Bromodomain, SP100C_like subfamily. The SP100C protein is a splice variant of SP100, a major component of PML-SP100 nuclear bodies (NBs), which are poorly understood. It is covalently modified by SUMO-1 and may play a role in processes at the chromatin level. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510785764 730 PEEQLKCEFLLLKVYCCSESSFFAKIPYYyyIREACQGLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHRASYKY 809
Cdd:cd05501    1 PEELLKCEFLLLKVYCMSKSGFFISKPYY--IRDYCQGIKEPMWLNKVKERLNERVYHTVEGFVRDMRLIFHNHKLFYKD 78

                         90       100
                 ....*....|....*....|....
gi 510785764 810 KDFGQMGFRLEAEFEKNFKEVFAI 833
Cdd:cd05501   79 DDFGQVGITLEKKFEKNFKEVFAI 102

PHD finger found in the Sp100/Sp140 family of nuclear body components; The Sp100/Sp140 family includes nuclear body proteins SP100, SP140, and similar proteins. Sp110, also termed interferon-induced protein 41/75, or speckled 110 kDa, or transcriptional coactivator 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. Sp110 gene polymorphisms may be associated with susceptibility to tuberculosis in Chinese population. Sp110 contains a Sp100-like domain, a SAND domain, a plant homeodomain (PHD) finger, and a bromodomain (BRD). SP140, also termed lymphoid-restricted homolog of Sp100 (LYSp100), or nuclear autoantigen Sp-140, or speckled 140 kDa, 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's viral infectivity factor (Vif) protein. Sp140 contains a nuclear localization signal, a dimerization domain (HSR or CARD domain), a SAND domain, a PHD finger, and a BRD.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 510785764 665 ECEVCRDGGELFCCDTCSRVFHEDCHIPPVEAERTPWNCIFC 706
Cdd:cd15626    1 KCEVCGQEGKLFCCCTCSRVFHEDCHIPPVEAQRSPWSCTFC 42

Bromodomain, SP100C_like subfamily. The SP100C protein is a splice variant of SP100, a major component of PML-SP100 nuclear bodies (NBs), which are poorly understood. It is covalently modified by SUMO-1 and may play a role in processes at the chromatin level. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510785764 730 PEEQLKCEFLLLKVYCCSESSFFAKIPYYyyIREACQGLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHRASYKY 809
Cdd:cd05501    1 PEELLKCEFLLLKVYCMSKSGFFISKPYY--IRDYCQGIKEPMWLNKVKERLNERVYHTVEGFVRDMRLIFHNHKLFYKD 78

                         90       100
                 ....*....|....*....|....
gi 510785764 810 KDFGQMGFRLEAEFEKNFKEVFAI 833
Cdd:cd05501   79 DDFGQVGITLEKKFEKNFKEVFAI 102

SAND domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 510785764   561 PLLPVTCGGVKGILHKKKLQQGILVKCIQTEDgKWFTPTEFEIKGGHARSKNWRLSVRCGGWPLRWLMENGFLP 634
Cdd:smart00258   1 SELPVTCGTVKGILYKKKFKCGISVKCIQYED-KWFTPKEFEIEGGKGKSKDWKRSIRCGGSSLRTLMENGTLD 73

bromo domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510785764   729 CPEEQLKCEFLLLKVYCCSESS----FFAKIPYYYYIREACQGLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHR 804
Cdd:smart00297   1 DPKLQKKLQELLKAVLDKLDSHplswPFLKPVSRKEAPDYYDIIKKPMDLKTIKKKLENGKYSSVEEFVADFNLMFSNAR 80

                           90       100
                   ....*....|....*....|....*..
gi 510785764   805 ASYKY-KDFGQMGFRLEAEFEKNFKEV 830
Cdd:smart00297  81 TYNGPdSEVYKDAKKLEKFFEKKLREL 107

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 510785764   666 CEVCR---DGGELFCCDTCSRVFHEDCHIPP--VEAERTPWNCIFC 706
Cdd:smart00249   2 CSVCGkpdDGGELLQCDGCDRWYHQTCLGPPllEEEPDGKWYCPKC 47

Transcription factor involved in chromatin remodeling, contains bromodomain [Chromatin structure and dynamics / Transcription];

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 510785764 755 IPYYYYIreacqgLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQN 802
Cdd:COG5076  178 YPDYYEI------IKSPMDLLTIQKKLKNGRYKSFEEFVSDLNLMFDN 219

Bromodomain, SP100C_like subfamily. The SP100C protein is a splice variant of SP100, a major component of PML-SP100 nuclear bodies (NBs), which are poorly understood. It is covalently modified by SUMO-1 and may play a role in processes at the chromatin level. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510785764 730 PEEQLKCEFLLLKVYCCSESSFFAKIPYYyyIREACQGLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHRASYKY 809
Cdd:cd05501    1 PEELLKCEFLLLKVYCMSKSGFFISKPYY--IRDYCQGIKEPMWLNKVKERLNERVYHTVEGFVRDMRLIFHNHKLFYKD 78

                         90       100
                 ....*....|....*....|....
gi 510785764 810 KDFGQMGFRLEAEFEKNFKEVFAI 833
Cdd:cd05501   79 DDFGQVGITLEKKFEKNFKEVFAI 102

SAND domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 510785764   561 PLLPVTCGGVKGILHKKKLQQGILVKCIQTEDgKWFTPTEFEIKGGHARSKNWRLSVRCGGWPLRWLMENGFLP 634
Cdd:smart00258   1 SELPVTCGTVKGILYKKKFKCGISVKCIQYED-KWFTPKEFEIEGGKGKSKDWKRSIRCGGSSLRTLMENGTLD 73

bromo domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510785764   729 CPEEQLKCEFLLLKVYCCSESS----FFAKIPYYYYIREACQGLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHR 804
Cdd:smart00297   1 DPKLQKKLQELLKAVLDKLDSHplswPFLKPVSRKEAPDYYDIIKKPMDLKTIKKKLENGKYSSVEEFVADFNLMFSNAR 80

                           90       100
                   ....*....|....*....|....*..
gi 510785764   805 ASYKY-KDFGQMGFRLEAEFEKNFKEV 830
Cdd:smart00297  81 TYNGPdSEVYKDAKKLEKFFEKKLREL 107

Bromodomain. Bromodomains are found in many chromatin-associated proteins and in nuclear histone acetyltransferases. They interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510785764 732 EQLKCEFLLLKVYCC--SESSFFAKIP-------YYYYIreacqglKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQN 802
Cdd:cd04369    1 LKKKLRSLLDALKKLkrDLSEPFLEPVdpkeapdYYEVI-------KNPMDLSTIKKKLKNGEYKSLEEFEADVRLIFSN 73

                         90       100
                 ....*....|....*....|....
gi 510785764 803 HRASYKYK-DFGQMGFRLEAEFEK 825
Cdd:cd04369   74 AKTYNGPGsPIYKDAKKLEKLFEK 97

PHD finger 1 found in PHD finger protein 12 (PHF12); PHF12, also termed PHD factor 1 (Pf1), is a plant homeodomain (PHD) zinc finger-containing protein that bridges the transducin-like enhancer of split (TLE) corepressor to the mSin3A-histone deacetylase (HDAC)-complex, and further represses transcription at targeted genes. PHF12 also interacts with MRG15 (mortality factor-related genes on chromosome 15), a member of the mortality factor (MORF) family of proteins implicated in regulating cellular senescence. PHF12 contains two plant-homeodomain (PHD) zinc fingers followed by a polybasic region. The PHD fingers function downstream of phosphoinositide signaling triggered by the interaction between polybasic regions and phosphoinositides. This model corresponds to the first PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 510785764 666 CEVCRDGGELFCCDTCSRVFHEDCHIPPVEAERTP---WNCIFC 706
Cdd:cd15533    2 CDSCGEGGDLLCCDRCPASFHLQCCNPPLDEEDLPpgeWLCHRC 45

PHD finger found in transcriptional intermediary factor 1 delta (TIF1delta); TIF1delta, also termed tripartite motif-containing protein 66 (TRIM66), is a novel heterochromatin protein 1 (HP1)-interacting member of the transcriptional intermediary factor1 (TIF1) family expressed by elongating spermatids. Like other TIF1 proteins, TIF1delta displays a potent trichostatin A (TSA)-sensitive repression function; TSA is a specific inhibitor of histone deacetylases. Moreover, TIF1delta plays an important role in heterochromatin-mediated gene silencing during postmeiotic phases of spermatogenesis. It functions as a negative regulator of postmeiotic genes acting through HP1 isotype gamma (HP1gamma) complex formation and centromere association. TIF1delta contains an N-terminal RBCC (RING finger, B-box zinc-fingers, coiled-coil), a plant homeodomain (PHD) finger, followed by a bromodomain in the C-terminal region.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 510785764 662 NLDECEVCRDGGELFCCDTCSRVFHEDCHIPPVEA-ERTPWNCIFCR 707
Cdd:cd15625    1 NEDFCAVCLNGGELLCCDRCPKVFHLSCHVPALLSfPVGEWVCTLCR 47

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        30        40
                 ....*....|....*....|....*....|....*....|..
gi 510785764 666 CEVCRDGGELFCCDTCSRVFHEDCHIPPVEAERT-PWNCIFC 706
Cdd:cd15532    2 CRVCKDGGELLCCDGCPSSYHLHCLNPPLAEIPDgDWFCPRC 43

PHD finger found in transcriptional intermediary factor 1 gamma (TIF1gamma); TIF1gamma, also termed tripartite motif-containing 33 (trim33), or ectodermin, or RFG7, or PTC7, is an E3-ubiquitin ligase that functions as a regulator of transforming growth factor beta (TGFbeta) signaling; it inhibits the Smad4-mediated TGFbeta response by interaction with Smad2/3 or ubiquitylation of Smad4. Moreover, TIF1gamma is an important regulator of transcription during hematopoiesis, as well as a key factor of tumorigenesis. Like other TIF1 family members, TIF1gamma also contains an intrinsic transcriptional silencing function. It can control erythroid cell fate by regulating transcription elongation. It can bind to the anaphase-promoting complex/cyclosome (APC/C) and promotes mitosis. TIF1gamma contains an N-terminal RBCC (RING finger, B-box zinc-fingers, coiled-coil), a plant homeodomain (PHD) finger, followed by a bromodomain in the C-terminal region.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 510785764 666 CEVCRDGGELFCCDTCSRVFHEDCHIPPVEA-ERTPWNCIFCR 707
Cdd:cd15624    2 CAVCQNGGDLLCCEKCPKVFHLTCHVPTLLSfPSGDWICTFCR 44

PHD finger found in PHD finger protein 21A (PHF21A); PHF21A (also termed BHC80a or BRAF35-HDAC complex protein BHC80) along with HDAC1/2, CtBP1, CoREST, and BRAF35, is associated with LSD1, a lysine (K)-specific histone demethylase. It inhibits LSD1-mediated histone demethylation in vitro. PHF21A is predominantly present in the central nervous system and spermatogenic cells and is one of the six components of BRAF-HDAC complex (BHC) involved in REST-dependent transcriptional repression of neuron-specific genes in non-neuronal cells. It acts as a scaffold protein in BHC in neuronal as well as non-neuronal cells and also plays a role in spermatogenesis. PHF21A contains a C-terminal plant homeodomain (PHD) finger that is responsible for the binding directly to each of five other components of BHC, and of organizing BHC mediating transcriptional repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 510785764 666 CEVCRDGGELFCCDTCSRVFHEDCHIPPV-EAERTPWNCIFC 706
Cdd:cd15523    2 CSVCRKSGELLMCDTCSLVYHLDCLDPPLkTIPKGMWICPKC 43

ADDz domain found in ATRX (alpha-thalassemia/mental retardation, X-linked); ADDz_ATRX is a PHD-like zinc finger domain of ATRX, which belongs to the SNF2 family of chromatin remodeling proteins. ATRX is a large chromatin-associated nuclear protein with two domains, ADDz_ATRX at the N-terminus, followed by a C-terminal ATPase/helicase domain. The ADDz_ATRX domain recognizes a specific methylated histone, and this interaction is required for heterochromatin localization of the ATRX protein. Missense mutations in either of the two ATRX domains lead to the X-linked alpha-thalassemia and mental retardation syndrome; however the mutations in the ADDz_ATRX domain produce a more severe disease phenotype that may also relate to disturbing unknown functions or interaction sites of this domain. The ADDz domain is also present in chromatin-associated proteins cytosine-5-methyltransferase 3 (Dnmt3); it 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 510785764 648 LKSQNNSSVDPCMRnlDECEVCRDGGELFCCDTCSRVFHEDC---HIPPVEAERT----PWNCIFCR 707
Cdd:cd11726   37 YNSGEFSKDEDGSD--EYCRWCGQGGDLICCDFCPNVFCKKCikrNLGRAELSRIeesdKWKCFVCD 101

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 510785764   666 CEVCR---DGGELFCCDTCSRVFHEDCHIPP--VEAERTPWNCIFC 706
Cdd:smart00249   2 CSVCGkpdDGGELLQCDGCDRWYHQTCLGPPllEEEPDGKWYCPKC 47

PHD finger 1 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 first PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 510785764 666 CEVCRDGGELFCCDTCSRVFHEDCHIPPVE-AERTPWNCIFC 706
Cdd:cd15531    2 CEVCQQGGEIILCDTCPRAYHLVCLDPELEkAPEGKWSCPHC 43

Bromodomain, TFIID-like subfamily. Human TAFII250 (or TAF250) is the largest subunit of TFIID, a large multi-domain complex, which initiates the assembly of the transcription machinery. TAFII250 contains two bromodomains that specifically bind to acetylated histone H4. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510785764 754 KIPYYYYIreacqgLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQN--------HRASYKYKDFGQMGFRLEAEFEK 825
Cdd:cd05511   29 KVPDYYKI------IKRPMDLQTIRKKISKHKYQSREEFLEDIELIVDNsvlyngpdSVYTKKAKEMLELAEELLAEREE 102

                 ..
gi 510785764 826 NF 827
Cdd:cd05511  103 KL 104

Bromodomain; Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 510785764  765 CQGLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQN 802
Cdd:pfam00439  30 YSVIKKPMDLSTIKKKLENGEYKSLAEFLADVKLIFSN 67

PHD finger 1 found in metal-response element-binding transcription factor 2 (MTF2); MTF2, also termed metal regulatory transcription factor 2, or metal-response element DNA-binding protein M96, or polycomb-like protein 2 (PCL2), complexes with the polycomb repressive complex-2 (PRC2) in embryonic stem cells and regulates the transcriptional networks during embryonic stem cell self-renewal and differentiation. It recruits the PRC2 complex to the inactive X chromosome and target loci in embryonic stem cells. Moreover, MTF2 is required for PRC2-mediated Hox cluster repression. It activates the Cdkn2a gene and promotes cellular senescence, thus suppressing the catalytic activity of PRC2 locally. MTF2 consists of an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain. This model corresponds to the first PHD finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 510785764 666 CEVCRDG-----GELFCCDTCSRVFHEDCHIPPVE----AERTPWNCIFC 706
Cdd:cd15578    2 CTVCQDGssespNEIVLCDKCGQGYHQLCHNPKIDssvlDPDVPWLCRQC 51

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
                 ....*....|....*....|....*....|....*....|....*..
gi 510785764 666 CEVCRDGG----ELFCCDTCSRVFHEDCHIPPVEAERTP--WNCIFC 706
Cdd:cd15489    2 CIVCGKGGdlggELLQCDGCGKWFHADCLGPPLSSFVPNgkWICPVC 48

PHD finger found in transcription intermediary factor 1-beta (TIF1-beta); TIF1-beta, also termed Kruppel-associated Box (KRAB)-associated protein 1 (KAP-1), or KRAB-interacting protein 1 (KRIP-1), or nuclear co-repressor KAP-1, or RING finger protein 96, or tripartite motif-containing protein 28 (TRIM28), or E3 SUMO-protein ligase TRIM28, acts as a nuclear co-repressor that plays a role in transcription and in DNA damage response. Upon DNA damage, the phosphorylation of KAP-1 on serine 824 by the ataxia telangiectasia-mutated (ATM) kinase enhances cell survival and facilitates chromatin relaxation and heterochromatic DNA repair. It also regulates CHD3 nucleosome remodeling during DNA double-strand break (DSB) response. Meanwhile, KAP-1 can be dephosphorylated by protein phosphatase PP4C in the DNA damage response. In addition, KAP-1 is a co-activator of the orphan nuclear receptor NGFI-B (or Nur77) and is involved in NGFI-B-dependent transcription. It is also a coiled-coil binding partner, substrate and activator of the c-Fes protein tyrosine kinase. TIF1-beta contains an N-terminal RBCC (RING finger, B-box zinc-fingers, coiled-coil), which can interact with KRAB zinc finger proteins (KRAB-ZFPs), MDM2, MM1, C/EBPbeta, and mediates homo- and heterodimerization, a plant homeodomain (PHD) finger followed by a bromodomain in the C-terminal region, which interact with SETDB1, Mi-2alpha and other proteins to form complexes with histone deacetylase or methyltransferase activity.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 510785764 666 CEVCRDGGELFCCDTCSRVFHEDCHIPPV-EAERTPWNCIFC 706
Cdd:cd15623    2 CRVCQKAGALVMCDQCEFCFHLDCHLPALqEVPGEDWKCLLC 43

PHD finger found in protein BS69; Protein BS69, also termed zinc finger MYND domain-containing protein 11 (ZMYND11 or ZMY11), is a ubiquitously expressed nuclear protein acting as a transcriptional co-repressor in association with various transcription factors. It was originally identified as an adenovirus 5 E1A-binding protein that inhibits E1A transactivation, as well as c-Myb transcription. It also mediates repression, at least in part, through interaction with the co-repressor N-CoR. Moreover, it interacts with Toll-interleukin 1 receptor domain (TIR)-containing adaptor molecule-1 (TICAM-1, also named TRIF) to facilitate NF-kappaB activation and type I IFN induction. It associates with PIAS1, a SUMO E3 enzyme, and Ubc9, a SUMO E2 enzyme, and plays an inhibitory role in muscle and neuronal differentiation. Moreover, BS69 regulates Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1)/C-terminal activation region 2 (CTAR2)-mediated NF-kappaB activation by interfering with the complex formation between TNFR-associated death domain protein (TRADD) and LMP1/CTAR2. It also cooperates with tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) in the regulation of EBV-derived LMP1/CTAR1-induced NF-kappaB activation. Furthermore, BS69 is involved in the p53-p21Cip1-mediated senescence pathway. BS69 contains a plant homeodomain (PHD) finger, a bromodomain, a proline-tryptophan-tryptophan-proline (PWWP) domain, and a Myeloid translocation protein 8, Nervy and DEAF-1 (MYND) domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 510785764 666 CEVCRDGGELFCCDTCSRVFHEDC-HIPPVEAERTPWNCIFC 706
Cdd:cd15537    2 CFECHAPGEVLPCSGCFRVYHSDClSEDFRPDSTSHWTCPVC 43

PHD finger 1 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 first PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 510785764 666 CEVCRDGGELFCCDTCSRVFHEDCHIPP-VEAERTPWNCIFC 706
Cdd:cd15559    2 CRVCHKLGDLLCCETCSAVYHLECVDPPlEEVPEEDWQCEVC 43

Bromodomain, SNF2-like subfamily, specific to fungi. SNF2 is a yeast protein involved in transcriptional activation, it is the catalytic component of the SWI/SNF ATP-dependent chromatin remodeling complex. The protein is essential for the regulation of gene expression (both positive and negative) of a large number of genes. The SWI/SNF complex changes chromatin structure by altering DNA-histone contacts within the nucleosome, which results in a re-positioning of the nucleosome and facilitates or represses the binding of gene-specific transcription factors. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

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gi 510785764 756 PYYYYIreacqgLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHRAsykYKDFGQMGFRLEAEFEKNFKEVF 831
Cdd:cd05519   37 PDYYVI------IKRPIALDQIKRRIEGRAYKSLEEFLEDFHLMFANART---YNQEGSIVYEDAVEMEKAFKKKY 103

Bromodomain, SNF2L2-like subfamily, specific to animals. SNF2L2 (SNF2-alpha) or SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 is a global transcriptional activator, which cooperates with nuclear hormone receptors to boost transcriptional activation. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

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                 ....*....|....*....|....*....|....*....|....*...
gi 510785764 755 IPYYYYIreacqgLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQN 802
Cdd:cd05516   37 LPEYYEL------IRKPVDFKKIKERIRNHKYRSLEDLEKDVMLLCQN 78

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
                 ....*....|....*....|....
gi 510785764 666 CEVCRDGGELFCCDTCSRVFHEDC 689
Cdd:cd15567    2 CFICSEGGSLICCESCPASFHPEC 25

PHD finger found in Schizosaccharomyces pombe SWM histone demethylase complex subunits Phf1 (Phf1p) and Phf2 (Phf2p); Phf1p and Phf2p are components of the SWM histone demethylase complex that specifically demethylates histone H3 at lysine 9 (H3K9me2), a specific tag for epigenetic transcriptional activation. They function as corepressors and play roles in regulating heterochromatin propagation and euchromatic transcription. Both Phf1p and Phf2p contain a plant homeodomain (PHD) finger.

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 510785764 666 CEVCRDG-----GELFCCDTCSRVFHEDCHIPPVEAE-----RTPWNCIFC 706
Cdd:cd15502    2 CIVCQRGhspksNRIVFCDGCNTPYHQLCHDPSIDDEvvedpDAEWFCKKC 52

PHD finger found in integrator complex subunit 12 (Int12) and similar proteins; Int12, also termed IntS12, or PHD finger protein 22, is a component of integrator, a multi-protein mediator of small nuclear RNA processing. The integrator complex directly interacts with the C-terminal domain of RNA polymerase II (RNAPII) largest subunit and mediates the 3' end processing of small nuclear RNAs (snRNAs) U1 and U2. Different from other components of integrator, Int12 contains a PHD finger, which is not required for snRNA 3' end cleavage. Instead, Int12 harbors a small microdomain at its N-terminus which is necessary and sufficient for Int12 function; this microdomain facilitates Int12 binding to Int1 and promotes snRNA 3' end formation.

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 510785764 666 CEVCRD-----GGELFCCDTCSRVFHEDCHIPPVEAE-----RTPWNCIFC 706
Cdd:cd15501    2 CVVCKQmdvtsGNQLVECQECHNLYHQECHKPPVTDKdvndpRLVWYCSRC 52

Bromodomain; WDR9 repeat II_like subfamily. WDR9 is a human gene located in the Down Syndrome critical region-2 of chromosome 21. It encodes for a nuclear protein containing WD40 repeats and two bromodomains, which may function as a transcriptional regulator involved in chromatin remodeling and play a role in embryonic development. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510785764 735 KCEFLLLKVYCCSESSFF------AKIPYYYYIreacqgLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHRA--- 805
Cdd:cd05496    9 QCKELVNLMWDCEDSEPFrqpvdlLKYPDYRDI------IDTPMDLGTVKETLFGGNYDDPMEFAKDVRLIFSNSKSytp 82

                         90       100
                 ....*....|....*....|....*
gi 510785764 806 SYKYKDFGqMGFRLEAEFEKNFKEV 830
Cdd:cd05496   83 NKRSRIYS-MTLRLSALFEEHIKKI 106

PHD finger 2 found in Histone-lysine N-methyltransferase 2D (KMT2D); KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named myeloid/lymphoid or mixed-lineage leukemia 4 (MLL4), a fourth human homolog of Drosophila trithorax, located on chromosome 12. KMT2D enzymatically generates trimethylated histone H3 Lys 4 (H3K4me3). It plays an essential role in differentiating the human pluripotent embryonal carcinoma cell line NTERA-2 clone D1 (NT2/D1) stem cells by activating differentiation-specific genes, such asHOXA1-3 and NESTIN. It is also a part of activating signal cointegrator-2 (ASC-2)-containing complex (ASCOM) that contains the transcriptional coactivator nuclear receptor coactivator 6 (NCOA6), KMT2C and KMT2D. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2D contains the catalytic domain SET, five plant homeodomain (PHD) fingers, two extended PHD (ePHD) fingers, Cys2HisCys5HisCys2His, a RING finger, an HMG (high-mobility group)-binding motif, and two FY-rich regions. This model corresponds to the second PHD finger.

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                 ....*....|....*....|....*....|....*....|....*
gi 510785764 666 CEVCRDGGE---LFCCDTCSRVFHEDCHIPPVEAERT-PWNCIFC 706
Cdd:cd15595    2 CQTCRKPGEdskMLVCEACDKGYHTFCLKPAMESLPTdSWKCKAC 46

PHD finger 1 found in PHD finger protein 19 (PHF19); PHF19, also termed Polycomb-like protein 3 (PCL3), is a component of the polycomb repressive complex 2 (PRC2), which is the major H3K27 methyltransferase that regulates pluripotency, differentiation, and tumorigenesis through catalysis of histone H3 lysine 27 trimethylation (H3K27me3) on chromatin. PHF19 consists of an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain. It binds trimethylated histone H3 Lys36 (H3K36me3) through its Tudor domain and recruits the PRC2 complex and the H3K36me3 demethylase NO66 to embryonic stem cell genes during differentiation. Moreover, PHF19 and its upstream regulator, Akt, play roles in the phenotype switch of melanoma cells from proliferative to invasive states. This model corresponds to the first PHD finger.

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 510785764 665 ECEVCRD-----GGELFCCDTCSRVFHEDCHIPPVEAER----TPWNCIFC 706
Cdd:cd15579    1 KCNVCLGkssgpLNEILICGKCGLGYHQQCHIPVVDSSDdpplTPWFCRRC 51

Bromodomain; brd1_like subfamily. BRD1 is a mammalian gene which encodes for a nuclear protein assumed to be a transcriptional regulator. BRD1 has been implicated with brain development and susceptibility to schizophrenia and bipolar affective disorder. Bromodomains are 110 amino acid long domains that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 510785764 768 LKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQN-----------HRASYKYKDFG 813
Cdd:cd05512   38 IKQPMDFSTMRKKLESQRYRTLEDFEADFNLIINNclaynakdtifYRAAVRLRDQG 94

PHD finger found in bromodomain adjacent to zinc finger domain protein BAZ1A and BAZ1B; BAZ1A, also termed ATP-dependent chromatin-remodeling protein, or ATP-utilizing chromatin assembly and remodeling factor 1 (ACF1), or CHRAC subunit ACF1, or Williams syndrome transcription factor-related chromatin-remodeling factor 180 (WCRF180), or WALp1, is a subunit of the conserved imitation switch (ISWI)-family ATP-dependent chromatin assembly and remodeling factor (ACF)/chromatin accessibility complex (CHRAC) chromatin remodeling complex, which is required for DNA replication through heterochromatin. It alters the remodeling properties of the ATPase motor protein sucrose nonfermenting-2 homolog (SNF2H). Moreover, BAZ1A and its complexes play important roles in DNA double-strand break (DSB) repair. It is essential for averting improper gene expression during spermatogenesis. It also regulates transcriptional repression of vitamin D3 receptor-regulated genes. BAZ1B, also termed Tyrosine-protein kinase BAZ1B, or Williams syndrome transcription factor (WSTF), or Williams-Beuren syndrome chromosomal region 10 protein, Williams-Beuren syndrome chromosomal region 9 protein, or WALp2, is a multifunctional protein implicated in several nuclear processes, including replication, transcription, and the DNA damage response. BAZ1B/WSTF, together with the imitation switch (ISWI) ATPase, forms a WSTF-ISWI chromatin remodeling complex (WICH), which transiently associates with the human inactive X chromosome (Xi) during late S-phase prior to BRCA1 and gamma-H2AX. Moreover, BAZ1B/WSTF, SNF2h, and nuclear myosin 1 (NM1) forms the chromatin remodeling complex B-WICH that is involved in regulating rDNA transcription. Both BAZ1A and BAZ1B contain a WAC motif, a DDT domain, BAZ 1 and BAZ 2 motifs, a WAKZ (WSTF/Acf1/KIAA0314/ZK783.4) motif, a plant homeodomain (PHD) finger, and a bromodomain.

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                 ....*....|....*....|....*....|....*....|....*
gi 510785764 666 CEVCR---DGGELFCCDTCSRVFHEDCHIPPV-EAERTPWNCIFC 706
Cdd:cd15544    2 CKVCRkkgDPDNMILCDGCDKAFHLYCLRPALrEVPSGDWFCPAC 46