Probable ubiquitin carboxyl-terminal hydrolase FAF-Y (USP9Y)
The protein contains 2555 amino acids for an estimated molecular weight of 291077 Da.
May function as a ubiquitin-protein or polyubiquitin hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. May therefore play an important regulatory role at the level of protein turnover by preventing degradation of proteins through the removal of conjugated ubiquitin. Essential component of TGF-beta/BMP signaling cascade. Deubiquitinates monoubiquitinated SMAD4, opposing the activity of E3 ubiquitin-protein ligase TRIM33. Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade. Deubiquitination of SMAD4 by USP9X re-empowers its competence to mediate TGF-beta signaling (By similarity). (updated: May 5, 2009)
Protein identification was indicated in the following studies:
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs7067496 | |
| dbSNP:rs2032596 | |
| dbSNP:rs20319 | |
| dbSNP:rs20320 | |
| dbSNP:rs2032606 |
The reference OMIM entry for this protein is 400005
Ubiquitin-specific protease 9, y chromosome; usp9y
Drosophila fat facets-related, y-linked; dffry
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 they termed DFFRX (300072). Y-specific cDNA clones were derived and the corresponding Y-specific locus designated 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 (e.g., 191342). Jones et al. (1996) mapped DFFRY to Yq11.2 by Southern analysis. They noted that in DFFRY there were multiple stop codons in the 3-prime region, suggesting that the Y locus may encode a truncated product or may represent a nonfunctional pseudogene. They detected expression of both DFFRX and DFFRY in developing human tissues. They found also that sequences detected by the EST 221 are widely expressed in adult human tissues. The coding regions of the DFFRY and DFFRX genes show 89% identity at the nucleotide level. In common with DFFRX, the potential amino acid sequence of DFFRY contains the conserved cys and his domains characteristic of ubiquitin C-terminal hydrolases. The human DFFRY mRNA is expressed in a wide range of adult and embryonic tissues, including testis, whereas the homologous mouse Dffry gene is expressed specifically in the testis. Brown et al. (1998) found that 3 azoospermic male patients had deletion of DFFRY from the Y chromosome. Two patients had a testicular phenotype that resembled Sertoli cell-only type I (see 400042), and the third (patient 'Sayer') had diminished spermatogenesis (see 400005.0002). In all 3 patients, the deletions extended from close to the 3-prime end into the gene, removing the entire coding sequence of DFFRY. Brown et al. (1998) showed that the mouse Dffry gene maps to the Sxr-b deletion interval on the shorter arm of the mouse Y chromosome and that its expression in mouse testis can first be detected between 7.5 and 10.5 days after birth when type A and B spermatogonia and preleptotene and leptotene spermatocytes are present. Sargent et al. (1999) refined the deletion breakpoints in 4 patients with AZFa male infertility. All patients had USP9Y and an anonymous EST, AZFaT1, deleted in their entirety, and 3 patients also had DBY (400010) deleted. The 3 patients with AZFaT1, USP9Y, and DBY deleted showed a severe Sertoli cell-only type I phenotype, whereas the patient who had retained DBY (SAYER, originally reported by Brown et al., 1998) showed a milder oligozoospermic phenotype (see 400005.0002). RT-PCR analysis of mouse testis RNA showed that Dby is expressed primarily in somatic cells, while Usp9y is expressed specifically in testis in a germ cell-dependent fashion. Sun et al. (1999) were the first to trace spermatogenic failure to a point mutation in a Y-linked gene or to a deletion of a single Y-linked gene. They sequenced the AZFa (see 415000) region of the Y chromosome and identified 2 previously described functional genes: USP9Y and DBY (400010). Screening of the 2 genes in 576 infertile and 96 fertile men revealed several sequence variants, most of which appeared to be heritable and of little functional consequen ... More on the omim web site
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 400005 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).