Human Gene HEXB (uc003kdf.4)
  Description: Homo sapiens hexosaminidase B (beta polypeptide) (HEXB), mRNA.
RefSeq Summary (NM_000521): Hexosaminidase B is the beta subunit of the lysosomal enzyme beta-hexosaminidase that, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Beta-hexosaminidase is composed of two subunits, alpha and beta, which are encoded by separate genes. Both beta-hexosaminidase alpha and beta subunits are members of family 20 of glycosyl hydrolases. Mutations in the alpha or beta subunit genes lead to an accumulation of GM2 ganglioside in neurons and neurodegenerative disorders termed the GM2 gangliosidoses. Beta subunit gene mutations lead to Sandhoff disease (GM2-gangliosidosis type II). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014].
Transcript (Including UTRs)
   Position: hg19 chr5:73,980,969-74,017,113 Size: 36,145 Total Exon Count: 14 Strand: +
Coding Region
   Position: hg19 chr5:73,981,086-74,017,000 Size: 35,915 Coding Exon Count: 14 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviews
Model InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:73,980,969-74,017,113)mRNA (may differ from genome)Protein (556 aa)
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MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: HEXB_HUMAN
DESCRIPTION: RecName: Full=Beta-hexosaminidase subunit beta; EC=3.2.1.52; AltName: Full=Beta-N-acetylhexosaminidase subunit beta; Short=Hexosaminidase subunit B; AltName: Full=Cervical cancer proto-oncogene 7 protein; Short=HCC-7; AltName: Full=N-acetyl-beta-glucosaminidase subunit beta; Contains: RecName: Full=Beta-hexosaminidase subunit beta chain B; Contains: RecName: Full=Beta-hexosaminidase subunit beta chain A; Flags: Precursor;
FUNCTION: Responsible for the degradation of GM2 gangliosides, and a variety of other molecules containing terminal N-acetyl hexosamines, in the brain and other tissues.
CATALYTIC ACTIVITY: Hydrolysis of terminal non-reducing N-acetyl- D-hexosamine residues in N-acetyl-beta-D-hexosaminides.
SUBUNIT: There are 3 forms of beta-hexosaminidase: hexosaminidase A is a trimer composed of one subunit alpha, one subunit beta chain A and one subunit beta chain B; hexosaminidase B is a tetramer of two subunit beta chains A and two subunit beta chains B; hexosaminidase S is a homodimer of two alpha subunits. The two beta chains are derived from the cleavage of the beta subunit.
SUBCELLULAR LOCATION: Lysosome.
PTM: N-linked glycans at Asn-142 and Asn-190 consist of Man(3)- GlcNAc(2) and Man(5 to 7)-GlcNAc(2), respectively.
PTM: The beta-A and beta-B chains are produced by proteolytic processing of the precursor beta chain.
DISEASE: Defects in HEXB are the cause of GM2-gangliosidosis type 2 (GM2G2) [MIM:268800]; also known as Sandhoff disease. GM2- gangliosidosis is an autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. GM2G2 is clinically indistinguishable from GM2- gangliosidosis type 1, presenting startle reactions, early blindness, progressive motor and mental deterioration, macrocephaly and cherry-red spots on the macula.
SIMILARITY: Belongs to the glycosyl hydrolase 20 family.
SEQUENCE CAUTION: Sequence=AAA51828.1; Type=Frameshift; Positions=21; Sequence=AAA68620.1; Type=Erroneous initiation;
WEB RESOURCE: Name=HEXBdb; Note=HEXB mutation database; URL="http://www.hexdb.mcgill.ca/?Topic=HEXBdb";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/HEXB";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): HEXB
CDC HuGE Published Literature: HEXB
Positive Disease Associations: dramatically different phenotypes
Related Studies:
  1. dramatically different phenotypes
    McInnes B et al. 1992, An unusual splicing mutation in the HEXB gene is associated with dramatically different phenotypes in patients from different racial backgrounds., The Journal of clinical investigation. 1992 Aug;90(2):306-14. [PubMed 1386607]

-  MalaCards Disease Associations
  MalaCards Gene Search: HEXB
Diseases sorted by gene-association score: sandhoff disease, infantile, juvenile, and adult forms* (1680), tay-sachs disease (29), mucolipidosis iv (17), gangliosidosis gm2 (13), lung abscess (7), lysosomal storage disease (5), sphingolipidosis (5), motor neuron disease (4)
* = 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: 60.03 RPKM in Cervix - Endocervix
Total median expression: 1392.16 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 -56.20117-0.480 Picture PostScript Text
3' UTR -14.70113-0.130 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
IPR025705 - Beta_hexosaminidase_sua/sub
IPR015883 - Glyco_hydro_20_cat-core
IPR015882 - Glyco_hydro_20b
IPR013781 - Glyco_hydro_catalytic_dom
IPR017853 - Glycoside_hydrolase_SF

Pfam Domains:
PF00728 - Glycosyl hydrolase family 20, catalytic domain
PF14845 - beta-acetyl hexosaminidase like

SCOP Domains:
51445 - (Trans)glycosidases
55545 - beta-N-acetylhexosaminidase-like domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1NOU - X-ray 1NOW - X-ray 1NP0 - X-ray 1O7A - X-ray MuPIT 1QBD - Model 2GJX - X-ray 2GK1 - X-ray 3LMY - X-ray


ModBase Predicted Comparative 3D Structure on P07686
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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 orthologGenome BrowserGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene DetailsGene Details Gene DetailsGene Details 
Gene SorterGene Sorter Gene SorterGene Sorter 
 RGDEnsemblFlyBaseWormBase 
 Protein SequenceProtein SequenceProtein SequenceProtein Sequence 
 AlignmentAlignmentAlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004553 hydrolase activity, hydrolyzing O-glycosyl compounds
GO:0004563 beta-N-acetylhexosaminidase activity
GO:0005515 protein binding
GO:0008375 acetylglucosaminyltransferase activity
GO:0016787 hydrolase activity
GO:0016798 hydrolase activity, acting on glycosyl bonds
GO:0042803 protein homodimerization activity
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0001501 skeletal system development
GO:0005975 carbohydrate metabolic process
GO:0006687 glycosphingolipid metabolic process
GO:0006689 ganglioside catabolic process
GO:0006874 cellular calcium ion homeostasis
GO:0007040 lysosome organization
GO:0007338 single fertilization
GO:0007341 penetration of zona pellucida
GO:0007605 sensory perception of sound
GO:0007626 locomotory behavior
GO:0008049 male courtship behavior
GO:0008152 metabolic process
GO:0008360 regulation of cell shape
GO:0008654 phospholipid biosynthetic process
GO:0009313 oligosaccharide catabolic process
GO:0019915 lipid storage
GO:0019953 sexual reproduction
GO:0030203 glycosaminoglycan metabolic process
GO:0030207 chondroitin sulfate catabolic process
GO:0030214 hyaluronan catabolic process
GO:0031323 regulation of cellular metabolic process
GO:0042340 keratan sulfate catabolic process
GO:0042552 myelination
GO:0043312 neutrophil degranulation
GO:0043615 astrocyte cell migration
GO:0044267 cellular protein metabolic process
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048477 oogenesis
GO:0050885 neuromuscular process controlling balance
GO:0050905 neuromuscular process

Cellular Component:
GO:0001669 acrosomal vesicle
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005764 lysosome
GO:0016020 membrane
GO:0035578 azurophil granule lumen
GO:0042582 azurophil granule
GO:0043202 lysosomal lumen
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AY643499 - Homo sapiens ENC-1AS mRNA, complete cds.
FJ224336 - Homo sapiens epididymis luminal protein 248 (HEL-248) mRNA, complete cds.
GQ472222 - Homo sapiens epididymis secretory protein Li 111 (HEL-S-111) mRNA, complete cds.
AK130002 - Homo sapiens cDNA FLJ26492 fis, clone KDN06302, highly similar to Beta-hexosaminidase beta chain precursor (EC 3.2.1.52).
AK122992 - Homo sapiens cDNA FLJ16753 fis, clone BRACE2035124, highly similar to Beta-hexosaminidase beta chain precursor (EC 3.2.1.52).
AF378118 - Homo sapiens cervical cancer proto-oncogene 7 mRNA, complete cds.
M13519 - Human N-acetyl-beta-glucosaminidase (HEXB) mRNA, 3' end.
AK130375 - Homo sapiens cDNA FLJ26865 fis, clone PRS08481, highly similar to Beta-hexosaminidase beta chain precursor (EC 3.2.1.52).
BC017378 - Homo sapiens hexosaminidase B (beta polypeptide), mRNA (cDNA clone MGC:1725 IMAGE:2967035), complete cds.
GQ891410 - Homo sapiens clone HEL-S-130 epididymis secretory sperm binding protein mRNA, complete cds.
JD019455 - Sequence 479 from Patent EP1572962.
CU675968 - Synthetic construct Homo sapiens gateway clone IMAGE:100020700 5' read HEXB mRNA.
JF432353 - Synthetic construct Homo sapiens clone IMAGE:100073544 hexosaminidase B (beta polypeptide) (HEXB) gene, encodes complete protein.
KJ896966 - Synthetic construct Homo sapiens clone ccsbBroadEn_06360 HEXB gene, encodes complete protein.
BT009919 - Homo sapiens hexosaminidase B (beta polypeptide) mRNA, complete cds.
JD029729 - Sequence 10753 from Patent EP1572962.
M19735 - Homo sapiens beta-hexosaminidase beta chain mRNA, complete cds.
JD019805 - Sequence 829 from Patent EP1572962.
M34906 - Human beta-hexosaminidase beta subunit (HEXB) mRNA, 5' end.
JD028716 - Sequence 9740 from Patent EP1572962.
JD019585 - Sequence 609 from Patent EP1572962.
JD026064 - Sequence 7088 from Patent EP1572962.
JD028900 - Sequence 9924 from Patent EP1572962.
JD028550 - Sequence 9574 from Patent EP1572962.
D10518 - Homo sapiens mRNA for beta-hexosaminidase, partial sequence.
D10519 - Homo sapiens mRNA for beta-hexosanimidase, partial sequence.
D10520 - Homo sapiens mRNA for beta-hexosaminidase, partial sequence.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00511 - Other glycan degradation
hsa00520 - Amino sugar and nucleotide sugar metabolism
hsa00531 - Glycosaminoglycan degradation
hsa00603 - Glycosphingolipid biosynthesis - globo series
hsa00604 - Glycosphingolipid biosynthesis - ganglio series
hsa01100 - Metabolic pathways
hsa04142 - Lysosome

Reactome (by CSHL, EBI, and GO)

Protein P07686 (Reactome details) participates in the following event(s):

R-HSA-6798751 Exocytosis of azurophil granule lumen proteins
R-HSA-1605632 Both hexosaminidase A and B can cleave GalNAc from globoside
R-HSA-1605595 Hexosaminidase A cleaves GalNAc from GM2 to form GM3
R-HSA-1638053 HEXA,B cleave the terminal GalNAc from keratan sulfate
R-HSA-2105001 HEXA,B cleaves the terminal GalNAc from DS
R-HSA-2162225 HEXA,B cleave the terminal GalNAc from small HA fragments
R-HSA-6798695 Neutrophil degranulation
R-HSA-168249 Innate Immune System
R-HSA-1660662 Glycosphingolipid metabolism
R-HSA-2022857 Keratan sulfate degradation
R-HSA-2024101 CS/DS degradation
R-HSA-2160916 Hyaluronan uptake and degradation
R-HSA-168256 Immune System
R-HSA-428157 Sphingolipid metabolism
R-HSA-1638074 Keratan sulfate/keratin metabolism
R-HSA-1793185 Chondroitin sulfate/dermatan sulfate metabolism
R-HSA-2142845 Hyaluronan metabolism
R-HSA-556833 Metabolism of lipids
R-HSA-1630316 Glycosaminoglycan metabolism
R-HSA-1430728 Metabolism
R-HSA-71387 Metabolism of carbohydrates

-  Other Names for This Gene
  Alternate Gene Symbols: HCC7, HEXB_HUMAN, NM_000521, NP_000512, P07686
UCSC ID: uc003kdf.4
RefSeq Accession: NM_000521
Protein: P07686 (aka HEXB_HUMAN)
CCDS: CCDS4022.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene HEXB:
sandhoff (Sandhoff Disease)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000521.3
exon count: 14CDS single in 3' UTR: no RNA size: 1919
ORF size: 1671CDS single in intron: no Alignment % ID: 99.95
txCdsPredict score: 3541.00frame shift in genome: no % Coverage: 99.06
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.