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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 30697367 114 RCVCGNSLETDSMIQCEDprCHVWQHVGCVILPDKPMDGNPPLPESFYCEIC 165
Cdd:cd15570   1 RCPCGSSMEDGSMIQCEG--CKTWQHMDCVLIPDKPADGLPELPSKFYCELC 50

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 30697367 114 RCVCGNSLETDSMIQCEDprCHVWQHVGCVILPDKPMDGNPPLPESFYCEIC 165
Cdd:cd15570   1 RCPCGSSMEDGSMIQCEG--CKTWQHMDCVLIPDKPADGLPELPSKFYCELC 50

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        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 30697367    115 CVCGNSLETDSMIQCEdpRCHVWQHVGCVILPDKPmdgnPPLPESFYCEIC 165
Cdd:smart00249   3 SVCGKPDDGGELLQCD--GCDRWYHQTCLGPPLLE----EEPDGKWYCPKC 47

SAP domain; The SAP (after SAF-A/B, Acinus and PIAS) motif is a putative DNA/RNA binding domain found in diverse nuclear and cytoplasmic proteins.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 30697367    11 LSYFRIKELKDVLTQLGLSKQGKKQELVDRILTLL 45
Cdd:pfam02037   1 LSKLTVAELKEELRKRGLPTSGKKAELIERLQEYL 35

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 30697367 114 RCVCGNSLETDSMIQCEDprCHVWQHVGCVILPDKPMDGNPPLPESFYCEIC 165
Cdd:cd15570   1 RCPCGSSMEDGSMIQCEG--CKTWQHMDCVLIPDKPADGLPELPSKFYCELC 50

SP-RING finger found in the Siz/PIAS RING (SP-RING) family of SUMO E3 ligases; The SP-RING family includes PIAS (protein inhibitor of activated STAT) proteins, Zmiz proteins, and Siz proteins from plants and fungi. PIAS proteins modulate the activity of several transcription factors and act as E3 ubiquitin ligases in the sumoylation pathway. There are four members: PIAS1, PIAS2 (also known as PIASx), PIAS3, and PIAS4 (also known as PIASy). PIAS proteins were initially identified as inhibitors of activated STAT only, but are now known to interact with and modulate several other proteins, including androgen receptor (AR), tumor suppressor p53, and the transforming growth factor-beta (TGF-beta) signaling protein SMAD. They interact with STATs in a cytokine-dependent manner. PIAS proteins have SUMO E3-ligase activity and interaction of PIAS proteins with transcription factors often results in sumoylation of that protein. Zmiz1 (Zimp10) and its homolog Zmiz2 (Zimp7) were initially identified in humans as androgen receptor (AR) interacting proteins that function as transcriptional co-activators. They interact with BRG1, the catalytic subunit of the SWI-SNF remodeling complex. They also associate with other hormone nuclear receptors and transcription factors such as p53 and Smad3/Smad4, and regulate transcription of specific target genes by altering their chromatin structure. SIZ1 proteins from plants and fungi are also founding members of this family. SIZ1-mediated conjugation of SUMO1 and SUMO2 to other intracellular proteins is essential in Arabidopsis. Yeast SIZ proteins are SUMO E3 ligases involved in a novel pathway of chromosome maintenance. They enhance SUMO modification to many substrates in vivo, but also exhibit unique substrate specificity. PIAS proteins contain a specific RING finger known as Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING (SP-RING) finger, which is essential for SUMO ligase activity. The SP-RING finger is a variant of the RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It binds a single Zn ion, instead of two ions bound by typical RING fingers.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 30697367 361 LRCPMSGSRIKVAGRFLPCVHMGCFDLDVFVELNQRSRKWQCPICLK 407
Cdd:cd16650   2 LRCPLSLKRIKTPARGKHCKHLQCFDLDSYLEFNKRKPTWKCPICDK 48

SP-RING finger found in zinc finger MIZ domain-containing protein 1 (Zmiz1) and similar proteins; Zmiz1, also known as PIAS-like protein Zimp10 (zinc finger-containing, Miz1, PIAS-like protein on chromosome 10) or retinoic acid-induced protein 17, is a novel PIAS-like protein that was initially identified as an androgen receptor (AR) interacting protein and functions as a transcriptional co-activator. It co-localizes with AR and small ubiquitin-like modifier SUMO-1, forms a protein complex at replication foci in the nucleus, and augments AR-mediated transcription. It also functions as a transcriptional co-activator of the p53 tumor suppressor that plays a critical role in cell cycle progression, DNA repair, and apoptosis. Moreover, Zmiz1 dysfunction may be associated with multiple autoimmune diseases and it has been implicated in the development, function, and survival of melanocytes. Zmiz1 also interacts with Smad3/4 proteins and augments Smad-mediated transcription, suggesting it is important in the regulation of the transforming growth factor beta (TGF-beta)/Smad signaling pathway and may have an inhibitory effect on the immune system. Zmiz1 is overexpressed in a significant percentage of human cutaneous squamous cell carcinoma (SCC), breast, ovarian, and colon cancers, suggesting it may play a broader role in epithelial cancers. It functionally interacts with NOTCH1 to promote C-MYC transcription and activity, and thus is involved in a variety of C-MYC-driven cancers. Zmiz1 contains a PAT domain, a highly conserved Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING (SP-RING) finger, also known as msx-interacting zinc finger (Miz domain), and a putative nuclear localization sequence (NLS), as well as a strong intrinsic transactivation domain within the C-terminus. The SP-RING finger is a variant of RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It binds a single Zn ion, instead of two ions bound by typical RING fingers.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30697367 359 VNLRCPMSGSRIKVAGRFLPCVHMGCFDLDVFVELNQRSRKWQCPICLKNYSVEHVIVDPY 419
Cdd:cd16822   2 VSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQY 62

SP-RING finger found in zinc finger MIZ domain-containing protein Zmiz1, Zmiz2, and similar proteins; This subfamily includes Zmiz1 (Zimp10) and its homolog Zmiz2 (Zimp7), both initially identified in humans as androgen receptor (AR) interacting proteins which function as transcriptional co-activators. They interact with BRG1, the catalytic subunit of the SWI-SNF remodeling complex. They also associate with other hormone nuclear receptors and transcription factors, such as p53 and Smad3/Smad4, and regulate transcription of specific target genes by altering their chromatin structure. This subfamily also includes tonalli (Tna), an ortholog identified in Drosophila. It genetically interacts with the ATP-dependent SWI/SNF and Mediator complexes, suggesting a potential role for the Zmiz proteins in chromatin remodeling. Zmiz proteins contain a highly conserved Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING (SP-RING) finger, also known as msx-interacting zinc finger (Miz domain), and a strong transactivation domain within the C-terminus. The SP-RING/Miz domain is highly conserved in members of the PIAS family and confers SUMO-conjugating activity. It is a variant of the RING finger, and lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It binds a single Zn ion, instead of two ions bound by typical RING fingers. The strong intrinsic transactivation domain facilitates Zmiz proteins to augment the transcriptional activity of nuclear hormone receptors and other transcriptional factors. They may act as transcriptional co-regulators.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 30697367 360 NLRCPMSGSRIKVAGRFLPCVHMGCFDLDVFVELNQRSRKWQCPICLK 407
Cdd:cd16791   1 SLKCPITFRRITLPARGHDCKHIQCFDLESYLQLNCERGTWRCPVCNK 48

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        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 30697367 114 RCVCGNSLETDSMIQCEdpRCHVWQHVGCV-ILPDKPmdgnpplPESFYCEIC 165
Cdd:cd15550   1 RCICGFEHDDGFMICCD--KCSVWQHGDCMgIDRENI-------PDSYLCEQC 44

SP-RING finger found in protein inhibitor of activated STAT protein 4 (PIAS4) and similar proteins; PIAS4, also known as PIASy or protein inhibitor of activated STAT protein gamma (PIAS-gamma), is an E3 SUMO-protein ligase that interacts with the androgen receptor (AR) and is involved in ubiquitin signaling pathways. It is associated with macro/microcephaly in the novel interstitial 19p13.3 microdeletion/microduplication syndrome. It also regulates the hypoxia signalling pathway by interacting with the tumor suppressor von Hippel-Lindau (VHL), which leads to VHL sumoylation, oligomerization, and impaired function during growth of pancreatic cancer cells. Moreover, PIAS4 acts as a direct binding partner for vitamin D receptor (VDR) and facilitates its modification with SUMO2. The process of SUMOylation modulates VDR-mediated signaling. As components of the DNA-damage response (DDR), PIAS4 together with PIAS1 promote responses to DNA double-strand breaks (DSBs). They are required for effective ubiquitin-adduct formation mediated by RNF8, RNF168, and BRCA1 at sites of DNA damage. PIAS4 contains an N-terminal SAP (scaffold attachment factor A/B (SAF-A/B), acinus and PIAS) box with the LXXLL signature, a PINT motif, a specific RING finger known as Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING (SP-RING) finger, and an acidic C-terminal domain. The SP-RING finger is a variant of RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It binds a single Zn ion, instead of two ions bound by typical RING fingers.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 30697367 359 VNLRCPMSGSRIKVAGRFLPCVHMGCFDLDVFVELNQRSRKWQCPICLK 407
Cdd:cd16821   5 VSLICPLVKMRLSVPCRAETCAHLQCFDAVFYLQMNEKKPTWTCPVCDK 53

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        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 30697367    115 CVCGNSLETDSMIQCEdpRCHVWQHVGCVILPDKPmdgnPPLPESFYCEIC 165
Cdd:smart00249   3 SVCGKPDDGGELLQCD--GCDRWYHQTCLGPPLLE----EEPDGKWYCPKC 47

SP-RING finger found in Saccharomyces cerevisiae E3 SUMO-protein ligase SIZ1, SIZ2, and similar proteins; Saccharomyces cerevisiae SIZ proteins, also known as SAP and Miz-finger domain-containing proteins, are Siz/PIAS RING (SP-RING) family SUMO E3 ligases, and may be involved in a novel pathway of chromosome maintenance. They enhance SUMO modification with many substrates in vivo, but also exhibit unique substrate specificity. SIZ1, also known as ubiquitin-like protein ligase 1 (Ull1), modifies both cytoplasmic and nuclear proteins. It functions as an E3 factor specific for septin components. SIZ1-dependent substrates include Cdc3 and Cdc11 (septin subunits), Prp45 (a splicing factor), and the proliferating cell nuclear antigen (PCNA). SIZ2, also known as NFI1, interacts with Smt3, SUMO/Smt3 conjugating enzyme Ubc9, and a septin component Cdc3. Members of this subfamily contain an N-terminal SAP (scaffold attachment factor A/B (SAF-A/B), acinus and PIAS) box with the LXXLL signature, a PINT motif, a specific RING finger known as Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING (SP-RING) finger, and an acidic C-terminal domain. The SP-RING finger is a variant of RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It binds a single Zn ion, instead of two ions bound by typical RING fingers.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 30697367 359 VNLRCPMSGSRIKVAGRFLPCVHMGCFDLDVFVELNQRSRKWQCPIC 405
Cdd:cd16793   4 MSLQCPISYTRMKYPSKSINCKHLQCFDALWFLHSQLQIPTWQCPVC 50

SAP domain; The SAP (after SAF-A/B, Acinus and PIAS) motif is a putative DNA/RNA binding domain found in diverse nuclear and cytoplasmic proteins.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 30697367    11 LSYFRIKELKDVLTQLGLSKQGKKQELVDRILTLL 45
Cdd:pfam02037   1 LSKLTVAELKEELRKRGLPTSGKKAELIERLQEYL 35

PHD finger found in Schizosaccharomyces pombe meiosis-specific protein hop1 (Hop1p) and similar proteins; Fission yeast Hop1p, also termed linear element-associated protein hop1, is an S. pombe homolog of the synaptonemal complex (SC)-associated protein Hop1 in Saccharomyces cerevisiae. In contrast to S. cerevisiae, S. pombe forms thin threads, known as linear elements (LinEs), in meiotic nuclei, instead of a canonical synaptonemal complex. LinEs contain Rec10 protein and are evolutionary relics of SC axial elements. Fission yeast Hop1p is a linear element (LinE)-associated protein. It also associates with Rec10, which plays a role in recruiting the recombination machinery to chromatin. Hop1p contains an N-terminal HORMA (for Hop1p, Rev7p, and MAD2) domain and a C-terminal plant homeodomain (PHD) finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 30697367 114 RCVCGNSLETDSMIQCEdpRCHVWQHVGCVILPDkpmDGNPPLPESFYCEIC 165
Cdd:cd15558   1 RCECGDWGEDGAMIQCA--FCDTWQHLLCYGFES---AKDPRIPDIHVCYRC 47

PHD finger found in PHD finger protein 20 (PHF20); PHF20, also termed Glioma-expressed antigen 2, or hepatocellular carcinoma-associated antigen 58, or novel zinc finger protein, or transcription factor TZP (referring to Tudor and zinc finger domain containing protein), is a regulator of NF-kappaB activation by disrupting recruitment of PP2A to p65. It also functions as a transcription factor that binds Akt and plays a role in Akt cell survival/growth signaling. Moreover, it transcriptionally regulates p53. The phosphorylation of PHF20 on Ser291 mediated by protein kinase B (PKB) is essential in tumorigenesis via the regulation of p53 mediated signaling. PHF20 contains an N-terminal malignant brain tumor (MBT) domain, two Tudor domains, a plant homeodomain (PHD) finger and the putative DNA-binding domains, AT hook and Cys2His2-type zinc finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 30697367 114 RCVCGNSLETDSMIQCEDprCHVWQHVGCV-ILPDKpmdgnppLPESFYCEIC 165
Cdd:cd15634   1 RCICEVQEENDFMIQCEE--CLCWQHGVCMgLLEDN-------VPEKYTCYIC 44

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        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 30697367 113 VRCVCGNSLETDSMIQCEdpRCHVWQHVGCVilpdkpmdGNPPLPESFYCEIC 165
Cdd:cd15548   1 IRCICGLYKDEGLMIQCE--KCMVWQHCDCM--------GVNDDVEHYLCEQC 43

PHD finger found in PHD finger protein 20 (PHF20) and PHD finger protein 20-like protein 1 (P20L1); PHF20, also termed Glioma-expressed antigen 2, or hepatocellular carcinoma-associated antigen 58, or novel zinc finger protein, or transcription factor TZP (referring to Tudor and zinc finger domain containing protein), is a regulator of NF-kappaB activation by disrupting recruitment of PP2A to p65. It also functions as a transcription factor that binds Akt and plays a role in Akt cell survival/growth signaling. Moreover, it transcriptionally regulates p53. The phosphorylation of PHF20 on Ser291 mediated by protein kinase B (PKB) is essential in tumorigenesis via the regulation of p53 mediated signaling. P20L1 is an active malignant brain tumor (MBT) domain-containing protein that binds to monomethylated lysine 142 on DNA (Cytosine-5) Methyltransferase 1 (DNMT1) (DNMT1K142me1) and colocalizes at the perinucleolar space in a SET7-dependent manner. Its MBT domain reads and controls enzyme levels of methylated DNMT1 in cells, thus representing a novel antagonist of DNMT1 proteasomal degradation. Both PHF20 and PHF20L1 contain an N-terminal MBT domain, two Tudor domains, a plant homeodomain (PHD) finger and the putative DNA-binding domains, AT hook and Cys2His2-type zinc finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 30697367 114 RCVCGNSLETDSMIQCEDprCHVWQHVGCVILpdkpmDGNPPLPESFYCEIC 165
Cdd:cd15549   1 HCICGVNEENGLMIQCEL--CLCWQHGVCMGI-----EEEESVPERYVCYVC 45

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        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 30697367 113 VRCVCGNSLETDSMIQCEdpRCHVWQHVGCVILPDKPMDGnpplPESFYCEIC 165
Cdd:cd15517   3 GICNLETAAVDELWVQCD--GCDKWFHQFCLGLSNERYAD----EDKFKCPNC 49

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        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 30697367 113 VRCVCGNSLETDSMIQCEDprCHVWQHVGCVilpdKPMDGNppLPESFYCEICR 166
Cdd:cd15632   2 VTCFCMKPFAGRPMIECNE--CHTWIHLSCA----KIRKSN--VPEVYVCQKCR 47