TXK is a member of the Tec family, which is a group of nonreceptor tyrosine kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal cysteine-rich region. TXK forms a complex with EF-1alpha and PARP1 that regulates interferon-gamma gene transcription in Th1 cells []. This entry represents the SH3 domain of TXK.
Proteins in this family contain a CPL domain, which is a C-terminal domain found in Penguin-like proteins, and Pumilio RNA-binding repeats. Proteins include the following:Pumilio homologue 3 (PUM3; also known as Puf-A), which inhibits the poly(ADP-ribosyl)ation activity of PARP1 and the degradation of PARP1 by CASP3 following genotoxic stress []. Tertiary structure determination has revealed that PUM3 has eleven PUM repeats arranged in an L-shape, and in contrast to classical PUF proteins, PUM3 forms sequence-independent interactions with DNA or RNA, mediated by conserved basic residues [].Pumilio homology domain family member 6 from Saccharomyces cerevisiae and Schizosaccharomyces pombe, which is an RNA-binding protein involved in post-transcriptional regulation and represses ASH1 mRNA translation. ASH1 is a a protein determinant for mating-type switching [].Protein penguin from Drosophila melanogaster.
This entry represents the testis-determining factor Sry (Sex-determining Region Y). Sry is a transcriptional activator that regulates a genetic switch inmale development. It is necessary and sufficient for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells []. Sry is involved in different aspects of gene regulation including promoter activation or repression and contains a high-mobility-group (HMG) box that recognises DNA by partial intercalation in the minor groove []. It binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3'. Sry also facilitates DNA bending and is involved in pre-mRNA splicing. It is also involved in maintenance of motor functions of dopaminergic neurons in the male adult brain. Sry interacts with a number of partners, including CALM, EP300 (modulates Sry DNA-binding activity), HDAC3, KPNB1, ZNF208 isoform KRAB-O, PARP1 (impaired Sry DNA-binding activity), SLC9A3R2 and WT1. The C-terminal nuclear localization signal in Sry HMG-box domain mediates nuclear import through importin beta 1 [].Defects in Sry can cause gonadal dysgenesis XY female type (GDXY) (OMIM:306100), which is also known as 'XY females' or Swyer syndrome []. Patients suffer rapid and early degeneration of their gonads, which prevents the development secondary sexual characteristics at puberty. Defects in Sry are also found Turner's Syndrome, a disease characterised by gonadal dysgenesis in a 45,X female type []. Defects in Sry can also cause true hermaphroditism (OMIM:235600), genetically heterogeneous condition whre patients have both mature ovarian and mature testicular tissue (46,XX, 46,XY or a mosaic of 46,XX/46,XY) [].
