By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2001) cloned PHF17, which they designated KIAA1807. The deduced 702-amino acid protein shares significant similarity with the human zinc finger protein BR140 (BRPF1; 602410). RT-PCR ELISA detected very high expression in whole adult brain and intermediate expression in all other tissues examined, including all specific brain regions tested.

Using VHL (608537) as bait in a yeast 2-hybrid screen of an adult human kidney cDNA library, Zhou et al. (2002) cloned PHF17, which they called JADE1. The deduced 509-amino acid protein has a calculated molecular mass of 58.4 kD. It has a PEST domain near its N-terminal end, 2 central plant homeodomains (PHDs), and candidate sites for N-glycosylation, myristoylation, and serine or threonine phosphorylation. Northern blot analysis detected transcripts of 6.0 and 3.6 kb with high expression in kidney, followed by moderate expression in pancreas and skeletal muscle, and low expression in all other examined tissues. Western blot analysis detected human and mouse Jade1 at 64 and 61 kD, respectively, with high expression in mouse and human kidney, moderate expression in human pancreas, liver, and heart and in mouse liver, and no expression in human brain. Western blot analysis of mouse kidney cortex and cultured cells revealed prominent expression in proximal tubule cells. Endogenous JADE1 localized to prominent nuclear speckles and diffuse cytoplasmic speckles in human renal cancer cells.

By database and genomic sequence analyses, Tzouanacou et al. (2003) identified several splice variants of mouse and human JADE1 that encode at least 2 protein isoforms, JADE1L and JADE1S. JADE1L likely corresponds to the 6.0-kb transcript reported by Zhou et al. (2002). The deduced 842-amino acid JADE1L protein has an N-terminal PEST motif, followed by 2 PHD zinc finger domains, a bipartite nuclear localization signal, and a C-terminal PEST motif. JADE1S corresponds to the JADE1 transcript cloned by Zhou et al. (2002). The deduced 510-amino acid JADE1S protein lacks the nuclear localization signal and C-terminal PEST motif of JADE1L. Jade1 was expressed in mouse primitive streak and tail bud and in other embryonic regions containing pluripotent or tissue-specific progenitor cells including early gastrulation epiblast and the ventricular zone of the cerebral cortex. Jade1 was also expressed in developing musculature and extraembryonic tissues.

By yeast 2-hybrid and immunoprecipitation analysis of endogenous and cotransfected proteins, Zhou et al. (2002) showed that VHL bound avidly and selectively to JADE1. Analysis of the binding between truncated proteins showed that the N terminus and the inter-PHD region of JADE1 were important for interaction with VHL. VHL increased the abundance of JADE1, primarily by prolonging JADE1 protein half-life.

Using reporter gene constructs, Panchenko et al. (2004) showed that JADE1 could activate transcription and that deletion of the PHD zinc fingers abolished transcriptional activity. JADE1 also promoted histone H4 (see 602822), but not histone H3 (see 602810) acetylation in a dose-dependent manner, and acetylation required the PHDs. A JADE1 mutant lacking the second PHD behaved in a dominant-negative manner. TIP60 (HTATIP; 601409), a histone acetyltransferase with histone H4/H2A specificity, physically associated with JADE1 and augmented JADE1 acetyltransferase function.

Zhou et al. (2005) found that expression of JADE1 was very low in all human renal carcinoma cell lines tested and was independent of VHL expression. Inhibition of proteasome activity increased JADE1 protein expression. JADE1 inhibited renal cancer cell growth, colony formation, and tumor formation in nude mice, and reduced the branching of renal cell growth in 3-dimensional cultures. JADE1 increased apoptosis and decreased levels of antiapoptotic BCL2 (151430), and antisense JADE1 increased cell growth rates. Zhou et al. (2005) concluded that JADE1 is a proapoptotic barrier to proliferation.

Tzouanacou et al. (2003) determined that the mouse Phf17 gene contains 13 exons, including 3 alternative noncoding first exons. They stated that the human PHF17 gene has a similar structure.

Stumpf (2024) mapped the JADE1 gene to chromosome 4q28.2 based on an alignment of the JADE1 sequence (GenBank AB058710) with the genomic sequence (GRCh38).

Tzouanacou et al. (2003) found that Jade1-null mouse embryos were viable and fertile and showed no obvious abnormalities compared to their wildtype or heterozygote littermates. However, Jade1-null animals were obtained at less than the expected mendelian ratio at weaning age.