PHD finger found in pygopus homolog 1 (PYGO1); PYGO1 is a homolog of Drosophila melanogaster protein pygopus (dPYGO), which is a fundamental Wnt signaling transcriptional component in Drosophila. It functions as a context-dependent beta-catenin coactivator, and binds di- and trimethylated lysine 4 of histone H3 (H3K4me2/3). PYGO1 is essential for the association with Legless (Lgs)/Bcl9 that acts as an adaptor between Pygopus (Pygo) and Arm/beta-catenin. PYGO1 contains a plant homeodomain (PHD) finger, which is important for Lgs/Bcl9 recognition as well as for the regulation of the Wnt/beta-catenin signaling pathway.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 99028874 339 YPCGICTNEVNDDQDAILCEASCQKWFHRICTGMTETAYGLLTAEASAVWGCDTCMA 395
Cdd:cd15635   1 YPCGICTNEVNDDQDAILCEASCQKWFHRICTGMTETAYGLLTAEASAVWGCDTCMA 57

PHD finger found in pygopus homolog 1 (PYGO1); PYGO1 is a homolog of Drosophila melanogaster protein pygopus (dPYGO), which is a fundamental Wnt signaling transcriptional component in Drosophila. It functions as a context-dependent beta-catenin coactivator, and binds di- and trimethylated lysine 4 of histone H3 (H3K4me2/3). PYGO1 is essential for the association with Legless (Lgs)/Bcl9 that acts as an adaptor between Pygopus (Pygo) and Arm/beta-catenin. PYGO1 contains a plant homeodomain (PHD) finger, which is important for Lgs/Bcl9 recognition as well as for the regulation of the Wnt/beta-catenin signaling pathway.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 99028874 339 YPCGICTNEVNDDQDAILCEASCQKWFHRICTGMTETAYGLLTAEASAVWGCDTCMA 395
Cdd:cd15635   1 YPCGICTNEVNDDQDAILCEASCQKWFHRICTGMTETAYGLLTAEASAVWGCDTCMA 57

PHD finger found in pygopus homolog 1 (PYGO1); PYGO1 is a homolog of Drosophila melanogaster protein pygopus (dPYGO), which is a fundamental Wnt signaling transcriptional component in Drosophila. It functions as a context-dependent beta-catenin coactivator, and binds di- and trimethylated lysine 4 of histone H3 (H3K4me2/3). PYGO1 is essential for the association with Legless (Lgs)/Bcl9 that acts as an adaptor between Pygopus (Pygo) and Arm/beta-catenin. PYGO1 contains a plant homeodomain (PHD) finger, which is important for Lgs/Bcl9 recognition as well as for the regulation of the Wnt/beta-catenin signaling pathway.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 99028874 339 YPCGICTNEVNDDQDAILCEASCQKWFHRICTGMTETAYGLLTAEASAVWGCDTCMA 395
Cdd:cd15635   1 YPCGICTNEVNDDQDAILCEASCQKWFHRICTGMTETAYGLLTAEASAVWGCDTCMA 57

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 99028874 340 PCGICTNEVNDDQDAILCEASCQKWFHRICTGMTETAYGLLTAEASAVWGCDTC 393
Cdd:cd15551   1 PCGICNNEVNDDDDAILCESSCNKWFHRTCTGLTESAYDLLTSEESAEWVCDSC 54

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 99028874 340 PCGICTNEVNDDQDA-ILCEaSCQKWFHRICTGMTETAYGLLtaeasAVWGCDTC 393
Cdd:cd15517   1 VCGICNLETAAVDELwVQCD-GCDKWFHQFCLGLSNERYADE-----DKFKCPNC 49

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.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 99028874 340 PCGICTNEVNDDQDAILCEASCQKWFHRICTGMT-ETA 376
Cdd:cd15687   3 PAVSCLQPEGEEVDWVQCDGSCNRWFHQVCVGVSaEMA 40

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 99028874    56 APPPNPNSDHLVAANPFDDSYNTISYKPLPSSNPYLGPGYPGFGGYSTFRMPPHVPPRMSSPYcGPYSLRNQPHPFPQNP 135
Cdd:pfam03154 184 PSPPPPGTTQAATAGPTPSAPSVPPQGSPATSQPPNQTQSTAAPHTLIQQTPTLHPQRLPSPH-PPLQPMTQPPPPSQVS 262

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 99028874   136 L---------GMGFNRPHAFNFGPhdnSNFGNPpynnvltqdinMPGQHFRQGSAENFSQIPPQNVGQVSNPDLASNFAP 206
Cdd:pfam03154 263 PqplpqpslhGQMPPMPHSLQTGP---SHMQHP-----------VPPQPFPLTPQSSQSQVPPGPSPAAPGQSQQRIHTP 328

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 99028874   207 GNNSNFTSPLETNHSFIPP-PNAFGQAKAPLpkqdfTQGATKTPNQNSSTHPPHLNMEDP 265
Cdd:pfam03154 329 PSQSQLQSQQPPREQPLPPaPLSMPHIKPPP-----TTPIPQLPNPQSHKHPPHLSGPSP 383