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This is the Wikipedia entry entitled "PHD finger". More...
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PHD finger Edit Wikipedia article
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PHD zinc finger. Zinc atoms shown in grey
|SCOPe||1f62 / SUPFAM|
The PHD finger was discovered in 1993 as a Cys4-His-Cys3 motif in the plant homeodomain (hence PHD) proteins HAT3.1 in Arabidopsis thaliana and maize ZmHox1a. The PHD finger motif resembles the metal binding RING domain (Cys3-His-Cys4) and FYVE domain. It occurs as a single finger, but often in clusters of two or three, and it also occurs together with other domains, such as the chromodomain and the bromodomain.
Role in epigenetics
The PHD finger, approximately 50-80 amino acids in length, is found in more than 100 human proteins. Several of the proteins it occurs in are found in the nucleus, and are involved in chromatin-mediated gene regulation. The PHD finger occurs in proteins such as the transcriptional co-activators p300 and CBP, Polycomb-like protein (Pcl), Trithorax-group proteins like ASH1L, ASH2L and MLL, the autoimmune regulator (AIRE), Mi-2 complex (part of histone deacetylase complex), the co-repressor TIF1, the JARID1-family of demethylases and many more.
The NMR structure of the PHD finger from human WSTF (Williams Syndrome Transcription Factor) shows that the conserved cysteines and histidine coordinate two Zn2+ ions. In general, the PHD finger adopts a globular fold, consisting of a two-stranded beta-sheet and an alpha-helix. The region consisting of these secondary structures and the residues involved in coordinating the zinc-ions are very conserved among species. The loop regions I and II are variable and could contribute functional specificity to the different PHD fingers.
Recently the PHD fingers of some proteins, including ING2, YNG1 and NURF, have been reported to bind to histone H3 tri-methylated on lysine 4 (H3K4me3), while other PHD fingers have tested negative in such assays. A protein called SMCX (or JARID1C) has a PHD finger, which has been reported to bind histone H3 tri-methylated lysine 9 (H3K9me3). Based on these recent publications, binding to tri-methylated lysines on histones may therefore be a property widespread among PHD fingers. Domains that bind to modified histones, are called epigenetic readers as they specifically recognize the modified version of the residue and binds to it. The modification H3K4me3 is associated with the transcription start site of active genes, while H3K9me3 is associated with inactive genes. The modifications of the histone lysines are dynamic, as there are methylases that add methyl groups to the lysines, and there are demethylases that remove methyl groups. The SMCX protein is actually a histone H3 lysine 4 demethylase, which means it is an enzyme that can remove the methyl groups of lysine 4 on histone 3 (making it H3K4me2 or H3K4me1). One can only speculate if the H3K9me3-binding of SMCX PHD domain provides a crosstalk between trimethylation of H3K9 and the demethylation of H3K4me3. Such crosstalks have been suggested earlier with other domains involved in chromatin regulation, and may provide a strictly coordinated regulation.
Another example is the PHD finger of the BHC80/PHF21A protein, which is a component of the LSD1 complex. In this complex, LSD1 specifically demethylates H3K4me2 to H3K4me0, and BHC80 binds H3K4me0 through its PHD finger to stabilize the complex at its target promoters, presumably to prevent further re-methylation. This is the first example of a PHD finger recognizing lysine methyl-zero status.
- Aasland R, Gibson TJ, Stewart AF (February 1995). "The PHD finger: implications for chromatin-mediated transcriptional regulation". Trends in Biochemical Sciences. 20 (2): 56â€“9. doi:10.1016/s0968-0004(00)88957-4. PMID 7701562.
- Pascual J, Martinez-Yamout M, Dyson HJ, Wright PE (December 2000). "Structure of the PHD zinc finger from human Williams-Beuren syndrome transcription factor". Journal of Molecular Biology. 304 (5): 723â€“9. doi:10.1006/jmbi.2000.4308. PMID 11124022.
- PeÃ±a PV, Davrazou F, Shi X, Walter KL, Verkhusha VV, Gozani O, Zhao R, Kutateladze TG (July 2006). "Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2". Nature. 442 (7098): 100â€“3. doi:10.1038/nature04814. PMC 3190580. PMID 16728977.
- Li H, Ilin S, Wang W, Duncan EM, Wysocka J, Allis CD, Patel DJ (July 2006). "Molecular basis for site-specific read-out of histone H3K4me3 by the BPTF PHD finger of NURF". Nature. 442 (7098): 91â€“5. doi:10.1038/nature04802. PMC 4690523. PMID 16728978.
- Iwase S, Lan F, Bayliss P, de la Torre-Ubieta L, Huarte M, Qi HH, Whetstine JR, Bonni A, Roberts TM, Shi Y (March 2007). "The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases". Cell. 128 (6): 1077â€“88. doi:10.1016/j.cell.2007.02.017. PMID 17320160.
- Lan F, Collins RE, De Cegli R, Alpatov R, Horton JR, Shi X, Gozani O, Cheng X, Shi Y (August 2007). "Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression". Nature. 448 (7154): 718â€“22. doi:10.1038/nature06034. PMC 2702779. PMID 17687328.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
PHD-finger Provide feedback
PHD folds into an interleaved type of Zn-finger chelating 2 Zn ions in a similar manner to that of the RING and FYVE domains . Several PHD fingers have been identified as binding modules of methylated histone H3 .
Pascual J, Martinez-Yamout M, Dyson HJ, Wright PE; , J Mol Biol 2000;304:723-729.: Structure of the PHD zinc finger from human williams-beuren syndrome transcription factor PUBMED:11124022 EPMC:11124022
Shi X, Kachirskaia I, Walter KL, Kuo JH, Lake A, Davrazou F, Chan SM, Martin DG, Fingerman IM, Briggs SD, Howe L, Utz PJ, Kutateladze TG, Lugovskoy AA, Bedford MT, Gozani O; , J Biol Chem. 2006; [Epub ahead of print]: Proteome-wide analysis in S. cerevisiae identifies several PHD fingers as novel direct and selective binding modules of histone H3 methylated at either lysine 4 or lysine 36. PUBMED:17142463 EPMC:17142463
Internal database links
|SCOOP:||BAH C1_1 C1_2 FANCL_C FYVE_2 PHD_2 PHD_4 Prok-RING_1 SET SNF2-rel_dom zf-C3HC4 zf-C3HC4_2 zf-HC5HC2H zf-HC5HC2H_2 zf-PHD-like zf-rbx1 zf-RING_11 zf-RING_2 zf-RING_5 zf-RING_UBOX Zf_RING|
|Similarity to PfamA using HHSearch:||PHD_2 Prok-RING_1 zf-PHD-like Zf_RING PHD_4|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR019787
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [ PUBMED:10529348 , PUBMED:15963892 , PUBMED:15718139 , PUBMED:17210253 , PUBMED:12665246 ]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few [ PUBMED:11179890 ]. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
This entry represents the PHD (homeodomain) zinc finger domain [ PUBMED:7701562 ], which is a C4HC3 zinc-finger-like motif 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.
The function of this domain is not yet known but in analogy with the LIM domain it could be involved in protein-protein interaction and be important for the assembly or activity of multicomponent complexes involved in transcriptional activation or repression. Alternatively, the interactions could be intra-molecular and be important in maintaining the structural integrity of the protein. In similarity to the RING finger and the LIM domain, the PHD finger is thought to bind two zinc ions.
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
Superfamily contains a number of zinc-fingers, of the FYVE/PHD type, which are found in several groups of proteins including myelin-associated oligodendrocytic basic proteins (MOBP) Rabphilins, melanophilins, exophilins and myosin-VIIA and Rab-interacting protein families.
The clan contains the following 13 members:ADD_ATRX ADD_DNMT3 FYVE FYVE_2 PHD PHD_2 PHD_4 PHD_Oberon RAG2_PHD zf-HC5HC2H zf-HC5HC2H_2 zf-PHD-like zf-piccolo
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
If you find these logos useful in your own work, please consider citing the following article:
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Author:||Pascual J , Bateman A|
|Number in seed:||71|
|Number in full:||51026|
|Average length of the domain:||50.00 aa|
|Average identity of full alignment:||30 %|
|Average coverage of the sequence by the domain:||5.61 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||31|
|Download:||download the raw HMM for this family|
Weight segments by...
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PHD domain has been found. There are 313 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.