SAND domain; The DNA binding activity of two proteins has been mapped to the SAND domain. The conserved KDWK motif is necessary for DNA binding, and it appears to be important for dimerization. This region is also found in the putative transcription factor RegA from the multicellular green alga Volvox cateri. This region of RegA is known as the VARL domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 528473945  327 FQAPSLPVSCVSLIGTLFKDRFATGRCGKSIRTKQHWFTPEEFVKEEPTLSDGLWKRDILCHGKTLNFLCEKKIL 401
Cdd:pfam01342   2 FDSPVLPVTCGAAKGLLHKKKFKQGISGKCIQNEDSWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

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 528473945 499 RLQCHYLLLCMYNEDIQKVFVKDPRPNvRRYSEFISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKFNRDNKFG 578
Cdd:cd05501    4 LLKCEFLLLKVYCMSKSGFFISKPYYI-RDYCQGIKEPMWLNKVKERLNERVYHTVEGFVRDMRLIFHNHKLFYKDDDFG 82

                         90       100
                 ....*....|....*....|
gi 528473945 579 QLGAKLKEIFEDEIQKIFFI 598
Cdd:cd05501   83 QVGITLEKKFEKNFKEVFAI 102

SAND domain; The DNA binding activity of two proteins has been mapped to the SAND domain. The conserved KDWK motif is necessary for DNA binding, and it appears to be important for dimerization. This region is also found in the putative transcription factor RegA from the multicellular green alga Volvox cateri. This region of RegA is known as the VARL domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 528473945  327 FQAPSLPVSCVSLIGTLFKDRFATGRCGKSIRTKQHWFTPEEFVKEEPTLSDGLWKRDILCHGKTLNFLCEKKIL 401
Cdd:pfam01342   2 FDSPVLPVTCGAAKGLLHKKKFKQGISGKCIQNEDSWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

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 528473945 499 RLQCHYLLLCMYNEDIQKVFVKDPRPNvRRYSEFISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKFNRDNKFG 578
Cdd:cd05501    4 LLKCEFLLLKVYCMSKSGFFISKPYYI-RDYCQGIKEPMWLNKVKERLNERVYHTVEGFVRDMRLIFHNHKLFYKDDDFG 82

                         90       100
                 ....*....|....*....|
gi 528473945 579 QLGAKLKEIFEDEIQKIFFI 598
Cdd:cd05501   83 QVGITLEKKFEKNFKEVFAI 102

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).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 528473945 428 ECNVCHSEGNLVCCDKCPRAFHPDCHLPAVNEEDSAwQWICTFC 471
Cdd:cd15541    1 WCAVCQNGGELLCCDKCPRVFHLDCHIPPIPEFPSG-EWSCSLC 43

SAND domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528473945   330 PSLPVSCVSLIGTLFKDRFATGRCGKSIRTKQHWFTPEEFVKEEPTLSDGLWKRDILCHGKTLNFLCEKKILD 402
Cdd:smart00258   1 SELPVTCGTVKGILYKKKFKCGISVKCIQYEDKWFTPKEFEIEGGKGKSKDWKRSIRCGGSSLRTLMENGTLD 73

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528473945 516 KVFVKDP-RPNVRRYSEFISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKFNRDNKF-GQLGAKLKEIFEDEIQ 593
Cdd:COG5076  167 SIFLGLPsKREYPDYYEIIKSPMDLLTIQKKLKNGRYKSFEEFVSDLNLMFDNCKLYNGPDSSvYVDAKELEKYFLKLIE 246

                 ....*
gi 528473945 594 KIFFI 598
Cdd:COG5076  247 EIPEE 251

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        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 528473945  429 CNVCHS---EGNLVCCDKCPRAFHPDCHLPAVNEEDSA-WQWICTFCMLR 474
Cdd:pfam00628   2 CAVCGKsddGGELVQCDGCDDWFHLACLGPPLDPAEIPsGEWLCPECKPK 51

SAND domain; The DNA binding activity of two proteins has been mapped to the SAND domain. The conserved KDWK motif is necessary for DNA binding, and it appears to be important for dimerization. This region is also found in the putative transcription factor RegA from the multicellular green alga Volvox cateri. This region of RegA is known as the VARL domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 528473945  327 FQAPSLPVSCVSLIGTLFKDRFATGRCGKSIRTKQHWFTPEEFVKEEPTLSDGLWKRDILCHGKTLNFLCEKKIL 401
Cdd:pfam01342   2 FDSPVLPVTCGAAKGLLHKKKFKQGISGKCIQNEDSWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

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 528473945 499 RLQCHYLLLCMYNEDIQKVFVKDPRPNvRRYSEFISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKFNRDNKFG 578
Cdd:cd05501    4 LLKCEFLLLKVYCMSKSGFFISKPYYI-RDYCQGIKEPMWLNKVKERLNERVYHTVEGFVRDMRLIFHNHKLFYKDDDFG 82

                         90       100
                 ....*....|....*....|
gi 528473945 579 QLGAKLKEIFEDEIQKIFFI 598
Cdd:cd05501   83 QVGITLEKKFEKNFKEVFAI 102

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 528473945 509 MYNEDIQKVFVKDPRP-NVRRYSEFISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKFNR-DNKFGQLGAKLKE 586
Cdd:cd04369   14 KLKRDLSEPFLEPVDPkEAPDYYEVIKNPMDLSTIKKKLKNGEYKSLEEFEADVRLIFSNAKTYNGpGSPIYKDAKKLEK 93

                 ....*.
gi 528473945 587 IFEDEI 592
Cdd:cd04369   94 LFEKLL 99

bromo domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 528473945   529 YSEFISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKFN-RDNKFGQLGAKLKEIFEDEIQKI 595
Cdd:smart00297  40 YYDIIKKPMDLKTIKKKLENGKYSSVEEFVADFNLMFSNARTYNgPDSEVYKDAKKLEKFFEKKLREL 107

Bromodomain; tif1_like subfamily. Tif1 (transcription intermediary factor 1) is a member of the tripartite motif (TRIM) protein family, which is characterized by a particular domain architecture. It functions by recruiting coactivators and/or corepressors to modulate transcription. Vertebrate Tif1-gamma, also labeled E3 ubiquitin-protein ligase TRIM33, plays a role in the control of hematopoiesis. Its homologue in Xenopus laevis, Ectodermin, has been shown to function in germ-layer specification and control of cell growth during embryogenesis. 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 528473945 502 CHYLLLCMYNEDIQKVFVKDPRPNVRRYSEFISDPMWLNRIKQKLKD---NMYQKFGEFASDFQLIFSNCRKFNR-DNKF 577
Cdd:cd05502    9 CERLLLELYCHELSLPFHEPVSPSVPNYYKIIKTPMDLSLIRKKLQPkspQHYSSPEEFVADVRLMFKNCYKFNEeDSEV 88

                         90
                 ....*....|....*....
gi 528473945 578 GQLGAKLKEIFEDEIQKIF 596
Cdd:cd05502   89 AQAGKELELFFEEQLKEIL 107

SAND domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528473945   330 PSLPVSCVSLIGTLFKDRFATGRCGKSIRTKQHWFTPEEFVKEEPTLSDGLWKRDILCHGKTLNFLCEKKILD 402
Cdd:smart00258   1 SELPVTCGTVKGILYKKKFKCGISVKCIQYEDKWFTPKEFEIEGGKGKSKDWKRSIRCGGSSLRTLMENGTLD 73

Bromodomain. BDF1/BDF2 like subfamily, restricted to fungi, repeat II. BDF1 and BDF2 are yeast transcription factors involved in the expression of a wide range of genes, including snRNAs; they are required for sporulation and DNA repair and protect histone H4 from deacetylation. 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 528473945 511 NEDIQKVFVKDPRP---NVRRYSEFISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKFNRD-NKFGQLGAKLKE 586
Cdd:cd05499   17 HSAYNWPFLDPVDPvalNIPNYFSIIKKPMDLGTISKKLQNGQYQSAKEFERDVRLIFKNCYTFNPEgTDVYMMGHQLEE 96

                 ....*
gi 528473945 587 IFEDE 591
Cdd:cd05499   97 VFNDK 101

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 528473945 428 ECNVCHSEGNLVCCDKCPRAFHPDCHLPAVNEEDSawQWICTFC 471
Cdd:cd15626    1 KCEVCGQEGKLFCCCTCSRVFHEDCHIPPVEAQRS--PWSCTFC 42

PHD finger found in transcription intermediary factor 1-alpha (TIF1-alpha); TIF1-alpha, also termed tripartite motif-containing protein 24 (TRIM24), or E3 ubiquitin-protein ligase TRIM24, or RING finger protein 82, belongs to the TRIM/RBCC protein family. It interacts specifically and in a ligand-dependent manner with the ligand binding domain (LBD) of several nuclear receptors (NRs), including retinoid X (RXR), retinoic acid (RAR), vitamin D3 (VDR), estrogen (ER), and progesterone (PR) receptors. It also associates with heterochromatin-associated factors HP1alpha, MOD1 (HP1beta) and MOD2 (HP1gamma), as well as vertebrate Kruppel-type (C2H2) zinc finger proteins that contain transcriptional silencing domain KRAB. TIF1-alpha is a ligand-dependent co-repressor of retinoic acid receptor (RAR) that interacts with multiple nuclear receptors in vitro via an LXXLL motif, and further acts as a gatekeeper of liver carcinogenesis. It also functions as an E3-ubiquitin ligase targeting p53 and is broadly associated with chromatin silencing. Moreover, it is a chromatin regulator that recognizes specific, combinatorial histone modifications through its C-terminal plant homeodomain (PHD)-Bromodomain (Bromo) region. In addition, it interacts with chromatin and estrogen receptor to activate estrogen-dependent genes associated with cellular proliferation and tumor development. TIF1-alpha 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 528473945 429 CNVCHSEGNLVCCDKCPRAFHPDCHLPAVNEEDSAwQWICTFC 471
Cdd:cd15622    2 CAVCQNGGELLCCEKCPKVFHLSCHVPTLMNFPSG-EWICTFC 43

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 528473945 429 CNVCHSEGNLVCCDKCPRAFHPDCHLPAVNEED-SAWQWICTFC 471
Cdd:cd15533    2 CDSCGEGGDLLCCDRCPASFHLQCCNPPLDEEDlPPGEWLCHRC 45

Bromodomain; Acf1_like or BAZ1A_like subfamily. Bromo adjacent to zinc finger 1A (BAZ1A) was identified as a novel human bromodomain gene by cDNA library screening. The Drosophila homologue, Acf1, is part of the CHRAC (chromatin accessibility complex) and regulates ISWI-induced nucleosome remodeling. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 528473945 529 YSEFISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKFN-RDNKFGQLGAKLKEIFEDEIQKI 595
Cdd:cd05504   45 YYDIIKKPMDLGTIKEKLNMGEYKLAEEFLSDIQLVFSNCFLYNpEHTSVYKAGTRLQRFFIKRCRKL 112

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 528473945 429 CNVCHSEGNLVCCDKCPRAFHPDCHLPAVNEEDSAwQWICTFC 471
Cdd:cd15624    2 CAVCQNGGDLLCCEKCPKVFHLTCHVPTLLSFPSG-DWICTFC 43

PHD finger 1 found in Saccharomyces cerevisiae transcriptional regulatory protein Rco1 and similar proteins; Rco1 is a component of the Rpd3S histone deacetylase complex that plays an important role at actively transcribed genes. Rco1 contains two plant homeodomain (PHD) fingers, which are required for the methylation of histone H3 lysine 36 (H3K36) nucleosome recognition by Rpd3S. This model corresponds to the first PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 528473945 429 CNVCHSEGNLVCCDKCPRAFHPDCHLPAVNEED-SAWQWICTFC 471
Cdd:cd15535    2 CSACGGYGSFLCCDGCPRSFHFSCLDPPLEEDNlPDDEWFCNEC 45

PHD finger 1 found in autoimmune regulator (AIRE); AIRE, also termed autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) protein, functions as a regulator of gene transcription in the thymus. It is essential for prevention of autoimmunity. AIRE plays a critical role in the induction of central tolerance. It promotes self-tolerance through tissue-specific antigen (TSA) expression. It also acts as an active regulator of chondrocyte differentiation. AIRE contains a homogeneously-staining region (HSR) or caspase-recruitment domain (CARD), a nuclear localization signal (NLS), a SAND (for Sp100, AIRE, nuclear phosphoprotein 41/75 or NucP41/75, and deformed epidermal auto regulatory factor 1 or Deaf1) domain, two plant homeodomain (PHD) fingers, and four LXXLL (where L stands for leucine) motifs. This model corresponds to the first PHD finger that recognizes the unmethylated tail of histone H3 and targets AIRE-dependent genes.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 528473945 428 ECNVCHSEGNLVCCDKCPRAFHPDCHLPAVNEEDSAwQWICTFC 471
Cdd:cd15539    1 ECAVCGDGGELLCCDGCPRAFHLACLVPPLTLIPSG-TWRCSSC 43

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 528473945   429 CNVCHS---EGNLVCCDKCPRAFHPDCHLPAVNEEDSAWQWICTFC 471
Cdd:smart00249   2 CSVCGKpddGGELLQCDGCDRWYHQTCLGPPLLEEEPDGKWYCPKC 47

Bromodomain; SPT7_like subfamily. SPT7 is a yeast protein that functions as a component of the transcription regulatory histone acetylation (HAT) complexes SAGA, SALSA, and SLIK. SAGA is involved in the RNA polymerase II-dependent transcriptional regulation of about 10% of all yeast genes. The SPT7 bromodomain has been shown to weakly interact with acetylated histone H3, but not H4. The human representative of this subfamily is cat eye syndrome critical region protein 2 (CECR2). 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
                 ....*....|....*....|....*....|....*....|....*.
gi 528473945 529 YSEFISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKFNRD 574
Cdd:cd05510   41 YYDIIKKPMDLGTMLKKLKNLQYKSKAEFVDDLNLIWKNCLLYNSD 86

Bromodomain, polybromo repeat V. Polybromo is a nuclear protein of unknown function, which contains 6 bromodomains. The human ortholog BAF180 is part of a SWI/SNF chromatin-remodeling complex, and it may carry out the functions of Yeast Rsc-1 and Rsc-2. It was shown that polybromo bromodomains bind to histone H3 at specific acetyl-lysine positions. Bromodomains are found in many chromatin-associated proteins and in nuclear histone acetyltransferases. They interact specifically with acetylated lysine, but not all the bromodomains in polybromo may bind to acetyl-lysine.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 528473945 529 YSEFISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKFN 572
Cdd:cd05515   39 YYDVIKKPIDMEKIRSKIEGNQYQSLDDMVSDFVLMFDNACKYN 82

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 528473945 429 CNVCHSEGNLVCCDKCPRAFHPDCHLPAVNEEDSAwQWICTFC 471
Cdd:cd15623    2 CRVCQKAGALVMCDQCEFCFHLDCHLPALQEVPGE-DWKCLLC 43

Bromodomain, polybromo repeat I. Polybromo is a nuclear protein of unknown function, which contains 6 bromodomains. The human ortholog BAF180 is part of a SWI/SNF chromatin-remodeling complex, and it may carry out the functions of Yeast Rsc-1 and Rsc-2. It was shown that polybromo bromodomains bind to histone H3 at specific acetyl-lysine positions. Bromodomains are found in many chromatin-associated proteins and in nuclear histone acetyltransferases. They interact specifically with acetylated lysine, but not all the bromodomains in polybromo may bind to acetyl-lysine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528473945 511 NEDIQKVFVKDP-RPNVRRYSEFISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKF-NRDNKFGQLGAKLKEIF 588
Cdd:cd05524   22 GRILCESFIRVPkRRNEPEYYEVVSNPIDLLKIQQKLKTEEYDDVDDLTADFELLINNAKAYyKPDSPEHKDACKLWELF 101

                 ....*..
gi 528473945 589 EDEIQKI 595
Cdd:cd05524  102 LSARNEV 108

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 528473945 525 NVRRYSEFISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKFNRDNKfgQLGAKLKEIFE 589
Cdd:cd05511   29 KVPDYYKIIKRPMDLQTIRKKISKHKYQSREEFLEDIELIVDNSVLYNGPDS--VYTKKAKEMLE 91

Bromodomain; ASH1_like sub-family. ASH1 (absent, small, or homeotic 1) is a member of the trithorax-group in Drosophila melanogaster, an epigenetic transcriptional regulator of HOX genes. Drosophila ASH1 has been shown to methylate specific lysines in histones H3 and H4. Mammalian ASH1 has been shown to methylate histone H3. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528473945 522 PRPNVRRYSEFISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKFN-RDNKFGQLGAKLKEIFED 590
Cdd:cd05525   34 SKKKNPDYYERITDPVDLSTIEKQILTGYYKTPEAFDSDMLKVFRNAEKYYgRKSPIGRDVCRLRKAYYQ 103

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
                 ....*....|....*....|....*....|....*....|....
gi 528473945 429 CNVCHSEGNLVCCDKCPRAFHPDC-HLPAVNEEdsawQWICTFC 471
Cdd:cd15567    2 CFICSEGGSLICCESCPASFHPEClGLEPPPEG----KFYCEDC 41

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 528473945 529 YSEFISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKF--NRDNKFGQLGAKLKEIFEDEIQKI 595
Cdd:cd05496   38 YRDIIDTPMDLGTVKETLFGGNYDDPMEFAKDVRLIFSNSKSYtpNKRSRIYSMTLRLSALFEEHIKKI 106

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 528473945 429 CNVCHSEGNLVCCDKCPRAFHPDCHLPAVNEEDSAwQWICTFC 471
Cdd:cd15559    2 CRVCHKLGDLLCCETCSAVYHLECVDPPLEEVPEE-DWQCEVC 43

PHD finger 4 found in nuclear SET domain-containing protein 2 (NSD2); NSD2, also termed histone-lysine N-methyltransferase NSD2, or multiple myeloma SET domain-containing protein (MMSET), or protein trithorax-5 Wolf-Hirschhorn syndrome candidate 1 protein (WHSC1), is overexpressed frequently in the t(4;14) translocation in 15% to 20% of multiple myeloma. It plays important roles in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. It also enhances androgen receptor (AR)-mediated transcription. The principal chromatin-regulatory activity of NSD2 is dimethylation of histone H3 at lysine 36 (H3K36me2). NSD2 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, a high mobility group (HMG) box, five PHD (plant-homeodomain) zinc fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP, HMG, and PHD fingers mediate chromatin interaction and recognition of histone marks. This model corresponds to the fourth PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 528473945 429 CNVCHSEGNLVCCDKCPRAFHPDChlpaVNEEDSAWQWICTFC 471
Cdd:cd15657    2 CFVCSKGGSLLCCESCPAAFHPDC----LNIEMPDGSWFCNDC 40

PHD finger 4 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 fourth PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 528473945 429 CNVCHSEGNLVCCDKCPRAFHPDChlpaVNEEDSAWQWICTFC 471
Cdd:cd15658    2 CFVCARGGRLLCCESCPASFHPEC----LSIEMPEGCWNCNEC 40

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 528473945 524 PNVRRYSEF---ISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKFNRDNKFgqlgaklkeIFED--EIQKIF 596
Cdd:cd05519   31 PSKKLYPDYyviIKRPIALDQIKRRIEGRAYKSLEEFLEDFHLMFANARTYNQEGSI---------VYEDavEMEKAF 99

PHD finger 2 found in monocytic leukemia zinc-finger protein (MOZ) and its factor (MORF); MOZ, also termed histone acetyltransferase KAT6A, YBF2/SAS3, SAS2 and TIP60 protein 3 (MYST-3), or runt-related transcription factor-binding protein 2, or zinc finger protein 220, is a MYST-type histone acetyltransferase (HAT) that functions as a coactivator for acute myeloid leukemia 1 protein (AML1)- and p53-dependent transcription. It possesses intrinsic HAT activity to acetylate both itself and lysine (K) residues on histone H2B, histone H3 (K14) and histone H4 (K5, K8, K12 and K16) in vitro and H3K9 in vivo. MOZ-related factor (MORF), also termed MOZ2, or histone acetyltransferase KAT6B, or MOZ, YBF2/SAS3, SAS2 and TIP60 protein 4 (MYST4), is a ubiquitously expressed transcriptional regulator with intrinsic HAT activity. It can interact with the Runt-domain transcription factor Runx2 and form a tetrameric complex with BRPFs, ING5, and EAF6. Both MOZ and MORF are catalytic subunits of HAT complexes that are required for normal developmental programs, such as hematopoiesis, neurogenesis, and skeletogenesis, and are also implicated in human leukemias. MOZ is also the catalytic subunit of a tetrameric inhibitor of growth 5 (ING5) complex, which specifically acetylates nucleosomal histone H3K14. Moreover, MOZ and MORF are involved in regulating transcriptional activation mediated by Runx2 (or Cbfa1), a Runt-domain transcription factor known to play important roles in T cell lymphomagenesis and bone development, and its homologs. MOZ contains a linker histone 1 and histone 5 domains and two plant homeodomain (PHD) fingers. In contrast, MORF contains an N-terminal region containing two PHD fingers, a putative HAT domain, an acidic region, and a C-terminal Ser/Met-rich domain. The family corresponds to the first PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 528473945 429 CNVCHSEG---NLVCCDKCPRAFHPDCHLPAVNEEDSAwQWICTFC 471
Cdd:cd15527    2 CSVCQDSGnadNLLFCDACDKGFHMECHDPPLTRMPKG-KWVCQIC 46

Bromodomain, polybromo repeat III. Polybromo is a nuclear protein of unknown function, which contains 6 bromodomains. The human ortholog BAF180 is part of a SWI/SNF chromatin-remodeling complex, and it may carry out the functions of Yeast Rsc-1 and Rsc-2. It was shown that polybromo bromodomains bind to histone H3 at specific acetyl-lysine positions. Bromodomains are found in many chromatin-associated proteins and in nuclear histone acetyltransferases. They interact specifically with acetylated lysine, but not all the bromodomains in polybromo may bind to acetyl-lysine.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 528473945 524 PNVRRYSEF---ISDPMWLNRIKQKLKDNMYQKFGEFASDFQLIFSNCRKFNRDN 575
Cdd:cd05520   31 PSKRKYPDYyqeIKNPISLQQIRTKLKNGEYETLEELEADLNLMFENAKRYNVPN 85

PHD finger 1 found in polycomb repressive complex 2 (PRC2)-associated polycomb-like (PCL) family proteins MTF2, PHF19, and similar proteins; The family includes two PCL family proteins, metal-response element-binding transcription factor 2 (MTF2/PCL2) and PHF19/PCL3, which are homologs of PHD finger protein1 (PHF1). PCL family proteins are accessory components of the polycomb repressive complex 2 (PRC2) core complex and all contain an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain. They specifically recognize tri-methylated H3K36 (H3K36me3) through their N-terminal Tudor domains. The interaction between their Tudor domains and H3K36me3 is critical for both the targeting and spreading of PRC2 into active chromatin regions and for the maintenance of optimal repression of poised developmental genes where PCL proteins, H3K36me3, and H3K27me3 coexist. Moreover, unlike other PHD finger-containing proteins, the first PHD fingers of PCL proteins do not display histone H3K4 binding affinity and they do not affect the Tudor domain binding to histones. This model corresponds to the first PHD finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 528473945 429 CNVC----HSEGNLVC-CDKCPRAFHPDCHLPAVNEED--SAWQWICTFCML 473
Cdd:cd15499    2 CSICggaeARDGNEILiCDKCDKGYHQLCHSPKVRTSPleGDEKWFCSRCVF 53