2ct2

Structural highlights

Disease

[TRI32_HUMAN] Defects in TRIM32 are the cause of limb-girdle muscular dystrophy type 2H (LGMD2H) [MIM:254110]; also known as muscular dystrophy Hutterite type. LGMD2H is an autosomal recessive degenerative myopathy characterized by pelvic girdle, shoulder girdle and quadriceps muscle weakness. Clinical phenotype and severity are highly variable. Disease progression is slow and most patients remain ambulatory into the sixth decade of life.^{[1] [2]} Defects in TRIM32 are the cause of Bardet-Biedl syndrome type 11 (BBS11) [MIM:209900]. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, autosomal recessive disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. A relatively high incidence of BBS is found in the mixed Arab populations of Kuwait and in Bedouin tribes throughout the Middle East, most likely due to the high rate of consaguinity in these populations and a founder effect.^[3]

Function

[TRI32_HUMAN] Has an E3 ubiquitin ligase activity. Ubiquitinates DTNBP1 (dysbindin) and promotes its degradation. May play a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo. Binds specifically to the activation domain of HIV-1 Tat and can also interact with the HIV-2 and EIAV Tat proteins in vivo.^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Frosk P, Weiler T, Nylen E, Sudha T, Greenberg CR, Morgan K, Fujiwara TM, Wrogemann K. Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene. Am J Hum Genet. 2002 Mar;70(3):663-72. Epub 2002 Jan 29. PMID:11822024 doi:S0002-9297(07)60269-9
2. ↑ Saccone V, Palmieri M, Passamano L, Piluso G, Meroni G, Politano L, Nigro V. Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H. Hum Mutat. 2008 Feb;29(2):240-7. PMID:17994549 doi:10.1002/humu.20633
3. ↑ Chiang AP, Beck JS, Yen HJ, Tayeh MK, Scheetz TE, Swiderski RE, Nishimura DY, Braun TA, Kim KY, Huang J, Elbedour K, Carmi R, Slusarski DC, Casavant TL, Stone EM, Sheffield VC. Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11). Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6287-92. Epub 2006 Apr 10. PMID:16606853 doi:10.1073/pnas.0600158103
4. ↑ Locke M, Tinsley CL, Benson MA, Blake DJ. TRIM32 is an E3 ubiquitin ligase for dysbindin. Hum Mol Genet. 2009 Jul 1;18(13):2344-58. doi: 10.1093/hmg/ddp167. Epub 2009 Apr , 6. PMID:19349376 doi:10.1093/hmg/ddp167