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 2502273130 252 NFSAELLPVTCGNLKGVLHKEKFKQGISVKSIQCqNGNWFTPSEFEMMGGYGKSKNWKLSLRCHNWPLKLLIQRNFL 328
Cdd:pfam01342   1 DFDSPVLPVTCGAAKGLLHKKKFKQGISGKCIQN-EDSWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 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 2502273130 360 KCEVCRDGGLLFCCDTCFRAFHEDCHIPTVEAEITPWSCIFC 401
Cdd:cd15626     1 KCEVCGQEGKLFCCCTCSRVFHEDCHIPPVEAQRSPWSCTFC 42

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 2502273130 252 NFSAELLPVTCGNLKGVLHKEKFKQGISVKSIQCqNGNWFTPSEFEMMGGYGKSKNWKLSLRCHNWPLKLLIQRNFL 328
Cdd:pfam01342   1 DFDSPVLPVTCGAAKGLLHKKKFKQGISGKCIQN-EDSWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

SAND domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2502273130  256 ELLPVTCGNLKGVLHKEKFKQGISVKSIQcQNGNWFTPSEFEMMGGYGKSKNWKLSLRCHNWPLKLLIQRNFLP 329
Cdd:smart00258   1 SELPVTCGTVKGILYKKKFKCGISVKCIQ-YEDKWFTPKEFEIEGGKGKSKDWKRSIRCGGSSLRTLMENGTLD 73

bromo domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2502273130  436 VQEPMWLDIIKKKLSDQAYCQVEDFVQDMRLIFRNHKITF-KDPKFGEMGFRLESKFEKSFKEV 498
Cdd:smart00297  44 IKKPMDLKTIKKKLENGKYSSVEEFVADFNLMFSNARTYNgPDSEVYKDAKKLEKFFEKKLREL 107

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 2502273130  361 CEVCR---DGGLLFCCDTCFRAFHEDCHIPTVEAEITP--WSCIFC 401
Cdd:smart00249   2 CSVCGkpdDGGELLQCDGCDRWYHQTCLGPPLLEEEPDgkWYCPKC 47

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2502273130 436 VQEPMWLDIIKKKLSDQAYCQVEDFVQDMRLIFRNHKI-TFKDPKFGEMGFRLESKFEKSFKEVF 499
Cdd:COG5076   185 IKSPMDLLTIQKKLKNGRYKSFEEFVSDLNLMFDNCKLyNGPDSSVYVDAKELEKYFLKLIEEIP 249

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 2502273130 252 NFSAELLPVTCGNLKGVLHKEKFKQGISVKSIQCqNGNWFTPSEFEMMGGYGKSKNWKLSLRCHNWPLKLLIQRNFL 328
Cdd:pfam01342   1 DFDSPVLPVTCGAAKGLLHKKKFKQGISGKCIQN-EDSWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

SAND domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2502273130  256 ELLPVTCGNLKGVLHKEKFKQGISVKSIQcQNGNWFTPSEFEMMGGYGKSKNWKLSLRCHNWPLKLLIQRNFLP 329
Cdd:smart00258   1 SELPVTCGTVKGILYKKKFKCGISVKCIQ-YEDKWFTPKEFEIEGGKGKSKDWKRSIRCGGSSLRTLMENGTLD 73

PHD finger found in the transcriptional intermediary factor 1 (TIF1) family and similar proteins; The TIF1 family of transcriptional cofactors includes TIF1alpha (TRIM24), TIF1beta (TRIM28), TIF1gamma (TRIM33), and TIF1delta (TRIM66), which are characterized by an N-terminal RING-finger B-box coiled-coil (RBCC/TRIM) motif and plant homeodomain (PHD) finger followed by a bromodomain in the C-terminal region. TIF1 proteins couple chromatin modifications to transcriptional regulation, signaling, and tumor suppression. They exert a deacetylase-dependent silencing effect when tethered to a promoter region. TIF1alpha, TIF1beta, and TIF1delta can homodimerize and contain a PXVXL motif necessary and sufficient for heterochromatin protein 1(HP1) binding. TIF1alpha and TIF1beta bind nuclear receptors and Kruppel-associated boxes (KRAB) specifically and respectively. In contrast, TIF1delta appears to lack nuclear receptor- and KRAB-binding activity. Moreover, TIF1delta is specifically involved in heterochromatin-mediated gene silencing during postmeiotic phases of spermatogenesis. TIF1gamma is structurally closely related to TIF1alpha and TIF1beta, but has very little functional features in common with them. It does not interact with the KRAB silencing domain of KOX1 or the heterochromatinic proteins HP1alpha, beta, and gamma. It cannot bind to nuclear receptors (NRs). This family also includes Sp100/Sp140 family proteins, the nuclear body SP100 and SP140. Sp110 is a leukocyte-specific component of the nuclear body. It may function as a nuclear hormone receptor transcriptional coactivator that may play a role in inducing differentiation of myeloid cells. It is also involved in resisting intracellular pathogens and functions as an important drug target for preventing intracellular pathogen diseases, such as tuberculosis, hepatic veno-occlusive disease, and intracellular cancers. SP140 is an interferon inducible nuclear leukocyte-specific protein involved in primary biliary cirrhosis and a risk factor in chronic lymphocytic leukemia. It is also implicated in innate immune response to human immunodeficiency virus type 1 (HIV-1) by binding to the virus viral infectivity factor (Vif) protein. Both Sp110 and Sp140 contain a SAND domain, a plant homeodomain (PHD) finger, and a bromodomain (BRD).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2502273130 361 CEVCRDGGLLFCCDTCFRAFHEDCHIPTV-EAEITPWSCIFC 401
Cdd:cd15541     2 CAVCQNGGELLCCDKCPRVFHLDCHIPPIpEFPSGEWSCSLC 43

Bromodomain. Bromodomains are found in many chromatin-associated proteins and in nuclear histone acetyltransferases. They interact specifically with acetylated lysine.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2502273130 436 VQEPMWLDIIKKKLSDQAYCQVEDFVQDMRLIFRNHKiTF--KDPKFGEMGFRLESKFEK 493
Cdd:cd04369    39 IKNPMDLSTIKKKLKNGEYKSLEEFEADVRLIFSNAK-TYngPGSPIYKDAKKLEKLFEK 97

Bromodomain. BDF1/BDF2 like subfamily, restricted to fungi, repeat I. 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        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2502273130 436 VQEPMWLDIIKKKLSDQAYCQVEDFVQDMRLIFRNhKITFKDPK--FGEMGFRLESKFEKS 494
Cdd:cd05500    43 IKKPMDLGTIERKLKSNVYTSVEEFTADFNLMVDN-CLTFNGPEhpVSQMGKRLQAAFEKH 102

PHD finger 1 found in PHD finger protein 12 (PHF12); PHF12, also termed PHD factor 1 (Pf1), is a plant homeodomain (PHD) zinc finger-containing protein that bridges the transducin-like enhancer of split (TLE) corepressor to the mSin3A-histone deacetylase (HDAC)-complex, and further represses transcription at targeted genes. PHF12 also interacts with MRG15 (mortality factor-related genes on chromosome 15), a member of the mortality factor (MORF) family of proteins implicated in regulating cellular senescence. PHF12 contains two plant-homeodomain (PHD) zinc fingers followed by a polybasic region. The PHD fingers function downstream of phosphoinositide signaling triggered by the interaction between polybasic regions and phosphoinositides. This model corresponds to the first PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2502273130 361 CEVCRDGGLLFCCDTCFRAFHEDCHIPTVEAEITP---WSCIFC 401
Cdd:cd15533     2 CDSCGEGGDLLCCDRCPASFHLQCCNPPLDEEDLPpgeWLCHRC 45

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2502273130 436 VQEPMWLDIIKKKLSDQAYCQVEDFVQDMRLIFRN-HKITFKDPKFGEMGFRLESKFEKSF 495
Cdd:cd05498    42 IKHPMDLSTIKKKLDNREYADAQEFAADVRLMFSNcYKYNPPDHPVHAMARKLQDVFEDRW 102

PHD-finger; PHD folds into an interleaved type of Zn-finger chelating 2 Zn ions in a similar manner to that of the RING and FYVE domains. Several PHD fingers have been identified as binding modules of methylated histone H3.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 2502273130 361 CEVCR---DGGLLFCCDTCFRAFHEDCHIPTVEAE---ITPWSCIFCR 402
Cdd:pfam00628   2 CAVCGksdDGGELVQCDGCDDWFHLACLGPPLDPAeipSGEWLCPECK 49

PHD finger 2 found in class II Chromodomain-Helicase-DNA binding (CHD) proteins; Class II CHD proteins includes chromodomain-helicase-DNA-binding protein CHD3, CHD4, and CHD5, which are nuclear and ubiquitously expressed chromatin remodelling ATPases generally associated with histone deacetylases (HDACs). They are involved in DNA Double Strand Break (DSB) signaling, DSB repair and/or p53-dependent pathways such as apoptosis and senescence, as well as in the maintenance of genomic stability, and/or cancer prevention. They function as subunits of the Nucleosome Remodelling and Deacetylase (NuRD) complex, which is generally associated with gene repression, heterochromatin formation, and overall chromatin compaction. In contrast to the class I CHD enzymes (CHD1 and CHD2), class II CHD proteins lack identifiable DNA-binding domains, but possess a C-terminal coiled-coil region. Moreover, in addition to the tandem chromodomains and a helicase domain, they all harbor tandem plant homeodomain (PHD) zinc fingers involved in the recognition of methylated histone tails. This model corresponds to the second PHD finger.

                          10        20
                  ....*....|....*....|....
gi 2502273130 361 CEVCRDGGLLFCCDTCFRAFHEDC 384
Cdd:cd15532     2 CRVCKDGGELLCCDGCPSSYHLHC 25

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 2502273130 361 CEVCRDGGLLFCCDTCFRAFHEDCHIPTVE-AEITPWSCIFC 401
Cdd:cd15531     2 CEVCQQGGEIILCDTCPRAYHLVCLDPELEkAPEGKWSCPHC 43

Bromodomain; Gcn5_like subfamily. Gcn5p is a histone acetyltransferase (HAT) which mediates acetylation of histones at lysine residues; such acetylation is generally correlated with the activation of transcription. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2502273130 436 VQEPMWLDIIKKKLSDQAYCQVEDFVQDMRLIFRNHKiTFKDPK--FGEMGFRLESKFEKSFKEV 498
Cdd:cd05509    38 IKKPMDLSTMEEKLENGYYVTLEEFVADLKLIFDNCR-LYNGPDteYYKCANKLEKFFWKKLKEL 101

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        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2502273130 436 VQEPMWLDIIKKKLSDQAYCQVEDFVQDMRLIFRNHKiTFKDP--KFGEMGFRLESKFEK 493
Cdd:cd05499    42 IKKPMDLGTISKKLQNGQYQSAKEFERDVRLIFKNCY-TFNPEgtDVYMMGHQLEEVFND 100

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 2502273130 361 CEVCRDGGLLFCCDTCFRAFHEDCHIPTVEaEITP--WSCIFC 401
Cdd:cd15623     2 CRVCQKAGALVMCDQCEFCFHLDCHLPALQ-EVPGedWKCLLC 43

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2502273130 361 CEVCRDGG----LLFCCDTCFRAFHEDCHIPTVEAEITP--WSCIFC 401
Cdd:cd15489     2 CIVCGKGGdlggELLQCDGCGKWFHADCLGPPLSSFVPNgkWICPVC 48

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2502273130 436 VQEPMWLDIIKKKLSDQAYCQVEDFVQDMRLIFRNHKiTFK--DPKFGEMGFRLESKFEK 493
Cdd:cd05503    37 IKKPMDFSTIREKLESGQYKTLEEFAEDVRLVFDNCE-TFNedDSEVGRAGHNMRKFFEK 95

PHD finger 4 found in nuclear receptor-binding SET domain-containing (NSD) proteins; The nuclear receptor binding SET domain (NSD) protein is a family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1, that are critical in maintaining chromatin integrity. Reducing NSD activity through specific lysine-HMTase inhibitors appears promising to help suppress cancer growth. NSD proteins have specific mono- and dimethylase activities for H3K36, and they play non-redundant roles during development. NSD1 plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. NSD2 is involved in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. NSD3 is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to development of acute myeloid leukemia. NSD proteins contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). This model corresponds to the fourth PHD finger.

                          10        20
                  ....*....|....*....|....
gi 2502273130 361 CEVCRDGGLLFCCDTCFRAFHEDC 384
Cdd:cd15567     2 CFICSEGGSLICCESCPASFHPEC 25

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 2502273130 360 KCEVC-----RDGGLLFCCDTCFRAFHEDCHIPTVEAEI----TPWSCIFC 401
Cdd:cd15499     1 TCSICggaeaRDGNEILICDKCDKGYHQLCHSPKVRTSPlegdEKWFCSRC 51

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 2502273130 361 CEVCRDG-----GLLFCCDTCFRAFHEDCHIPTVEAEI----TPWSCIFC 401
Cdd:cd15578     2 CTVCQDGssespNEIVLCDKCGQGYHQLCHNPKIDSSVldpdVPWLCRQC 51

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2502273130 361 CEVCRDGGLLFCCDTCFRAFHEDCHipTVEAEITPWSCIFCR 402
Cdd:cd15657     2 CFVCSKGGSLLCCESCPAAFHPDCL--NIEMPDGSWFCNDCR 41

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
                  ....*....|....*....|....*....|....*....|....*....
gi 2502273130 361 CEVCRDGGLLFCCDTCFRAFHEDC---HIPTVEAEIT----PWSCIFCR 402
Cdd:cd11726    53 CRWCGQGGDLICCDFCPNVFCKKCikrNLGRAELSRIeesdKWKCFVCD 101

Bromodomain, polybromo repeat IV. Polybromo is a nuclear protein of unknown function, which contains 6 bromodomains. The human ortholog BAF180 is part of a SWI/SNF chromatin-remodeling complex, and it may carry out the functions of Yeast Rsc-1 and Rsc-2. It was shown that polybromo bromodomains bind to histone H3 at specific acetyl-lysine positions. Bromodomains are found in many chromatin-associated proteins and in nuclear histone acetyltransferases. They interact specifically with acetylated lysine, but not all the bromodomains in polybromo may bind to acetyl-lysine.

                          10        20        30
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gi 2502273130 436 VQEPMWLDIIKKKLSDQAYCQVEDFVQDMRLIFRN 470
Cdd:cd05518    43 ILEPIDLKTIEHNIRNDKYATEEELMDDFKLMFRN 77

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 2502273130 360 KCEVCRDG-GLLFCCDTCFRAFHEDCHIP 387
Cdd:cd15540     1 RCGVCRGGrGDLLRCPQCLQAFHWHCHFP 29

PHD finger found in Schizosaccharomyces pombe SWM histone demethylase complex subunits Phf1 (Phf1p) and Phf2 (Phf2p); Phf1p and Phf2p are components of the SWM histone demethylase complex that specifically demethylates histone H3 at lysine 9 (H3K9me2), a specific tag for epigenetic transcriptional activation. They function as corepressors and play roles in regulating heterochromatin propagation and euchromatic transcription. Both Phf1p and Phf2p contain a plant homeodomain (PHD) finger.

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gi 2502273130 360 KCEVCRDG-----GLLFCCDTCFRAFHEDCHIPTVEAEI-----TPWSCIFC 401
Cdd:cd15502     1 VCIVCQRGhspksNRIVFCDGCNTPYHQLCHDPSIDDEVvedpdAEWFCKKC 52

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 2502273130 361 CEVCRDGGLLFCCD--TCFRAFHEDC 384
Cdd:cd15568     2 CFRCGDGGDLVLCDfkGCPKVYHLSC 27

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 2502273130 436 VQEPMWLDIIKKKLSDQAYCQVEDFVQDMRLIFRN-------HKITFKdpkfgeMGFRLESKFEKSFKE 497
Cdd:cd05504    49 IKKPMDLGTIKEKLNMGEYKLAEEFLSDIQLVFSNcflynpeHTSVYK------AGTRLQRFFIKRCRK 111