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   13-FEB-2019, entry version 165.
DE   RecName: Full=Beta-mannosidase;
DE            EC=3.2.1.25;
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN MANSB, AND VARIANT ILE-253.
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
RT   of a 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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
CC   -!- FUNCTION: Exoglycosidase that cleaves the single beta-linked
CC       mannose residue from the non-reducing end of all N-linked
CC       glycoprotein oligosaccharides.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Hydrolysis of terminal, non-reducing beta-D-mannose
CC         residues in beta-D-mannosides.; EC=3.2.1.25;
CC   -!- PATHWAY: Glycan metabolism; N-glycan degradation.
CC   -!- SUBCELLULAR LOCATION: Lysosome.
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
CC       of symptoms and age of onset. The disease is associated with a
CC       range of neurological involvement, including various degrees of
CC       mental retardation in most of the cases, hearing loss and speech
CC       impairment, hypotonia, epilepsy and peripheral neuropathy.
CC       Affected individuals have a profound reduction in beta A
CC       mannosidase activity in plasma, fibroblasts and leukocytes.
CC       {ECO:0000269|PubMed:9384606}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 2 family.
CC       {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   UniGene; Hs.480415; -.
DR   ProteinModelPortal; O00462; -.
DR   BioGrid; 110299; 32.
DR   STRING; 9606.ENSP00000226578; -.
DR   BindingDB; O00462; -.
DR   ChEMBL; CHEMBL3903; -.
DR   CAZy; GH2; Glycoside Hydrolase Family 2.
DR   GlyConnect; 1041; -.
DR   iPTMnet; O00462; -.
DR   PhosphoSitePlus; O00462; -.
DR   BioMuta; MANBA; -.
DR   EPD; O00462; -.
DR   jPOST; O00462; -.
DR   MaxQB; O00462; -.
DR   PaxDb; O00462; -.
DR   PeptideAtlas; O00462; -.
DR   PRIDE; O00462; -.
DR   ProteomicsDB; 47912; -.
DR   DNASU; 4126; -.
DR   Ensembl; ENST00000226578; ENSP00000226578; ENSG00000109323.
DR   Ensembl; ENST00000647097; ENSP00000495247; ENSG00000109323.
DR   GeneID; 4126; -.
DR   KEGG; hsa:4126; -.
DR   UCSC; uc003hwg.4; human.
DR   CTD; 4126; -.
DR   DisGeNET; 4126; -.
DR   EuPathDB; HostDB:ENSG00000109323.8; -.
DR   GeneCards; MANBA; -.
DR   H-InvDB; HIX0022086; -.
DR   HGNC; HGNC:6831; MANBA.
DR   HPA; HPA053478; -.
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   eggNOG; KOG2230; Eukaryota.
DR   eggNOG; COG3250; LUCA.
DR   GeneTree; ENSGT00390000001670; -.
DR   HOGENOM; HOG000186862; -.
DR   HOVERGEN; HBG052404; -.
DR   InParanoid; O00462; -.
DR   KO; K01192; -.
DR   OMA; KGHTMGA; -.
DR   OrthoDB; 517710at2759; -.
DR   PhylomeDB; O00462; -.
DR   TreeFam; TF105723; -.
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
DR   Reactome; R-HSA-8853383; Lysosomal oligosaccharide catabolism.
DR   UniPathway; UPA00280; -.
DR   ChiTaRS; MANBA; human.
DR   GeneWiki; Beta-mannosidase; -.
DR   GenomeRNAi; 4126; -.
DR   PRO; PR:O00462; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   Bgee; ENSG00000109323; Expressed in 208 organ(s), highest expression level in leukocyte.
DR   ExpressionAtlas; O00462; baseline and differential.
DR   Genevisible; O00462; HS.
DR   GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome.
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:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0004567; F:beta-mannosidase activity; IBA:GO_Central.
DR   GO; GO:0005537; F:mannose binding; IEA:Ensembl.
DR   GO; GO:0006464; P:cellular protein modification process; NAS:UniProtKB.
DR   GO; GO:0006516; P:glycoprotein catabolic process; IBA:GO_Central.
DR   GO; GO:0046355; P:mannan catabolic process; IBA:GO_Central.
DR   GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome.
DR   GO; GO:0009313; P:oligosaccharide catabolic process; TAS:Reactome.
DR   Gene3D; 2.60.120.260; -; 1.
DR   Gene3D; 2.60.40.10; -; 2.
DR   InterPro; IPR036156; Beta-gal/glucu_dom_sf.
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   Pfam; PF02836; Glyco_hydro_2_C; 1.
DR   SUPFAM; SSF49303; SSF49303; 3.
DR   SUPFAM; SSF49785; SSF49785; 1.
DR   SUPFAM; SSF51445; SSF51445; 1.
PE   2: Evidence at transcript level;
KW   Complete proteome; Glycoprotein; Glycosidase; Hydrolase; Lysosome;
KW   Polymorphism; Reference proteome; Signal.
FT   SIGNAL        1     17       {ECO:0000255}.
FT   CHAIN        18    879       Beta-mannosidase.
FT                                /FTId=PRO_0000012166.
FT   ACT_SITE    457    457       Proton donor. {ECO:0000250}.
FT   CARBOHYD     28     28       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD     35     35       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD     77     77       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    280    280       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    284    284       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    297    297       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    302    302       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    763    763       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   VARIANT     253    253       V -> I (in dbSNP:rs227368).
FT                                {ECO:0000269|PubMed:9384606}.
FT                                /FTId=VAR_026232.
FT   VARIANT     253    253       V -> L (in dbSNP:rs227368).
FT                                /FTId=VAR_059311.
FT   VARIANT     701    701       T -> M (in dbSNP:rs2866413).
FT                                {ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_026233.
FT   CONFLICT     70     70       Y -> H (in Ref. 1; AAC39573).
FT                                {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
//