FYVE domain like superfamily; FYVE domain is a 60-80 residue double zinc finger motif-containing module named after the four proteins, Fab1, YOTB, Vac1, and EEA1. The canonical FYVE domains are distinguished from other zinc fingers by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P, also termed PI3P)-binding site. They are found in many membrane trafficking regulators, including EEA1, Hrs, Vac1p, Vps27p, and FENS-1, which locate to early endosomes, specifically bind PtdIns3P, and play important roles in vesicular traffic and in signal transduction. Some proteins, such as rabphilin-3A and alpha-Rab3-interacting molecules (RIMs), are also involved in membrane trafficking and bind to members of the Rab subfamily of GTP hydrolases. However, they contain FYVE-related domains that are structurally similar to the canonical FYVE domains but lack the three signature sequences. At this point, they may not bind to phosphoinositides. In addition, this superfamily also contains the third group of proteins, caspase-associated ring proteins CARP1 and CARP2. They do not localize to membranes in the cell and are involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10, which are distinguished from other FYVE-type proteins. Moreover, these proteins have an altered sequence in the basic ligand binding patch and lack the WxxD motif that is conserved only in phosphoinositide binding FYVE domains. Thus they constitute a family of unique FYVE-type domains called FYVE-like domains. The FYVE domain is structurally similar to the RING domain and the PHD finger. This superfamily also includes ADDz zinc finger domain, which is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28872778  47 RNIEDICICCGSLQVHTQHPLFEGGICAPCKDKFLDALFLYDDDGYQSYCSICCSGETLLICGNPDCTRCYCFECVDSLV 126
Cdd:cd11727   1 RSIEEICICCGSLQIHTQHPLFHGGICAPCTEKFLEAFFLYDEDGYQAYCTICCSGETLLMCDDPDCTRCYCFECVDSLV 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 28872778 127 GPGTSGKVHAMSNWVCYLCLPSSRSGLLQRRRKWRSQLKAFYD 169
Cdd:cd11727  81 GPGTSEKVKATNNWVCFLCLPSSRSGLLQRKRKWRSQLKAFYD 123

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 28872778  47 RNIEDICICCGSLQVHTQHPLFEGGICAPCKDKFLDALFLYDDDGYQSYCSICCSGETLLICGNPDCTRCYCFECVDSLV 126
Cdd:cd11727   1 RSIEEICICCGSLQIHTQHPLFHGGICAPCTEKFLEAFFLYDEDGYQAYCTICCSGETLLMCDDPDCTRCYCFECVDSLV 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 28872778 127 GPGTSGKVHAMSNWVCYLCLPSSRSGLLQRRRKWRSQLKAFYD 169
Cdd:cd11727  81 GPGTSEKVKATNNWVCFLCLPSSRSGLLQRKRKWRSQLKAFYD 123

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 28872778  47 RNIEDICICCGSLQVHTQHPLFEGGICAPCKDKFLDALFLYDDDGYQSYCSICCSGETLLICGNPDCTRCYCFECVDSLV 126
Cdd:cd11727   1 RSIEEICICCGSLQIHTQHPLFHGGICAPCTEKFLEAFFLYDEDGYQAYCTICCSGETLLMCDDPDCTRCYCFECVDSLV 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 28872778 127 GPGTSGKVHAMSNWVCYLCLPSSRSGLLQRRRKWRSQLKAFYD 169
Cdd:cd11727  81 GPGTSEKVKATNNWVCFLCLPSSRSGLLQRKRKWRSQLKAFYD 123

ADDz domain found in DNA (cytosine-5) methyltransferases (C5-MTases) 3 (Dnmt3); Dnmt3 is a de novo DNA methyltransferase family that includes two active enzymes Dnmt3a and -3b and one regulatory factor Dnmt3l. The ADDz domain of Dnmt3 is located in the C-terminal region of Dnmt3, which is an active catalytic domain in Dnmt3a and -b, but lacks some residues for enzymatic activity in Dnmt3l. DNA methylation is an important epigenetic mechanism involved in diverse biological processes such as embryonic development, gene expression, and genomic imprinting. The ADDz_Dnmt3 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 28872778  49 IEDICICCGSLQV--HTQHPLFEGGICAPCKDKFLDALFLYDDDGYQSYCSICCSGETLLICGNPDCTRCYCFECVDSLV 126
Cdd:cd11725   1 IEDICLACGSLEVseTSDHPFFEGGLCKNCKERFLECIFLFDDDGYQMYCTICGGGGEVVLCDNPDCTRVYCTECLDLLL 80

                        90       100
                ....*....|....*....|....*...
gi 28872778 127 GPGTSGKVHAMSNWVCYLCLPSSRSGLL 154
Cdd:cd11725  81 GPGAVAKILESDPWFCFLCSPESNSLLG 108

ADDz domain found in DNA (cytosine-5) methyltransferases (C5-MTases) 3a (Dnmt3a); Dnmt3a is a member of the Dnmt3 family and is a protein with de novo DNA methyltransferase activity. Dnmt3 family members are Dnmt3a, Dnmt3b, and Dnmt3l the non-enzymatic regulatory factor. Dnmt3a is recruited by Dnmt3l to unmethylated histone H3 and methylates the target. Dnmt3a has a variable region at the N-terminus, followed by a conserved PWWP region and the cysteine-rich ADDz domain. ADDz_Dnmt3a is an active catalytic domain of Dnmt3a. DNA methylation is an important epigenetic mechanism involved in diverse biological processes such as embryonic development, gene expression, and genomic imprinting. The methyltransferase activity of Dnmt3a is not only responsible for the establishment of DNA methylation pattern, but is also essential for the inheritance of these patterns during mitosis. The ADDz_Dnmt3 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. A knockout of Dnmt3a has been shown to be lethal in the mouse model.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28872778  47 RNIEDICICCGSLQVHTQHPLFEGGICAPCKDKFLDALFLYDDDGYQSYCSICCSGETLLICGNPDCTRCYCFECVDSLV 126
Cdd:cd11729   2 RNIEDICISCGSLNVTLEHPLFIGGMCQNCKNCFLECAYQYDDDGYQSYCTICCGGREVLMCGNNNCCRCFCVECVDLLV 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 28872778 127 GPGTSGKVHAMSNWVCYLCLPSSRSGLLQRRRKWRSQLKAFY 168
Cdd:cd11729  82 GPGAAQAAIKEDPWNCYMCGHKGTYGLLRRREDWPSRLQMFF 123

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 28872778  54 ICCGSLQVHT----QHPLFEGGICAPCKDKFLDALFLYDDDGYQSYCSICCSGETLLICGNpdCTRCYCFECVDSLVGPG 129
Cdd:cd11726   7 ACGEQLNHFSkevhRHPVLKVLICKSCLKFYNSGEFSKDEDGSDEYCRWCGQGGDLICCDF--CPNVFCKKCIKRNLGRA 84

                        90
                ....*....|....*...
gi 28872778 130 TSGKVHAMSNWVCYLCLP 147
Cdd:cd11726  85 ELSRIEESDKWKCFVCDP 102