This is the conserved C-terminal half of the protein KIAA1109 which is the fragile site-associated protein FSA (PUBMED:16545529). Genome-wide-association studies showed this protein linked to the susceptibility to coeliac disease (PUBMED:17558408). The protein may also be associated with polycystic kidney disease (PUBMED:16632497).
This is the conserved C-terminal half of the protein KIAA1109, which is the fragile site-associated protein FSA [ (PUBMED:16545529) ]. Genome-wide-association studies showed this protein to linked to the susceptibility to coeliac disease [ (PUBMED:17558408) ]. The protein may also be associated with polycystic kidney disease [ (PUBMED:16632497) ].
Family alignment:
There are 1204 FSA_C domains in 1202 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing FSA_C domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with FSA_C domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing FSA_C domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
A genome-wide association study for celiac disease identifies risk variants inthe region harboring IL2 and IL21.
Nat Genet. 2007; 39: 827-9
Display abstract
We tested 310,605 SNPs for association in 778 individuals with celiac disease and1,422 controls. Outside the HLA region, the most significant finding (rs13119723;P = 2.0 x 10(-7)) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block.We independently confirmed association in two further collections (strongestassociation at rs6822844, 24 kb 5' of IL21; meta-analysis P = 1.3 x 10(-14), oddsratio = 0.63), suggesting that genetic variation in this region predisposes toceliac disease.
G8: a novel domain associated with polycystic kidney disease and non-syndromichearing loss.
Bioinformatics. 2006; 22: 2189-91
Display abstract
We report a novel protein domain-G8-which contains five repeated beta-strandpairs and is present in some disease-related proteins such as PKHD1, KIAA1199,TMEM2 as well as other uncharacterized proteins. Most G8-containing proteins are predicted to be membrane-integral or secreted. The G8 domain may be involved inextracellular ligand binding and catalysis. It has been reported that mis-sensemutations in the two G8 domains of human PKHD1 protein resulted in a less stable protein and are associated with autosomal-recessive polycystic kidney disease,indicating the importance of the domain structure. G8 is also present in theN-terminus of some non-syndromic hearing loss disease-related proteins such asKIAA1109 and TMEM2. Discovery of G8 domain will be important for the research of the structure/function of related proteins and beneficial for the development of novel therapeutics. Contact: liangsp@hunnu.edu.cn
Molecular cloning of Chinese hamster 1q31 chromosomal fragile site DNA that isimportant to mdr1 gene amplification reveals a novel gene whose expression isassociated with spermatocyte and adipocyte differentiation.
Gene. 2006; 372: 44-52
Display abstract
DNA amplification plays important roles in the development of drug resistance andtumor progression. One mechanism of DNA amplification involves thebreakage-fusion-bridge (BFB) cycle. We previously reported that in Chinesehamster ovary (CHO) cell line, breakage at fragile site 1q31 was associated with mdr1 gene amplification through the BFB mechanism. To elucidate the molecularbasis of BFB-mediated DNA amplification, we cloned 1q31 fragile site DNA from aChinese hamster cell line containing an integrated neomycin-resistance marker.Sequence analyses revealed many characteristics similar to those in other common fragile sites. Moreover, this fragile site contains an evolutionarily conservednovel gene, designated fragile site-associated (FSA) gene. FSA encodes aapproximately 16-kb mRNA, from which an unusually large open reading frame (orf) of 5005 amino acids can be deduced. The C-terminal portion of FSA shares astriking sequence similarity to that of Caenorhabditi elegans lipid depleted-3(lpd-3) gene whose function has been demonstrated to involve in lipid storage. Wealso demonstrated that expression of FSA is associated with the developmentalprograms of spermatogenesis and adipogenesis. Our results suggest that theChinese hamster 1q31 fragile site has many important functions includingregulation of mdr1 amplification and differentiation of adipocytes andspermatocytes.
Links (links to other resources describing this domain)
