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7  structures 1384  species 0  interactions 8028  sequences 244  architectures

Family: PHD_2 (PF13831)

Summary: PHD-finger

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This is the Wikipedia entry entitled "PHD finger". More...

PHD finger Edit Wikipedia article

PHD-finger
PDB 1f62 EBI.jpg
PHD zinc finger. Zinc atoms shown in grey
Identifiers
SymbolPHD
PfamPF00628
Pfam clanCL0390
InterProIPR019787
PROSITEPS50016
SCOPe1f62 / SUPFAM
OPM superfamily59
OPM protein1vfy

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.[1] 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.

Structure

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.

Function

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.

References

  1. ^ Schindler U, Beckmann H, Cashmore AR (July 1993). "HAT3.1, a novel Arabidopsis homeodomain protein containing a conserved cysteine-rich region". The Plant Journal. 4 (1): 137–50. doi:10.1046/j.1365-313x.1993.04010137.x. PMID 8106082.

Further reading

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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 [2]. Several PHD fingers have been identified as binding modules of methylated histone H3 [3].

Literature references

  1. Aasland R, Gibson TJ, Stewart AF; , Trends Biochem Sci 1995;20:56-59.: The PHD finger: implications for chromatin-mediated transcriptional regulation. PUBMED:7701562 EPMC:7701562

  2. 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

  3. 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

External database links

This tab holds annotation information from the InterPro database.

No InterPro data for this Pfam family.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan zf-FYVE-PHD (CL0390), which has the following description:

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

Alignments

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...

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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.

  Seed
(22)
Full
(8028)
Representative proteomes UniProt
(13572)
RP15
(1019)
RP35
(3147)
RP55
(6555)
RP75
(9137)
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PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(22)
Full
(8028)
Representative proteomes UniProt
(13572)
RP15
(1019)
RP35
(3147)
RP55
(6555)
RP75
(9137)
Alignment:
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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.

  Seed
(22)
Full
(8028)
Representative proteomes UniProt
(13572)
RP15
(1019)
RP35
(3147)
RP55
(6555)
RP75
(9137)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

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...

Trees

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.

Curation View help on the curation process

Seed source: Jackhmmer:P55198
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Coggill P
Number in seed: 22
Number in full: 8028
Average length of the domain: 35.40 aa
Average identity of full alignment: 48 %
Average coverage of the sequence by the domain: 3.36 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 28.0 28.0
Trusted cut-off 28.0 28.0
Noise cut-off 27.9 27.9
Model length: 36
Family (HMM) version: 8
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Structures

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_2 domain has been found. There are 7 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.

Protein Predicted structure External Information
A0A0B4KGP1 View 3D Structure Click here
A0A0G2K5I7 View 3D Structure Click here
A0A0P0VQ70 View 3D Structure Click here
A0A0P0XQ57 View 3D Structure Click here
A0A0R0EQU1 View 3D Structure Click here
A0A0R0GL68 View 3D Structure Click here
A0A0R0KNZ6 View 3D Structure Click here
A0A0R0KNZ6 View 3D Structure Click here
A0A0R4IS80 View 3D Structure Click here
A0A1D6EV07 View 3D Structure Click here
A0A1D6FGS6 View 3D Structure Click here
A0A1D6G0P9 View 3D Structure Click here
A0A1D6HLC9 View 3D Structure Click here
A0A1D6I0U5 View 3D Structure Click here
A0A1D6LV13 View 3D Structure Click here
A0A1D6MFV1 View 3D Structure Click here
A0A1D6QDT4 View 3D Structure Click here
A0A1D8PME5 View 3D Structure Click here
A0A1P8APX1 View 3D Structure Click here
A0A1P8APX1 View 3D Structure Click here
A0A368UGE2 View 3D Structure Click here
B1AR10 View 3D Structure Click here
B2KF05 View 3D Structure Click here
B2RRD7 View 3D Structure Click here
D3ZM64 View 3D Structure Click here
D3ZMD3 View 3D Structure Click here
D3ZUW8 View 3D Structure Click here
D4A411 View 3D Structure Click here
E7F8E2 View 3D Structure Click here
F1LS62 View 3D Structure Click here
F1M6J5 View 3D Structure Click here
F1QFR1 View 3D Structure Click here
F1QNG0 View 3D Structure Click here
F1QPD2 View 3D Structure Click here
F1R0J6 View 3D Structure Click here
F6P390 View 3D Structure Click here
F8W451 View 3D Structure Click here
G3V9F5 View 3D Structure Click here
G5E8P1 View 3D Structure Click here
H9GXF8 View 3D Structure Click here
I1JYS9 View 3D Structure Click here
I1KA40 View 3D Structure Click here
I1KA40 View 3D Structure Click here
I1KAR4 View 3D Structure Click here
I1KHV6 View 3D Structure Click here
I1KWS1 View 3D Structure Click here
I3ITH4 View 3D Structure Click here
K7KGC4 View 3D Structure Click here
K7MEU6 View 3D Structure Click here
K7MN78 View 3D Structure Click here
K7MV89 View 3D Structure Click here
M0RB75 View 3D Structure Click here
O54826 View 3D Structure Click here
O75164 View 3D Structure Click here
O94953 View 3D Structure Click here
O95696 View 3D Structure Click here
P0CB22 View 3D Structure Click here
P34447 View 3D Structure Click here
P55197 View 3D Structure Click here
P55201 View 3D Structure Click here
Q1LUQ0 View 3D Structure Click here
Q20318 View 3D Structure Click here
Q54QM3 View 3D Structure Click here
Q5ANJ1 View 3D Structure Click here
Q5BJ10 View 3D Structure Click here
Q5NAU4 View 3D Structure Click here
Q6IE81 View 3D Structure Click here
Q6IE82 View 3D Structure Click here
Q6K431 View 3D Structure Click here
Q6ZPI0 View 3D Structure Click here
Q6ZQF7 View 3D Structure Click here
Q7JVP4 View 3D Structure Click here
Q7SXB5 View 3D Structure Click here
Q7ZVP1 View 3D Structure Click here
Q803A0 View 3D Structure Click here
Q8BW72 View 3D Structure Click here
Q8GZ42 View 3D Structure Click here
Q8VCD7 View 3D Structure Click here
Q91VY5 View 3D Structure Click here
Q9C5X4 View 3D Structure Click here
Q9GRZ5 View 3D Structure Click here
Q9H3R0 View 3D Structure Click here
Q9M364 View 3D Structure Click here
Q9N3F6 View 3D Structure Click here
Q9NQC1 View 3D Structure Click here
Q9SUE7 View 3D Structure Click here
Q9ULD4 View 3D Structure Click here