The detailed entries of the Imprinted Gene Catalogue database were created by Benjamin Tycko, Columbia University, New York and are updated by Ian Morison


 

Detailed entry for Gene:

Ube3a (and Ube3a-as)

Chromosome:

Human Chr15q11-q13
Mouse Chr7 (central)

Links:

OMIM

Imprinting:

The paternal allele of Ube3a is silenced in hippocampal and cerebellar neurons; there is biallelic expression in many other tissues (Albrecht U et al, 1997; Rougeulle C et al, 1997; Vu TH et al, 1997). The Ube3a-as transcript is imprinted oppositely to Ube3a and extends at least 148 exons from the 5' end of SNURF-SNRPN (Rougeulle C et al, 1998; Runte M et al, 2001).

Gene Product:

Ube3a encodes a ubiquitin conjugating enzyme; E3 ubiquitin ligase. The protein contains a hect-motif, which is a catalytic domain for ubiquitin ligation shared by many E3 proteins.

Functional Data:

Proteins are conjugated to ubiquitin in a series of reactions catalyzed by activating (E1), conjugating (E2), and ligase (E3) enzymes. The Ube3a gene encodes the E6AP ubiquitin-protein ligase (E3), which is a cellular protein first identified by its ability to mediate the degradation of the p53 tumor suppressor protein, acting in conjunction with the human papillomavirus E6 protein (Huibregtse JM et al, 1991; Scheffner M et al, 1993). A separate line of research, based on positional cloning, led to the finding that this protein is mutated in Angelman syndrome (AS). AS is a neurodevelopmental disorder associated with severe mental retardation. This condition was linked to the Chr15q11-q13 imprinted domain by evidence from UPDs, interstitial chromosomal deletions and genetic linkage (Lalande M et al, 1999; Nicholls RD et al, 1989; Wagstaff J et al, 1993). Mice lacking expression of Ube3a (mat-/pat+) show a subtle neurological deficit, including reduced learning and deficient long-term potentiation of synaptic transmission (Jiang YH et al, 1998). Increased levels of p53 protein were observed in the hippocampal and cerebellar neurons of these mice . These mice therefore model some aspects of AS in humans. Point mutations in UBE3A cause some cases of AS, while other cases (pat-UPD and deletion categories) are presumed to be due to loss of expression of this gene (Kishino T et al, 1997; Malzac P et al, 1998; Matsuura T et al, 1997).

 

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