PROSITE documentation PDOC50016

Zinc finger PHD-type signature and profile

The Plant Homeodomain (PHD) type zinc finger (C4HC3) [1] is found in nuclear proteins thought to be involved in chromatin-mediated transcriptional regulation. The PHD finger motif is reminiscent of, but distinct from the C3HC4-type RING finger. A general function of the PHD finger is not yet known, but in the CREB-binding protein (CBP) it is an integral part of the enzymatic core of the acetyltransferase domain and is also a key contributor to the transcriptional activity of CBP.

The 3D structure of Williams-Beuren Syndrome transcription factor (see <PDB:1F62>) reveals that the PHD finger coordinates two atoms of zinc in a cross-braced manner [2]. This atypical conformation is also shared by the FYVE (see <PDOC50178> and RING fingers (see <PDOC00449>). The two zinc sites are located at opposite ends of a short β-sheet. This feature is also shared by the RING finger and the FYVE domain, but the structure differ in the surrounding loops that vary significantly in length and sequence and could explain the wide variety of functions between these three domains.

Single or multiple PHD fingers are found in the following proteins:

• Drosophila trithorax protein and the homologous mammalian protein HRX (also known as ALL1, MLL and Htrx). The trithorax gene is required for proper regulation of the homeotic genes in flies [3]. The HRX gene is involved in translocations in acute lymphoblastic leukemia. Trithorax has 4 PHD fingers. The most C-terminal one in HRX is degenerated.
• Drosophila Polycomblike, a protein encoded by a Polycomb-group gene. Polycomblike and the Polycomb-group genes are required for correct regulation of the homeotic genes in flies. These genes counteract the effects of the trithorax-group genes presumably by creating an inactive chromatin structure [4]. Polycomblike has 2 PHD fingers.
• Human Xe169 and murine Smcx, proteins encoded by X-linked genes that escape X-chromosome inactivation. Murine Smcy is a related gene on the Y chromo- some. Xe169 has 2 PHD fingers.
• Human RBP2, a Xe169-related protein thought to bind to the Rb protein.
• Human Br140 (also known as peregrin), a protein which also has a bromodomain.
• Medicago sativa Alfin-1, a presumptive transcription factor.
• A group of plant homeobox-containg proteins such as Arabidopsis HAT3 and PRHA, maize ZMHOX1a, parsley PRHP.
• Human Mi-2 autoantigen.
• Drosophila shuttle craft protein.
• Human BS69, a protein that binds adenovirus E1A.
• Murine CBP (CREB-binding protein), the closely related human E1A binding protein p300, and YNJ1, a related protein from C.elegans
• Mammalian zinc-finger protein of the 'requiem' family.
• Human TIF1, a putative transcriptional mediator for nuclear receptors.

The consensus pattern we developed start at the first cysteine and end at the last one, whereas the profile we developed spans the complete domain.