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{{Infobox_gene}}
'''Beta-hexosaminidase subunit beta''' is an [[enzyme]] that in humans is encoded by the ''HEXB'' [[gene]].<ref name="pmid2579389">{{cite journal | vauthors = O'Dowd BF, Quan F, Willard HF, Lamhonwah AM, Korneluk RG, Lowden JA, Gravel RA, Mahuran DJ | title = Isolation of cDNA clones coding for the beta subunit of human beta-hexosaminidase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 82 | issue = 4 | pages = 1184–8 | date = February 1985 | pmid = 2579389 | pmc = 397219 | doi = 10.1073/pnas.82.4.1184 }}</ref><ref name="pmid3013851">{{cite journal | vauthors = Korneluk RG, Mahuran DJ, Neote K, Klavins MH, O'Dowd BF, Tropak M, Willard HF, Anderson MJ, Lowden JA, Gravel RA | title = 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 | journal = The Journal of Biological Chemistry | volume = 261 | issue = 18 | pages = 8407–13 | date = June 1986 | pmid = 3013851 | pmc =  | doi =  }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: HEXB hexosaminidase B (beta polypeptide)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3074| accessdate = }}</ref>


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).<ref name="entrez"/>


<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
== Structure ==
{{PBB_Controls
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
=== Gene ===
{{GNF_Protein_box
The ''HEXB'' gene lies on the [[chromosome]] location of 5q13.3 and consists of 15 [[exons]], spanning 35-40Kb.
| image = PBB_Protein_HEXB_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1nou.
| PDB = {{PDB2|1nou}}, {{PDB2|1now}}, {{PDB2|1np0}}, {{PDB2|1o7a}}, {{PDB2|2gjx}}, {{PDB2|2gk1}}
| Name = Hexosaminidase B (beta polypeptide)
| HGNCid = 4879
| Symbol = HEXB
| AltSymbols =; ENC-1AS
| OMIM = 606873
| ECnumber = 
| Homologene = 437
| MGIid = 96074
| GeneAtlas_image1 = PBB_GE_HEXB_201944_at_tn.png
| Function = {{GNF_GO|id=GO:0004563 |text = beta-N-acetylhexosaminidase activity}} {{GNF_GO|id=GO:0016798 |text = hydrolase activity, acting on glycosyl bonds}} {{GNF_GO|id=GO:0042803 |text = protein homodimerization activity}} {{GNF_GO|id=GO:0043169 |text = cation binding}} {{GNF_GO|id=GO:0046982 |text = protein heterodimerization activity}}
| Component = {{GNF_GO|id=GO:0001669 |text = acrosome}} {{GNF_GO|id=GO:0016020 |text = membrane}}
| Process = {{GNF_GO|id=GO:0001501 |text = skeletal development}} {{GNF_GO|id=GO:0005975 |text = carbohydrate metabolic process}} {{GNF_GO|id=GO:0006687 |text = glycosphingolipid metabolic process}} {{GNF_GO|id=GO:0006689 |text = ganglioside catabolic process}} {{GNF_GO|id=GO:0006874 |text = cellular calcium ion homeostasis}} {{GNF_GO|id=GO:0007040 |text = lysosome organization and biogenesis}} {{GNF_GO|id=GO:0007341 |text = penetration of zona pellucida}} {{GNF_GO|id=GO:0007605 |text = sensory perception of sound}} {{GNF_GO|id=GO:0007626 |text = locomotory behavior}} {{GNF_GO|id=GO:0008049 |text = male courtship behavior}} {{GNF_GO|id=GO:0008152 |text = metabolic process}} {{GNF_GO|id=GO:0008654 |text = phospholipid biosynthetic process}} {{GNF_GO|id=GO:0009313 |text = oligosaccharide catabolic process}} {{GNF_GO|id=GO:0019915 |text = sequestering of lipid}} {{GNF_GO|id=GO:0019953 |text = sexual reproduction}} {{GNF_GO|id=GO:0030203 |text = glycosaminoglycan metabolic process}} {{GNF_GO|id=GO:0031323 |text = regulation of cellular metabolic process}} {{GNF_GO|id=GO:0042552 |text = myelination}} {{GNF_GO|id=GO:0044267 |text = cellular protein metabolic process}} {{GNF_GO|id=GO:0048157 |text = oogenesis}} {{GNF_GO|id=GO:0050885 |text = regulation of balance}} {{GNF_GO|id=GO:0050905 |text = neuromuscular process}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3074
    | Hs_Ensembl = ENSG00000049860
    | Hs_RefseqProtein = NP_000512
    | Hs_RefseqmRNA = NM_000521
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 5
    | Hs_GenLoc_start = 74016725
    | Hs_GenLoc_end = 74052869
    | Hs_Uniprot = P07686
    | Mm_EntrezGene = 15212
    | Mm_Ensembl = ENSMUSG00000021665
    | Mm_RefseqmRNA = NM_010422
    | Mm_RefseqProtein = NP_034552
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 13
    | Mm_GenLoc_start = 98277106
    | Mm_GenLoc_end = 98298969
    | Mm_Uniprot = Q3TXR9
  }}
}}
'''Hexosaminidase B (beta polypeptide)''', also known as '''HEXB''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: HEXB hexosaminidase B (beta polypeptide)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3074| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
=== Protein ===
{{PBB_Summary
| section_title =  
| summary_text = 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).<ref name="entrez">{{cite web | title = Entrez Gene: HEXB hexosaminidase B (beta polypeptide)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3074| accessdate = }}</ref>
}}


==References==
HEXB consists of 556 [[amino acid]] residues and weighs 63111Da.
{{reflist}}
 
==Further reading==
== Function ==
{{refbegin | 2}}
 
{{PBB_Further_reading
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]].<ref name="Bateman_2011">{{cite journal | vauthors = Bateman KS, Cherney MM, Mahuran DJ, Tropak M, James MN | title = Crystal structure of β-hexosaminidase B in complex with pyrimethamine, a potential pharmacological chaperone | journal = Journal of Medicinal Chemistry | volume = 54 | issue = 5 | pages = 1421–9 | date = March 2011 | pmid = 21265544 | pmc = 3201983 | doi = 10.1021/jm101443u }}</ref> 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]].<ref>{{cite journal | vauthors = Sonnino S, Chigorno V | title = Ganglioside molecular species containing C18- and C20-sphingosine in mammalian nervous tissues and neuronal cell cultures | journal = Biochimica et Biophysica Acta | volume = 1469 | issue = 2 | pages = 63–77 | date = September 2000 | pmid = 10998569 | doi=10.1016/s0005-2736(00)00210-8}}</ref>
| citations =  
 
*{{cite journal | author=Mahuran DJ |title=The biochemistry of HEXA and HEXB gene mutations causing GM2 gangliosidosis. |journal=Biochim. Biophys. Acta |volume=1096 |issue= 2 |pages= 87-94 |year= 1991 |pmid= 1825792 |doi= }}
== Clinical significance ==
*{{cite journal  | author=Mahuran DJ |title=Biochemical consequences of mutations causing the GM2 gangliosidoses. |journal=Biochim. Biophys. Acta |volume=1455 |issue= 2-3 |pages= 105-38 |year= 1999 |pmid= 10571007 |doi=  }}
 
*{{cite journal | author=Gilbert F, Kucherlapati R, Creagan RP, ''et al.'' |title=Tay-Sachs' and Sandhoff's diseases: the assignment of genes for hexosaminidase A and B to individual human chromosomes. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=72 |issue= 1 |pages= 263-7 |year= 1975 |pmid= 1054503 |doi= }}
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.<ref name="Bateman_2011" /> Patients present with neurosomatic manifestations. Therapeutic effects of Hex subunit gene transduction have been examined on Sandhoff disease model mice.<ref name="Itakura_2006">{{cite journal | vauthors = Itakura T, Kuroki A, Ishibashi Y, Tsuji D, Kawashita E, Higashine Y, Sakuraba H, Yamanaka S, Itoh K | title = Inefficiency in GM2 ganglioside elimination by human lysosomal beta-hexosaminidase beta-subunit gene transfer to fibroblastic cell line derived from Sandhoff disease model mice | journal = Biological & Pharmaceutical Bulletin | volume = 29 | issue = 8 | pages = 1564–9 | date = August 2006 | pmid = 16880605 | doi=10.1248/bpb.29.1564}}</ref> 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.<ref>{{cite journal | vauthors = Matsuoka K, Tamura T, Tsuji D, Dohzono Y, Kitakaze K, Ohno K, Saito S, Sakuraba H, Itoh K | title = Therapeutic potential of intracerebroventricular replacement of modified human β-hexosaminidase B for GM2 gangliosidosis | journal = Molecular Therapy | volume = 19 | issue = 6 | pages = 1017–24 | date = June 2011 | pmid = 21487393 | pmc = 3129794 | doi = 10.1038/mt.2011.27 }}</ref>
*{{cite journal  | author=McInnes B, Potier M, Wakamatsu N, ''et al.'' |title=An unusual splicing mutation in the HEXB gene is associated with dramatically different phenotypes in patients from different racial backgrounds. |journal=J. Clin. Invest. |volume=90 |issue= 2 |pages= 306-14 |year= 1992 |pmid= 1386607 |doi=  }}
 
*{{cite journal  | author=Bolhuis PA, Bikker H |title=Deletion of the 5'-region in one or two alleles of HEXB in 15 out of 30 patients with Sandhoff disease. |journal=Hum. Genet. |volume=90 |issue= 3 |pages= 328-9 |year= 1993 |pmid= 1487253 |doi= }}
== Interactions ==
*{{cite journal | author=Wakamatsu N, Kobayashi H, Miyatake T, Tsuji S |title=A novel exon mutation in the human beta-hexosaminidase beta subunit gene affects 3' splice site selection. |journal=J. Biol. Chem. |volume=267 |issue= 4 |pages= 2406-13 |year= 1992 |pmid= 1531140 |doi= }}
 
*{{cite journal  | author=Banerjee P, Siciliano L, Oliveri D, ''et al.'' |title=Molecular basis of an adult form of beta-hexosaminidase B deficiency with motor neuron disease. |journal=Biochem. Biophys. Res. Commun. |volume=181 |issue= 1 |pages= 108-15 |year= 1992 |pmid= 1720305 |doi=  }}
HEXB has been found to interact with [[HEXA]]<ref>{{cite journal | vauthors = Gort L, de Olano N, Macías-Vidal J, Coll MA | title = GM2 gangliosidoses in Spain: analysis of the HEXA and HEXB genes in 34 Tay-Sachs and 14 Sandhoff patients | journal = Gene | volume = 506 | issue = 1 | pages = 25–30 | date = September 2012 | pmid = 22789865 | doi = 10.1016/j.gene.2012.06.080 }}</ref> and [[ganglioside]].<ref name="Itakura_2006" />
*{{cite journal  | author=Boose JA, Tifft CJ, Proia RL, Myerowitz R |title=Synthesis of a human lysosomal enzyme, beta-hexosaminidase B, using the baculovirus expression system. |journal=Protein Expr. Purif. |volume=1 |issue= 2 |pages= 111-20 |year= 1992 |pmid= 1967020 |doi=  }}
{{-}}
*{{cite journal  | author=Mahuran DJ |title=Characterization of human placental beta-hexosaminidase I2. Proteolytic processing intermediates of hexosaminidase A. |journal=J. Biol. Chem. |volume=265 |issue= 12 |pages= 6794-9 |year= 1990 |pmid= 2139028 |doi=  }}
*{{cite journal  | author=Neote K, McInnes B, Mahuran DJ, Gravel RA |title=Structure and distribution of an Alu-type deletion mutation in Sandhoff disease. |journal=J. Clin. Invest. |volume=86 |issue= 5 |pages= 1524-31 |year= 1990 |pmid= 2147027 |doi=  }}
*{{cite journal | author=Neote K, Brown CA, Mahuran DJ, Gravel RA |title=Translation initiation in the HEXB gene encoding the beta-subunit of human beta-hexosaminidase. |journal=J. Biol. Chem. |volume=265 |issue= 34 |pages= 20799-806 |year= 1991 |pmid= 2147427 |doi=  }}
*{{cite journal  | author=Dlott B, d'Azzo A, Quon DV, Neufeld EF |title=Two mutations produce intron insertion in mRNA and elongated beta-subunit of human beta-hexosaminidase. |journal=J. Biol. Chem. |volume=265 |issue= 29 |pages= 17921-7 |year= 1990 |pmid= 2170400 |doi=  }}
*{{cite journal  | author=Nakano T, Suzuki K |title=Genetic cause of a juvenile form of Sandhoff disease. Abnormal splicing of beta-hexosaminidase beta chain gene transcript due to a point mutation within intron 12. |journal=J. Biol. Chem. |volume=264 |issue= 9 |pages= 5155-8 |year= 1989 |pmid= 2522450 |doi=  }}
*{{cite journal  | author=Hubbes M, Callahan J, Gravel R, Mahuran D |title=The amino-terminal sequences in the pro-alpha and -beta polypeptides of human lysosomal beta-hexosaminidase A and B are retained in the mature isozymes. |journal=FEBS Lett. |volume=249 |issue= 2 |pages= 316-20 |year= 1989 |pmid= 2525487 |doi= }}
*{{cite journal  | author=O'Dowd BF, Quan F, Willard HF, ''et al.'' |title=Isolation of cDNA clones coding for the beta subunit of human beta-hexosaminidase. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=82 |issue= 4 |pages= 1184-8 |year= 1985 |pmid= 2579389 |doi=  }}
*{{cite journal  | author=Bikker H, van den Berg FM, Wolterman RA, ''et al.'' |title=Demonstration of a Sandhoff disease-associated autosomal 50-kb deletion by field inversion gel electrophoresis. |journal=Hum. Genet. |volume=81 |issue= 3 |pages= 287-8 |year= 1989 |pmid= 2921040 |doi=  }}
*{{cite journal | author=Bolhuis PA, Oonk JG, Kamp PE, ''et al.'' |title=Ganglioside storage, hexosaminidase lability, and urinary oligosaccharides in adult Sandhoff's disease. |journal=Neurology |volume=37 |issue= 1 |pages= 75-81 |year= 1987 |pmid= 2948136 |doi= }}
*{{cite journal  | author=Proia RL |title=Gene encoding the human beta-hexosaminidase beta chain: extensive homology of intron placement in the alpha- and beta-chain genes. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=85 |issue= 6 |pages= 1883-7 |year= 1988 |pmid= 2964638 |doi=  }}
*{{cite journal  | author=Mahuran DJ, Neote K, Klavins MH, ''et al.'' |title=Proteolytic processing of pro-alpha and pro-beta precursors from human beta-hexosaminidase. Generation of the mature alpha and beta a beta b subunits. |journal=J. Biol. Chem. |volume=263 |issue= 10 |pages= 4612-8 |year= 1988 |pmid= 2965147 |doi= }}
}}
{{refend}}


{{WikiDoc Help Menu}}
== References ==
{{reflist|33em}}


== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Mahuran DJ | title = The biochemistry of HEXA and HEXB gene mutations causing GM2 gangliosidosis | journal = Biochimica et Biophysica Acta | volume = 1096 | issue = 2 | pages = 87–94 | date = February 1991 | pmid = 1825792 | doi = 10.1016/0925-4439(91)90044-A }}
* {{cite journal | vauthors = Mahuran DJ | title = Biochemical consequences of mutations causing the GM2 gangliosidoses | journal = Biochimica et Biophysica Acta | volume = 1455 | issue = 2-3 | pages = 105–38 | date = October 1999 | pmid = 10571007 | doi = 10.1016/S0925-4439(99)00074-5 }}
* {{cite journal | vauthors = Gilbert F, Kucherlapati R, Creagan RP, Murnane MJ, Darlington GJ, Ruddle FH | title = Tay-Sachs' and Sandhoff's diseases: the assignment of genes for hexosaminidase A and B to individual human chromosomes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 72 | issue = 1 | pages = 263–7 | date = January 1975 | pmid = 1054503 | pmc = 432284 | doi = 10.1073/pnas.72.1.263 }}
* {{cite journal | vauthors = McInnes B, Potier M, Wakamatsu N, Melancon SB, Klavins MH, Tsuji S, Mahuran DJ | title = An unusual splicing mutation in the HEXB gene is associated with dramatically different phenotypes in patients from different racial backgrounds | journal = The Journal of Clinical Investigation | volume = 90 | issue = 2 | pages = 306–14 | date = August 1992 | pmid = 1386607 | pmc = 443103 | doi = 10.1172/JCI115863 }}
* {{cite journal | vauthors = Bolhuis PA, Bikker H | title = Deletion of the 5'-region in one or two alleles of HEXB in 15 out of 30 patients with Sandhoff disease | journal = Human Genetics | volume = 90 | issue = 3 | pages = 328–9 | date = November 1992 | pmid = 1487253 | doi = 10.1007/bf00220096 }}
* {{cite journal | vauthors = Wakamatsu N, Kobayashi H, Miyatake T, Tsuji S | title = A novel exon mutation in the human beta-hexosaminidase beta subunit gene affects 3' splice site selection | journal = The Journal of Biological Chemistry | volume = 267 | issue = 4 | pages = 2406–13 | date = February 1992 | pmid = 1531140 | doi =  }}
* {{cite journal | vauthors = Banerjee P, Siciliano L, Oliveri D, McCabe NR, Boyers MJ, Horwitz AL, Li SC, Dawson G | title = Molecular basis of an adult form of beta-hexosaminidase B deficiency with motor neuron disease | journal = Biochemical and Biophysical Research Communications | volume = 181 | issue = 1 | pages = 108–15 | date = November 1991 | pmid = 1720305 | doi = 10.1016/S0006-291X(05)81388-9 }}
* {{cite journal | vauthors = Boose JA, Tifft CJ, Proia RL, Myerowitz R | title = Synthesis of a human lysosomal enzyme, beta-hexosaminidase B, using the baculovirus expression system | journal = Protein Expression and Purification | volume = 1 | issue = 2 | pages = 111–20 | date = November 1990 | pmid = 1967020 | doi = 10.1016/1046-5928(90)90003-H }}
* {{cite journal | vauthors = Mahuran DJ | title = Characterization of human placental beta-hexosaminidase I2. Proteolytic processing intermediates of hexosaminidase A | journal = The Journal of Biological Chemistry | volume = 265 | issue = 12 | pages = 6794–9 | date = April 1990 | pmid = 2139028 | doi =  }}
* {{cite journal | vauthors = Neote K, McInnes B, Mahuran DJ, Gravel RA | title = Structure and distribution of an Alu-type deletion mutation in Sandhoff disease | journal = The Journal of Clinical Investigation | volume = 86 | issue = 5 | pages = 1524–31 | date = November 1990 | pmid = 2147027 | pmc = 296899 | doi = 10.1172/JCI114871 }}
* {{cite journal | vauthors = Neote K, Brown CA, Mahuran DJ, Gravel RA | title = Translation initiation in the HEXB gene encoding the beta-subunit of human beta-hexosaminidase | journal = The Journal of Biological Chemistry | volume = 265 | issue = 34 | pages = 20799–806 | date = December 1990 | pmid = 2147427 | doi =  }}
* {{cite journal | vauthors = Dlott B, d'Azzo A, Quon DV, Neufeld EF | title = Two mutations produce intron insertion in mRNA and elongated beta-subunit of human beta-hexosaminidase | journal = The Journal of Biological Chemistry | volume = 265 | issue = 29 | pages = 17921–7 | date = October 1990 | pmid = 2170400 | doi =  }}
* {{cite journal | vauthors = Nakano T, Suzuki K | title = Genetic cause of a juvenile form of Sandhoff disease. Abnormal splicing of beta-hexosaminidase beta chain gene transcript due to a point mutation within intron 12 | journal = The Journal of Biological Chemistry | volume = 264 | issue = 9 | pages = 5155–8 | date = March 1989 | pmid = 2522450 | doi =  }}
* {{cite journal | vauthors = Hubbes M, Callahan J, Gravel R, Mahuran D | title = The amino-terminal sequences in the pro-alpha and -beta polypeptides of human lysosomal beta-hexosaminidase A and B are retained in the mature isozymes | journal = FEBS Letters | volume = 249 | issue = 2 | pages = 316–20 | date = June 1989 | pmid = 2525487 | doi = 10.1016/0014-5793(89)80649-0 }}
* {{cite journal | vauthors = Bikker H, van den Berg FM, Wolterman RA, de Vijlder JJ, Bolhuis PA | title = Demonstration of a Sandhoff disease-associated autosomal 50-kb deletion by field inversion gel electrophoresis | journal = Human Genetics | volume = 81 | issue = 3 | pages = 287–8 | date = February 1989 | pmid = 2921040 | doi = 10.1007/BF00279006 }}
* {{cite journal | vauthors = Bolhuis PA, Oonk JG, Kamp PE, Ris AJ, Michalski JC, Overdijk B, Reuser AJ | title = Ganglioside storage, hexosaminidase lability, and urinary oligosaccharides in adult Sandhoff's disease | journal = Neurology | volume = 37 | issue = 1 | pages = 75–81 | date = January 1987 | pmid = 2948136 | doi = 10.1212/wnl.37.1.75 }}
* {{cite journal | vauthors = Proia RL | title = Gene encoding the human beta-hexosaminidase beta chain: extensive homology of intron placement in the alpha- and beta-chain genes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 6 | pages = 1883–7 | date = March 1988 | pmid = 2964638 | pmc = 279885 | doi = 10.1073/pnas.85.6.1883 }}
* {{cite journal | vauthors = Mahuran DJ, Neote K, Klavins MH, Leung A, Gravel RA | title = Proteolytic processing of pro-alpha and pro-beta precursors from human beta-hexosaminidase. Generation of the mature alpha and beta a beta b subunits | journal = The Journal of Biological Chemistry | volume = 263 | issue = 10 | pages = 4612–8 | date = April 1988 | pmid = 2965147 | doi =  }}
{{refend}}
{{PDB Gallery|geneid=3074}}


{{WikiDoc Sources}}
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{{Glycolipid/sphingolipid metabolism enzymes}}

Latest revision as of 08:45, 9 February 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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Wikidata
View/Edit Human

Beta-hexosaminidase subunit beta is an enzyme that in humans is encoded by the HEXB gene.[1][2][3]

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).[3]

Structure

Gene

The HEXB gene lies on the chromosome location of 5q13.3 and consists of 15 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.[4] 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.[5]

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.[4] Patients present with neurosomatic manifestations. Therapeutic effects of Hex subunit gene transduction have been examined on Sandhoff disease model mice.[6] 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.[7]

Interactions

HEXB has been found to interact with HEXA[8] and ganglioside.[6]

References

  1. ↑ 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 397219. PMID 2579389.
  2. ↑ 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.
  3. ↑ 3.0 3.1 "Entrez Gene: HEXB hexosaminidase B (beta polypeptide)".
  4. ↑ 4.0 4.1 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.
  5. ↑ 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. doi:10.1016/s0005-2736(00)00210-8. PMID 10998569.
  6. ↑ 6.0 6.1 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.
  7. ↑ 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.
  8. ↑ 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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