Jones et al. (1996) reported that an expressed sequence tag (EST 221) derived from human adult testis shares homology with the Drosophila fat facets (faf) gene. They detected related sequences on both the human X and Y chromosomes. They used EST 221 to derive clones covering the complete open reading frame of the X-specific locus, which they termed DFFRX. Y-specific cDNA clones were derived, and they termed that locus DFFRY. Over the 2 regions corresponding to nucleotides 6 to 1901 and nucleotides 5815 to 7907 of the DFFRX sequence, the X- and Y-specific sequences share 91% and 88% identity, respectively. Both putative gene products contain conserved cysteine and histidine domains that have been described in ubiquitin C-terminal hydrolases,
NCBI Summary:
This gene is a member of the peptidase C19 family and encodes a protein that is similar to ubiquitin-specific proteases. Though this gene is located on the X chromosome, it escapes X-inactivation. Mutations in this gene have been associated with Turner syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
FAM deubiquitylating enzyme is essential for preimplantation mouse embryo development. Pantaleon M et al. FAM is a developmentally regulated substrate-specific deubiquitylating enzyme. It binds the cell adhesion and signalling molecules beta-catenin and AF-6 in vitro, and stabilises both in mammalian cell culture. To determine if FAM is required at the earliest stages of mouse development we examined its expression and function in preimplantation mouse embryos. FAM is expressed at all stages of preimplantation development from ovulation to implantation. Exposure of two-cell embryos to FAM-specific antisense, but not sense, oligodeoxynucleotides resulted in depletion of the FAM protein and failure of the embryos to develop to blastocysts. Loss of FAM had two physiological effects, namely, a decrease in cleavage rate and an inhibition of cell adhesive events. Depletion of FAM protein was mirrored by a loss of beta-catenin such that very little of either protein remained following 72h culture. The residual beta-catenin was localised to sites of cell-cell contact suggesting that the cytoplasmic pool of beta-catenin is stabilised by FAM. Although AF-6 levels initially decreased they returned to normal. However, the nascent protein was mislocalised at the apical surface of blastomeres. Therefore FAM is required for preimplantation mouse embryo development and regulates beta-catenin and AF-6 in vivo.
Northern blot analysis of 16 different adult human tissues with the EST 221 revealed expression in all tissues. Jones et al. (1996). Noma T, et al reported Stage- and sex-dependent expressions of Usp9x, an X-linked mouse ortholog of Drosophila Fat facets, during gonadal development and oogenesis in mice.
Expression regulated by
Comment
Ovarian localization
Oocyte
Comment
The requirement of faf for normal oocyte development in Drosophila combined with the map location and escape from X-inactivation of DFFRX raises the possibility that the human homologue plays a role in the defects of oocyte proliferation and subsequent gonadal degeneration found in Turner syndrome.
237 EXPRESSION PATTERNS OF DEUBIQUITYLATING FACTORS (Usp9x AND Af-6) IN GERM CELLS OF WILD TYPE AND TRANSGENIC PIGS. Oh MY et al. The ubiquitin (ub)-mediated degradation of certain regulatory proteins plays critical roles in various functions, including cell cycle, signal transduction, transcription regulation and endocytosis. Usp9x is stage dependently expressed in the germ cells during mouse gametogenesis. Af-6, a cell junction protein, has been identified as a substrate of Usp9x, indicating a possible association between Usp9x and Af-6 in spermatogenesis and oogenesis. In this study, we examined the expression patterns of Usp9x and Af-6 and their intracellular localization in transgenic pig testes and ovary. In both Sertoli and granulosa cells, Af-6 was continuously expressed throughout postnatal and adult stages. Both Af-6 and Usp9x were enriched at the sites of Sertoli-spermatid junctions, especially at stage IV. In granulosa cells, Usp9x was strongly expressed in primary follicles, but its expression rapidly decreased after the late-secondary follicle stage. On the other hand, the expression of both Usp9x and Af-6 was weak in transgenic pigs, with low expression in the Sertoli cells and relatively stronger expression in Graafian follicles. This study suggests that Usp9x and Af-6 were deubiquitylated in Sertoli and follicle cells in wild type and transgenic pigs.
Follicle stages
Comment
Phenotypes
POF (premature ovarian failure)
Mutations
2 mutations
Species: human
Mutation name: None
type: naturally occurring fertility: subfertile Comment: In Drosophila the faf gene has been shown to be important in eye function and in oocyte development. The high degree of conservation between the Drosophila faf gene and the DFFRX sequence led Jones et al. (1996) to conclude that DFFRX has an important function in humans. They mapped DFFRX to Xp11.4 by somatic cell hybrid analysis and a YAC library screen. They noted that the map location coincides with the region of the X chromosome defined by partial deletions as being critical for the major stigmata associated with Turner syndrome. They raised the possibility that DFFRX plays a role in the defects of oocyte proliferation and subsequent gonadal degeneration found in Turner syndrome.
Species: human
Mutation name: type: naturally occurring fertility: subfertile Comment: Copy number variants on the X chromosome in women with primary ovarian insufficiency. Knauff EA et al. (2011) To investigate whether submicroscopic copy number variants (CNVs) on the X chromosome can be identified in women with primary ovarian insufficiency (POI), defined as spontaneous secondary amenorrhea before 40 years of age accompanied by follicle-stimulating hormone levels above 40 IU/L on at least two occasions. Analysis of intensity data of single nucleotide polymorphism (SNP) probes generated by genomewide Illumina 370k CNV BeadChips, followed by the validation of identified loci using a custom designed ultra-high-density comparative genomic hybridization array containing 48,325 probes evenly distributed over the X chromosome. Multicenter genetic cohort study in the Netherlands. 108 Dutch Caucasian women with POI, 97 of whom passed quality control, who had a normal karyogram and absent fragile X premutation, and 235 healthy Dutch Caucasian women as controls. None. Amount and locus of X chromosomal microdeletions or duplications. Intensity differences between SNP probes identify microdeletions and duplications. The initial analysis identified an overrepresentation of deletions in POI patients. Moreover, CNVs in two genes on the Xq21.3 locus (i.e., PCDH11X and TGIF2LX) were statistically significantly associated with the POI phenotype. Mean size of identified CNVs was 262 kb. However, in the validation study the identified putative Xq21.3 deletions samples did not show deviations in intensities in consecutive probes. X chromosomal submicroscopic CNVs do not play a major role in Caucasian POI patients. We provide guidelines on how submicroscopic cytogenetic POI research should be conducted.//////////////////