JADE1 is a protein that in humans is encoded by the JADE1 gene.
Family A small family of proteins named Gene for Apoptosis and Differentiation (JADE) includes three members encoded by individual genes: Plant Homeo-domain-17 (PHF17, JADE1), PHF16 (JADE3), and PHF15 (JADE2). All JADE family proteins bear two notable mid molecule domains: the canonical Plant Homeo-domain (PHD) zinc finger and extended PHD-like zinc finger. JADE1 therefore is classified as a member of the PHD protein family. There are two known protein products of the PHF17 gene, the full length JADE1 (JADE1L) and its splice variant missing the C-terminal fragment also called short isoform (JADE1S).
Discovery Nagase et al. cloned and sequenced 100 individual cDNAs from fetal brain cDNA library, including clone KIAA1807 which was designated PHF17. The predicted 702-amino acid protein product of that clone was similar to the human zinc finger protein BR140 (BRPF1). Based on sequence database analysis the study suggested that PHF17 may function in nucleic acid managing pathway. Using yeast two hybrid pull down approach to search for new partners of protein product of the Von Hippel Lindau gene (pVHL) another study identified cDNA which matched to KIAA1807 clone. The protein product of that cDNA was given name JADE1 (Jade-1, PHF17). The deduced 509 amino acid long protein product of JADE1 cDNA was further confirmed as physical partner of pVHL. In a genetic screen study searching for genes involved in embryogenesis, the mouse orthologue of JADE1 was identified. That study, provided first characterization of the JADE1 gene and defined novel JADE family. The study yielded mice with knock out of JADE1 gene. Jade1 transcripts in both humans and mice undergo alternative splicing and polyadenylation producing two major transcripts, the full length 6 kb mRNA and 3.6 kb mRNA. Two resultant protein products of the JADE1 gene were designated JADE1S for the short (which is same as(3)) and JADE1L for the long isoform. Several minor transcripts are also detected. The database analysis revealed two additional JADE1 paralogues and members of JADE family, JADE2, and JADE3. JADE3 is identical to E9 protein identified in an earlier independent study which suggested role in apoptosis for PHF16/JADE3/E9 in breast cancer cells. JADE1 has been mapped to chromosome 4 (4q26-q27). JADE1 is conserved and its orthologues have been found or predicted in most every metazoan. Gene structure and sequences, variants, conservation, orthologues and paralogs, JADE1 phylogenetic tree and large scale screening of JADE1 tissue expression can be found in several extensive databases (https://www.genecards.org; http://useast.ensembl.org).
Structure The full length JADE1 polypeptide bears one canonical and one extended PHD zinc finger domain. Other domains include the N-terminal candidate PEST domain, enhancer of polycomb-like domain and the C-terminal nuclear localization (NLS) signal (prosite.expasy.org). JADE1 protein is a target for post translational modifications, including phosphorylation (Fig 1 Six amino acid residues were identified to be phosphorylated in cell cycle-dependent manner via Aurora A kinase pathway. JADE1 is a target of phosphorylation by Casein kinase 2 (CK2). In addition, multiple phosphorylation sites are found by high throughput screening approaches and in silico analysis. Summary schematic for JADE1L and JADE1S protein phosphorylation sites with references is found in. Proteins bearing tandem canonical and extended PHD fingers form a small subfamily within the large PHD protein family (www.genenames.org). Other proteins bearing tandem of PHD fingers and related to JADE1 include proteins that are components of chromatin binding and modifying complexes BRPF1, BRPF3 and BRD1. The crystal structure of JADE1 PHD domains has not been solved. Canonical PHD finger motif has signature C4HC3, represents relatively small, stable structure, and is distinct from the C3HC4 type RING finger. PHD domains are able to recognize and bind specific methylated lysine of histone H3, which defines these domains as epigenetic histone code readers. Reviews describing structure and properties of PHD fingers in depth are available.
Cellular function JADE1 proteins are multifunctional and interact with several protein partners.
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