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 1958803196 646 PEEQLKCELLLLTIYCCPKSGFFIRKPKKRKEDFPDLQEHMWLNKIKHRLNKKAYHSVQHFVGDMRLIFQNHSKFYK-SR 724
Cdd:cd05501     1 PEELLKCEFLLLKVYCMSKSGFFISKPYYIRDYCQGIKEPMWLNKVKERLNERVYHTVEGFVRDMRLIFHNHKLFYKdDD 80

                          90       100
                  ....*....|....*....|..
gi 1958803196 725 FKNLGVIVGNKFEKTFKSVFSI 746
Cdd:cd05501    81 FGQVGITLEKKFEKNFKEVFAI 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 1958803196 578 ACKVCGQRRRVRPCATCRKCYHKNCHIPPVEVQSGPWHCAFC 619
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 1958803196 646 PEEQLKCELLLLTIYCCPKSGFFIRKPKKRKEDFPDLQEHMWLNKIKHRLNKKAYHSVQHFVGDMRLIFQNHSKFYK-SR 724
Cdd:cd05501     1 PEELLKCEFLLLKVYCMSKSGFFISKPYYIRDYCQGIKEPMWLNKVKERLNERVYHTVEGFVRDMRLIFHNHKLFYKdDD 80

                          90       100
                  ....*....|....*....|..
gi 1958803196 725 FKNLGVIVGNKFEKTFKSVFSI 746
Cdd:cd05501    81 FGQVGITLEKKFEKNFKEVFAI 102

SAND domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958803196  477 ELLVTCGKVVGTLYKEKLNQGIHVKSIQStEGKWFTPLEFEIEGGYEKCKNWRQSIRCSGWPLKELIKRGELQ 549
Cdd:smart00258   2 ELPVTCGTVKGILYKKKFKCGISVKCIQY-EDKWFTPKEFEIEGGKGKSKDWKRSIRCGGSSLRTLMENGTLD 73

bromo domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803196  645 SPEEQLKCELLLLTIYCC----PKSGFFIRKPKKRK-EDFPDL-QEHMWLNKIKHRLNKKAYHSVQHFVGDMRLIFQNHS 718
Cdd:smart00297   1 DPKLQKKLQELLKAVLDKldshPLSWPFLKPVSRKEaPDYYDIiKKPMDLKTIKKKLENGKYSSVEEFVADFNLMFSNAR 80

                           90       100
                   ....*....|....*....|....*
gi 1958803196  719 KFYK--SRFKNLGVIVGNKFEKTFK 741
Cdd:smart00297  81 TYNGpdSEVYKDAKKLEKFFEKKLR 105

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        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803196 668 FIRKPKKR-KEDFPDLQEH-MWLNKIKHRLNKKAYHSVQHFVGDMRLIFQNHSKFYKSRF 725
Cdd:pfam00439  17 FLEPVDPDeYPDYYSVIKKpMDLSTIKKKLENGEYKSLAEFLADVKLIFSNARTYNGPGS 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 1958803196 646 PEEQLKCELLLLTIYCCPKSGFFIRKPKKRKEDFPDLQEHMWLNKIKHRLNKKAYHSVQHFVGDMRLIFQNHSKFYK-SR 724
Cdd:cd05501     1 PEELLKCEFLLLKVYCMSKSGFFISKPYYIRDYCQGIKEPMWLNKVKERLNERVYHTVEGFVRDMRLIFHNHKLFYKdDD 80

                          90       100
                  ....*....|....*....|..
gi 1958803196 725 FKNLGVIVGNKFEKTFKSVFSI 746
Cdd:cd05501    81 FGQVGITLEKKFEKNFKEVFAI 102

SAND domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958803196  477 ELLVTCGKVVGTLYKEKLNQGIHVKSIQStEGKWFTPLEFEIEGGYEKCKNWRQSIRCSGWPLKELIKRGELQ 549
Cdd:smart00258   2 ELPVTCGTVKGILYKKKFKCGISVKCIQY-EDKWFTPKEFEIEGGKGKSKDWKRSIRCGGSSLRTLMENGTLD 73

bromo domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803196  645 SPEEQLKCELLLLTIYCC----PKSGFFIRKPKKRK-EDFPDL-QEHMWLNKIKHRLNKKAYHSVQHFVGDMRLIFQNHS 718
Cdd:smart00297   1 DPKLQKKLQELLKAVLDKldshPLSWPFLKPVSRKEaPDYYDIiKKPMDLKTIKKKLENGKYSSVEEFVADFNLMFSNAR 80

                           90       100
                   ....*....|....*....|....*
gi 1958803196  719 KFYK--SRFKNLGVIVGNKFEKTFK 741
Cdd:smart00297  81 TYNGpdSEVYKDAKKLEKFFEKKLR 105

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 1958803196 644 MSPEEQLKCELLLLTIYCCPKSGFFIRKPKKRKEDFPDLQEH-MWLNKIKHRLNKKA---YHSVQHFVGDMRLIFQNHSK 719
Cdd:cd05502     1 LSPIDQRKCERLLLELYCHELSLPFHEPVSPSVPNYYKIIKTpMDLSLIRKKLQPKSpqhYSSPEEFVADVRLMFKNCYK 80

                  ...
gi 1958803196 720 FYK 722
Cdd:cd05502    81 FNE 83

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 1958803196 579 CKVCGQRRRVRPCATCRKCYHKNCHIPPV-EVQSGPWHCAFC 619
Cdd:cd15623     2 CRVCQKAGALVMCDQCEFCFHLDCHLPALqEVPGEDWKCLLC 43

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958803196 676 KEDFPDLQEH----MWLNKIKHRLNKKAYHSVQHFVGDMRLIFQN-------HSKFYKSrfknlgvivGNKFEKTFK 741
Cdd:cd05509    28 KEEAPDYYDVikkpMDLSTMEEKLENGYYVTLEEFVADLKLIFDNcrlyngpDTEYYKC---------ANKLEKFFW 95

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 1958803196 633 CHKESEVLKRKMSPEEQLKCELllltiyccpksgfFIRKPKKRKEdfPD----LQEHMWLNKIKHRLNKKAYHSVQHFVG 708
Cdd:cd05524     7 CQELYDTIRNYKSEDGRILCES-------------FIRVPKRRNE--PEyyevVSNPIDLLKIQQKLKTEEYDDVDDLTA 71

                          90
                  ....*....|....
gi 1958803196 709 DMRLIFQNHSKFYK 722
Cdd:cd05524    72 DFELLINNAKAYYK 85

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
                  ....*....|....*....|....*....|
gi 1958803196 591 CATCRKCYHKNCHIPPVEVQ-SGPWHCAFC 619
Cdd:cd15527    17 CDACDKGFHMECHDPPLTRMpKGKWVCQIC 46

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 1958803196 579 CKVCGQRRRVRP----CATCRKCYHKNCHIPPVE--VQSGPWHCAFC 619
Cdd:cd15489     2 CIVCGKGGDLGGellqCDGCGKWFHADCLGPPLSsfVPNGKWICPVC 48

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803196 663 PKSGFFIRKPKKRkeDFPD----LQEHMWLNKIKHRLNKKAYHSVQHFVGDMRLIFQNhSKFYKSRfknlGVIV---GNK 735
Cdd:cd05519    22 KLSELFLEKPSKK--LYPDyyviIKRPIALDQIKRRIEGRAYKSLEEFLEDFHLMFAN-ARTYNQE----GSIVyedAVE 94

                  ....*....
gi 1958803196 736 FEKTFKSVF 744
Cdd:cd05519    95 MEKAFKKKY 103

Bromodomain, repeat II in Rsc1/2_like subfamily, specific to fungi. Rsc1 and Rsc2 are components of the RSC complex (remodeling the structure of chromatin), are essential for transcriptional control, and have a specific domain architecture including two bromodomains. The RSC complex has also been linked to homologous recombination and nonhomologous end-joining repair of DNA double strand breaks. 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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958803196 676 KEDFPD----LQEHMWLNKIKHRLNKKAYHSVQHFVGDMRLIFQNHSKFYKS 723
Cdd:cd05522    34 KAREPEyyqeISNPISLDDIKKKVKRRKYKSFDQFLNDLNLMFENAKLYNEN 85

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 1958803196 579 CKVCGQRRRVRPCATCRKCYHKNCHIPPV-EVQSGPWHCAFC 619
Cdd:cd15539     2 CAVCGDGGELLCCDGCPRAFHLACLVPPLtLIPSGTWRCSSC 43

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 1958803196 579 CKVCGQRRRVRPCATCRKCYHKNCHIPPV-EVQSGPWHCAFC 619
Cdd:cd15622     2 CAVCQNGGELLCCEKCPKVFHLSCHVPTLmNFPSGEWICTFC 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 1958803196 579 CKVCGQRRRVRPCATCRKCYHKNCHIPP-VEVQSGPWHCAFCK 620
Cdd:cd15624     2 CAVCQNGGDLLCCEKCPKVFHLTCHVPTlLSFPSGDWICTFCR 44

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 1958803196  579 CKVCGQRRRVRP---CATCRKCYHKNCHIPP--VEVQSGPWHCAFC 619
Cdd:smart00249   2 CSVCGKPDDGGEllqCDGCDRWYHQTCLGPPllEEEPDGKWYCPKC 47

PHD finger 1 found in lysine-specific demethylase 5B (KDM5B); KDM5B (also termed Cancer/testis antigen 31 (CT31), Histone demethylase JARID1B, Jumonji/ARID domain-containing protein 1B (JARID1B), PLU-1, or retinoblastoma-binding protein 2 homolog 1 (RBP2-H1 or RBBP2H1A)) is a member of the JARID subfamily within the JmjC proteins. It has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of pregnant females and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis. KDM5B acts as a histone demethylase that catalyzes the removal of trimethylation of lysine 4 on histone H3 (H3K4me3), induced by polychlorinated biphenyls (PCBs). It also mediates demethylation of H3K4me2 and H3K4me1. Moreover, KDM5B functions as a negative regulator of hematopoietic stem cell (HSC) self-renewal and progenitor cell activity. KDM5B has also been shown to interact with the DNA binding transcription factors BF-1 and PAX9, as well as TIEG1/KLF10 (transforming growth factor-beta inducible early gene-1/Kruppel-like transcription factor 10), and possibly function as a transcriptional corepressor. KDM5B contains the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers. This model corresponds to the first PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1958803196 578 ACKVCGQ---RRRVRPCATCRKCYHKNCHIPPV-EVQSGPWHCAFC 619
Cdd:cd15603     1 VCLVCGSgndEDRLLLCDGCDDSYHTFCLIPPLhDVPKGDWRCPKC 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        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1958803196 579 CKVCGQRRRVRPCATCRKCYHKNCHIPPV-EVQSGPWHCAFC 619
Cdd:cd15532     2 CRVCKDGGELLCCDGCPSSYHLHCLNPPLaEIPDGDWFCPRC 43

PHD finger 5 found in Histone-lysine N-methyltransferase 2C (KMT2C) and PHD finger 4 found in KMT2D; KMT2C, also termed myeloid/lymphoid or mixed-lineage leukemia protein 3 (MLL3), or homologous to ALR protein, is a histone H3 lysine 4 (H3K4) lysine methyltransferase that functions as a circadian factor contributing to genome-scale circadian transcription. It is a component of a large complex that acts as a coactivator of multiple transcription factors, including the bile acid (BA)-activated nuclear receptor, farnesoid X receptor (FXR), a critical player in BA homeostasis. The MLL3 complex is essential for p53 transactivation of small heterodimer partner (SHP). KMT2C 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 its paralog MLL4. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named MLL4, a fourth human homolog of Drosophila trithorax, located on chromosome 12. It enzymatically generates trimethylated histone H3 Lysine 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 as HOXA1-3 and NESTIN. KMT2D is also a part of ASCOM. Both KMT2C and KMT2D contain the catalytic domain SET, several plant homeodomain (PHD) fingers, 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 fifth PHD finger of KMT2C and the fourth PHD finger of KMT2D.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1958803196 579 CKVCGQRR---RVRPCATCRKCYHKNCHIPPVE-VQSGPWHCAFC 619
Cdd:cd15513     2 CEGCGKASdesRLLLCDDCDISYHTYCLDPPLQtVPKGGWKCKWC 46

PHD domain 2 found in Histone-lysine N-methyltransferase 2B (KMT2B); KMT2B, also termed trithorax homolog 2 or WW domain-binding protein 7 (WBP-7), is encoded by the gene that was first named myeloid/lymphoid or mixed-lineage leukemia 2 (MLL2), a second human homolog of Drosophila trithorax, located on chromosome 19. It belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2) and is vital for normal mammalian embryonic development. KMT2B functions as the catalytic subunit in the MLL2 complex, which contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex. The MLL2 complex is highly active and specific for histone 3lysine 4 (H3K4) methylation, which stimulates chromatin transcription in a SAM- and H3K4-dependent manner. Moreover, KMT2B plays a critical role in memory formation through mediating hippocampal H3K4 di- and trimethylation. It is also required for RNA polymerase II association and protection from DNA methylation at the MagohB CpG island promoter. KMT2B contains a CxxC (x for any residue) zinc finger domain, three plant homeodomain (PHD), an extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain. This model corresponds to the second PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1958803196 579 CKVCGQRRRVRP----CATCRKCYHKNCHIP----PVEVQSGPWHCAFC 619
Cdd:cd15591     2 CHVCGRKNKESKplleCERCRNCYHPACLGPnypkPANRKKRPWICSAC 50

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 1958803196 579 CKVCGQRRRVRPCATCRKCYHKNCHIPP-VEVQSGPWHCAFC 619
Cdd:cd15559     2 CRVCHKLGDLLCCETCSAVYHLECVDPPlEEVPEEDWQCEVC 43

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 1958803196 579 CKVCGQRRRVRPCATCRKCYHKNCHIPPVE-VQSGPWHCAFC 619
Cdd:cd15531     2 CEVCQQGGEIILCDTCPRAYHLVCLDPELEkAPEGKWSCPHC 43

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958803196 668 FIRKPKKRKEdfPDLQEH----MWLNKIKHRLNKKAYHSVQHFVGDMRLIFQNHSKFY 721
Cdd:cd05525    29 FINLPSKKKN--PDYYERitdpVDLSTIEKQILTGYYKTPEAFDSDMLKVFRNAEKYY 84