disease:Defects in SRY are a cause of gonadal dysgenesis XY female type (GDXY) [MIM:306100]; also known as 'XY females' or Swyer syndrome. Patients are found to have a 46 ,XY karyotype. They suffer rapid and early degeneration of their gonads , which are present in the adult as 'streak gonads' , consisting mainly of fibrous tissue and variable amounts of ovarian stroma. As a result these patients do not develop secondary sexual characteristics at puberty. The external genitalia in these subjects are completely female , and Muellerian structures are normal. In contrast , subjects with 46 ,XY partial gonadal dysgenesis have ambiguous genitalia , a mix of Muellerian and Wolffian structures , and dysgenic gonads. ,disease:Defects in SRY are a cause of true hermaphroditism [MIM:235600]. A true hermaphrodite must have both mature ovarian and mature testicular tissue with histologic evidence of follicles and tubules , respectively. It is a genetically heterogeneous condition. The genotype of most affected individuals is 46 ,XX , but many have 46 ,XY or a mosaic of 46 ,XX/46 ,XY. True hermaphroditism can be caused also by chromosomal translocation. ,disease:Defects in SRY are found in Turner syndrome , a disease characterized by gonadal dysgenesis with short stature , "streak gonads" , variable abnormalities such as webbing of the neck , cubitus valgus , cardiac defects , low posterior hair line. The phenotype is female. Turner syndrome has its basis in a 45 ,X chromosomal aberration. ,function:Transcriptional regulator which control a genetic switch in male 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 (By similarity) . In male adult brain involved in the maintenance of motor functions of dopaminergic neurons (By similarity) . Involved in different aspects of gene regulation including promoter activation or repression (By similarity) . Facilitates DNA bending. SRY HMG box recognizes DNA by partial intercalation in the minor groove. Also involved in pre-mRNA splicing. Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3'. ,miscellaneous:DNA binding and bending properties of the HMG domains of human and mouse SRY differ form each other. Human SRY shows more extensive minor groove contacts with DNA and a lower specificity of sequence recognition than mouse SRY. ,online information:SRY entry ,online information:The tenuous nature of sex - Issue 80 of March 2007 ,PTM:Phosphorylated on serine residues by PKA. Phosphorylation by PKA enhances its DNA-binding activity and stimulates transcription repression. Acetylation of Lys-136 contributes to its nuclear localization and enhances its interaction with KPNB1. Deacetylated by HDAC3. Poly-ADP-ribosylated by PARP1. ADP-ribosylation reduces its DNA-binding activity. ,similarity:Belongs to the SRY family. ,similarity:Contains 1 HMG box DNA-binding domain. ,subcellular location:Colocalizes with SOX6 in speckles. Colocalizes with CAML in the nucleus. Colocalizes in the nucleus with ZNF208 isoform KRAB-O and tyrosine hydroxylase (TH) . ,subunit:Interacts with CALM , EP300 , HDAC3 , KPNB1 , ZNF208 isoform KRAB-O , PARP1 , SLC9A3R2 and WT1. The interaction with EP300 modulates its DNA-binding activity. The interaction with KPNB1 is sensitive to dissociation by Ran in the GTP-bound form (By similarity) . Interaction with PARP1 impaired its DNA-binding activity. ,
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