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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036920   374 LNIEMQLKAYEIEKRLSTADLFRFPNFETICWYVGKHILDIFRGLRENRRHPASYLVHGGKALNLAFRAWTRKEALPDHE 453
Cdd:pfam17811    1 LNIEMQLRAYEIEKRLKTPDLFKFPNFETICWYVAKHLLETLRELREEGRRPAEYLVRGVKALLIALKSWTRKEALTEHE 80

                           90       100
                   ....*....|....*....|....
gi 768036920   454 DEIPETVRTVQLIKDLAREIRLVE 477
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 768036920   270 YCLMSVRDSYTDFHIDFGGT-SVWYHVLKGEKIFYLIrPTNANLTLFECWSSSSNQN----EMFFGDQVD---------K 335
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLySINYLHFGAPKVWYII-PPEYAEKFEKVLSDHFGGEqpddLLHLNTIISpkqlrengiP 79

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 768036920   336 CYKCSVKQGQTLFIPTGWIHAVLTPVDCLAFGGNF 370
Cdd:pfam02373   80 VYRFVQKPGEFVFTFPGWYHQVFNLGFNIAEAVNF 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 768036920   374 LNIEMQLKAYEIEKRLSTADLFRFPNFETICWYVGKHILDIFRGLRENRRHPASYLVHGGKALNLAFRAWTRKEALPDHE 453
Cdd:pfam17811    1 LNIEMQLRAYEIEKRLKTPDLFKFPNFETICWYVAKHLLETLRELREEGRRPAEYLVRGVKALLIALKSWTRKEALTEHE 80

                           90       100
                   ....*....|....*....|....
gi 768036920   454 DEIPETVRTVQLIKDLAREIRLVE 477
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 768036920   270 YCLMSVRDSYTDFHIDFGGT-SVWYHVLKGEKIFYLIrPTNANLTLFECWSSSSNQN----EMFFGDQVD---------K 335
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLySINYLHFGAPKVWYII-PPEYAEKFEKVLSDHFGGEqpddLLHLNTIISpkqlrengiP 79

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 768036920   336 CYKCSVKQGQTLFIPTGWIHAVLTPVDCLAFGGNF 370
Cdd:pfam02373   80 VYRFVQKPGEFVFTFPGWYHQVFNLGFNIAEAVNF 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 768036920     43 YC-LCRLPYDvTRFMIECDMCQDWFHGSCVGVEEEKAADIDLYHCPNC 89
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 768036920   374 LNIEMQLKAYEIEKRLSTADLFRFPNFETICWYVGKHILDIFRGLRENRRHPASYLVHGGKALNLAFRAWTRKEALPDHE 453
Cdd:pfam17811    1 LNIEMQLRAYEIEKRLKTPDLFKFPNFETICWYVAKHLLETLRELREEGRRPAEYLVRGVKALLIALKSWTRKEALTEHE 80

                           90       100
                   ....*....|....*....|....
gi 768036920   454 DEIPETVRTVQLIKDLAREIRLVE 477
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 768036920   43 YCLCRLPYDVTRFMIECDMCQDWFHGSCVGVEEEKAADIDLYHCPNC 89
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
                  ....*....|....*....|....*....|....*....|....*...
gi 768036920   43 YCLCRLPYDVTRFMIECDMCQDWFHGSCVGVEEEKAADIDLYHCPNCE 90
Cdd:cd15641     1 YCICRLPYDVTRFMIECDACKDWFHGSCVGVEEEEAPDIDIYHCPNCE 48

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 768036920   43 YCLCRLPYDvTRFMIECDMCQDWFHGSCVGVEEEK----AADIDLYHCPNC 89
Cdd:cd15552     1 YCICRKPHN-NRFMICCDRCEEWFHGDCVGITEAQgkemEENIEEYVCPKC 50

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 768036920   270 YCLMSVRDSYTDFHIDFGGT-SVWYHVLKGEKIFYLIrPTNANLTLFECWSSSSNQN----EMFFGDQVD---------K 335
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLySINYLHFGAPKVWYII-PPEYAEKFEKVLSDHFGGEqpddLLHLNTIISpkqlrengiP 79

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 768036920   336 CYKCSVKQGQTLFIPTGWIHAVLTPVDCLAFGGNF 370
Cdd:pfam02373   80 VYRFVQKPGEFVFTFPGWYHQVFNLGFNIAEAVNF 114

A domain family that is part of the cupin metalloenzyme superfamily; Probable enzymes, but of unknown functions, that regulate chromatin reorganisation processes (Clissold and Ponting, in press).

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 768036920    235 RLSNLVETPKivrKLSWVENLWPEecvFERPNVQKYCLMSVRDSYTDFHIDFGGTSVWYHVLKG 298
Cdd:smart00558    1 QLWNLAKLPF---KLNLLSDLPED---IPGPDVGPYLYMGMAGSTTPWHIDDYDLVNYLHQGAG 58

PHD finger found in Transcription factor 19 (TCF-19), Lysine-specific demethylase KDM5A and KDM5B, and other similar proteins; TCF-19 was identified as a putative trans-activating factor with expression beginning at the late G1-S boundary in dividing cells. It 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. 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 interaction 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. This family also includes Caenorhabditis elegans Lysine-specific demethylase 7 homolog (ceKDM7A). ceKDM7A (also termed JmjC domain-containing protein 1.2, PHD finger protein 8 homolog, or PHF8 homolog) is a plant homeodomain (PHD)- and JmjC domain-containing protein that functions as a histone demethylase specific for H3K9me2 and H3K27me2. The binding of the PHD finger to H3K4me3 guides H3K9me2- and H3K27me2-specific demethylation by its catalytic JmjC domain in a trans-histone regulation mechanism. In addition, this family includes plant protein OBERON 1 and OBERON 2, Alfin1-like (AL) proteins, histone acetyltransferases (HATs) HAC, and AT-rich interactive domain-containing protein 4 (ARID4).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 768036920   46 CRLP-YDVTRFMIECDMCQDWFHGSCVGVEEEKAADIDLYHCPNC 89
Cdd:cd15517     5 CNLEtAAVDELWVQCDGCDKWFHQFCLGLSNERYADEDKFKCPNC 49

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 768036920   43 YCLCRLPYDvTRFMIECDMCQDWFHGSCVGVEEEKAADIDLYHCPNC 89
Cdd:cd16039     1 YCICQKPDD-GRWMIACDGCDEWYHFTCVNIPEADVELVDSFFCPPC 46

PHD finger found in transcription initiation factor TFIID subunit 3 (TAF3); TAF3 (also termed 140 kDa TATA box-binding protein-associated factor, TBP-associated factor 3, transcription initiation factor TFIID 140 kDa subunit (TAF140), or TAFII-140, is an integral component of TFIID) is a general initiation factor (GTF) that plays a key role in preinitiation complex (PIC) assembly through core promoter recognition. The interaction of H3K4me3 with TAF3 directs global TFIID recruitment to active genes, which regulates gene-selective functions of p53 in response to genotoxic stress. TAF3 is highly enriched in embryonic stem cells and is required for endoderm lineage differentiation and prevents premature specification of neuroectoderm and mesoderm. Moreover, TAF3, along with TRF3, forms a complex that is essential for myogenic differentiation. TAF3 contains a plant homeodomain (PHD) finger. This family also includes Drosophila melanogaster BIP2 (Bric-a-brac interacting protein 2) protein, which functions as an interacting partner of D. melanogaster p53 (Dmp53).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 768036920   43 YC-LCRLPYDVtRFMIECDMCQDWFHGSCVGVEEEkAADIDLYHCPNC 89
Cdd:cd15522     1 ICpICKKPDDG-SPMIGCDECDDWYHWECVGITDE-PPEEDDWFCPKC 46

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 768036920   43 YCLCRLPydVTRFMIECDMCQDWFHGSCVG 72
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 768036920   45 LCRLPYDvTRFMIECDMCQDWFHGSCVGVEEEKAADIDL----YHCPNC 89
Cdd:cd15638     4 FCKKPHG-NRFMVGCGRCDDWFHGDCVGLSLSQAQQMEEedkeYVCVKC 51

PHD finger 3 found in Lysine-specific demethylase 5A (KDM5A), 5B (KDM5B), and similar proteins; The family includes KDM5A and KDM5B, both of which belong to the JARID subfamily within the JmjC proteins. KDM5A, also termed Histone demethylase JARID1A, or 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 the trimethylated histone H3 lysine 4 (H3K4me3) demethylase. It also displays DNA-binding activities that can recognize the specific DNA sequence CCGCCC. 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), 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 asTIEG1/KLF10 (transforming growth factor-beta inducible early gene-1/Kruppel-like transcription factor 10), and possibly function as a transcriptional corepressor. The family also includes the 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 three plant homeodomain (PHD) fingers. This model corresponds to the third PHD finger.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 768036920   59 CDMCQDWFHGSCVGVEEEKAADIDLYHCPNC 89
Cdd:cd15610    20 CDGCEEWFHLLCVGLSPEEVAEDEDYICPSC 50

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
                   ....*....|....*....|....*....|....*....|....*....
gi 768036920    43 YC-LCRLPyDVTRFMIECDMCQDWFHGSCVGVEEEKAADID-LYHCPNC 89
Cdd:pfam00628    1 YCaVCGKS-DDGGELVQCDGCDDWFHLACLGPPLDPAEIPSgEWLCPEC 48

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 768036920   46 CRLPYDVTRFMIECDMCQDWFHGSCVGVEEEKAADIDL-YHCP 87
Cdd:cd15609     7 CCLPQDETVSWVQCDDCDQWYHVACVGCDYNAVKDPDAdFHCG 49

PHD finger found in PHD finger protein 23 (PHF23); PHF23, also termed PHD-containing protein JUNE-1, is a hypothetical protein with a plant homeodomain (PHD) finger. It is encoded by gene PHF23 that acts as a candidate fusion partner for the nucleoporin gene NUP98. The NUP98-PHF23 fusion results from a cryptic translocation t(11;17)(p15;p13) in acute myeloid leukemia (AML).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 768036920   44 CLCRLPYdVTRFMIECDMCQDWFHGSCVGVEEEKAADIdlYHCPNC 89
Cdd:cd15631     2 CYCGKPF-AGRPMIECSQCGTWIHLSCAKIKKSNVPDF--FYCQKC 44

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 768036920   43 YCLCRLPYDVTrfMIECD--MCQ-DWFHGSCVGVeeeKAADIDLYHCPNC 89
Cdd:cd15505     1 YCICNQVSYGE--MVACDnpNCPiEWFHFECVGL---TAKPKGKWYCPEC 45

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 768036920   44 CLCRLPYDVTrfMIECDMCQDWFHGSCVGV 73
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 768036920   42 VYCLCRLpYDVTRFMIECDMCQDWFHGSCVGVEeekaADIDLYHCPNC 89
Cdd:cd15548     1 IRCICGL-YKDEGLMIQCEKCMVWQHCDCMGVN----DDVEHYLCEQC 43

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.

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                  ....*....|....*....|....*....|....*....|....*...
gi 768036920   42 VYCLCRLPYdVTRFMIECDMCQDWFHGSCVGVEEEKAADIdlYHCPNC 89
Cdd:cd15632     2 VTCFCMKPF-AGRPMIECNECHTWIHLSCAKIRKSNVPEV--YVCQKC 46

PHD finger found in E3 ubiquitin-protein ligase SHPRH; SHPRH, also termed SNF2, histone-linker, PHD and RING finger domain-containing helicase, belongs to the SWI2/SNF2 family of ATP-dependent chromatin remodeling enzymes, containing the Cys3HisCys4 RING-finger characteristic of E3 ubiquitin ligases. It plays a key role in the error-free branch of DNA damage tolerance. As functional homologs of Saccharomyces cerevisiae Rad5, SHPRH and its closely-related protein, helicase like transcription factor (HLTF), act as ubiquitin ligases that cooperatively mediate Ubc13-Mms2-dependent polyubiquitination of proliferating cell nuclear antigen (PCNA) and maintain genomic stability. SHPRH contains a SNF2 domain, a H1.5 (linker histone H1 and H5) domain, a plant homeodomain (PHD) finger, a Cys3HisCys4 RING-finger, and a C-terminal helicase domain.

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                  ....*....|....*....|....*....|...
gi 768036920   57 IECDMCQDWFHGSCVGVEEEkAADIDLYHCPNC 89
Cdd:cd15547    16 VQCLKCGLWQHAECVNYDEE-SDKREPYLCPHC 47

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 768036920   57 IECD-MCQDWFHGSCVGVEEEKAADIDlYHCPNC 89
Cdd:cd15687    18 VQCDgSCNRWFHQVCVGVSAEMAEKED-YICVSC 50

PHD finger 2 found in lysine-specific demethylase 5B (KDM5B); KDM5B (also termed Cancer/testis antigen 31 (CT31), Histone demethylase JARID1B, Jumonji/ARID domain-containing protein 1B (JARID1B), retinoblastoma-binding protein 2 homolog 1 (RBP2-H1 or RBBP2H1A), or PLU-1) 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 second PHD finger.

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gi 768036920   44 CLCRLPYDVTrfMIECDMCQDWFHGSCVGVEEEkAADIDLYHCPNC 89
Cdd:cd15607     2 CVCQKAPMAP--MIQCELCRDAFHSGCVTAPSD-PQGPQAWLCPQC 44

PHD finger 2 found in polycomb repressive complex 2 (PRC2)-associated polycomb-like (PCL) family proteins MTF2, PHF19, and similar proteins; The PCL family includes PHD finger protein1 (PHF1) and its homologs metal-response element-binding transcription factor 2 (MTF2/PCL2) and PHF19/PCL3, which are accessory components of the Polycomb repressive complex 2 (PRC2) core complex and all contain an N-terminal Tudor domain followed by two plant homeodomain (PHD) fingers, and a C-terminal MTF2 domain. PCL proteins specifically recognize tri-methylated H3K36 (H3K36me3) through their N-terminal Tudor domains. The interaction between their Tudor domains and H3K36me3 is critical for both the targeting and spreading of PRC2 into active chromatin regions and for the maintenance of optimal repression of poised developmental genes where PCL proteins, H3K36me3, and H3K27me3 coexist. Moreover, unlike other PHD finger-containing proteins, the first PHD finger of PCL proteins do not display histone H3K4 binding affinity and they do not affect the Tudor domain binding to histones. This model corresponds to the second PHD finger.

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gi 768036920   43 YCLCRLPYDVTRFMIECDMCQDWFHGSCV 71
Cdd:cd15503     1 YCYCGGPGEWNLKMLQCCKCRQWFHEACL 29

PHD finger found in yeast orthologs of ING tumor suppressor family; The yeast orthologs of the plant homeodomain (PHD) finger-containing ING tumor suppressor family consists of chromatin modification-related protein YNG1 (Yng1p), YNG2 (Yng2p), and transcriptional regulatory protein PHO23 (Pho23p). Yng1p, also termed ING1 homolog 1, is one of the components of the NuA3 histone acetyltransferase (HAT) complex. Its PHD finger binding to H3 Trimethylated at K4 (H3K4me3) promotes NuA3 H3 HAT activity at K14 of H3 on chromatin. Yng2p, also termed ESA1-associated factor 4, or ING1 homolog 2, is a subunit of the NuA4 HAT complex. It plays a critical role in intra-S-phase DNA damage response. Pho23p is part of the Rpd3/Sin3 histone deacetylase (HDAC) complex. It is required for the normal function of Rpd3 in the silencing of rDNA, telomeric, and mating-type loci. Yng1p and Pho23p inhibit p53-dependent transcription. In contrast, Yng2p has the opposite effect. All family members contain an N-terminal ING histone-binding domain and a C-terminal PHD finger.

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gi 768036920   43 YCLC-RLPYDVtrfMIECD--MCQ-DWFHGSCVGVEEEKAADidlYHCPNCEV 91
Cdd:cd15587     1 YCYCrRVSFGE---MVACDnpDCKiEWFHFECVGLTETPKGK---WYCSDCKV 47

PHD finger found in Schizosaccharomyces pombe Set1 complex component ash2 (spAsh2p) and similar proteins; spAsh2p, also termed Set1C component ash2, or COMPASS component ash2, or complex proteins associated with set1 protein ash2, or Lid2 complex component ash2, or Lid2C component ash2, is orthologous to Drosophila melanogaster Ash2 protein. Both spAsh2p and D. melanogaster Ash2 contain a plant homeodomain (PHD) finger and a SPRY domain. In contrast, its counterpart in Saccharomyces cerevisiae, Bre2p, has no PHD finger and is not included in this family. spAsh2p shows histone H3 Lys4 (H3K4) methyltransferase activity through its PHD finger. It also interacts with Lid2p in S. pombe. Human Ash2L contains an atypical PHD finger that lacks part of the Cys4HisCys3 signature characteristic of PHD fingers, it binds to only one zinc ion through the second half of the motif and does not have histone tail binding activity.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 768036920   43 YCLCRLPYDVTRFMIECDMCQDWFHGSCVGVEEEKAADIDL---YHCPNC 89
Cdd:cd15583     1 YCYCGKDRNLGEVELQCSICLKWFHAKCVSIDNGSCLPFMTnyqFVCKRC 50