ID MA2B1_BOVIN Reviewed; 999 AA. AC Q29451; F1MMX7; O02848; O19138; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 16-OCT-2013, sequence version 4. DT 27-MAR-2024, entry version 155. 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 Contains: DE RecName: Full=Lysosomal alpha-mannosidase A peptide; DE Contains: DE RecName: Full=Lysosomal alpha-mannosidase B peptide; DE Contains: DE RecName: Full=Lysosomal alpha-mannosidase C peptide; DE Contains: DE RecName: Full=Lysosomal alpha-mannosidase D peptide; DE Contains: DE RecName: Full=Lysosomal alpha-mannosidase E peptide; DE Flags: Precursor; GN Name=MAN2B1; Synonyms=MANB; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], PARTIAL PROTEIN SEQUENCE, AND RP VARIANTS AM HIS-221 AND LEU-321. RC TISSUE=Kidney; RX PubMed=9208932; DOI=10.1111/j.1432-1033.1997.00410.x; RA Tollersrud O.-K., Berg T., Healy P., Evjen G., Ramachandran U., Nilssen O.; RT "Purification of bovine lysosomal alpha-mannosidase, characterization of RT its gene and determination of two mutations that cause alpha- RT mannosidosis."; RL Eur. J. Biochem. 246:410-419(1997). RN [2] RP SEQUENCE REVISION TO 358. RA Berg T.; RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Hereford; RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42; RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D., RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G., RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.; RT "A whole-genome assembly of the domestic cow, Bos taurus."; RL Genome Biol. 10:R42.01-R42.10(2009). RN [4] RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 52-999 IN COMPLEX WITH ZINC ION, RP COFACTOR, ACTIVE SITE, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-134; RP ASN-634; ASN-681 AND ASN-755. RX PubMed=12634058; DOI=10.1016/s0022-2836(03)00172-4; RA Heikinheimo P., Helland R., Leiros H.-K.S., Leiros I., Karlsen S., RA Evjen G., Ravelli R., Schoehn G., Ruigrok R., Tollersrud O.-K., RA McSweeney S., Hough E.; RT "The structure of bovine lysosomal alpha-mannosidase suggests a novel RT mechanism for low-pH activation."; RL J. Mol. Biol. 327:631-644(2003). CC -!- FUNCTION: Necessary for the catabolism of N-linked carbohydrates CC released during glycoprotein turnover. 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; CC Evidence={ECO:0000269|PubMed:12634058}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:12634058}; CC -!- SUBUNIT: Homodimer. CC -!- SUBCELLULAR LOCATION: Lysosome. CC -!- PTM: Processed into 5 peptides of 35/38 kDa (A), 11/13 kDa (B) and 22 CC kDa (C), 38 kDa (D) and 13/15 kDa (E). The A, B and C peptides are CC disulfide-linked into a 67 kDa complex. CC -!- PTM: Heavily glycosylated. Some sugar chains are of the high-mannose CC type. 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. The disease CC manifests itself by head tremor, aggressive tendency, ataxia, failure CC to thrive, and early death. {ECO:0000269|PubMed:9208932}. 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; L31373; AAB67726.2; -; mRNA. DR EMBL; U97694; AAC48763.1; -; Genomic_DNA. DR EMBL; U97686; AAC48763.1; JOINED; Genomic_DNA. DR EMBL; U97687; AAC48763.1; JOINED; Genomic_DNA. DR EMBL; U97688; AAC48763.1; JOINED; Genomic_DNA. DR EMBL; U97689; AAC48763.1; JOINED; Genomic_DNA. DR EMBL; U97690; AAC48763.1; JOINED; Genomic_DNA. DR EMBL; U97691; AAC48763.1; JOINED; Genomic_DNA. DR EMBL; U97692; AAC48763.1; JOINED; Genomic_DNA. DR EMBL; U97693; AAC48763.1; JOINED; Genomic_DNA. DR EMBL; DAAA02019388; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR RefSeq; NP_776986.2; NM_174561.2. DR PDB; 1O7D; X-ray; 2.70 A; A=51-348, B=349-432, C=433-591, D=592-873, E=874-999. DR PDBsum; 1O7D; -. DR AlphaFoldDB; Q29451; -. DR SMR; Q29451; -. DR STRING; 9913.ENSBTAP00000064540; -. DR ChEMBL; CHEMBL1932902; -. DR CAZy; GH38; Glycoside Hydrolase Family 38. DR GlyCosmos; Q29451; 8 sites, No reported glycans. DR iPTMnet; Q29451; -. DR PaxDb; 9913-ENSBTAP00000008193; -. DR Ensembl; ENSBTAT00000070599.1; ENSBTAP00000064540.1; ENSBTAG00000006241.5. DR GeneID; 282272; -. DR KEGG; bta:282272; -. DR CTD; 4125; -. DR VEuPathDB; HostDB:ENSBTAG00000006241; -. DR VGNC; VGNC:108504; MAN2B1. DR eggNOG; KOG1959; Eukaryota. DR GeneTree; ENSGT01030000234638; -. DR HOGENOM; CLU_004690_2_0_1; -. DR InParanoid; Q29451; -. DR OMA; LEFIWRP; -. DR OrthoDB; 5474711at2759; -. DR TreeFam; TF313840; -. DR BRENDA; 3.2.1.24; 908. DR Reactome; R-BTA-6798695; Neutrophil degranulation. DR Reactome; R-BTA-8853383; Lysosomal oligosaccharide catabolism. DR EvolutionaryTrace; Q29451; -. DR PRO; PR:Q29451; -. DR Proteomes; UP000009136; Chromosome 7. DR Bgee; ENSBTAG00000006241; Expressed in caput epididymis and 105 other cell types or tissues. DR ExpressionAtlas; Q29451; baseline and differential. DR GO; GO:0005615; C:extracellular space; IEA:Ensembl. DR GO; GO:0043202; C:lysosomal lumen; IEA:Ensembl. DR GO; GO:0005764; C:lysosome; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl. DR GO; GO:0004559; F:alpha-mannosidase activity; IBA:GO_Central. DR GO; GO:0030246; F:carbohydrate binding; IEA:InterPro. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0007611; P:learning or memory; IEA:Ensembl. DR GO; GO:0006013; P:mannose metabolic process; IEA:Ensembl. DR GO; GO:0009313; P:oligosaccharide catabolic process; IEA:Ensembl. DR GO; GO:0036211; P:protein modification process; IEA:Ensembl. 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 3D-structure; Direct protein sequencing; Disease variant; Disulfide bond; KW Glycoprotein; Glycosidase; Hydrolase; Lysosome; Metal-binding; KW Reference proteome; Signal; Zinc; Zymogen. FT SIGNAL 1..50 FT CHAIN 51..999 FT /note="Lysosomal alpha-mannosidase" FT /id="PRO_0000012060" FT CHAIN 51..347 FT /note="Lysosomal alpha-mannosidase A peptide" FT /id="PRO_0000012061" FT CHAIN 348..431 FT /note="Lysosomal alpha-mannosidase B peptide" FT /id="PRO_0000012062" FT CHAIN 432..590 FT /note="Lysosomal alpha-mannosidase C peptide" FT /id="PRO_0000012063" FT PROPEP 591..621 FT /evidence="ECO:0000255" FT /id="PRO_0000012064" FT CHAIN 622..871 FT /note="Lysosomal alpha-mannosidase D peptide" FT /id="PRO_0000012065" FT CHAIN 872..999 FT /note="Lysosomal alpha-mannosidase E peptide" FT /id="PRO_0000012066" FT REGION 1..25 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 197 FT /note="Nucleophile" FT /evidence="ECO:0000269|PubMed:12634058" FT BINDING 73 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:12634058, FT ECO:0007744|PDB:1O7D" FT BINDING 75 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:12634058, FT ECO:0007744|PDB:1O7D" FT BINDING 197 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:12634058, FT ECO:0007744|PDB:1O7D" FT BINDING 448 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:12634058, FT ECO:0007744|PDB:1O7D" FT CARBOHYD 134 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12634058, FT ECO:0007744|PDB:1O7D" FT CARBOHYD 369 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 499 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 634 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12634058, FT ECO:0007744|PDB:1O7D" FT CARBOHYD 640 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 681 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12634058, FT ECO:0007744|PDB:1O7D" FT CARBOHYD 755 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12634058, FT ECO:0007744|PDB:1O7D" FT CARBOHYD 919 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT DISULFID 56 FT /note="Interchain (with C-360)" FT /evidence="ECO:0000269|PubMed:12634058, FT ECO:0007744|PDB:1O7D" FT DISULFID 269..274 FT /evidence="ECO:0000269|PubMed:12634058" FT DISULFID 360 FT /note="Interchain (with C-56)" FT /evidence="ECO:0000269|PubMed:12634058, FT ECO:0007744|PDB:1O7D" FT DISULFID 414 FT /note="Interchain (with C-474)" FT /evidence="ECO:0000269|PubMed:12634058, FT ECO:0007744|PDB:1O7D" FT DISULFID 474 FT /note="Interchain (with C-414)" FT /evidence="ECO:0000269|PubMed:12634058, FT ECO:0007744|PDB:1O7D" FT DISULFID 495..503 FT /evidence="ECO:0000269|PubMed:12634058" FT VARIANT 221 FT /note="R -> H (in AM; Galloway cattle)" FT /evidence="ECO:0000269|PubMed:9208932" FT VARIANT 321 FT /note="F -> L (in AM; Angus cattle)" FT /evidence="ECO:0000269|PubMed:9208932" FT CONFLICT 176 FT /note="G -> R (in Ref. 1; AAB67726/AAC48763)" FT /evidence="ECO:0000305" FT CONFLICT 512..550 FT /note="Missing (in Ref. 1; AAC48763)" FT /evidence="ECO:0000305" FT STRAND 61..70 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 76..80 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 82..87 FT /evidence="ECO:0007829|PDB:1O7D" FT TURN 91..93 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 98..111 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 117..119 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 122..130 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 134..145 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 148..153 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 155..157 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 161..163 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 166..184 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 185..188 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 191..200 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 203..211 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 216..220 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 224..232 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 236..241 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 244..246 FT /evidence="ECO:0007829|PDB:1O7D" FT TURN 248..251 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 252..257 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 290..305 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 308..317 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 326..341 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 351..355 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 358..367 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 392..394 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 398..420 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 436..444 FT /evidence="ECO:0007829|PDB:1O7D" FT TURN 448..452 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 457..486 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 498..500 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 504..508 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 510..518 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 520..522 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 524..532 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 537..540 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 542..544 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 550..553 FT /evidence="ECO:0007829|PDB:1O7D" FT TURN 555..557 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 560..568 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 572..580 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 595..597 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 599..605 FT /evidence="ECO:0007829|PDB:1O7D" FT TURN 607..609 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 611..617 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 623..625 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 627..635 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 653..657 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 659..661 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 666..671 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 676..683 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 686..692 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 697..705 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 716..723 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 731..736 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 739..745 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 750..752 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 761..763 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 765..774 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 776..786 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 788..790 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 797..805 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 811..813 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 822..825 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 826..837 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 838..853 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 857..862 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 880..883 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 890..898 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 901..907 FT /evidence="ECO:0007829|PDB:1O7D" FT TURN 912..919 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 924..927 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 929..943 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 947..950 FT /evidence="ECO:0007829|PDB:1O7D" FT HELIX 951..953 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 978..981 FT /evidence="ECO:0007829|PDB:1O7D" FT STRAND 986..994 FT /evidence="ECO:0007829|PDB:1O7D" SQ SEQUENCE 999 AA; 112919 MW; C86DE7532925DB10 CRC64; MVGDARPSGV RAGGCRGAVG SRTSSRALRP PLPPLSSLFV LFLAAPCAWA AGYKTCPKVK PDMLNVHLVP HTHDDVGWLK TVDQYFYGIY NNIQPAGVQY ILDSVISSLL ANPTRRFIYV EIAFFSRWWR QQTNATQKIV RELVRQGRLE FANGGWVMND EATTHYGAII DQMTLGLRFL EETFGSDGRP RVAWHIDPFG HSREQASLFA QMGFDGFFFG RLDYQDKKVR KKTLQMEQVW RASTSLKPPT ADLFTSVLPN MYNPPEGLCW DMLCADKPVV EDTRSPEYNA KELVRYFLKL ATDQGKLYRT KHTVMTMGSD FQYENANTWF KNLDKLIQLV NAQQRANGIR VNVLYSTPAC YLWELNKANL SWSVKKDDFF PYADGPYMFW TGYFSSRPAL KRYERLSYNF LQVCNQLEAL AGPAANVGPY GSGDSAPLNE AMAVLQHHDA VSGTSRQHVA NDYARQLSEG WRPCEVLMSN ALAHLSGLKE DFAFCRKLNI SICPLTQTAE RFQVIVYNPL GRKVDWMVRL PVSKHVYLVK DPGGKIVPSD VVTIPSSDSQ ELLFSALVPA VGFSIYSVSQ MPNQRPQKSW SRDLVIQNEY LRARFDPNTG LLMELENLEQ NLLLPVRQAF YWYNASTGNN LSSQASGAYI FRPNQNKPLF VSHWAQTHLV KASLVQEVHQ NFSAWCSQVV RLYPRQRHLE LEWTVGPIPV GDGWGKEVIS RFDTALATRG LFYTDSNGRE ILERRRNYRP TWKLNQTEPV AGNYYPVNSR IYITDGNMQL TVLTDRSQGG SSLRDGSLEL MVHRRLLKDD ARGVGEPLNK EGSGLWVRGR HLVLLDKKET AAARHRLQAE MEVLAPQVVL AQGGGARYRL EKAPRTQFSG LRRELPPSVR LLTLARWGPE TLLLRLEHQF AVGEDSGRNL SSPVTLDLTN LFSAFTITNL RETTLAANQL LAYASRLQWT TDTGPTPHPS PSRPVSATIT LQPMEIRTFL ASVQWEEDG //