This entry represents the zinc-ribbon domain found in RCHY1 and related proteins. RCHY1, also known as Pirh2, is a ubiquitin E3 ligase that mediates E3-dependent ubiquitination and proteasomal degradation of target proteins, including p53/TP53, P73, HDAC1 and CDKN1B [, ].
The TRPS1 gene encodes a multi zinc-finger nuclear regulator of chondrocyte proliferation and differentiation []. Mutations in the gene cause trichorhinophalangeal syndrome (TRPS), an autosomal dominant skeletal dysplasia []. The Trps1 protein also acts as regulator of histone deacetylation, interacting with two histone deacetylases, Hdac1 and Hdac4, thereby increasing their activity [].
MIER1, MIER2, MIER3 are ELM-SAINT domain-containing proteins that have been purified with HDAC1 and/or HDAC2, and most likely represent components of distinct histone deacetylase (HDAC) complexes formed around ELM-SANT scaffolds [, ].The gene encoding mesoderm induction early response protein 3 (MIER3) has been identified as a candidate cancer susceptibility gene [].
This leucine zipper-containing domain is found in apoptosis antagonizing transcription factor (AATF, also known as Che-1) and related proteins. AATF may function as a general inhibitor of the histone deacetylase HDAC1 []. AATF has been shown to inhibit the abberant production of the amyloid beta peptide 1-42 by direct interaction with Par4 []. This interaction occurs via the leucine zipper.
FKBP3, also known as FKBP25, contains the N-terminal basic tilted helix bundle (BTHB) domain and the C-terminal PPIase domain. It is a nuclear prolyl isomerase that interacts directlywith nucleic acids []. It interacts with the histone deacetylases HDAC1 and HDAC2 as well as with their transcriptional regulator Yin Yang 1 (YY1) []. It is also a microtubule-associated protein that shuttles between nucleus and cytoplasm and stabilizes the microtubule network by direct binding of the C-terminal PPIase domain []. It plays a role in the proliferation of non-small cell type lung cancer cells (NSCLC) by modulating Sp1/HDAC2/p27 [].
Members of the ING (inhibitor of growth protein) family of tumour suppressors regulate cell cycle progression, senescence, apoptosis, and DNA repair as important cofactors of p53. Inhibitorof growth protein 2 (ING2) seems to be involved in p53/TP53 activation and p53/TP53-dependent apoptotic pathways, probably by enhancing acetylation of p53/TP53 []. It is also a component of a chromatin-modifying complex containing the transcriptional co-repressor SIN3A and HDAC1 (histone deacetylase 1), which is involved in deacetylation of nucleosomal histones [, ]. The stability of ING2 is regulated by nuclear phosphatidylinositol-5-phosphate at discrete chromatin targets in response to DNA damage [, ].
In mammals, SAP25 is involved in the transcriptional repression mediated by the mSIN3 complex, which consists of at least SAP30, SAP45/Sds3, SAP130, SAP180/BCAA, RBP1, HDAC1 (histone deacetylase1), HDAC2, RbAp46, and RbAp48 []. The mSIN3 complex can be recruited by sequence-specific DNA binding transcription factors and chromatin-binding proteins to specific regions of the genome and regulate their transcription []. SAP25 binds to the the PAH1 domain of mSin3A and changes the conformation of the complex that affects its protein-protein interaction []. SAP25 can be actively exported from the nucleus to cytoplasm by a CRM1-dependent nuclear export pathway. Its localisation is regulated by promyelocytic leukemia protein (PML), which induces a nuclear accumulation of SAP25 [].
This entry represents the PHD domain of ING2.Members of the ING (inhibitor of growth protein) family of tumour suppressors regulate cell cycle progression, senescence, apoptosis, and DNA repair as important cofactors of p53. Inhibitor of growth protein 2 (ING2) seems to be involved in p53/TP53 activation and p53/TP53-dependent apoptotic pathways, probably by enhancing acetylation of p53/TP53 []. It is also a component of a chromatin-modifying complex containing the transcriptional co-repressor SIN3A and HDAC1 (histone deacetylase 1), which is involved in deacetylation of nucleosomal histones [, ]. The stability of ING2 is regulated by nuclear phosphatidylinositol-5-phosphate at discrete chromatin targets in response to DNA damage [, ].
SAMSN1 (also known as HACS1 or NASH1) is a member of the SH3/SAM adapter molecules family. It is strongly up-regulated in primary B cells upon differentiation and proliferation-inducing stimuli and functions as an endogenous immunoinhibitor. It has been found to regulate cell spreading and polarization []. 14-3-3 proteins interact and control nucleo-cytoplasmic shuttling of SAMSN1. In the nucleus, SAMSN1 interacts with the SAP30/HDAC1 complex and regulates the activity of HDAC1 [].This entry represents the SAM domain of SAMSN1. The SAM domain is a predicted protein-protein interaction domain.
Teashirt 3 is a transcriptional regulator involved in developmental processes []. It has function in association with APBB1, SET and HDAC factors as a transcriptional repressor, that inhibits the expression of CASP4. TSHZ3-mediated transcription repression involves the recruitment of histone deacetylases HDAC1 and HDAC2. It associates with chromatin in a region surrounding the CASP4 transcriptional start site(s). It regulates the development of neurons involved in both respiratory rhythm and airflow control []. It promotes maintenance of nucleus ambiguus (nA) motoneurons, which govern upper airway function, and establishes a respiratory rhythm generator (RRG) activity compatible with survival at birth. It is involved in the differentiation of the proximal uretic smooth muscle cells during developmental processes []. It is involved in the up-regulation of myocardin, that directs the expression of smooth muscle cells in the proximal ureter [].
This entry represents the PR/SET domain found in PR domain zinc finger protein 5 (PRDM5). PRDM5 is a sequence-specific DNA-binding transcription factor that represses transcription at least in part by recruitment of the histone methyltransferase EHMT2/G9A and histone deacetylases such as HDAC1 []. Mutation of the PRDM5 gene has been linked to Brittle cornea syndrome 2 (BCS2) [].The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains []. They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes [].
