DEDDh 3'-5' exonuclease domain of RNA exonuclease 1, -3 and similar eukaryotic proteins; This subfamily is composed of RNA exonuclease 1 (REX1 or Rex1p), REX3 (or Rex3p), and similar eukaryotic proteins. In yeast, REX1 and REX3 are required for 5S rRNA and MRP (mitochondrial RNA processing) RNA maturation, respectively. They are DEDDh-type DnaQ-like 3'-5' exonucleases containing three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific Hx(4)D conserved pattern at ExoIII. These motifs are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis. REX1 is the major exonuclease responsible for pre-tRNA trail trimming and may also be involved in nuclear CCA turnover. REX proteins function in the processing and maturation of many RNA species, similar to the function of Escherichia coli RNase T.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445 143 FGLDCEVCLTSMGKELTRISLVTEGGYCLIDELVKPDLKILDYLTSFTGITKEILNPVTTKLKDVQKLLRELLPPDAVLV 222
Cdd:cd06145     1 FALDCEMCYTTDGLELTRVTVVDENGKVVLDELVKPDGEIVDYNTRFSGITEEMLENVTTTLEDVQKKLLSLISPDTILV 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907182445 223 GHCLDLDLRVLKMIHPYVIDTSLLYAGKQGRRFK--LTFLARVILGKDIQCpNKLGRDGIEDARAALELLQ 291
Cdd:cd06145    81 GHSLENDLKALKLIHPRVIDTAILFPHPRGPPYKpsLKNLAKKYLGRDIQQ-GEGGHDSVEDARAALELVK 150

RNA recognition motif (RRM) superfamily; RRM, also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), is a highly abundant domain in eukaryotes found in proteins involved in post-transcriptional gene expression processes including mRNA and rRNA processing, RNA export, and RNA stability. This domain is 90 amino acids in length and consists of a four-stranded beta-sheet packed against two alpha-helices. RRM usually interacts with ssRNA, but is also known to interact with ssDNA as well as proteins. RRM binds a variable number of nucleotides, ranging from two to eight. The active site includes three aromatic side-chains located within the conserved RNP1 and RNP2 motifs of the domain. The RRM domain is found in a variety heterogeneous nuclear ribonucleoproteins (hnRNPs), proteins implicated in regulation of alternative splicing, and protein components of small nuclear ribonucleoproteins (snRNPs).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907182445 504 IYVAGIGETFKEHLLEQS-NLFPDLEAVILPKEVKSRKQKNYCFLKFKTVNSAQVALEILKGkDWKLKGRNA 574
Cdd:cd12274     1 IYVSGFKKSLTEEDLQERfSQLSDLEAVFLPKDLQSGKHKKYCFLKFRSSQSAQAALDIITG-EWKLKGRRA 71

DEDDh 3'-5' exonuclease domain of RNA exonuclease 1, -3 and similar eukaryotic proteins; This subfamily is composed of RNA exonuclease 1 (REX1 or Rex1p), REX3 (or Rex3p), and similar eukaryotic proteins. In yeast, REX1 and REX3 are required for 5S rRNA and MRP (mitochondrial RNA processing) RNA maturation, respectively. They are DEDDh-type DnaQ-like 3'-5' exonucleases containing three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific Hx(4)D conserved pattern at ExoIII. These motifs are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis. REX1 is the major exonuclease responsible for pre-tRNA trail trimming and may also be involved in nuclear CCA turnover. REX proteins function in the processing and maturation of many RNA species, similar to the function of Escherichia coli RNase T.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445 143 FGLDCEVCLTSMGKELTRISLVTEGGYCLIDELVKPDLKILDYLTSFTGITKEILNPVTTKLKDVQKLLRELLPPDAVLV 222
Cdd:cd06145     1 FALDCEMCYTTDGLELTRVTVVDENGKVVLDELVKPDGEIVDYNTRFSGITEEMLENVTTTLEDVQKKLLSLISPDTILV 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907182445 223 GHCLDLDLRVLKMIHPYVIDTSLLYAGKQGRRFK--LTFLARVILGKDIQCpNKLGRDGIEDARAALELLQ 291
Cdd:cd06145    81 GHSLENDLKALKLIHPRVIDTAILFPHPRGPPYKpsLKNLAKKYLGRDIQQ-GEGGHDSVEDARAALELVK 150

exonuclease domain in DNA-polymerase alpha and epsilon chain, ribonuclease T and other exonucleases;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445  142 LFGLDCE-VCLTSMGKELTRISLV-TEGG--YCLIDELVKPDLKILDYLTSFTGITKEILNPvTTKLKDVQKLLRELLPP 217
Cdd:smart00479   2 LVVIDCEtTGLDPGKDEIIEIAAVdVDGGeiIEVFDTYVKPDRPITDYATEIHGITPEMLDD-APTFEEVLEELLEFLRG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445  218 DAVLVGHCLDLDLRVLKMIHP----------YVIDTSLLYAGKQGRRFK--LTFLARVILGKDIQCPNklgrDGIEDARA 285
Cdd:smart00479  81 RILVAGNSAHFDLRFLKLEHPrlgikqppklPVIDTLKLARATNPGLPKysLKKLAKRLLLEVIQRAH----RALDDARA 156

                          170
                   ....*....|...
gi 1907182445  286 ALELLQYFLKYGP 298
Cdd:smart00479 157 TAKLFKKLLERLE 169

poly-U binding splicing factor, half-pint family; The proteins represented by this model contain three RNA recognition motifs (rrm: pfam00076) and have been characterized as poly-pyrimidine tract binding proteins associated with RNA splicing factors. In the case of PUF60 (GP|6176532), in complex with p54, and in the presence of U2AF, facilitates association of U2 snRNP with pre-mRNA.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445 406 MSTVYAGPFSKDCNVGALKKVFSSLGPVHSITL----VLETYRPYFSIQYEVLEAAQLALETMNGSLLEGSCIRVRRlvT 481
Cdd:TIGR01645 107 MCRVYVGSISFELREDTIRRAFDPFGPIKSINMswdpATGKHKGFAFVEYEVPEAAQLALEQMNGQMLGGRNIKVGR--P 184

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907182445 482 ELTLECDTLVRELEQDSENQGTIYVAGIGETFKEHLLEQS-NLFPDLEAVILPKEVKSRKQKNYCFLKFKTVNSAQVAL 559
Cdd:TIGR01645 185 SNMPQAQPIIDMVQEEAKKFNRIYVASVHPDLSETDIKSVfEAFGEIVKCQLARAPTGRGHKGYGFIEYNNLQSQSEAI 263

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907182445  408 TVYAGPFSKDCNVGALKKVFSSLGPVHSITLVLETY----RPYFSIQYEVLEAAQLALETMNGSLLEGSCIRV 476
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRDKEtgksKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

DNA polymerase III, alpha subunit (gram-positive type) [Replication, recombination and repair];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445 173 DELVKPDLKILDYLTSFTGITKEILN--PvttKLKDVQKLLRELLpPDAVLVGHCLDLDLRVLKM--------IHPYVID 242
Cdd:COG2176    45 STLVNPGRPIPPFITELTGITDEMVAdaP---PFEEVLPEFLEFL-GDAVLVAHNASFDLGFLNAalkrlglpFDNPVLD 120

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907182445 243 TSLL--YAGKQGRRFKLTFLARViLGKDIQcpnklGR-DGIEDARAALELLQYFLK 295
Cdd:COG2176   121 TLELarRLLPELKSYKLDTLAER-LGIPLE-----DRhRALGDAEATAELFLKLLE 170

RNA recognition motif (RRM) domain [Translation, ribosomal structure and biogenesis];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907182445 406 MSTVYAGPFSKDCNVGALKKVFSSLGPVHSITLVL--ETYRP--YFSIQYEVLEAAQLALETMNGSLLEGSCIRVR 477
Cdd:COG0724     1 SMKIYVGNLPYSVTEEDLRELFSEYGEVTSVKLITdrETGRSrgFGFVEMPDDEEAQAAIEALNGAELMGRTLKVN 76

DEDDh 3'-5' exonuclease domain of RNA exonuclease 1, -3 and similar eukaryotic proteins; This subfamily is composed of RNA exonuclease 1 (REX1 or Rex1p), REX3 (or Rex3p), and similar eukaryotic proteins. In yeast, REX1 and REX3 are required for 5S rRNA and MRP (mitochondrial RNA processing) RNA maturation, respectively. They are DEDDh-type DnaQ-like 3'-5' exonucleases containing three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific Hx(4)D conserved pattern at ExoIII. These motifs are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis. REX1 is the major exonuclease responsible for pre-tRNA trail trimming and may also be involved in nuclear CCA turnover. REX proteins function in the processing and maturation of many RNA species, similar to the function of Escherichia coli RNase T.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445 143 FGLDCEVCLTSMGKELTRISLVTEGGYCLIDELVKPDLKILDYLTSFTGITKEILNPVTTKLKDVQKLLRELLPPDAVLV 222
Cdd:cd06145     1 FALDCEMCYTTDGLELTRVTVVDENGKVVLDELVKPDGEIVDYNTRFSGITEEMLENVTTTLEDVQKKLLSLISPDTILV 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907182445 223 GHCLDLDLRVLKMIHPYVIDTSLLYAGKQGRRFK--LTFLARVILGKDIQCpNKLGRDGIEDARAALELLQ 291
Cdd:cd06145    81 GHSLENDLKALKLIHPRVIDTAILFPHPRGPPYKpsLKNLAKKYLGRDIQQ-GEGGHDSVEDARAALELVK 150

RNA recognition motif 1 (RRM1) found in vertebrate putative RNA exonuclease NEF-sp; This subfamily corresponds to the RRM1 of NEF-sp., including uncharacterized putative RNA exonuclease NEF-sp found in vertebrates. Although its cellular functions remains unclear, NEF-sp contains an exonuclease domain and two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), suggesting it may possess both exonuclease and RNA-binding activities.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907182445 408 TVYAGPFSKDCNVGALKKVFSSLGPVHSITLVLETYRPYFSIQYEVLEAAQLALETMNGSLLEGSCIRVRR 478
Cdd:cd12273     1 TVYAGPFEKSFCLKSVKRLFRSCGPVQSLTVVTETYQPYVCVQYEVLEAAQLAVETLDGALVDGHCIKVQR 71

exonuclease domain in DNA-polymerase alpha and epsilon chain, ribonuclease T and other exonucleases;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445  142 LFGLDCE-VCLTSMGKELTRISLV-TEGG--YCLIDELVKPDLKILDYLTSFTGITKEILNPvTTKLKDVQKLLRELLPP 217
Cdd:smart00479   2 LVVIDCEtTGLDPGKDEIIEIAAVdVDGGeiIEVFDTYVKPDRPITDYATEIHGITPEMLDD-APTFEEVLEELLEFLRG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445  218 DAVLVGHCLDLDLRVLKMIHP----------YVIDTSLLYAGKQGRRFK--LTFLARVILGKDIQCPNklgrDGIEDARA 285
Cdd:smart00479  81 RILVAGNSAHFDLRFLKLEHPrlgikqppklPVIDTLKLARATNPGLPKysLKKLAKRLLLEVIQRAH----RALDDARA 156

                          170
                   ....*....|...
gi 1907182445  286 ALELLQYFLKYGP 298
Cdd:smart00479 157 TAKLFKKLLERLE 169

DEDDh 3'-5' exonuclease domain of the eukaryotic exoribonuclease PAN2; PAN2 is the catalytic subunit of poly(A) nuclease (PAN), a Pab1p-dependent 3'-5' exoribonuclease which plays an important role in the posttranscriptional maturation of pre-mRNAs. PAN catalyzes the deadenylation of poly(A) tails, which are initially synthesized to default lengths of 70 to 90, to mRNA-specific lengths of 55 to 71. Pab1p and PAN also play a role in the export and decay of mRNA. PAN2 contains a DEDDh-type DnaQ-like 3'-5' exonuclease domain with three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific Hx(4)D conserved pattern at ExoIII. These motifs are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445 158 LTRISLV----TEGGYCLIDELVKPDLKILDYLTSFTGITKEILNPVT-----TKLKDVQKLLRELLPPDAVLVGHCLDL 228
Cdd:cd06143    33 LARVSVVrgegELEGVPFIDDYISTTEPVVDYLTRFSGIKPGDLDPKTssknlTTLKSAYLKLRLLVDLGCIFVGHGLAK 112

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907182445 229 DLRVLKMIHP--YVIDTSLLYAGKQGRRFKLTFLARVILGKDIQCPNklgRDGIEDARAALELLQ 291
Cdd:cd06143   113 DFRVINIQVPkeQVIDTVELFHLPGQRKLSLRFLAWYLLGEKIQSET---HDSIEDARTALKLYR 174

poly-U binding splicing factor, half-pint family; The proteins represented by this model contain three RNA recognition motifs (rrm: pfam00076) and have been characterized as poly-pyrimidine tract binding proteins associated with RNA splicing factors. In the case of PUF60 (GP|6176532), in complex with p54, and in the presence of U2AF, facilitates association of U2 snRNP with pre-mRNA.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445 406 MSTVYAGPFSKDCNVGALKKVFSSLGPVHSITL----VLETYRPYFSIQYEVLEAAQLALETMNGSLLEGSCIRVRRlvT 481
Cdd:TIGR01645 107 MCRVYVGSISFELREDTIRRAFDPFGPIKSINMswdpATGKHKGFAFVEYEVPEAAQLALEQMNGQMLGGRNIKVGR--P 184

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907182445 482 ELTLECDTLVRELEQDSENQGTIYVAGIGETFKEHLLEQS-NLFPDLEAVILPKEVKSRKQKNYCFLKFKTVNSAQVAL 559
Cdd:TIGR01645 185 SNMPQAQPIIDMVQEEAKKFNRIYVASVHPDLSETDIKSVfEAFGEIVKCQLARAPTGRGHKGYGFIEYNNLQSQSEAI 263

Exonuclease; This family includes a variety of exonuclease proteins, such as ribonuclease T and the epsilon subunit of DNA polymerase III.;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445 145 LDCE-VCLTSMGKELTRISLV-TEGGYCLIDE----LVKPDL--KILDYLTSFTGITKEILnPVTTKLKDVQKLLRELLP 216
Cdd:pfam00929   3 IDLEtTGLDPEKDEIIEIAAVvIDGGENEIGEtfhtYVKPTRlpKLTDECTKFTGITQAML-DNKPSFEEVLEEFLEFLR 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445 217 PDAVLVGH-------CLDLDLRVLKMIH----PYVIDT-SLLYAGKQGRRF-KLTFLARVILGKDIQCPNklgrDGIEDA 283
Cdd:pfam00929  82 KGNLLVAHnasfdvgFLRYDDKRFLKKPmpklNPVIDTlILDKATYKELPGrSLDALAEKLGLEHIGRAH----RALDDA 157

                  ....*..
gi 1907182445 284 RAALELL 290
Cdd:pfam00929 158 RATAKLF 164

DEDDh 3'-5' exonuclease domain family; DEDDh exonucleases, part of the DnaQ-like (or DEDD) exonuclease superfamily, catalyze the excision of nucleoside monophosphates at the DNA or RNA termini in the 3'-5' direction. These proteins contain four invariant acidic residues in three conserved sequence motifs termed ExoI, ExoII and ExoIII. DEDDh exonucleases are classified as such because of the presence of specific Hx(4)D conserved pattern at the ExoIII motif. The four conserved acidic residues are clustered around the active site and serve as ligands for the two metal ions required for catalysis. Most DEDDh exonucleases are the proofreading subunits (epsilon) or domains of bacterial DNA polymerase III, the main replicating enzyme in bacteria, which functions as the chromosomal replicase. Other members include other DNA and RNA exonucleases such as RNase T, Oligoribonuclease, and RNA exonuclease (REX), among others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445 173 DELVKPDLKILDYLTSFTGITKEILNPVTTkLKDVQKLLRELLPpDAVLVGHCLDLDLRVLK---------MIHPYVIDT 243
Cdd:cd06127    36 ETLVNPGRPIPPEATAIHGITDEMLADAPP-FEEVLPEFLEFLG-GRVLVAHNASFDLRFLNrelrrlggpPLPNPWIDT 113

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907182445 244 SLLYA--GKQGRRFKLTFLARVILGkdiqCPNKLGRDGIEDARAALELLQ 291
Cdd:cd06127   114 LRLARrlLPGLRSHRLGLLLAERYG----IPLEGAHRALADALATAELLL 159

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445 422 ALKKVFSSLGPVHSITLV-LET--YRPYFSIQYEVLEAAQLALETMNGSLLEGSCIRVRRLVTEltlecdtLVRELEQDs 498
Cdd:TIGR01628 104 ALFDTFSKFGNILSCKVAtDENgkSRGYGFVHFEKEESAKAAIQKVNGMLLNDKEVYVGRFIKK-------HEREAAPL- 175

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907182445 499 ENQGTIYVAGIGETF-KEHLLEQSNLFPDLEAVILPKEvKSRKQKNYCFLKFKTVNSAQVALEILKGK 565
Cdd:TIGR01628 176 KKFTNLYVKNLDPSVnEDKLRELFAKFGEITSAAVMKD-GSGRSRGFAFVNFEKHEDAAKAVEEMNGK 242

DNA polymerase III, alpha subunit (gram-positive type) [Replication, recombination and repair];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445 173 DELVKPDLKILDYLTSFTGITKEILN--PvttKLKDVQKLLRELLpPDAVLVGHCLDLDLRVLKM--------IHPYVID 242
Cdd:COG2176    45 STLVNPGRPIPPFITELTGITDEMVAdaP---PFEEVLPEFLEFL-GDAVLVAHNASFDLGFLNAalkrlglpFDNPVLD 120

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907182445 243 TSLL--YAGKQGRRFKLTFLARViLGKDIQcpnklGR-DGIEDARAALELLQYFLK 295
Cdd:COG2176   121 TLELarRLLPELKSYKLDTLAER-LGIPLE-----DRhRALGDAEATAELFLKLLE 170

RNA recognition motif 2 (RRM2) found in vertebrate RNA-binding protein RBM23, RBM39 and similar proteins; This subfamily corresponds to the RRM2 of RBM39 (also termed HCC1), a nuclear autoantigen that contains an N-terminal arginine/serine rich (RS) motif and three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). An octapeptide sequence called the RS-ERK motif is repeated six times in the RS region of RBM39. Although the cellular function of RBM23 remains unclear, it shows high sequence homology to RBM39 and contains two RRMs. It may possibly function as a pre-mRNA splicing factor.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907182445 423 LKKVFSSLGPVHSITLVLET----YRPYFSIQYEVLEAAQLALETMNGSLLEGSCIRVrRLVTE 482
Cdd:cd12284    15 LRGIFEPFGKIEFVQLQKDPetgrSKGYGFIQFRDAEDAKKALEQLNGFELAGRPMKV-GHVTE 77

RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain); The RRM motif is probably diagnostic of an RNA binding protein. RRMs are found in a variety of RNA binding proteins, including various hnRNP proteins, proteins implicated in regulation of alternative splicing, and protein components of snRNPs. The motif also appears in a few single stranded DNA binding proteins. The RRM structure consists of four strands and two helices arranged in an alpha/beta sandwich, with a third helix present during RNA binding in some cases The C-terminal beta strand (4th strand) and final helix are hard to align and have been omitted in the SEED alignment The LA proteins have an N terminal rrm which is included in the seed. There is a second region towards the C terminus that has some features characteriztic of a rrm but does not appear to have the important structural core of a rrm. The LA proteins are one of the main autoantigens in Systemic lupus erythematosus (SLE), an autoimmune disease.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445 409 VYAGPFSKDCNVGALKKVFSSLGPVHSITLVL---ETYRPYFSIQYEVLEAAQLALETMNGSLLEGSCIR 475
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRdetGRSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

RNA recognition motif (RRM) found in cold inducible RNA binding protein (CIRBP), RNA binding motif protein 3 (RBM3) and similar proteins; This subfamily corresponds to the RRM domain of two structurally related heterogenous nuclear ribonucleoproteins, CIRBP (also termed CIRP or A18 hnRNP) and RBM3 (also termed RNPL), both of which belong to a highly conserved cold shock proteins family. The cold shock proteins can be induced after exposure to a moderate cold-shock and other cellular stresses such as UV radiation and hypoxia. CIRBP and RBM3 may function in posttranscriptional regulation of gene expression by binding to different transcripts, thus allowing the cell to response rapidly to environmental signals. However, the kinetics and degree of cold induction are different between CIRBP and RBM3. Tissue distribution of their expression is different. CIRBP and RBM3 may be differentially regulated under physiological and stress conditions and may play distinct roles in cold responses of cells. CIRBP, also termed glycine-rich RNA-binding protein CIRP, is localized in the nucleus and mediates the cold-induced suppression of cell cycle progression. CIRBP also binds DNA and possibly serves as a chaperone that assists in the folding/unfolding, assembly/disassembly and transport of various proteins. RBM3 may enhance global protein synthesis and the formation of active polysomes while reducing the levels of ribonucleoprotein complexes containing microRNAs. RBM3 may also serve to prevent the loss of muscle mass by its ability to decrease cell death. Furthermore, RBM3 may be essential for cell proliferation and mitosis. Both, CIRBP and RBM3, contain an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), that is involved in RNA binding, and C-terminal glycine-rich domain (RGG motif) that probably enhances RNA-binding via protein-protein and/or protein-RNA interactions. Like CIRBP, RBM3 can also bind to both RNA and DNA via its RRM domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907182445 407 STVYAGPFSKDCNVGALKKVFSSLGPVHSITLVL--ETYRP--YFSIQYEVLEAAQLALETMNGSLLEGSCIRV 476
Cdd:cd12449     1 GKLFVGGLSFDTNEQSLEEVFSKYGQISEVVVVKdrETQRSrgFGFVTFENPDDAKDAMMAMNGKSLDGRQIRV 74

RNA recognition motif 1 (RRM1) found in type I polyadenylate-binding proteins; This subfamily corresponds to the RRM1 of type I poly(A)-binding proteins (PABPs), highly conserved proteins that bind to the poly(A) tail present at the 3' ends of most eukaryotic mRNAs. They have been implicated in the regulation of poly(A) tail length during the polyadenylation reaction, translation initiation, mRNA stabilization by influencing the rate of deadenylation and inhibition of mRNA decapping. The family represents type I polyadenylate-binding proteins (PABPs), including polyadenylate-binding protein 1 (PABP-1 or PABPC1), polyadenylate-binding protein 3 (PABP-3 or PABPC3), polyadenylate-binding protein 4 (PABP-4 or APP-1 or iPABP), polyadenylate-binding protein 5 (PABP-5 or PABPC5), polyadenylate-binding protein 1-like (PABP-1-like or PABPC1L), polyadenylate-binding protein 1-like 2 (PABPC1L2 or RBM32), polyadenylate-binding protein 4-like (PABP-4-like or PABPC4L), yeast polyadenylate-binding protein, cytoplasmic and nuclear (PABP or ACBP-67), and similar proteins. PABP-1 is a ubiquitously expressed multifunctional protein that may play a role in 3' end formation of mRNA, translation initiation, mRNA stabilization, protection of poly(A) from nuclease activity, mRNA deadenylation, inhibition of mRNA decapping, and mRNP maturation. Although PABP-1 is thought to be a cytoplasmic protein, it is also found in the nucleus. PABP-1 may be involved in nucleocytoplasmic trafficking and utilization of mRNP particles. PABP-1 contains four copies of RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), a less well conserved linker region, and a proline-rich C-terminal conserved domain (CTD). PABP-3 is a testis-specific poly(A)-binding protein specifically expressed in round spermatids. It is mainly found in mammalian and may play an important role in the testis-specific regulation of mRNA homeostasis. PABP-3 shows significant sequence similarity to PABP-1. However, it binds to poly(A) with a lower affinity than PABP-1. Moreover, PABP-1 possesses an A-rich sequence in its 5'-UTR and allows binding of PABP and blockage of translation of its own mRNA. In contrast, PABP-3 lacks the A-rich sequence in its 5'-UTR. PABP-4 is an inducible poly(A)-binding protein (iPABP) that is primarily localized to the cytoplasm. It shows significant sequence similarity to PABP-1 as well. The RNA binding properties of PABP-1 and PABP-4 appear to be identical. PABP-5 is encoded by PABPC5 gene within the X-specific subinterval, and expressed in fetal brain and in a range of adult tissues in mammals, such as ovary and testis. It may play an important role in germ cell development. Moreover, unlike other PABPs, PABP-5 contains only four RRMs, but lacks both the linker region and the CTD. PABP-1-like and PABP-1-like 2 are the orthologs of PABP-1. PABP-4-like is the ortholog of PABP-5. Their cellular functions remain unclear. The family also includes yeast PABP, a conserved poly(A) binding protein containing poly(A) tails that can be attached to the 3'-ends of mRNAs. The yeast PABP and its homologs may play important roles in the initiation of translation and in mRNA decay. Like vertebrate PABP-1, the yeast PABP contains four RRMs, a linker region, and a proline-rich CTD as well. The first two RRMs are mainly responsible for specific binding to poly(A). The proline-rich region may be involved in protein-protein interactions.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907182445 410 YAGPFSKDCNVGALKKVFSSLGPVHSITLV--LETYRP--YFSIQYEVLEAAQLALETMNGSLLEGSCIRV 476
Cdd:cd12378     3 YVGDLHPDVTEAMLYEKFSPAGPVLSIRVCrdAVTRRSlgYAYVNFQQPADAERALDTLNFDVIKGKPIRI 73

RNA recognition motif (RRM) found in cyclophilin-33 (Cyp33) and similar proteins; This subfamily corresponds to the RRM of Cyp33, also termed peptidyl-prolyl cis-trans isomerase E (PPIase E), or cyclophilin E, or rotamase E. Cyp33 is a nuclear RNA-binding cyclophilin with an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal PPIase domain. Cyp33 possesses RNA-binding activity and preferentially binds to polyribonucleotide polyA and polyU, but hardly to polyG and polyC. It binds specifically to mRNA, which can stimulate its PPIase activity. Moreover, Cyp33 interacts with the third plant homeodomain (PHD3) zinc finger cassette of the mixed lineage leukemia (MLL) proto-oncoprotein and a poly-A RNA sequence through its RRM domain. It further mediates downregulation of the expression of MLL target genes HOXC8, HOXA9, CDKN1B, and C-MYC, in a proline isomerase-dependent manner. Cyp33 also possesses a PPIase activity that catalyzes cis-trans isomerization of the peptide bond preceding a proline, which has been implicated in the stimulation of folding and conformational changes in folded and unfolded proteins. The PPIase activity can be inhibited by the immunosuppressive drug cyclosporin A.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907182445 409 VYAGPFSKDCNVGALKKVFSSLGPVHSITLVL----ETYRPYFSIQYEVLEAAQLALETMNGSLLEGSCIRV 476
Cdd:cd12347     1 LYVGGLAEEVDEKVLHAAFIPFGDIVDIQIPLdyetEKHRGFAFVEFEEAEDAAAAIDNMNESELFGRTIRV 72

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445 401 TKWTQMSTVYAGPFSKDCNVGALKKVFSSLGPVHSITLVLE---TYRPYFSIQYEVLEAAQLALETMNG----SLLEGSC 473
Cdd:TIGR01628 173 APLKKFTNLYVKNLDPSVNEDKLRELFAKFGEITSAAVMKDgsgRSRGFAFVNFEKHEDAAKAVEEMNGkkigLAKEGKK 252

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182445 474 IRVRRLV--TELTLECDTLVRELEQDSENQG---TIYVAGIGETFKEHLLEQsnLFPDLEAVILPKEV--KSRKQKNYCF 546
Cdd:TIGR01628 253 LYVGRAQkrAEREAELRRKFEELQQERKMKAqgvNLYVKNLDDTVTDEKLRE--LFSECGEITSAKVMldEKGVSRGFGF 330

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907182445 547 LKFKTVNSAQVALEILKGKdwKLKGRN---ALTPR------HLQAWLKDIHPE-PAMPMGlRIVPPLMERHIFRTR 612
Cdd:TIGR01628 331 VCFSNPEEANRAVTEMHGR--MLGGKPlyvALAQRkeqrraHLQDQFMQLQPRmRQLPMG-SPMGGAMGQPPYYGQ 403

RNA recognition motif (RRM) found in cleavage stimulation factor subunit 2 (CSTF2), cleavage stimulation factor subunit 2 tau variant (CSTF2T) and similar proteins; This subgroup corresponds to the RRM domain of CSTF2, its tau variant and eukaryotic homologs. CSTF2, also termed cleavage stimulation factor 64 kDa subunit (CstF64), is the vertebrate conterpart of yeast mRNA 3'-end-processing protein RNA15. It is expressed in all somatic tissues and is one of three cleavage stimulatory factor (CstF) subunits required for polyadenylation. CstF64 contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a CstF77-binding domain, a repeated MEARA helical region and a conserved C-terminal domain reported to bind the transcription factor PC-4. During polyadenylation, CstF interacts with the pre-mRNA through the RRM of CstF64 at U- or GU-rich sequences within 10 to 30 nucleotides downstream of the cleavage site. CSTF2T, also termed tauCstF64, is a paralog of the X-linked cleavage stimulation factor CstF64 protein that supports polyadenylation in most somatic cells. It is expressed during meiosis and subsequent haploid differentiation in a more limited set of tissues and cell types, largely in meiotic and postmeiotic male germ cells, and to a lesser extent in brain. The loss of CSTF2T will cause male infertility, as it is necessary for spermatogenesis and fertilization. Moreover, CSTF2T is required for expression of genes involved in morphological differentiation of spermatids, as well as for genes having products that function during interaction of motile spermatozoa with eggs. It promotes germ cell-specific patterns of polyadenylation by using its RRM to bind to different sequence elements downstream of polyadenylation sites than does CstF64.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907182445 406 MSTVYAGPFSKDCNVGALKKVFSSLGPVHSITLVL--ETYRP--YFSIQYEVLEAAQLALETMNGSLLEGSCIRV 476
Cdd:cd12671     6 LRSVFVGNIPYEATEEQLKDIFSEVGPVVSFRLVYdrETGKPkgYGFCEYQDQETALSAMRNLNGYELNGRALRV 80

RNA recognition motif 1 (RRM1) found in granule-associated RNA binding proteins p40-TIA-1 and TIAR; This subfamily corresponds to the RRM1 of nucleolysin TIA-1 isoform p40 (p40-TIA-1 or TIA-1) and nucleolysin TIA-1-related protein (TIAR), both of which are granule-associated RNA binding proteins involved in inducing apoptosis in cytotoxic lymphocyte (CTL) target cells. TIA-1 and TIAR share high sequence similarity. They are expressed in a wide variety of cell types. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis.TIAR is mainly localized in the nucleus of hematopoietic and nonhematopoietic cells. It is translocated from the nucleus to the cytoplasm in response to exogenous triggers of apoptosis. Both, TIA-1 and TIAR, bind specifically to poly(A) but not to poly(C) homopolymers. They are composed of three N-terminal highly homologous RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. TIA-1 and TIAR interact with RNAs containing short stretches of uridylates and their RRM2 can mediate the specific binding to uridylate-rich RNAs. The C-terminal auxiliary domain may be responsible for interacting with other proteins. In addition, TIA-1 and TIAR share a potential serine protease-cleavage site (Phe-Val-Arg) localized at the junction between their RNA binding domains and their C-terminal auxiliary domains.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907182445 410 YAGPFSKDCNVGALKKVFSSLGPVHSITLVLETYR--PYFSIQYEVLEAAQLALETMNGSLLEGSCIRV 476
Cdd:cd12352     2 YVGNLDRQVTEDLILQLFSQIGPCKSCKMITEHGGndPYCFVEFYEHNHAAAALQAMNGRKILGKEVKV 70

RNA recognition motif 1 (RRM1) found in yeast protein gar2 and similar proteins; This subfamily corresponds to the RRM1 of yeast protein gar2, a novel nucleolar protein required for 18S rRNA and 40S ribosomal subunit accumulation. It shares similar domain architecture with nucleolin from vertebrates and NSR1 from Saccharomyces cerevisiae. The highly phosphorylated N-terminal domain of gar2 is made up of highly acidic regions separated from each other by basic sequences, and contains multiple phosphorylation sites. The central domain of gar2 contains two closely adjacent N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The C-terminal RGG (or GAR) domain of gar2 is rich in glycine, arginine and phenylalanine residues.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907182445 408 TVYAGPFSKDCNVGALKKVFSSLGPVHSITLVLE----TYRPYFSIQYEVLEAAQLALETMNGSLLEGSCIRV 476
Cdd:cd12447     1 TLFVGGLSWNVDDPWLKKEFEKYGGVISARVITDrgsgRSKGYGYVDFATPEAAQKALAAMSGKEIDGRQINV 73

RNA recognition motif 2 (RRM2) found in Nicotiana sylvestris chloroplastic 33 kDa ribonucleoprotein (NsCP33) and similar proteins; The family includes NsCP33, Arabidopsis thaliana chloroplastic 31 kDa ribonucleoprotein (CP31A) and mitochondrial glycine-rich RNA-binding protein 2 (AtGR-RBP2). NsCP33 may be involved in splicing and/or processing of chloroplast RNA's. AtCP31A, also called RNA-binding protein 1/2/3 (AtRBP33), or RNA-binding protein CP31A, or RNA-binding protein RNP-T, or RNA-binding protein cp31, is required for specific RNA editing events in chloroplasts and stabilizes specific chloroplast mRNAs, as well as for normal chloroplast development under cold stress conditions by stabilizing transcripts of numerous mRNAs under these conditions. CP31A may modulate telomere replication through RNA binding domains. AtGR-RBP2, also called AtRBG2, or glycine-rich protein 2 (AtGRP2), or mitochondrial RNA-binding protein 1a (At-mRBP1a), plays a role in RNA transcription or processing during stress. It binds RNAs and DNAs sequence with a preference to single-stranded nucleic acids. AtGR-RBP2 displays strong affinity to poly(U) sequence. It exerts cold and freezing tolerance, probably by exhibiting an RNA chaperone activity during the cold and freezing adaptation process. Some members in this family contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the second RRM motif.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907182445 408 TVYAGPFSKDCNVGALKKVFSSLGPVHSITLVL--ETYRpyfS-----IQYEVLEAAQLALETMNGSLLEGSCIRVR 477
Cdd:cd21608     1 KLYVGNLSWDTTEDDLRDLFSEFGEVESAKVITdrETGR---SrgfgfVTFSTAEAAEAAIDALNGKELDGRSIVVN 74

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein D0 (hnRNP D0) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP D0, also termed AU-rich element RNA-binding protein 1, a UUAG-specific nuclear RNA binding protein that may be involved in pre-mRNA splicing and telomere elongation. hnRNP D0 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), in the middle and an RGG box rich in glycine and arginine residues in the C-terminal part. Each of RRMs can bind solely to the UUAG sequence specifically.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1907182445 504 IYVAGIG-ETFKEHLLEQSNLFPDLEAVILPKEVKSRKQKNYCFLKFK 550
Cdd:cd12583     2 IFVGGLSpDTPEEKIREYFGAFGEVESIELPMDNKTNKRRGFCFITFK 49

RNA recognition motif 5 (RRM5) found in RNA-binding protein 19 (RBM19 or RBD-1) and similar proteins; This subfamily corresponds to the RRM5 of RBM19 and RRM4 of MRD1. RBM19, also termed RNA-binding domain-1 (RBD-1), is a nucleolar protein conserved in eukaryotes involved in ribosome biogenesis by processing rRNA and is essential for preimplantation development. It has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907182445 422 ALKKVFSSLGPVHSITLV--LETYRPYFS-----IQYEVLEAAQLALETMNGSLLEG 471
Cdd:cd12318    16 ALKKHFEKCGPIRSVTIAkkKDPKGPLLSmgygfVEFKSPEAAQKALKQLQGTVLDG 72

RNA recognition motif 1 (RRM1) found in yeast nucleolar protein 3 (Npl3p) and similar proteins; This subfamily corresponds to the RRM1 of Npl3p, also termed mitochondrial targeting suppressor 1 protein, or nuclear polyadenylated RNA-binding protein 1. Npl3p is a major yeast RNA-binding protein that competes with 3'-end processing factors, such as Rna15, for binding to the nascent RNA, protecting the transcript from premature termination and coordinating transcription termination and the packaging of the fully processed transcript for export. It specifically recognizes a class of G/U-rich RNAs. Npl3p is a multi-domain protein containing two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), separated by a short linker and a C-terminal domain rich in glycine, arginine and serine residues.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907182445 410 YAGPFSKDCNVGALKKVFSSLGPVHSITLVLEtyRPYFSIQYEVLEAAQLALETMNGSLLEGSCIRV 476
Cdd:cd12340     3 FVRPFPPDTSESAIREIFSPYGPVKEVKMLSD--SNFAFVEFEELEDAIRAKDSVHGRVLNNEPLYV 67