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 1958802754 597 PQEQLKCEYVLLRVYCCSESSFFSKMPYYyyeRRLYCfcgvsgtpgnvnaepwysrssgyfphqfremaVGVQEPMWLDI 676
Cdd:cd05501     1 PEELLKCEFLLLKVYCMSKSGFFISKPYY---IRDYC--------------------------------QGIKEPMWLNK 45

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958802754 677 IKRKLSDQAYSQVEDFVQDMRLIFRNHRITFKDPKFGEMGLILESKFEKSFKEAFAI 733
Cdd:cd05501    46 VKERLNERVYHTVEGFVRDMRLIFHNHKLFYKDDDFGQVGITLEKKFEKNFKEVFAI 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 1958802754 533 ECEVCRDGGTLFCCDTCSRAFHEECHIPAVEAEVTPWSCIFC 574
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 1958802754 597 PQEQLKCEYVLLRVYCCSESSFFSKMPYYyyeRRLYCfcgvsgtpgnvnaepwysrssgyfphqfremaVGVQEPMWLDI 676
Cdd:cd05501     1 PEELLKCEFLLLKVYCMSKSGFFISKPYY---IRDYC--------------------------------QGIKEPMWLNK 45

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958802754 677 IKRKLSDQAYSQVEDFVQDMRLIFRNHRITFKDPKFGEMGLILESKFEKSFKEAFAI 733
Cdd:cd05501    46 VKERLNERVYHTVEGFVRDMRLIFHNHKLFYKDDDFGQVGITLEKKFEKNFKEVFAI 102

SAND domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958802754  445 ELLPVTCGNLKGVLHKDKFKQGISVMSIQcQDGNWVTPPEFEIMGGHGRSKNWKLSLRCYNWPLKLLIQRNFLP 518
Cdd:smart00258   1 SELPVTCGTVKGILYKKKFKCGISVKCIQ-YEDKWFTPKEFEIEGGKGKSKDWKRSIRCGGSSLRTLMENGTLD 73

bromo domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958802754  597 PQEQLKCEYVLLRVYCCSESSFFSKMPYyyyerrlycfcgvsgTPGNVNAEPWYSRssgyfphqfremavGVQEPMWLDI 676
Cdd:smart00297   2 PKLQKKLQELLKAVLDKLDSHPLSWPFL---------------KPVSRKEAPDYYD--------------IIKKPMDLKT 52

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1958802754  677 IKRKLSDQAYSQVEDFVQDMRLIFRNHRITF-KDPKFGEMGLILESKFEKSFKEA 730
Cdd:smart00297  53 IKKKLENGKYSSVEEFVADFNLMFSNARTYNgPDSEVYKDAKKLEKFFEKKLREL 107

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
                  ....*....|....*....|....*....|....*....|....*...
gi 1958802754 534 CEVCR---DGGTLFCCDTCSRAFHEECHIPAVEAEVTP---WSCIFCR 575
Cdd:pfam00628   2 CAVCGksdDGGELVQCDGCDDWFHLACLGPPLDPAEIPsgeWLCPECK 49

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 1958802754  534 CEVCR---DGGTLFCCDTCSRAFHEECHIPAVEAEVTP--WSCIFC 574
Cdd:smart00249   2 CSVCGkpdDGGELLQCDGCDRWYHQTCLGPPLLEEEPDgkWYCPKC 47

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 1958802754 597 PQEQLKCEYVLLRVYCCSESSFFSKMPYYyyeRRLYCfcgvsgtpgnvnaepwysrssgyfphqfremaVGVQEPMWLDI 676
Cdd:cd05501     1 PEELLKCEFLLLKVYCMSKSGFFISKPYY---IRDYC--------------------------------QGIKEPMWLNK 45

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958802754 677 IKRKLSDQAYSQVEDFVQDMRLIFRNHRITFKDPKFGEMGLILESKFEKSFKEAFAI 733
Cdd:cd05501    46 VKERLNERVYHTVEGFVRDMRLIFHNHKLFYKDDDFGQVGITLEKKFEKNFKEVFAI 102

SAND domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958802754  445 ELLPVTCGNLKGVLHKDKFKQGISVMSIQcQDGNWVTPPEFEIMGGHGRSKNWKLSLRCYNWPLKLLIQRNFLP 518
Cdd:smart00258   1 SELPVTCGTVKGILYKKKFKCGISVKCIQ-YEDKWFTPKEFEIEGGKGKSKDWKRSIRCGGSSLRTLMENGTLD 73

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 1958802754 533 ECEVCRDGGTLFCCDTCSRAFHEECHIPAV-EAEVTPWSCIFC 574
Cdd:cd15541     1 WCAVCQNGGELLCCDKCPRVFHLDCHIPPIpEFPSGEWSCSLC 43

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958802754 668 VQEPMWLDIIKRKLSDQAYSQVEDFVQDMRLIFRNHRiTF--KDPKFGEMGLILESKFEK 725
Cdd:cd04369    39 IKNPMDLSTIKKKLKNGEYKSLEEFEADVRLIFSNAK-TYngPGSPIYKDAKKLEKLFEK 97

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 1958802754 530 NSDECEVCRDGGTLFCCDTCSRAFHEECHIPAVEA-EVTPWSCIFCR 575
Cdd:cd15625     1 NEDFCAVCLNGGELLCCDRCPKVFHLSCHVPALLSfPVGEWVCTLCR 47

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 1958802754 533 ECEVCRDGGTLFCCDTCSRAFHEEC-HIPAVEAEVTPWSCIFC 574
Cdd:cd15539     1 ECAVCGDGGELLCCDGCPRAFHLAClVPPLTLIPSGTWRCSSC 43

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 1958802754 668 VQEPMWLDIIKRKLSDQAYSQVEDFVQDMRLIFRN 702
Cdd:pfam00439  33 IKKPMDLSTIKKKLENGEYKSLAEFLADVKLIFSN 67

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 1958802754 534 CEVCRDGGTLFCCDTCSRAFHEECHIPAVEAEVT-PWSCIFCR 575
Cdd:cd15624     2 CAVCQNGGDLLCCEKCPKVFHLTCHVPTLLSFPSgDWICTFCR 44

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 1958802754 534 CEVCRDGGTLFCCDTCSRAFHEECHIPAVE-AEVTPWSCIFC 574
Cdd:cd15531     2 CEVCQQGGEIILCDTCPRAYHLVCLDPELEkAPEGKWSCPHC 43

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958802754 668 VQEPMWLDIIKRKLSDQAYSQVEDFVQDMRLIFRNHRI-TFKDPKFGEMGLILESKFEKSFKE 729
Cdd:COG5076   185 IKSPMDLLTIQKKLKNGRYKSFEEFVSDLNLMFDNCKLyNGPDSSVYVDAKELEKYFLKLIEE 247

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 1958802754 534 CEVCRDGG---TLFCCDTCSRAFHEECHIPAV-EAEVTPWSCIFC 574
Cdd:cd15527     2 CSVCQDSGnadNLLFCDACDKGFHMECHDPPLtRMPKGKWVCQIC 46

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 1958802754 534 CEVCRDGGTLFCCDTCSRAFHEEC 557
Cdd:cd15532     2 CRVCKDGGELLCCDGCPSSYHLHC 25

Bromodomain; Gcn5_like subfamily. Gcn5p is a histone acetyltransferase (HAT) which mediates acetylation of histones at lysine residues; such acetylation is generally correlated with the activation of transcription. 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 1958802754 668 VQEPMWLDIIKRKLSDQAYSQVEDFVQDMRLIFRNHRiTFKDPK--FGEMGLILESKFEKSFKE 729
Cdd:cd05509    38 IKKPMDLSTMEEKLENGYYVTLEEFVADLKLIFDNCR-LYNGPDteYYKCANKLEKFFWKKLKE 100

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 1958802754 534 CEVCRDGGT-----LFCCDTCSRAFHEECHIPAVEAEV----TPWSCIFC 574
Cdd:cd15578     2 CTVCQDGSSespneIVLCDKCGQGYHQLCHNPKIDSSVldpdVPWLCRQC 51

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 1958802754 534 CEVCRDGGTLFCCDTCSRAFHEEC 557
Cdd:cd15567     2 CFICSEGGSLICCESCPASFHPEC 25

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
                  ....*....|....*....|....*..
gi 1958802754 533 ECEVCRDGGTLFCCD--TCSRAFHEEC 557
Cdd:cd15568     1 ECFRCGDGGDLVLCDfkGCPKVYHLSC 27

Bromodomain, uncharacterized subfamily specific to plants. Might function as a global transcription factor. 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 1958802754 668 VQEPMWLDIIKRKLSDQAYSQVEDFVQDMRLIFRNhRITFKDPK--FGEMGLILESKFEK 725
Cdd:cd05506    39 IKKPMDLGTVKKKLEKGEYSSPEEFAADVRLTFAN-AMRYNPPGndVHTMAKELLKIFET 97

Bromodomain, polybromo repeat IV. 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
                  ....*....|....*....|....*....|....*..
gi 1958802754 668 VQEPMWLDIIKRKLSDQAYSQVEDFVQDMRLIFRNHR 704
Cdd:cd05518    43 ILEPIDLKTIEHNIRNDKYATEEELMDDFKLMFRNAR 79

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 1958802754 534 CEVCRDGGTLFCCDTCSRAFHEECHIPAVEAEVT-PWSCIFC 574
Cdd:cd15523     2 CSVCRKSGELLMCDTCSLVYHLDCLDPPLKTIPKgMWICPKC 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.

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                  ....*....|....*....|....*....|....*....|..
gi 1958802754 534 CEVCRDGGTLFCCDTCSRAFHEEC-HIPAVEAEVTPWSCIFC 574
Cdd:cd15559     2 CRVCHKLGDLLCCETCSAVYHLECvDPPLEEVPEEDWQCEVC 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.

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                  ....*....|....*....|....*....|....*
gi 1958802754 668 VQEPMWLDIIKRKLSDQAYSQVEDFVQDMRLIFRN 702
Cdd:cd05511    37 IKRPMDLQTIRKKISKHKYQSREEFLEDIELIVDN 71

PHD finger 2 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 second PHD finger that may play a critical role in the activation of gene transcription.

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gi 1958802754 533 ECEVCRDGGT-LFCCDTCSRAFHEECHIPA 561
Cdd:cd15540     1 RCGVCRGGRGdLLRCPQCLQAFHWHCHFPS 30

Bromodomain, cbp_like subfamily. Cbp (CREB binding protein or CREBBP) is an acetyltransferase acting on histone, which gives a specific tag for transcriptional activation and also acetylates non-histone proteins. CREBBP binds specifically to phosphorylated CREB protein and augments the activity of phosphorylated CREB to activate transcription of cAMP-responsive genes. 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 1958802754 668 VQEPMWLDIIKRKLSDQAYSQVEDFVQDMRLIFRN 702
Cdd:cd05495    43 VKNPMDLSTIRRKLDTGQYQDPWQYVDDVWLMFDN 77

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.

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                  ....*....|....*....|....*....|....*....|..
gi 1958802754 534 CEVCRDGGTLFCCDTCSRAFHEECHipAVEAEVTPWSCIFCR 575
Cdd:cd15657     2 CFVCSKGGSLLCCESCPAAFHPDCL--NIEMPDGSWFCNDCR 41

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.

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                  ....*....|....*....|....*....|....*....|...
gi 1958802754 534 CEVCRDGGTLFCCDTCSRAFHEEChIPAVEAEVTP--WSCIFC 574
Cdd:cd15537     2 CFECHAPGEVLPCSGCFRVYHSDC-LSEDFRPDSTshWTCPVC 43

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.

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                  ....*....|....*....|....*....|....*
gi 1958802754 668 VQEPMWLDIIKRKLSDQAYSQVEDFVQDMRLIFRN 702
Cdd:cd05504    49 IKKPMDLGTIKEKLNMGEYKLAEEFLSDIQLVFSN 83