Disease relevance of DDX3Y

• We investigated the function of DDX3Y, the Y chromosome AZFa region encoding a putative DEAD-box RNA helicase protein, the loss of which results in oligozoospermia or azoospermia in humans [1].
• Use of HLA-DQ5-expressing female Epstein-Barr virus transformed B lymphoblastoid cell lines transfected with various H-Y genes and loaded with overlapping peptides demonstrated that both T cell clones are specific for a peptide encoded by DDX3Y [2].
• We examined the immune response to DBY, a model H-Y minor histocompatibility antigen (mHA) in a male patient with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplant from a human histocompatibility leukocyte antigen (HLA)-identical female sibling [3].
• Deletion and expression analysis of AZFa genes on the human Y chromosome revealed a major role for DBY in male infertility [4].
• Plasma dopamine beta-hydroxylase (DBY) activity, urinary catecholamine (CA) and vanillylmandelic acid (VMA) were studied pre- and postoperatively in 20 patients with pheochromocytoma [5].

High impact information on DDX3Y

• There is no Ube1y1 homolog in man, and DBY, either alone or in conjunction with USP9Y, is the favored candidate for an early spermatogenic role [6].
• This dual DBX/DBY antigen is the first mHA to be identified in the context of chronic GVHD [3].
• This epitope screen revealed a high frequency CD4(+) T cell response to a single DBY peptide that persisted from 8 to 21 mo after transplant [3].
• Minor histocompatibility antigen DBY elicits a coordinated B and T cell response after allogeneic stem cell transplantation [3].
• This antibody response was mapped to two DBY peptides beginning at positions 118 and 536 [3].

Biological context of DDX3Y

• The human DDX3Y amino acid sequence is similar to that of the X chromosome gene DDX3X (91.7% homology) [1].
• A comparative study of DDX3X and DDX3Y was performed to determine the significance of DDX3Y for cell growth and spermatogenesis [1].
• The decreased ratio of DDX3Yt1/DDX3Y transcript in impaired spermatogenesis suggests that the DDX3Yt1 transcript is under-expressed in impaired spermatogenesis [7].
• Minor Histocompatibility Antigen DDX3Y Induces HLA-DQ5-Restricted T Cell Responses with Limited TCR-Vbeta Usage Both In Vivo and In Vitro [2].
• In testis tissue sections, DBY protein was found predominantly in spermatogonia, whereas DBX protein was expressed after meiosis in spermatids [8].

Anatomical context of DDX3Y

• The AZFa gene DBY (DDX3Y) is widely transcribed but the protein is limited to the male germ cells by translation control [8].
• Here we report that human Y- and X-encoded DEAD box RNA helicase proteins DDX3Y and DDX3X are interchangeable and have an essential function: both proteins rescued a temperature-sensitive mutant hamster cell line (tsET24) that was otherwise incapable of growth at a nonpermissive temperature [1].
• Our results suggest that T cells recognizing the HLA-DQ5/DDX3Y T cell epitope might be characterized by a relatively limited TCR-beta repertoire [2].
• Moreover, the T cell clone responded equally to mature HLA-DRB1*1501 male and female dendritic cells, indicating that both DBY and DBX peptides were endogenously processed [3].
• Expression analysis of AZFa genes and their X-homologues revealed ubiquitous expression for all of them except DBY; this gene produces a long transcript which is ubiquitously expressed in addition to a shorter transcript which is only expressed in the testis, suggesting a specific role for DBY in the spermatogenic process [4].

Associations of DDX3Y with chemical compounds

• As a control for the IsY clones, a second mutant receptor was expressed with a substitution of phenylalanine 1310 with tyrosine only (DBY clones) [9].

Other interactions of DDX3Y

• RESULTS: The expression of USP9Y, USP9X and DDX3Y was found in all the specimens tested, whereas DDX3Yt1 expression was diminished or undetectable in several biopsies with impaired spermatogenesis [7].
• By using denaturing HPLC, these two genes, as well as DBY and DFFRY, were screened for polymorphic sites in 53-72 representatives of the five continents [10].
• We have designed a duplex PCR combining an amplicon from MAOA marking the X chromosome and an amplicon from DDX3Y marking the Y chromosome [11].
• It contains three genes, USP9Y, DBY and UTY, but only the former two can be at present considered candidate genes for the infertile phenotype associated with deletion of this interval [12].

Analytical, diagnostic and therapeutic context of DDX3Y

• Quantitative PCR was performed in some biopsies to determine the ratio of the testis-specific transcript DDX3Yt1 to the total DDX3Y transcription [7].
• Using Western blot and enzyme-linked immunosorbent assay (ELISA), we found that 50% of male patients who received stem cell grafts from female donors developed antibody responses to recombinant DBY protein [13].

References