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 27-MAR-2024, entry version 103. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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.ENSCPOP00000017509; -. DR CAZy; GH38; Glycoside Hydrolase Family 38. DR GlyCosmos; Q8VHC8; 10 sites, No reported glycans. 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; 5474711at2759; -. 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 CDD; cd10810; GH38N_AMII_LAM_like; 1. DR Gene3D; 2.60.40.1360; -; 1. DR Gene3D; 3.20.110.10; Glycoside hydrolase 38, N terminal domain; 1. DR Gene3D; 1.20.1270.50; Glycoside hydrolase family 38, central domain; 2. DR Gene3D; 2.60.40.1180; Golgi alpha-mannosidase II; 1. DR InterPro; IPR011013; Gal_mutarotase_sf_dom. 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 InterPro; IPR048534; Man2a1-like_dom. DR PANTHER; PTHR11607; ALPHA-MANNOSIDASE; 1. DR PANTHER; PTHR11607:SF3; LYSOSOMAL ALPHA-MANNOSIDASE; 1. DR Pfam; PF09261; Alpha-mann_mid; 1. DR Pfam; PF07748; Glyco_hydro_38C; 1. DR Pfam; PF01074; Glyco_hydro_38N; 1. DR Pfam; PF21260; Laman-like_dom; 1. DR SMART; SM00872; Alpha-mann_mid; 1. DR SUPFAM; SSF88688; Families 57/38 glycoside transferase middle domain; 1. DR SUPFAM; SSF74650; Galactose mutarotase-like; 1. DR SUPFAM; SSF88713; Glycoside hydrolase/deacetylase; 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 //