forkhead associated (FHA) domain found in transcription factor 19 (TCF-19) and similar proteins; TCF-19, also called 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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117414156   3 PCFQLLRI----GGGRGGDLYTFHPPAgagCTYRLGHRADLCDVALRPQQEPGLISGIHAELHAEPRG-DDWRVSLEDHS 77
Cdd:cd22685    1 PCFQLLRIglsaSRSEPRDLYTFRPDL---CEYRIGRNPEVCDVFLCSSQHPNLISREHAEIHAERDGnGNWKVLIEDRS 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 117414156  78 SQGTLVNNVRLPRGHRLELSDGDLLTFGPEGP------PGTSPSEFYFMFQQV 124
Cdd:cd22685   78 TNGTYVNDVRLQDGQRRELSDGDTITFGHKNGrrvkqwPYQKSSEFYFLFQKV 130

Predicted component of the type VI protein secretion system, contains a FHA domain [Signal transduction mechanisms, Intracellular trafficking, secretion, and vesicular transport];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117414156  19 YTFHPPAGagctyRLGhRADLCDVALRPQQepGLISGIHAELhaepRGDDWRVSLEDHSSQGTLVNN--VRLPRGHRLEL 96
Cdd:COG3456   21 ATFGRGGG-----TIG-RSADCDWVLPDPD--RSVSRRHAEI----RFRDGAFCLTDLSTNGTFLNGsdHPLGPGRPVRL 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117414156  97 SDGDLLTFGPegppgtspseFYFmfqQVRVKPQDFAAITIPRSRGEARVGAGFRPMLPSQGAPQRPLSTFSPAPKATLIL 176
Cdd:COG3456   89 RDGDRLRIGD----------YEI---RVEISGEDEGADDPLAAAPEPAVSSPSNLSDTEAAPDAALAFSFSLDPLEALDE 155

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117414156 177 NSIGSLSkLRPQPLTFSPSWGGPKSLPVPAPPGEM------GTTPSAPPQRNRRKSVHRVLAEL 234
Cdd:COG3456  156 AATEAPA-TADDPPSLLPEDWLPSAAPVADEAAAQaidqlpSAAAPAPEPEPAADADHALLAAL 218

forkhead associated (FHA) domain found in transcription factor 19 (TCF-19) and similar proteins; TCF-19, also called 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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117414156   3 PCFQLLRI----GGGRGGDLYTFHPPAgagCTYRLGHRADLCDVALRPQQEPGLISGIHAELHAEPRG-DDWRVSLEDHS 77
Cdd:cd22685    1 PCFQLLRIglsaSRSEPRDLYTFRPDL---CEYRIGRNPEVCDVFLCSSQHPNLISREHAEIHAERDGnGNWKVLIEDRS 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 117414156  78 SQGTLVNNVRLPRGHRLELSDGDLLTFGPEGP------PGTSPSEFYFMFQQV 124
Cdd:cd22685   78 TNGTYVNDVRLQDGQRRELSDGDTITFGHKNGrrvkqwPYQKSSEFYFLFQKV 130

Forkhead associated (FHA) domain, binds pSer, pThr, pTyr [Signal transduction mechanisms];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117414156  30 TYRLGhRADLCDVALrpqqEPGLISGIHAELhaEPRGDDWRVslED-HSSQGTLVNNVRLPRGHRleLSDGDLLTFGP 106
Cdd:COG1716   22 PLTIG-RAPDNDIVL----DDPTVSRRHARI--RRDGGGWVL--EDlGSTNGTFVNGQRVTEPAP--LRDGDVIRLGK 88

Predicted component of the type VI protein secretion system, contains a FHA domain [Signal transduction mechanisms, Intracellular trafficking, secretion, and vesicular transport];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117414156  19 YTFHPPAGagctyRLGhRADLCDVALRPQQepGLISGIHAELhaepRGDDWRVSLEDHSSQGTLVNN--VRLPRGHRLEL 96
Cdd:COG3456   21 ATFGRGGG-----TIG-RSADCDWVLPDPD--RSVSRRHAEI----RFRDGAFCLTDLSTNGTFLNGsdHPLGPGRPVRL 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117414156  97 SDGDLLTFGPegppgtspseFYFmfqQVRVKPQDFAAITIPRSRGEARVGAGFRPMLPSQGAPQRPLSTFSPAPKATLIL 176
Cdd:COG3456   89 RDGDRLRIGD----------YEI---RVEISGEDEGADDPLAAAPEPAVSSPSNLSDTEAAPDAALAFSFSLDPLEALDE 155

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117414156 177 NSIGSLSkLRPQPLTFSPSWGGPKSLPVPAPPGEM------GTTPSAPPQRNRRKSVHRVLAEL 234
Cdd:COG3456  156 AATEAPA-TADDPPSLLPEDWLPSAAPVADEAAAQaidqlpSAAAPAPEPEPAADADHALLAAL 218

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
                   ....*....|....*....|....*....|....*....
gi 117414156   302 EETVAWVQCDGCDVWFHVACVGCSIQAAREAD-FRCPGC 339
Cdd:smart00249   9 DDGGELLQCDGCDRWYHQTCLGPPLLEEEPDGkWYCPKC 47

Forkhead associated domain; Found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 117414156    31 YRLGHRADLCDVALRPQQepglISGIHAELHAEPRGddwRVSLEDHSS-QGTLVNNVRL 88
Cdd:smart00240   1 VTIGRSSEDCDIQLDGPS----ISRRHAVIVYDGGG---RFYLIDLGStNGTFVNGKRI 52

forkhead associated (FHA) domain found in transcription factor 19 (TCF-19) and similar proteins; TCF-19, also called 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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117414156   3 PCFQLLRI----GGGRGGDLYTFHPPAgagCTYRLGHRADLCDVALRPQQEPGLISGIHAELHAEPRG-DDWRVSLEDHS 77
Cdd:cd22685    1 PCFQLLRIglsaSRSEPRDLYTFRPDL---CEYRIGRNPEVCDVFLCSSQHPNLISREHAEIHAERDGnGNWKVLIEDRS 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 117414156  78 SQGTLVNNVRLPRGHRLELSDGDLLTFGPEGP------PGTSPSEFYFMFQQV 124
Cdd:cd22685   78 TNGTYVNDVRLQDGQRRELSDGDTITFGHKNGrrvkqwPYQKSSEFYFLFQKV 130

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        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 117414156 291 PCAAPCCCLPQEETVAWVQCDGCDVWFHVACVGCSIQAARE-ADFRCPGC 339
Cdd:cd15610    1 SCSAKQCLKPTGDEVNWVQCDGCEEWFHLLCVGLSPEEVAEdEDYICPSC 50

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        40
                 ....*....|....*....|....*....|....*....|....*....
gi 117414156 292 CAAPCCCLPQEETVAWVQCDG-CDVWFHVACVGCSIQAAREADFRCPGC 339
Cdd:cd15687    2 CPAVSCLQPEGEEVDWVQCDGsCNRWFHQVCVGVSAEMAEKEDYICVSC 50

PHD finger 3 found in Lysine-specific demethylase 5A (KDM5A); 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 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 third PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 117414156 292 CAAPCCCLPQEETVAWVQCDG-CDVWFHVACVGCSIQAAREADFRCPGC 339
Cdd:cd15686    3 CAAQNCQRPCKDKVDWVQCDGgCDEWFHQVCVGVSPEMAENEDYICINC 51

FHA domain; The FHA (Forkhead-associated) domain is a phosphopeptide binding motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117414156   31 YRLGhRADLCDVALRPQQepglISGIHAELHaepRGDDWRVSLEDH-SSQGTLVNNVRLPRgHRLELSDGDLLTF 104
Cdd:pfam00498   1 VTIG-RSPDCDIVLDDPS----VSRRHAEIR---YDGGGRFYLEDLgSTNGTFVNGQRLGP-EPVRLKDGDVIRL 66

forkhead associated (FHA) domain found in nibrin and similar proteins; Nibrin (NBN), also called cell cycle regulatory protein p95, or Nijmegen breakage syndrome protein 1 (NBS1), is a novel DNA double-strand break repair protein that is mutated in Nijmegen breakage syndrome. It is a component of the MRE11-RAD50-NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity. Nibrin modulates the DNA damage signal sensing by recruiting PI3/PI4-kinase family members ATM, ATR, and probably DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to the DNA damage sites and activating their functions. It can also recruit MRE11 and RAD50 to the proximity of DSBs by an interaction with the histone H2AX. Nibrin also functions in telomere length maintenance by generating the 3' overhang which serves as a primer for telomerase dependent telomere elongation. Nibrin is a major player in the control of intra-S-phase checkpoint. This subfamily also includes Schizosaccharomyces pombe DNA repair and telomere maintenance protein Nbs1 and Arabidopsis thaliana AtNbs1. SpNbs1 is an FHA domain-containing protein required for DNA damage repair and S-phase DNA damage checkpoint. It is involved in telomere length maintenance and maintenance of chromatin structure. AtNbs1 is a component of MRN complex. It also functions in the very early stages of meiosis. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117414156  18 LYTFHPPAG------AGCTYRLGhRADlCDVALRPQQEpglISGIHAEL---HAEPRGDDW----RVSLEDHSSQGTLVN 84
Cdd:cd22667    3 LLSEQDGAGtsyyllPGGEYTVG-RKD-CDIIIVDDSS---ISRKHATLtvlHPEANLSDPdtrpELTLKDLSKYGTFVN 77

                         90       100
                 ....*....|....*....|.
gi 117414156  85 NVRLPRGHRLELSDGDLLTFG 105
Cdd:cd22667   78 GEKLKGGSEVTLKDGDVITFG 98

forkhead associated (FHA) domain found in checkpoint with forkhead and RING finger domains protein (CHFR); CHFR, also called RING finger protein 196 (RNF196), is a checkpoint protein that delays entry into mitosis in response to stress. It functions as an E3 ubiquitin ligase that ubiquitinates and degrades its target proteins, such as Aurora-A, Plk1, Kif22 and PARP-1, which are critical for proper mitotic transitions. It also plays an important role in cell cycle progression and tumor suppression and is negatively regulated by SUMOylation-mediated proteasomal ubiquitylation. Moreover, CHFR is involved in the early stage of the DNA damage response, which mediates the crosstalk between ubiquitination and poly-ADP-ribosylation. CHFR contains a fork head associated-(FHA) domain and a RING-HC finger. The CHFR FHA domain has been crystallized as a segment-swapped dimer. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 117414156  36 RADLCDVALrpqqePG--LISGIHAELHAEPRGddwRVSLEDHSSQGTLVNNVRLPRGHRLELSDGDLLTF 104
Cdd:cd22672   27 RAKDCDLSF-----PGnkLVSGDHCKIIRDEKG---QVWLEDTSTNGTLVNKVKVVKGQKVELKHGDVIYL 89

forkhead associated (FHA) domain found in Saccharomyces cerevisiae meiosis-specific serine/threonine-protein kinase MEK1 and similar proteins; MEK1 (EC 2.7.11.1), also known as MRE4, is a meiosis-specific protein kinase required for chromosome synapsis and meiotic recombination. The recruitment and activation of MEK1 require the phosphorylation of the chromosome axis protein Hop1 at Thr318 (pT318), which is necessary for recognition by the MEK1 FHA domain. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117414156  31 YRLGhRADLCDVALrpqQEPgLISGIHAELHA---EPRGDDwRVSLEDHSSQGTLVNNVRLPRGHRLELSDGDLLTFgpe 107
Cdd:cd22670   24 ITIG-RSPSCDIVI---NDP-FVSRTHCRIYSvqfDESSAP-LVYVEDLSSNGTYLNGKLIGRNNTVLLSDGDVIEI--- 94

                         90
                 ....*....|....*..
gi 117414156 108 gppgtsPSEFYFMFQQV 124
Cdd:cd22670   95 ------AHSATFVYVHN 105

first forkhead associated (FHA) domain found in Saccharomyces cerevisiae Serine/threonine-protein kinase RAD53 and similar proteins; RAD53, also called CHEK2 homolog, or serine-protein kinase 1 (Spk1), is a nuclear protein kinase that phosphorylates proteins on serine, threonine, and tyrosine. It controls S-phase checkpoint as well as G1 and G2 DNA damage checkpoints and prevents entry into anaphase and mitotic exit after DNA damage via regulation of the Polo kinase CDC5. It may be involved in the phosphorylation of RPH1. RAD53 contains two FHA domains. This model corresponds to the first one. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117414156  31 YRLGhRADLCDVALRPQQepglISGIHAE-LHAEPRGDDWRVSLEDHSSQGTLVNNVRLPRGHRLELSDGDLLTFGpEGP 109
Cdd:cd22689   47 WTFG-RHPACDYHLGNSR----LSNKHFQiLLGESDPSDGNVLLNDISSNGTWLNGQRLEKNSNQLLSQGDEITIG-VGV 120

                 ....*.
gi 117414156 110 PGTSPS 115
Cdd:cd22689  121 TGDILS 126

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 117414156 298 CLPQEETVAWVQCDGCDVWFHVACVGCSIQAAREADFRCPGC 339
Cdd:cd15522    5 CKKPDDGSPMIGCDECDDWYHWECVGITDEPPEEDDWFCPKC 46

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
                  ....*....|....*....|....*....|....*.
gi 117414156  307 WVQCDGCDVWFHVACVGCSIQAAR--EADFRCPGCR 340
Cdd:pfam00628  14 LVQCDGCDDWFHLACLGPPLDPAEipSGEWLCPECK 49

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
                 ....*....|....*....|....*....|....*....|....*....
gi 117414156 296 CCCLPQEETVAWVQCDGCDVWFHVACVGCSIQAAREA-----DFRCPGC 339
Cdd:cd15552    2 CICRKPHNNRFMICCDRCEEWFHGDCVGITEAQGKEMeenieEYVCPKC 50

PHD finger found in histone lysine demethylase PHF8; 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. PHF8 contains an N-terminal plant homeodomain (PHD) finger followed by a JmjC domain. The PHD finger mediates binding to nucleosomes at active gene promoters and the JmjC domain catalyzes the demethylation of mono- or dimethyl-lysines.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 117414156 297 CCLPQEETVAWVQCDGCDVWFHVACVGCSIQAAREAD-FRCPGCR 340
Cdd:cd15642    5 CRLPYDVTRFMIECDVCQDWFHGSCVGVEEEKAAEIDlYHCPNCQ 49

forkhead associated (FHA) domain found in sarcolemmal membrane-associated protein (SLMAP) and similar proteins; SLMAP, also called sarcolemmal-associated protein (SLAP), is a tail-anchored protein involved in fundamental cellular processes, such as myoblast fusion, cell cycle progression, and chromosomal inheritance. It is a cardiac membrane protein that plays an important role in E-C coupling and the adrenergic response of the heart. Overexpression of the SLMAP gene has been associated with diabetes and endothelial dysfunction of macro- and micro-blood vessels. SLMAP contains an N-terminal FHA domain, which is a small phosphopeptide recognition module.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 117414156  57 HAELHAEPrGDDWrvsLED-HSSQGTLVNNVRLPRGHRL----ELSDGDLLTFG 105
Cdd:cd22679   53 HALLWYDD-GKFY---LQDtKSSNGTFVNNQRLSKGSEEseprELHSGDIVQFG 102

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.

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gi 117414156 296 CCC-LPQEETVAWVQCDGCDVWFHVACVGCSIQAAREAD-FRCPGC 339
Cdd:cd15554    2 CICrQPYDVTRFMIECDVCKDWFHGSCVGVEEHQANDIErYHCPNC 47

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.

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gi 117414156 308 VQCDGCDVWFHVACVGCSIQAAREADFRCPGC 339
Cdd:cd15556   15 IACDVCEVWQHTRCVGIADNEEPPDHFLCRRC 46

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

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gi 117414156 307 WVQCDGCDVWFHVACVGCSIQ-AAREADFRCPGC 339
Cdd:cd15613   15 WICCDVCEKWYHGKCVKITPAkAEHIKQYKCPSC 48

forkhead associated (FHA) domain found in proliferation marker protein Ki-67 and similar proteins; Ki-67, also called antigen identified by monoclonal antibody Ki-67, antigen KI-67, or antigen Ki67, acts as a biological surfactant to disperse mitotic chromosomes. It is required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly. Ki-67 binds DNA with a preference for supercoiled DNA and AT-rich DNA. It may also play a role in chromatin organization. Ki-67 contains an FHA domain at its N-terminus. The FHA domain is a small phosphopeptide recognition module.

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gi 117414156  36 RADLCDVALrpqQEPGlISGIHAELHAEPRGddwRVSLEDHSS-QGTLVNNVRLPrgHRLELSDGDLLTFG 105
Cdd:cd22673   27 RDLSCDIRI---QLPG-VSREHCRIEVDENG---KAYLENLSTtNPTLVNGKAIE--KSAELKDGDVITIG 88

forkhead associated (FHA) domain found in Saccharomyces cerevisiae DNA damage response protein kinase DUN1 and similar proteins; DUN1 is a protein kinase that controls the DNA damage response in yeast. It phosphorylates SML1 on serine residues and cooperates with the PAN deadenylation complex in the regulation of RAD5 mRNA levels and cell survival in response to replicational stress. It contains an FHA domain, which is a small phosphopeptide recognition module.

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gi 117414156  36 RADLCDVALrpqqEPGLISGIHAELHAEPRGDDwrvSLEDHSSQGTLVNNVRLpRGHRLELSDGDLLTFG 105
Cdd:cd22683   27 RSRSCDLVL----SDPSISRFHAELRLEQNGIN---VIDNNSANGTFINGKRI-KGKTYILKNGDIIVFG 88

forkhead associated (FHA) domain found in protein phosphatase 1 regulatory inhibitor subunit 8 (PPP1R8) and similar proteins; PPP1R8, also called nuclear inhibitor of protein phosphatase 1 (NIPP-1), is an inhibitor subunit of the major nuclear protein phosphatase-1 (PP-1). It has RNA-binding activity but does not cleave RNA and may target PP-1 to RNA-associated substrates. It may also be involved in pre-mRNA splicing and binds DNA and might act as a transcriptional repressor. PPP1R8 seems to be required for cell proliferation. PPP1R8 contains an FHA domain that mediates interactions with threonine-phosphorylated maternal embryonic leucine zipper kinase (MELK). The FHA domain is a small phosphopeptide recognition module.

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gi 117414156  31 YRLGHRADLCDVALRPQQepglISGIHAEL--HaeprGDDWRVSLED-HSSQGTLVNNVRLPRGHRLELSDGDLLTFG 105
Cdd:cd22674   29 YLFGRNSDVCDFVLDHPS----CSRVHAALvyH----KHLNRVFLIDlGSTHGTFVGGIRLEPHKPQQLPIDSTLRFG 98

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.

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gi 117414156 302 EEtvAWVQCDGCDVWFHVAC--VGCSIQAAREADFRCPGC 339
Cdd:cd15614   36 EE--AWVQCDKCERWQHQICglYNGRRNADETAEYVCPLC 73