RNA recognition motif (RRM) found in vertebrate RNA-binding protein with multiple splicing 2 (RBP-MS2); This subfamily corresponds to the RRM of RBP-MS2, encoded by RBPMS2 gene, a paralog of RNA-binding protein with multiple splicing (RBP-MS). The biological function of RBP-MS2 remains unclear. Like RBP-MS, RBP-MS2 contains an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34915990  30 VRTLFVSGLPVDIKPRELYLLFRPFKGYEGSLIKLTARQPVGFVIFDSRAGAEAAKNALNGIRFDPENPQTLRLEF 105
Cdd:cd12683   1 VRTLFVSGLPVDIKPRELYLLFRPFKGYEGSLIKLTSKQPVGFVTFDSRAGAEAAKNALNGIRFDPENPQTLRLEF 76

RNA recognition motif (RRM) found in vertebrate RNA-binding protein with multiple splicing 2 (RBP-MS2); This subfamily corresponds to the RRM of RBP-MS2, encoded by RBPMS2 gene, a paralog of RNA-binding protein with multiple splicing (RBP-MS). The biological function of RBP-MS2 remains unclear. Like RBP-MS, RBP-MS2 contains an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34915990  30 VRTLFVSGLPVDIKPRELYLLFRPFKGYEGSLIKLTARQPVGFVIFDSRAGAEAAKNALNGIRFDPENPQTLRLEF 105
Cdd:cd12683   1 VRTLFVSGLPVDIKPRELYLLFRPFKGYEGSLIKLTSKQPVGFVTFDSRAGAEAAKNALNGIRFDPENPQTLRLEF 76

RNA recognition motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 34915990     32 TLFVSGLPVDIKPRELYLLFRPFKGYEGSLI---KLTAR-QPVGFVIFDSRAGAEAAKNALNGIRFD 94
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLvrdKETGKsKGFAFVEFESEEDAEKALEALNGKELD 67

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34915990  32 TLFVSGLPVDIKPRELYLLFRPF-----------------KGYegslikltarqpvGFVIFDSRAGAEAAKNALNGIRFD 94
Cdd:COG0724   3 KIYVGNLPYSVTEEDLRELFSEYgevtsvklitdretgrsRGF-------------GFVEMPDDEEAQAAIEALNGAELM 69

RNA recognition motif (RRM) found in vertebrate RNA-binding protein with multiple splicing 2 (RBP-MS2); This subfamily corresponds to the RRM of RBP-MS2, encoded by RBPMS2 gene, a paralog of RNA-binding protein with multiple splicing (RBP-MS). The biological function of RBP-MS2 remains unclear. Like RBP-MS, RBP-MS2 contains an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34915990  30 VRTLFVSGLPVDIKPRELYLLFRPFKGYEGSLIKLTARQPVGFVIFDSRAGAEAAKNALNGIRFDPENPQTLRLEF 105
Cdd:cd12683   1 VRTLFVSGLPVDIKPRELYLLFRPFKGYEGSLIKLTSKQPVGFVTFDSRAGAEAAKNALNGIRFDPENPQTLRLEF 76

RNA recognition motif (RRM) found in RNA-binding protein with multiple splicing (RBP-MS)-like proteins; This subfamily corresponds to the RRM of RNA-binding proteins with multiple splicing (RBP-MS)-like proteins, including protein products of RBPMS genes (RBP-MS and its paralogue RBP-MS2), the Drosophila couch potato (cpo), and Caenorhabditis elegans Mec-8 genes. RBP-MS may be involved in regulation of mRNA translation and localization during Xenopus laevis development. It has also been shown to physically interact with Smad2, Smad3 and Smad4, and stimulates Smad-mediated transactivation. Cpo may play an important role in regulating normal function of the nervous system, whereas mutations in Mec-8 affect mechanosensory and chemosensory neuronal function. All members contain a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). Some uncharacterized family members contain two RRMs; this subfamily includes their RRM1. Their RRM2 shows high sequence homology to the RRM of yeast proteins scw1, Whi3, and Whi4.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34915990  31 RTLFVSGLPVDIKPRELYLLFRPFKGYEGSLIKLTAR--QPVGFVIFDSRAGAEAAKNALNGIRFDPENPQTLRLE 104
Cdd:cd12420   1 RTLFVSGLPLDVKERELYNLFRPLPGYEASQLKFTGKntQPVGFVTFESRAAAEAAKDALQGMRFDPDTPQVLRLE 76

RNA recognition motif (RRM) found in Arabidopsis thaliana nuclear speckle RNA-binding protein A (AtNSRA) and similar protein; AtNSRA is an alternative splicing (AS) regulator that binds to specific mRNAs and modulates auxin effects on the transcriptome. It can be displaced from its targets upon binding to AS competitor long non-coding RNA (ASCO-RNA). Members in this family contain an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34915990  31 RTLFVSGLPVDIKPRELYLLFRPFKGYEG-SLI----KLTARQPVGFVIFDSRAGAEAAKNALNGIRFDPENPQ--TLRL 103
Cdd:cd21618   4 STLYVEGLPLDATEREVAHIFRPFPGFKSvRLVpkegKRGRKLVLCFVDFADAQQAAAALETLQGYRLDEDDSDskGLRI 83

                ....
gi 34915990 104 EFAK 107
Cdd:cd21618  84 SFAR 87

RNA recognition motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 34915990     32 TLFVSGLPVDIKPRELYLLFRPFKGYEGSLI---KLTAR-QPVGFVIFDSRAGAEAAKNALNGIRFD 94
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLvrdKETGKsKGFAFVEFESEEDAEKALEALNGKELD 67

RNA recognition motif 2 (RRM2) found in the U1A/U2B"/SNF protein family; This subfamily corresponds to the RRM2 of U1A/U2B"/SNF protein family, containing Drosophila sex determination protein SNF and its two mammalian counterparts, U1 small nuclear ribonucleoprotein A (U1 snRNP A or U1-A or U1A) and U2 small nuclear ribonucleoprotein B" (U2 snRNP B" or U2B"), all of which consist of two RNA recognition motifs (RRMs) connected by a variable, flexible linker. SNF is an RNA-binding protein found in the U1 and U2 snRNPs of Drosophila where it is essential in sex determination and possesses a novel dual RNA binding specificity. SNF binds with high affinity to both Drosophila U1 snRNA stem-loop II (SLII) and U2 snRNA stem-loop IV (SLIV). It can also bind to poly(U) RNA tracts flanking the alternatively spliced Sex-lethal (Sxl) exon, as does Drosophila Sex-lethal protein (SXL). U1A is an RNA-binding protein associated with the U1 snRNP, a small RNA-protein complex involved in pre-mRNA splicing. U1A binds with high affinity and specificity to stem-loop II (SLII) of U1 snRNA. It is predominantly a nuclear protein that shuttles between the nucleus and the cytoplasm independently of interactions with U1 snRNA. Moreover, U1A may be involved in RNA 3'-end processing, specifically cleavage, splicing and polyadenylation, through interacting with a large number of non-snRNP proteins. U2B", initially identified to bind to stem-loop IV (SLIV) at the 3' end of U2 snRNA, is a unique protein that comprises of the U2 snRNP. Additional research indicates U2B" binds to U1 snRNA stem-loop II (SLII) as well and shows no preference for SLIV or SLII on the basis of binding affinity. U2B" does not require an auxiliary protein for binding to RNA and its nuclear transport is independent on U2 snRNA binding.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 34915990  31 RTLFVSGLPVDIKPRELYLLFRPFKGYEGslIKLTARQPVGFVIFDSRAGAEAAKNALNGIRFDPENP 98
Cdd:cd12247   3 KILFLQNLPEETTKEMLEMLFNQFPGFKE--VRLVPRRGIAFVEFETEEQATVALQALQGFKITPGHA 68

RNA recognition motif 2 (RRM2) found in the Hu proteins family; This subfamily corresponds to the RRM2 of Hu proteins family which represents a group of RNA-binding proteins involved in diverse biological processes. Since the Hu proteins share high homology with the Drosophila embryonic lethal abnormal vision (ELAV) protein, the Hu family is sometimes referred to as the ELAV family. Drosophila ELAV is exclusively expressed in neurons and is required for the correct differentiation and survival of neurons in flies. The neuronal members of the Hu family include Hu-antigen B (HuB or ELAV-2 or Hel-N1), Hu-antigen C (HuC or ELAV-3 or PLE21), and Hu-antigen D (HuD or ELAV-4), which play important roles in neuronal differentiation, plasticity and memory. HuB is also expressed in gonads. Hu-antigen R (HuR or ELAV-1 or HuA) is the ubiquitously expressed Hu family member. It has a variety of biological functions mostly related to the regulation of cellular response to DNA damage and other types of stress. Moreover, HuR has an anti-apoptotic function during early cell stress response. It binds to mRNAs and enhances the expression of several anti-apoptotic proteins, such as p21waf1, p53, and prothymosin alpha. HuR also has pro-apoptotic function by promoting apoptosis when cell death is unavoidable. Furthermore, HuR may be important in muscle differentiation, adipogenesis, suppression of inflammatory response and modulation of gene expression in response to chronic ethanol exposure and amino acid starvation. Hu proteins perform their cytoplasmic and nuclear molecular functions by coordinately regulating functionally related mRNAs. In the cytoplasm, Hu proteins recognize and bind to AU-rich RNA elements (AREs) in the 3' untranslated regions (UTRs) of certain target mRNAs, such as GAP-43, vascular epithelial growth factor (VEGF), the glucose transporter GLUT1, eotaxin and c-fos, and stabilize those ARE-containing mRNAs. They also bind and regulate the translation of some target mRNAs, such as neurofilament M, GLUT1, and p27. In the nucleus, Hu proteins function as regulators of polyadenylation and alternative splicing. Each Hu protein contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 may cooperate in binding to an ARE. RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 34915990  33 LFVSGLPVDIKPRELYLLFRPFkgyeGSLIklTAR----------QPVGFVIFDSRAGAEAAKNALNG 90
Cdd:cd12652   3 LYVSGLPKTMTQKELEQLFSQF----GRII--TSRilcdnvtglsRGVGFIRFDKRVEAERAIKALNG 64

RNA recognition motif 1 (RRM1) found in the U1A/U2B"/SNF protein family; This subfamily corresponds to the RRM1 of U1A/U2B"/SNF protein family which contains Drosophila sex determination protein SNF and its two mammalian counterparts, U1 small nuclear ribonucleoprotein A (U1 snRNP A or U1-A or U1A) and U2 small nuclear ribonucleoprotein B" (U2 snRNP B" or U2B"), all of which consist of two RNA recognition motifs (RRMs), connected by a variable, flexible linker. SNF is an RNA-binding protein found in the U1 and U2 snRNPs of Drosophila where it is essential in sex determination and possesses a novel dual RNA binding specificity. SNF binds with high affinity to both Drosophila U1 snRNA stem-loop II (SLII) and U2 snRNA stem-loop IV (SLIV). It can also bind to poly(U) RNA tracts flanking the alternatively spliced Sex-lethal (Sxl) exon, as does Drosophila Sex-lethal protein (SXL). U1A is an RNA-binding protein associated with the U1 snRNP, a small RNA-protein complex involved in pre-mRNA splicing. U1A binds with high affinity and specificity to stem-loop II (SLII) of U1 snRNA. It is predominantly a nuclear protein that shuttles between the nucleus and the cytoplasm independently of interactions with U1 snRNA. Moreover, U1A may be involved in RNA 3'-end processing, specifically cleavage, splicing and polyadenylation, through interacting with a large number of non-snRNP proteins. U2B", initially identified to bind to stem-loop IV (SLIV) at the 3' end of U2 snRNA, is a unique protein that comprises of the U2 snRNP. Additional research indicates U2B" binds to U1 snRNA stem-loop II (SLII) as well and shows no preference for SLIV or SLII on the basis of binding affinity. Moreover, U2B" does not require an auxiliary protein for binding to RNA, and its nuclear transport is independent of U2 snRNA binding.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34915990  32 TLFVSGLPVDIKPRE----LYLLFRPFkgyeGSLIKLTARQPVG-----FVIFDSRAGAEAAKNALNGIRF-DpenpQTL 101
Cdd:cd12246   1 TLYINNLNEKIKKDElkrsLYALFSQF----GPVLDIVASKSLKmrgqaFVVFKDVESATNALRALQGFPFyG----KPM 72

                ....*.
gi 34915990 102 RLEFAK 107
Cdd:cd12246  73 RIQYAK 78

RNA recognition motif (RRM) found in yeast cell wall integrity protein scw1 and similar proteins; This subfamily corresponds to the RRM of the family including yeast cell wall integrity protein scw1, yeast Whi3 protein, yeast Whi4 protein and similar proteins. The strong cell wall protein 1, scw1, is a nonessential cytoplasmic RNA-binding protein that regulates septation and cell-wall structure in fission yeast. It may function as an inhibitor of septum formation, such that its loss of function allows weak SIN signaling to promote septum formation. It's RRM domain shows high homology to two budding yeast proteins, Whi3 and Whi4. Whi3 is a dose-dependent modulator of cell size and has been implicated in cell cycle control in the yeast Saccharomyces cerevisiae. It functions as a negative regulator of ceroid-lipofuscinosis, neuronal 3 (Cln3), a G1 cyclin that promotes transcription of many genes to trigger the G1/S transition in budding yeast. It specifically binds the CLN3 mRNA and localizes it into discrete cytoplasmic loci that may locally restrict Cln3 synthesis to modulate cell cycle progression. Moreover, Whi3 plays a key role in cell fate determination in budding yeast. The RRM domain is essential for Whi3 function. Whi4 is a partially redundant homolog of Whi3, also containing one RRM. Some uncharacterized family members of this subfamily contain two RRMs; their RRM1 shows high sequence homology to the RRM of RNA-binding protein with multiple splicing (RBP-MS)-like proteins.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34915990  32 TLFVSGLPVDIKPRELYLLFRPFKGYEGSLIKLTARQPVGFVIFDSRAGAEAAKNALNGIRFDPENPQTLRLEFAK 107
Cdd:cd12245   4 TLFVANLGPNVSEQELRQLFSRQPGFRRLRMHNKGGGPVCFVEFEDVPFATQALNHLQGAILSSSDRGGIRIEYAK 79

RNA recognition motif 1 (RRM1) found in the p54nrb/PSF/PSP1 family; This subfamily corresponds to the RRM1 of the p54nrb/PSF/PSP1 family, including 54 kDa nuclear RNA- and DNA-binding protein (p54nrb or NonO or NMT55), polypyrimidine tract-binding protein (PTB)-associated-splicing factor (PSF or POMp100), paraspeckle protein 1 (PSP1 or PSPC1), which are ubiquitously expressed and are conserved in vertebrates. p54nrb is a multi-functional protein involved in numerous nuclear processes including transcriptional regulation, splicing, DNA unwinding, nuclear retention of hyperedited double-stranded RNA, viral RNA processing, control of cell proliferation, and circadian rhythm maintenance. PSF is also a multi-functional protein that binds RNA, single-stranded DNA (ssDNA), double-stranded DNA (dsDNA) and many factors, and mediates diverse activities in the cell. PSP1 is a novel nucleolar factor that accumulates within a new nucleoplasmic compartment, termed paraspeckles, and diffusely distributes in the nucleoplasm. The cellular function of PSP1 remains unknown currently. This subfamily also includes some p54nrb/PSF/PSP1 homologs from invertebrate species, such as the Drosophila melanogaster gene no-ontransient A (nonA) encoding puff-specific protein Bj6 (also termed NONA) and Chironomus tentans hrp65 gene encoding protein Hrp65. D. melanogaster NONA is involved in eye development and behavior, and may play a role in circadian rhythm maintenance, similar to vertebrate p54nrb. C. tentans Hrp65 is a component of nuclear fibers associated with ribonucleoprotein particles in transit from the gene to the nuclear pore. All family members contain a DBHS domain (for Drosophila behavior, human splicing), which comprises two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a charged protein-protein interaction module. PSF has an additional large N-terminal domain that differentiates it from other family members.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 34915990  33 LFVSGLPVDIKPRELYLLFRPFKgyEGSLIKLTARQPVGFVIFDSRAGAEAAKNALNGIrfdPENPQTLRLEF 105
Cdd:cd12332   4 LFVGNLPNDITEEEFKELFQKYG--EVSEVFLNKGKGFGFIRLDTRANAEAAKAELDGT---PRKGRQLRVRF 71

RNA recognition motif 3 (RRM3) found in yeast negative growth regulatory protein NGR1 (RBP1), yeast protein NAM8 and similar proteins; This subfamily corresponds to the RRM3 of NGR1 and NAM8. NGR1, also termed RNA-binding protein RBP1, is a putative glucose-repressible protein that binds both RNA and single-stranded DNA (ssDNA) in yeast. It may function in regulating cell growth in early log phase, possibly through its participation in RNA metabolism. NGR1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a glutamine-rich stretch that may be involved in transcriptional activity. In addition, NGR1 has an asparagine-rich region near the carboxyl terminus which also harbors a methionine-rich region. The family also includes protein NAM8, which is a putative RNA-binding protein that acts as a suppressor of mitochondrial splicing deficiencies when overexpressed in yeast. It may be a non-essential component of the mitochondrial splicing machinery. Like NGR1, NAM8 contains two RRMs.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 34915990  32 TLFVSGLPVDIKPRELYLLFRPFkgyeGSL--IKLTARQPVGFVIFDSRAGAEAAKNALNG 90
Cdd:cd12346   3 TVFVGGLDPNVTEEDLRVLFGPF----GEIvyVKIPPGKGCGFVQFVNRASAEAAIQKLQG 59

RNA recognition motif 2 (RRM2) found in Drosophila melanogaster sex determination protein SNF and similar proteins; This subgroup corresponds to the RRM2 of SNF (Sans fille), also termed U1 small nuclear ribonucleoprotein A (U1 snRNP A or U1-A or U1A), an RNA-binding protein found in the U1 and U2 snRNPs of Drosophila. It is essential in Drosophila sex determination and possesses a novel dual RNA binding specificity. SNF binds with high affinity to both Drosophila U1 snRNA stem-loop II (SLII) and U2 snRNA stem-loop IV (SLIV). It can also bind to poly(U) RNA tracts flanking the alternatively spliced Sex-lethal (Sxl) exon, as does Drosophila Sex-lethal protein (SXL). SNF contains two RNA recognition motifs (RRMs); it can self-associate through RRM1, and each RRM can recognize poly(U) RNA binding independently.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 34915990  31 RTLFVSGLPVDIKPRELYLLFRPFKGYEGSLIkLTARQPVGFVIFDSRAGAEAAKNALNGIRFDPENpqTLRLEFAK 107
Cdd:cd12479   6 QILFLTNLPEETNEMMLSMLFNQFPGFKEVRL-VPGRHDIAFVEFENEVQSAAAKEALQGFKITPTH--AMKITFAK 79

RNA recognition motif (RRM) found in Pre-mRNA-splicing factor RBM22 and similar proteins; This subgroup corresponds to the RRM of RBM22 (also known as RNA-binding motif protein 22, or Zinc finger CCCH domain-containing protein 16), a newly discovered RNA-binding motif protein which belongs to the SLT11 gene family. SLT11 gene encoding protein (Slt11p) is a splicing factor in yeast, which is required for spliceosome assembly. Slt11p has two distinct biochemical properties: RNA-annealing and RNA-binding activities. RBM22 is the homolog of SLT11 in vertebrate. It has been reported to be involved in pre-splicesome assembly and to interact with the Ca2+-signaling protein ALG-2. It also plays an important role in embryogenesis. RBM22 contains a conserved RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a zinc finger of the unusual type C-x8-C-x5-C-x3-H, and a C-terminus that is unusually rich in the amino acids Gly and Pro, including sequences of tetraprolines.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 34915990  30 VRTLFVSGLPVDIKPRELYLLFRPFkgyeGSL--IKLTARQPVGFVIFDSRAGAEAA 84
Cdd:cd12224   1 ITTLYVGGLGDKITEKDLRDHFYQF----GEIrsITVVARQQCAFVQFTTRQAAERA 53

RNA recognition motif 3 (RRM3) found in CELF/Bruno-like family of RNA binding proteins CELF1, CELF2, CELF3, CELF4, CELF5, CELF6 and similar proteins; This subgroup corresponds to the RRM3 of the CUGBP1 and ETR-3-like factors (CELF) or BRUNOL (Bruno-like) proteins, a family of structurally related RNA-binding proteins involved in the regulation of pre-mRNA splicing in the nucleus and in the control of mRNA translation and deadenylation in the cytoplasm. The family contains six members: CELF-1 (also termed BRUNOL-2, or CUG-BP1, or NAPOR, or EDEN-BP), CELF-2 (also termed BRUNOL-3, or ETR-3, or CUG-BP2, or NAPOR-2), CELF-3 (also termed BRUNOL-1, or TNRC4, or ETR-1, or CAGH4, or ER DA4), CELF-4 (also termed BRUNOL-4), CELF-5 (also termed BRUNOL-5), CELF-6 (also termed BRUNOL-6). They all contain three highly conserved RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C-terminus of the protein. The low sequence conservation of the linker region is highly suggestive of a large variety in the co-factors that associate with the various CELF family members. Based on both sequence similarity and function, the CELF family can be divided into two subfamilies, the first containing CELFs 1 and 2, and the second containing CELFs 3, 4, 5, and 6. The different CELF proteins may act through different sites on at least some substrates. Furthermore, CELF proteins may interact with each other in varying combinations to influence alternative splicing in different contexts.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34915990  33 LFVSGLPVDIKPRELYLLFRPFkgyeGSLI-------KLTAR-QPVGFVIFDSRAGAEAAKNALNG 90
Cdd:cd12362   1 LFVYHLPNEFTDQDLYQLFAPF----GNVVsakvfvdKNTGRsKGFGFVSYDNPLSAQAAIKAMNG 62

RNA recognition motif (RRM) found in eukaryotic translation initiation factor 3 subunit G (eIF-3G) and similar proteins; This subfamily corresponds to the RRM of eIF-3G and similar proteins. eIF-3G, also termed eIF-3 subunit 4, or eIF-3-delta, or eIF3-p42, or eIF3-p44, is the RNA-binding subunit of eIF3, a large multisubunit complex that plays a central role in the initiation of translation by binding to the 40 S ribosomal subunit and promoting the binding of methionyl-tRNAi and mRNA. eIF-3G binds 18 S rRNA and beta-globin mRNA, and therefore appears to be a nonspecific RNA-binding protein. eIF-3G is one of the cytosolic targets and interacts with mature apoptosis-inducing factor (AIF). eIF-3G contains one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). This family also includes yeast eIF3-p33, a homolog of vertebrate eIF-3G, plays an important role in the initiation phase of protein synthesis in yeast. It binds both, mRNA and rRNA, fragments due to an RRM near its C-terminus.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 34915990  32 TLFVSGLPVDIKPRELYLLFRPFkgyeGSLIKLT------ARQPVGF--VIFDSRAGAEAAKNALNGIRFD 94
Cdd:cd12408   1 TIRVTNLSEDATEEDLRELFRPF----GPISRVYlakdkeTGQSKGFafVTFETREDAERAIEKLNGFGYD 67

RNA recognition motif 2 (RRM2) found in vertebrate Hu-antigen B (HuB); This subgroup corresponds to the RRM2 of HuB, also termed ELAV-like protein 2 (ELAV-2), or ELAV-like neuronal protein 1, or nervous system-specific RNA-binding protein Hel-N1 (Hel-N1), one of the neuronal members of the Hu family. The neuronal Hu proteins play important roles in neuronal differentiation, plasticity and memory. HuB is also expressed in gonads. It is up-regulated during neuronal differentiation of embryonic carcinoma P19 cells. Like other Hu proteins, HuB contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 may cooperate in binding to an AU-rich RNA element (ARE). RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 34915990  33 LFVSGLPVDIKPRELYLLFRPFKGYEGSLI---KLTA-RQPVGFVIFDSRAGAEAAKNALNGIRfDPENPQTLRLEFA 106
Cdd:cd12775   8 LYVSGLPKTMTQKELEQLFSQYGRIITSRIlvdQVTGvSRGVGFIRFDKRIEAEEAIKGLNGQK-PPGATEPITVKFA 84

RNA recognition motif (RRM) found in U2-associated protein SR140 and similar proteins; This subgroup corresponds to the RRM of SR140 (also termed U2 snRNP-associated SURP motif-containing protein orU2SURP, or 140 kDa Ser/Arg-rich domain protein) which is a putative splicing factor mainly found in higher eukaryotes. Although it is initially identified as one of the 17S U2 snRNP-associated proteins, the molecular and physiological function of SR140 remains unclear. SR140 contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a SWAP/SURP domain that is found in a number of pre-mRNA splicing factors in the middle region, and a C-terminal arginine/serine-rich domain (RS domain).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34915990  33 LFVSGLPVDIKPRELYLLFRPFkGYEGSLIKLTARQP--------VGFVIFDSRAGAEAAKNALNGIrfDPENpQTLRLE 104
Cdd:cd12223   4 LYVGNLPPSVTEEVLLREFGRF-GPLASVKIMWPRTEeerrrnrnCGFVAFMSRADAERAMRELNGK--DVMG-YELKLG 79

                ....
gi 34915990 105 FAKA 108
Cdd:cd12223  80 WGKA 83

RNA recognition motif (RRM) found in Saccharomyces cerevisiae protein Nrd1, Schizosaccharomyces pombe Rpb7-binding protein seb1 and similar proteins; This subfamily corresponds to the RRM of Nrd1 and Seb1. Nrd1 is a novel heterogeneous nuclear ribonucleoprotein (hnRNP)-like RNA-binding protein encoded by gene NRD1 (for nuclear pre-mRNA down-regulation) from yeast S. cerevisiae. It is implicated in 3' end formation of small nucleolar and small nuclear RNAs transcribed by polymerase II, and plays a critical role in pre-mRNA metabolism. Nrd1 contains an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a short arginine-, serine-, and glutamate-rich segment similar to the regions rich in RE and RS dipeptides (RE/RS domains) in many metazoan splicing factors, and a proline- and glutamine-rich C-terminal domain (P+Q domain) similar to domains found in several yeast hnRNPs. Disruption of NRD1 gene is lethal to yeast cells. Its N-terminal domain is sufficient for viability, which may facilitate interactions with RNA polymerase II where Nrd1 may function as an auxiliary factor. By contrast, the RRM, RE/RS domains, and P+Q domain are dispensable. Seb1 is an RNA-binding protein encoded by gene seb1 (for seven binding) from fission yeast S. pombe. It is essential for cell viability and bound directly to Rpb7 subunit of RNA polymerase II. Seb1 is involved in processing of polymerase II transcripts. It also contains one RRM motif and a region rich in arginine-serine dipeptides (RS domain).

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gi 34915990  31 RTLFVSGLPVDIKPRELYLLFRPFKGYEGSLIKLTARQpvGFVIFDSRAGAEAAKNALNGIRF 93
Cdd:cd12331   4 RTLFIGGVTLNMKEWDLRSVFKRFGEVQSVILNNSRRH--AFVKMYSRHEAENALQAMEKVPD 64

RNA recognition motif 1 (RRM1) found in vertebrate polypyrimidine tract-binding protein (PTB)-associated-splicing factor (PSF); This subgroup corresponds to the RRM1 of PSF, also termed proline- and glutamine-rich splicing factor, or 100 kDa DNA-pairing protein (POMp100), or 100 kDa subunit of DNA-binding p52/p100 complex, a multifunctional protein that mediates diverse activities in the cell. It is ubiquitously expressed and highly conserved in vertebrates. PSF binds not only RNA but also both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) and facilitates the renaturation of complementary ssDNAs. Besides, it promotes the formation of D-loops in superhelical duplex DNA, and is involved in cell proliferation. PSF can also interact with multiple factors. It is an RNA-binding component of spliceosomes and binds to insulin-like growth factor response element (IGFRE). PSF functions as a transcriptional repressor interacting with Sin3A and mediating silencing through the recruitment of histone deacetylases (HDACs) to the DNA binding domain (DBD) of nuclear hormone receptors. Additionally, PSF is an essential pre-mRNA splicing factor and is dissociated from PTB and binds to U1-70K and serine-arginine (SR) proteins during apoptosis. PSF forms a heterodimer with the nuclear protein p54nrb, also known as non-POU domain-containing octamer-binding protein (NonO). The PSF/p54nrb complex displays a variety of functions, such as DNA recombination and RNA synthesis, processing, and transport. PSF contains two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), which are responsible for interactions with RNA and for the localization of the protein in speckles. It also contains an N-terminal region rich in proline, glycine, and glutamine residues, which may play a role in interactions recruiting other molecules.

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gi 34915990  33 LFVSGLPVDIKPRELYLLFRPFKgyEGSLIKLTARQPVGFVIFDSRAGAEAAKNALNGIrfdPENPQTLRLEF 105
Cdd:cd12587   4 LFVGNLPADITEDEFKRLFAKYG--EPGEVFINKGKGFGFIKLESRALAEIAKAELDDT---PMRGRQLRVRF 71

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

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gi 34915990  32 TLFVSGLPVDIKPRELYLLFRPF-----------------KGYegslikltarqpvGFVIFDSRAGAEAAKNALNGIRFD 94
Cdd:COG0724   3 KIYVGNLPYSVTEEDLRELFSEYgevtsvklitdretgrsRGF-------------GFVEMPDDEEAQAAIEALNGAELM 69

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor 3 (SRSF3) and similar proteins; This subfamily corresponds to the RRM of two serine/arginine (SR) proteins, serine/arginine-rich splicing factor 3 (SRSF3) and serine/arginine-rich splicing factor 7 (SRSF7). SRSF3, also termed pre-mRNA-splicing factor SRp20, modulates alternative splicing by interacting with RNA cis-elements in a concentration- and cell differentiation-dependent manner. It is also involved in termination of transcription, alternative RNA polyadenylation, RNA export, and protein translation. SRSF3 is critical for cell proliferation, and tumor induction and maintenance. It can shuttle between the nucleus and cytoplasm. SRSF7, also termed splicing factor 9G8, plays a crucial role in both constitutive splicing and alternative splicing of many pre-mRNAs. Its localization and functions are tightly regulated by phosphorylation. SRSF7 is predominantly present in the nuclear and can shuttle between nucleus and cytoplasm. It cooperates with the export protein, Tap/NXF1, helps mRNA export to the cytoplasm, and enhances the expression of unspliced mRNA. Moreover, SRSF7 inhibits tau E10 inclusion through directly interacting with the proximal downstream intron of E10, a clustering region for frontotemporal dementia with Parkinsonism (FTDP) mutations. Both SRSF3 and SRSF7 contain a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal RS domain rich in serine-arginine dipeptides. The RRM domain is involved in RNA binding, and the RS domain has been implicated in protein shuttling and protein-protein interactions.

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gi 34915990  33 LFVSGLPVDIKPRELYLLFRPFkgyeGSLIKL-TARQPVG--FVIFDSRAGAEAAKNALNGIRFdpeNPQTLRLEFAK 107
Cdd:cd12373   2 VYVGNLGPRVTKRELEDAFEKY----GPLRNVwVARNPPGfaFVEFEDPRDAEDAVRALDGRRI---CGSRVRVELSR 72

RNA recognition motif 4 (RRM4) found in yeast multiple RNA-binding domain-containing protein 1 (MRD1) and similar proteins; This subfamily corresponds to the RRM4 of MRD1which is encoded by a novel yeast gene MRD1 (multiple RNA-binding domain). It is well-conserved in yeast and its homologs exist in all eukaryotes. MRD1 is present in the nucleolus and the nucleoplasm. It interacts with the 35 S precursor rRNA (pre-rRNA) and U3 small nucleolar RNAs (snoRNAs). MRD1 is essential for the initial processing at the A0-A2 cleavage sites in the 35 S pre-rRNA. It contains 5 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), which may play an important structural role in organizing specific rRNA processing events.

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gi 34915990  32 TLFVSGLPVDIKPRELYLLFRPFKGYEGSLIKLTA--RQP-------VGFVIFDSRAGAEAAKNALNGIRFD 94
Cdd:cd12319   2 TLFVKNLNFSTTNQHLTDVFKHLDGFVFARVKTKPdpKRPgktlsmgFGFVGFKTKEQAQAALKAMDGFVLD 73

RNA recognition motif (RRM) found in yeast mitochondrial escape protein 2 (Yme2p) and similar proteins; This subfamily corresponds to the RRM of Yme2p, also termed protein RNA12, an inner mitochondrial membrane protein that plays a critical role in mitochondrial DNA transactions. It may serve as a mediator of nucleoid structure and number in mitochondria of the yeast Saccharomyces cerevisiae. Yme2p contains an exonuclease domain, an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal domain.

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gi 34915990  31 RTLFVSGLPVDIKPRELYLLFRPFkgyeGSLIKLTARQP-----VGFVIFDSRAGAEAAKNALNGIRFDPENpQTLRLEF 105
Cdd:cd12433   5 RTIRVEFEGPELSQEELYSLFRPY----GRINDITPPPPdslprYATVTFRRIRGAIAAKNCLHGYVVNEGG-TRLRIQY 79