Jumonji helical domain; This 4-helix bundle domain is associated with the Jumonji domain pfam02373.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528518168   342 LNIDMQLRAYEIEKRLSTADLFKFPNFETVCWYVGKHLLDTFRGLRENRRHPATYLVHGAKALNNAFRGWTRKESLGEHE 421
Cdd:pfam17811    1 LNIEMQLRAYEIEKRLKTPDLFKFPNFETICWYVAKHLLETLRELREEGRRPAEYLVRGVKALLIALKSWTRKEALTEHE 80

                           90       100
                   ....*....|....*....|....
gi 528518168   422 QEIPDTIKTQQLVKDLAKEIRLVE 445
Cdd:pfam17811   81 DEIPETIKPVQLIKDLSKEIRHVE 104

RmlC-like cupin superfamily; This superfamily contains proteins similar to the RmlC (dTDP (deoxythymidine diphosphates)-4-dehydrorhamnose 3,5-epimerase)-like cupins. RmlC is a dTDP-sugar isomerase involved in the synthesis of L-rhamnose, a saccharide required for the virulence of some pathogenic bacteria. Cupins are a functionally diverse superfamily originally discovered based on the highly conserved motif found in germin and germin-like proteins. This conserved motif forms a beta-barrel fold found in all of the cupins, giving rise to the name cupin ('cupa' is the Latin term for small barrel). The active site of members of this superfamily is generally located at the center of a conserved barrel and usually includes a metal ion. The different functional classes in this superfamily include single domain bacterial isomerases and epimerases involved in the modification of cell wall carbohydrates, two domain bicupins such as the desiccation-tolerant seed storage globulins, and multidomain nuclear transcription factors involved in legume root nodulation.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528518168   238 YCLMGVKDSYTDFHIDFGGT-SVWYHVLRGEKIFYLI---RPTAANLSLFERWSSSSNQNELFFGDQVD---------MC 304
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLySINYLHFGAPKVWYIIppeYAEKFEKVLSDHFGGEQPDDLLHLNTIISpkqlrengiPV 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 528518168   305 YKCSVKQGNTLFIPTGWIHAVLTPVDCLAFGGNF 338
Cdd:pfam02373   81 YRFVQKPGEFVFTFPGWYHQVFNLGFNIAEAVNF 114

Jumonji helical domain; This 4-helix bundle domain is associated with the Jumonji domain pfam02373.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528518168   342 LNIDMQLRAYEIEKRLSTADLFKFPNFETVCWYVGKHLLDTFRGLRENRRHPATYLVHGAKALNNAFRGWTRKESLGEHE 421
Cdd:pfam17811    1 LNIEMQLRAYEIEKRLKTPDLFKFPNFETICWYVAKHLLETLRELREEGRRPAEYLVRGVKALLIALKSWTRKEALTEHE 80

                           90       100
                   ....*....|....*....|....
gi 528518168   422 QEIPDTIKTQQLVKDLAKEIRLVE 445
Cdd:pfam17811   81 DEIPETIKPVQLIKDLSKEIRHVE 104

JmjC domain, hydroxylase; The JmjC domain belongs to the Cupin superfamily. JmjC-domain proteins may be protein hydroxylases that catalyze a novel histone modification. This is confirmed to be a hydroxylase: the human JmjC protein named Tyw5p unexpectedly acts in the biosynthesis of a hypermodified nucleoside, hydroxy-wybutosine, in tRNA-Phe by catalysing hydroxylation.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528518168   238 YCLMGVKDSYTDFHIDFGGT-SVWYHVLRGEKIFYLI---RPTAANLSLFERWSSSSNQNELFFGDQVD---------MC 304
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLySINYLHFGAPKVWYIIppeYAEKFEKVLSDHFGGEQPDDLLHLNTIISpkqlrengiPV 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 528518168   305 YKCSVKQGNTLFIPTGWIHAVLTPVDCLAFGGNF 338
Cdd:pfam02373   81 YRFVQKPGEFVFTFPGWYHQVFNLGFNIAEAVNF 114

PHD zinc finger; 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.

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*...
gi 528518168      7 YC-LCRLPYDvTRFMIECDVCQDWFHGSCVGVEEDKAAEIDLYHCPNC 53
Cdd:smart00249    1 YCsVCGKPDD-GGELLQCDGCDRWYHQTCLGPPLLEEEPDGKWYCPKC 47

Jumonji helical domain; This 4-helix bundle domain is associated with the Jumonji domain pfam02373.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528518168   342 LNIDMQLRAYEIEKRLSTADLFKFPNFETVCWYVGKHLLDTFRGLRENRRHPATYLVHGAKALNNAFRGWTRKESLGEHE 421
Cdd:pfam17811    1 LNIEMQLRAYEIEKRLKTPDLFKFPNFETICWYVAKHLLETLRELREEGRRPAEYLVRGVKALLIALKSWTRKEALTEHE 80

                           90       100
                   ....*....|....*....|....
gi 528518168   422 QEIPDTIKTQQLVKDLAKEIRLVE 445
Cdd:pfam17811   81 DEIPETIKPVQLIKDLSKEIRHVE 104

PHD finger found in PHF2, PHF8 and KDM7; This family includes PHF2, PHF8, KDM7, and similar proteins. PHF2, also termed GRC5, or PHD finger protein 2, is a histone lysine demethylase ubiquitously expressed in various tissues. PHF8, also termed PHD finger protein 8, or KDM7B, is a monomethylated histone H4 lysine 20(H4K20me1) demethylase that transcriptionally regulates many cell cycle genes. It also preferentially acts on H3K9me2 and H3K9me1. PHF8 is modulated by CDC20-containing anaphase-promoting complex (APC (cdc20)) and plays an important role in the G2/M transition. It acts as a critical molecular sensor for mediating retinoic acid (RA) treatment response in RAR alpha-fusion-induced leukemia. Moreover, PHF8 is essential for cytoskeleton dynamics and is associated with X-linked mental retardation. KDM7, also termed JmjC domain-containing histone demethylation protein 1D (JHDM1D), or KIAA1718, is a dual histone demethylase that catalyzes demethylation of monomethylated and dimethylated H3K9 (H3K9me2/me1) and H3K27 (H3K27me2/me1), which functions as an eraser of silencing marks on chromatin during brain development. It also plays a tumor-suppressive role by regulating angiogenesis. All family members contain a plant homeodomain (PHD) finger and a JmjC domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 528518168    7 YCLCRLPYDVTRFMIECDVCQDWFHGSCVGVEEDKAAEIDLYHCPNC 53
Cdd:cd15554     1 YCICRQPYDVTRFMIECDVCKDWFHGSCVGVEEHQANDIERYHCPNC 47

PHD finger found in lysine-specific demethylase PHF2; PHF2, also termed GRC5, or PHD finger protein 2, is a histone lysine demethylase ubiquitously expressed in various tissues. It contains a plant homeodomain (PHD) finger and a JmjC domain and plays an important role in adipogenesis. The PHD finger domain can recognize trimethylated histone H3 lysine 4 (H3K4me3). PHF2 also has dimethylated histone H3 lysine 9(H3K9me2) demethylase activity and acts as a coactivator of several metabolism-related transcription factors. Moreover, it can demethylate ARID5B and further forms a complex with demethylated ARD5B to bind the promoter regions of target genes. The overexpression of PHF2 is involved in the progression of esophageal squamous cell carcinoma (ESCC).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 528518168    7 YCLCRLPYDVTRFMIECDVCQDWFHGSCVGVEEDKAAEIDLYHCPNCQVT 56
Cdd:cd15641     1 YCICRLPYDVTRFMIECDACKDWFHGSCVGVEEEEAPDIDIYHCPNCEKT 50

PHD finger found in PHD finger protein 3 (PHF3), and death-inducer obliterator variants Dido1, Dido2, and Dido3; PHF3 is a human homolog of yeast protein bypass of Ess1 (Bye1), a nuclear protein with a domain resembling the central domain in the transcription elongation factor TFIIS. It is ubiquitously expressed in normal tissues including brain, but its expression is significantly reduced or lost in glioblastomas. PHF3 contains an N-terminal plant homeodomain (PHD) finger, a central RNA polymerase II (Pol II)-binding TFIIS-like domain (TLD) domain, and a C-terminal Spen paralogue and orthologue C-terminal (SPOC) domain. This family also includes Dido gene encoding three alternative splicing variants (Dido1, 2, and 3), which have been implicated in a number of cellular processes such as apoptosis and chromosomal segregation, particularly in the hematopoietic system. Dido1 is important for maintaining embryonic stem (ES) cells and directly regulates the expression of pluripotency factors. It is the shortest isoform that contains only a highly conserved PHD finger responsible for the binding of histone H3 with a higher affinity for trimethylated lysine4 (H3K4me3). Gene Dido1 is a Bone morphogenetic protein (BMP) target gene and promotes BMP-induced melanoma progression. It also triggers apoptosis after nuclear translocation and caspase upregulation. Dido3 is the largest isoform and is ubiquitously expressed in all human tissues. It is dispensable for ES cell self-renewal and pluripotency, but is involved in the maintenance of stem cell genomic stability and tumorigenesis. Dido3 contains a PHD finger, a transcription elongation factor S-II subunit M (TFSIIM) domain, a SPOC module, and a long C-terminal region (CT) of unknown homology.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 528518168    7 YCLCRLPYDvTRFMIECDVCQDWFHGSCVGVEE----DKAAEIDLYHCPNC 53
Cdd:cd15552     1 YCICRKPHN-NRFMICCDRCEEWFHGDCVGITEaqgkEMEENIEEYVCPKC 50

PHD finger found in CXXC-type zinc finger protein 1 (Cfp1); Cfp1, also termed CpG-binding protein, or PHD finger and CXXC domain-containing protein 1 (PCCX1), is a specificity factor that binds to unmethylated CpGs and links H3K4me3 with CpG islands (CGIs). It integrates both promoter CpG content and gene activity for accurate trimethylation of histone H3 Lys 4 (H3K4me3) deposition in embryonic stem cells. Moreover, Cfp1 is an essential component of the SETD1 histone H3K4 methyltransferase complex and functions as a critical regulator of histone methylation, cytosine methylation, cellular differentiation, and vertebrate development. Cfp1 contains a plant homeodomain (PHD) finger, a CXXC domain, and a CpG binding protein zinc finger C-terminal domain. Its CXXC domain selectively binds to non-methylated CpG islands, following by a preference for a guanosine nucleotide.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 528518168    7 YCLCRLPyDVTRFMIECDVCQDWFHGSCVGVEEDKAAEIDLYHCPNC 53
Cdd:cd15553     1 YCICRSS-DISRFMIGCDNCEEWYHGDCINITEKEAKAIKEWYCQQC 46

PHD finger found in death-inducer obliterator variants Dido1, Dido2, and Dido3; This family includes three alternative splicing variants (Dido1, 2, and 3) encoded by the Dido gene, which have been implicated in a number of cellular processes such as apoptosis and chromosomal segregation, particularly in the hematopoietic system. Dido1, also termed DIO-1, or death-associated transcription factor 1 (DATF-1), is important for maintaining embryonic stem (ES) cells and directly regulates the expression of pluripotency factors. It is the shortest isoform that contains only a highly conserved plant homeodomain (PHD) finger responsible for the binding of histone H3 with a higher affinity for trimethylated lysine 4 (H3K4me3). Gene Dido is a Bonemorphogenetic protein (BMP) target gene, which promotes BMP-induced melanoma progression. It also triggers apoptosis after nuclear translocation and caspase upregulation. Dido3 is the largest isoform ubiquitously expressed in all human tissues. It is dispensable for ES cell self-renewal and pluripotency, but involved in the maintenance of stem cell genomic stability and tumorigenesis. Dido3 contains a PHD finger, a transcription elongation factor S-II subunit M (TFSIIM) domain, aspen paralog and ortholog (SPOC) module, and a long C-terminal region (CT) of unknown homology. Its PHD finger interacts with H3K4me3.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 528518168    6 VYCLCRLPYDvTRFMIECDVCQDWFHGSCVGVEEDKAAEIDL----YHCPNC 53
Cdd:cd15639     4 LYCICRQPHN-NRFMICCDRCEEWFHGDCVGITEARGRLLERngedYICPNC 54

PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) finger typically characterized as Cys4HisCys3, and a non-canonical extended PHD finger, characterized as Cys2HisCys5HisCys2His. Variations include the RAG2 PHD finger characterized by Cys3His2Cys2His and the PHD finger 5 found in nuclear receptor-binding SET domain-containing proteins characterized by Cys4HisCys2His. The PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. Single or multiple copies of PHD fingers have been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors. The PHD finger domain SF is structurally similar to the RING and FYVE_like superfamilies.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 528518168    7 YC-LCRLPYDVTRFMIECDVCQDWFHGSCVGVEEDKAAEIDLYHCPNC 53
Cdd:cd15489     1 SCiVCGKGGDLGGELLQCDGCGKWFHADCLGPPLSSFVPNGKWICPVC 48

PHD finger found in Set1 complex component SPP1; Set1C component SPP1, also called COMPASS component Spp1, or Complex proteins associated with set1 protein Spp1, or Suppressor of PRP protein 1, is a component of the COMPASS complex that links histone methylation to initiation of meiotic recombination. It induces double-strand break (DSB) formation by tethering to recombinationally cold regions. SPP1 interacts with H3K4me3 and Mer2, a protein required for DSB formation, to promote recruitment of potential meiotic DSB sites to the chromosomal axis. SPP1 contains a PHD finger, a zinc binding motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 528518168    7 YCLCRLPYDvTRFMIECDVCQDWFHGSCVGVEEDKAAEIDLYHCPNC 53
Cdd:cd16039     1 YCICQKPDD-GRWMIACDGCDEWYHFTCVNIPEADVELVDSFFCPPC 46

PHD finger found in plant Alfin1-like (AL) proteins; AL proteins are ubiquitously expressed nuclear proteins existing only in plants. They are involved in chromatin regulation by binding to tri- and dimethylated histone H3 at lysine 4 (H3K4me3/2), the active histone markers, through their plant homeodomain (PHD) fingers.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 528518168   10 CRLPYDVTRFMIECDVCQDWFHGSCVGVEEDKAAEIDLYHCPNC 53
Cdd:cd15613     5 CGGNYTADEFWICCDVCEKWYHGKCVKITPAKAEHIKQYKCPSC 48

PHD finger 2 found in Lysine-specific demethylase 5A (KDM5A); KDM5A (also termed Histone demethylase JARID1A, Jumonji/ARID domain-containing protein 1A, or Retinoblastoma-binding protein 2 (RBBP-2 or RBP2)) was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation. It is involved in transcription through interacting with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK, and BMAL1. KDM5A functions as a trimethylated histone H3 lysine 4 (H3K4me3) demethylase that belongs to the JARID subfamily within the JmjC proteins. It also displays DNA-binding activities that can recognize the specific DNA sequence CCGCCC. KDM5A contains the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers. This model corresponds to the second PHD finger.

                          10        20        30
                  ....*....|....*....|....*....|
gi 528518168    7 YCLCRLPydVTRFMIECDVCQDWFHGSCVG 36
Cdd:cd15606     1 YCICRKP--FSGFMLQCELCKDWFHSSCVP 28

PHD finger found in PHD finger protein 3 (PHF3); PHF3 is a human homolog of yeast protein bypass of Ess1 (Bye1), a nuclear protein with a domain resembling the central domain in the transcription elongation factor TFIIS. It is ubiquitously expressed in normal tissues including brain, but its expression is significantly reduced or lost in glioblastomas. PHF3 contains an N-terminal plant homeodomain (PHD) finger, a central RNA polymerase II (Pol II)-binding TFIIS-like domain (TLD) domain, and a C-terminal Spen paralogue and orthologue C-terminal (SPOC) domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 528518168    9 LCRLPYDvTRFMIECDVCQDWFHGSCVGVEEDKAAEIDL----YHCPNC 53
Cdd:cd15638     4 FCKKPHG-NRFMVGCGRCDDWFHGDCVGLSLSQAQQMEEedkeYVCVKC 51

PHD finger found in mixed lineage leukemia 5 (MLL5); MLL5 is a histone methyltransferase that plays a key role in hematopoiesis, spermatogenesis and cell cycle progression. It contains a single plant homeodomain (PHD) finger followed by a catalytic SET domain. MLL5 can be recruited to E2F1-responsive promoters to stimulate H3K4 trimethylation and transcriptional activation by binding to the cell cycle regulator host cell factor (HCF-1), thereby facilitating the cell cycle G1 to S phase transition. It is also involved in mitotic fidelity and genomic integrity by modulating the stability of the chromosomal passenger complex (CPC) via the interaction with Borealin. Moreover, MLL5 is a component of a complex associated with retinoic acid receptor that requires GlcN Acylation of its SET domain in order to activate its histone lysine methyltransferase activity. It also participates in the camptothecin (CPT)-induced p53 activation. Furthermore, MLL5 indirectly regulates H3K4 methylation, represses cyclin A2 (CycA) expression, and promotes myogenic differentiation.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 528518168    8 CLCRLPYDVtRFMIECDVCQDWFHGSCVGVEEDKAAeiDLYHCPNC 53
Cdd:cd15550     2 CICGFEHDD-GFMICCDKCSVWQHGDCMGIDRENIP--DSYLCEQC 44

PHD-finger; 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.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 528518168     7 YC-LCRLPyDVTRFMIECDVCQDWFHGSCVGVEEDKAAEID-LYHCPNCQV 55
Cdd:pfam00628    1 YCaVCGKS-DDGGELVQCDGCDDWFHLACLGPPLDPAEIPSgEWLCPECKP 50

PHD finger 2 found in Lysine-specific demethylase KDM5A, KDM5B, KDM5C, KDM5D, and similar proteins; The JARID subfamily within the JmjC proteins includes Lysine-specific demethylase KDM5A, KDM5B, KDM5C, KDM5D and a Drosophila homolog protein, little imaginal discs (Lid). KDM5A was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation. It is involved in transcription through interacting with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK, and BMAL1. KDM5B has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of the pregnant female and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis. Both KDM5A and KDM5B function as trimethylated histone H3 lysine 4 (H3K4me3) demethylases. KDM5C is a H3K4 trimethyl-histone demethylase that catalyzes demethylation of H3K4me3 and H3K4me2 to H3K4me1. It plays a role in neuronal survival and dendrite development. KDM5C defects are associated with X-linked mental retardation (XLMR). KDM5D is a male-specific antigen that shows a demethylase activity specific for di- and tri-methylated histone H3K4 (H3K4me3 and H3K4me2), and has a male-specific function as a histone H3K4 demethylase by recruiting a meiosis-regulatory protein, MSH5, to condensed DNA. KDM5D directly interacts with a polycomb-like protein Ring6a/MBLR, and plays a role in regulation of transcriptional initiation through H3K4 demethylation. The family also includes Drosophila melanogaster protein little imaginal discs (Lid) that functions as a JmjC-dependent trimethyl histone H3K4 (H3K4me3) demethylase, which is required for dMyc-induced cell growth. It positively regulates Hox gene expression in S2 cells. Members in this family contain the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as two or three plant homeodomain (PHD) fingers. This model corresponds to the second PHD finger.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 528518168    7 YCLCRlpYDVTRFMIECDVCQDWFHGSCVGV 37
Cdd:cd15516     1 ICLCG--KALAAGMLQCELCQDWFHGSCVAV 29

PHD finger found in the inhibitor of growth (ING) protein family; The ING family includes a group of tumor suppressors, ING1-5, which act as readers and writers of the histone epigenetic code, affecting DNA damage response, chromatin remodeling, cellular senescence, differentiation, cell cycle regulation and apoptosis. They may have a general role in mediating the cellular response to genotoxic stress through binding to and regulating the activities of histone acetyltransferase (HAT) and histone deacetylase (HDAC) chromatin remodeling complexes. All ING proteins contain an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 528518168    7 YCLCRLPYDVTrfMIECD--VCQ-DWFHGSCVGVeedKAAEIDLYHCPNC 53
Cdd:cd15505     1 YCICNQVSYGE--MVACDnpNCPiEWFHFECVGL---TAKPKGKWYCPEC 45

PHD finger found in PHD finger protein 13 (PHF13); PHF13, also termed survival time-associated PHD finger protein in ovarian cancer 1 (SPOC1), is a novel plant homeodomain (PHD) finger-containing protein that shows strong expression in spermatogonia and ovarian cancer cells, modulates chromatin structure and mitotic chromosome condensation, and is important for proper cell division. It is also required for spermatogonial stem cell differentiation and sustained spermatogenesis. The overexpression of PHF13 associates with unresectable carcinomas and shorter survival in ovarian cancer.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 528518168    6 VYCLCRLPYdVTRFMIECDVCQDWFHGSCVGVEEDKAAEIdlYHCPNCQ 54
Cdd:cd15632     2 VTCFCMKPF-AGRPMIECNECHTWIHLSCAKIRKSNVPEV--YVCQKCR 47

PHD finger found in Transcription factor 19 (TCF-19) and similar proteins; TCF-19, also termed transcription factor SC1, was identified as a putative trans-activating factor with expression beginning at the late G1-S boundary in dividing cells. It also functions as a novel islet factor necessary for proliferation and survival in the INS-1 beta cell line. It plays an important role in susceptibility to both Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM); it has been suggested that it may positively impact beta cell mass under conditions of beta cell stress and increased insulin demand. TCF-19 contains an N-terminal fork head association domain (FHA), a proline rich region, and a C-terminal plant homeodomain (PHD) finger. The FHA domain may serve as a nuclear signaling domain or as a phosphoprotein binding domain. The proline rich region is a common characteristic of trans-activating factors. The PHD finger may allow TCF-19 to interact with chromatin via methylated histone H3.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 528518168   10 CRLPYDVTRFMIECDVCQDWFHGSCVGVEEDKAAEIDL-YHCP 51
Cdd:cd15609     7 CCLPQDETVSWVQCDDCDQWYHVACVGCDYNAVKDPDAdFHCG 49

PHD finger 2 found in Lysine-specific demethylase 5C (KDM5C) and 5D (KDM5D); The family includes KDM5C and KDM5D, both of which belong to the JARID subfamily within the JmjC proteins. KDM5C (also termed Histone demethylase JARID1C, Jumonji/ARIDdomain-containing protein 1C, SmcX, or Xe169) is a H3K4 trimethyl-histone demethylase that catalyzes demethylation of H3K4me3 and H3K4me2 to H3K4me1. It plays a role in neuronal survival and dendrite development. KDM5C defects are associated with X-linked mental retardation (XLMR). KDM5D (also termed Histocompatibility Y antigen (H-Y), Histone demethylase JARID1D, Jumonji/ARID domain-containing protein 1D, or SmcY) is a male-specific antigen that shows a demethylase activity specific for di- and tri-methylated histone H3K4 (H3K4me3 and H3K4me2), and has a male-specific function as a histone H3K4 demethylase by recruiting a meiosis-regulatory protein, MSH5, to condensed DNA. KDM5D directly interacts with a polycomb-like protein Ring6a/MBLR, and plays a role in regulation of transcriptional initiation through H3K4 demethylation. Both KDM5C and KDM5D contain the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as two plant homeodomain (PHD) fingers. This model corresponds to the second PHD finger.

                          10        20        30
                  ....*....|....*....|....*....|
gi 528518168    8 CLCRLPYDVTrfMIECDVCQDWFHGSCVGV 37
Cdd:cd15608     2 CVCGQPPRPG--MLRCHLCQDWFHGGCVSF 29

PHD finger found in histone-lysine N-methyltransferase ASH1L; ASH1L, also termed ASH1-like protein, or absent small and homeotic disks protein 1 homolog, or lysine N-methyltransferase 2H, is a protein belonging to the Trithorax family. It methylates Lys36 of histone H3 independently of transcriptional elongation to promote the establishment of Hox gene expression by counteracting Polycomb silencing. It can suppress interleukin-6 (IL-6), and tumor necrosis factor (TNF) production in Toll-like receptor (TLR)-triggered macrophages, and inflammatory autoimmune diseases by inducing the ubiquitin-editing enzyme A20. ASH1L contains an associated with SET domain (AWS), a SET domain, a post-SET domain, a bromodomain, a bromo-adjacent homology domain (BAH), and a plant homeodomain (PHD) finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 528518168    6 VYCLCRLpYDVTRFMIECDVCQDWFHGSCVGVEEDkaaeIDLYHCPNC 53
Cdd:cd15548     1 IRCICGL-YKDEGLMIQCEKCMVWQHCDCMGVNDD----VEHYLCEQC 43

PHD finger found in Arabidopsis thaliana protein OBERON 1, OBERON 2, and similar proteins mainly found in plants; Included in this family are OBERON 1 (OBE1, or potyvirus VPg-interacting protein 2) and OBERON 2 (OBE2, or potyvirus VPg-interacting protein 1), which have been involved in the maintenance and/or establishment of the meristems in Arabidopsis. They interact with potyvirus VPg-interacting proteins (PVIP1 and 2) and act as central regulators in auxin-mediated control of development. Both OBE1and OBE2 contain a plant homeodomain (PHD) finger. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins.

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gi 528518168   21 IECDVCQDWFHGSC----------VGVEEDKAAEIDLYHCPNC 53
Cdd:cd15612    18 IGCDVCSHWTHTDCairsgeismgVSLKGVEGSTEMEFHCRAC 60

PHD finger 3 found in lysine-specific demethylase 5B (KDM5B); KDM5B, also termed Cancer/testis antigen 31 (CT31), or Histone demethylase JARID1B, or Jumonji/ARID domain-containing protein 1B (JARID1B), or PLU-1, or retinoblastoma-binding protein 2 homolog 1 (RBP2-H1 or RBBP2H1A), is a member of the JARID subfamily within the JmjC proteins. It has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of the pregnant female and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis. KDM5B acts as a histone demethylase that catalyzes the removal of trimethylation of lysine 4 on histone H3 (H3K4me3), induced by polychlorinated biphenyls (PCBs). It also mediates demethylation of H3K4me2 and H3K4me1. Moreover, KDM5B functions as a negative regulator of hematopoietic stem cell (HSC) self-renewal and progenitor cell activity. KDM5B has also been shown to interact with the DNA binding transcription factors BF-1 and PAX9, as well as TIEG1/KLF10 (transforming growth factor-beta inducible early gene-1/Kruppel-like transcription factor 10), and possibly function as a transcriptional corepressor. KDM5B contains the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers. This model corresponds to the third PHD finger.

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gi 528518168   21 IECD-VCQDWFHGSCVGVEEDKAAEIDlYHCPNC 53
Cdd:cd15687    18 VQCDgSCNRWFHQVCVGVSAEMAEKED-YICVSC 50

PHD finger 2 found in metal-response element-binding transcription factor 2 (MTF2); MTF2, also termed metal regulatory transcription factor 2, or metal-response element DNA-binding protein M96, or Polycomb-like protein 2 (PCL2), complexes with the Polycomb repressive complex-2 (PRC2) in embryonic stem cells and regulates the transcriptional networks during embryonic stem cell self-renewal and differentiation. It recruits the PRC2 complex to the inactive X chromosome and target loci in embryonic stem cells. Moreover, MTF2 is required for PRC2-mediated Hox cluster repression. It activates the Cdkn2a gene and promotes cellular senescence, thus suppressing the catalytic activity of PRC2 locally. MTF2 consists of an N-terminal Tudor domain followed by two plant homeodomain (PHD) fingers, and a C-terminal MTF2 domain. This model corresponds to the second PHD finger.

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gi 528518168    7 YCLCRLPYDVTRFMIECDVCQDWFHGSCV 35
Cdd:cd15580     1 YCYCGGPGDWYLKMLQCCKCKQWFHEACV 29

PHD domain found in Saccharomyces cerevisiae bypass of ESS1 protein 1 (Bye1p), the E3 Sumo Ligase SIZ1, and similar proteins; Yeast Bye1p is a nuclear transcription factor with a domain resembling the central domain in the transcription elongation factor TFIIS and plays an inhibitory role during transcription elongation. It functions as a multicopy suppressor of Ess1, a peptidyl-prolyl cis-trans isomerase involved in proline isomerization of the C-terminal domain (CTD) of RNA polymerase II (Pol II). Bye1p contains an N-terminal plant homeodomain (PHD) finger, a central Pol II-binding TFIIS-like domain (TLD) domain, and a C-terminal Spen paralogue and orthologue C-terminal (SPOC) domain. The PHD domain binds to a histone H3 tail peptide containing trimethylated lysine 4 (H3K4me3). The TLD domain is responsible for the association with chromatin. Plant SIZ1 protein is a SUMO (small ubiquitin-related modifier) E3 ligase that facilitates conjugation of SUMO to substrate target proteins (sumoylation) and belongs to the protein inhibitor of activated STAT (PIAS) protein family. It negatively regulates abscisic acid (ABA) signaling, which is dependent on the bZIP transcripton factor ABI5. It also modulates plant growth and plays a role in drought stress response likely through the regulation of gene expression. SIZ1 functions as a floral repressor that not only represses the salicylic acid (SA)-dependent pathway, but also promotes FLOWERING LOCUS C (FLC) expression by repressing FLOWERING LOCUS D (FLD) activity through sumoylation. SIZ1 contains a PHD finger, which specifically binds methylated histone H3 at lysine 4 and arginine 2.

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gi 528518168    8 CLCRLPyDVTRFMIECDVCQDWFHGSCVGVEEDKAA---EID-LYHCPNC 53
Cdd:cd15570     2 CPCGSS-MEDGSMIQCEGCKTWQHMDCVLIPDKPADglpELPsKFYCELC 50

PHD finger found in inhibitor of growth protein 3 (ING3) and similar proteins; ING3, also termed p47ING3, is one member of the inhibitor of growth (ING) family of type II tumor suppressors. It is ubiquitously expressed and has been implicated in transcription modulation, cell cycle control, and the induction of apoptosis. It is an important subunit of human NuA4 histone acetyltransferase complex, which regulates the acetylation of histones H2A and H4. Moreover, ING3 promotes ultraviolet (UV)-induced apoptosis through the Fas/caspase-8-dependent pathway in melanoma cells. It physically interacts with subunits of E3 ligase Skp1-Cullin-F-boxprotein complex (SCF complex) and is degraded by the SCF (F-box protein S-phase kinase-associated protein 2, Skp2)-mediated ubiquitin-proteasome system. It also acts as a suppression factor during tumorigenesis and progression of hepatocellular carcinoma (HCC). ING3 contains an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 528518168    7 YCLCR-LPYDVtrfMIECD--VCQ-DWFHGSCVGVEEDKAAEidlYHCPNC 53
Cdd:cd15585     1 YCICNqVSYGE---MVGCDndDCPiEWFHYGCVGLTEAPKGK---WYCPQC 45

PHD finger found in PYGO proteins; The family includes Drosophila melanogaster protein pygopus (dPYGO) and its two homologs, PYGO1 and PYGO2. dPYGO is a fundamental Wnt signaling transcriptional component in Drosophila. PYGO1 is essential for the association with Legless (Lgs)/Bcl9 that acts an adaptor between Pygopus (Pygo) and Arm/beta-catenin. dPYGO and PYGO2 function as context-dependent beta-catenin coactivators, and they bind di- and trimethylated lysine 4 of histone H3 (H3K4me2/3). Moreover, PYGO2 acts as a histone methylation reader, and a chromatin remodeler in a testis-specific and Wnt-unrelated manner. It also mediates chromatin regulation and links Wnt signaling and Notch signaling to suppress the luminal/alveolar differentiation competence of mammary stem and basal cells. PYGO2 also plays a new role in rRNA transcription during cancer cell growth. It regulates mammary tumor initiation and heterogeneity in MMTV-Wnt1 mice. All family members contain a plant homeodomain (PHD) finger.

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gi 528518168   21 IECDV-CQDWFHGSCVGVEED-----KAAEIDLYHCPNC 53
Cdd:cd15551    16 ILCESsCNKWFHRTCTGLTESaydllTSEESAEWVCDSC 54