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-NOV-2009, entry version 86.
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 LYSOSOMAL
RP   BETA-MANNOSIDASIS, AND VARIANT ILE-253.
RX   MEDLINE=98046009; 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: Hydrolysis of terminal, non-reducing beta-D-
CC       mannose residues in beta-D-mannosides.
CC   -!- PATHWAY: Glycan metabolism; N-glycan degradation.
CC   -!- SUBCELLULAR LOCATION: Lysosome.
CC   -!- DISEASE: Defects in MANBA are the cause of a mild disorder that
CC       affects peripheral and central nervous system myelin.
CC   -!- DISEASE: Defects in MANBA are the cause of lysosomal beta-
CC       mannosidosis [MIM:248510]. Beta-mannosidosis is an autosomal
CC       recessive lysosomal storage disease of glycoprotein catabolism.
CC       Clinical features are heterogeneous with a wide range of symptoms
CC       and age of onset. The disease is associated with a range of
CC       neurological involvement, including various degrees of mental
CC       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-mannosidase
CC       activity in plasma, fibroblasts and leukocytes.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 2 family.
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MANBA";
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DR   EMBL; U60337; AAC39573.1; -; mRNA.
DR   EMBL; AF213884; AAF35233.1; -; Genomic_DNA.
DR   EMBL; BC015743; AAH15743.1; -; mRNA.
DR   IPI; IPI00298793; -.
DR   RefSeq; NP_005899.3; -.
DR   UniGene; Hs.480415; -.
DR   STRING; O00462; -.
DR   CAZy; GH2; Glycoside Hydrolase Family 2.
DR   PhosphoSite; O00462; -.
DR   PeptideAtlas; O00462; -.
DR   PRIDE; O00462; -.
DR   Ensembl; ENST00000226578; ENSP00000226578; ENSG00000109323; Homo sapiens.
DR   GeneID; 4126; -.
DR   KEGG; hsa:4126; -.
DR   NMPDR; fig|9606.3.peg.24477; -.
DR   UCSC; uc003hwg.1; human.
DR   CTD; 4126; -.
DR   GeneCards; GC04M103771; -.
DR   H-InvDB; HIX0022086; -.
DR   HGNC; HGNC:6831; MANBA.
DR   MIM; 248510; phenotype.
DR   MIM; 609489; gene.
DR   Orphanet; 118; Beta-mannosidosis.
DR   PharmGKB; PA30577; -.
DR   HOGENOM; O00462; -.
DR   HOVERGEN; O00462; -.
DR   OMA; FVRKEQC; -.
DR   BRENDA; 3.2.1.25; 247.
DR   NextBio; 16200; -.
DR   ArrayExpress; O00462; -.
DR   Bgee; O00462; -.
DR   CleanEx; HS_MANBA; -.
DR   Genevestigator; O00462; -.
DR   GermOnline; ENSG00000109323; Homo sapiens.
DR   GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0004567; F:beta-mannosidase activity; TAS:ProtInc.
DR   GO; GO:0043169; F:cation binding; IEA:InterPro.
DR   GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR   GO; GO:0006464; P:protein modification process; NAS:UniProtKB.
DR   InterPro; IPR006103; Glyco_hydro_2_TIM.
DR   InterPro; IPR013781; Glyco_hydro_sg_catalytic.
DR   Gene3D; G3DSA:3.20.20.80; Glyco_hydro_cat; 1.
DR   Pfam; PF02836; Glyco_hydro_2_C; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Glycoprotein; Glycosidase; Hydrolase; Lysosome;
KW   Polymorphism; Signal.
FT   SIGNAL        1     17       Potential.
FT   CHAIN        18    879       Beta-mannosidase.
FT                                /FTId=PRO_0000012166.
FT   ACT_SITE    457    457       Proton donor (By similarity).
FT   CARBOHYD     28     28       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD     35     35       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD     77     77       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    280    280       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    284    284       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    297    297       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    302    302       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    763    763       N-linked (GlcNAc...) (Potential).
FT   VARIANT     253    253       V -> I (in dbSNP:rs227368).
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                                /FTId=VAR_026233.
FT   CONFLICT     70     70       Y -> H (in Ref. 1; AAC39573).
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
//