macrodomain, Af1521-like family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. The macrodomains in this family show similarity to Af1521, a protein from Archaeoglobus fulgidus containing a stand-alone macrodomain. Af1521 binds ADP-ribose and exhibits phosphatase activity toward ADP-ribose-1"-monophosphate (Appr-1"-p). Also included in this family are the N-terminal (or first) macrodomains of BAL (B-aggressive lymphoma) proteins which contain multiple macrodomains, such as the first macrodomain of mono-ADP-ribosyltransferase PARP14 (PARP-14, also known as ADP-ribosyltransferase diphtheria toxin-like 8, ATRD8, B aggressive lymphoma protein 2, or BAL2). Most BAL proteins also contain a C-terminal PARP active site and are also named as PARPs. Human BAL1 (or PARP-9) was originally identified as a risk-related gene in diffuse large B-cell lymphoma that promotes malignant B-cell migration. Some BAL family proteins exhibit PARP activity. Poly (ADP-ribosyl)ation is an immediate DNA-damage-dependent post-translational modification of histones and other nuclear proteins. BAL proteins may also function as transcriptional repressors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  792 GVTLIVHEGDLSLFPVDVVVNAANESLKHIDGLAGTLSKAAGPSLQAECDLIVKKGGMVPPGNAVISKAGKLPCRYVIHA 871
Cdd:cd02907     1 GIKVSVYKGDITKEKVDAIVNAANERLKHGGGVAGAISKAGGPEIQEECDKYIKKNGKLRVGEVVVTSAGKLPCKYVIHA 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 300793858  872 VGPRWKGDKVLECVNLLKKAVKQSLTLAEEYKCQSIAIPAISSGIFDFPLDLCVASIASAIKDNVQQKQNtHSVKKIYL 950
Cdd:cd02907    81 VGPRWSGGSKEECEDLLYKAVLNSLEEAEELKATSIAIPAISSGIFGFPLDLCAEAIVEAIKDFSESNSS-SSLKEIRL 158

macrodomain superfamily; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Macrodomains include the yeast macrodomain Poa1 which is a phosphatase of ADP-ribose-1"-phosphate, a by-product of tRNA splicing. Some macrodomains have ADPr-unrelated binding partners such as the coronavirus SUD-N (N-terminal subdomain) and SUD-M (middle subdomain) of the SARS-unique domain (SUD) which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). Macrodomains regulate a wide variety of cellular and organismal processes, including DNA damage repair, signal transduction, and immune response.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  998 PEGLNIRLIEEGVQNAEAHAIVNSVSSDLiLNKGPLSQAFLESAGPELQEELTKagQGVSVSVGTVLQTSGCNLNSRSIF 1077
Cdd:cd02903     5 IGGITVQLVKGDITKEKTDVIVNSVSSDL-LLKGGVSKAILKAAGPELQDECAN--QGKQPASGDVIVTSGGNLPCKYVY 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858 1078 HVVTPPWKSNNsewsLKIMKNIIRDCLRTTEDLSLQSIAFPAIGTGNLGFPKPEFAKLIISEVLKFSSRNQLKTLQEVQF 1157
Cdd:cd02903    82 HVVLPHYNPGN----EKTLKDIVRKCLEKAENYKMSSISFPAIGTGNLGFPKDVVAEIMIDEVLKFSSKNPSSSLKEVRF 157

                         170       180
                  ....*....|....*....|
gi 300793858 1158 LLHPKdhENIQAFLDEFDKR 1177
Cdd:cd02903   158 VIFPP--ETLQAFSDELAKR 175

RNA recognition motif 1 in vertebrate poly [ADP-ribose] polymerase 14 (PARP-14); This subfamily corresponds to the RRM1 of PARP-14, also termed aggressive lymphoma protein 2, a member of the B aggressive lymphoma (BAL) family of macrodomain-containing PARPs. It is expressed in B lymphocytes and interacts with the IL-4-induced transcription factor Stat6. It plays a fundamental role in the regulation of IL-4-induced B-cell protection against apoptosis after irradiation or growth factor withdrawal. It mediates IL-4 effects on the levels of gene products that regulate cell survival, proliferation, and lymphomagenesis. PARP-14 acts as a transcriptional switch for Stat6-dependent gene activation. In the presence of IL-4, PARP-14 activates transcription by facilitating the binding of Stat6 to the promoter and release of HDACs from the promoter with an IL-4 signal. In contrast, in the absence of a signal, PARP-14 acts as a transcriptional repressor by recruiting HDACs. Moreover, the absence of PARP-14 protects against Myc-induced developmental block and lymphoma. Thus, PARP-14 may play an important role in Myc-induced oncogenesis. Research indicates that PARP-14 is also a binding partner with phosphoglucose isomerase (PGI)/ autocrine motility factor (AMF). It can inhibit PGI/AMF ubiquitination, thus contributing to its stabilization and secretion. PARP-14 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), three tandem macro domains, and C-terminal region with sequence homology to PARP catalytic domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858    6 PFPLLVEGSWGPDPPKNLINKLQMYFQSRKKSGGGECEVVPEPGNPARFLVLFSPEDVRQNVLEKENHELvWQGKGTFKM 85
Cdd:cd12300     1 PFPLLVEGDWDPSPPKKLKNKLEKYFQSKKRSGGGECTVETEGPSPQTARVSFVNEEVRERVLEKKEHEI-LQGEGTVRL 79

                  ...
gi 300793858   86 TVQ 88
Cdd:cd12300    80 TVK 82

macrodomain, Af1521-like family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. The macrodomains in this family show similarity to Af1521, a protein from Archaeoglobus fulgidus containing a stand-alone macrodomain. Af1521 binds ADP-ribose and exhibits phosphatase activity toward ADP-ribose-1"-monophosphate (Appr-1"-p). Also included in this family are the N-terminal (or first) macrodomains of BAL (B-aggressive lymphoma) proteins which contain multiple macrodomains, such as the first macrodomain of mono-ADP-ribosyltransferase PARP14 (PARP-14, also known as ADP-ribosyltransferase diphtheria toxin-like 8, ATRD8, B aggressive lymphoma protein 2, or BAL2). Most BAL proteins also contain a C-terminal PARP active site and are also named as PARPs. Human BAL1 (or PARP-9) was originally identified as a risk-related gene in diffuse large B-cell lymphoma that promotes malignant B-cell migration. Some BAL family proteins exhibit PARP activity. Poly (ADP-ribosyl)ation is an immediate DNA-damage-dependent post-translational modification of histones and other nuclear proteins. BAL proteins may also function as transcriptional repressors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  792 GVTLIVHEGDLSLFPVDVVVNAANESLKHIDGLAGTLSKAAGPSLQAECDLIVKKGGMVPPGNAVISKAGKLPCRYVIHA 871
Cdd:cd02907     1 GIKVSVYKGDITKEKVDAIVNAANERLKHGGGVAGAISKAGGPEIQEECDKYIKKNGKLRVGEVVVTSAGKLPCKYVIHA 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 300793858  872 VGPRWKGDKVLECVNLLKKAVKQSLTLAEEYKCQSIAIPAISSGIFDFPLDLCVASIASAIKDNVQQKQNtHSVKKIYL 950
Cdd:cd02907    81 VGPRWSGGSKEECEDLLYKAVLNSLEEAEELKATSIAIPAISSGIFGFPLDLCAEAIVEAIKDFSESNSS-SSLKEIRL 158

ADP-ribose-binding protein;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  792 GVTLIVHEGDLSLFPVDVVVNAANESLKHIDGLAGTLSKAAGPSLQAECDLIVKKGGMVPPGNAVISKAGKLPCRYVIHA 871
Cdd:PRK00431    2 GMRIEVVQGDITELEVDAIVNAANSSLLGGGGVDGAIHRAAGPEILEECRELRQQQGPCPTGEAVITSAGRLPAKYVIHT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  872 VGPRWkGDKVLECVNLLKKAVKQSLTLAEEYKCQSIAIPAISSGIFDFPLDLCVASIASAIKDNVQQKQnthSVKKIYLV 951
Cdd:PRK00431   82 VGPVW-RGGEDNEAELLASAYRNSLRLAAELGLRSIAFPAISTGVYGYPLEDAARIAVKTVREFLTRHK---SPEEVYFV 157

                         170
                  ....*....|....*
gi 300793858  952 DVSAKVAKAFAEAVK 966
Cdd:PRK00431  158 CYDEEAYRLYERLLT 172

Poly(ADP-ribose) polymerases catalyse the covalent attachment of ADP-ribose units from NAD+ to itself and to a limited number of other DNA binding proteins, which decreases their affinity for DNA. Poly(ADP-ribose) polymerase is a regulatory component induced by DNA damage. The carboxyl-terminal region is the most highly conserved region of the protein. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes pleotropic effects in mammalian species through modulating gene expression. TCCD indicible PARP (TiPARP) is a target of TCDD that may contribute to multiple responses to TCDD by modulating protein function through poly ADP-ribosylation

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858 1665 QLFHGTEFGSLAQLNSNGFNRSYAGKNATAYGKGTYFAVNASYSAHDTYSKPDANGKKYMYYVRVLTGNYTQGNASLIVP 1744
Cdd:cd01439     1 LLFHGTSADAVEAICRHGFDRRFCGKHGTMYGKGSYFAKNASYSHQYSKKSPKADGLKEMFLARVLTGDYTQGHPGYRRP 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 300793858 1745 PSRDPQNATDLFDTVADNVINPSIFVVFYDNQAYPEYLITF 1785
Cdd:cd01439    81 PLKPSGVELDRYDSCVDNVSNPSIFVIFSDVQAYPEYLITY 121

Macro domain; The Macro or A1pp domain is a module of about 180 amino acids which can bind ADP-ribose (an NAD metabolite) or related ligands. Binding to ADP-ribose could be either covalent or non-covalent: in certain cases it is believed to bind non-covalently; while in other cases (such as Aprataxin) it appears to bind both non-covalently through a zinc finger motif, and covalently through a separate region of the protein. This domain is found in a number of otherwise unrelated proteins. It is found at the C-terminus of the macro-H2A histone protein 4 and also in the non-structural proteins of several types of ssRNA viruses such as NSP3 from alpha-viruses and coronaviruses. This domain is also found on its own in a family of proteins from bacteria, archaebacteria and eukaryotes. The 3D structure of the SARS-CoV Macro domain has a mixed alpha/beta fold consisting of a central seven-stranded twisted mixed beta sheet sandwiched between two alpha helices on one face, and three on the other. The final alpha-helix, located on the edge of the central beta-sheet, forms the C terminus of the protein. The crystal structure of AF1521 (a Macro domain-only protein from Archaeoglobus fulgidus) has also been reported and compared with other Macro domain containing proteins. Several Macro domain only proteins are shorter than AF1521, and appear to lack either the first strand of the beta-sheet or the C-terminal helix 5. Well conserved residues form a hydrophobic cleft and cluster around the AF1521-ADP-ribose binding site.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858   811 VNAANESLKHIDGLAGTLSKAAGPSLQAECDLIVKKGgmVPPGNAVISKAGKLPCRYVIHAVGPRWKGDKVLECVNLLKK 890
Cdd:pfam01661    1 VNAANSRLLGGGGVAGAIHRAAGPELLEECRELKKGG--CPTGEAVVTPGGNLPAKYVIHTVGPTWRHGGSHGEEELLES 78

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 300793858   891 AVKQSLTLAEEYKCQSIAIPAISSGIFDFPLDLcVASIA 929
Cdd:pfam01661   79 CYRNALALAEELGIKSIAFPAISTGIYGFPWEE-AARIA 116

Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by reciprocal PSI-BLAST searches (unpublished results, and Pehrson _ Fuji).

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858    795 LIVHEGDLSLFPVDVVVNAANESLKHIDGLAGTLSKAAGPSLQAEcDLIVKKGGMVPPGNAVISKAGKLPCRYVIHAVGP 874
Cdd:smart00506    2 LKVVKGDITKPRADAIVNAANSDGAHGGGVAGAIARAAGKALSKE-EVRKLAGGECPVGTAVVTEGGNLPAKYVIHAVGP 80

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....
gi 300793858    875 RWkGDKVLECVNLLKKAVKQSLTLAEEYKCQSIAIPAISSGIFDFPLDLCVASI 928
Cdd:smart00506   81 RA-SGHSKEGFELLENAYRNCLELAIELGITSVALPLIGTGIYGVPKDRSAQAL 133

O-acetyl-ADP-ribose deacetylase (regulator of RNase III), contains Macro domain [Translation, ribosomal structure and biogenesis];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858 1013 AEAHAIVNSVSSDLILNKGpLSQAFLESAGPELQEELTKAGQGVSVSVGTVLQTSGCNLNSRSIFHVVTPPWKSNNsEWS 1092
Cdd:COG2110    11 LDVDAIVNAANSSLLGGGG-VAGAIHRAAGPELLEECRRLCKQGGCPTGEAVITPAGNLPAKYVIHTVGPVWRGGG-PSE 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858 1093 LKIMKNIIRDCLRTTEDLSLQSIAFPAIGTGNLGFPKPEFAKLIISEVLKFSSRNqlKTLQEVQFLLH-PKDHENIQAFL 1171
Cdd:COG2110    89 EELLASCYRNSLELAEELGIRSIAFPAIGTGVGGFPWEEAAPIAVETLRDFLEEH--PSLEEVRFVLFdEEDYEAYRRAL 166

                  ..
gi 300793858 1172 DE 1173
Cdd:COG2110   167 AR 168

O-acetyl-ADP-ribose deacetylase (regulator of RNase III), contains Macro domain [Translation, ribosomal structure and biogenesis];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858 1216 FQVATGDIIKEVADVIVNSTSCTFNLKSGVSKAILEGAGQNVEQECSRLAQQGK----EYIVTGGGLLKCKSIIHV---- 1287
Cdd:COG2110     1 IEIVQGDITELDVDAIVNAANSSLLGGGGVAGAIHRAAGPELLEECRRLCKQGGcptgEAVITPAGNLPAKYVIHTvgpv 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858 1288 -DGGNDVKRSV--SCI---LEECEQRSFSSICLPAIGTGSAQQDPKVVAKAVLDAIEEFVQKKSvqAVKRVKVVIFQPHI 1361
Cdd:COG2110    81 wRGGGPSEEELlaSCYrnsLELAEELGIRSIAFPAIGTGVGGFPWEEAAPIAVETLRDFLEEHP--SLEEVRFVLFDEED 158

                         170
                  ....*....|
gi 300793858 1362 LQFFYDNMKE 1371
Cdd:COG2110   159 YEAYRRALAR 168

Macro domain; The Macro or A1pp domain is a module of about 180 amino acids which can bind ADP-ribose (an NAD metabolite) or related ligands. Binding to ADP-ribose could be either covalent or non-covalent: in certain cases it is believed to bind non-covalently; while in other cases (such as Aprataxin) it appears to bind both non-covalently through a zinc finger motif, and covalently through a separate region of the protein. This domain is found in a number of otherwise unrelated proteins. It is found at the C-terminus of the macro-H2A histone protein 4 and also in the non-structural proteins of several types of ssRNA viruses such as NSP3 from alpha-viruses and coronaviruses. This domain is also found on its own in a family of proteins from bacteria, archaebacteria and eukaryotes. The 3D structure of the SARS-CoV Macro domain has a mixed alpha/beta fold consisting of a central seven-stranded twisted mixed beta sheet sandwiched between two alpha helices on one face, and three on the other. The final alpha-helix, located on the edge of the central beta-sheet, forms the C terminus of the protein. The crystal structure of AF1521 (a Macro domain-only protein from Archaeoglobus fulgidus) has also been reported and compared with other Macro domain containing proteins. Several Macro domain only proteins are shorter than AF1521, and appear to lack either the first strand of the beta-sheet or the C-terminal helix 5. Well conserved residues form a hydrophobic cleft and cluster around the AF1521-ADP-ribose binding site.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  1019 VNSVSSDLiLNKGPLSQAFLESAGPELQEELTKAGQGvSVSVGTVLQTSGCNLNSRSIFHVVTPPWKSNNSEWSLKIMKN 1098
Cdd:pfam01661    1 VNAANSRL-LGGGGVAGAIHRAAGPELLEECRELKKG-GCPTGEAVVTPGGNLPAKYVIHTVGPTWRHGGSHGEEELLES 78

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 300793858  1099 IIRDCLRTTEDLSLQSIAFPAIGTGNLGFPKPEFAKLI 1136
Cdd:pfam01661   79 CYRNALALAEELGIKSIAFPAISTGIYGFPWEEAARIA 116

ADP-ribose-binding protein;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858 1014 EAHAIVNSVSSDLiLNKGPLSQAFLESAGPELQEE-LTKAGQGVSVSVGTVLQTSGCNLNSRSIFHVVTPPWKSNNSEWS 1092
Cdd:PRK00431   16 EVDAIVNAANSSL-LGGGGVDGAIHRAAGPEILEEcRELRQQQGPCPTGEAVITSAGRLPAKYVIHTVGPVWRGGEDNEA 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858 1093 LKiMKNIIRDCLRTTEDLSLQSIAFPAIGTGNLGFPKPEFAKLIISEVLKFSSRnqLKTLQEVQFLLHpkDHENIQAFLD 1172
Cdd:PRK00431   95 EL-LASAYRNSLRLAAELGLRSIAFPAISTGVYGYPLEDAARIAVKTVREFLTR--HKSPEEVYFVCY--DEEAYRLYER 169

                  ....*...
gi 300793858 1173 EFDKRSNG 1180
Cdd:PRK00431  170 LLTQQGDE 177

Macro domain; The Macro or A1pp domain is a module of about 180 amino acids which can bind ADP-ribose (an NAD metabolite) or related ligands. Binding to ADP-ribose could be either covalent or non-covalent: in certain cases it is believed to bind non-covalently; while in other cases (such as Aprataxin) it appears to bind both non-covalently through a zinc finger motif, and covalently through a separate region of the protein. This domain is found in a number of otherwise unrelated proteins. It is found at the C-terminus of the macro-H2A histone protein 4 and also in the non-structural proteins of several types of ssRNA viruses such as NSP3 from alpha-viruses and coronaviruses. This domain is also found on its own in a family of proteins from bacteria, archaebacteria and eukaryotes. The 3D structure of the SARS-CoV Macro domain has a mixed alpha/beta fold consisting of a central seven-stranded twisted mixed beta sheet sandwiched between two alpha helices on one face, and three on the other. The final alpha-helix, located on the edge of the central beta-sheet, forms the C terminus of the protein. The crystal structure of AF1521 (a Macro domain-only protein from Archaeoglobus fulgidus) has also been reported and compared with other Macro domain containing proteins. Several Macro domain only proteins are shorter than AF1521, and appear to lack either the first strand of the beta-sheet or the C-terminal helix 5. Well conserved residues form a hydrophobic cleft and cluster around the AF1521-ADP-ribose binding site.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  1232 VNSTSCTFNLKSGVSKAILEGAGQNVEQECSRLAQQGK---EYIVTGGGLLKCKSIIHVDG-----GNDVKRS---VSC- 1299
Cdd:pfam01661    1 VNAANSRLLGGGGVAGAIHRAAGPELLEECRELKKGGCptgEAVVTPGGNLPAKYVIHTVGptwrhGGSHGEEellESCy 80

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 300793858  1300 --ILEECEQRSFSSICLPAIGTGSAQQDPKVVAKA 1332
Cdd:pfam01661   81 rnALALAEELGIKSIAFPAISTGIYGFPWEEAARI 115

macrodomain, Af1521-like family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. The macrodomains in this family show similarity to Af1521, a protein from Archaeoglobus fulgidus containing a stand-alone macrodomain. Af1521 binds ADP-ribose and exhibits phosphatase activity toward ADP-ribose-1"-monophosphate (Appr-1"-p). Also included in this family are the N-terminal (or first) macrodomains of BAL (B-aggressive lymphoma) proteins which contain multiple macrodomains, such as the first macrodomain of mono-ADP-ribosyltransferase PARP14 (PARP-14, also known as ADP-ribosyltransferase diphtheria toxin-like 8, ATRD8, B aggressive lymphoma protein 2, or BAL2). Most BAL proteins also contain a C-terminal PARP active site and are also named as PARPs. Human BAL1 (or PARP-9) was originally identified as a risk-related gene in diffuse large B-cell lymphoma that promotes malignant B-cell migration. Some BAL family proteins exhibit PARP activity. Poly (ADP-ribosyl)ation is an immediate DNA-damage-dependent post-translational modification of histones and other nuclear proteins. BAL proteins may also function as transcriptional repressors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  792 GVTLIVHEGDLSLFPVDVVVNAANESLKHIDGLAGTLSKAAGPSLQAECDLIVKKGGMVPPGNAVISKAGKLPCRYVIHA 871
Cdd:cd02907     1 GIKVSVYKGDITKEKVDAIVNAANERLKHGGGVAGAISKAGGPEIQEECDKYIKKNGKLRVGEVVVTSAGKLPCKYVIHA 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 300793858  872 VGPRWKGDKVLECVNLLKKAVKQSLTLAEEYKCQSIAIPAISSGIFDFPLDLCVASIASAIKDNVQQKQNtHSVKKIYL 950
Cdd:cd02907    81 VGPRWSGGSKEECEDLLYKAVLNSLEEAEELKATSIAIPAISSGIFGFPLDLCAEAIVEAIKDFSESNSS-SSLKEIRL 158

ADP-ribose-binding protein;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  792 GVTLIVHEGDLSLFPVDVVVNAANESLKHIDGLAGTLSKAAGPSLQAECDLIVKKGGMVPPGNAVISKAGKLPCRYVIHA 871
Cdd:PRK00431    2 GMRIEVVQGDITELEVDAIVNAANSSLLGGGGVDGAIHRAAGPEILEECRELRQQQGPCPTGEAVITSAGRLPAKYVIHT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  872 VGPRWkGDKVLECVNLLKKAVKQSLTLAEEYKCQSIAIPAISSGIFDFPLDLCVASIASAIKDNVQQKQnthSVKKIYLV 951
Cdd:PRK00431   82 VGPVW-RGGEDNEAELLASAYRNSLRLAAELGLRSIAFPAISTGVYGYPLEDAARIAVKTVREFLTRHK---SPEEVYFV 157

                         170
                  ....*....|....*
gi 300793858  952 DVSAKVAKAFAEAVK 966
Cdd:PRK00431  158 CYDEEAYRLYERLLT 172

Poly(ADP-ribose) polymerases catalyse the covalent attachment of ADP-ribose units from NAD+ to itself and to a limited number of other DNA binding proteins, which decreases their affinity for DNA. Poly(ADP-ribose) polymerase is a regulatory component induced by DNA damage. The carboxyl-terminal region is the most highly conserved region of the protein. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes pleotropic effects in mammalian species through modulating gene expression. TCCD indicible PARP (TiPARP) is a target of TCDD that may contribute to multiple responses to TCDD by modulating protein function through poly ADP-ribosylation

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858 1665 QLFHGTEFGSLAQLNSNGFNRSYAGKNATAYGKGTYFAVNASYSAHDTYSKPDANGKKYMYYVRVLTGNYTQGNASLIVP 1744
Cdd:cd01439     1 LLFHGTSADAVEAICRHGFDRRFCGKHGTMYGKGSYFAKNASYSHQYSKKSPKADGLKEMFLARVLTGDYTQGHPGYRRP 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 300793858 1745 PSRDPQNATDLFDTVADNVINPSIFVVFYDNQAYPEYLITF 1785
Cdd:cd01439    81 PLKPSGVELDRYDSCVDNVSNPSIFVIFSDVQAYPEYLITY 121

macrodomain, O-acetyl-ADP-ribose (OAADPr) family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. This family includes eukaryotic macrodomain proteins such as human MacroD1 and MacroD2, and bacterial proteins such as Escherichia coli YmdB; these have been shown to be O-acetyl-ADP-ribose (OAADPr) deacetylases that efficiently catalyze the hydrolysis of OAADPr to produce ADP-ribose and free acetate. OAADPr is a sirtuin reaction product generated from the NAD+-dependent protein deacetylation reactions and has been implicated as a signaling molecule. By acting on mono-ADP-ribosylated substrates, OAADPr deacetylases may reverse cellular ADP-ribosylation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  795 LIVHEGDLSLFPVDVVVNAANESL---KHIDGlagTLSKAAGPSLQAECDLIvkkGGMVPPGNAVISKAGKLPCRYVIHA 871
Cdd:cd02908     2 ISLWRGDITKLEVDAIVNAANSSLlggGGVDG---AIHRAAGPELLEECRKL---GGVCPTGEAKITPGYNLPAKYVIHT 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  872 VGPRWKGDKVLECvNLLKKAVKQSLTLAEEYKCQSIAIPAISSGIFDFPLDLcVASIA-SAIKDNVQQkqnTHSVKKIYL 950
Cdd:cd02908    76 VGPIGEGGVEEEP-ELLASCYRSSLELALENGLKSIAFPCISTGIYGYPNEE-AAEIAlNTVREWLEE---HDKIDRIIF 150

                  .
gi 300793858  951 V 951
Cdd:cd02908   151 V 151

RNA recognition motif 1 in vertebrate poly [ADP-ribose] polymerase 14 (PARP-14); This subfamily corresponds to the RRM1 of PARP-14, also termed aggressive lymphoma protein 2, a member of the B aggressive lymphoma (BAL) family of macrodomain-containing PARPs. It is expressed in B lymphocytes and interacts with the IL-4-induced transcription factor Stat6. It plays a fundamental role in the regulation of IL-4-induced B-cell protection against apoptosis after irradiation or growth factor withdrawal. It mediates IL-4 effects on the levels of gene products that regulate cell survival, proliferation, and lymphomagenesis. PARP-14 acts as a transcriptional switch for Stat6-dependent gene activation. In the presence of IL-4, PARP-14 activates transcription by facilitating the binding of Stat6 to the promoter and release of HDACs from the promoter with an IL-4 signal. In contrast, in the absence of a signal, PARP-14 acts as a transcriptional repressor by recruiting HDACs. Moreover, the absence of PARP-14 protects against Myc-induced developmental block and lymphoma. Thus, PARP-14 may play an important role in Myc-induced oncogenesis. Research indicates that PARP-14 is also a binding partner with phosphoglucose isomerase (PGI)/ autocrine motility factor (AMF). It can inhibit PGI/AMF ubiquitination, thus contributing to its stabilization and secretion. PARP-14 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), three tandem macro domains, and C-terminal region with sequence homology to PARP catalytic domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858    6 PFPLLVEGSWGPDPPKNLINKLQMYFQSRKKSGGGECEVVPEPGNPARFLVLFSPEDVRQNVLEKENHELvWQGKGTFKM 85
Cdd:cd12300     1 PFPLLVEGDWDPSPPKKLKNKLEKYFQSKKRSGGGECTVETEGPSPQTARVSFVNEEVRERVLEKKEHEI-LQGEGTVRL 79

                  ...
gi 300793858   86 TVQ 88
Cdd:cd12300    80 TVK 82

RNA recognition motif 2 in vertebrate poly [ADP-ribose] polymerase 14 (PARP-14); This subgroup corresponds to the RRM2 of PARP-14, also termed aggressive lymphoma protein 2, a member of the B aggressive lymphoma (BAL) family of macrodomain-containing PARPs. It is expressed in B lymphocytes and interacts with the IL-4-induced transcription factor Stat6. It plays a fundamental role in the regulation of IL-4-induced B-cell protection against apoptosis after irradiation or growth factor withdrawal. It mediates IL-4 effects on the levels of gene products that regulate cell survival, proliferation, and lymphomagenesis. PARP-14 acts as a transcriptional switch for Stat6-dependent gene activation. In the presence of IL-4, PARP-14 activates transcription by facilitating the binding of Stat6 to the promoter and release of HDACs from the promoter with an IL-4 signal. In contrast, in the absence of a signal, PARP-14 acts as a transcriptional repressor by recruiting HDACs. Absence of PARP-14 protects against Myc-induced developmental block and lymphoma. Thus, PARP-14 may play an important role in Myc-induced oncogenesis. Additional research indicates that PARP-14 is also a binding partner with phosphoglucose isomerase (PGI)/ autocrine motility factor (AMF). It can inhibit PGI/AMF ubiquitination, thus contributing to its stabilization and secretion. PARP-14 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), three tandem macro domains, and C-terminal region with sequence homology to PARP catalytic domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 300793858  223 TNVVRVENLPPGVDDYQLQLFFENPFNGGGRVARVECFPEESSALVEFCDSKVLDTIMAKKHSFNKMPLSVFPYY 297
Cdd:cd12543     1 TCKIRAENLPPNTNSDYLMLYFENPYNGGIEVDGVTVDPEEESAIITFADPKDVQKIIALKHQFNKMPFSVLPYY 75

macrodomain, macroH2A-like family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Members of this family are similar to macroH2A, a variant of the major-type core histone H2A, which contains an N-terminal H2A domain and a C-terminal nonhistone macrodomain. Histone macroH2A is enriched on the inactive X chromosome of mammalian female cells. It does not bind poly ADP-ribose, but does bind the monomeric SirT1 metabolite O-acetyl-ADP-ribose (OAADPR) with high affinity through its macrodomain. This family also includes the ADP-ribose binding macrodomain of the macroH2A variant, macroH2A1.1. The macroH2A1.1 isoform inhibits PARP1-dependent DNA-damage induced chromatin dynamics. The putative ADP-ribose binding pocket of the human macroH2A2 macrodomain exhibits marked structural differences compared with the macroH2A1.1 variant.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  778 LKEQKCYLqrdigpGVTLIVHEGDLSLFPVDVVVNAANESLKHIDGLAGTLSKAAGPSLQAECDLIVKKGGMVPPGNAVI 857
Cdd:cd02904     9 LSEKKLFL------GQKLTVVQGDIASIKADAIVHPTNATFYLGGEVGSALEKAGGKEFVEEVKELRKSNGPLEVAGAAI 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  858 SKAGKLPCRYVIHAVGPRWKGDKvleCVNLLKKAVKQSLTLAEEYKCQSIAIPAISSGIFDFPLDLCVASIASAIKD--- 934
Cdd:cd02904    83 SPGHNLPAKFVIHCNSPSWGSDK---CEELLEKTVKNCLALADEKKLKSVAFPSIGSGRNGFPKQTAAQTILKAISNyfv 159

                         170
                  ....*....|....*..
gi 300793858  935 NVQqkqnTHSVKKIYLV 951
Cdd:cd02904   160 SVM----SSSLKQIYFV 172

Macrodomain, uncharacterized family similar to Thermus thermophilus hypothetical protein Ttha0132; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Macrodomains include the yeast macrodomain Poa1 which is a phosphatase of ADP-ribose-1"-phosphate, a by-product of tRNA splicing. Some macrodomains have ADPr-unrelated binding partners such as the coronavirus SUD-N (N-terminal subdomain) and SUD-M (middle subdomain) of the SARS-unique domain (SUD) which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). Macrodomains regulate a wide variety of cellular and organismal processes, including DNA damage repair, signal transduction, and immune response. This family is composed of uncharacterized proteins containing a stand-alone macrodomain, similar to Thermus thermophilus hypothetical protein Ttha0132.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  795 LIVHEGDLSLFPVDVVVNAANESLKHIDGLAGTLSKAAGPSLQAECDlivkKGGMVPPGNAVISKAGKLPCRYVIHAVG- 873
Cdd:cd03330     2 LIVVQGDITEQDADAIVNAANRRLLMGSGVAGAIKRKGGEEIEREAM----RKGPIRVGEAVETGAGKLPAKYVIHAAVm 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  874 PRWkGDKVLECVnllKKAVKQSLTLAEEYKCQSIAIPAISSGIFDFPLDLCVASIASAIK 933
Cdd:cd03330    78 GMP-GRSSEESI---RDATRNALAKAEELGLESVAFPAIGTGVGGFPVEEVARIMLEEIK 133

macrodomain, Af1521-like family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. The macrodomains in this family show similarity to Af1521, a protein from Archaeoglobus fulgidus containing a stand-alone macrodomain. Af1521 binds ADP-ribose and exhibits phosphatase activity toward ADP-ribose-1"-monophosphate (Appr-1"-p). Also included in this family are the N-terminal (or first) macrodomains of BAL (B-aggressive lymphoma) proteins which contain multiple macrodomains, such as the first macrodomain of mono-ADP-ribosyltransferase PARP14 (PARP-14, also known as ADP-ribosyltransferase diphtheria toxin-like 8, ATRD8, B aggressive lymphoma protein 2, or BAL2). Most BAL proteins also contain a C-terminal PARP active site and are also named as PARPs. Human BAL1 (or PARP-9) was originally identified as a risk-related gene in diffuse large B-cell lymphoma that promotes malignant B-cell migration. Some BAL family proteins exhibit PARP activity. Poly (ADP-ribosyl)ation is an immediate DNA-damage-dependent post-translational modification of histones and other nuclear proteins. BAL proteins may also function as transcriptional repressors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858 1017 AIVNSVSSDLiLNKGPLSQAFLESAGPELQEELTKA--GQGvSVSVGTVLQTSGCNLNSRSIFHVVTPPWKSNNSEWSLK 1094
Cdd:cd02907    18 AIVNAANERL-KHGGGVAGAISKAGGPEIQEECDKYikKNG-KLRVGEVVVTSAGKLPCKYVIHAVGPRWSGGSKEECED 95

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 300793858 1095 IMKNIIRDCLRTTEDLSLQSIAFPAIGTGNLGFPKPEFAKLIISEVLKFSSRNQLKTLQEVQF 1157
Cdd:cd02907    96 LLYKAVLNSLEEAEELKATSIAIPAISSGIFGFPLDLCAEAIVEAIKDFSESNSSSSLKEIRL 158

macrodomain, B-aggressive lymphoma (BAL)-like family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Members of this family show similarity to BAL (B-aggressive lymphoma) proteins, which contain one to three macrodomains. Most BAL family macrodomains belong to this family except for the most N-terminal domain in multiple-domain containing proteins. This family includes the second and third macrodomains of mono-ADP-ribosyltransferase PARP14 (PARP-14, also known as ADP-ribosyltransferase diphtheria toxin-like 8, ATRD8, B aggressive lymphoma protein 2, or BAL2). Most BAL proteins also contain a C-terminal PARP active site and are also named as PARPs. Human BAL1 (or PARP-9) was originally identified as a risk-related gene in diffuse large B-cell lymphoma that promotes malignant B-cell migration. Some BAL family proteins exhibit PARP activity. Poly (ADP-ribosyl)ation is an immediate DNA-damage-dependent post-translational modification of histones and other nuclear proteins. BAL proteins may also function as transcriptional repressors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  790 GPGVTLIVHEGDLSLFPVDVVVNAANESLKHIDGLAGTLSKAAGPSLQAECDlivKKGGMVPPGNAVISKAGKLPCRYVI 869
Cdd:cd02903     5 IGGITVQLVKGDITKEKTDVIVNSVSSDLLLKGGVSKAILKAAGPELQDECA---NQGKQPASGDVIVTSGGNLPCKYVY 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300793858  870 HAVGPRWKGDKvlecVNLLKKAVKQSLTLAEEYKCQSIAIPAISSGIFDFPLDLCVASIASAIKDNVQQKQNThSVKKIY 949
Cdd:cd02903    82 HVVLPHYNPGN----EKTLKDIVRKCLEKAENYKMSSISFPAIGTGNLGFPKDVVAEIMIDEVLKFSSKNPSS-SLKEVR 156

                         170
                  ....*....|..
gi 300793858  950 LVDVSAKVAKAF 961
Cdd:cd02903   157 FVIFPPETLQAF 168