HSR domain; The Sp100 protein is a constituent of nuclear domains, also known as nuclear dots (NDs). An ND-targeting region that coincides with a homodimerization domain was mapped in Sp100. Sequences similar to the Sp100 homodimerization/ND-targeting region occur in several other proteins and constitute a novel protein motif, termed HSR domain (for homogeneously-staining region). The HSR domain has also been named ASS (AIRE, Sp-100 and Sp140). This domain is usually found at the amino terminus of proteins that contain a SAND domain pfam01342.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530369719   38 CPEPIFRFFRENKVEIASAITRPFPFLMGLRDRSFISEQMYEHFQEAFRNLVPVTRVMYCVLSELEKTFGWSHLEALFSR 117
Cdd:pfam03172   1 LEEALFQHFKENKVEIAYAIKKPFPFLEGLRDHSFITEKMYKESLEACRNLVPVQRVVYNVLSELEKTFSLSLLEALFSD 80

                          90
                  ....*....|....*....
gi 530369719  118 INLMAYPDLNEIYRSFQNV 136
Cdd:pfam03172  81 VNLKEYPDLIEILKSFPNV 99

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 530369719  534 DFKAPLLPVTCGGVKGILHKKKLQQGILVKCIQTEDgKWFTPTEFEIKGGHARSKNWRLSVRCGGWPLRWLMENGFL 610
Cdd:pfam01342   1 DFDSPVLPVTCGAAKGLLHKKKFKQGISGKCIQNED-SWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

HSR domain; The Sp100 protein is a constituent of nuclear domains, also known as nuclear dots (NDs). An ND-targeting region that coincides with a homodimerization domain was mapped in Sp100. Sequences similar to the Sp100 homodimerization/ND-targeting region occur in several other proteins and constitute a novel protein motif, termed HSR domain (for homogeneously-staining region). The HSR domain has also been named ASS (AIRE, Sp-100 and Sp140). This domain is usually found at the amino terminus of proteins that contain a SAND domain pfam01342.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530369719   38 CPEPIFRFFRENKVEIASAITRPFPFLMGLRDRSFISEQMYEHFQEAFRNLVPVTRVMYCVLSELEKTFGWSHLEALFSR 117
Cdd:pfam03172   1 LEEALFQHFKENKVEIAYAIKKPFPFLEGLRDHSFITEKMYKESLEACRNLVPVQRVVYNVLSELEKTFSLSLLEALFSD 80

                          90
                  ....*....|....*....
gi 530369719  118 INLMAYPDLNEIYRSFQNV 136
Cdd:pfam03172  81 VNLKEYPDLIEILKSFPNV 99

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 530369719  534 DFKAPLLPVTCGGVKGILHKKKLQQGILVKCIQTEDgKWFTPTEFEIKGGHARSKNWRLSVRCGGWPLRWLMENGFL 610
Cdd:pfam01342   1 DFDSPVLPVTCGAAKGLLHKKKFKQGISGKCIQNED-SWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

bromo domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530369719   706 CPEEQLKCEFLLLKVYCCSESS----FFAKIPYYYYIREACQGLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHR 781
Cdd:smart00297   1 DPKLQKKLQELLKAVLDKLDSHplswPFLKPVSRKEAPDYYDIIKKPMDLKTIKKKLENGKYSSVEEFVADFNLMFSNAR 80

                           90       100
                   ....*....|....*....|....*..
gi 530369719   782 ASYKY-KDFGQMGFRLEAEFEKNFKEV 807
Cdd:smart00297  81 TYNGPdSEVYKDAKKLEKFFEKKLREL 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        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 530369719  643 CEVCR---DGGELFCCDTCSRVFHEDCHIPPVEAERTP---WNCIFCRMK 686
Cdd:pfam00628   2 CAVCGksdDGGELVQCDGCDDWFHLACLGPPLDPAEIPsgeWLCPECKPK 51

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 530369719  742 CQGLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQN 779
Cdd:pfam00439  30 YSVIKKPMDLSTIKKKLENGEYKSLAEFLADVKLIFSN 67

HSR domain; The Sp100 protein is a constituent of nuclear domains, also known as nuclear dots (NDs). An ND-targeting region that coincides with a homodimerization domain was mapped in Sp100. Sequences similar to the Sp100 homodimerization/ND-targeting region occur in several other proteins and constitute a novel protein motif, termed HSR domain (for homogeneously-staining region). The HSR domain has also been named ASS (AIRE, Sp-100 and Sp140). This domain is usually found at the amino terminus of proteins that contain a SAND domain pfam01342.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530369719   38 CPEPIFRFFRENKVEIASAITRPFPFLMGLRDRSFISEQMYEHFQEAFRNLVPVTRVMYCVLSELEKTFGWSHLEALFSR 117
Cdd:pfam03172   1 LEEALFQHFKENKVEIAYAIKKPFPFLEGLRDHSFITEKMYKESLEACRNLVPVQRVVYNVLSELEKTFSLSLLEALFSD 80

                          90
                  ....*....|....*....
gi 530369719  118 INLMAYPDLNEIYRSFQNV 136
Cdd:pfam03172  81 VNLKEYPDLIEILKSFPNV 99

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 530369719  534 DFKAPLLPVTCGGVKGILHKKKLQQGILVKCIQTEDgKWFTPTEFEIKGGHARSKNWRLSVRCGGWPLRWLMENGFL 610
Cdd:pfam01342   1 DFDSPVLPVTCGAAKGLLHKKKFKQGISGKCIQNED-SWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

bromo domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530369719   706 CPEEQLKCEFLLLKVYCCSESS----FFAKIPYYYYIREACQGLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHR 781
Cdd:smart00297   1 DPKLQKKLQELLKAVLDKLDSHplswPFLKPVSRKEAPDYYDIIKKPMDLKTIKKKLENGKYSSVEEFVADFNLMFSNAR 80

                           90       100
                   ....*....|....*....|....*..
gi 530369719   782 ASYKY-KDFGQMGFRLEAEFEKNFKEV 807
Cdd:smart00297  81 TYNGPdSEVYKDAKKLEKFFEKKLREL 107

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 530369719 642 ECEVCRDGGELFCCDTCSRVFHEDCHIPPV-EAERTPWNCIFC 683
Cdd:cd15541    1 WCAVCQNGGELLCCDKCPRVFHLDCHIPPIpEFPSGEWSCSLC 43

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 530369719 705 MCPEEQLKCEFLLLKVYCCSESSFF-----AKIPYYYYIreacqgLKEPMWLDKIKKRLNE----HgYPQVEGFVQDMRL 775
Cdd:cd05502    1 LSPIDQRKCERLLLELYCHELSLPFhepvsPSVPNYYKI------IKTPMDLSLIRKKLQPkspqH-YSSPEEFVADVRL 73

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 530369719 776 IFQNhraSYKY----KDFGQMGFRLEAEFEKNFKEVF 808
Cdd:cd05502   74 MFKN---CYKFneedSEVAQAGKELELFFEEQLKEIL 107

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 530369719 642 ECEVCRDGGELFCCDTCSRVFHEDCHIPPV-EAERTPWNCIFC 683
Cdd:cd15539    1 ECAVCGDGGELLCCDGCPRAFHLACLVPPLtLIPSGTWRCSSC 43

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 530369719 639 NLDECEVCRDGGELFCCDTCSRVFHEDCHIPPVEA-ERTPWNCIFCR 684
Cdd:cd15625    1 NEDFCAVCLNGGELLCCDRCPKVFHLSCHVPALLSfPVGEWVCTLCR 47

Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. 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 530369719 731 KIPYYYYIreacqgLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNhraSYKYKDFG----QMGFRLEAEFEKNF 804
Cdd:cd05498   34 GLHDYHDI------IKHPMDLSTIKKKLDNREYADAQEFAADVRLMFSN---CYKYNPPDhpvhAMARKLQDVFEDRW 102

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 530369719 643 CEVCRDGGELFCCDTCSRVFHEDCHIPPVEA-ERTPWNCIFC 683
Cdd:cd15622    2 CAVCQNGGELLCCEKCPKVFHLSCHVPTLMNfPSGEWICTFC 43

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530369719 733 PYYYyireacQGLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHRasyKYKDFGQMGFRLEAEFEKNFKEV 807
Cdd:cd05522   38 PEYY------QEISNPISLDDIKKKVKRRKYKSFDQFLNDLNLMFENAK---LYNENDSQEYKDAVLLEKEARLL 103

ADDz domain found in ATRX (alpha-thalassemia/mental retardation, X-linked); ADDz_ATRX is a PHD-like zinc finger domain of ATRX, which belongs to the SNF2 family of chromatin remodeling proteins. ATRX is a large chromatin-associated nuclear protein with two domains, ADDz_ATRX at the N-terminus, followed by a C-terminal ATPase/helicase domain. The ADDz_ATRX domain recognizes a specific methylated histone, and this interaction is required for heterochromatin localization of the ATRX protein. Missense mutations in either of the two ATRX domains lead to the X-linked alpha-thalassemia and mental retardation syndrome; however the mutations in the ADDz_ATRX domain produce a more severe disease phenotype that may also relate to disturbing unknown functions or interaction sites of this domain. The ADDz domain is also present in chromatin-associated proteins cytosine-5-methyltransferase 3 (Dnmt3); it is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger. PHD zinc finger domains have been identified in more than 40 proteins that are mainly involved in chromatin mediated transcriptional control; the classical PHD zinc finger has a C4-H-C3 motif that spans about 50-80 amino acids. In ADDz, the conserved histidine residue of the PHD finger is replaced by a cysteine, and an additional zinc finger C2-C2 like motif is located about twenty residues upstream of the C4-C-C3 motif.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530369719 625 LKSQNNSSVDPCMRnlDECEVCRDGGELFCCDTCSRVFHEDC---HIPPVEAERT----PWNCIFCR 684
Cdd:cd11726   37 YNSGEFSKDEDGSD--EYCRWCGQGGDLICCDFCPNVFCKKCikrNLGRAELSRIeesdKWKCFVCD 101

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 530369719 734 YYYYIreacqglKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHRaSYKYKD--FGQMGFRLEAEFEKNFKEV 807
Cdd:cd05509   34 YYDVI-------KKPMDLSTMEEKLENGYYVTLEEFVADLKLIFDNCR-LYNGPDteYYKCANKLEKFFWKKLKEL 101

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 530369719 643 CEVCRDGGELFCCDTCSRVFHEDCHIPPVE-AERTPWNCIFC 683
Cdd:cd15531    2 CEVCQQGGEIILCDTCPRAYHLVCLDPELEkAPEGKWSCPHC 43

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        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530369719 726 SSFFAKIP-------YYYYIreacqglKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHRA-----SYKYKD 788
Cdd:cd05515   24 SLIFMRLPskseypdYYDVI-------KKPIDMEKIRSKIEGNQYQSLDDMVSDFVLMFDNACKynepdSQIYKD 91

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 530369719 643 CEVCRDGGE---LFCCDTCSRVFHEDCHIPPVEAERT-PWNCIFC 683
Cdd:cd15527    2 CSVCQDSGNadnLLFCDACDKGFHMECHDPPLTRMPKgKWVCQIC 46

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 530369719 643 CEVCRDG-----GELFCCDTCSRVFHEDCHIPPVE----AERTPWNCIFC 683
Cdd:cd15578    2 CTVCQDGssespNEIVLCDKCGQGYHQLCHNPKIDssvlDPDVPWLCRQC 51

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 530369719 643 CEVCRDGGELFCCDTCSRVFHEDCHIPPV-EAERTPWNCIFC 683
Cdd:cd15623    2 CRVCQKAGALVMCDQCEFCFHLDCHLPALqEVPGEDWKCLLC 43

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.

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                 ....*....|....*....|....*....|....*....|....
gi 530369719 642 ECEVCRDGGELFCCD--TCSRVFHEDChippVEAERTP---WNC 680
Cdd:cd15568    1 ECFRCGDGGDLVLCDfkGCPKVYHLSC----LGLEKPPggkWIC 40

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 530369719 732 IPYYYYIreacqgLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQ-----NHRASYKYKdfgqMGFRLEAEFEKNFKE 806
Cdd:cd05504   42 VPDYYDI------IKKPMDLGTIKEKLNMGEYKLAEEFLSDIQLVFSncflyNPEHTSVYK----AGTRLQRFFIKRCRK 111

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 530369719 643 CEVCRDGGELFCCDTCSRVFHEDCHIPP-VEAERTPWNCIFC 683
Cdd:cd15559    2 CRVCHKLGDLLCCETCSAVYHLECVDPPlEEVPEEDWQCEVC 43

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

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                 ....*....|....*....|....*....|....*....|....*...
gi 530369719 732 IPYYYYIreacqgLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQN 779
Cdd:cd05516   37 LPEYYEL------IRKPVDFKKIKERIRNHKYRSLEDLEKDVMLLCQN 78

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.

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gi 530369719 643 CEVC-----RDGGELFCCDTCSRVFHEDCHIPPV----EAERTPWNCIFC 683
Cdd:cd15499    2 CSICggaeaRDGNEILICDKCDKGYHQLCHSPKVrtspLEGDEKWFCSRC 51

PHD finger found in PHD finger protein 21B (PHF21B); PHF21B is a plant homeodomain (PHD) finger-containing protein whose biological function remains unclear. It shows high sequence similarity with PHF21A, which is associated with LSD1, a lysine (K)-specific histone demethylase and inhibits LSD1-mediated histone demethylation in vitro. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins.

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                 ....*....|....*....|....*....|....*....|..
gi 530369719 643 CEVCRDGGELFCCDTCSRVFHEDCHIPPVE-AERTPWNCIFC 683
Cdd:cd15524    2 CAACKRGGNLQPCGTCPRAYHLDCLDPPLKtAPKGVWVCPKC 43

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

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 530369719 643 CEVCRD-----GGELFCCDTCSRVFHEDCHIPPVEAE-----RTPWNCIFC 683
Cdd:cd15501    2 CVVCKQmdvtsGNQLVECQECHNLYHQECHKPPVTDKdvndpRLVWYCSRC 52

PHD finger 1 found in Schizosaccharomyces pombe Lid2 complex component Lid2p and similar proteins; Lid2p is a trimethyl H3K4 (H3K4me3) demethylase responsible for H3K4 hypomethylation in heterochromatin. It interacts with the histone lysine-9 methyltransferase, Clr4, through the Dos1/Clr8-Rik1 complex, and mediates H3K9 methylation and small RNA production. It also acts cooperatively with the histone modification enzymes Set1 and Lsd1 and plays an essential role in cross-talk between H3K4 and H3K9 methylation in euchromatin. Lid2p contains a JmjC domain, three PHD fingers and a JmjN domain. This model corresponds to the first PHD finger.

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gi 530369719 643 CEVC---RDGGELFCCDTCSRVFHEDCHIPPVEAE-RTPWNCIFC 683
Cdd:cd15519    2 CEVCgldDNEGEVLLCDGCDAEYHTSCLDPPLGEIpPGTWFCPSC 46

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

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 530369719 745 LKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQN-----------HRASYKYKDFG 790
Cdd:cd05512   38 IKQPMDFSTMRKKLESQRYRTLEDFEADFNLIINNclaynakdtifYRAAVRLRDQG 94

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

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                 ....*....|....*....|....*....|....*....|....*
gi 530369719 643 CEVCRDGGE---LFCCDTCSRVFHEDCHIPPVEAERT-PWNCIFC 683
Cdd:cd15595    2 CQTCRKPGEdskMLVCEACDKGYHTFCLKPAMESLPTdSWKCKAC 46

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 530369719 643 CEVCRDGGELFCCDTCSRVFHEDCHipPVEAERTPWNCIFCR 684
Cdd:cd15657    2 CFVCSKGGSLLCCESCPAAFHPDCL--NIEMPDGSWFCNDCR 41

PHD finger found in Arabidopsis thaliana pathogenesis-related homeodomain protein (PRHA) and similar proteins; PRHA is a homeodomain protein encoded by a single-copy Arabidopsis thaliana homeobox gene, prha. It shows the capacity to bind to TAATTG core sequence elements but requires additional adjacent bases for high-affinity binding. PRHA contains a plant homeodomain (PHD) finger, a homeodomain, peptide repeats and a putative leucine zipper dimerization domain.

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                 ....*....|....*....|....*....|....*....|....
gi 530369719 646 CRDGGELFCCD-TCSRVFHEDCHIPPVEAERTP-----WNCIFC 683
Cdd:cd15504   10 ASPDNDILLCDgGCNRAYHQKCLEPPLLTEDIPpedegWLCPLC 53

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

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                 ....*....|....*....|....*....|....*....|....*
gi 530369719 643 CEVCR---DGGELFCCDTCSRVFHEDCHIPPV-EAERTPWNCIFC 683
Cdd:cd15544    2 CKVCRkkgDPDNMILCDGCDKAFHLYCLRPALrEVPSGDWFCPAC 46