Williams-Beuren syndrome DDT (WSD), D-TOX E motif; This family represents the combined alpha-helical module found in diverse eukaryotic chromatin proteins. Based on the Ioc3 structure, the N-terminus of this module is inferred to interact with nucleosomal linker DNA and the SLIDE domain of ISWI proteins. The resulting complex forms a protein ruler that measures out the spacing between two adjacent nucleosomes. The acidic residue from the GxD signature at the N-terminus is a major determinant of the interaction between the ISWI and WHIM motifs. The N-terminal portion also contacts the inter-nucleosomal linker DNA. The module shows a great domain architectural diversity and is often combined with other modified histone peptide recognizing and DNA binding domains, some of which discriminate methylated DNA. The WSD module constitutes the inter-nucleosomal linker DNA binding site in the major groove of DNA, and was first identified as WSD, the D-TOX E motif of plant homeodomains homologous with the mutant transcription factor causing Williams-Beuren syndrome in association with the DDT-domain.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 392892481   410 LRSQPIGRDRYGRYYWFI---VRRLVVQSLDETELYYYSTVPQLYQLLQKLDR 459
Cdd:pfam15613    1 IRSLPLGRDRRYNRYWWFdpgTGRLFVESPSDGEWGVYSSKEQLDALIASLNP 53

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392892481    4 PRGRSKRKHPSESGNSSIADsedpsestsssRPRRSRLPKRYfddgySPPPTKKRAAQRETPSDAEEVEVKIEEISVRST 83
Cdd:PHA03247  348 PLGFPKRRRPTWTPPSSLED-----------LSAGRHHPKRA-----SLPTRKRRSARHAATPFARGPGGDDQTRPAAPV 411

                          90       100
                  ....*....|....*....|....
gi 392892481   84 PASTPAPKSTSKARGRPKKNPTPP 107
Cdd:PHA03247  412 PASVPTPAPTPVPASAPPPPATPL 435

DDT domain; The DDT domain is named after (DNA binding homeobox and Different Transcription factors) and is approximately 60 residues in length. Along with the WHIM motifs, it comprises an entirely alpha helical module found in diverse eukaryotic chromatin proteins. Based on the structure of Ioc3, this module is inferred to interact with nucleosomal linker DNA and the SLIDE domain of ISWI proteins. The resulting complex forms a protein ruler that measures out the spacing between two adjacent nucleosomes. In particular, the DDT domain, in combination with the WHIM1 and WHIM2 motifs form the SLIDE domain binding pocket.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 392892481   198 SIMDAVEIYEILRSYHRTLRITPFTFEDFCAALISHNNSC-IMAEVHMALLRNCLK 252
Cdd:pfam02791    2 AFGDLLMVWEFLNSFGEVLGLSPFTLDDFEEALLCTEEPSeLLDEIHCALLKALVR 57

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 392892481    350 CRVCGKS--SGRVVGCTQCEAAFHVECSHLKPFPEV----LVCNIC 389
Cdd:smart00249    2 CSVCGKPddGGELLQCDGCDRWYHQTCLGPPLLEEEpdgkWYCPKC 47

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392892481    4 PRGRSKRKHPSESGNSSIADsedpsestsssRPRRSRLPKRYfddgySPPPTKKRAAQRETPSDAEEVEVKIEEISVRST 83
Cdd:PHA03247  348 PLGFPKRRRPTWTPPSSLED-----------LSAGRHHPKRA-----SLPTRKRRSARHAATPFARGPGGDDQTRPAAPV 411

                          90       100
                  ....*....|....*....|....
gi 392892481   84 PASTPAPKSTSKARGRPKKNPTPP 107
Cdd:PHA03247  412 PASVPTPAPTPVPASAPPPPATPL 435

DDT domain; The DDT domain is named after (DNA binding homeobox and Different Transcription factors) and is approximately 60 residues in length. Along with the WHIM motifs, it comprises an entirely alpha helical module found in diverse eukaryotic chromatin proteins. Based on the structure of Ioc3, this module is inferred to interact with nucleosomal linker DNA and the SLIDE domain of ISWI proteins. The resulting complex forms a protein ruler that measures out the spacing between two adjacent nucleosomes. In particular, the DDT domain, in combination with the WHIM1 and WHIM2 motifs form the SLIDE domain binding pocket.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 392892481   198 SIMDAVEIYEILRSYHRTLRITPFTFEDFCAALISHNNSC-IMAEVHMALLRNCLK 252
Cdd:pfam02791    2 AFGDLLMVWEFLNSFGEVLGLSPFTLDDFEEALLCTEEPSeLLDEIHCALLKALVR 57

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 392892481    350 CRVCGKS--SGRVVGCTQCEAAFHVECSHLKPFPEV----LVCNIC 389
Cdd:smart00249    2 CSVCGKPddGGELLQCDGCDRWYHQTCLGPPLLEEEpdgkWYCPKC 47

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        30        40
                  ....*....|....*....|....*....|....*....|.
gi 392892481  350 CRVCGKSsGRVVGCTQCEAAFHVECSHLKPFPE-VLVCNIC 389
Cdd:cd15567     2 CFICSEG-GSLICCESCPASFHPECLGLEPPPEgKFYCEDC 41

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
                  ....*....|....*....|....*....|....
gi 392892481  350 CRVCGKSsGRVVGCTQCEAAFHVECsHLKPFPEV 383
Cdd:cd15623     2 CRVCQKA-GALVMCDQCEFCFHLDC-HLPALQEV 33

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.

                          10        20
                  ....*....|....*....|....*
gi 392892481  350 CRVCGKSSGRVVGCTQCEAAFHVEC 374
Cdd:cd15540     2 CGVCRGGRGDLLRCPQCLQAFHWHC 26