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 973201388 1106 IEDFCLSCGTPQTEIFHPLFEGSLCLKCKDNFTETLYRYDEDGYQSYCTVCCAGLEVILCGNASCCRCFCLDCLDILVGP 1185
Cdd:cd11728     1 IEDFCLSCGRSNPATFHPLFEGGLCITCKDRFLELFYMYDDDGYQSYCTVCCEGRELLLCGNASCCRCFCVDCLEVLVGP 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 973201388 1186 GTFDKLKEVDPWSCYMCLPSQRYGVLKRREDWSIRVQEFF 1225
Cdd:cd11728    81 GTAAKAKEQDPWSCYMCLPQRCYGVLKRRTDWSVRLQEFF 120

DNA-cytosine methylase [Replication, recombination and repair];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388 1247 RRPIRVLSLFDGI---ATGylvLKDLGFKVEryIASEICEDSIAVGMIKHEGRIEHVHDVRTITKKHIAewGPFDLLIGG 1323
Cdd:COG0270     1 SKKLTVIDLFAGAgglSLG---FEKAGFEVV--FAVEIDPDACETYRANFPEAKVIEGDIRDIDPEELI--PDVDLLIGG 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388 1324 SPCNDLSIVNPaRKGlFEGT-GRLFFEYYRLLNILKPKegdnrpfFWLFENVVAM----GVRDKTDICRFLE-----CNP 1393
Cdd:COG0270    74 PPCQPFSVAGK-RKG-LEDPrGTLFFEFIRIVEELRPK-------AFVLENVPGLlssdKGKTFEEILKELEelgyrVDY 144

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388 1394 VLIDA----VkvsPAHRARYF----WGNLPGMNRPLASSQSDKLDLQDCLEHGRQAKFSKV--RTITTRPNsikqGKSEI 1463
Cdd:COG0270   145 KVLNAadygV---PQNRERVFivgfRKDLDLFEFPEPTHLKPYVTVGDALEDLPDAHEARYlsETITAGYG----GGGRF 217

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 973201388 1464 LpvvmnGKEDNLWCT--ELERIFGFPRHYTDVNNmgRGSRQKVLGRSWSVPVIRHLFAPLKDYF 1525
Cdd:COG0270   218 L-----HPGEPRRLTvrEAARLQGFPDDFKFPGS--KTQAYRQIGNAVPPPLAEAIAKAILKAL 274

ADDz domain found in DNA (cytosine-5) methyltransferases (C5-MTases) 3b (Dnmt3b); ADDz_Dnmt3b is an active catalytic domain of Dnmt3b. Dnmt3b is a member of the Dnmt3 family and is a de novo DNA methyltransferases that has an N-terminal variable region followed by a conserved PWWP region and the cysteine-rich ADDz domain. 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. Dnmt3b is ubiquitously expressed in most adult tissues. 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 Dnmt3b has been shown to be lethal in the mouse model.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388 1106 IEDFCLSCGTPQTEIFHPLFEGSLCLKCKDNFTETLYRYDEDGYQSYCTVCCAGLEVILCGNASCCRCFCLDCLDILVGP 1185
Cdd:cd11728     1 IEDFCLSCGRSNPATFHPLFEGGLCITCKDRFLELFYMYDDDGYQSYCTVCCEGRELLLCGNASCCRCFCVDCLEVLVGP 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 973201388 1186 GTFDKLKEVDPWSCYMCLPSQRYGVLKRREDWSIRVQEFF 1225
Cdd:cd11728    81 GTAAKAKEQDPWSCYMCLPQRCYGVLKRRTDWSVRLQEFF 120

Cysteine rich ADD domain in DNMT3; This is a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, AD-DATRX) found in DNMT3A proteins. The ADD domains of the DNMT3 family have a decisive role in blocking DNMT activity in the areas of the genome with chromatin containing methylated H3K4. Furthermore, the ADD domain of DNMMT3A (ADD-3A) competes with the chromodomain (CD) of heterochromatin protein 1 alpha (HP1alpha, CDHP1alpha) for binding to the H3 tail. The DNA methyltransferase (DNMT) 3 family members DNMT3A and DNMT3B and the DNMT3-like non-enzymatic regulatory factor DNMT3L, are involved in de-novo establishment of DNA methylation patterns in early mammalian development.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 973201388  1091 SRVQMVREVLQKGKNIEDFCLSCGTPQTEIFHPLFEGSLCLKCKDNFTETLYRYDE 1146
Cdd:pfam17980    1 SREQMVYEVRENKRNIEDFCLSCGSLNVHTFHPLFEGGLCQKCKDNFLETLYRYDE 56

Microtubule-binding protein involved in cell cycle control [Cell division and chromosome partitioning / Cytoskeleton];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388   14 DAGDKYDRVELLAWLNDSLQTKFTKVEQICSGAAYCQLMDWLFpGSMDLNKIKFQAQEELEFIHNYNLLQKSFRKTGVTK 93
Cdd:COG5217     2 DKALVESREELLFWENVVVRLDLQRIEDCGEGFAMQQIHDSIY-VDLPDSLVRFPWIAEYKHPGNGKILQLLFSDYGIDK 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 973201388   94 VIPVDELVKGAFQINFQFLKWFKKFFDANFYGQIYNALTAREGQ 137
Cdd:COG5217    81 AVLVLVLVRCKLQDNLEFLQWLKDHWVRNLGHISYDRNARRLGR 124

C-5 cytosine-specific DNA methylase;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388  1250 IRVLSLFDGIATGYLVLKDLGFKVerYIASEICEDSIAVGMIKHEGRIEHvhDVRTITKKHIAEwgpFDLLIGGSPCNDL 1329
Cdd:pfam00145    1 FKFIDLFAGIGGFRLGLEQAGFEC--VAANEIDKSAAKTYEANFPKVPIG--DITLIDIKDIPD---IDILTGGFPCQDF 73

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 973201388  1330 SIVNpARKGLFEGTGRLFFEYYRLLNILKPKegdnrpfFWLFENV 1374
Cdd:pfam00145   74 SIAG-KQKGFEDTRGTLFFEIIRIIKEKKPK-------AFLLENV 110

DNA-methyltransferase (dcm); All proteins in this family for which functions are known are DNA-cytosine methyltransferases. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388  1252 VLSLFDGIATGYLVLKDLGFKVerYIASEIceDSIAVGMikHEGRIEHVH---DVRTITKKHIAEwgpFDLLIGGSPCND 1328
Cdd:TIGR00675    1 FIDLFAGIGGIRLGFEQAGFKC--VFASEI--DKYAQKT--YEANFGNKVpfgDITKISPSDIPD---FDILLGGFPCQP 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388  1329 LSIvnpARKGL-FEGT-GRLFFEYYRLLNILKPKegdnrpfFWLFENVVAMGVRDK----TDICRFLE-------CNpvL 1395
Cdd:TIGR00675   72 FSI---AGKRKgFEDTrGTLFFEIVRILKEKKPK-------FFLLENVKGLVSHDKgrtfKVIIETLEelgykvyYK--V 139

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388  1396 IDAV--KVsPAHRAR-------YFWGNLPgMNRPLASSQSDKLDLQDCLEHG---------------------------- 1438
Cdd:TIGR00675  140 LNAKdfGV-PQNRERiyivgfrDFDDKLN-FEFPKPIYVAKKKRIGDLLDLSvdleekyylseekknglllllenmrkke 217

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388  1439 -----------RQAKFSKVRTITTRPNSIKQGKSEIlPVVMNGKEDN-------LWCTELERIFGFPRHYTDvnNMGRGS 1500
Cdd:TIGR00675  218 gtgeqigsfynRESKSSIIRTLSARGYTFVKGGKSV-LIVPHKSTVVhpgrirrLTPRECARLQGFPDDFKF--PVSDSQ 294

                          330
                   ....*....|....*
gi 973201388  1501 RQKVLGRSWSVPVIR 1515
Cdd:TIGR00675  295 LYKQAGNAVVVPVIE 309

Calponin homology (CH) domain; The CH domain is found in both cytoskeletal proteins and signal transduction proteins. The CH domain is involved in actin binding in some members of the family. However in calponins there is evidence that the CH domain is not involved in its actin binding activity. Most member proteins have from two to four copies of the CH domain, however some proteins such as calponin have only a single copy.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388    23 ELLAWLNDSLQTKFTKV------EQICSGAAYCQLMDWLFPGSMDLNKIKFQAQEELEfihNYNL-LQKSFRKTGVTKV- 94
Cdd:pfam00307    6 ELLRWINSHLAEYGPGVrvtnftTDLRDGLALCALLNKLAPGLVDKKKLNKSEFDKLE---NINLaLDVAEKKLGVPKVl 82

                           90       100
                   ....*....|....*....|....*...
gi 973201388    95 IPVDELVKGAfqiNFQFLKWFKKFFDAN 122
Cdd:pfam00307   83 IEPEDLVEGD---NKSVLTYLASLFRRF 107

ADDz domain found in DNA (cytosine-5) methyltransferases (C5-MTases) 3b (Dnmt3b); ADDz_Dnmt3b is an active catalytic domain of Dnmt3b. Dnmt3b is a member of the Dnmt3 family and is a de novo DNA methyltransferases that has an N-terminal variable region followed by a conserved PWWP region and the cysteine-rich ADDz domain. 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. Dnmt3b is ubiquitously expressed in most adult tissues. 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 Dnmt3b has been shown to be lethal in the mouse model.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388 1106 IEDFCLSCGTPQTEIFHPLFEGSLCLKCKDNFTETLYRYDEDGYQSYCTVCCAGLEVILCGNASCCRCFCLDCLDILVGP 1185
Cdd:cd11728     1 IEDFCLSCGRSNPATFHPLFEGGLCITCKDRFLELFYMYDDDGYQSYCTVCCEGRELLLCGNASCCRCFCVDCLEVLVGP 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 973201388 1186 GTFDKLKEVDPWSCYMCLPSQRYGVLKRREDWSIRVQEFF 1225
Cdd:cd11728    81 GTAAKAKEQDPWSCYMCLPQRCYGVLKRRTDWSVRLQEFF 120

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 973201388 1104 KNIEDFCLSCGTPQTEIFHPLFEGSLCLKCKDNFTETLYRYDEDGYQSYCTVCCAGLEVILCGNASCCRCFCLDCLDILV 1183
Cdd:cd11729     2 RNIEDICISCGSLNVTLEHPLFIGGMCQNCKNCFLECAYQYDDDGYQSYCTICCGGREVLMCGNNNCCRCFCVECVDLLV 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 973201388 1184 GPGTFDKLKEVDPWSCYMCLPSQRYGVLKRREDWSIRVQEFFVNN 1228
Cdd:cd11729    82 GPGAAQAAIKEDPWNCYMCGHKGTYGLLRRREDWPSRLQMFFANN 126

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 973201388 1106 IEDFCLSCGTPQTEI--FHPLFEGSLCLKCKDNFTETLYRYDEDGYQSYCTVCCAGLEVILCGNASCCRCFCLDCLDILV 1183
Cdd:cd11725     1 IEDICLACGSLEVSEtsDHPFFEGGLCKNCKERFLECIFLFDDDGYQMYCTICGGGGEVVLCDNPDCTRVYCTECLDLLL 80

                          90       100
                  ....*....|....*....|....*...
gi 973201388 1184 GPGTFDKLKEVDPWSCYMCLPSQRYGVL 1211
Cdd:cd11725    81 GPGAVAKILESDPWFCFLCSPESNSLLG 108

ATRX, Dnmt3 and Dnmt3l PHD-like zinc finger domain (ADDz); The ADDz zinc finger domain is present in the chromatin-associated proteins cytosine-5-methyltransferase 3 (Dnmt3) and ATRX, a SNF2 type transcription factor protein. The Dnmt3 family includes two active DNA methyltransferases, Dnmt3a and -3b, and one regulatory factor Dnmt3l. DNA methylation is an important epigenetic mechanism involved in diverse biological processes such as embryonic development, gene expression, and genomic imprinting. The ADDz 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 973201388 1106 IEDFCLSCGTPQTEIFHPLFEGSLCLKCKDNFTETLYRYDEDGYQSYCTVCCAGLEVILCGNASCCRCFCLDCLDILVGP 1185
Cdd:cd11672     1 IEDICIACGSLVVIYRHPLFQGGICKNCKKYFLSDDISYDDDGYQSYCRICCEGGNLLCCGNNFCHRCFCKECVDRLVGP 80

                          90
                  ....*....|....*....
gi 973201388 1186 GTFDKLKEVDPWSCYMCLP 1204
Cdd:cd11672    81 GELSTMDENNQWYCYICHP 99

PWWP domain found in the DNA (cytosine-5)-methyltransferase 3 (DNMT3) family; The DNMT3 family includes DNMT3A and DNMT3B, which are required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNMT3A, also called DNA methyltransferase HsaIIIA, DNA MTase HsaIIIA, or M.HsaIIIA, modifies DNA in a non-processive manner and also methylates non-CpG sites. It may preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. DNMT3A is recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites. DNMT3B, also called DNA methyltransferase HsaIIIB, DNA MTase HsaIIIB, or M.HsaIIIB, may preferentially methylate nucleosomal DNA within the nucleosome core region. DNMT3B may function as a transcriptional co-repressor by associating with CBX4 and independently of DNA methylation. Members of this family contains a PWWP domain that is responsible for establishing DNA methylation patterns during embryogenesis and gametogenesis. In tumorigenesis, DNA methylation by DNMT3B is known to play a role in the inactivation of tumor suppressor genes. In addition, a point mutation in the PWWP domain of DNMT3B has been identified in patients with ICF (immunodeficiency, centromeric instability, and facial anomalie) syndrome , a rare autosomal recessive disorder characterized by hypomethylation of classical satellite DNA.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388  927 VGELVWGKVKGFSWWPGLVVGWKSKQIPTA---MRKVEWFGDGMFSEIYTERLLPFSAFSKCFCnSSFATLPAYKDAIFQ 1003
Cdd:cd05835     2 IGDLVWAKLKGSPWWPGIVVSHKDCGQKPPaegSVWVFWFGDHKVSEVPLDKILPFAEFFNKFY-ISKNSSKLYKKAVYE 80

                  ....*....
gi 973201388 1004 SLEMVSERS 1012
Cdd:cd05835    81 ALKEAAERS 89

Microtubule-binding protein involved in cell cycle control [Cell division and chromosome partitioning / Cytoskeleton];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388   14 DAGDKYDRVELLAWLNDSLQTKFTKVEQICSGAAYCQLMDWLFpGSMDLNKIKFQAQEELEFIHNYNLLQKSFRKTGVTK 93
Cdd:COG5217     2 DKALVESREELLFWENVVVRLDLQRIEDCGEGFAMQQIHDSIY-VDLPDSLVRFPWIAEYKHPGNGKILQLLFSDYGIDK 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 973201388   94 VIPVDELVKGAFQINFQFLKWFKKFFDANFYGQIYNALTAREGQ 137
Cdd:COG5217    81 AVLVLVLVRCKLQDNLEFLQWLKDHWVRNLGHISYDRNARRLGR 124

PWWP (Pro-Trp-Trp-Pro) domain; The PWWP domain, named for a conserved Pro-Trp-Trp-Pro motif, is a small domain consisting of 100-150 amino acids and is composed of a five-stranded antiparallel beta-barrel followed by a helical region. It is found in numerous proteins that are involved in cell division, growth, and differentiation. Most PWWP-domain proteins seem to be nuclear, often DNA-binding, proteins that function as transcription factors regulating a variety of developmental processes. PWWP domains specifically recognize DNA and histone methylated lysines at the level of the nucleosome. Based on the fact that other regions of PWWP-domain proteins are responsible for nuclear localization and DNA-binding, is likely that the PWWP domain acts as a site for protein-protein binding interactions, influencing chromatin remodeling and thereby regulating transcriptional processes. Some PWWP-domain proteins have been linked to cancer or other diseases; some are known to function as growth factors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388  928 GELVWGKVKGFSWWPGLVVGWKSKQIPTAMRK------VEWFGDGMFSEIYTERLLPFSAFSKCFCNSSFATLPAYKDAI 1001
Cdd:cd05162     1 GDLVWAKLKGYPWWPARVVDPEELPEEVGKKKkkggvlVQFFGDNDYAWVKSKNIKPFEEGFKKEFKKKKKKSKKFKKAV 80

                  ....*
gi 973201388 1002 FQSLE 1006
Cdd:cd05162    81 EEAEE 85

PWWP domain; The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif. The domain binds to Histone-4 methylated at lysine-20, H4K20me, suggesting that it is methyl-lysine recognition motif. Removal of two conserved aromatic residues in a hydrophobic cavity created by this domain within the full-length protein, Pdp1, abolishes the interaction o f the protein with H4K20me3. In fission yeast, Set9 is the sole enzyme that catalyzes all three states of H4K20me, and Set9-mediated H4K20me is required for efficient recruitment of checkpoint protein Crb2 to sites of DNA damage. The methylation of H4K20 is involved in a diverse array of cellular processes, such as organizing higher-order chromatin, maintaining genome stability, and regulating cell-cycle progression.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 973201388   928 GELVWGKVKGFSWWPGLVVGWKSKQIPTAMRK-------VEWFGDGMFSEIYTERLLPFSAFSKCFC---NSSFATLPAY 997
Cdd:pfam00855    1 GDLVWAKLKGYPWWPARVVDPEELPENVLKPKkkdgeylVRFFGDSEFAWVKPKDLKPFDEGDEFEYlkkKKKKKKKKAF 80

                   ....
gi 973201388   998 KDAI 1001
Cdd:pfam00855   81 KKAL 84

domain with conserved PWWP motif; conservation of Pro-Trp-Trp-Pro residues

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 973201388    925 FSVGELVWGKVKGFSWWPGLVVGWKSkqIPTAMRK---------VEWFGDGMFSEIYTERLLP 978
Cdd:smart00293    1 FKPGDLVWAKMKGFPWWPALVISPKM--TPDNIMKrksdenlypVLFFGDKDTAWIPSSKLFP 61

PWWP domain found in the PWWP domain-containing protein 2 (PWWP2) family; The PWWP2 family includes PWWP2A and its paralog PWWP2B. PWWP2A is a H2A.Z-specific chromatin binding protein which may play an important role in the neural crest stem cell migration and differentiation during early development. It is also required for proper mitosis progression. PWWP2A and PWWP2B form a stable complex with NuRD subunits MTA1/2/3:HDAC1/2:RBBP4/7, but not with MBD2/3, p66alpha/beta, and CHD3/4. The PWWP domain specifically recognizes DNA and histone methylated lysines.

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gi 973201388  922 GKGFSVGELVWGKVKGFSWWPGLVVG-WKSK------QIPTAmrKVEWFGDGMFSEIYTERLLPF 979
Cdd:cd20140     1 GRTLRVGDIVWGKIHGFPWWPGRILSiTVSRddngelSTQEA--HVSWFGSSTTSYMPCSQLYPF 63

PWWP domain found in methyl-CpG-binding domain protein 5 (MBD5) and similar proteins; MBD5, is a methyl-CpG-binding protein that binds to heterochromatin. It does not interact with either methylated or unmethylated DNA. MBD5 acts as a transcriptional regulator responsible for 2q23.1 deletion syndrome. It belongs to the MBD family proteins, which play central roles in transcriptional regulation and development. The PWWP domain specifically recognizes DNA and histone methylated lysines.

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gi 973201388  925 FSVGELVWGKVKGFSWWPG-LVVGWKSKQIPTAMRKVEWFGDGMFSEIYTERLLPFS 980
Cdd:cd20141     1 FNVGDLVWGQIRGFPSWPGkLVSENDVGKTNEGKVWVSWFGDHSFGQVEPDKLKTLS 57

PWWP domain found in glyoxylate reductase 1 (GLYR1) and similar proteins; GLYR1, also called 3-hydroxyisobutyrate dehydrogenase-like protein, cytokine-like nuclear factor N-PAC, nuclear protein NP60, or nuclear protein of 60 kDa, is a putative oxidoreductase that is recruited on chromatin and promotes KDM1B demethylase activity. It recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3). GLYR1 enhances the activity of MAP2K4 and MAP2K6 kinases to phosphorylate p38-alpha. In addition to the PWWP domain, GLYR1 also contains an AT-hook and a C-terminal NAD-binding domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

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gi 973201388  925 FSVGELVWGKVKGFSWWPGLVVG-WKSKQIPTAMRKVEW---FGDGMFSEIYTERLLPFSAFSKCFCNSSfaTLPAYKDA 1000
Cdd:cd05836     1 FKIGDLVWAKMKGFPPWPGKIVNpPPDLKKPPRKKKMHCvyfFGSENYAWIEDENIKPYEEFKEEMLKSK--KSAGFKDA 78

                  .
gi 973201388 1001 I 1001
Cdd:cd05836    79 V 79

first PWWP domain found in nuclear receptor-binding SET domain-containing (NSD) proteins; The nuclear receptor binding SET domain (NSD) protein family consists of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1 that are critical in maintaining the chromatin integrity. Reducing NSD activity through specific lysine-HMTase inhibitors appears promising in suppressing cancer growth. NSD proteins have specific mono- and dimethylase activities for H3K36, and play nonredundant 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, through 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 (C5HCH). This model corresponds to the first PWWP domain. This family also includes Drosophila melanogaster maternal-effect sterile 4 (dMes4) that may act as a histone-lysine N-methyltransferase required for wing morphogenesis. The PWWP domain specifically recognizes DNA and histone methylated lysines.

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gi 973201388  927 VGELVWGKVKGFSWWPGLVV-----GWKSKQIPTAMRK-----VEWFGD-GMFSEIYTERLLPF 979
Cdd:cd20144     1 VGDLVWAKVSGHPWWPCMVTydpesGLYTKIKGSGGRTyrqyhVQFFGDnGERGWVSEKSLMPF 64

PWWP domain found in Arabidopsis thaliana histone-lysine N-methyltransferase trithorax-like proteins ATX1, ATX2, and similar proteins; This family includes A. thaliana ATX1 and ATX2, which are sister paralogs originating from a segmental chromosomal duplication. They are plant counterparts of the Drosophila melanogaster trithorax (TRX) and mammalian mixed-lineage leukemia (MLL1) proteins. ATX1, also called protein SET domain group 27, or trithorax-homolog protein 1 (TRX-homolog protein 1), is a methyltransferase that trimethylates histone H3 at lysine 4 (H3K4me3). It also acts as a histone modifier and as a positive effector of gene expression. ATX1 regulates transcription from diverse classes of genes implicated in biotic and abiotic stress responses. It is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways. ATX2, also called protein SET domain group 30, or trithorax-homolog protein 2 (TRX-homolog protein 2), is involved in dimethylating histone H3 at lysine 4 (H3K4me2). Both ATX1 and ATX2 are multi-domain containing proteins that consist of an N-terminal PWWP domain, FYRN- and FYRC (DAST, domain associated with SET in trithorax) domains, a canonical plant homeodomain (PHD) domain, a non-canonical extended PHD (ePHD) domain, and a C-terminal SET domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

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gi 973201388  926 SVGELVWGKVKGFSWWPGLVV---------GWKSKQIPTAMRKVEWFGDGMFSEIYTERLLPFS 980
Cdd:cd20142     1 SPGDVVWAKVKGYPMWPALVIdeehaercgLEANRPGKKGTVPVQFFGTYEVARLNPKKVVGFS 64

PWWP domain found in zinc finger CW-type PWWP domain protein 1 (ZCWPW1) and similar proteins; ZCWPW1 is a histone H3K4me3 reader. It is associated with late-onset Alzheimer's disease (LOAD). In addition to the PWWP domain, ZCWPW1 contains a zinc finger CW (zf-CW) domain that is a histone modification reader for the histone H3 tail with trimethylated K4. The PWWP domain specifically recognizes DNA and histone methylated lysines.

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gi 973201388  925 FSVGELVWGKVKGFSWWPGLV 945
Cdd:cd20145     6 YTPGSLVWAKMPGYPWWPAMV 26

PWWP domain found in protein BS69, protein kinase C-binding protein 1 (PRKCBP1) and similar proteins; Protein BS69, also called zinc finger MYND domain-containing protein 11 (ZMYND11 or ZMY11), is a ubiquitously expressed nuclear protein acting as a transcriptional co-repressor in association with various transcription factors. It was originally identified as an adenovirus 5 E1A-binding protein that inhibits E1A transactivation, as well as c-Myb transcription. BS69 is a multi-domain protein, containing bromo, plant homeodomain (PHD), proline-tryptophan-tryptophan-proline (PWWP), and MYeloid translocation protein 8, Nervy and DEAF-1 (MYND) domains. The specific role of the PWWP domain within BS69 is not clearly identified, but BS69 functions in chromatin remodeling, consistent with other PWWP-containing proteins. PRKCBP1, also called cutaneous T-cell lymphoma-associated antigen se14-3 (CTCL-associated antigen se14-3), Rack7, or zinc finger MYND domain-containing protein 8 (ZMYND8), is a novel receptor for activated C-kinase (RACK)-like protein that may play an important role in the activation and regulation of PKC-beta I, and the PKC signaling cascade. It also has been identified as a formin homology-2-domain containing protein 1 (FHOD1)-binding protein that may be involved in FHOD1-regulated actin polymerization and transcription. Moreover, PRKCBP1 may function as a REST co-repressor 2 (RCOR2) interacting factor. They form a RCOR2/ZMYND8 complex which might be involved in the regulation of neural differentiation. PRKCBP1 contains a PHD finger, a bromodomain, and a PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

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gi 973201388  929 ELVWGKVKGFSWWPGLVVGWKSKQIptamrKVEWFGDgmfseiYTERLLP 978
Cdd:cd05841     8 PLVWVKLDGFPFWPAKVMGTKDGQV-----DVRFFGD------YDRAWLP 46

PWWP domain found in Arabidopsis thaliana histone-lysine N-methyltransferase trithorax-like protein ATX3, ATX4, ATX5, and similar proteins; The family includes A. thaliana ATX3 (also called protein SET domain group 14, or trithorax-homolog protein 3), ATX4 (also called protein SET domain group 16, or trithorax-homolog protein 4) and ATX5 (also called protein SET domain group 29, or trithorax-homolog protein 5), which belong to the histone-lysine methyltransferase family. They show distinct phylogenetic origins from the family of ATX1 and ATX2. They are multi-domain containing protein that consists of an N-terminal PWWP domain, a canonical plant homeodomain (PHD) domain, a non-canonical extended PHD (ePHD) domain, and a C-terminal SET domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

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gi 973201388  928 GELVWGKVKGFSWWPGLVV 946
Cdd:cd20143     3 GDLVWAKVGTHPFWPARVV 21