Sentrin-specific protease 3 (SENP3, MEROPS identifier C48.003) is an isopeptidase that releases SUMO2 and SUMO3 monomers from sumoylated substrates by hydrolysing the isopeptide bond []. SENP3 is a cysteine peptidase with a fold similar to that of adenain, and has the catalytic triad His, Asp, Cys, the reverse of the order in papain. Among the proteins that are deconjugated by SENP3 are MEF2D [], CDCA8 [], EP300 [], and nucleophosmin []. SENP3 is a component of the 5FMC []and MLL1/MLL complexes [].
CBP (CREB-binding protein) and p300 (also known as CREBBP or KAT3A and EP300 or KAT3B, respectively) are two histone acetyltransferases (HATs) that associate with and acetylate transcriptional regulators and chromatin. The catalytic core of animal CBP-p300 contains a bromodomain, a CH2 region containing a discontinuous PHD domain interrupted by this RING domain, and a HAT domain. Bromodomain-RING-PHD forms a compact module in which the RING domain is juxtaposed with the HAT substrate-binding site. This ring domain contains only a single zinc ion-binding cluster instead of two; instead of a second zinc atom, a network of hydrophobic interactions stabilizes the domain. The RING domain has an inhibitory role. Disease mutations that disrupt RING attachment lead to upregulation of HAT activity. HAT regulation may require repositioning of the RING domain to facilitate access to an otherwise partially occluded HAT active site. Plant CBP-p300 type HATs lack a bromodomain whose role in the animal animal CBP-p300's is to bind acetylated histones; it has been suggested that these plant proteins may utilize a different domain or another bromodomain protein to perform this function [].
CBP (CREB-binding protein) and p300 (also known as CREBBP or KAT3A and EP300 or KAT3B, respectively) are two histone acetyltransferases (HATs) that associate with and acetylate transcriptional regulators and chromatin. The catalytic core of animal CBP-p300 contains a bromodomain, a CH2 region containing a discontinuous PHD domain interrupted by this RING domain, and a HAT domain. Bromodomain-RING-PHD forms a compact module in which the RING domain is juxtaposed with the HAT substrate-binding site. This ring domain contains only a single zinc ion-binding cluster instead of two; instead of a second zinc atom, a network of hydrophobic interactions stabilizes the domain. The RING domain has an inhibitory role. Disease mutations that disrupt RING attachment lead to upregulation of HAT activity. HAT regulation may require repositioning of the RING domain to facilitate access to an otherwise partially occluded HAT active site. Plant CBP-p300 type HATs lack a bromodomain whose role in the animal animal CBP-p300's is to bind acetylated histones; it has been suggested that these plant proteins may utilize a different domain or another bromodomain protein to perform this function []. This RING domain has also been referred to as DUF902.
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) [].
