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 2462590685  801 GVVLIVQQGDLARLPVDVVVNASNEDLKHYGGLAAALSKAAGPELQADCDQIVKREGRLLPGNATISKAGKLPYHHVIHA 880
Cdd:cd02907      1 GIKVSVYKGDITKEKVDAIVNAANERLKHGGGVAGAISKAGGPEIQEECDKYIKKNGKLRVGEVVVTSAGKLPCKYVIHA 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462590685  881 VGPRWSGYEAPRCVYLLRRAVQLSLCLAEKYKYRSIAIPAISSGVFGFPLGRCVETIVSAIKEnFQFKKDGHCLKEIYL 959
Cdd:cd02907     81 VGPRWSGGSKEECEDLLYKAVLNSLEEAEELKATSIAIPAISSGIFGFPLDLCAEAIVEAIKD-FSESNSSSSLKEIRL 158

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 2462590685    6 SFPLLVEGSWGPDPPKNLNTKLQMYFQSPKRSGGGECEVRQDPRSPSRFLVFFYPEDVRQKVLERKNHELvWQGKGTFKL 85
Cdd:cd12300      1 PFPLLVEGDWDPSPPKKLKNKLEKYFQSKKRSGGGECTVETEGPSPQTARVSFVNEEVRERVLEKKEHEI-LQGEGTVRL 79

                   ...
gi 2462590685   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 2462590685  801 GVVLIVQQGDLARLPVDVVVNASNEDLKHYGGLAAALSKAAGPELQADCDQIVKREGRLLPGNATISKAGKLPYHHVIHA 880
Cdd:cd02907      1 GIKVSVYKGDITKEKVDAIVNAANERLKHGGGVAGAISKAGGPEIQEECDKYIKKNGKLRVGEVVVTSAGKLPCKYVIHA 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462590685  881 VGPRWSGYEAPRCVYLLRRAVQLSLCLAEKYKYRSIAIPAISSGVFGFPLGRCVETIVSAIKEnFQFKKDGHCLKEIYL 959
Cdd:cd02907     81 VGPRWSGGSKEECEDLLYKAVLNSLEEAEELKATSIAIPAISSGIFGFPLDLCAEAIVEAIKD-FSESNSSSSLKEIRL 158

ADP-ribose-binding protein;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462590685  801 GVVLIVQQGDLARLPVDVVVNASNEDLKHYGGLAAALSKAAGPELQADCDQIVKREGRLLPGNATISKAGKLPYHHVIHA 880
Cdd:PRK00431     2 GMRIEVVQGDITELEVDAIVNAANSSLLGGGGVDGAIHRAAGPEILEECRELRQQQGPCPTGEAVITSAGRLPAKYVIHT 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462590685  881 VGPRWSGyEAPRCVYLLRRAVQLSLCLAEKYKYRSIAIPAISSGVFGFPLGRCVETIVSAIKEnfqFKKDGHCLKEIYLV 960
Cdd:PRK00431    82 VGPVWRG-GEDNEAELLASAYRNSLRLAAELGLRSIAFPAISTGVYGYPLEDAARIAVKTVRE---FLTRHKSPEEVYFV 157

                          170
                   ....*....|....*
gi 2462590685  961 DVSEKTVEAFAEAVK 975
Cdd:PRK00431   158 CYDEEAYRLYERLLT 172

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 2462590685    6 SFPLLVEGSWGPDPPKNLNTKLQMYFQSPKRSGGGECEVRQDPRSPSRFLVFFYPEDVRQKVLERKNHELvWQGKGTFKL 85
Cdd:cd12300      1 PFPLLVEGDWDPSPPKKLKNKLEKYFQSKKRSGGGECTVETEGPSPQTARVSFVNEEVRERVLEKKEHEI-LQGEGTVRL 79

                   ...
gi 2462590685   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 2462590685  227 TNTIRVENLPPGADDYSLKLFFENPYNGGGRVANVEYFPEESSALIEFFDRKVLDTIMATKLDFNKMPLSVFPYY 301
Cdd:cd12543      1 TCKIRAENLPPNTNSDYLMLYFENPYNGGIEVDGVTVDPEEESAIITFADPKDVQKIIALKHQFNKMPFSVLPYY 75

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 2462590685  1018 LVKEGVQNAKTDVVVNSVPLDLVLSRGpLSKSLLEKAGPEL-QEELDTVGQGvAVSMGTVLKTSSWNLDCRYVLHVVAPE 1096
Cdd:smart00506    4 VVKGDITKPRADAIVNAANSDGAHGGG-VAGAIARAAGKALsKEEVRKLAGG-ECPVGTAVVTEGGNLPAKYVIHAVGPR 81

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|..
gi 2462590685  1097 WRNGSTSSLKIMEDIIRECMEITESLSLKSIAFPAIGTGNLGFPKNIFAELI 1148
Cdd:smart00506   82 ASGHSKEGFELLENAYRNCLELAIELGITSVALPLIGTGIYGVPKDRSAQAL 133

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 2462590685 1044 GPLSKSLLEKAGPELQEELDTVGQGVaVSMGTVLKTSSWNLDCRYVLHVVAPEWRN-GSTSSLKIMEDIIRECMEITESL 1122
Cdd:pfam01661   12 GGVAGAIHRAAGPELLEECRELKKGG-CPTGEAVVTPGGNLPAKYVIHTVGPTWRHgGSHGEEELLESCYRNALALAEEL 90

                           90       100
                   ....*....|....*....|....*.
gi 2462590685 1123 SLKSIAFPAIGTGNLGFPKNIFAELI 1148
Cdd:pfam01661   91 GIKSIAFPAISTGIYGFPWEEAARIA 116

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 2462590685  801 GVVLIVQQGDLARLPVDVVVNASNEDLKHYGGLAAALSKAAGPELQADCDQIVKREGRLLPGNATISKAGKLPYHHVIHA 880
Cdd:cd02907      1 GIKVSVYKGDITKEKVDAIVNAANERLKHGGGVAGAISKAGGPEIQEECDKYIKKNGKLRVGEVVVTSAGKLPCKYVIHA 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462590685  881 VGPRWSGYEAPRCVYLLRRAVQLSLCLAEKYKYRSIAIPAISSGVFGFPLGRCVETIVSAIKEnFQFKKDGHCLKEIYL 959
Cdd:cd02907     81 VGPRWSGGSKEECEDLLYKAVLNSLEEAEELKATSIAIPAISSGIFGFPLDLCAEAIVEAIKD-FSESNSSSSLKEIRL 158

ADP-ribose-binding protein;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462590685  801 GVVLIVQQGDLARLPVDVVVNASNEDLKHYGGLAAALSKAAGPELQADCDQIVKREGRLLPGNATISKAGKLPYHHVIHA 880
Cdd:PRK00431     2 GMRIEVVQGDITELEVDAIVNAANSSLLGGGGVDGAIHRAAGPEILEECRELRQQQGPCPTGEAVITSAGRLPAKYVIHT 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462590685  881 VGPRWSGyEAPRCVYLLRRAVQLSLCLAEKYKYRSIAIPAISSGVFGFPLGRCVETIVSAIKEnfqFKKDGHCLKEIYLV 960
Cdd:PRK00431    82 VGPVWRG-GEDNEAELLASAYRNSLRLAAELGLRSIAFPAISTGVYGYPLEDAARIAVKTVRE---FLTRHKSPEEVYFV 157

                          170
                   ....*....|....*
gi 2462590685  961 DVSEKTVEAFAEAVK 975
Cdd:PRK00431   158 CYDEEAYRLYERLLT 172

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 2462590685    6 SFPLLVEGSWGPDPPKNLNTKLQMYFQSPKRSGGGECEVRQDPRSPSRFLVFFYPEDVRQKVLERKNHELvWQGKGTFKL 85
Cdd:cd12300      1 PFPLLVEGDWDPSPPKKLKNKLEKYFQSKKRSGGGECTVETEGPSPQTARVSFVNEEVRERVLEKKEHEI-LQGEGTVRL 79

                   ...
gi 2462590685   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 2462590685  227 TNTIRVENLPPGADDYSLKLFFENPYNGGGRVANVEYFPEESSALIEFFDRKVLDTIMATKLDFNKMPLSVFPYY 301
Cdd:cd12543      1 TCKIRAENLPPNTNSDYLMLYFENPYNGGIEVDGVTVDPEEESAIITFADPKDVQKIIALKHQFNKMPFSVLPYY 75

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 2462590685  820 VNASNEDLKHYGGLAAALSKAAGPELQADCDQIVKreGRLLPGNATISKAGKLPYHHVIHAVGPRWSGYEAPRCVYLLRR 899
Cdd:pfam01661    1 VNAANSRLLGGGGVAGAIHRAAGPELLEECRELKK--GGCPTGEAVVTPGGNLPAKYVIHTVGPTWRHGGSHGEEELLES 78

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2462590685  900 AVQLSLCLAEKYKYRSIAIPAISSGVFGFPLGRCVETI 937
Cdd:pfam01661   79 CYRNALALAEELGIKSIAFPAISTGIYGFPWEEAARIA 116

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 2462590685  800 PGVVLIVQQGDLARLPVDVVVNASNEDLKHYGGLAAALSKAAGPELQADCDQivkregrLLPGNAT----ISKAGKLPYH 875
Cdd:cd02903      6 GGITVQLVKGDITKEKTDVIVNSVSSDLLLKGGVSKAILKAAGPELQDECAN-------QGKQPASgdviVTSGGNLPCK 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462590685  876 HVIHAVGPRWSgyeaPRCVYLLRRAVQLSLCLAEKYKYRSIAIPAISSGVFGFPLGRCVETIVSAIkENFQFKKDGHCLK 955
Cdd:cd02903     79 YVYHVVLPHYN----PGNEKTLKDIVRKCLEKAENYKMSSISFPAIGTGNLGFPKDVVAEIMIDEV-LKFSSKNPSSSLK 153

                          170
                   ....*....|....*
gi 2462590685  956 EIYLVDVSEKTVEAF 970
Cdd:cd02903    154 EVRFVIFPPETLQAF 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 2462590685 1026 AKTDVVVNSVPLDLVLSRGpLSKSLLEKAGPELQEELDTVGQGVAVSMGTVLKTSSWNLDCRYVLHVVAPEWRNGSTSSL 1105
Cdd:COG2110     11 LDVDAIVNAANSSLLGGGG-VAGAIHRAAGPELLEECRRLCKQGGCPTGEAVITPAGNLPAKYVIHTVGPVWRGGGPSEE 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462590685 1106 KIMEDIIRECMEITESLSLKSIAFPAIGTGNLGFPKNIFAELIISEVFKFSSKNqlKTLQEVHFLLHpsDHENIQAFSDE 1185
Cdd:COG2110     90 ELLASCYRNSLELAEELGIRSIAFPAIGTGVGGFPWEEAAPIAVETLRDFLEEH--PSLEEVRFVLF--DEEDYEAYRRA 165

                   ...
gi 2462590685 1186 FAR 1188
Cdd:COG2110    166 LAR 168

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 2462590685  804 LIVQQGDLARLPVDVVVNASNEDLKHYGGLAAALSKAAGPELQADCDqivkREGRLLPGNATISKAGKLPYHHVIHAVG- 882
Cdd:cd03330      2 LIVVQGDITEQDADAIVNAANRRLLMGSGVAGAIKRKGGEEIEREAM----RKGPIRVGEAVETGAGKLPAKYVIHAAVm 77

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462590685  883 PRW--SGYEAprcvylLRRAVQLSLCLAEKYKYRSIAIPAISSGVFGFPLGRCVETIVSAIKE 943
Cdd:cd03330     78 GMPgrSSEES------IRDATRNALAKAEELGLESVAFPAIGTGVGGFPVEEVARIMLEEIKK 134

RNA recognition motif 1 and 2 in poly [ADP-ribose] polymerase PARP-10, RNA recognition motif 2 in PARP-14, RNA recognition motif in N-myc-interactor (Nmi), interferon-induced 35 kDa protein (IFP 35), RNA-binding protein 43 (RBM43) and similar proteins; This subfamily corresponds to the RRM1 and RRM2 of PARP-10, RRM2 of PARP-14, RRM of N-myc-interactor (Nmi), interferon-induced 35 kDa protein (IFP 35) and RNA-binding protein 43 (RBM43). PARP-10 is a novel oncoprotein c-Myc-interacting protein with poly(ADP-ribose) polymerase activity. It is localized to the nuclear and cytoplasmic compartments. In addition to PARP activity, PARP-10 is also involved in the control of cell proliferation by inhibiting c-Myc- and E1A-mediated cotransformation of primary cells. PARP-10 may also play a role in nuclear processes including the regulation of chromatin, gene transcription, and nuclear/cytoplasmic transport. PARP-10 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two overlapping C-terminal domains composed of a glycine-rich region and a region with homology to catalytic domains of PARP enzymes (PARP domain). In addition, PARP-10 contains two ubiquitin-interacting motifs (UIM). PARP-14, also termed aggressive lymphoma protein 2, is a member of the B aggressive lymphoma (BAL) family of macrodomain-containing PARPs. Like PARP-10, PARP-14 also includes two RRMs at the N-terminus. Nmi, also termed N-myc and STAT interactor, is an interferon inducible protein that interacts with c-Myc, N-Myc, Max and c-Fos, and other transcription factors containing bHLH-ZIP, bHLH or ZIP domains. Besides binding Myc proteins, Nmi also associates with all the Stat family of transcription factors except Stat2. In response to cytokine (e.g. IL-2 and IFN-gamma) stimulation, Nmi can enhance Stat-mediated transcriptional activity through recruiting the Stat1 and Stat5 transcriptional coactivators, CREB-binding protein (CBP) and p300. IFP 35 is an interferon-induced leucine zipper protein that can specifically form homodimers. Distinct from known bZIP proteins, IFP 35 lacks a basic domain critical for DNA binding. In addition, IFP 35 may negatively regulate other bZIP transcription factors by protein-protein interaction. For instance, it can form heterodimers with B-ATF, a member of the AP1 transcription factor family. Both Nmi and IFP35 harbor one RRM. RBM43 is a putative RNA-binding protein containing one RRM, but its biological function remains unclear.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462590685  228 NTIRVENLPPG-ADDYSLKLFFENPYNGGGRVANVEYFPEESSALIEFFDRKVLDTIMAT-KLDFNKMPLSVFP 299
Cdd:cd12301      1 RSVLVTGLPEAeALDDKLELYFENSRSGGGDVEDVEYLGEKGSAVVTFKDHKVAQRVLAQkKHPLNGMQLSVRP 74

X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The X-domain, also called Mac1, is the macrodomain found in riboviral non-structural protein 3 (Nsp3), including the Nsp3 of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) as well as SARS-CoV-2, and other coronaviruses (alpha-, beta-, gamma-, and deltacoronavirus), among others. The SARS-CoV-2 Nsp3 Mac1 is highly conserved among all CoVs, and binds to and hydrolyzes mono-ADP-ribose (MAR) from target proteins. It appears to counter host-mediated antiviral ADP-ribosylation, a post-translational modification that is part of the host response to viral infections. Mac1 is essential for pathogenesis in multiple animal models of CoV infection, implicating it as a virulence factor and potential therapeutic target. Assays show that the de-MARylating activity leads to a rapid loss of substrate, and that Mac1 could not hydrolyze poly-ADP-ribose; thus, Mac1 is a MAR-hydrolase (mono-ADP ribosylhydrolase). Mac1 was originally named ADP-ribose-1"-phosphatase (ADRP) based on data demonstrating that it could remove the phosphate group from ADP-ribose-1"-phosphate; however, activity was modest and was unclear why this would impact a virus infection. This family also includes the X-domain of Avian infectious bronchitis virus (IBV) strain Beaudette coronavirus that does not bind ADP-ribose; the triple glycine sequence found in the X-domains of SARS-CoV and human coronavirus 229E (HCoV229E), which are involved in ADP-ribose binding, is not conserved in the IBV X-domain. SARS-CoVs have two other macrodomains referred to as the SUD-N (N-terminal subdomain, or Mac2) and SUD-M (middle SUD subdomain, or Mac3) of the SARS-unique domain (SUD), which also do not bind ADP-ribose; these bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). SARS-CoV SUD-N and SUD-M are not included in this group.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462590685  817 DVVVNASNEDLKHYGGLAAALSKAAGPELQADCDQIvKREGRLLPGNATISKAGKLpYHHVIHAVGPRWSGYEAPRcvyL 896
Cdd:cd21557      2 DVVVNAANENLKHGGGVAGAIYKATGGAFQKESDYI-KKNGPLKVGTAVLLPGHGL-AKNIIHVVGPRKRKGQDDQ---L 76

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 2462590685  897 LRRAvqlslclaekYK-----YRSIAIPAISSGVFGFPL 930
Cdd:cd21557     77 LAAA----------YKavnkeYGSVLTPLLSAGIFGVPP 105

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 2462590685 1013 GLQMLLVKEGVQNAKTDVVVNSVPLDLVLSrGPLSKSLLEKAGPELQEELDTVGQ--------GVAVSMGTvlktsswNL 1084
Cdd:cd02904     17 GQKLTVVQGDIASIKADAIVHPTNATFYLG-GEVGSALEKAGGKEFVEEVKELRKsngplevaGAAISPGH-------NL 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462590685 1085 DCRYVLHVVAPEWrnGSTSSLKIMEDIIRECMEITESLSLKSIAFPAIGTGNLGFPKNIFAELI---ISEVFKFSSKNQL 1161
Cdd:cd02904     89 PAKFVIHCNSPSW--GSDKCEELLEKTVKNCLALADEKKLKSVAFPSIGSGRNGFPKQTAAQTIlkaISNYFVSVMSSSL 166

                          170       180
                   ....*....|....*....|....*..
gi 2462590685 1162 KtlqEVHFLLhpSDHENIQAFSDEFAR 1188
Cdd:cd02904    167 K---QIYFVL--FDMESIGIYTSELAK 188

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 2462590685 1029 DVVVNSVPLDLVLSRGpLSKSLLEKAGPELQEELDTVGQGVAVSMGTVLKTSSWNLDCRYVLHVVAPEWRnGSTSSLKIM 1108
Cdd:cd02749      1 DAIVNPANNDLYLGGG-VAKAISKKAGGDLQEECEERKKNGYLKVGEVAVTKGGNLPARYIIHVVGPVAS-SKKKTYEPL 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2462590685 1109 EDIIRECMEITESLSLKSIAFPAIGTGNLGFPKNIFAELIISE 1151
Cdd:cd02749     79 KKCVKNCLSLADEKGLKSVAFPAIGTGIAGFPPEEAARIMLEA 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 2462590685 1053 KAGPELQEELDTVGQGVAVsmGTVLKTSSWNLDCRYVLHVVAPEWRNGSTSSLKIMEDIIRECMEITESLSLKSIAFPAI 1132
Cdd:cd02908     38 AAGPELLEECRKLGGVCPT--GEAKITPGYNLPAKYVIHTVGPIGEGGVEEEPELLASCYRSSLELALENGLKSIAFPCI 115

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2462590685 1133 GTGNLGFPKNIFAELIISEVFKFSSKNQlkTLQEVHFLLHPSDHENI 1179
Cdd:cd02908    116 STGIYGYPNEEAAEIALNTVREWLEEHD--KIDRIIFVVFLDEDYKI 160

protein-ADP-ribose hydrolase;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462590685 1053 KAGPELQEELD--TVGQGVAVSMGTVLKTSSWNLDCRYVLHVVAPEWRNGSTSslKIMEDII----RECMEITESLSLKS 1126
Cdd:PRK04143   126 FAGVQLRLDCAeiMTEQGRKEATGQAKITRAYNLPAKYVIHTVGPIIRKQPVS--PIRADLLascyRSCLKLAEKAGLKS 203

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2462590685 1127 IAFPAIGTGNLGFPKNIFAELIISEVFKFSSKNQLK 1162
Cdd:PRK04143   204 IAFCCISTGVFGFPKEEAAEIAIKTVLSWLKENPSK 239

RNA recognition motif 1 and 2 in poly [ADP-ribose] polymerase PARP-10, RNA recognition motif 2 in PARP-14, RNA recognition motif in N-myc-interactor (Nmi), interferon-induced 35 kDa protein (IFP 35), RNA-binding protein 43 (RBM43) and similar proteins; This subfamily corresponds to the RRM1 and RRM2 of PARP-10, RRM2 of PARP-14, RRM of N-myc-interactor (Nmi), interferon-induced 35 kDa protein (IFP 35) and RNA-binding protein 43 (RBM43). PARP-10 is a novel oncoprotein c-Myc-interacting protein with poly(ADP-ribose) polymerase activity. It is localized to the nuclear and cytoplasmic compartments. In addition to PARP activity, PARP-10 is also involved in the control of cell proliferation by inhibiting c-Myc- and E1A-mediated cotransformation of primary cells. PARP-10 may also play a role in nuclear processes including the regulation of chromatin, gene transcription, and nuclear/cytoplasmic transport. PARP-10 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two overlapping C-terminal domains composed of a glycine-rich region and a region with homology to catalytic domains of PARP enzymes (PARP domain). In addition, PARP-10 contains two ubiquitin-interacting motifs (UIM). PARP-14, also termed aggressive lymphoma protein 2, is a member of the B aggressive lymphoma (BAL) family of macrodomain-containing PARPs. Like PARP-10, PARP-14 also includes two RRMs at the N-terminus. Nmi, also termed N-myc and STAT interactor, is an interferon inducible protein that interacts with c-Myc, N-Myc, Max and c-Fos, and other transcription factors containing bHLH-ZIP, bHLH or ZIP domains. Besides binding Myc proteins, Nmi also associates with all the Stat family of transcription factors except Stat2. In response to cytokine (e.g. IL-2 and IFN-gamma) stimulation, Nmi can enhance Stat-mediated transcriptional activity through recruiting the Stat1 and Stat5 transcriptional coactivators, CREB-binding protein (CBP) and p300. IFP 35 is an interferon-induced leucine zipper protein that can specifically form homodimers. Distinct from known bZIP proteins, IFP 35 lacks a basic domain critical for DNA binding. In addition, IFP 35 may negatively regulate other bZIP transcription factors by protein-protein interaction. For instance, it can form heterodimers with B-ATF, a member of the AP1 transcription factor family. Both Nmi and IFP35 harbor one RRM. RBM43 is a putative RNA-binding protein containing one RRM, but its biological function remains unclear.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2462590685   26 KLQMYFQSPkRSGGGECEVRQDPRSPSRFLVFFYPEDVRQKVLERKNHEL 75
Cdd:cd12301     17 KLELYFENS-RSGGGDVEDVEYLGEKGSAVVTFKDHKVAQRVLAQKKHPL 65

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.