HEXB
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesHEXB, ENC-1AS, HEL-248, HEL-S-111, hexosaminidase subunit beta
External IDsOMIM: 606873 MGI: 96074 HomoloGene: 437 GeneCards: HEXB
Orthologs
SpeciesHumanMouse
Entrez

3074

15212

Ensembl

ENSG00000049860

ENSMUSG00000021665

UniProt

P07686

P20060

RefSeq (mRNA)

NM_001292004
NM_000521

NM_010422

RefSeq (protein)

NP_000512
NP_001278933

NP_034552

Location (UCSC)Chr 5: 74.64 – 74.72 MbChr 13: 97.31 – 97.33 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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

Gene

The HEXB gene lies on the chromosome location of 5q13.3 and consists of 14 exons, spanning 35-40Kb.

Protein

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

Function

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

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

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

References

  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:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  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. Bibcode:1985PNAS...82.1184O. doi:10.1073/pnas.82.4.1184. PMC 397219. 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. doi:10.1016/S0021-9258(19)83927-3. 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 3201983. 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 (BBA) - Reviews on Biomembranes. 1469 (2): 63–77. doi:10.1016/s0005-2736(00)00210-8. 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. doi:10.1248/bpb.29.1564. 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 3129794. 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

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