HEXB

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HEXB
Protein HEXB PDB 1nou.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases HEXB, ENC-1AS, HEL-248, HEL-S-111, hexosaminidase subunit beta
External IDs OMIM: 606873 MGI: 96074 HomoloGene: 437 GeneCards: HEXB
Gene location (Human)
Chromosome 5 (human)
Chr. Chromosome 5 (human)[1]
Chromosome 5 (human)
Genomic location for HEXB
Genomic location for HEXB
Band 5q13.3 Start 74,640,023 bp[1]
End 74,722,647 bp[1]
RNA expression pattern
PBB GE HEXB 201944 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001292004
NM_000521

NM_010422

RefSeq (protein)

NP_000512
NP_001278933

NP_034552

Location (UCSC) Chr 5: 74.64 – 74.72 Mb Chr 5: 97.18 – 97.2 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Beta-hexosaminidase subunit beta is an enzyme that in humans is encoded by the HEXB gene.[5][6][7]

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).[7]

Structure[edit]

Gene[edit]

The HEXB gene lies on the chromosome location of 5q13.3 and consists of 15 exons, spanning 35-40Kb.

Protein[edit]

HEXB consists of 556 amino acid residues and weighs 63111Da.

Function[edit]

HEXB is one of the two subunits forming β-hexosaminidase which functions as a glycosyl hydrolase that remove β-linked nonreducing-terminal GalNAc or GlcNAc residues in the lysosome.[8] Inability of HEXB will lead toβ-hexosaminidase defect and result in a group of recessive disorders called GM2 gangliosidoses, characterized by the accumulation of GM2 ganglioside.[9]

Clinical significance[edit]

Genetic defects in HEXB can result in the accumulation of GM2 ganglioside in neural tissues and two of three lysosomal storage diseases collectively known as GM2 gangliosidosis, of which Sandhoff disease (defects in the β subunit) is the best studied one.[8] Patients present with neurosomatic manifestations. Therapeutic effects of Hex subunit gene transduction have been examined on Sandhoff disease model mice.[10] Intracerebroventricular administration of the modified β-hexosaminidase B to Sandhoff mode mice restored the β-hexosaminidase activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma.[11]

Interactions[edit]

HEXB has been found to interact with HEXA[12] and ganglioside.[10]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000049860 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021665 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ O'Dowd BF, Quan F, Willard HF, Lamhonwah AM, Korneluk RG, Lowden JA, Gravel RA, Mahuran DJ (February 1985). "Isolation of cDNA clones coding for the beta subunit of human beta-hexosaminidase". Proceedings of the National Academy of Sciences of the United States of America. 82 (4): 1184–8. doi:10.1073/pnas.82.4.1184. PMC 397219Freely accessible. PMID 2579389. 
  6. ^ Korneluk RG, Mahuran DJ, Neote K, Klavins MH, O'Dowd BF, Tropak M, Willard HF, Anderson MJ, Lowden JA, Gravel RA (June 1986). "Isolation of cDNA clones coding for the alpha-subunit of human beta-hexosaminidase. Extensive homology between the alpha- and beta-subunits and studies on Tay-Sachs disease". The Journal of Biological Chemistry. 261 (18): 8407–13. PMID 3013851. 
  7. ^ a b "Entrez Gene: HEXB hexosaminidase B (beta polypeptide)". 
  8. ^ a b Bateman KS, Cherney MM, Mahuran DJ, Tropak M, James MN (March 2011). "Crystal structure of β-hexosaminidase B in complex with pyrimethamine, a potential pharmacological chaperone". Journal of Medicinal Chemistry. 54 (5): 1421–9. doi:10.1021/jm101443u. PMC 3201983Freely accessible. PMID 21265544. 
  9. ^ Sonnino S, Chigorno V (September 2000). "Ganglioside molecular species containing C18- and C20-sphingosine in mammalian nervous tissues and neuronal cell cultures". Biochimica et Biophysica Acta. 1469 (2): 63–77. PMID 10998569. 
  10. ^ a b Itakura T, Kuroki A, Ishibashi Y, Tsuji D, Kawashita E, Higashine Y, Sakuraba H, Yamanaka S, Itoh K (August 2006). "Inefficiency in GM2 ganglioside elimination by human lysosomal beta-hexosaminidase beta-subunit gene transfer to fibroblastic cell line derived from Sandhoff disease model mice". Biological & Pharmaceutical Bulletin. 29 (8): 1564–9. PMID 16880605. 
  11. ^ Matsuoka K, Tamura T, Tsuji D, Dohzono Y, Kitakaze K, Ohno K, Saito S, Sakuraba H, Itoh K (June 2011). "Therapeutic potential of intracerebroventricular replacement of modified human β-hexosaminidase B for GM2 gangliosidosis". Molecular Therapy. 19 (6): 1017–24. doi:10.1038/mt.2011.27. PMC 3129794Freely accessible. PMID 21487393. 
  12. ^ Gort L, de Olano N, Macías-Vidal J, Coll MA (September 2012). "GM2 gangliosidoses in Spain: analysis of the HEXA and HEXB genes in 34 Tay-Sachs and 14 Sandhoff patients". Gene. 506 (1): 25–30. doi:10.1016/j.gene.2012.06.080. PMID 22789865. 

Further reading[edit]