sex-determining region Y protein; testis-determining factor (SRY, TDF)

Function

• transcriptional regulator which controls a genetic switch in male development
• necessary & sufficient for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells (putative)
• in male adult brain, role in maintenance of motor functions of dopaminergic neurons
• role in different aspects of gene regulation including promoter activation or repression (putative)
• 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' interacts with CALM, EP300, HDAC3, KPNB1, ZNF208 isoform KRAB-O, PARP1, SLC9A3R2 & WT1
• interaction with EP300 modulates its DNA-binding activity
• interaction with KPNB1 is sensitive to dissociation by Ran in the GTP-bound form
• interaction with PARP1 impairs its DNA-binding activity (putative)
• phosphorylated on Ser by PKA; phosphorylation by PKA enhances its DNA-binding activity & stimulates transcription repression
• acetylation of Lys-136 contributes to its nuclear localization & enhances its interaction with KPNB1
• deacetylated by HDAC3
• poly-ADP-ribosylated by PARP1; ADP-ribosylation reduces its DNA-binding activity

Structure

• belongs to the SRY family
• contains 1 HMG box DNA-binding domain

Compartment

• nuclear speckle, cytoplasm
• colocalizes with SOX6 in nuclear speckles
• colocalizes with CAML in the nucleus
• colocalizes in the nucleus with ZNF208 isoform KRAB-O & tyrosine hydroxylase (putative)

Pathology

• defects in SRY are a cause of gonadal dysgenesis XY female type
• defects in SRY are found in Turner syndrome
• defects in SRY are a cause of true hermaphroditism

Comparative biology

• DNA binding & bending properties of the HMG domains of human & mouse SRY differ form each other
• human SRY shows more extensive minor groove contacts with DNA & a lower specificity of sequence recognition than mouse SRY

More general terms

• DNA-binding protein
• transcription factor (TF)

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:6736
• OMIM: https://mirror.omim.org/entry/480000
• UniProt: http://www.uniprot.org/uniprot/Q05066.html