DnaQ-like (or DEDD) 3'-5' exonuclease domain superfamily; The DnaQ-like exonuclease superfamily is a structurally conserved group of 3'-5' exonucleases, which catalyze the excision of nucleoside monophosphates at the DNA or RNA termini in the 3'-5' direction. It is also called the DEDD superfamily, after the four invariant acidic residues present in the catalytic site of its members. The superfamily consists of DNA- and RNA-processing enzymes such as the proofreading domains of DNA polymerases, other DNA exonucleases, RNase D, RNase T, Oligoribonuclease and RNA exonucleases (REX). The DnaQ-like exonuclease domain contains three conserved sequence motifs termed ExoI, ExoII and ExoIII, which are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis. The conservation patterns of the three motifs may vary among different subfamilies. DnaQ-like exonucleases are classified as DEDDy or DEDDh exonucleases depending on the variation of motif III as YX(3)D or HX(4)D, respectively. The significance of the motif differences is still unclear. Almost all RNase families in this superfamily are present only in eukaryotes and bacteria, but not in archaea, suggesting a later origin, which in some cases are accompanied by horizontal gene transfer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182439 225 FGLDCEVCLTSMGKELTRISLVTEGGYCLIDELVKPDLKILDYLTSFTGITKEILNPVTTKLKDVQKLLRELLPPDAVLV 304
Cdd:cd06145     1 FALDCEMCYTTDGLELTRVTVVDENGKVVLDELVKPDGEIVDYNTRFSGITEEMLENVTTTLEDVQKKLLSLISPDTILV 80

                          90
                  ....*....|...
gi 1907182439 305 GHCLDLDLRVLKI 317
Cdd:cd06145    81 GHSLENDLKALKL 93

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 1907182439 520 IYVAGIGETFKEHLLEQS-NLFPDLEAVILPKEVKSRKQKNYCFLKFKTVNSAQVALEILKGkDWKLKGRNA 590
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 1907182439 225 FGLDCEVCLTSMGKELTRISLVTEGGYCLIDELVKPDLKILDYLTSFTGITKEILNPVTTKLKDVQKLLRELLPPDAVLV 304
Cdd:cd06145     1 FALDCEMCYTTDGLELTRVTVVDENGKVVLDELVKPDGEIVDYNTRFSGITEEMLENVTTTLEDVQKKLLSLISPDTILV 80

                          90
                  ....*....|...
gi 1907182439 305 GHCLDLDLRVLKI 317
Cdd:cd06145    81 GHSLENDLKALKL 93

RNA recognition motif 2 (RRM2) found in vertebrate putative RNA exonuclease NEF-sp; This subfamily corresponds to the RRM2 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 1907182439 520 IYVAGIGETFKEHLLEQS-NLFPDLEAVILPKEVKSRKQKNYCFLKFKTVNSAQVALEILKGkDWKLKGRNA 590
Cdd:cd12274     1 IYVSGFKKSLTEEDLQERfSQLSDLEAVFLPKDLQSGKHKKYCFLKFRSSQSAQAALDIITG-EWKLKGRRA 71

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 1907182439 422 MSTVYAGPFSKDCNVGALKKVFSSLGPVHSITL----VLETYRPYFSIQYEVLEAAQLALETMNGSLLEGSCIRVRRlvT 497
Cdd:TIGR01645 107 MCRVYVGSISFELREDTIRRAFDPFGPIKSINMswdpATGKHKGFAFVEYEVPEAAQLALEQMNGQMLGGRNIKVGR--P 184

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907182439 498 ELTLECDTLVRELEQDSENQGTIYVAGIGETFKEHLLEQS-NLFPDLEAVILPKEVKSRKQKNYCFLKFKTVNSAQVAL 575
Cdd:TIGR01645 185 SNMPQAQPIIDMVQEEAKKFNRIYVASVHPDLSETDIKSVfEAFGEIVKCQLARAPTGRGHKGYGFIEYNNLQSQSEAI 263

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907182439  519 TIYVAGIGETFKEHLLEQ--SNlFPDLEAVILPKEVKSRKQKNYCFLKFKTVNSAQVALEILKGKdwKLKGR 588
Cdd:smart00360   1 TLFVGNLPPDTTEEELRElfSK-FGKVESVRLVRDKETGKSKGFAFVEFESEEDAEKALEALNGK--ELDGR 69

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907182439 422 MSTVYAGPFSKDCNVGALKKVFSSLGPVHSITLVL--ETYRP--YFSIQYEVLEAAQLALETMNGSLLEGSCIRVR 493
Cdd:COG0724     1 SMKIYVGNLPYSVTEEDLRELFSEYGEVTSVKLITdrETGRSrgFGFVEMPDDEEAQAAIEALNGAELMGRTLKVN 76

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 1907182439 227 LDCE-VCLTSMGKELTRISLV-TEGGYCLIDE----LVKPDL--KILDYLTSFTGITKEILnPVTTKLKDVQKLLRELLP 298
Cdd:pfam00929   3 IDLEtTGLDPEKDEIIEIAAVvIDGGENEIGEtfhtYVKPTRlpKLTDECTKFTGITQAML-DNKPSFEEVLEEFLEFLR 81

                  ....*...
gi 1907182439 299 PDAVLVGH 306
Cdd:pfam00929  82 KGNLLVAH 89

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 1907182439 225 FGLDCEVCLTSMGKELTRISLVTEGGYCLIDELVKPDLKILDYLTSFTGITKEILNPVTTKLKDVQKLLRELLPPDAVLV 304
Cdd:cd06145     1 FALDCEMCYTTDGLELTRVTVVDENGKVVLDELVKPDGEIVDYNTRFSGITEEMLENVTTTLEDVQKKLLSLISPDTILV 80

                          90
                  ....*....|...
gi 1907182439 305 GHCLDLDLRVLKI 317
Cdd:cd06145    81 GHSLENDLKALKL 93

RNA recognition motif 2 (RRM2) found in vertebrate putative RNA exonuclease NEF-sp; This subfamily corresponds to the RRM2 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 1907182439 520 IYVAGIGETFKEHLLEQS-NLFPDLEAVILPKEVKSRKQKNYCFLKFKTVNSAQVALEILKGkDWKLKGRNA 590
Cdd:cd12274     1 IYVSGFKKSLTEEDLQERfSQLSDLEAVFLPKDLQSGKHKKYCFLKFRSSQSAQAALDIITG-EWKLKGRRA 71

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182439  224 LFGLDCE-VCLTSMGKELTRISLV-TEGG--YCLIDELVKPDLKILDYLTSFTGITKEILNPvTTKLKDVQKLLRELLPP 299
Cdd:smart00479   2 LVVIDCEtTGLDPGKDEIIEIAAVdVDGGeiIEVFDTYVKPDRPITDYATEIHGITPEMLDD-APTFEEVLEELLEFLRG 80

                           90
                   ....*....|....*..
gi 1907182439  300 DAVLVGHCLDLDLRVLK 316
Cdd:smart00479  81 RILVAGNSAHFDLRFLK 97

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 1907182439 422 MSTVYAGPFSKDCNVGALKKVFSSLGPVHSITL----VLETYRPYFSIQYEVLEAAQLALETMNGSLLEGSCIRVRRlvT 497
Cdd:TIGR01645 107 MCRVYVGSISFELREDTIRRAFDPFGPIKSINMswdpATGKHKGFAFVEYEVPEAAQLALEQMNGQMLGGRNIKVGR--P 184

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907182439 498 ELTLECDTLVRELEQDSENQGTIYVAGIGETFKEHLLEQS-NLFPDLEAVILPKEVKSRKQKNYCFLKFKTVNSAQVAL 575
Cdd:TIGR01645 185 SNMPQAQPIIDMVQEEAKKFNRIYVASVHPDLSETDIKSVfEAFGEIVKCQLARAPTGRGHKGYGFIEYNNLQSQSEAI 263

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 1907182439 240 LTRISLV----TEGGYCLIDELVKPDLKILDYLTSFTGITKEILNPVT-----TKLKDVQKLLRELLPPDAVLVGHCLDL 310
Cdd:cd06143    33 LARVSVVrgegELEGVPFIDDYISTTEPVVDYLTRFSGIKPGDLDPKTssknlTTLKSAYLKLRLLVDLGCIFVGHGLAK 112

                  ....*..
gi 1907182439 311 DLRVLKI 317
Cdd:cd06143   113 DFRVINI 119

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907182439  424 TVYAGPFSKDCNVGALKKVFSSLGPVHSITLVLETY----RPYFSIQYEVLEAAQLALETMNGSLLEGSCIRV 492
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRDKEtgksKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907182439  519 TIYVAGIGETFKEHLLEQ--SNlFPDLEAVILPKEVKSRKQKNYCFLKFKTVNSAQVALEILKGKdwKLKGR 588
Cdd:smart00360   1 TLFVGNLPPDTTEEELRElfSK-FGKVESVRLVRDKETGKSKGFAFVEFESEEDAEKALEALNGK--ELDGR 69

RNA recognition motif 2 (RRM2) found in (U)-binding-splicing factor PUF60 and similar proteins; This subfamily corresponds to the RRM2 of PUF60, also termed FUSE-binding protein-interacting repressor (FBP-interacting repressor or FIR), or Ro-binding protein 1 (RoBP1), or Siah-binding protein 1 (Siah-BP1). PUF60 is an essential splicing factor that functions as a poly-U RNA-binding protein required to reconstitute splicing in depleted nuclear extracts. Its function is enhanced through interaction with U2 auxiliary factor U2AF65. PUF60 also controls human c-myc gene expression by binding and inhibiting the transcription factor far upstream sequence element (FUSE)-binding-protein (FBP), an activator of c-myc promoters. PUF60 contains two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbors another RRM and binds to tryptophan-containing linear peptide motifs (UHM ligand motifs, ULMs) in several nuclear proteins. Research indicates that PUF60 binds FUSE as a dimer, and only the first two RRM domains participate in the single-stranded DNA recognition.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182439 439 LKKVFSSLGPVHSITLVLE----TYRPYFSIQYEVLEAAQLALETMNGSLLEGSCIRVRR 494
Cdd:cd12371    17 IKSVFEAFGKIKSCSLAPDpetgKHKGYGFIEYENPQSAQDAIASMNLFDLGGQYLRVGR 76

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 1907182439 425 VYAGPFSKDCNVGALKKVFSSLGPVHSITLVL---ETYRPYFSIQYEVLEAAQLALETMNGSLLEGSCIR 491
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 1907182439 423 STVYAGPFSKDCNVGALKKVFSSLGPVHSITLVL--ETYRP--YFSIQYEVLEAAQLALETMNGSLLEGSCIRV 492
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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907182439 426 YAGPFSKDCNVGALKKVFSSLGPVHSITLV--LETYRP--YFSIQYEVLEAAQLALETMNGSLLEGSCIRV 492
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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907182439 425 VYAGPFSKDCNVGALKKVFSSLGPVHSITLVL----ETYRPYFSIQYEVLEAAQLALETMNGSLLEGSCIRV 492
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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182439 417 TKWTQMSTVYAGPFSKDCNVGALKKVFSSLGPVHSITLVLE---TYRPYFSIQYEVLEAAQLALETMNG----SLLEGSC 489
Cdd:TIGR01628 173 APLKKFTNLYVKNLDPSVNEDKLRELFAKFGEITSAAVMKDgsgRSRGFAFVNFEKHEDAAKAVEEMNGkkigLAKEGKK 252

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182439 490 IRVRRLV--TELTLECDTLVRELEQDSENQG---TIYVAGIGETFKEHLLEQsnLFPDLEAVILPKEV--KSRKQKNYCF 562
Cdd:TIGR01628 253 LYVGRAQkrAEREAELRRKFEELQQERKMKAqgvNLYVKNLDDTVTDEKLRE--LFSECGEITSAKVMldEKGVSRGFGF 330

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907182439 563 LKFKTVNSAQVALEILKGKdwKLKGRN---ALTPR------HLQAWLKDIHPE-PAMPMGlRIVPPLMERHIFRTR 628
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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907182439 422 MSTVYAGPFSKDCNVGALKKVFSSLGPVHSITLVL--ETYRP--YFSIQYEVLEAAQLALETMNGSLLEGSCIRV 492
Cdd:cd12671     6 LRSVFVGNIPYEATEEQLKDIFSEVGPVVSFRLVYdrETGKPkgYGFCEYQDQETALSAMRNLNGYELNGRALRV 80

RNA recognition motif 1 (RRM1) found in nucleolysin TIA-1 isoform p40 (p40-TIA-1) and similar proteins; This subgroup corresponds to the RRM1 of TIA-1, the 40-kDa isoform of T-cell-restricted intracellular antigen-1 (TIA-1) and a cytotoxic granule-associated RNA-binding protein mainly found in the granules of cytotoxic lymphocytes. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis, and functions as the granule component responsible for inducing apoptosis in cytolytic lymphocyte (CTL) targets. It is 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 interacts with RNAs containing short stretches of uridylates and its RRM2 can mediate the specific binding to uridylate-rich RNAs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907182439 424 TVYAGPFSKDCNVGALKKVFSSLGPVHSITLVLETY--RPYFSIQYEVLEAAQLALETMNGSLLEGSCIRV 492
Cdd:cd12615     1 TLYVGNLSRDVTEALILQLFSQIGPCKNCKMIMDTAgnDPYCFVEFHEHRHAAAALAAMNGRKIMGKEVKV 71

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907182439 424 TVYAGPFSKDCNVGALKKVFSSLGPVHSITLVLE----TYRPYFSIQYEVLEAAQLALETMNGSLLEGSCIRV 492
Cdd:cd12447     1 TLFVGGLSWNVDDPWLKKEFEKYGGVISARVITDrgsgRSKGYGYVDFATPEAAQKALAAMSGKEIDGRQINV 73

splicing factor, CC1-like family; This model represents a subfamily of RNA splicing factors including the Pad-1 protein (N. crassa), CAPER (M. musculus) and CC1.3 (H.sapiens). These proteins are characterized by an N-terminal arginine-rich, low complexity domain followed by three (or in the case of 4 H. sapiens paralogs, two) RNA recognition domains (rrm: pfam00706). These splicing factors are closely related to the U2AF splicing factor family (TIGR01642). A homologous gene from Plasmodium falciparum was identified in the course of the analysis of that genome at TIGR and was included in the seed.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907182439 439 LKKVFSSLGPVHSITLVLETY----RPYFSIQYEVLEAAQLALETMNGSLLEGSCIRV--RRLVTELTlECDTLVRELEQ 512
Cdd:TIGR01622 231 LRQIFEPFGEIEFVQLQKDPEtgrsKGYGFIQFRDAEQAKEALEKMNGFELAGRPIKVglGNDFTPES-DANLAQRFQDQ 309

                          90       100
                  ....*....|....*....|....
gi 1907182439 513 DSENQGTIyvaGIGETFKEHLLEQ 536
Cdd:TIGR01622 310 DGSAFSGA---GLNTPARSQLMRK 330

RNA recognition motif 1 (RRM1) found in chloroplastic plastid-specific 30S ribosomal protein 2 (PSRP-2) and similar proteins; PSRP-2, also called chloroplastic 30S ribosomal protein 2, or chloroplastic small ribosomal subunit protein cS22, is a component of the chloroplast ribosome (chloro-ribosome), a dedicated translation machinery responsible for the synthesis of chloroplast genome-encoded proteins, including proteins of the transcription and translation machinery and components of the photosynthetic apparatus. It binds single strand DNA (ssDNA) and RNA in vitro. It exhibits RNA chaperone activity and regulates negatively resistance responses to abiotic stresses during seed germination (e.g. salt, dehydration, and low temperature) and seedling growth (e.g. salt). The family also includes Nicotiana sylvestris chloroplastic 33 kDa ribonucleoprotein (NsCP33) and Arabidopsis thaliana chloroplastic 31 kDa ribonucleoprotein (AtCP31A). 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. 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 first RRM motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907182439 425 VYAGPFSKDCNVGALKKVFSSLGPVHSITLVLETY----RPYFSIQYEVLEAAQLALETMNGSLLEGSCIRVR 493
Cdd:cd21609     2 LYVGNIPRNVTSEELAKIFEEAGTVEIAEVMYDRYtgrsRGFGFVTMGSVEDAKAAIEKLNGTEVGGREIKVN 74

RNA recognition motif (RRM) found in transformer-2 protein homolog TRA2-alpha, TRA2-beta and similar proteins; This subfamily corresponds to the RRM of two mammalian homologs of Drosophila transformer-2 (Tra2), TRA2-alpha, TRA2-beta (also termed SFRS10), and similar proteins found in eukaryotes. TRA2-alpha is a 40-kDa serine/arginine-rich (SR) protein that specifically binds to gonadotropin-releasing hormone (GnRH) exonic splicing enhancer on exon 4 (ESE4) and is necessary for enhanced GnRH pre-mRNA splicing. It strongly stimulates GnRH intron A excision in a dose-dependent manner. In addition, TRA2-alpha can interact with either 9G8 or SRp30c, which may also be crucial for ESE-dependent GnRH pre-mRNA splicing. TRA2-beta is a serine/arginine-rich (SR) protein that controls the pre-mRNA alternative splicing of the calcitonin/calcitonin gene-related peptide (CGRP), the survival motor neuron 1 (SMN1) protein and the tau protein. Both, TRA2-alpha and TRA2-beta, contains a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), flanked by the N- and C-terminal arginine/serine (RS)-rich regions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907182439 439 LKKVFSSLGPVHSITLVLETY----RPYFSIQYEVLEAAQLALETMNGSLLEGSCIRV 492
Cdd:cd12363    18 LREVFSRYGPIEKVQVVYDQQtgrsRGFGFVYFESVEDAKEAKERLNGQEIDGRRIRV 75

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).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907182439 438 ALKKVFSSLGPVHSITLV--LETYRPYFS-----IQYEVLEAAQLALETMNGSLLEG 487
Cdd:cd12318    16 ALKKHFEKCGPIRSVTIAkkKDPKGPLLSmgygfVEFKSPEAAQKALKQLQGTVLDG 72

RNA recognition motif 1 (RRM1) found in (U)-binding-splicing factor PUF60 and similar proteins; This subfamily corresponds to the RRM1 of PUF60, also termed FUSE-binding protein-interacting repressor (FBP-interacting repressor or FIR), or Ro-binding protein 1 (RoBP1), or Siah-binding protein 1 (Siah-BP1). PUF60 is an essential splicing factor that functions as a poly-U RNA-binding protein required to reconstitute splicing in depleted nuclear extracts. Its function is enhanced through interaction with U2 auxiliary factor U2AF65. PUF60 also controls human c-myc gene expression by binding and inhibiting the transcription factor far upstream sequence element (FUSE)-binding-protein (FBP), an activator of c-myc promoters. PUF60 contains two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbors another RRM and binds to tryptophan-containing linear peptide motifs (UHM ligand motifs, ULMs) in several nuclear proteins. Research indicates that PUF60 binds FUSE as a dimer, and only the first two RRM domains participate in the single-stranded DNA recognition.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907182439 520 IYVAGIGETFKEHLLEQS-NLFPDLEAVILPKEVKSRKQKNYCFLKFKTVNSAQVALEILKGkdWKLKGRN 589
Cdd:cd12370     3 VYVGSIYFELGEDTIRQAfAPFGPIKSIDMSWDPVTMKHKGFAFVEYEVPEAAQLALEQMNG--VMLGGRN 71

RNA recognition motif 2 (RRM2) found in granule-associated RNA binding proteins (p40-TIA-1 and TIAR), and yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1; This subfamily corresponds to the RRM3 of TIA-1, TIAR, and PUB1. Nucleolysin TIA-1 isoform p40 (p40-TIA-1 or TIA-1) and nucleolysin TIA-1-related protein (TIAR) are granule-associated RNA binding proteins involved in inducing apoptosis in cytotoxic lymphocyte (CTL) target cells. They share high sequence similarity and 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. This subfamily also includes a yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1, termed ARS consensus-binding protein ACBP-60, or poly uridylate-binding protein, or poly(U)-binding protein, which has been identified as both a heterogeneous nuclear RNA-binding protein (hnRNP) and a cytoplasmic mRNA-binding protein (mRNP). It may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm. PUB1 is distributed in both, the nucleus and the cytoplasm, and binds to poly(A)+ RNA (mRNA or pre-mRNA). Although it is one of the major cellular proteins cross-linked by UV light to polyadenylated RNAs in vivo, PUB1 is nonessential for cell growth in yeast. PUB1 also binds to T-rich single stranded DNA (ssDNA); however, there is no strong evidence implicating PUB1 in the mechanism of DNA replication. PUB1 contains three RRMs, and a GAR motif (glycine and arginine rich stretch) that is located between RRM2 and RRM3.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907182439 424 TVYAGPFSKDCNVGALKKVFSSLGPVHSITLVLEtyRPYFSIQYEVLEAAQLALETMNGSLLEGSCIR 491
Cdd:cd12354     2 TVYVGNITKGLTEALLQQTFSPFGQILEVRVFPD--KGYAFIRFDSHEAATHAIVSVNGTIINGQAVK 67

RNA recognition motif 3 (RRM3) found in heterogeneous nuclear ribonucleoprotein R (hnRNP R) and similar proteins; This subfamily corresponds to the RRM3 in hnRNP R, hnRNP Q, and APOBEC-1 complementation factor (ACF). hnRNP R is a ubiquitously expressed nuclear RNA-binding protein that specifically bind mRNAs with a preference for poly(U) stretches and has been implicated in mRNA processing and mRNA transport, and also acts as a regulator to modify binding to ribosomes and RNA translation. hnRNP Q is also a ubiquitously expressed nuclear RNA-binding protein. It has been identified as a component of the spliceosome complex, as well as a component of the apobec-1 editosome, and has been implicated in the regulation of specific mRNA transport. ACF is an RNA-binding subunit of a core complex that interacts with apoB mRNA to facilitate C to U RNA editing. It may also act as an apoB mRNA recognition factor and chaperone and play a key role in cell growth and differentiation. This family also includes two functionally unknown RNA-binding proteins, RBM46 and RBM47. All members contain three conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907182439 439 LKKVFSSLGPVHSITLVletyRPYFSIQYEVLEAAQLALETMNGSLLEGSCIRV 492
Cdd:cd12251    18 LRELFSEYGKVERVKKI----KDYAFVHFEERDDAVKAMEEMNGKELEGSEIEV 67