Short conserved domain in transcriptional regulators; Plus3 domains occur in the Saccharomyces cerevisiae Rtf1p protein, which interacts with Spt6p, and in parsley CIP, which interacts with the bZIP protein CPRF1.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002302009   504 AIDMHNINLIYLRRSLLEDLIDdNGTFSDKITGAFVRIRTPCVGQKQDIYRLVKVLGTHKVAERYSVGKKTTDHALEILN 583
Cdd:smart00719    1 AIVFDNLNLLRLRRSLVEELLK-PPTFESKVVGCFVRVKIGPNDQKQPIYRLVQVTGVKEADKPYSLGGKTTNVLLEVLN 79

                            90       100       110
                    ....*....|....*....|....*....|
gi 1002302009   584 LDKKEVITMDTISNQDFTEEECKRLRQSMK 613
Cdd:smart00719   80 GDSEKVVQINFISNQDFTEEEFQRWKQAIK 109

SWIB/MDM2 domain; This family includes the SWIB domain and the MDM2 domain. The p53-associated protein (MDM2) is an inhibitor of the p53 tumour suppressor gene binding the transactivation domain and down regulating the ability of p53 to activate transcription. This family contains the p53 binding domain of MDM2.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1002302009  373 SSELLEFIGhmrngdISYISQFDVQILLLEYVKQKNLRDPRRKSQIICDARLANLFRKPHVGHFEMLKLLEMHF 446
Cdd:pfam02201    6 SPELAELLG------EEELSRPEVVKALWEYIKENNLQDPEDKREIICDEKLKKLFGGDRVKFFEMPKLLSPHL 73

transcriptional regulator ICP4; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002302009 1338 QDDQNNEMWSLSSPTPTlQPSGIGADTKGASCAiEEVIVAQGNSGVVEPSPALEkkRIEKVPSASIDRGVPEQVKPKSDA 1417
Cdd:PHA03307    82 NESRSTPTWSLSTLAPA-SPAREGSPTPPGPSS-PDPPPPTPPPASPPPSPAPD--LSEMLRPVGSPGPPPAASPPAAGA 157

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002302009 1418 ALSPEESRKPSGLQLSstYLQGSTKSSGLPPSGTSLDGGIEPSGLLPSGTSLEWGTKISGVQSSASSLEGSKKAFVRQPS 1497
Cdd:PHA03307   158 SPAAVASDAASSRQAA--LPLSSPEETARAPSSPPAEPPPSTPPAAASPRPPRRSSPISASASSPAPAPGRSAADDAGAS 235

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002302009 1498 GSSlegnTKASGRQPSGSSiegskkPSDRQPSGASQEGNTKPSGWQQSVSSLEGGTKPSGwkpsisidtntkasgwlrSS 1577
Cdd:PHA03307   236 SSD----SSSSESSGCGWG------PENECPLPRPAPITLPTRIWEASGWNGPSSRPGPA------------------SS 287

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1002302009 1578 SSPDVGRKASAWQS-SGSSPVAGSSKASGWQPSPRESSKSKPNSTW----GAGQSRNSSSHQSTTPTAKYSSETPRRQ 1650
Cdd:PHA03307   288 SSSPRERSPSPSPSsPGSGPAPSSPRASSSSSSSRESSSSSTSSSSessrGAAVSPGPSPSRSPSPSRPPPPADPSSP 365

Short conserved domain in transcriptional regulators; Plus3 domains occur in the Saccharomyces cerevisiae Rtf1p protein, which interacts with Spt6p, and in parsley CIP, which interacts with the bZIP protein CPRF1.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002302009   504 AIDMHNINLIYLRRSLLEDLIDdNGTFSDKITGAFVRIRTPCVGQKQDIYRLVKVLGTHKVAERYSVGKKTTDHALEILN 583
Cdd:smart00719    1 AIVFDNLNLLRLRRSLVEELLK-PPTFESKVVGCFVRVKIGPNDQKQPIYRLVQVTGVKEADKPYSLGGKTTNVLLEVLN 79

                            90       100       110
                    ....*....|....*....|....*....|
gi 1002302009   584 LDKKEVITMDTISNQDFTEEECKRLRQSMK 613
Cdd:smart00719   80 GDSEKVVQINFISNQDFTEEEFQRWKQAIK 109

PHD finger 5 found in nuclear receptor-binding SET domain-containing (NSD) proteins; The nuclear receptor binding SET domain (NSD) protein is a family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1, that are critical in maintaining chromatin integrity. Reducing NSD activity through specific lysine-HMTase inhibitors appears promising to help suppress cancer growth. NSD proteins have specific mono- and dimethylase activities for H3K36, and they play non-redundant roles during development. NSD1 plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. NSD2 is involved in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. NSD3 is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD proteins contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). This model corresponds to the fifth PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1002302009  152 VCFICFDGGNLVVCDKKGCTKVYHPACIKRDEsffRSRAKWTCGWH 197
Cdd:cd15568      1 ECFRCGDGGDLVLCDFKGCPKVYHLSCLGLEK---PPGGKWICPWH 43

SWIB/MDM2 domain found in SWIB/MDM2 homologous proteins; This family includes Schizosaccharomyces pombe upstream activation factor subunit spp27, Saccharomyces cerevisiae upstream activation factor subunit UAF30, Chlamydiae DNA topoisomerase/SWIB domain fusion protein, Arabidopsis thaliana zinc finger CCCH domain-containing proteins, AtC3H19 and AtC3H44, and similar proteins. S. pombe spp27, also termed upstream activation factor 27 KDa subunit (p27), or upstream activation factor 30 KDa subunit (p30), or upstream activation factor subunit uaf30, is a component of the UAF (upstream activation factor) complex which interacts with the upstream element of the RNA polymerase I promoter and forms a stable preinitiation complex. S. cerevisiae UAF30, also termed upstream activation factor 30 KDa subunit (p30), is a non-essential component of the UAF. It seems to play a role in silencing transcription by RNA polymerase II. The SWIB domain found in Chlamydiae DNA topoisomerase may play a role in chromatin condensation-decondensation, which is characteristic of the chlamydial developmental cycle and not found in any other types of bacteria. AtC3H19, also termed protein needed for RDR2-independent DNA methylation (NERD), is a plant-specific GW repeat- and PHD finger-containing protein that plays a central role in integrating RNA silencing and chromatin signals in 21 nt small-interfering RNA (siRNA)-dependent DNA methylation on the cytosine pathway, leading to transcriptional gene silencing of specific sequences. This family also includes many uncharacterized proteins containing two copies of SWIB/MDM2 domain.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1002302009  371 WASSELLEFIGHmrngdiSYISQFDVQILLLEYVKQKNLRDPRRKSQIICDARLANLFRKPHVGHFEMLKLLEMHF 446
Cdd:cd10567      2 KLSPELAAFLGV------SELSRTEVVKKLWAYIKENNLQDPKNKREILCDEKLKKVFGKDEVVMFEMNKLLSKHL 71

GYF domain; The GYF domain is named because of the presence of Gly-Tyr-Phe residues. The GYF domain is a proline-binding domain in CD2-binding protein Swiss:O95400.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1002302009  787 WHYKDPSGSVQGPFTLLQLSKW--AAYFPRDLRIWLTFESEQNSL 829
Cdd:pfam02213    1 WEYKDPQGEVQGPFSSAEMQEWykAGYFPDDLPVRRVGDTEFYPL 45

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*....
gi 1002302009   152 VCFIC---FDGGNLVVCDkkGCTKVYHPACIKRDESFFRSRAKWTCGWH 197
Cdd:smart00249    1 YCSVCgkpDDGGELLQCD--GCDRWYHQTCLGPPLLEEEPDGKWYCPKC 47

Transcription factor involved in TATA site selection and in elongation by RNA polymerase II [Transcription];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002302009  481 SDKRRKIHKKIERESPANLEDYaaidmhniNLIYLRRSLLEDLIDDNGtFSDKITGAFVRIRtpcVGQK--QDIYRLVKV 558
Cdd:COG5296    192 SYAEEAVEDISRTDDFAELYDF--------NQCRVGRDMVARNVFKPI-FEDEVIGCFTRVR---IGERggYLVYRIVGV 259

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002302009  559 LGTHKVAERYSVGKKTTDHALEILNLDKKEVITMDTISNQDFTEEECKRLRQSMKCGLITRLKVGDIHEKAK-------- 630
Cdd:COG5296    260 GKGSTYSKPYGRKEVKTNRYLDVSTGRTYKVFRINNISNSPFLREEYQRVWRSFKVGKLSMPSIAKVKEKYDklvdtmgr 339

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1002302009  631 ----------IFQLLRVNDWLEN---EKQRLSHLRDRASETGRRKQLRE 666
Cdd:COG5296    340 rlsdkeiskmVACKDEVHPKRSNvihEKTELRQKRQRAIELKNKKAAME 388

Zinc finger domain; This is a zinc finger domain found in Zinc finger CCCH-type with G patch domain-containing proteins such as ZIP. Functional studies indicate that ZIP specifically targets EGFR and represses its transcription, and that the zinc finger and the coiled-coil domains are central to that process.

                           10
                   ....*....|....*....
gi 1002302009 1733 CRYYENGYCRKGTSCQFLH 1751
Cdd:pfam18345    1 CKFFLKGRCRYGDKCRFAH 19

serine-rich protein; This serine-rich protein belongs to a family with large size (over 1000 amino acids), which a highly serine-rich central region that averages over 300 aa in length. Species encoding members of this family of proteins tend to be anaerobic bacteria, including Gram-positive bacteria of the human gut microbiome and Chloroflexi from marine sediments.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002302009 1465 SGTSLEWGTKISGVQSSASSLEgskkafVRQPSGSSLEGNTKASGRQPSGSSIEGSKKPSDRQPSGASqegntkpsgWQQ 1544
Cdd:NF033849   323 SSHSQSSSYNVSSGTGVSSSHS------DGTSQSTSISHSESSSESTGTSVGHSTSSSVSSSESSSRS---------SSS 387

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002302009 1545 SVSSLEGGTKPSGWKPSISIDTNTKAS-GWLRSSSSPDVGRKASAWQSSGSSpvAGSSKASGWQPSPRESSKSKPNSTWG 1623
Cdd:NF033849   388 GVSGGFSGGIAGGGVTSEGLGASQGGSeGWGSGDSVQSVSQSYGSSSSTGTS--SGHSDSSSHSTSSGQADSVSQGTSWS 465

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1002302009 1624 AGQSrNSSSHQSTTPTAKYSSE-----TPRRQGNNNTNSAGWGDSLGN 1666
Cdd:NF033849   466 EGTG-TSQGQSVGTSESWSTSQsetdsVGDSTGTSESVSQGDGRSTGR 512

Short conserved domain in transcriptional regulators; Plus3 domains occur in the Saccharomyces cerevisiae Rtf1p protein, which interacts with Spt6p, and in parsley CIP, which interacts with the bZIP protein CPRF1.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002302009   504 AIDMHNINLIYLRRSLLEDLIDdNGTFSDKITGAFVRIRTPCVGQKQDIYRLVKVLGTHKVAERYSVGKKTTDHALEILN 583
Cdd:smart00719    1 AIVFDNLNLLRLRRSLVEELLK-PPTFESKVVGCFVRVKIGPNDQKQPIYRLVQVTGVKEADKPYSLGGKTTNVLLEVLN 79

                            90       100       110
                    ....*....|....*....|....*....|
gi 1002302009   584 LDKKEVITMDTISNQDFTEEECKRLRQSMK 613
Cdd:smart00719   80 GDSEKVVQINFISNQDFTEEEFQRWKQAIK 109

PHD finger 5 found in nuclear receptor-binding SET domain-containing (NSD) proteins; The nuclear receptor binding SET domain (NSD) protein is a family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1, that are critical in maintaining chromatin integrity. Reducing NSD activity through specific lysine-HMTase inhibitors appears promising to help suppress cancer growth. NSD proteins have specific mono- and dimethylase activities for H3K36, and they play non-redundant roles during development. NSD1 plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. NSD2 is involved in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. NSD3 is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD proteins contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). This model corresponds to the fifth PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1002302009  152 VCFICFDGGNLVVCDKKGCTKVYHPACIKRDEsffRSRAKWTCGWH 197
Cdd:cd15568      1 ECFRCGDGGDLVLCDFKGCPKVYHLSCLGLEK---PPGGKWICPWH 43

SWIB/MDM2 domain found in SWIB/MDM2 homologous proteins; This family includes Schizosaccharomyces pombe upstream activation factor subunit spp27, Saccharomyces cerevisiae upstream activation factor subunit UAF30, Chlamydiae DNA topoisomerase/SWIB domain fusion protein, Arabidopsis thaliana zinc finger CCCH domain-containing proteins, AtC3H19 and AtC3H44, and similar proteins. S. pombe spp27, also termed upstream activation factor 27 KDa subunit (p27), or upstream activation factor 30 KDa subunit (p30), or upstream activation factor subunit uaf30, is a component of the UAF (upstream activation factor) complex which interacts with the upstream element of the RNA polymerase I promoter and forms a stable preinitiation complex. S. cerevisiae UAF30, also termed upstream activation factor 30 KDa subunit (p30), is a non-essential component of the UAF. It seems to play a role in silencing transcription by RNA polymerase II. The SWIB domain found in Chlamydiae DNA topoisomerase may play a role in chromatin condensation-decondensation, which is characteristic of the chlamydial developmental cycle and not found in any other types of bacteria. AtC3H19, also termed protein needed for RDR2-independent DNA methylation (NERD), is a plant-specific GW repeat- and PHD finger-containing protein that plays a central role in integrating RNA silencing and chromatin signals in 21 nt small-interfering RNA (siRNA)-dependent DNA methylation on the cytosine pathway, leading to transcriptional gene silencing of specific sequences. This family also includes many uncharacterized proteins containing two copies of SWIB/MDM2 domain.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1002302009  371 WASSELLEFIGHmrngdiSYISQFDVQILLLEYVKQKNLRDPRRKSQIICDARLANLFRKPHVGHFEMLKLLEMHF 446
Cdd:cd10567      2 KLSPELAAFLGV------SELSRTEVVKKLWAYIKENNLQDPKNKREILCDEKLKKVFGKDEVVMFEMNKLLSKHL 71

GYF domain; The GYF domain is named because of the presence of Gly-Tyr-Phe residues. The GYF domain is a proline-binding domain in CD2-binding protein Swiss:O95400.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1002302009  787 WHYKDPSGSVQGPFTLLQLSKW--AAYFPRDLRIWLTFESEQNSL 829
Cdd:pfam02213    1 WEYKDPQGEVQGPFSSAEMQEWykAGYFPDDLPVRRVGDTEFYPL 45

Contains conserved Gly-Tyr-Phe residues; Proline-binding domain in CD2-binding protein. Contains conserved Gly-Tyr-Phe residues.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 1002302009   785 KVWHYKDPSGSVQGPFTLLQLSKW--AAYFPRDLRIWLTFESEQNSLLLTEVLS 836
Cdd:smart00444    1 VLWLYKDPDGEIQGPFTASQMSQWyqAGYFPDSLQIKRLNEPPYETLGDLDRLL 54

PHD finger 5 found in nuclear SET domain-containing protein 3 (NSD3); NSD3, also termed histone-lysine N-methyltransferase NSD3, or protein whistle, or WHSC1-like 1 isoform 9 with methyltransferase activity to lysine, or Wolf-Hirschhorn syndrome candidate 1-like protein 1 (WHSC1-like protein 1, or WHSC1L1), is a lysine methyltransferase encoded by gene NSD3, which is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD3 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, five plant-homeodomain (PHD) zinc fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD fingers are involved in protein-protein interactions. This model corresponds to the fifth PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1002302009  153 CFICFDGGNLVVCDKKGCTKVYHPACIKRDESFFrsrAKWTCGWH 197
Cdd:cd15661      2 CFQCGDGGELVMCDKKDCPKAYHLLCLNLTQPPY---GKWECPWH 43

SWI complex, BAF60b domains;

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*...
gi 1002302009   400 LLEYVKQKNLRDPRRKSQIICDARLANLFRKPHVGHFEMLKLLEMHFH 447
Cdd:smart00151   29 LWEYIKEHNLQDPQNKREILCDSKLEQIFGKDRMDMFEMNKLLTPHLI 76

PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) finger typically characterized as Cys4HisCys3, and a non-canonical extended PHD finger, characterized as Cys2HisCys5HisCys2His. Variations include the RAG2 PHD finger characterized by Cys3His2Cys2His and the PHD finger 5 found in nuclear receptor-binding SET domain-containing proteins characterized by Cys4HisCys2His. The PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. Single or multiple copies of PHD fingers have been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors. The PHD finger domain SF is structurally similar to the RING and FYVE_like superfamilies.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1002302009  152 VCFICFDGGN----LVVCDKkgCTKVYHPACIKRDESFFRSRAKWTCGWH 197
Cdd:cd15489      1 SCIVCGKGGDlggeLLQCDG--CGKWFHADCLGPPLSSFVPNGKWICPVC 48

ADDz domain found in DNA (cytosine-5) methyltransferases (C5-MTases) 3 (Dnmt3); Dnmt3 is a de novo DNA methyltransferase family that includes two active enzymes Dnmt3a and -3b and one regulatory factor Dnmt3l. The ADDz domain of Dnmt3 is located in the C-terminal region of Dnmt3, which is an active catalytic domain in Dnmt3a and -b, but lacks some residues for enzymatic activity in Dnmt3l. DNA methylation is an important epigenetic mechanism involved in diverse biological processes such as embryonic development, gene expression, and genomic imprinting. The ADDz_Dnmt3 domain is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger. PHD zinc finger domains have been identified in more than 40 proteins that are mainly involved in chromatin mediated transcriptional control; the classical PHD zinc finger has a C4-H-C3 motif that spans about 50-80 amino acids. In ADDz, the conserved histidine residue of the PHD finger is replaced by a cysteine, and an additional zinc finger C2-C2 like motif is located about twenty residues upstream of the C4-C-C3 motif.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002302009  146 EDDEDVVCFICFDGGNLVVCDKKGCTKVYHPACIKR--DESFFR---SRAKWTCgwHLCS 200
Cdd:cd11725     43 DDGYQMYCTICGGGGEVVLCDNPDCTRVYCTECLDLllGPGAVAkilESDPWFC--FLCS 100

transcriptional regulator ICP4; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002302009 1338 QDDQNNEMWSLSSPTPTlQPSGIGADTKGASCAiEEVIVAQGNSGVVEPSPALEkkRIEKVPSASIDRGVPEQVKPKSDA 1417
Cdd:PHA03307    82 NESRSTPTWSLSTLAPA-SPAREGSPTPPGPSS-PDPPPPTPPPASPPPSPAPD--LSEMLRPVGSPGPPPAASPPAAGA 157

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002302009 1418 ALSPEESRKPSGLQLSstYLQGSTKSSGLPPSGTSLDGGIEPSGLLPSGTSLEWGTKISGVQSSASSLEGSKKAFVRQPS 1497
Cdd:PHA03307   158 SPAAVASDAASSRQAA--LPLSSPEETARAPSSPPAEPPPSTPPAAASPRPPRRSSPISASASSPAPAPGRSAADDAGAS 235

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002302009 1498 GSSlegnTKASGRQPSGSSiegskkPSDRQPSGASQEGNTKPSGWQQSVSSLEGGTKPSGwkpsisidtntkasgwlrSS 1577
Cdd:PHA03307   236 SSD----SSSSESSGCGWG------PENECPLPRPAPITLPTRIWEASGWNGPSSRPGPA------------------SS 287

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1002302009 1578 SSPDVGRKASAWQS-SGSSPVAGSSKASGWQPSPRESSKSKPNSTW----GAGQSRNSSSHQSTTPTAKYSSETPRRQ 1650
Cdd:PHA03307   288 SSSPRERSPSPSPSsPGSGPAPSSPRASSSSSSSRESSSSSTSSSSessrGAAVSPGPSPSRSPSPSRPPPPADPSSP 365

zinc finger;

                            10        20
                    ....*....|....*....|
gi 1002302009  1732 ICRYYENGYCRKGTSCQFLH 1751
Cdd:smart00356    6 LCKFFKRGYCPRGDRCKFAH 25

PHD finger 2 found in class II Chromodomain-Helicase-DNA binding (CHD) proteins; Class II CHD proteins includes chromodomain-helicase-DNA-binding protein CHD3, CHD4, and CHD5, which are nuclear and ubiquitously expressed chromatin remodelling ATPases generally associated with histone deacetylases (HDACs). They are involved in DNA Double Strand Break (DSB) signaling, DSB repair and/or p53-dependent pathways such as apoptosis and senescence, as well as in the maintenance of genomic stability, and/or cancer prevention. They function as subunits of the Nucleosome Remodelling and Deacetylase (NuRD) complex, which is generally associated with gene repression, heterochromatin formation, and overall chromatin compaction. In contrast to the class I CHD enzymes (CHD1 and CHD2), class II CHD proteins lack identifiable DNA-binding domains, but possess a C-terminal coiled-coil region. Moreover, in addition to the tandem chromodomains and a helicase domain, they all harbor tandem plant homeodomain (PHD) zinc fingers involved in the recognition of methylated histone tails. This model corresponds to the second PHD finger.

                           10        20
                   ....*....|....*....|....*....
gi 1002302009  152 VCFICFDGGNLVVCDkkGCTKVYHPACIK 180
Cdd:cd15532      1 FCRVCKDGGELLCCD--GCPSSYHLHCLN 27

PHD finger 4 found in nuclear receptor-binding SET domain-containing (NSD) proteins; The nuclear receptor binding SET domain (NSD) protein is a family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1, that are critical in maintaining chromatin integrity. Reducing NSD activity through specific lysine-HMTase inhibitors appears promising to help suppress cancer growth. NSD proteins have specific mono- and dimethylase activities for H3K36, and they play non-redundant roles during development. NSD1 plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. NSD2 is involved in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. NSD3 is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to development of acute myeloid leukemia. NSD proteins contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). This model corresponds to the fourth PHD finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1002302009  153 CFICFDGGNLVVCDkkGCTKVYHPACIKRDESffrsrakwTCGWHLCSTC 202
Cdd:cd15567      2 CFICSEGGSLICCE--SCPASFHPECLGLEPP--------PEGKFYCEDC 41

DNA topoisomerase III; Provisional

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                   ....*....|....*....|....*....|....*....|....*.
gi 1002302009  400 LLEYVKQKNLRDPRRKSQIICDARLANLFRKPHVGHFEMLKLLEMH 445
Cdd:PRK14724   940 LWDYIKANNLQDPADKRAINADAKLRPVFGKDQVTMFELAGIVGKH 985

PHD finger found in the transcriptional intermediary factor 1 (TIF1) family and similar proteins; The TIF1 family of transcriptional cofactors includes TIF1alpha (TRIM24), TIF1beta (TRIM28), TIF1gamma (TRIM33), and TIF1delta (TRIM66), which are characterized by an N-terminal RING-finger B-box coiled-coil (RBCC/TRIM) motif and plant homeodomain (PHD) finger followed by a bromodomain in the C-terminal region. TIF1 proteins couple chromatin modifications to transcriptional regulation, signaling, and tumor suppression. They exert a deacetylase-dependent silencing effect when tethered to a promoter region. TIF1alpha, TIF1beta, and TIF1delta can homodimerize and contain a PXVXL motif necessary and sufficient for heterochromatin protein 1(HP1) binding. TIF1alpha and TIF1beta bind nuclear receptors and Kruppel-associated boxes (KRAB) specifically and respectively. In contrast, TIF1delta appears to lack nuclear receptor- and KRAB-binding activity. Moreover, TIF1delta is specifically involved in heterochromatin-mediated gene silencing during postmeiotic phases of spermatogenesis. TIF1gamma is structurally closely related to TIF1alpha and TIF1beta, but has very little functional features in common with them. It does not interact with the KRAB silencing domain of KOX1 or the heterochromatinic proteins HP1alpha, beta, and gamma. It cannot bind to nuclear receptors (NRs). This family also includes Sp100/Sp140 family proteins, the nuclear body SP100 and SP140. Sp110 is a leukocyte-specific component of the nuclear body. It may function as a nuclear hormone receptor transcriptional coactivator that may play a role in inducing differentiation of myeloid cells. It is also involved in resisting intracellular pathogens and functions as an important drug target for preventing intracellular pathogen diseases, such as tuberculosis, hepatic veno-occlusive disease, and intracellular cancers. SP140 is an interferon inducible nuclear leukocyte-specific protein involved in primary biliary cirrhosis and a risk factor in chronic lymphocytic leukemia. It is also implicated in innate immune response to human immunodeficiency virus type 1 (HIV-1) by binding to the virus viral infectivity factor (Vif) protein. Both Sp110 and Sp140 contain a SAND domain, a plant homeodomain (PHD) finger, and a bromodomain (BRD).

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                   ....*....|....*....|....*....|....*....|....*....|..
gi 1002302009  152 VCFICFDGGNLVVCDKkgCTKVYHPAC----IKRDESFFrsrakWTCGwhLC 199
Cdd:cd15541      1 WCAVCQNGGELLCCDK--CPRVFHLDChippIPEFPSGE-----WSCS--LC 43

PHD finger 2 found in nuclear receptor-binding SET domain-containing (NSD) proteins; The nuclear receptor binding SET domain (NSD) protein is a family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1, that are critical in maintaining chromatin integrity. Reducing NSD activity through specific lysine-HMTase inhibitors appears promising to help suppress cancer growth. NSD proteins have specific mono- and dimethylase activities for H3K36, and they play non-redundant roles during development. NSD1 plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. NSD2 is involved in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. NSD3 is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD proteins contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). This model corresponds to the second PHD finger.

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                   ....*....|....*....|....*....|....*....|....*....|
gi 1002302009  153 CFICF----DGGNLVVCDKKGCTKVYHPACIKRDESFFRSRAKW-TCGWH 197
Cdd:cd15565      2 CFVCKklgsVGGEVFKCSVASCGKFYHEECLKKWPLTTISDSKKfRCPLH 51