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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340707886   7 GIVSCTACGQQVNHFqKDSIYRHPSLQVLICKNCFKYYMSDDISRDSDGMDEQCRWCAEGGNLICCDFCHNAFCKKCILR 86
Cdd:cd11726    1 RRVRCTACGEQLNHF-SKEVHRHPVLKVLICKSCLKFYNSGEFSKDEDGSDEYCRWCGQGGDLICCDFCPNVFCKKCIKR 79

                         90       100
                 ....*....|....*....|....
gi 340707886  87 NLGRRELStIMDENNQWYCYICHP 110
Cdd:cd11726   80 NLGRAELS-RIEESDKWKCFVCDP 102

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340707886   7 GIVSCTACGQQVNHFqKDSIYRHPSLQVLICKNCFKYYMSDDISRDSDGMDEQCRWCAEGGNLICCDFCHNAFCKKCILR 86
Cdd:cd11726    1 RRVRCTACGEQLNHF-SKEVHRHPVLKVLICKSCLKFYNSGEFSKDEDGSDEYCRWCGQGGDLICCDFCPNVFCKKCIKR 79

                         90       100
                 ....*....|....*....|....
gi 340707886  87 NLGRRELStIMDENNQWYCYICHP 110
Cdd:cd11726   80 NLGRAELS-RIEESDKWKCFVCDP 102

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340707886   7 GIVSCTACGQQVNHFqKDSIYRHPSLQVLICKNCFKYYMSDDISRDSDGMDEQCRWCAEGGNLICCDFCHNAFCKKCILR 86
Cdd:cd11726    1 RRVRCTACGEQLNHF-SKEVHRHPVLKVLICKSCLKFYNSGEFSKDEDGSDEYCRWCGQGGDLICCDFCPNVFCKKCIKR 79

                         90       100
                 ....*....|....*....|....
gi 340707886  87 NLGRRELStIMDENNQWYCYICHP 110
Cdd:cd11726   80 NLGRAELS-RIEESDKWKCFVCDP 102

Cysteine Rich ADD domain; This is a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, AD-DATRX) found in ATRX proteins. Chromatin-associated human protein ATRX was originally identified because mutations in the ATRX gene cause a severe form of syndromal X-linked mental retardation called ATR-X syndrome. Mutations or knockdown of ATRX expression cause diverse effects, including altered patterns of DNA methylation, a telomere-dysfunction phenotype, aberrant chromosome segregation, premature sister chromatid separation and changes in gene expression. ATRX localizes predominantly to large, tandemly repeated regions (such as telomeres, centromeres and ribosomal DNA) associated with heterochromatin, and studies show that it directs H3.3 deposition to pericentric and telomeric heterochromatin. The ADD domain of ATRX, in which most syndrome-causing mutations occur, engages the N-terminal tail of histone H3 through two rigidly oriented binding pockets, one for unmodified Lys4 and the other for di- or trimethylated Lys9. Mutations in the ATRX ADD domain cause mislocalization of ATRX protein to heterochromatin, and this may contribute to understanding the underlying etiology of ATRX syndrome. Structure analysis of the ADD domain of ATRX revealed that it contains a PHD zinc-finger domain packed against a GATA-like zinc finger. Same structure is also found in the DNMT3 DNA methyltransferases and DNMT3L.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 340707886    6 MGIVSCTACGQQVNHFQKDSIYRHPSLQVLICKNCFKYYMSDDISRDS 53
Cdd:pfam17981   9 SSIVNCTACGQQVNHFQRDSIYQHPVLKVLICKSCFKYYMSDDISKDE 56

ADDz domain found in DNA (cytosine-5) methyltransferases (C5-MTases) 3 like (Dnmt3l); Dnmt3l is a regulator of DNA methylation, which acts by recognizing unmethylated histone H3 tails and interacting with Dnmt3a to stimulate its de novo DNA methylation activity. The ADDz_Dnmt3l domain is located in the C-terminal region of Dnmt3l that otherwise lacks some residues required for DNA methyltransferase activity. DNA methylation is an important epigenetic mechanism involved in diverse biological processes such as embryonic development, gene expression, and genomic imprinting. Dnmt3l is also associating with HDAC1 and acts as a transcriptional repressor. The ADDz_Dnmt3l domain is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger. PHD zinc finger domains have been identified in more than 40 proteins that are mainly involved in chromatin mediated transcriptional control; the classical PHD zinc finger has a C4-H-C3 motif that spans about 50-80 amino acids. In ADDz, the conserved histidine residue of the PHD finger is replaced by a cysteine, and an additional zinc finger C2-C2 like motif is located about twenty residues upstream of the C4-C-C3 motif.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340707886  11 CTACGQQVNHFQkdsiyrHPSLQVLICKNCFKYYMSDDISRDSDGMDEQCRWCAEGGNLICCD--FCHNAFCKKCILRNL 88
Cdd:cd11727    7 CICCGSLQIHTQ------HPLFHGGICAPCTEKFLEAFFLYDEDGYQAYCTICCSGETLLMCDdpDCTRCYCFECVDSLV 80

                         90       100
                 ....*....|....*....|..
gi 340707886  89 GRRELSTIMDENNqWYCYICHP 110
Cdd:cd11727   81 GPGTSEKVKATNN-WVCFLCLP 101