ID   MANBA_CAPHI             Reviewed;         879 AA.
AC   Q95327;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1997, sequence version 1.
DT   27-MAR-2024, entry version 114.
DE   RecName: Full=Beta-mannosidase;
DE            EC=3.2.1.25 {ECO:0000305|PubMed:1556126, ECO:0000305|PubMed:7228876};
DE   AltName: Full=Lysosomal beta A mannosidase;
DE   AltName: Full=Mannanase;
DE            Short=Mannase;
DE   Flags: Precursor;
GN   Name=MANBA;
OS   Capra hircus (Goat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Caprinae; Capra.
OX   NCBI_TaxID=9925;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND DISEASE.
RC   TISSUE=Kidney;
RX   PubMed=8921369; DOI=10.1006/geno.1996.0519;
RA   Leipprandt J.R., Kraemer S.A., Haithcock B.E., Chen H., Dyme J.L.,
RA   Cavanagh K.T., Friderici K.H., Jones M.Z.;
RT   "Caprine beta-mannosidase: sequencing and characterization of the cDNA and
RT   identification of the molecular defect of caprine beta-mannosidosis.";
RL   Genomics 37:51-56(1996).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, PATHWAY, DISEASE, SUBCELLULAR LOCATION, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=7228876; DOI=10.1016/s0021-9258(19)69384-1;
RA   Jones M.Z., Dawson G.;
RT   "Caprine beta-mannosidosis. Inherited deficiency of beta-D-mannosidase.";
RL   J. Biol. Chem. 256:5185-5188(1981).
RN   [3]
RP   CATALYTIC ACTIVITY, GLYCOSYLATION, AND TISSUE SPECIFICITY.
RX   PubMed=1556126; DOI=10.1016/s0021-9258(18)42678-6;
RA   Sopher B.L., Traviss C.E., Cavanagh K.T., Jones M.Z., Friderici K.H.;
RT   "Purification and characterization of goat lysosomal beta-mannosidase using
RT   monoclonal and polyclonal antibodies.";
RL   J. Biol. Chem. 267:6178-6182(1992).
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:0000269|PubMed:7228876}.
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:1556126, ECO:0000305|PubMed:7228876};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 5. {ECO:0000269|PubMed:7228876};
CC   -!- PATHWAY: Glycan metabolism; N-glycan degradation.
CC       {ECO:0000269|PubMed:7228876}.
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q8K2I4}.
CC   -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000305|PubMed:7228876}.
CC   -!- TISSUE SPECIFICITY: Detected in kidney (at protein level)
CC       (PubMed:1556126). Found in spleen and to a lesser extent in liver. Not
CC       detected in kidney or brain. {ECO:0000269|PubMed:1556126}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:1556126}.
CC   -!- DISEASE: Note=Defects in MANBA cause beta-mannosidosis, a severe
CC       disorder that affects peripheral and central nervous system myelin
CC       resulting in tremor, nystagmus, ataxia and early death. The primary
CC       storage products associated with the enzyme deficiency are the
CC       trisaccharide Man-beta-1-4-GlcNAc-beta-1-4-GlcNAc and the disaccharide
CC       Man-beta-1-4-GlcNAc. {ECO:0000269|PubMed:7228876,
CC       ECO:0000269|PubMed:8921369}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 2 family. {ECO:0000305}.
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DR   EMBL; U46067; AAC48665.1; -; mRNA.
DR   RefSeq; NP_001272620.1; NM_001285691.1.
DR   AlphaFoldDB; Q95327; -.
DR   SMR; Q95327; -.
DR   STRING; 9925.ENSCHIP00000023174; -.
DR   CAZy; GH2; Glycoside Hydrolase Family 2.
DR   GlyCosmos; Q95327; 4 sites, No reported glycans.
DR   GeneID; 100750234; -.
DR   KEGG; chx:100750234; -.
DR   CTD; 4126; -.
DR   OrthoDB; 2504097at2759; -.
DR   BRENDA; 3.2.1.25; 1166.
DR   UniPathway; UPA00280; -.
DR   Proteomes; UP000291000; Unassembled WGS sequence.
DR   Proteomes; UP000694566; Unplaced.
DR   Proteomes; UP000694900; Genome assembly.
DR   GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0004567; F:beta-mannosidase activity; ISS:UniProtKB.
DR   GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR   GO; GO:0006516; P:glycoprotein catabolic process; ISS:UniProtKB.
DR   Gene3D; 2.60.120.260; Galactose-binding domain-like; 1.
DR   Gene3D; 3.20.20.80; Glycosidases; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 3.
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   PANTHER; PTHR43730; BETA-MANNOSIDASE; 1.
DR   PANTHER; PTHR43730:SF1; BETA-MANNOSIDASE; 1.
DR   Pfam; PF02836; Glyco_hydro_2_C; 1.
DR   Pfam; PF17753; Ig_mannosidase; 1.
DR   Pfam; PF17786; Mannosidase_ig; 1.
DR   SUPFAM; SSF51445; (Trans)glycosidases; 1.
DR   SUPFAM; SSF49303; beta-Galactosidase/glucuronidase domain; 3.
DR   SUPFAM; SSF49785; Galactose-binding domain-like; 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_0000012165"
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        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        297
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        803
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         56
FT                   /note="R -> Q"
FT   VARIANT         340
FT                   /note="T -> S"
SQ   SEQUENCE   879 AA;  101386 MW;  2B96F03596B480C0 CRC64;
     MLLRLLLLLA PCGAGFATEV VSISLRGNWK IHNGNGSLQL PAAVPGCVHS ALFNKRIIKD
     PYYRFNNLDY RWIALDNWTY IKKFKLHSDM SEWNKVNLVF EGIDTVAVVL LNSVPIGKTD
     NMFRRYSFDI THMVKAVNII EVRFQSPVIY ANQRSERHTA YWVPPNCPPP VQDGECHVNF
     IRKMQCSFGW DWGPSFPTQG IWKDVRIEAY NICHLNYFMF TPIYDNYMET WNLKIESSFD
     VVSSKLVSGE AIVAIPELNI QQRNNIELRH GERTVKLFVK IDKAVIVETW WPHGHGNQTG
     YDMTVTFELD GGLRFEKSAK VYFRTVELVE EPIQNSPGLT FYFKINGLPI FLKGSNWIPA
     DSFQDRVTSD MLRLLLQSVV DANMNALRVW GGGIYEQDEF YELCDELGIM IWQDFMFACA
     LYPTDEDFMD SVREEVTHQV RRLKSHPSII TWSGNNENEA ALMMGWYDTK PGYLHTYIKD
     YVTLYVKNIR TIVLEGDQTR PFIISSPTNG AKTTAEGWLS PNPYDLNYGD VHFYDYMSDC
     WNWRTFPKAR FVSEYGYQSW PSFSTLEKVS SEEDWSYESS FALHRQHLIN GNSEMLQQIE
     LHFKLPNSAD QLRRFKDTLY LTQVMQAQCV KTETEFYRRS RNEIVDGKGH TMGALYWQLN
     DIWQAPSWSS LEYGGKWKML HYFARRFFAP LLPVGFEDKD VLFIYGVSDL PSDHQMMLTV
     RVHTWSSLEL VCSELTNPFV MKAGESVVLY SKPVPELLKG CPGCTRQSCV VSFYLSTDGE
     LLSPINYHFL SSLKNAKGLH KANITATISQ QGNTFVFDLK TSAVAPFVWL DVGSIPGRFS
     DNGFLMTEKT RTVFFYPWKP TSKSELEQSF HVTSLADTY
//