The domain within your query sequence starts at position 329 and ends at position 375; the E-value for the PHD domain shown below is 8.9e-11.

CCNLCGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLCL

PHD

PHD zinc finger

• SMART accession number: SM00249
• Description: The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.
• Interpro abstract (IPR001965):

  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.

There are 144042 PHD domains in 86307 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: transcription

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Ragvin A et al.
• Nucleosome binding by the bromodomain and PHD finger of the transcriptional cofactor p300.
• J Mol Biol. 2004; 337: 773-88

The PHD finger and the bromodomain are small protein domains that occur in many proteins associated with phenomena related to chromatin. The bromodomain has been shown to bind acetylated lysine residues on histone tails. Lysine acetylation is one of several histone modifications that have been proposed to form the basis for a mechanism for recording epigenetically stable marks in chromatin, known as the histone code. The bromodomain is therefore thought to read a part of the histone code. Since PHD fingers often occur in proteins next to bromodomains, we have tested the hypothesis that the PHD finger can also interact with nucleosomes. Using two different in vitro assays, we found that the bromodomain/PHD finger region of the transcriptional cofactor p300 can bind to nucleosomes that have a high degree of histone acetylation. In a nucleosome retention assay, both domains were required for binding. Replacement of the p300 PHD finger with other PHD fingers resulted in loss of nucleosome binding. In an electrophoretic mobility shift assay, each domain alone showed, however, nucleosome-binding activity. The binding of the isolated PHD finger to nucleosomes was independent of the histone acetylation levels. Our data are consistent with a model where the two domains cooperate in nucleosome binding. In this model, both the bromodomain and the PHD finger contact the nucleosome while simultaneously interacting with each other.

• Townsley FM, Thompson B, Bienz M
• Pygopus residues required for its binding to Legless are critical for transcription and development.
• J Biol Chem. 2004; 279: 5177-83

Pygopus and Legless/Bcl-9 are recently discovered core components of the Wnt signaling pathway that are required for the transcriptional activity of Armadillo/beta-catenin and T cell factors. It has been proposed that they are part of a tri-partite adaptor chain (Armadillo>Legless>Pygopus) that recruits transcriptional co-activator complexes to DNA-bound T cell factor. Here, we identify four conserved residues at the putative PHD domain surface of Drosophila and mouse Pygopus that are required for their binding to Legless in vitro and in vivo. The same residues are also critical for the transactivation potential of DNA-tethered Pygopus in transfected mammalian cells and for rescue activity of pygopus mutant embryos. These residues at the Legless>Pygopus interface thus define a specific molecular target for blocking Wnt signaling during development and cancer.

• Aravind L, Iyer LM, Koonin EV
• Scores of RINGS but no PHDs in ubiquitin signaling.
• Cell Cycle. 2003; 2: 123-6

Recently, it has been reported that PHD fingers of MEKK1 kinase and a family of viral and cellular membrane proteins have E3 ubiquitin ligase activity. Here we describe unique sequence and structural signatures that distinguish PHD fingers from RING fingers, which function primarily as E3 ubiquitin ligases, and demonstrate that the Zn-binding modules of the above proteins are distinct versions of the RING domain rather than PHD fingers. Thus, currently available data reveal extreme versatility of RINGs and their derivatives that function as E3 ubiquitin ligases but provide no evidence of this activity among PHD fingers whose principal function appears to involve specific protein-protein and possibly protein-DNA interactions in chromatin.

• Fair K, Anderson M, Bulanova E, Mi H, Tropschug M, Diaz MO
• Protein interactions of the MLL PHD fingers modulate MLL target gene regulation in human cells.
• Mol Cell Biol. 2001; 21: 3589-97

The PHD fingers of the human MLL and Drosophila trx proteins have strong amino acid sequence conservation but their function is unknown. We have determined that these fingers mediate homodimerization and binding of MLL to Cyp33, a nuclear cyclophilin. These two proteins interact in vitro and in vivo in mammalian cells and colocalize at specific nuclear subdomains. Overexpression of the Cyp33 protein in leukemia cells results in altered expression of HOX genes that are targets for regulation by MLL. These alterations are suppressed by cyclosporine and are not observed in cell lines that express a mutant MLL protein without PHD fingers. These results suggest that binding of Cyp33 to MLL modulates its effects on the expression of target genes.

• Schultz DC, Friedman JR, Rauscher FJ 3rd
• Targeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD and bromodomains of KAP-1 form a cooperative unit that recruits a novel isoform of the Mi-2alpha subunit of NuRD.
• Genes Dev. 2001; 15: 428-43

Macromolecular complexes containing histone deacetylase and ATPase activities regulate chromatin dynamics and are vitally responsible for transcriptional gene silencing in eukaryotes. The mechanisms that target these assemblies to specific loci are not as well understood. We show that the corepressor KAP-1, via its PHD (plant homeodomain) and bromodomain, links the superfamily of Kruppel associated box (KRAB) zinc finger proteins (ZFP) to the NuRD complex. We demonstrate that the tandem PHD finger and bromodomain of KAP-1, an arrangement often found in cofactor proteins but functionally ill-defined, form a cooperative unit that is required for transcriptional repression. Substitution of highly related PHD fingers or bromodomains failed to restore repression activity, suggesting high specificity in their cooperative function. Moreover, single amino acid substitutions in either the bromodomain or PHD finger, including ones that mimic disease-causing mutations in the hATRX PHD finger, abolish repression. A search for effectors of this repression function yielded a novel isoform of the Mi-2alpha protein, an integral component of the NuRD complex. Endogenous KAP-1 is associated with Mi-2alpha and other components of NuRD, and KAP-1-mediated silencing requires association with NuRD and HDAC activity. These data suggest the KRAB-ZFP superfamily of repressors functions to target the histone deacetylase and chromatin remodeling activities of the NuRD complex to specific gene promoters in vivo.

• Aasland R, Gibson TJ, Stewart AF
• The PHD finger: implications for chromatin-mediated transcriptional regulation.
• Trends Biochem Sci. 1995; 20: 56-9

• Schindler U, Beckmann H, Cashmore AR
• HAT3.1, a novel Arabidopsis homeodomain protein containing a conserved cysteine-rich region.
• Plant J. 1993; 4: 137-50

Homeodomain proteins have been shown to play a major role in the development of various organisms. A novel Arabidopsis homeodomain protein has been isolated based on its capability to interact with a DNA motif derived from the light-induced cab-E promoter of Nicotiana plumbaginifolia. The homeodomain of this protein, designated HAT3.1, differs substantially from those in other plant homeobox proteins identified so far. Furthermore, HAT3.1 is unique among other Arabidopsis proteins in that it does not contain a leucine zipper motif following the homeodomain. HAT3.1 is further characterized by an N-terminal region that shares substantial sequence similarity with the maize homeodomain protein Zmhox1a. Within this conserved region, the presence of eight regularly spaced cysteine/histidine residues was observed reminiscent of other metal-binding domains. Based on the strong evolutionary conservation of this domain, it is proposed that this region represents a novel protein-motif which is denoted PHD-finger (plant homeodomain-finger). In vitro DNA binding studies demonstrated that HAT3.1 is capable of interacting with any DNA fragment larger than 100 bp. Interestingly, a deletion of the N-terminal PHD-finger domain completely abolished DNA binding, suggesting that this region may play an important functional role in protein-protein or protein-DNA interaction. HAT3.1 mRNA was primarily detected in root tissue, implying a regulatory function of this protein in root development.

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
22.22	map00380	Tryptophan metabolism
22.22	map04530	Tight junction
11.11	map00310	Lysine degradation
11.11	map00230	Purine metabolism
7.41	map04110	Cell cycle
7.41	map04111	Cell cycle - yeast
3.70	map03020	RNA polymerase
3.70	map00564	Glycerophospholipid metabolism
3.70	map00190	Oxidative phosphorylation
3.70	map04070	Phosphatidylinositol signaling system
3.70	map00561	Glycerolipid metabolism

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with PHD domain which could be assigned to a KEGG orthologous group, and not all proteins containing PHD domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of PHD domains in PDB

PDB code	Title
1f62	WSTF-PHD
1fp0	SOLUTION STRUCTURE OF THE PHD DOMAIN FROM THE KAP-1 COREPRESSOR
1mm2	Solution structure of the 2nd PHD domain from Mi2b
1mm3	Solution structure of the 2nd PHD domain from Mi2b with C-terminal loop replaced by corresponding loop from WSTF
1we9	Solution structure of PHD domain in nucleic acid binding protein-like NP_197993
1wee	Solution structure of PHD domain in PHD finger family protein
1wem	Solution structure of PHD domain in death inducer-obliterator 1(DIO-1)
1wen	Solution structure of PHD domain in ING1-like protein BAC25079
1wep	Solution structure of PHD domain in PHF8
1wes	Solution structure of PHD domain in inhibitor of growth family, member 1-like
1weu	Solution structure of PHD domain in ING1-like protein BAC25009
1wev	Solution structure of PHD domain in protein NP_082203
1wew	Solution structure of PHD domain in DNA-binding family protein AAM98074
1x4i	Solution structure of PHD domain in inhibitor of growth protein 3 (ING3)
1xwh	NMR structure of the first phd finger of autoimmune regulator protein (AIRE1): insights into apeced
2dx8	Crystal Structure Analysis of the PHD domain of the Transcription Coactivator Pygophus
2e6r	Solution structure of the PHD domain in SmcY protein
2e6s	Solution structure of the PHD domain in RING finger protein 107
2f6j	Crystal structure of PHD finger-linker-bromodomain fragment of human BPTF in the H3(1-15)K4me3 bound state
2f6n	Crystal structure of PHD finger-linker-bromodomain fragment of human BPTF in the free form
2fsa	Crystal structure of PHD finger-linker-bromodomain fragment of human BPTF in the H3(1-15)K4ME2 bound state
2fui	NMR solution structure of PHD finger fragment of human BPTF in free state
2fuu	NMR solution structure of the PHD domain from the human BPTF in complex with H3(1-15)K4me3 peptide
2g6q	Crystal structure of ING2 PHD finger in complex with H3K4Me3 peptide
2jmi	NMR solution structure of PHD finger fragment of Yeast Yng1 protein in free state
2jmj	NMR solution structure of the PHD domain from the yeast YNG1 protein in complex with H3(1-9)K4me3 peptide
2k16	Solution structure of the free TAF3 PHD domain
2k17	Solution structure of the TAF3 PHD domain in complex with a H3K4me3 peptide
2k1j	Plan homeodomain finger of tumour supressor ING4
2ke1	Molecular Basis of non-modified histone H3 tail Recognition by the First PHD Finger of Autoimmune Regulator
2kft	NMR Solution structure of the first PHD finger domain of human Autoimmune Regulator (AIRE) in complex with Histone H3(1-20Cys) Peptide
2kgg	Solution Structure of JARID1A C-terminal PHD finger
2kgi	Solution structure of JARID1A C-terminal PHD finger in complex with H3(1-9)K4me3
2ku3	Solution structure of BRD1 PHD1 finger
2ku7	Solution structure of MLL1 PHD3-Cyp33 RRM chimeric protein
2kwj	Solution structures of the double PHD fingers of human transcriptional protein DPF3 bound to a histone peptide containing acetylation at lysine 14
2kwk	Solution structures of the double PHD fingers of human transcriptional protein DPF3b bound to a H3 peptide wild type
2kwn	Solution structure of the double PHD (plant homeodomain) fingers of human transcriptional protein DPF3b bound to a histone H4 peptide containing acetylation at Lysine 16
2kwo	Solution structure of the double PHD (plant homeodomain) fingers of human transcriptional protein DPF3b bound to a histone H4 peptide containing N-terminal acetylation at Serine 1
2kyu	The solution structure of the PHD3 finger of MLL
2l43	Structural basis for histone code recognition by BRPF2-PHD1 finger
2l5u	Structure of the first PHD finger (PHD1) from CHD4 (Mi2b)
2l75	Solution structure of CHD4-PHD2 in complex with H3K9me3
2lgg	Structure of PHD domain of UHRF1 in complex with H3 peptide
2lgk	NMR Structure of UHRF1 PHD domains in a complex with histone H3 peptide
2lgl	NMR structure of the UHRF1 PHD domain
2ln0	Structure of MOZ
2lq6	Solution structure of BRD1 PHD2 finger
2lri	NMR structure of the second PHD finger of AIRE (AIRE-PHD2)
2lv9	Solution NMR structure of the PHD domain of human MLL5, Northeast structural genomics consortium target HR6512A
2m1r	PHD domain of ING4 N214D mutant
2m3h	Structure of Dido PHD domain
2m85	PHD Domain from Human SHPRH
2ma5	Solution NMR structure of PHD type Zinc finger domain of Lysine-specific demethylase 5B (PLU-1/JARID1B) from Homo sapiens, Northeast Structural Genomics Consortium (NESG) Target HR7375C
2md7	NMR structure of human Sp140 PHD finger trans conformer
2md8	NMR structure of Sp140 PHD finger cis conformer
2miq	Solution NMR Structure of PHD Type 1 Zinc Finger Domain 1 of Lysine-specific Demethylase Lid from Drosophila melanogaster, Northeast Structural Genomics Consortium (NESG) Target FR824J
2mny	2MNY
2mnz	2MNZ
2mum	2MUM
2naa	2NAA
2pnx	The PHD finger of ING4 in complex with an H3K4Me3 histone peptide
2puy	Crystal Structure of the BHC80 PHD finger
2qic	Crystal Structure of the ING1 PHD Finger in complex with a Histone H3K4ME3 peptide
2ri7	Crystal structure of PHD finger-linker-bromodomain Y17E mutant from human BPTF in the H3(1-9)K4ME2 bound state
2ro1	NMR Solution Structures of Human KAP1 PHD finger-bromodomain
2rsd	Solution structure of the plant homeodomain (PHD) of the E3 SUMO ligase Siz1 from rice
2vnf	MOLECULAR BASIS OF HISTONE H3K4ME3 RECOGNITION BY ING4
2vp7	Decoding of methylated histone H3 tail by the Pygo-BCL9 Wnt signaling complex
2vpb	Decoding of methylated histone H3 tail by the Pygo-BCL9 Wnt signaling complex
2vpd	Decoding of methylated histone H3 tail by the Pygo-BCL9 Wnt signaling complex
2vpe	Decoding of methylated histone H3 tail by the Pygo-BCL9 Wnt signaling complex
2vpg	Decoding of methylated histone H3 tail by the Pygo-BCL9 Wnt signaling complex
2xb1	Crystal structure of the human Pygo2 PHD finger in complex with the B9L HD1 domain
2yql	Solution structure of the PHD domain in PHD finger protein 21A
2ysm	Solution structure of the first and second PHD domain from Myeloid/lymphoid or mixed-lineage leukemia protein 3 homolog
2yt5	Solution structure of the PHD domain of Metal-response element-binding transcription factor 2
2yyr	Structural analysis of PHD domain of Pygopus complexed with trimethylated histone H3 peptide
3ask	Structure of UHRF1 in complex with histone tail
3asl	Structure of UHRF1 in complex with histone tail
3c6w	Crystal structure of the ING5 PHD finger in complex with H3K4me3 peptide
3gl6	Crystal structure of JARID1A-PHD3 complexed with H3(1-9)K4me3 peptide
3kqi	crystal structure of PHF2 PHD domain complexed with H3K4Me3 peptide
3kv4	Structure of PHF8 in complex with histone H3
3kv5	Structure of KIAA1718, human Jumonji demethylase, in complex with N-oxalylglycine
3kv6	Structure of KIAA1718, human Jumonji demethylase, in complex with alpha-ketoglutarate
3lqh	Crystal structure of MLL1 PHD3-Bromo in the free form
3lqi	Crystal structure of MLL1 PHD3-Bromo complexed with H3(1-9)K4me2 peptide
3lqj	Crystal structure of MLL1 PHD3-Bromo complexed with H3(1-9)K4me3 peptide
3n9l	ceKDM7A from C.elegans, complex with H3K4me3 peptide and NOG
3n9m	ceKDM7A from C.elegans, alone
3n9n	ceKDM7A from C.elegans, complex with H3K4me3K9me2 peptide and NOG
3n9o	ceKDM7A from C.elegans, complex with H3K4me3 peptide, H3K9me2 peptide and NOG
3n9p	ceKDM7A from C.elegans, complex with H3K4me3K27me2 peptide and NOG
3n9q	ceKDM7A from C.elegans, complex with H3K4me3 peptide, H3K27me2 peptide and NOG
3o33	Crystal structure of TRIM24 PHD-Bromo in the free state
3o34	Crystal structure of TRIM24 PHD-Bromo complexed with H3(13-32)K23ac peptide
3o35	Crystal structure of TRIM24 PHD-Bromo complexed with H3(23-31)K27ac peptide
3o36	Crystal structure of TRIM24 PHD-Bromo complexed with H4(14-19)K16ac peptide
3o37	Crystal structure of TRIM24 PHD-Bromo complexed with H3(1-10)K4 peptide
3o70	PHD-type zinc finger of human PHD finger protein 13
3o7a	Crystal structure of PHF13 in complex with H3K4me3
3puq	CEKDM7A from C.Elegans, complex with alpha-KG
3pur	CEKDM7A from C.Elegans, complex with D-2-HG
3qzv	Crystal Structure of BPTF PHD-linker-bromo in complex with histone H4K12ac peptide
3shb	Crystal Structure of PHD Domain of UHRF1
3sou	Structure of UHRF1 PHD finger in complex with histone H3 1-9 peptide
3sow	Structure of UHRF1 PHD finger in complex with histone H3K4me3 1-9 peptide
3sox	Structure of UHRF1 PHD finger in the free form
3t6r	Structure of UHRF1 in complex with unmodified H3 N-terminal tail
3u5m	Crystal structure of TRIM33 PHD-Bromo in the free state
3u5n	Crystal structure of the complex of TRIM33 PHD-Bromo and H3(1-20)K9me3K14ac histone peptide
3u5o	Crystal structure of the complex of TRIM33 PHD-Bromo and H3(1-22)K9me3K14acK18ac histone peptide
3u5p	Crystal structure of the complex of TRIM33 PHD-Bromo and H3(1-28)K9me3K14acK18acK23ac histone peptide
3v43	Crystal structure of MOZ
3zpv	Crystal structure of Drosophila Pygo PHD finger in complex with Legless HD1 domain
3zvy	PHD finger of human UHRF1 in complex with unmodified histone H3 N- terminal tail
3zvz	PHD finger of human UHRF1
4bbq	Crystal structure of the CXXC and PHD domain of Human Lysine-specific Demethylase 2A (KDM2A)(FBXL11)
4bxz	RNA Polymerase II-Bye1 complex
4cos	Crystal structure of the PHD-Bromo-PWWP cassette of human PRKCBP1
4gnd	Crystal Structure of NSD3 tandem PHD5-C5HCH domains
4gne	Crystal Structure of NSD3 tandem PHD5-C5HCH domains complexed with H3 peptide 1-7
4gnf	Crystal Structure of NSD3 tandem PHD5-C5HCH domains complexed with H3 peptide 1-15
4gng	Crystal Structure of NSD3 tandem PHD5-C5HCH domains complexed with H3K9me3 peptide
4gy5	Crystal structure of the tandem tudor domain and plant homeodomain of UHRF1 with Histone H3K9me3
4l58	Crystal structure of the MLL5 PHD finger in complex with H3K4me3
4l7x	Crystal structure of the DIDO PHD finger in complex with H3K4me3
4ljn	Crystal Structure of MOZ double PHD finger
4lk9	Crystal Structure of MOZ double PHD finger histone H3 tail complex
4lka	Crystal Structure of MOZ double PHD finger histone H3K9ac complex
4llb	Crystal Structure of MOZ double PHD finger histone H3K14ac complex
4nn2	Protein Crystal Structure of Human Borjeson-Forssman-Lehmann Syndrome Associated Protein PHF6
4o64	Zinc fingers of KDM2B
4ptb	Crystal structure of human SP100 PHD-Bromodomain in the free state
4q6f	Crystal structure of human BAZ2A PHD zinc finger in complex with unmodified H3K4 histone peptide
4qf2	4QF2
4qf3	4QF3
4tvr	4TVR
4up0	4UP0
4up5	4UP5
4yab	4YAB
4yad	4YAD
4yat	4YAT
4yax	4YAX
4ybm	4YBM
4ybs	4YBS
4ybt	4YBT
4yc9	4YC9
4zql	4ZQL
5b73	5B73
5b75	5B75
5b76	5B76
5b77	5B77
5b78	5B78
5b79	5B79
5c11	5C11
5c13	5C13
5ceh	5CEH
5dag	5DAG
5dah	5DAH
5erc	5ERC
5fb0	5FB0
5fb1	5FB1
5hh7	5HH7
5i3l	5I3L
5k4l	5K4L
5tab	5TAB
5tbn	5TBN
5tdr	5TDR
5tdw	5TDW

Links (links to other resources describing this domain)

• INTERPRO: IPR001965
• PFAM: PHD