycoprotein
CC oligosaccharides. {ECO:0000305|PubMed:12890191,
CC ECO:0000305|PubMed:30552791}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of terminal, non-reducing beta-D-mannose residues
CC in beta-D-mannosides.; EC=3.2.1.25;
CC Evidence={ECO:0000305|PubMed:12890191, ECO:0000305|PubMed:16904924,
CC ECO:0000305|PubMed:18565776, ECO:0000305|PubMed:30552791};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 4.5-5. {ECO:0000269|PubMed:30552791};
CC -!- PATHWAY: Glycan metabolism; N-glycan degradation.
CC {ECO:0000269|PubMed:12890191, ECO:0000269|PubMed:30552791}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q8K2I4}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Detected in pancreas, kidney and
CC placenta, ands at lower levels in liver, lung, brain, heart and muscle.
CC {ECO:0000269|PubMed:9384606}.
CC -!- DISEASE: Mannosidosis, beta A, lysosomal (MANSB) [MIM:248510]: An
CC autosomal recessive lysosomal storage disease of glycoprotein
CC catabolism. Clinical features are heterogeneous with a wide range of
CC symptoms and age of onset. The disease is associated with a range of
CC neurological involvement, including various degrees of intellectual
CC disability in most of the cases, hearing loss and speech impairment,
CC hypotonia, epilepsy and peripheral neuropathy. Affected individuals
CC have a profound reduction in beta A mannosidase activity in plasma,
CC fibroblasts and leukocytes. {ECO:0000269|PubMed:12890191,
CC ECO:0000269|PubMed:16904924, ECO:0000269|PubMed:18565776,
CC ECO:0000269|PubMed:30552791, ECO:0000269|PubMed:9384606}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 2 family. {ECO:0000305}.
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DR EMBL; U60337; AAC39573.1; -; mRNA.
DR EMBL; AF213884; AAF35233.1; -; Genomic_DNA.
DR EMBL; BC015743; AAH15743.1; -; mRNA.
DR CCDS; CCDS3658.1; -.
DR RefSeq; NP_005899.3; NM_005908.3.
DR AlphaFoldDB; O00462; -.
DR SMR; O00462; -.
DR BioGRID; 110299; 115.
DR IntAct; O00462; 13.
DR STRING; 9606.ENSP00000226578; -.
DR BindingDB; O00462; -.
DR ChEMBL; CHEMBL3903; -.
DR CAZy; GH2; Glycoside Hydrolase Family 2.
DR GlyConnect; 1041; 2 N-Linked glycans (1 site).
DR GlyGen; O00462; 8 sites, 2 N-linked glycans (1 site).
DR iPTMnet; O00462; -.
DR PhosphoSitePlus; O00462; -.
DR BioMuta; MANBA; -.
DR EPD; O00462; -.
DR jPOST; O00462; -.
DR MassIVE; O00462; -.
DR MaxQB; O00462; -.
DR PaxDb; O00462; -.
DR PeptideAtlas; O00462; -.
DR PRIDE; O00462; -.
DR ProteomicsDB; 47912; -.
DR Antibodypedia; 26046; 71 antibodies from 22 providers.
DR DNASU; 4126; -.
DR Ensembl; ENST00000647097.2; ENSP00000495247.1; ENSG00000109323.11.
DR GeneID; 4126; -.
DR KEGG; hsa:4126; -.
DR MANE-Select; ENST00000647097.2; ENSP00000495247.1; NM_005908.4; NP_005899.3.
DR UCSC; uc003hwg.4; human.
DR CTD; 4126; -.
DR DisGeNET; 4126; -.
DR GeneCards; MANBA; -.
DR HGNC; HGNC:6831; MANBA.
DR HPA; ENSG00000109323; Low tissue specificity.
DR MalaCards; MANBA; -.
DR MIM; 248510; phenotype.
DR MIM; 609489; gene.
DR neXtProt; NX_O00462; -.
DR OpenTargets; ENSG00000109323; -.
DR Orphanet; 118; Beta-mannosidosis.
DR PharmGKB; PA30577; -.
DR VEuPathDB; HostDB:ENSG00000109323; -.
DR eggNOG; KOG2230; Eukaryota.
DR GeneTree; ENSGT00390000001670; -.
DR InParanoid; O00462; -.
DR OMA; KRQWKGP; -.
DR OrthoDB; 517710at2759; -.
DR PhylomeDB; O00462; -.
DR TreeFam; TF105723; -.
DR PathwayCommons; O00462; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-8853383; Lysosomal oligosaccharide catabolism.
DR SignaLink; O00462; -.
DR UniPathway; UPA00280; -.
DR BioGRID-ORCS; 4126; 6 hits in 1080 CRISPR screens.
DR ChiTaRS; MANBA; human.
DR GeneWiki; Beta-mannosidase; -.
DR GenomeRNAi; 4126; -.
DR Pharos; O00462; Tchem.
DR PRO; PR:O00462; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; O00462; protein.
DR Bgee; ENSG00000109323; Expressed in monocyte and 168 other tissues.
DR ExpressionAtlas; O00462; baseline and differential.
DR Genevisible; O00462; HS.
DR GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004567; F:beta-mannosidase activity; IDA:UniProtKB.
DR GO; GO:0005537; F:mannose binding; IEA:Ensembl.
DR GO; GO:0006516; P:glycoprotein catabolic process; ISS:UniProtKB.
DR GO; GO:0009313; P:oligosaccharide catabolic process; TAS:Reactome.
DR GO; GO:0036211; P:protein modification process; NAS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR036156; Beta-gal/glucu_dom_sf.
DR InterPro; IPR041625; Beta-mannosidase_Ig.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR006103; Glyco_hydro_2_cat.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR041447; Mannosidase_ig.
DR Pfam; PF02836; Glyco_hydro_2_C; 1.
DR Pfam; PF17753; Ig_mannosidase; 1.
DR Pfam; PF17786; Mannosidase_ig; 1.
DR SUPFAM; SSF49303; SSF49303; 3.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF51445; SSF51445; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Glycosidase; Hydrolase; Lysosome;
KW Reference proteome; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..879
FT /note="Beta-mannosidase"
FT /id="PRO_0000012166"
FT ACT_SITE 457
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q8K2I4"
FT ACT_SITE 554
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8K2I4"
FT BINDING 190..192
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8K2I4"
FT BINDING 456
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8K2I4"
FT CARBOHYD 28
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 35
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 284
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 302
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 763
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 167..176
FT /evidence="ECO:0000250|UniProtKB:Q8K2I4"
FT DISULFID 540..629
FT /evidence="ECO:0000250|UniProtKB:Q8K2I4"
FT DISULFID 732..761
FT /evidence="ECO:0000250|UniProtKB:Q8K2I4"
FT DISULFID 764..769
FT /evidence="ECO:0000250|UniProtKB:Q8K2I4"
FT VARIANT 182
FT /note="R -> W (in MANSB; nearly complete loss of enzyme
FT activity; dbSNP:rs374377679)"
FT /evidence="ECO:0000269|PubMed:16904924,
FT ECO:0000269|PubMed:18565776, ECO:0000269|PubMed:30552791"
FT /id="VAR_081392"
FT VARIANT 253
FT /note="V -> I (decreased enzyme activity; dbSNP:rs227368)"
FT /evidence="ECO:0000269|PubMed:18565776,
FT ECO:0000269|PubMed:9384606"
FT /id="VAR_026232"
FT VARIANT 253
FT /note="V -> L (in dbSNP:rs227368)"
FT /id="VAR_059311"
FT VARIANT 392
FT /note="G -> E (in MANSB; nearly complete loss of enzyme
FT activity)"
FT /evidence="ECO:0000269|PubMed:16904924,
FT ECO:0000269|PubMed:18565776, ECO:0000269|PubMed:30552791"
FT /id="VAR_081393"
FT VARIANT 466..879
FT /note="Missing (in MANSB; complete loss of enzyme
FT activity)"
FT /evidence="ECO:0000269|PubMed:16904924,
FT ECO:0000269|PubMed:30552791"
FT /id="VAR_081394"
FT VARIANT 505
FT /note="S -> P (in MANSB; nearly complete loss of enzyme
FT activity; dbSNP:rs121434334)"
FT /evidence="ECO:0000269|PubMed:18565776,
FT ECO:0000269|PubMed:30552791"
FT /id="VAR_081395"
FT VARIANT 701
FT /note="T -> M (in dbSNP:rs2866413)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_026233"
FT MUTAGEN 638
FT /note="R->H: No effect on enzyme activity (in vitro)."
FT /evidence="ECO:0000269|PubMed:30552791"
FT MUTAGEN 641
FT /note="R->H: No effect on enzyme activity (in vitro).
FT Decreased protein stability."
FT /evidence="ECO:0000269|PubMed:30552791"
FT MUTAGEN 749
FT /note="L->H: No effect on enzyme activity (in vitro). No
FT effect on protein stability."
FT /evidence="ECO:0000269|PubMed:30552791"
FT CONFLICT 70
FT /note="Y -> H (in Ref. 1; AAC39573)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 879 AA; 100895 MW; FE8173A4276B722E CRC64;
MRLHLLLLLA LCGAGTTAAE LSYSLRGNWS ICNGNGSLEL PGAVPGCVHS ALFQQGLIQD
SYYRFNDLNY RWVSLDNWTY SKEFKIPFEI SKWQKVNLIL EGVDTVSKIL FNEVTIGETD
NMFNRYSFDI TNVVRDVNSI ELRFQSAVLY AAQQSKAHTR YQVPPDCPPL VQKGECHVNF
VRKEQCSFSW DWGPSFPTQG IWKDVRIEAY NICHLNYFTF SPIYDKSAQE WNLEIESTFD
VVSSKPVGGQ VIVAIPKLQT QQTYSIELQP GKRIVELFVN ISKNITVETW WPHGHGNQTG
YNMTVLFELD GGLNIEKSAK VYFRTVELIE EPIKGSPGLS FYFKINGFPI FLKGSNWIPA
DSFQDRVTSE LLRLLLQSVV DANMNTLRVW GGGIYEQDEF YELCDELGIM VWQDFMFACA
LYPTDQGFLD SVTAEVAYQI KRLKSHPSII IWSGNNENEE ALMMNWYHIS FTDRPIYIKD
YVTLYVKNIR ELVLAGDKSR PFITSSPTNG AETVAEAWVS QNPNSNYFGD VHFYDYISDC
WNWKVFPKAR FASEYGYQSW PSFSTLEKVS STEDWSFNSK FSLHRQHHEG GNKQMLYQAG
LHFKLPQSTD PLRTFKDTIY LTQVMQAQCV KTETEFYRRS RSEIVDQQGH TMGALYWQLN
DIWQAPSWAS LEYGGKWKML HYFAQNFFAP LLPVGFENEN TFYIYGVSDL HSDYSMTLSV
RVHTWSSLEP VCSRVTERFV MKGGEAVCLY EEPVSELLRR CGNCTRESCV VSFYLSADHE
LLSPTNYHFL SSPKEAVGLC KAQITAIISQ QGDIFVFDLE TSAVAPFVWL DVGSIPGRFS
DNGFLMTEKT RTILFYPWEP TSKNELEQSF HVTSLTDIY
