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 1958803217  23 ELIFQHFKRQKVAISNAIKNPFPFLEGLRDHELITAKMYEDLQDSYRALVRVQEVIYRALDKLEKIFSMKVLYEVFSNVN 102
Cdd:pfam03172   3 EALFQHFKENKVEIAYAIKKPFPFLEGLRDHSFITEKMYKESLEACRNLVPVQRVVYNVLSELEKTFSLSLLEALFSDVN 82

                          90
                  ....*....|....*..
gi 1958803217 103 MEKYPDLQLIYQSFERV 119
Cdd:pfam03172  83 LKEYPDLIEILKSFPNV 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 1958803217 417 DFSSNELLVTCGKVVGTLYKEKLNQGIHVKSIQsTEGKWFTPLEFEIEGGYEKCKNWRQSIRCSGWPLKELIKRGEL 493
Cdd:pfam01342   1 DFDSPVLPVTCGAAKGLLHKKKFKQGISGKCIQ-NEDSWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 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 1958803217  23 ELIFQHFKRQKVAISNAIKNPFPFLEGLRDHELITAKMYEDLQDSYRALVRVQEVIYRALDKLEKIFSMKVLYEVFSNVN 102
Cdd:pfam03172   3 EALFQHFKENKVEIAYAIKKPFPFLEGLRDHSFITEKMYKESLEACRNLVPVQRVVYNVLSELEKTFSLSLLEALFSDVN 82

                          90
                  ....*....|....*..
gi 1958803217 103 MEKYPDLQLIYQSFERV 119
Cdd:pfam03172  83 LKEYPDLIEILKSFPNV 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 1958803217 417 DFSSNELLVTCGKVVGTLYKEKLNQGIHVKSIQsTEGKWFTPLEFEIEGGYEKCKNWRQSIRCSGWPLKELIKRGEL 493
Cdd:pfam01342   1 DFDSPVLPVTCGAAKGLLHKKKFKQGISGKCIQ-NEDSWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 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 1958803217 523 ACKVCGQRRRVRPCATCRKCYHKNCHIPPVEVQSGPWHCAFC 564
Cdd:cd15626     1 KCEVCGQEGKLFCCCTCSRVFHEDCHIPPVEAQRSPWSCTFC 42

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803217 579 HKESEVLKRKMS-------PEEQLKCELL---LLTIYCCPKSGFFIRKPKKRkeDFPDL----QEHMWLNKIKHRLNKKA 644
Cdd:COG5076   125 HLKTSVKKRKTPkiedellYADNKAIAKFkkqLFLRDGRFLSSIFLGLPSKR--EYPDYyeiiKSPMDLLTIQKKLKNGR 202

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1958803217 645 YHSVQHFVGDMRLIFQNhskFYKSRFKNLGVIV-GNKFEKTFKSVFS 690
Cdd:COG5076   203 YKSFEEFVSDLNLMFDN---CKLYNGPDSSVYVdAKELEKYFLKLIE 246

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 1958803217  524 CKVCGQRRRVRP---CATCRKCYHKNCHIPP--VEVQSGPWHCAFC 564
Cdd:smart00249   2 CSVCGKPDDGGEllqCDGCDRWYHQTCLGPPllEEEPDGKWYCPKC 47

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 1958803217  23 ELIFQHFKRQKVAISNAIKNPFPFLEGLRDHELITAKMYEDLQDSYRALVRVQEVIYRALDKLEKIFSMKVLYEVFSNVN 102
Cdd:pfam03172   3 EALFQHFKENKVEIAYAIKKPFPFLEGLRDHSFITEKMYKESLEACRNLVPVQRVVYNVLSELEKTFSLSLLEALFSDVN 82

                          90
                  ....*....|....*..
gi 1958803217 103 MEKYPDLQLIYQSFERV 119
Cdd:pfam03172  83 LKEYPDLIEILKSFPNV 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 1958803217 417 DFSSNELLVTCGKVVGTLYKEKLNQGIHVKSIQsTEGKWFTPLEFEIEGGYEKCKNWRQSIRCSGWPLKELIKRGEL 493
Cdd:pfam01342   1 DFDSPVLPVTCGAAKGLLHKKKFKQGISGKCIQ-NEDSWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 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 1958803217 523 ACKVCGQRRRVRPCATCRKCYHKNCHIPPVEVQSGPWHCAFC 564
Cdd:cd15626     1 KCEVCGQEGKLFCCCTCSRVFHEDCHIPPVEAQRSPWSCTFC 42

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 1958803217 593 EQLKCELLLLTIYCC--PKSGFFIRKPKKRkeDFPD----LQEHMWLNKIKHRLNKKAYHSVQHFVGDMRLIFQNHSKFY 666
Cdd:cd04369     1 LKKKLRSLLDALKKLkrDLSEPFLEPVDPK--EAPDyyevIKNPMDLSTIKKKLKNGEYKSLEEFEADVRLIFSNAKTYN 78

                          90       100
                  ....*....|....*....|...
gi 1958803217 667 KSrfKNLGVIVGNKFEKTFKSVF 689
Cdd:cd04369    79 GP--GSPIYKDAKKLEKLFEKLL 99

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 1958803217 524 CKVCGQRRRVRPCATCRKCYHKNCHIPPV-EVQSGPWHCAFC 564
Cdd:cd15541     2 CAVCQNGGELLCCDKCPRVFHLDCHIPPIpEFPSGEWSCSLC 43

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803217 579 HKESEVLKRKMS-------PEEQLKCELL---LLTIYCCPKSGFFIRKPKKRkeDFPDL----QEHMWLNKIKHRLNKKA 644
Cdd:COG5076   125 HLKTSVKKRKTPkiedellYADNKAIAKFkkqLFLRDGRFLSSIFLGLPSKR--EYPDYyeiiKSPMDLLTIQKKLKNGR 202

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1958803217 645 YHSVQHFVGDMRLIFQNhskFYKSRFKNLGVIV-GNKFEKTFKSVFS 690
Cdd:COG5076   203 YKSFEEFVSDLNLMFDN---CKLYNGPDSSVYVdAKELEKYFLKLIE 246

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
                  ....*....|....*....|....*....|....*....|....*
gi 1958803217 622 EDFPDLQEH-MWLNKIKHRLNKKAYHSVQHFVGDMRLIFQNHSKF 665
Cdd:cd05498    36 HDYHDIIKHpMDLSTIKKKLDNREYADAQEFAADVRLMFSNCYKY 80

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803217 610 SGFFIRKPKKrkEDFPD----LQEHMWLNKIKHRLNKKAYHSVQHFVGDMRLIFQNHSKF 665
Cdd:cd05515    24 SLIFMRLPSK--SEYPDyydvIKKPIDMEKIRSKIEGNQYQSLDDMVSDFVLMFDNACKY 81

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 1958803217 536 CATCRKCYHKNCHIPPVEVQ-SGPWHCAFC 564
Cdd:cd15527    17 CDACDKGFHMECHDPPLTRMpKGKWVCQIC 46

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1958803217 524 CKVCGQRRRVRPCATCRKCYHKNCHIPPVEVQ-SGPWHCAFC 564
Cdd:cd15524     2 CAACKRGGNLQPCGTCPRAYHLDCLDPPLKTApKGVWVCPKC 43

Bromodomain; Acf1_like or BAZ1A_like subfamily. Bromo adjacent to zinc finger 1A (BAZ1A) was identified as a novel human bromodomain gene by cDNA library screening. The Drosophila homologue, Acf1, is part of the CHRAC (chromatin accessibility complex) and regulates ISWI-induced nucleosome remodeling. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803217 597 CELLLLTIYCCPKSGFFIRkPKKRKE--DFPD-LQEHMWLNKIKHRLNKKAYHSVQHFVGDMRLIFQN-------HSKFY 666
Cdd:cd05504    17 LEQLLVEIVKHKDSWPFLR-PVSKIEvpDYYDiIKKPMDLGTIKEKLNMGEYKLAEEFLSDIQLVFSNcflynpeHTSVY 95

                  .
gi 1958803217 667 K 667
Cdd:cd05504    96 K 96

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958803217 523 ACKVCGQ-----RRRVRPCATCRKCYHKNCHIPPV--EVQSGP---WHCAFC 564
Cdd:cd15501     1 SCVVCKQmdvtsGNQLVECQECHNLYHQECHKPPVtdKDVNDPrlvWYCSRC 52

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 1958803217 524 CKVCGQRRRVRPCATCRKCYHKNCHIPPV-EVQSGPWHCAFC 564
Cdd:cd15539     2 CAVCGDGGELLCCDGCPRAFHLACLVPPLtLIPSGTWRCSSC 43

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1958803217 524 CKVCGQRRR---VRPCATCRKCYHKNCHIPPV-EVQSGPWHCAFC 564
Cdd:cd15519     2 CEVCGLDDNegeVLLCDGCDAEYHTSCLDPPLgEIPPGTWFCPSC 46

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958803217 524 CKVCGQRRRVRP-----CATCRKCYHKNCHIPPVEVQ----SGPWHCAFC 564
Cdd:cd15499     2 CSICGGAEARDGneiliCDKCDKGYHQLCHSPKVRTSplegDEKWFCSRC 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 1958803217  524 CKVCGQRRRVRP---CATCRKCYHKNCHIPP--VEVQSGPWHCAFC 564
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 1958803217 523 ACKVCGQ---RRRVRPCATCRKCYHKNCHIPPV-EVQSGPWHCAFC 564
Cdd:cd15603     1 VCLVCGSgndEDRLLLCDGCDDSYHTFCLIPPLhDVPKGDWRCPKC 46

PHD finger found in Remodeling and spacing factor 1 (Rsf-1); Rsf-1, also termed HBV pX-associated protein 8, or Hepatitis B virus X-associated protein alpha (HBxAPalpha), or p325 subunit of RSF chromatin-remodeling complex, is a novel nuclear protein with histone chaperon function. It is a subunit of an ISWI chromatin remodeling complex, remodeling and spacing factor (RSF), and plays a role in mediating ATPase-dependent chromatin remodeling and conferring tumor aggressiveness in common carcinomas. As an ataxia-telangiectasia mutated (ATM)-dependent chromatin remodeler, Rsf-1 facilitates DNA damage checkpoints and homologous recombination repair. It regulates the mitotic spindle checkpoint and chromosome instability through the association with serine/threonine kinase BubR1 (BubR1) and Hepatitis B virus (HBV) X protein (HBx) in the chromatin fraction during mitosis. It also interacts with cyclin E1 and promotes tumor development. Rsf-1 contains a plant homeodomain (PHD) finger.

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                  ....*....|....*....|....*....|....*....|....*.
gi 1958803217 523 ACKVCGQR---RRVRPCATCRKCYHKNCHIPPV-EVQSGPWHCAFC 564
Cdd:cd15543     1 PCRKCGLSdhpEWILLCDRCDAGYHTACLRPPLmIIPDGNWFCPPC 46

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.

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                  ....*....|....*....|....*....|....*....|....*
gi 1958803217 524 CKVCGQRR---RVRPCATCRKCYHKNCHIPPVE-VQSGPWHCAFC 564
Cdd:cd15513     2 CEGCGKASdesRLLLCDDCDISYHTYCLDPPLQtVPKGGWKCKWC 46

PHD finger found in PHD finger protein 21A (PHF21A); PHF21A (also termed BHC80a or BRAF35-HDAC complex protein BHC80) along with HDAC1/2, CtBP1, CoREST, and BRAF35, is associated with LSD1, a lysine (K)-specific histone demethylase. It inhibits LSD1-mediated histone demethylation in vitro. PHF21A is predominantly present in the central nervous system and spermatogenic cells and is one of the six components of BRAF-HDAC complex (BHC) involved in REST-dependent transcriptional repression of neuron-specific genes in non-neuronal cells. It acts as a scaffold protein in BHC in neuronal as well as non-neuronal cells and also plays a role in spermatogenesis. PHF21A contains a C-terminal plant homeodomain (PHD) finger that is responsible for the binding directly to each of five other components of BHC, and of organizing BHC mediating transcriptional repression.

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                  ....*....|....*....|....*....|....*....|...
gi 1958803217 523 ACKVCGQRRRVRPCATCRKCYHKNCHIPPV-EVQSGPWHCAFC 564
Cdd:cd15523     1 FCSVCRKSGELLMCDTCSLVYHLDCLDPPLkTIPKGMWICPKC 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958803217 613 FIRKPKKRKEdfPDLQEH----MWLNKIKHRLNKKAYHSVQHFVGDMRLIFQNHSKFY 666
Cdd:cd05525    29 FINLPSKKKN--PDYYERitdpVDLSTIEKQILTGYYKTPEAFDSDMLKVFRNAEKYY 84

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 1958803217 631 MWLNKIKHRLNKKAYHSVQHFVGDMRLIFQNHSKF 665
Cdd:cd05503    41 MDFSTIREKLESGQYKTLEEFAEDVRLVFDNCETF 75