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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17540064 211 CGGCGKFTHEddlialeeekkkekekplmskkkshhhkkNDFQWIGCDSCQTWYHFLCSGLEQFEYYLYEKFFCPKC 287
Cdd:cd15517   2 CGICNLETAA-----------------------------VDELWVQCDGCDKWFHQFCLGLSNERYADEDKFKCPNC 49

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17540064   600 NLEMQMRVYHLEnairKEIRSEEKFYFPNFELLHWMYMRNvLLEKITEANQEGSDMREQeknIWTASQIMKAEMERWMDR 679
Cdd:pfam17811   2 NIEMQLRAYEIE----KRLKTPDLFKFPNFETICWYVAKH-LLETLRELREEGRRPAEY---LVRGVKALLIALKSWTRK 73

                  ....*..
gi 17540064   680 ELRLGPE 686
Cdd:pfam17811  74 EALTEHE 80

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17540064 211 CGGCGKFTHEddlialeeekkkekekplmskkkshhhkkNDFQWIGCDSCQTWYHFLCSGLEQFEYYLYEKFFCPKC 287
Cdd:cd15517   2 CGICNLETAA-----------------------------VDELWVQCDGCDKWFHQFCLGLSNERYADEDKFKCPNC 49

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17540064   600 NLEMQMRVYHLEnairKEIRSEEKFYFPNFELLHWMYMRNvLLEKITEANQEGSDMREQeknIWTASQIMKAEMERWMDR 679
Cdd:pfam17811   2 NIEMQLRAYEIE----KRLKTPDLFKFPNFETICWYVAKH-LLETLRELREEGRRPAEY---LVRGVKALLIALKSWTRK 73

                  ....*..
gi 17540064   680 ELRLGPE 686
Cdd:pfam17811  74 EALTEHE 80

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
                   ....*....|....*....|....*....|....*....|...
gi 17540064    482 EYLPED-QRPKVEQFCLAGMAGSYTDFHVDFGGSSVYYHILKG 523
Cdd:smart00558  16 SDLPEDiPGPDVGPYLYMGMAGSTTPWHIDDYDLVNYLHQGAG 58

Peptidase family M13; M13 peptidases are well-studied proteases found in a wide range of organizms including mammals and bacteria. In mammals they participate in processes such as cardiovascular development, blood-pressure regulation, nervous control of respiration, and regulation of the function of neuropeptides in the central nervous system. In bacteria they may be used for digestion of milk.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17540064   384 PGFDLEDVVKIMG-SDYEVDTIDVYNQStYSMKLDtfrKLFRDTKNRPL-----------LYNFLSLEFSD-----NNEM 446
Cdd:pfam05649 223 PGIDWKAYLNAAGlPDVPSDEVIVSQPE-YLKALS---KLLAETPLRTLknyliwrlvrsLAPYLSDEFRDanfefYGTL 298

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 17540064   447 KEIAKPPRFVQEISMVNRLWPDVSGAEYIKllqreEYLPEDQRPKVEQ 494
Cdd:pfam05649 299 SGTKQRPRWKRCVSLVNGLLGEALGRLYVK-----KYFPEEAKARVEE 341

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17540064 211 CGGCGKFTHEddlialeeekkkekekplmskkkshhhkkNDFQWIGCDSCQTWYHFLCSGLEQFEYYLYEKFFCPKC 287
Cdd:cd15517   2 CGICNLETAA-----------------------------VDELWVQCDGCDKWFHQFCLGLSNERYADEDKFKCPNC 49

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17540064   600 NLEMQMRVYHLEnairKEIRSEEKFYFPNFELLHWMYMRNvLLEKITEANQEGSDMREQeknIWTASQIMKAEMERWMDR 679
Cdd:pfam17811   2 NIEMQLRAYEIE----KRLKTPDLFKFPNFETICWYVAKH-LLETLRELREEGRRPAEY---LVRGVKALLIALKSWTRK 73

                  ....*..
gi 17540064   680 ELRLGPE 686
Cdd:pfam17811  74 EALTEHE 80

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
                   ....*....|....*....|....*....|....*....|...
gi 17540064    482 EYLPED-QRPKVEQFCLAGMAGSYTDFHVDFGGSSVYYHILKG 523
Cdd:smart00558  16 SDLPEDiPGPDVGPYLYMGMAGSTTPWHIDDYDLVNYLHQGAG 58

PHD finger 2 and 3 found in bromodomain and PHD finger-containing transcription factor (BPTF); BPTF, also termed nucleosome-remodeling factor subunit BPTF, or fetal Alz-50 clone 1 protein (FAC1), or fetal Alzheimer antigen, functions as a transcriptional regulator that exhibits altered expression and subcellular localization during neuronal development and neurodegenerative diseases such as Alzheimer's disease. It interacts with the human orthologue of the Kelch-like Ech-associated protein (Keap1). Its function and subcellular localization can be regulated by Keap1. Moreover, BPTF is a novel DNA-binding protein that recognizes the DNA sequence CACAACAC and represses transcription through this site in a phosphorylation-dependent manner. Furthermore, BPTF interacts with the Myc-associated zinc finger protein (ZF87/MAZ) and alters its transcriptional activity, which has been implicated in gene regulation in neurodegeneration. Some family members contain two or three plant homeodomain (PHD) fingers, which may be involved in complex formation with histone H3 trimethylated at K4 (H3K4me3). This family corresponds to the second and third PHD fingers.

                        10        20        30
                ....*....|....*....|....*....|....
gi 17540064 254 WIGCDSCQTWYHFLCSGLEQFEYYLYEKFFCPKC 287
Cdd:cd15560  14 YIGCDRCQDWFHGRCVGILQSEAEKIDEYVCPQC 47

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
                ....*....|....*....|....*....|...
gi 17540064 255 IGCDSCQTWYHFLCSGLEQFEYYLYEKFFCPKC 287
Cdd:cd16039  14 IACDGCDEWYHFTCVNIPEADVELVDSFFCPPC 46

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 17540064 250 NDFQWIGCDSCQTWYHFLCSGLEQFEYYLYEKFFCPKC 287
Cdd:cd15610  13 DEVNWVQCDGCEEWFHLLCVGLSPEEVAEDEDYICPSC 50

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
                ....*....|....*....|....*....|...
gi 17540064 255 IGCDSCQTWYHFLCSGLEQFEYYLYEKFFCPKC 287
Cdd:cd15554  15 IECDVCKDWFHGSCVGVEEHQANDIERYHCPNC 47

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
                ....*....|....*....|....*....|....*...
gi 17540064 250 NDFQWIGCDSCQTWYHFLCSGLEQFEYYLYEKFFCPKC 287
Cdd:cd15613  11 ADEFWICCDVCEKWYHGKCVKITPAKAEHIKQYKCPSC 48

PHD finger found in Arabidopsis thaliana histone acetyltransferases (HATs) HAC and similar proteins; This family includes A. thaliana HACs (HAC1/2/4/5/12), which are histone acetyltransferases of the p300/CREB-binding protein (CBP) co-activator family. CBP-type HAT proteins are also found in animals, but absent in fungi. The domain architecture of CBP-type HAT proteins differs between plants and animals. Members in this family contain an N-terminal partially conserved KIX domain, a Zf-TAZ domain, a Cysteine rich CBP-type HAT domain that harbors a plant homeodomain (PHD) finger, a Zf-ZZ domain, and a Zf-TAZ domain. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 17540064 253 QWIGCDSCQTWYHFLCsGL--------EQFEYYlyekffCPKC 287
Cdd:cd15614  38 AWVQCDKCERWQHQIC-GLyngrrnadETAEYV------CPLC 73

PHD finger found in Arabidopsis thaliana PHD finger protein MALE MEIOCYTE DEATH 1 (MMD1), PHD finger protein MALE STERILITY 1 (MS1), and similar proteins; MMD1 is a plant homeodomain (PHD) finger protein expressed in male meiocytes. It is encoded by the gene DUET, which is required for male meiotic chromosome organization and progression. MMD1 has been implicated in the regulation of gene expression during meiosis. The mmd1 mutation triggers cell death in male meiocytes. MS1 is a nuclear transcriptional activator that is important for tapetal development and pollen wall biosynthesis. It contains a Leu zipper-like domain and a PHD finger motif, both of which are essential for its function.

                        10        20        30
                ....*....|....*....|....*....|...
gi 17540064 255 IGCDSCQTWYHFLCSGLEQFEyYLYEKFFCPKC 287
Cdd:cd15556  15 IACDVCEVWQHTRCVGIADNE-EPPDHFLCRRC 46

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
                ....*....|....*....|....*....|...
gi 17540064 255 IGCDSCQTWYHFLCSGLEQFEyyLYEKFFCPKC 287
Cdd:cd15550  14 ICCDKCSVWQHGDCMGIDREN--IPDSYLCEQC 44