Human Gene MAN2B1 (uc002mub.2) Description and Page Index
  Description: Homo sapiens mannosidase, alpha, class 2B, member 1 (MAN2B1), transcript variant 1, mRNA.
RefSeq Summary (NM_000528): This gene encodes an enzyme that hydrolyzes terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides. Its activity is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover and it is member of family 38 of glycosyl hydrolases. The full length protein is processed in two steps. First, a 49 aa leader sequence is cleaved off and the remainder of the protein is processed into 3 peptides of 70 kDa, 42 kDa (D) and 13/15 kDa (E). Next, the 70 kDa peptide is further processed into three peptides (A, B and C). The A, B and C peptides are disulfide-linked. Defects in this gene have been associated with lysosomal alpha-mannosidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010].
Transcript (Including UTRs)
   Position: hg19 chr19:12,757,322-12,777,591 Size: 20,270 Total Exon Count: 24 Strand: -
Coding Region
   Position: hg19 chr19:12,757,434-12,777,515 Size: 20,082 Coding Exon Count: 24 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr19:12,757,322-12,777,591)mRNA (may differ from genome)Protein (1011 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCEUniProtKB

-  Comments and Description Text from UniProtKB
  ID: MA2B1_HUMAN
DESCRIPTION: RecName: Full=Lysosomal alpha-mannosidase; Short=Laman; EC=3.2.1.24; AltName: Full=Lysosomal acid alpha-mannosidase; AltName: Full=Mannosidase alpha class 2B member 1; AltName: Full=Mannosidase alpha-B; Contains: RecName: Full=Lysosomal alpha-mannosidase A peptide; Contains: RecName: Full=Lysosomal alpha-mannosidase B peptide; Contains: RecName: Full=Lysosomal alpha-mannosidase C peptide; Contains: RecName: Full=Lysosomal alpha-mannosidase D peptide; Contains: RecName: Full=Lysosomal alpha-mannosidase E peptide; Flags: Precursor;
FUNCTION: Necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover. Cleaves all known types of alpha-mannosidic linkages.
CATALYTIC ACTIVITY: Hydrolysis of terminal, non-reducing alpha-D- mannose residues in alpha-D-mannosides.
COFACTOR: Binds 1 zinc ion per subunit (By similarity).
SUBCELLULAR LOCATION: Lysosome.
PTM: First processed into 3 peptides of 70 kDa, 42 kDa (D) and 13/15 kDa (E). The 70 kDa peptide is further processed into three peptides (A, B and C). The A, B and C peptides are disulfide- linked.
PTM: Heavily glycosylated.
DISEASE: Defects in MAN2B1 are the cause of lysosomal alpha- mannosidosis (AM) [MIM:248500]. AM is a lysosomal storage disease characterized by accumulation of unbranched oligosaccharide chains. This accumulation is expressed histologically as cytoplasmic vacuolation predominantly in the CNS and parenchymatous organs. Depending on the clinical findings at the age of onset, a severe infantile (type I) and a mild juvenile (type II) form of alpha-mannosidosis are recognized. There is considerable variation in the clinical expression with mental retardation, recurrent infections, impaired hearing and Hurler- like skeletal changes being the most consistent abnormalities.
SIMILARITY: Belongs to the glycosyl hydrolase 38 family.
SEQUENCE CAUTION: Sequence=AAB03816.1; Type=Erroneous initiation; Sequence=AAC50812.1; Type=Erroneous initiation;
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MAN2B1";
WEB RESOURCE: Name=Mendelian genes mannosidase, alpha, class 2B, member 1 (MAN2B1); Note=Leiden Open Variation Database (LOVD); URL="http://www.lovd.nl/MAN2B1";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): MAN2B1
CDC HuGE Published Literature: MAN2B1

-  MalaCards Disease Associations
  MalaCards Gene Search: MAN2B1
Diseases sorted by gene-association score: mannosidosis, alpha-, types i and ii* (1321), alpha-mannosidosis, infantile form* (350), alpha-mannosidosis, adult form* (350), mannosidosis (62), mannosidosis, beta (10), lysosomal storage disease (8), dysostosis (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 54.12 RPKM in Spleen
Total median expression: 803.58 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -42.6076-0.561 Picture PostScript Text
3' UTR -35.90112-0.321 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011013 - Glyco_hydro-type_carb-bd
IPR011330 - Glyco_hydro/deAcase_b/a-brl
IPR013780 - Glyco_hydro_13_b
IPR011682 - Glyco_hydro_38_C
IPR015341 - Glyco_hydro_38_cen_dom
IPR000602 - Glyco_hydro_38_core

Pfam Domains:
PF01074 - Glycosyl hydrolases family 38 N-terminal domain
PF07748 - Glycosyl hydrolases family 38 C-terminal domain
PF09261 - Alpha mannosidase middle domain

SCOP Domains:
88688 - Families 57/38 glycoside transferase middle domain
74650 - Galactose mutarotase-like
88713 - Glycoside hydrolase/deacetylase

ModBase Predicted Comparative 3D Structure on O00754
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene Details  Gene DetailsGene Details 
Gene Sorter  Gene SorterGene Sorter 
  EnsemblFlyBaseWormBase 
  Protein SequenceProtein SequenceProtein Sequence 
  AlignmentAlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003824 catalytic activity
GO:0004559 alpha-mannosidase activity
GO:0016787 hydrolase activity
GO:0016798 hydrolase activity, acting on glycosyl bonds
GO:0030246 carbohydrate binding
GO:0046872 metal ion binding

Biological Process:
GO:0005975 carbohydrate metabolic process
GO:0006013 mannose metabolic process
GO:0006464 cellular protein modification process
GO:0006517 protein deglycosylation
GO:0008152 metabolic process
GO:0009313 oligosaccharide catabolic process
GO:0043312 neutrophil degranulation

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005764 lysosome
GO:0035578 azurophil granule lumen
GO:0043202 lysosomal lumen
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  LF208198 - JP 2014500723-A/15701: Polycomb-Associated Non-Coding RNAs.
BC000736 - Homo sapiens mannosidase, alpha, class 2B, member 1, mRNA (cDNA clone MGC:2113 IMAGE:3504417), complete cds.
AB209921 - Homo sapiens mRNA for mannosidase, alpha, class 2B, member 1 precursor variant protein.
AK291572 - Homo sapiens cDNA FLJ76867 complete cds, highly similar to Homo sapiens mannosidase, alpha, class 2B, member 1 (MAN2B1), mRNA.
AK303418 - Homo sapiens cDNA FLJ54572 complete cds, highly similar to Lysosomal alpha-mannosidase precursor (EC 3.2.1.24).
U05572 - Human lysosomal alpha-mannosidase (MANB) mRNA, complete cds.
U60266 - Homo sapiens lysosomal alpha-mannosidase (manB) mRNA, complete cds.
JD329009 - Sequence 310033 from Patent EP1572962.
JD464618 - Sequence 445642 from Patent EP1572962.
JD398895 - Sequence 379919 from Patent EP1572962.
U68382 - Human lysosomal acid alpha-mannosidase (MANB) mRNA, alternatively spliced transcript, complete cds.
U68567 - Human lysosomal acid alpha-mannosidase mRNA, complete cds.
JD466361 - Sequence 447385 from Patent EP1572962.
DQ891878 - Synthetic construct clone IMAGE:100004508; FLH180868.01X; RZPDo839G11134D mannosidase, alpha, class 2B, member 1 (MAN2B1) gene, encodes complete protein.
DQ895066 - Synthetic construct Homo sapiens clone IMAGE:100009526; FLH180864.01L; RZPDo839G11133D mannosidase, alpha, class 2B, member 1 (MAN2B1) gene, encodes complete protein.
AB527181 - Synthetic construct DNA, clone: pF1KB5675, Homo sapiens MAN2B1 gene for mannosidase, alpha, class 2B, member 1, without stop codon, in Flexi system.
LF373421 - JP 2014500723-A/180924: Polycomb-Associated Non-Coding RNAs.
LF373419 - JP 2014500723-A/180922: Polycomb-Associated Non-Coding RNAs.
LF373416 - JP 2014500723-A/180919: Polycomb-Associated Non-Coding RNAs.
JD437159 - Sequence 418183 from Patent EP1572962.
MA608998 - JP 2018138019-A/180924: Polycomb-Associated Non-Coding RNAs.
MA608996 - JP 2018138019-A/180922: Polycomb-Associated Non-Coding RNAs.
MA608993 - JP 2018138019-A/180919: Polycomb-Associated Non-Coding RNAs.
MA443775 - JP 2018138019-A/15701: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00511 - Other glycan degradation
hsa04142 - Lysosome

BioCarta from NCI Cancer Genome Anatomy Project
h_aMANpathway - Steps in the Glycosylation of Mammalian N-linked Oligosaccarides
h_eradPathway - ER┐associated degradation (ERAD) Pathway

Reactome (by CSHL, EBI, and GO)

Protein O00754 (Reactome details) participates in the following event(s):

R-HSA-6798751 Exocytosis of azurophil granule lumen proteins
R-HSA-8853686 MAN2B1 hydrolyses GlcNAc (Man)5 to GlcNAc (Man)3
R-HSA-6798695 Neutrophil degranulation
R-HSA-168249 Innate Immune System
R-HSA-8853383 Lysosomal oligosaccharide catabolism
R-HSA-168256 Immune System
R-HSA-71387 Metabolism of carbohydrates
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: LAMAN, MA2B1_HUMAN, MANB, NM_000528, NP_000519, O00754, O15330, Q16680, Q93094, Q9BW13
UCSC ID: uc002mub.2
RefSeq Accession: NM_000528
Protein: O00754 (aka MA2B1_HUMAN or M2B1_HUMAN)
CCDS: CCDS32919.1, CCDS54224.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene MAN2B1:
a-mannosidosis (Alpha-Mannosidosis)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000528.3
exon count: 24CDS single in 3' UTR: no RNA size: 3231
ORF size: 3036CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 5989.00frame shift in genome: no % Coverage: 99.78
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.