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 578803560   38 CPEPIFRFFRENKVEIASAITRPFPFLMGLRDRSFISEQMYEHFQEAFRNLVPVTRVMYCVLSELEKTFGWSHLEALFSR 117
Cdd:pfam03172   1 LEEALFQHFKENKVEIAYAIKKPFPFLEGLRDHSFITEKMYKESLEACRNLVPVQRVVYNVLSELEKTFSLSLLEALFSD 80

                          90
                  ....*....|....*....
gi 578803560  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 578803560  584 DFKAPLLPVTCGGVKGILHKKKLQQGILVKCIQTEDgKWFTPTEFEIKGGHARSKNWRLSVRCGGWPLRWLMENGFL 660
Cdd:pfam01342   1 DFDSPVLPVTCGAAKGLLHKKKFKQGISGKCIQNED-SWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578803560 259 RTYSTAPGEKQGEEEGRNSPRKRNQDKEKYQESPEGRDKETFDLKTPQvTNEGEPEKGLCLLPGEGEEGSDDcSEMCDGE 338
Cdd:PHA03169  59 RAVAEQGHRQTESDTETAEESRHGEKEERGQGGPSGSGSESVGSPTPS-PSGSAEELASGLSPENTSGSSPE-SPASHSP 136

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578803560 339 EPQEASSSlarcgsvsclsaETFDLKTPQVTNEGEPEKELSLLPGEGEEGSDDcSEMCDGEERQEASSSLARRGSVSSEL 418
Cdd:PHA03169 137 PPSPPSHP------------GPHEPAPPESHNPSPNQQPSSFLQPSHEDSPEE-PEPPTSEPEPDSPGPPQSETPTSSPP 203

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 578803560 419 ENHPMNEEGE--SEELASSLLYDNVPGAEQSAYENEKcscvmcfSEEVPGSPEARTESDQACG 479
Cdd:PHA03169 204 PQSPPDEPGEpqSPTPQQAPSPNTQQAVEHEDEPTEP-------EREGPPFPGHRSHSYTVVG 259

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 578803560   38 CPEPIFRFFRENKVEIASAITRPFPFLMGLRDRSFISEQMYEHFQEAFRNLVPVTRVMYCVLSELEKTFGWSHLEALFSR 117
Cdd:pfam03172   1 LEEALFQHFKENKVEIAYAIKKPFPFLEGLRDHSFITEKMYKESLEACRNLVPVQRVVYNVLSELEKTFSLSLLEALFSD 80

                          90
                  ....*....|....*....
gi 578803560  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 578803560  584 DFKAPLLPVTCGGVKGILHKKKLQQGILVKCIQTEDgKWFTPTEFEIKGGHARSKNWRLSVRCGGWPLRWLMENGFL 660
Cdd:pfam01342   1 DFDSPVLPVTCGAAKGLLHKKKFKQGISGKCIQNED-SWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

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 578803560 692 ECEVCRDGGELFCCDTCSRVFHEDCHIPPVEAERTPWNCIFC 733
Cdd:cd15626    1 KCEVCGQEGKLFCCCTCSRVFHEDCHIPPVEAQRSPWSCTFC 42

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 578803560  693 CEVCR---DGGELFCCDTCSRVFHEDCHIPPVEAERTP---WNCIFCRMK 736
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        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 578803560  792 CQGLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHRaSYKKEDCVETAQ 844
Cdd:pfam00439  30 YSVIKKPMDLSTIKKKLENGEYKSLAEFLADVKLIFSNAR-TYNGPGSVIYKA 81

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578803560 259 RTYSTAPGEKQGEEEGRNSPRKRNQDKEKYQESPEGRDKETFDLKTPQvTNEGEPEKGLCLLPGEGEEGSDDcSEMCDGE 338
Cdd:PHA03169  59 RAVAEQGHRQTESDTETAEESRHGEKEERGQGGPSGSGSESVGSPTPS-PSGSAEELASGLSPENTSGSSPE-SPASHSP 136

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578803560 339 EPQEASSSlarcgsvsclsaETFDLKTPQVTNEGEPEKELSLLPGEGEEGSDDcSEMCDGEERQEASSSLARRGSVSSEL 418
Cdd:PHA03169 137 PPSPPSHP------------GPHEPAPPESHNPSPNQQPSSFLQPSHEDSPEE-PEPPTSEPEPDSPGPPQSETPTSSPP 203

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 578803560 419 ENHPMNEEGE--SEELASSLLYDNVPGAEQSAYENEKcscvmcfSEEVPGSPEARTESDQACG 479
Cdd:PHA03169 204 PQSPPDEPGEpqSPTPQQAPSPNTQQAVEHEDEPTEP-------EREGPPFPGHRSHSYTVVG 259

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 578803560   38 CPEPIFRFFRENKVEIASAITRPFPFLMGLRDRSFISEQMYEHFQEAFRNLVPVTRVMYCVLSELEKTFGWSHLEALFSR 117
Cdd:pfam03172   1 LEEALFQHFKENKVEIAYAIKKPFPFLEGLRDHSFITEKMYKESLEACRNLVPVQRVVYNVLSELEKTFSLSLLEALFSD 80

                          90
                  ....*....|....*....
gi 578803560  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 578803560  584 DFKAPLLPVTCGGVKGILHKKKLQQGILVKCIQTEDgKWFTPTEFEIKGGHARSKNWRLSVRCGGWPLRWLMENGFL 660
Cdd:pfam01342   1 DFDSPVLPVTCGAAKGLLHKKKFKQGISGKCIQNED-SWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

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 578803560 692 ECEVCRDGGELFCCDTCSRVFHEDCHIPPVEAERTPWNCIFC 733
Cdd:cd15626    1 KCEVCGQEGKLFCCCTCSRVFHEDCHIPPVEAQRSPWSCTFC 42

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 578803560 692 ECEVCRDGGELFCCDTCSRVFHEDCHIPPV-EAERTPWNCIFC 733
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 578803560 755 MCPEEQLKCEFLLLKVYCCSESSFF-----AKIPYYYYIreacqgLKEPMWLDKIKKRLNE----HgYPQVEGFVQDMRL 825
Cdd:cd05502    1 LSPIDQRKCERLLLELYCHELSLPFhepvsPSVPNYYKI------IKTPMDLSLIRKKLQPkspqH-YSSPEEFVADVRL 73

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 578803560 826 IFQNHrASYKKEDCvETAQDNASEQSWAGRQSEEsVYP 863
Cdd:cd05502   74 MFKNC-YKFNEEDS-EVAQAGKELELFFEEQLKE-ILP 108

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 578803560 692 ECEVCRDGGELFCCDTCSRVFHEDCHIPPV-EAERTPWNCIFC 733
Cdd:cd15539    1 ECAVCGDGGELLCCDGCPRAFHLACLVPPLtLIPSGTWRCSSC 43

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 578803560 693 CEVCRDGGELFCCDTCSRVFHEDCHIPPVEAERT-PWNCIFC 733
Cdd:cd15532    2 CRVCKDGGELLCCDGCPSSYHLHCLNPPLAEIPDgDWFCPRC 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 578803560 693 CEVCRDGGELFCCDTCSRVFHEDCHIPPVEA-ERTPWNCIFC 733
Cdd:cd15622    2 CAVCQNGGELLCCEKCPKVFHLSCHVPTLMNfPSGEWICTFC 43

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 578803560  693 CEVCR---DGGELFCCDTCSRVFHEDCHIPPVEAERTP---WNCIFCRMK 736
Cdd:pfam00628   2 CAVCGksdDGGELVQCDGCDDWFHLACLGPPLDPAEIPsgeWLCPECKPK 51

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 578803560   693 CEVCR---DGGELFCCDTCSRVFHEDCHIPP--VEAERTPWNCIFC 733
Cdd:smart00249   2 CSVCGkpdDGGELLQCDGCDRWYHQTCLGPPllEEEPDGKWYCPKC 47

PHD finger 1 found in class II Chromodomain-Helicase-DNA binding (CHD) proteins; Class II CHD proteins includes chromodomain-helicase-DNA-binding protein CHD3, CHD4, and CHD5, which are nuclear and ubiquitously expressed chromatin remodelling ATPases generally associated with histone deacetylases (HDACs). They are involved in DNA Double Strand Break (DSB) signaling, DSB repair and/or p53-dependent pathways such as apoptosis and senescence, as well as in the maintenance of genomic stability, and/or cancer prevention. They function as subunits of the Nucleosome Remodelling and Deacetylase (NuRD) complex, which is generally associated with gene repression, heterochromatin formation, and overall chromatin compaction. In contrast to the class I CHD enzymes (CHD1 and CHD2), class II CHD proteins lack identifiable DNA-binding domains, but possess a C-terminal coiled-coil region. Moreover, in addition to the tandem chromodomains and a helicase domain, they all harbor tandem plant homeodomain (PHD) zinc fingers involved in the recognition of methylated histone tails. This model corresponds to the first PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 578803560 693 CEVCRDGGELFCCDTCSRVFHEDCHIPPVE-AERTPWNCIFC 733
Cdd:cd15531    2 CEVCQQGGEIILCDTCPRAYHLVCLDPELEkAPEGKWSCPHC 43

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 578803560 693 CEVCRDGGE---LFCCDTCSRVFHEDCHIPPVEAERT-PWNCIFC 733
Cdd:cd15527    2 CSVCQDSGNadnLLFCDACDKGFHMECHDPPLTRMPKgKWVCQIC 46

Bromodomain. BDF1/BDF2 like subfamily, restricted to fungi, repeat II. BDF1 and BDF2 are yeast transcription factors involved in the expression of a wide range of genes, including snRNAs; they are required for sporulation and DNA repair and protect histone H4 from deacetylation. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 578803560 782 IPYYYYIreacqgLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQN 829
Cdd:cd05499   35 IPNYFSI------IKKPMDLGTISKKLQNGQYQSAKEFERDVRLIFKN 76

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 578803560 693 CEVCRDG-----GELFCCDTCSRVFHEDCHIPPVE----AERTPWNCIFC 733
Cdd:cd15578    2 CTVCQDGssespNEIVLCDKCGQGYHQLCHNPKIDssvlDPDVPWLCRQC 51

PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) finger typically characterized as Cys4HisCys3, and a non-canonical extended PHD finger, characterized as Cys2HisCys5HisCys2His. Variations include the RAG2 PHD finger characterized by Cys3His2Cys2His and the PHD finger 5 found in nuclear receptor-binding SET domain-containing proteins characterized by Cys4HisCys2His. The PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. Single or multiple copies of PHD fingers have been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors. The PHD finger domain SF is structurally similar to the RING and FYVE_like superfamilies.

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                 ....*....|....*....|....*....|....*....|....*..
gi 578803560 693 CEVCRDGG----ELFCCDTCSRVFHEDCHIPPVEAERTP--WNCIFC 733
Cdd:cd15489    2 CIVCGKGGdlggELLQCDGCGKWFHADCLGPPLSSFVPNgkWICPVC 48

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 578803560 692 ECEVCRDGGELFCCD--TCSRVFHEDChippVEAERTP---WNC 730
Cdd:cd15568    1 ECFRCGDGGDLVLCDfkGCPKVYHLSC----LGLEKPPggkWIC 40

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578803560 784 YYYYIreacqglKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHRaSYKKED 838
Cdd:cd05509   34 YYDVI-------KKPMDLSTMEEKLENGYYVTLEEFVADLKLIFDNCR-LYNGPD 80

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 578803560 693 CEVCRDGGELFCCDTCSRVFHEDC-HIPPVEAERTPWNCIFC 733
Cdd:cd15537    2 CFECHAPGEVLPCSGCFRVYHSDClSEDFRPDSTSHWTCPVC 43

Bromodomain, Brdt_like subfamily, repeat I. 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 578803560 782 IPYYYYIreacqgLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHRASYKKED 838
Cdd:cd05497   37 LPDYHKI------IKTPMDLGTIKKRLENNYYWSASECIQDFNTMFTNCYIYNKPGD 87

Bromodomain, BAZ2A/BAZ2B_like subfamily. Bromo adjacent to zinc finger 2A (BAZ2A) and 2B (BAZ2B) were identified as a novel human bromodomain gene by cDNA library screening. BAZ2A is also known as Tip5 (Transcription termination factor I-interacting protein 5) and hWALp3. The proteins may play roles in transcriptional regulation. Human Tip5 is part of a complex termed NoRC (nucleolar remodeling complex), which induces nucleosome sliding and may play a role in the regulation of the rDNA locus. 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 578803560 782 IPYYYYIreacqgLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQN 829
Cdd:cd05503   30 VPGYRKI------IKKPMDFSTIREKLESGQYKTLEEFAEDVRLVFDN 71

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 578803560 693 CEVC-----RDGGELFCCDTCSRVFHEDCHIPPV----EAERTPWNCIFC 733
Cdd:cd15499    2 CSICggaeaRDGNEILICDKCDKGYHQLCHSPKVrtspLEGDEKWFCSRC 51

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

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578803560 783 PYYYYIreacqgLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHRaSYKKE 837
Cdd:cd05519   37 PDYYVI------IKRPIALDQIKRRIEGRAYKSLEEFLEDFHLMFANAR-TYNQE 84

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 578803560 693 CEVCRD-----GGELFCCDTCSRVFHEDCHIPPVEAE-----RTPWNCIFC 733
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 578803560 693 CEVC---RDGGELFCCDTCSRVFHEDCHIPPVEAE-RTPWNCIFC 733
Cdd:cd15519    2 CEVCgldDNEGEVLLCDGCDAEYHTSCLDPPLGEIpPGTWFCPSC 46

PHD finger 4 found in nuclear SET domain-containing protein 3 (NSD3); NSD3, also termed histone-lysine N-methyltransferase NSD3, or protein whistle, or WHSC1-like 1 isoform 9 with methyltransferase activity to lysine, or Wolf-Hirschhorn syndrome candidate 1-like protein 1 (WHSC1-like protein 1, or WHSC1L1), is a lysine methyltransferase encoded by gene NSD3, which is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD3 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, five plant-homeodomain (PHD) zinc fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD fingers are involved in protein-protein interactions. This model corresponds to the fourth PHD finger.

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                 ....*....|....*....|....*....|....*....|.
gi 578803560 693 CEVCRDGGELFCCDTCSRVFHEDCHipPVEAERTPWNCIFC 733
Cdd:cd15658    2 CFVCARGGRLLCCESCPASFHPECL--SIEMPEGCWNCNEC 40

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 578803560 693 CEVCRDGGELFCCDTCSRVFHEDCHipPVEAERTPWNCIFCR 734
Cdd:cd15657    2 CFVCSKGGSLLCCESCPAAFHPDCL--NIEMPDGSWFCNDCR 41

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 578803560 692 ECEVCRDG-GELFCCDTCSRVFHEDCHIP 719
Cdd:cd15540    1 RCGVCRGGrGDLLRCPQCLQAFHWHCHFP 29

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

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gi 578803560 782 IPYYYYIreacqgLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQN 829
Cdd:COG5076  178 YPDYYEI------IKSPMDLLTIQKKLKNGRYKSFEEFVSDLNLMFDN 219

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578803560 783 PYYYYIreacqgLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHRASYKKE 837
Cdd:cd05524   39 PEYYEV------VSNPIDLLKIQQKLKTEEYDDVDDLTADFELLINNAKAYYKPD 87