Gene: [05q13/HEXB] hexosaminidase B, beta polypeptide; gangliosidosis GM2, type II (Sandhoff disease); motor neuron disease, progressive;
COM | To avoid
confusion it should be noted that 'beta-N-' in enzyme name (-N- is often
omitted) indicates the cleaving hexosamine structure, while 'beta-' without
'N' indicates an enzyme subunit. Sometimes the beta subunit is designated
as B2 to notify that it is a part of an active enzyme as one of two
covalently bound (via -S-S- bridge) peptides (28 kD beta-A and 27 kD beta-B) produced by proteolysis of a 63 kD pre-beta-polypeptide." |
GEN | [1] The gene length: 37 kb. Exons: 14 (556 aa), introns: 13
(Bikker-1989; Paw-1989). cDNA is 2.2 kb; ex1=100 amino acids, ex2=49,
ex3=21, ex4=16, ex5=37, ex6=34, ex7=43, ex8=61, ex9=29, ex10=24, ex11=58,
ex12=31, ex13=34, ex14=19. int1=3.9 kb, int2=4.1, int3=3.2, int4=0.2,
int5=7.7, int6=8.2, int7=2.1, int8=0.8, int9=1.4, int10=0.5, int11=1.4,
int12=0.3, int13=0.37 kb; int2 comprises two HindIII sites, one of which
(3'-site) is polymorphic. [2] The promoter region: Standard TATA box is absent but 3 GGGCGGG sites are found in positions -14, -80 and -126 upstream transcription initiation site (capping), as well as the complementary inverted CCGCCC site. A putative additional CAAT promoter (cacCAATtt) is in position -333. In general, promoter region structure is typical for housekeeping genes. There are two GC sites in open reading frame: GGGCGG in position +27, or 23 bp upstream to the first initiator codon [3] Poly(A)-signal g |
FUN | Systematic name: beta-N-acetyl-D-hexosaminide N-acetylhexosaminohydrolase. The enzyme catalyzes hydrolysis of terminal non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides." |
FAG | The gene coding for alpha subunit, or hexosaminidase A (its deficiency causes Tay-Sachs gangliosidosis GM2/I) is located on chr 15q (GEM:15q2/HEXA)." |
PAT | [1] The deficiency of
both hexosaminidases is the pathogenetic basis of Sandhoff disease
sometimes named as amaurotic idiocy. As a result ganglioside GM2 is
accumulated in nervous system and internal organs. [2] Psychomotoric retardation, hepatosplenomegaly, doll-like face, and macrocephaly are typical for Sandhoff disease. As the disease progresses, myoclonic seizures and spastic tetraparesis appear. Life span is 2 to 3 years." |
FOG | The inheritance mode: autosomal recessive. |
HET | It is obvious from the subunit composition that beta subunit deficiency affects both main isoforms, A and B (in case of Sandhoff disease), whereas the isoform A only is deficient in Tay-Sachs disease (alpha subunit mutation, see GEM:15q2/HEXA). However, clinical cases have been described, in which beta peptide deficiency impairs the assembling of B but not A isoform (i.e. HEXB activity decreases while HEXA activity remains normal); see spinal amyotrophy description in Hancock-1985." |
MOP | See GEM:15q2/HEXA. |
LIN | Loci: GEM:00.0/SCZD1. [1] HEXB ? SCZD1 (Kennedy-1988,1989; Sherrington-1989; Wood-1989)." |
REF | LOC "Balestrazzi P &: Hum Genet, 64, 305-308, 1983 MUT,GEN,PRO "Bikker H &: Hum Genet, 81, 287-288, 1989 MUT,FOG,PAT,PHE "Cashman &: Ann Neurol, 19, 568-572, 1986 LOC "Dana S &: Mol Cell Biol, 2, 1220-1228, 1982 LOC "Fox MF &: CCG, 38, 45-49, 1984 LOC "George DL, Francke: CCG, 22, (HGM4), 408-411, 1978 LOC "George DL, Francke: Somat Cell Genet, 3, 629-638, 1977 LOC "Gilbert F &: PNAS, 72, 263-267, 1975 LIN,MAG "Giuffra &: CCG, 51, (HGM10), 1004-1005, 1989 MUT,FOG,PAT,PHE "Hancock &: BBRC, 130, N3, 1185-1192, 1985 PRO,MUT,MOP "Hara Y &: Hum Genet, 94, 136-140, 1994 COM,LIN,PAT "Kennedy JL &: Schizophrenia Bull, 15, 0-0, 1989 COM,LIN,PAT "Kennedy JL &: Nature, 336, 167-170, 1988 PRO,SEQ,EXP,EVO "Korneluk RG &: JBC, 261, 8407-8413, 1986 MOP,STR,EVO,EXP "Mahuran DJ &: JBC, 263, N10, 4612-4618, 1988 MOP,STR,EVO,EXP "Mahuran DJ &: PNAS, 79, 1602-1605, 1982 MUT,GEN,PRO "Nakano T, Suzuki: JBC, 264, N9, 5155-5158, 1989 GEN,SEQ,STR,MOP "Neote K &: Genomics, 3, N4, 279-286, 1988 PRO,EXP,LOC,MOL "O'Dowd BF &: PNAS, 82, N4 (1 Feb), 1184-1188, 1985 MUT,GEN,PRO "Paw BH &: PNAS, 86, N7, 2413-2417, 1989 GEN,SEQ,STR,MOP "Proia RL: PNAS, 85, N6, 1883-1887, 1988 COM,LIN,PAT "Sherrington &: CCG, 51, (HGM10), 1077, 1989 PRO,MUT,MOP "Weiffenbach B &: Genomics, 10, 173-185, 1991 LIN,MAG "Weiffenbach B &: CCG, 51, (HGM10), 1104-1105, 1989 COM,LIN,PAT "Wood &: CCG, 51, (HGM10), 1110, 1989 |
SWI | SWISSPROT: P07686 |
KEY | lys, mtbd, carb, neu |
CLA | coding, basic |
LOC | 05 q13 |
MIM | MIM: 268800 |
EZN | ENZYME: 3.2.1.52 |
