We will be switching to the new UniProt website on Tuesday, June 28. Please explore and share your feedback.
Take me to UniProt BETA
UniProtKB - O00462 (MANBA_HUMAN)
Protein
Beta-mannosidase
Gene
MANBA
Organism
Homo sapiens (Human)
Status
Functioni
Exoglycosidase that cleaves the single beta-linked mannose residue from the non-reducing end of all N-linked glycoprotein oligosaccharides.
2 PublicationsCatalytic activityi
- Hydrolysis of terminal, non-reducing beta-D-mannose residues in beta-D-mannosides.4 Publications EC:3.2.1.25
pH dependencei
Optimum pH is 4.5-5.1 Publication
: N-glycan degradation Pathwayi
This protein is involved in the pathway N-glycan degradation, which is part of Glycan metabolism.2 PublicationsView all proteins of this organism that are known to be involved in the pathway N-glycan degradation and in Glycan metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 456 | SubstrateBy similarity | 1 | |
Active sitei | 457 | Proton donorBy similarity | 1 | |
Active sitei | 554 | NucleophileBy similarity | 1 |
GO - Molecular functioni
- beta-mannosidase activity Source: UniProtKB
- mannose binding Source: Ensembl
GO - Biological processi
- cellular protein modification process Source: UniProtKB
- glycoprotein catabolic process Source: UniProtKB
- oligosaccharide catabolic process Source: Reactome
Keywordsi
Molecular function | Glycosidase, Hydrolase |
Enzyme and pathway databases
PathwayCommonsi | O00462 |
Reactomei | R-HSA-6798695, Neutrophil degranulation R-HSA-8853383, Lysosomal oligosaccharide catabolism |
SignaLinki | O00462 |
UniPathwayi | UPA00280 |
Protein family/group databases
CAZyi | GH2, Glycoside Hydrolase Family 2 |
Names & Taxonomyi
Protein namesi | Recommended name: Beta-mannosidase (EC:3.2.1.253 Publications)Alternative name(s): Lysosomal beta A mannosidase Mannanase Short name: Mannase |
Gene namesi | Name:MANBA Synonyms:MANB1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6831, MANBA |
MIMi | 609489, gene |
neXtProti | NX_O00462 |
VEuPathDBi | HostDB:ENSG00000109323 |
Subcellular locationi
Lysosome
- Lysosome Curated
Lysosome
- azurophil granule membrane Source: Reactome
- lysosomal lumen Source: Reactome
Plasma Membrane
- plasma membrane Source: Reactome
Keywords - Cellular componenti
LysosomePathology & Biotechi
Involvement in diseasei
Mannosidosis, beta A, lysosomal (MANSB)5 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive lysosomal storage disease of glycoprotein catabolism. Clinical features are heterogeneous with a wide range of symptoms and age of onset. The disease is associated with a range of neurological involvement, including various degrees of mental retardation in most of the cases, hearing loss and speech impairment, hypotonia, epilepsy and peripheral neuropathy. Affected individuals have a profound reduction in beta A mannosidase activity in plasma, fibroblasts and leukocytes.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_081392 | 182 | R → W in MANSB; nearly complete loss of enzyme activity. 3 PublicationsCorresponds to variant dbSNP:rs374377679Ensembl. | 1 | |
Natural variantiVAR_081393 | 392 | G → E in MANSB; nearly complete loss of enzyme activity. 3 Publications | 1 | |
Natural variantiVAR_081394 | 466 – 879 | Missing in MANSB; complete loss of enzyme activity. 2 PublicationsAdd BLAST | 414 | |
Natural variantiVAR_081395 | 505 | S → P in MANSB; nearly complete loss of enzyme activity. 2 PublicationsCorresponds to variant dbSNP:rs121434334EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 638 | R → H: No effect on enzyme activity (in vitro). 1 Publication | 1 | |
Mutagenesisi | 641 | R → H: No effect on enzyme activity (in vitro). Decreased protein stability. 1 Publication | 1 | |
Mutagenesisi | 749 | L → H: No effect on enzyme activity (in vitro). No effect on protein stability. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 4126 |
MalaCardsi | MANBA |
MIMi | 248510, phenotype |
OpenTargetsi | ENSG00000109323 |
Orphaneti | 118, Beta-mannosidosis |
PharmGKBi | PA30577 |
Miscellaneous databases
Pharosi | O00462, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3903 |
Genetic variation databases
BioMutai | MANBA |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 17 | Sequence analysisAdd BLAST | 17 | |
ChainiPRO_0000012166 | 18 – 879 | Beta-mannosidaseAdd BLAST | 862 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 28 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 35 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 77 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 167 ↔ 176 | By similarity | ||
Glycosylationi | 280 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 284 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 297 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 302 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 540 ↔ 629 | By similarity | ||
Disulfide bondi | 732 ↔ 761 | By similarity | ||
Glycosylationi | 763 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 764 ↔ 769 | By similarity |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | O00462 |
jPOSTi | O00462 |
MassIVEi | O00462 |
MaxQBi | O00462 |
PaxDbi | O00462 |
PeptideAtlasi | O00462 |
PRIDEi | O00462 |
ProteomicsDBi | 47912 |
PTM databases
GlyConnecti | 1041, 2 N-Linked glycans (1 site) |
GlyGeni | O00462, 8 sites, 2 N-linked glycans (1 site) |
iPTMneti | O00462 |
PhosphoSitePlusi | O00462 |
Expressioni
Tissue specificityi
Ubiquitous. Detected in pancreas, kidney and placenta, ands at lower levels in liver, lung, brain, heart and muscle.1 Publication
Gene expression databases
Bgeei | ENSG00000109323, Expressed in monocyte and 219 other tissues |
ExpressionAtlasi | O00462, baseline and differential |
Genevisiblei | O00462, HS |
Organism-specific databases
HPAi | ENSG00000109323, Low tissue specificity |
Interactioni
Subunit structurei
Monomer.
By similarityProtein-protein interaction databases
BioGRIDi | 110299, 115 interactors |
IntActi | O00462, 13 interactors |
STRINGi | 9606.ENSP00000226578 |
Chemistry databases
BindingDBi | O00462 |
Miscellaneous databases
RNActi | O00462, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 190 – 192 | Substrate bindingBy similarity | 3 |
Sequence similaritiesi
Belongs to the glycosyl hydrolase 2 family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG2230, Eukaryota |
GeneTreei | ENSGT00390000001670 |
InParanoidi | O00462 |
OMAi | KRQWKGP |
OrthoDBi | 517710at2759 |
PhylomeDBi | O00462 |
TreeFami | TF105723 |
Family and domain databases
Gene3Di | 2.60.40.10, 2 hits |
InterProi | View protein in InterPro IPR036156, Beta-gal/glucu_dom_sf IPR041625, Beta-mannosidase_Ig IPR008979, Galactose-bd-like_sf IPR006103, Glyco_hydro_2_cat IPR017853, Glycoside_hydrolase_SF IPR013783, Ig-like_fold IPR041447, Mannosidase_ig |
Pfami | View protein in Pfam PF02836, Glyco_hydro_2_C, 1 hit PF17753, Ig_mannosidase, 1 hit PF17786, Mannosidase_ig, 1 hit |
SUPFAMi | SSF49303, SSF49303, 3 hits SSF49785, SSF49785, 1 hit SSF51445, SSF51445, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 12 potential isoforms that are computationally mapped.Show allAlign All
O00462-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MRLHLLLLLA LCGAGTTAAE LSYSLRGNWS ICNGNGSLEL PGAVPGCVHS
60 70 80 90 100
ALFQQGLIQD SYYRFNDLNY RWVSLDNWTY SKEFKIPFEI SKWQKVNLIL
110 120 130 140 150
EGVDTVSKIL FNEVTIGETD NMFNRYSFDI TNVVRDVNSI ELRFQSAVLY
160 170 180 190 200
AAQQSKAHTR YQVPPDCPPL VQKGECHVNF VRKEQCSFSW DWGPSFPTQG
210 220 230 240 250
IWKDVRIEAY NICHLNYFTF SPIYDKSAQE WNLEIESTFD VVSSKPVGGQ
260 270 280 290 300
VIVAIPKLQT QQTYSIELQP GKRIVELFVN ISKNITVETW WPHGHGNQTG
310 320 330 340 350
YNMTVLFELD GGLNIEKSAK VYFRTVELIE EPIKGSPGLS FYFKINGFPI
360 370 380 390 400
FLKGSNWIPA DSFQDRVTSE LLRLLLQSVV DANMNTLRVW GGGIYEQDEF
410 420 430 440 450
YELCDELGIM VWQDFMFACA LYPTDQGFLD SVTAEVAYQI KRLKSHPSII
460 470 480 490 500
IWSGNNENEE ALMMNWYHIS FTDRPIYIKD YVTLYVKNIR ELVLAGDKSR
510 520 530 540 550
PFITSSPTNG AETVAEAWVS QNPNSNYFGD VHFYDYISDC WNWKVFPKAR
560 570 580 590 600
FASEYGYQSW PSFSTLEKVS STEDWSFNSK FSLHRQHHEG GNKQMLYQAG
610 620 630 640 650
LHFKLPQSTD PLRTFKDTIY LTQVMQAQCV KTETEFYRRS RSEIVDQQGH
660 670 680 690 700
TMGALYWQLN DIWQAPSWAS LEYGGKWKML HYFAQNFFAP LLPVGFENEN
710 720 730 740 750
TFYIYGVSDL HSDYSMTLSV RVHTWSSLEP VCSRVTERFV MKGGEAVCLY
760 770 780 790 800
EEPVSELLRR CGNCTRESCV VSFYLSADHE LLSPTNYHFL SSPKEAVGLC
810 820 830 840 850
KAQITAIISQ QGDIFVFDLE TSAVAPFVWL DVGSIPGRFS DNGFLMTEKT
860 870
RTILFYPWEP TSKNELEQSF HVTSLTDIY
Computationally mapped potential isoform sequencesi
There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PFW2 | E9PFW2_HUMAN | Beta-mannosidase | MANBA | 822 | Annotation score: | ||
A0A2R8YEC9 | A0A2R8YEC9_HUMAN | Beta-mannosidase | MANBA | 925 | Annotation score: | ||
A0A2R8Y524 | A0A2R8Y524_HUMAN | Beta-mannosidase | MANBA | 886 | Annotation score: | ||
A0A2R8Y4U7 | A0A2R8Y4U7_HUMAN | Beta-mannosidase | MANBA | 509 | Annotation score: | ||
A0A2R8Y211 | A0A2R8Y211_HUMAN | Beta-mannosidase | MANBA | 365 | Annotation score: | ||
A0A2R8YCE9 | A0A2R8YCE9_HUMAN | Beta-mannosidase | MANBA | 413 | Annotation score: | ||
A0A2R8YE79 | A0A2R8YE79_HUMAN | Beta-mannosidase | MANBA | 397 | Annotation score: | ||
A0A2R8Y7A7 | A0A2R8Y7A7_HUMAN | Beta-mannosidase | MANBA | 215 | Annotation score: | ||
A0A2R8Y7N1 | A0A2R8Y7N1_HUMAN | Beta-mannosidase | MANBA | 230 | Annotation score: | ||
D6RA01 | D6RA01_HUMAN | Beta-mannosidase | MANBA | 68 | Annotation score: | ||
There are more potential isoformsShow all |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 70 | Y → H in AAC39573 (PubMed:9384606).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_081392 | 182 | R → W in MANSB; nearly complete loss of enzyme activity. 3 PublicationsCorresponds to variant dbSNP:rs374377679Ensembl. | 1 | |
Natural variantiVAR_026232 | 253 | V → I Decreased enzyme activity. 2 PublicationsCorresponds to variant dbSNP:rs227368EnsemblClinVar. | 1 | |
Natural variantiVAR_059311 | 253 | V → L. Corresponds to variant dbSNP:rs227368EnsemblClinVar. | 1 | |
Natural variantiVAR_081393 | 392 | G → E in MANSB; nearly complete loss of enzyme activity. 3 Publications | 1 | |
Natural variantiVAR_081394 | 466 – 879 | Missing in MANSB; complete loss of enzyme activity. 2 PublicationsAdd BLAST | 414 | |
Natural variantiVAR_081395 | 505 | S → P in MANSB; nearly complete loss of enzyme activity. 2 PublicationsCorresponds to variant dbSNP:rs121434334EnsemblClinVar. | 1 | |
Natural variantiVAR_026233 | 701 | T → M1 PublicationCorresponds to variant dbSNP:rs2866413EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U60337 mRNA Translation: AAC39573.1 AF213884 Genomic DNA Translation: AAF35233.1 BC015743 mRNA Translation: AAH15743.1 |
CCDSi | CCDS3658.1 |
RefSeqi | NP_005899.3, NM_005908.3 |
Genome annotation databases
Ensembli | ENST00000647097.2; ENSP00000495247.1; ENSG00000109323.11 |
GeneIDi | 4126 |
KEGGi | hsa:4126 |
MANE-Selecti | ENST00000647097.2; ENSP00000495247.1; NM_005908.4; NP_005899.3 |
UCSCi | uc003hwg.4, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U60337 mRNA Translation: AAC39573.1 AF213884 Genomic DNA Translation: AAF35233.1 BC015743 mRNA Translation: AAH15743.1 |
CCDSi | CCDS3658.1 |
RefSeqi | NP_005899.3, NM_005908.3 |
3D structure databases
AlphaFoldDBi | O00462 |
SMRi | O00462 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 110299, 115 interactors |
IntActi | O00462, 13 interactors |
STRINGi | 9606.ENSP00000226578 |
Chemistry databases
BindingDBi | O00462 |
ChEMBLi | CHEMBL3903 |
Protein family/group databases
CAZyi | GH2, Glycoside Hydrolase Family 2 |
PTM databases
GlyConnecti | 1041, 2 N-Linked glycans (1 site) |
GlyGeni | O00462, 8 sites, 2 N-linked glycans (1 site) |
iPTMneti | O00462 |
PhosphoSitePlusi | O00462 |
Genetic variation databases
BioMutai | MANBA |
Proteomic databases
EPDi | O00462 |
jPOSTi | O00462 |
MassIVEi | O00462 |
MaxQBi | O00462 |
PaxDbi | O00462 |
PeptideAtlasi | O00462 |
PRIDEi | O00462 |
ProteomicsDBi | 47912 |
Protocols and materials databases
Antibodypediai | 26046, 70 antibodies from 21 providers |
DNASUi | 4126 |
Genome annotation databases
Ensembli | ENST00000647097.2; ENSP00000495247.1; ENSG00000109323.11 |
GeneIDi | 4126 |
KEGGi | hsa:4126 |
MANE-Selecti | ENST00000647097.2; ENSP00000495247.1; NM_005908.4; NP_005899.3 |
UCSCi | uc003hwg.4, human |
Organism-specific databases
CTDi | 4126 |
DisGeNETi | 4126 |
GeneCardsi | MANBA |
HGNCi | HGNC:6831, MANBA |
HPAi | ENSG00000109323, Low tissue specificity |
MalaCardsi | MANBA |
MIMi | 248510, phenotype 609489, gene |
neXtProti | NX_O00462 |
OpenTargetsi | ENSG00000109323 |
Orphaneti | 118, Beta-mannosidosis |
PharmGKBi | PA30577 |
VEuPathDBi | HostDB:ENSG00000109323 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2230, Eukaryota |
GeneTreei | ENSGT00390000001670 |
InParanoidi | O00462 |
OMAi | KRQWKGP |
OrthoDBi | 517710at2759 |
PhylomeDBi | O00462 |
TreeFami | TF105723 |
Enzyme and pathway databases
UniPathwayi | UPA00280 |
PathwayCommonsi | O00462 |
Reactomei | R-HSA-6798695, Neutrophil degranulation R-HSA-8853383, Lysosomal oligosaccharide catabolism |
SignaLinki | O00462 |
Miscellaneous databases
BioGRID-ORCSi | 4126, 6 hits in 1080 CRISPR screens |
ChiTaRSi | MANBA, human |
GeneWikii | Beta-mannosidase |
GenomeRNAii | 4126 |
Pharosi | O00462, Tchem |
PROi | PR:O00462 |
RNActi | O00462, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000109323, Expressed in monocyte and 219 other tissues |
ExpressionAtlasi | O00462, baseline and differential |
Genevisiblei | O00462, HS |
Family and domain databases
Gene3Di | 2.60.40.10, 2 hits |
InterProi | View protein in InterPro IPR036156, Beta-gal/glucu_dom_sf IPR041625, Beta-mannosidase_Ig IPR008979, Galactose-bd-like_sf IPR006103, Glyco_hydro_2_cat IPR017853, Glycoside_hydrolase_SF IPR013783, Ig-like_fold IPR041447, Mannosidase_ig |
Pfami | View protein in Pfam PF02836, Glyco_hydro_2_C, 1 hit PF17753, Ig_mannosidase, 1 hit PF17786, Mannosidase_ig, 1 hit |
SUPFAMi | SSF49303, SSF49303, 3 hits SSF49785, SSF49785, 1 hit SSF51445, SSF51445, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | MANBA_HUMAN | |
Accessioni | O00462Primary (citable) accession number: O00462 Secondary accession number(s): Q96BC3, Q9NYX9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | August 16, 2004 | |
Last modified: | May 25, 2022 | |
This is version 183 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Glycosyl hydrolases
Classification of glycosyl hydrolase families and list of entries - Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families