MA2B1_CAVPO
ID MA2B1_CAVPO Reviewed; 1007 AA.
AC Q8VHC8; Q8VHC6; Q8VHC7;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 99.
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 Flags: Precursor;
GN Name=MAN2B1; Synonyms=MANB;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT AM TRP-227, AND VARIANT ILE-55.
RX PubMed=11959458; DOI=10.1016/s0925-4439(01)00081-3;
RA Berg T., Hopwood J.J.;
RT "Alpha-mannosidosis in the guinea pig: cloning of the lysosomal alpha-
RT mannosidase cDNA and identification of a missense mutation causing alpha-
RT mannosidosis.";
RL Biochim. Biophys. Acta 1586:169-176(2002).
CC -!- FUNCTION: Necessary for the catabolism of N-linked carbohydrates
CC released during glycoprotein turnover. {ECO:0000250}.
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 -!- DISEASE: Note=Defects in MAN2B1 are the cause of lysosomal alpha-
CC mannosidosis (AM). AM is a lysosomal storage disease characterized by
CC accumulation of unbranched oligosaccharide chains.
CC {ECO:0000269|PubMed:11959458}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 38 family. {ECO:0000305}.
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DR EMBL; AY036153; AAL58982.1; -; mRNA.
DR EMBL; AY036154; AAL58983.1; -; mRNA.
DR EMBL; AY036155; AAL58984.1; -; mRNA.
DR RefSeq; NP_001244175.1; NM_001257246.1.
DR AlphaFoldDB; Q8VHC8; -.
DR SMR; Q8VHC8; -.
DR STRING; 10141.ENSCPOP00000002084; -.
DR CAZy; GH38; Glycoside Hydrolase Family 38.
DR GeneID; 100718205; -.
DR KEGG; cpoc:100718205; -.
DR CTD; 4125; -.
DR eggNOG; KOG1959; Eukaryota.
DR HOGENOM; CLU_004690_2_0_1; -.
DR InParanoid; Q8VHC8; -.
DR OrthoDB; 201312at2759; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0004559; F:alpha-mannosidase activity; IEA:UniProtKB-EC.
DR GO; GO:0030246; F:carbohydrate binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006013; P:mannose metabolic process; IEA:InterPro.
DR Gene3D; 1.20.1270.50; -; 2.
DR Gene3D; 2.60.40.1180; -; 1.
DR Gene3D; 3.20.110.10; -; 1.
DR InterPro; IPR011013; Gal_mutarotase_sf_dom.
DR InterPro; IPR041147; GH38_C.
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 Pfam; PF09261; Alpha-mann_mid; 1.
DR Pfam; PF17677; Glyco_hydro38C2; 1.
DR Pfam; PF07748; Glyco_hydro_38C; 1.
DR Pfam; PF01074; Glyco_hydro_38N; 1.
DR SMART; SM00872; Alpha-mann_mid; 1.
DR SUPFAM; SSF74650; SSF74650; 1.
DR SUPFAM; SSF88688; SSF88688; 1.
DR SUPFAM; SSF88713; SSF88713; 1.
PE 1: Evidence at protein level;
KW Disease variant; Disulfide bond; Glycoprotein; Glycosidase; Hydrolase;
KW Lysosome; Metal-binding; Reference proteome; Signal; Zinc.
FT SIGNAL 1..47
FT /evidence="ECO:0000255"
FT CHAIN 48..1007
FT /note="Lysosomal alpha-mannosidase"
FT /id="PRO_0000012067"
FT ACT_SITE 194
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 70
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 72
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 194
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 444
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 365
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 495
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 540
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 639
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 686
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 760
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 927
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 53..356
FT /evidence="ECO:0000250"
FT DISULFID 266..271
FT /evidence="ECO:0000250"
FT DISULFID 410..470
FT /evidence="ECO:0000250"
FT DISULFID 491..499
FT /evidence="ECO:0000250"
FT VARIANT 55
FT /note="M -> I"
FT /evidence="ECO:0000269|PubMed:11959458"
FT VARIANT 227
FT /note="R -> W (in AM)"
FT /evidence="ECO:0000269|PubMed:11959458"
SQ SEQUENCE 1007 AA; 113184 MW; C128EB9948A44D41 CRC64;
MGASVLPLGL GAGDCQSSSG RRMSACLPRT ALSFLLSLLL ATPGARAAGY ETCPMVQPGM
LNVHLVAHTH DDVGWLKTVD QYYWGIHNDL QQAGVQYILD SVISALLAEP TRRFVYVEMA
FFSRWWHQQT NETQEVVRRL VRQGRLEFAN GGWVMNDEAA THYGAIVDQM TLGLRFLEDT
FGSDGRPRVA WHIDPFGHSR EQASLFAQMG FDGVFFGRID YQDKLVRKKR REMELVWRAS
ASLKAPAADL FTGVLPNNYG PPEGLCWDVL CADPPVVDDP RSPEYNAKKL VSYFLQLATA
QGRYYRTNHT VMTMGSDFQY ENANTWFKNL DKLIQLVNMQ QANGSRVHVL YSTPACYLWE
LNKANLTWPV KEDDFFPYAD GPHMFWTGYF SSRPALKRYE RLSYNFLQVC NQLEAQVGPA
ANVGPYGHGD SSPLNQAMAV LQHHDAVSGT SKQHVADDYA RQLAAGWGPC EVLLSNALAK
LSGSKETFLF CRDLNISICP FSQTSERFQV LVYNPLGRKV DRMVRLPVRK GLFLIKDPGN
NTVPSTVVEL TSSGNPELLF PALVPALGFS VYSVTRVSDQ NPQTRSQHSR PQKYSSPVLS
IKNEYLRASF HPDTGLLSMI EVLDRKLTLP VNQAFFWYNA SVGDKRSSQA SGAYIFRPSQ
QWPFPVSHLA RTRLVKTALV QEVHQNFTAW CSQVVRLYSG QRHLELEWTV GPIPVGDKWG
KEIISRFDTP LETGGVFFTD SNGREVLERR RDYRPSWKLN QTEPVAGNYY PVNSRIYITD
GKMQLTVLTD RSQGGSSMSD GSLELMVHRR LLKDDGRGVG EALQEPGSGG WVRGRHLLLL
DTAREAAAEH RLLAEKELLA PQLVLAPGQG PSYHHDHHEA VPRKQFSGLR RQLPPSVRLL
TLARWGPDTL LLRLEHQFAL GEDSSRNLSL PVTLDLQDLF STFTITRLQE TTLAANQLRA
SASRLKWTTE IDPISRPAVP RLDPSSITLQ PMEIRTFVAS VQWEENS
