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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 23296313 153 PNNILFIHNLPIETNSMMLQLLFEQYPGFKEIRMIEaKPGIAFVEYEDDVQSSMAMQALQGFKITPQNPMVVS 225
Cdd:cd12247   1 PNKILFLQNLPEETTKEMLEMLFNQFPGFKEVRLVP-RRGIAFVEFETEEQATVALQALQGFKITPGHAMKIS 72

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 23296313 153 PNNILFIHNLPIETNSMMLQLLFEQYPGFKEIRMIEaKPGIAFVEYEDDVQSSMAMQALQGFKITPQNPMVVS 225
Cdd:cd12247   1 PNKILFLQNLPEETTKEMLEMLFNQFPGFKEVRLVP-RRGIAFVEFETEEQATVALQALQGFKITPGHAMKIS 72

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 23296313   157 LFIHNLPIETNSMMLQLLFEQYPGFKEIRMI----EAKPGIAFVEYEDDVQSSMAMQALQGFKI 216
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVrdetGRSKGFAFVEFEDEEDAEKAIEALNGKEL 64

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 23296313    12 IYIKHINEKIKKEELKRslycLFSQFGRL--LDVVALKTPKLRGQAWVVFTEVTAASNAVRQMQNFPFYDKPMR 83
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKD----LFSKFGPIksIRLVRDETGRSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 23296313 157 LFIHNLPIETNSMMLQLLFEQYPGFKEIRMI------EAKpGIAFVEYEDDVQSSMAMQALQGFKITpQNPMVVSFAK 228
Cdd:COG0724   4 IYVGNLPYSVTEEDLRELFSEYGEVTSVKLItdretgRSR-GFGFVEMPDDEEAQAAIEALNGAELM-GRTLKVNEAR 79

RNA recognition motif 1 in U2 small nuclear ribonucleoprotein B" (U2B") and similar proteins; This subgroup corresponds to the RRM1 of U2B" (also termed U2 snRNP B") a unique protein that comprises the U2 snRNP. It was initially identified as binding to stem-loop IV (SLIV) at the 3' end of U2 snRNA. 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. In addition, the nuclear transport of U2B" is independent of U2 snRNA binding. U2B" contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). It also contains a nuclear localization signal (NLS) in the central domain. However, nuclear import of U2B'' does not depend on this NLS. The N-terminal RRM is sufficient to direct U2B" to the nucleus.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23296313   9 NQSIYIKHINEKIKKEELKRSLYCLFSQFGRLLDVVALKTPKLRGQAWVVFTEVTAASNAVRQMQNFPFYDKPMRIQYAK 88
Cdd:cd12478   1 NHTIYINNINDKIKKEELKRSLYALFSQFGHVVDIVALKTMKMRGQAFVIFKELSSATNALRQLQGFPFYGKPMRIQYAK 80

                        90
                ....*....|.
gi 23296313  89 SKSDYVTKAEG 99
Cdd:cd12478  81 TDSDIVSKMRG 91

RNA recognition motif 1 (RRM1) found in vertebrate U1 small nuclear ribonucleoprotein A (U1A); This subgroup corresponds to the RRM1 of U1A (also termed U1 snRNP A or U1-A), 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 and it also shuttles between the nucleus and the cytoplasm independently of interactions with U1 snRNA. U1A may be involved in RNA 3'-end processing, specifically cleavage, splicing and polyadenylation, through interacting with a large number of non-snRNP proteins, including polypyrimidine tract binding protein (PTB), polypyrimidine-tract binding protein-associated factor (PSF), and non-POU-domain-containing, octamer-binding (NONO), DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 (DDX5). It also binds to a flavivirus NS5 protein and plays an important role in virus replication. U1A contains two RNA recognition motifs (RRMs); the N-terminal RRM (RRM1) binds tightly and specifically to the U1 snRNA SLII and its own 3'-UTR, while in contrast, the C-terminal RRM (RRM2) does not appear to associate with any RNA and may be free to bind other proteins. U1A also contains a proline-rich region, and a nuclear localization signal (NLS) in the central domain that is responsible for its nuclear import.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23296313   8 PNQSIYIKHINEKIKKEELKRSLYCLFSQFGRLLDVVALKTPKLRGQAWVVFTEVTAASNAVRQMQNFPFYDKPMRIQYA 87
Cdd:cd12477   2 PNHTIYINNLNEKIKKDELKKSLHAIFSRFGQILDILVSRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQYA 81

                ....*
gi 23296313  88 KSKSD 92
Cdd:cd12477  82 KTDSD 86

RNA recognition motif 2 (RRM2) found in vertebrate U2 small nuclear ribonucleoprotein B" (U2B"); This subgroup corresponds to the RRM1 of U2B" (also termed U2 snRNP B"), a unique protein that comprises the U2 snRNP. It was initially identified to bind to stem-loop IV (SLIV) at the 3' end of U2 snRNA. 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 of U2 snRNA binding. U2B" contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). It also contains a nuclear localization signal (NLS) in the central domain. However, nuclear import of U2B'' does not depend on this NLS. The N-terminal RRM is sufficient to direct U2B" to the nucleus.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 23296313 152 PPNNILFIHNLPIETNSMMLQLLFEQYPGFKEIRMIEAKPGIAFVEYEDDVQSSMAMQALQGFKITPQNPMVVSFAKK 229
Cdd:cd12481   3 PPNYILFLNNLPEETNEMMLSMLFNQFPGFKEVRLVPGRHDIAFVEFENEAQAGAARDALQGFKITPSHAMKITYAKK 80

RNA recognition motif 2 (RRM2) found in vertebrate U1 small nuclear ribonucleoprotein A (U1 snRNP A or U1-A or U1A); This subgroup corresponds to the RRM2 of U1A (also termed U1 snRNP A or U1-A), 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. U1A may be involved in RNA 3'-end processing, specifically cleavage, splicing and polyadenylation, through interacting with a large number of non-snRNP proteins, including polypyrimidine tract binding protein (PTB), polypyrimidine-tract binding protein-associated factor (PSF), and non-POU-domain-containing, octamer-binding (NONO), DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 (DDX5). U1A also binds to a flavivirus NS5 protein and plays an important role in virus replication. It contains two RNA recognition motifs (RRMs); the N-terminal RRM (RRM1) binds tightly and specifically to the U1 snRNA SLII and its own 3'-UTR, while in contrast, the C-terminal RRM (RRM2) does not appear to associate with any RNA and it may be free for binding other proteins. U1A also contains a proline-rich region, and a nuclear localization signal (NLS) in the central domain that is responsible for its nuclear import.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23296313 142 PFQPSGQDtmPPNNILFIHNLPIETNSMMLQLLFEQYPGFKEIRMIEAKPGIAFVEYEDDVQSSMAMQALQGFKITPQNP 221
Cdd:cd12480   1 PPQPVSEN--PPNHILFLTNLPEETNELMLSMLFNQFPGFKEVRLVPGRHDIAFVEFDNEVQAGAAREALQGFKITQSNA 78

                ....*...
gi 23296313 222 MVVSFAKK 229
Cdd:cd12480  79 MKISFAKK 86

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 23296313 153 PNNILFIHNLPIETNSMMLQLLFEQYPGFKEIRMI--EAKPG----IAFVEYEDDVQSSMAMQALQGFKITPQNP----M 222
Cdd:cd21618   2 ASSTLYVEGLPLDATEREVAHIFRPFPGFKSVRLVpkEGKRGrklvLCFVDFADAQQAAAALETLQGYRLDEDDSdskgL 81

                ....*.
gi 23296313 223 VVSFAK 228
Cdd:cd21618  82 RISFAR 87

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 23296313     11 SIYIKHINEKIKKEELKRslycLFSQFGRLLDVVALK---TPKLRGQAWVVFTEVTAASNAVRQMQNFPFYDKPMRI 84
Cdd:smart00360   1 TLFVGNLPPDTTEEELRE----LFSKFGKVESVRLVRdkeTGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 23296313   157 LFIHNLPIETNSMMLQLLFEQYPGFKEIRMI----EAKPGIAFVEYEDDVQSSMAMQALQGFKI 216
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVrdetGRSKGFAFVEFEDEEDAEKAIEALNGKEL 64

RNA recognition motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 23296313    157 LFIHNLPIETNSMMLQLLFEQYPGFKEIRMIEAKP-----GIAFVEYEDDVQSSMAMQALQGFKI 216
Cdd:smart00360   2 LFVGNLPPDTTEEELRELFSKFGKVESVRLVRDKEtgkskGFAFVEFESEEDAEKALEALNGKEL 66

RNA recognition motif 2 (RRM2) found in yeast meiotic activator RIM4 and similar proteins; This subfamily corresponds to the RRM2 of RIM4, also termed regulator of IME2 protein 4, a putative RNA binding protein that is expressed at elevated levels early in meiosis. It functions as a meiotic activator required for both the IME1- and IME2-dependent pathways of meiotic gene expression, as well as early events of meiosis, such as meiotic division and recombination, in Saccharomyces cerevisiae. RIM4 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The family also includes a putative RNA-binding protein termed multicopy suppressor of sporulation protein Msa1. It is a putative RNA-binding protein encoded by a novel gene, msa1, from the fission yeast Schizosaccharomyces pombe. Msa1 may be involved in the inhibition of sexual differentiation by controlling the expression of Ste11-regulated genes, possibly through the pheromone-signaling pathway. Like RIM4, Msa1 also contains two RRMs, both of which are essential for the function of Msa1.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 23296313  11 SIYIKHINEKIKKEELKRslycLFSQFGRLLDVVALKTPKLRGQ-AWVVFTEVTAASNAVRQMQNFPFYDKPMRIQY 86
Cdd:cd12454   5 SIFVGQLDPKTTDSELFR----RFSKYGKIVDCKLIKRPEPVNAfAFLRFESEEAAEAAVEEENHSEFLNKQIRVQK 77

RNA recognition motif (RRM) found in pre-mRNA branch site protein p14 (SF3B14) and similar proteins; This subfamily corresponds to the RRM of SF3B14 (also termed p14), a 14 kDa protein subunit of SF3B which is a multiprotein complex that is an integral part of the U2 small nuclear ribonucleoprotein (snRNP) and the U11/U12 di-snRNP. SF3B is essential for the accurate excision of introns from pre-messenger RNA and has been involved in the recognition of the pre-mRNA's branch site within the major and minor spliceosomes. SF3B14 associates directly with another SF3B subunit called SF3B155. It is also present in both U2- and U12-dependent spliceosomes and may contribute to branch site positioning in both the major and minor spliceosome. Moreover, SF3B14 interacts directly with the pre-mRNA branch adenosine early in spliceosome assembly and within the fully assembled spliceosome. SF3B14 contains one well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 23296313 154 NNILFIHNLPIETNSMMLQLLFEQYPGFKEIRMIEAKP--GIAFVEYEDDVQSSMAMQALQGF 214
Cdd:cd12241   2 NRILYVRNLPYKISSEELYDLFGKYGAIRQIRIGNTKEtrGTAFVVYEDIFDAKNACDHLSGF 64

RNA recognition motif 1 (RRM1) found in yeast meiotic activator RIM4 and similar proteins; This subfamily corresponds to the RRM1 of RIM4, also termed regulator of IME2 protein 4, a putative RNA binding protein that is expressed at elevated levels early in meiosis. It functions as a meiotic activator required for both the IME1- and IME2-dependent pathways of meiotic gene expression, as well as early events of meiosis, such as meiotic division and recombination, in Saccharomyces cerevisiae. RIM4 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The family also includes a putative RNA-binding protein termed multicopy suppressor of sporulation protein Msa1. It is a putative RNA-binding protein encoded by a novel gene, msa1, from the fission yeast Schizosaccharomyces pombe. Msa1 may be involved in the inhibition of sexual differentiation by controlling the expression of Ste11-regulated genes, possibly through the pheromone-signaling pathway. Like RIM4, Msa1 also contains two RRMs, both of which are essential for the function of Msa1.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23296313   8 PNQSIYIKHINEKIKKEELKRSLYCLFSQFGRLLDVVALKTPKLRGQAWVVFTEVTAASNAVRQMQNFPFYDKPMRIQYA 87
Cdd:cd12453   1 PSACLFVASLSSARSDEELCAAVTNHFSKWGELLNVKVLKDWSNRPYAFVQYTNTEDAKNALVNGHNTLLDGRHLRVEKA 80

                .
gi 23296313  88 K 88
Cdd:cd12453  81 K 81

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor SRSF10, SRSF12 and similar proteins; This subfamily corresponds to the RRM of SRSF10 and SRSF12. SRSF10, also termed 40 kDa SR-repressor protein (SRrp40), or FUS-interacting serine-arginine-rich protein 1 (FUSIP1), or splicing factor SRp38, or splicing factor, arginine/serine-rich 13A (SFRS13A), or TLS-associated protein with Ser-Arg repeats (TASR). It is a serine-arginine (SR) protein that acts as a potent and general splicing repressor when dephosphorylated. It mediates global inhibition of splicing both in M phase of the cell cycle and in response to heat shock. SRSF10 emerges as a modulator of cholesterol homeostasis through the regulation of low-density lipoprotein receptor (LDLR) splicing efficiency. It also regulates cardiac-specific alternative splicing of triadin pre-mRNA and is required for proper Ca2+ handling during embryonic heart development. In contrast, the phosphorylated SRSF10 functions as a sequence-specific splicing activator in the presence of a nuclear cofactor. It activates distal alternative 5' splice site of adenovirus E1A pre-mRNA in vivo. Moreover, SRSF10 strengthens pre-mRNA recognition by U1 and U2 snRNPs. SRSF10 localizes to the nuclear speckles and can shuttle between nucleus and cytoplasm. SRSF12, also termed 35 kDa SR repressor protein (SRrp35), or splicing factor, arginine/serine-rich 13B (SFRS13B), or splicing factor, arginine/serine-rich 19 (SFRS19), is a serine/arginine (SR) protein-like alternative splicing regulator that antagonizes authentic SR proteins in the modulation of alternative 5' splice site choice. For instance, it activates distal alternative 5' splice site of the adenovirus E1A pre-mRNA in vivo. Both, SRSF10 and SRSF12, contain a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C-terminal RS domain rich in serine-arginine dipeptides.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23296313  11 SIYIKHINEKIKKEELKRslycLFSQFGRLLDV---VALKTPKLRGQAWVVFTEVTAASNAVRQMQNFPFYDKPMRIQYA 87
Cdd:cd12312   2 SLFVRNVADDTRPDDLRR----EFGRYGPIVDVyipLDFYTRRPRGFAYIQFEDVRDAEDALYYLDRTRFLGREIEIQFA 77

                .
gi 23296313  88 K 88
Cdd:cd12312  78 Q 78

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor 10 (SRSF10) and similar proteins; This subgroup corresponds to the RRM of SRSF10, also termed 40 kDa SR-repressor protein (SRrp40), or FUS-interacting serine-arginine-rich protein 1 (FUSIP1), or splicing factor SRp38, or splicing factor, arginine/serine-rich 13A (SFRS13A), or TLS-associated protein with Ser-Arg repeats (TASR). SRSF10 is a serine-arginine (SR) protein that acts as a potent and general splicing repressor when dephosphorylated. It mediates global inhibition of splicing both in M phase of the cell cycle and in response to heat shock. SRSF10 emerges as a modulator of cholesterol homeostasis through the regulation of low-density lipoprotein receptor (LDLR) splicing efficiency. It also regulates cardiac-specific alternative splicing of triadin pre-mRNA and is required for proper Ca2+ handling during embryonic heart development. In contrast, the phosphorylated SRSF10 functions as a sequence-specific splicing activator in the presence of a nuclear cofactor. It activates distal alternative 5' splice site of adenovirus E1A pre-mRNA in vivo. Moreover, SRSF10 strengthens pre-mRNA recognition by U1 and U2 snRNPs. SRSF10 localizes to the nuclear speckles and can shuttle between nucleus and cytoplasm. It contains a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C-terminal RS domain rich in serine-arginine dipeptides.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23296313   7 PPNQSIYIKHINEKIKKEELKRSlyclFSQFGRLLDV---VALKTPKLRGQAWVVFTEVTAASNAVRQMQNFPFYDKPMR 83
Cdd:cd12559   3 PPNTSLFVRNVADDTRSEDLRRE----FGRYGPIVDVyvpLDFYTRRPRGFAYVQFEDVRDAEDALHNLDRKWICGRQIE 78

                ....*
gi 23296313  84 IQYAK 88
Cdd:cd12559  79 IQFAQ 83

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
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 23296313 157 LFIHNLPIETNSMMLQLLFEQYPGFKEIRMIEAKpGIAFVEYEDDVQSSMAMQALQGF 214
Cdd:cd12340   2 LFVRPFPPDTSESAIREIFSPYGPVKEVKMLSDS-NFAFVEFEELEDAIRAKDSVHGR 58

RNA recognition motif 2 (RRM2) found in RNA-binding protein 28 (RBM28) and similar proteins; This subfamily corresponds to the RRM2 of RBM28 and Nop4p. RBM28 is a specific nucleolar component of the spliceosomal small nuclear ribonucleoproteins (snRNPs), possibly coordinating their transition through the nucleolus. It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), and may play a role in the maturation of both small nuclear and ribosomal RNAs. RBM28 has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an extremely acidic region between RRM2 and RRM3. The family also includes nucleolar protein 4 (Nop4p or Nop77p) encoded by YPL043W from Saccharomyces cerevisiae. It is an essential nucleolar protein involved in processing and maturation of 27S pre-rRNA and biogenesis of 60S ribosomal subunits. Nop4p also contains four RRMs.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23296313  20 KIKKEELKRslycLFSQFGRLLDVVALKTP--KLRGQAWVVFTEVTAASNAVRQMQNFPFYDKPMRIQYA 87
Cdd:cd12414  10 KCTEDDLKK----LFSKFGKVLEVTIPKKPdgKLRGFAFVQFTNVADAAKAIKGMNGKKIKGRPVAVDWA 75

RNA recognition motif (RRM) found in Zinc finger CCHC-type and RNA-binding motif-containing protein 1 (ZCRB1) and similar proteins; This subfamily corresponds to the RRM of ZCRB1, also termed MADP-1, or U11/U12 small nuclear ribonucleoprotein 31 kDa protein (U11/U12 snRNP 31 or U11/U12-31K), a novel multi-functional nuclear factor, which may be involved in morphine dependence, cold/heat stress, and hepatocarcinoma. It is located in the nucleoplasm, but outside the nucleolus. ZCRB1 is one of the components of U11/U12 snRNPs that bind to U12-type pre-mRNAs and form a di-snRNP complex, simultaneously recognizing the 5' splice site and branchpoint sequence. ZCRB1 is characterized by an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a CCHC-type Zinc finger motif. In addition, it contains core nucleocapsid motifs, and Lys- and Glu-rich domains.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 23296313  30 LYCLFSQFGRLLDVVALK---TPKLRGQAWVVFTEVTAASNAVRQMQN 74
Cdd:cd12393  18 LHQIFSKYGKVVKVTILKdkeTRKSKGVAFVLFLDRESAHNAVRAMNN 65

RNA recognition motif 1 (RRM1) found in plant Mei2-like proteins; This subgroup corresponds to the RRM1 of Mei2-like proteins that represent an ancient eukaryotic RNA-binding proteins family. Their corresponding Mei2-like genes appear to have arisen early in eukaryote evolution, been lost from some lineages such as Saccharomyces cerevisiae and metazoans, and diversified in the plant lineage. The plant Mei2-like genes may function in cell fate specification during development, rather than as stimulators of meiosis. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The C-terminal RRM (RRM3) is unique to Mei2-like proteins and it is highly conserved between plants and fungi. Up to date, the intracellular localization, RNA target(s), cellular interactions and phosphorylation states of Mei2-like proteins in plants remain unclear.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 23296313 156 ILFIHNLPIETNSMMLQLLFEQypgFKEIRMI--EAKP-GIAFVEYEDDVQSSMAMQALQG 213
Cdd:cd12524   3 TLFVRNINSSVEDEELRALFEQ---FGEIRTLytACKHrGFIMVSYYDIRAAQSAKRALQG 60

RNA recognition motif 3 (RRM3) found in ribonucleoprotein PTB-binding raver-1, raver-2 and similar proteins; This subfamily corresponds to the RRM3 of raver-1 and raver-2. Raver-1 is a ubiquitously expressed heterogeneous nuclear ribonucleoprotein (hnRNP) that serves as a co-repressor of the nucleoplasmic splicing repressor polypyrimidine tract-binding protein (PTB)-directed splicing of select mRNAs. It shuttles between the cytoplasm and the nucleus and can accumulate in the perinucleolar compartment, a dynamic nuclear substructure that harbors PTB. Raver-1 also modulates focal adhesion assembly by binding to the cytoskeletal proteins, including alpha-actinin, vinculin, and metavinculin (an alternatively spliced isoform of vinculin) at adhesion complexes, particularly in differentiated muscle tissue. Raver-2 is a novel member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. It shows high sequence homology to raver-1. Raver-2 exerts a spatio-temporal expression pattern during embryogenesis and is mainly limited to differentiated neurons and glia cells. Although it displays nucleo-cytoplasmic shuttling in heterokaryons, raver2 localizes to the nucleus in glia cells and neurons. Raver-2 can interact with PTB and may participate in PTB-mediated RNA-processing. However, there is no evidence indicating that raver-2 can bind to cytoplasmic proteins. Both, raver-1 and raver-2, contain three N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two putative nuclear localization signals (NLS) at the N- and C-termini, a central leucine-rich region, and a C-terminal region harboring two [SG][IL]LGxxP motifs. They binds to RNA through the RRMs. In addition, the two [SG][IL]LGxxP motifs serve as the PTB-binding motifs in raver1. However, raver-2 interacts with PTB through the SLLGEPP motif only.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 23296313 157 LFIHNLPIE-TNSMMLQLLFEQY--PGFKEIRMIEAKP-GIAFVEYEDDVQSSMAMQALQGFKITPQnPMVVSF 226
Cdd:cd12390   5 LFVDRLPKDfRDGSELRKLFSQVgkPTFCQLAMGNGVPrGFAFVEFASAEDAEEAQQLLNGHDLQGS-PIRVSF 77

RNA recognition motif 4 (RRM4) found in SMART/HDAC1-associated repressor protein (SHARP) and similar proteins; This subfamily corresponds to the RRM of SHARP, also termed Msx2-interacting protein (MINT), or SPEN homolog, is an estrogen-inducible transcriptional repressor that interacts directly with the nuclear receptor corepressor SMRT, histone deacetylases (HDACs) and components of the NuRD complex. SHARP recruits HDAC activity and binds to the steroid receptor RNA coactivator SRA through four conserved N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), further suppressing SRA-potentiated steroid receptor transcription activity. Thus, SHARP has the capacity to modulate both liganded and nonliganded nuclear receptors. SHARP also has been identified as a component of transcriptional repression complexes in Notch/RBP-Jkappa signaling pathways. In addition to the N-terminal RRMs, SHARP possesses a C-terminal SPOC domain (Spen paralog and ortholog C-terminal domain), which is highly conserved among Spen proteins.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 23296313   8 PNQSIYIKHINEKIKKEELKRSlyclFSQFGRLLDVValkTPKLRGQAWVVFTEVTAASNAVRQMQNFPFYDKPMRIQY 86
Cdd:cd12351   6 PTNCVWLDGLSENVTEQYLTRH----FCRYGPVVKVV---IDRQKGMALVLYDEVECAQAAVKETKGRKIGGRKIQVDF 77

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 23296313   9 NQSIYIKHINEKIKKEELKRslycLFSQFGRLLDVvalKTPKLRGQAWVVFTEVTAASNAVRQMQNFPFYDKPMRI 84
Cdd:cd12346   1 NTTVFVGGLDPNVTEEDLRV----LFGPFGEIVYV---KIPPGKGCGFVQFVNRASAEAAIQKLQGTPIGGSRIRL 69

hnRNP-L/PTB/hephaestus splicing factor family; Included in this family of heterogeneous ribonucleoproteins are PTB (polypyrimidine tract binding protein) and hnRNP-L. These proteins contain four RNA recognition motifs (rrm: pfam00067).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23296313    30 LYCLFSQFGRLLDVVALKTPKLRgQAWVVFTEVTAASNAVRQMQNFPFYDK--PMRIQYAKSKS-----------DYVTK 96
Cdd:TIGR01649 113 LYQIFNPYGKVLRIVTFTKNNVF-QALVEFESVNSAQHAKAALNGADIYNGccTLKIEYAKPTRlnvkyndddsrDYTNP 191

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23296313    97 AegsfVPKEKKMKQEEKVERKRHAEETQQPSM--PNGATTQNGMPVP------------------------PFQPSGQDT 150
Cdd:TIGR01649 192 D----LPGRRDPGLDQTHRQRQPALLGQHPSSygHDGYSSHGGPLAPlaggdrmgpphgppsryrpayeaaPLAPAISSY 267

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 23296313   151 MP----PNNILFIHNL-PIETNSMMLQLLFEQYPGFKEIRMIEAKPGIAFVEYEDDVQSSMAMQALQGFKI 216
Cdd:TIGR01649 268 GPagggPGSVLMVSGLhQEKVNCDRLFNLFCVYGNVERVKFMKNKKETALIEMADPYQAQLALTHLNGVKL 338

RNA recognition motif 1 (RRM1) found in RNA-binding protein 28 (RBM28) and similar proteins; This subfamily corresponds to the RRM1 of RBM28 and Nop4p. RBM28 is a specific nucleolar component of the spliceosomal small nuclear ribonucleoproteins (snRNPs), possibly coordinating their transition through the nucleolus. It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), and may play a role in the maturation of both small nuclear and ribosomal RNAs. RBM28 has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an extremely acidic region between RRM2 and RRM3. The family also includes nucleolar protein 4 (Nop4p or Nop77p) encoded by YPL043W from Saccharomyces cerevisiae. It is an essential nucleolar protein involved in processing and maturation of 27S pre-rRNA and biogenesis of 60S ribosomal subunits. Nop4p also contains four RRMs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23296313  11 SIYIKHINEKIKKEELKRslycLFSQFG--RLLDVVALK-TPKLRGQAWVVFTEVTAASNAVRQMQNFPFYDKPMRIQYA 87
Cdd:cd12413   1 TLFVRNLPYDTTDEQLEE----LFSDVGpvKRCFVVKDKgKDKCRGFGYVTFALAEDAQRALEEVKGKKFGGRKIKVELA 76

                ...
gi 23296313  88 KSK 90
Cdd:cd12413  77 KKK 79

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23296313 157 LFIHNLPIETNSMMLQLLFEQYPGFKEIRmIEAKP-----------GIAFVEYEDDVQSSMAMQALQGFKITPQNpMVVS 225
Cdd:cd12319   3 LFVKNLNFSTTNQHLTDVFKHLDGFVFAR-VKTKPdpkrpgktlsmGFGFVGFKTKEQAQAALKAMDGFVLDGHK-LEVK 80

                ....
gi 23296313 226 FAKK 229
Cdd:cd12319  81 FSHR 84

RNA recognition motif (RRM) found in vertebrate RNA-binding protein with multiple splicing (RBP-MS); This subfamily corresponds to the RRM of RBP-MS, also termed heart and RRM expressed sequence (hermes), an RNA-binding proteins found in various vertebrate species. It contains an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). RBP-MS physically interacts with Smad2, Smad3 and Smad4 and plays a role in regulation of Smad-mediated transcriptional activity. In addition, RBP-MS may be involved in regulation of mRNA translation and localization during Xenopus laevis development.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23296313 157 LFIHNLPIETNSMMLQLLFEQYPGFKE--IRMIEAKPgIAFVEYEDDVQSSMAMQALQGFKITPQNPMVV 224
Cdd:cd12682   4 LFVSGLPLDIKPRELYLLFRPFKGYEGslIKLTSKQP-VGFVSFDSRSEAEAAKNALNGIRFDPEIPQTL 72

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 23296313  11 SIYIKHINEKIKKEELKRSlyclFSQFGRLLDVvalKTPKLRGQAWVVFTEVTAASNAVRQMQNFPFYDKPMR 83
Cdd:cd12354   2 TVYVGNITKGLTEALLQQT----FSPFGQILEV---RVFPDKGYAFIRFDSHEAATHAIVSVNGTIINGQAVK 67

RNA recognition motif (RRM) found in the Aly/REF family; This subfamily corresponds to the RRM of Aly/REF family which includes THO complex subunit 4 (THOC4, also termed Aly/REF), S6K1 Aly/REF-like target (SKAR, also termed PDIP3 or PDIP46) and similar proteins. THOC4 is an mRNA transporter protein with a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). It is involved in RNA transportation from the nucleus, and was initially identified as a transcription coactivator of LEF-1 and AML-1 for the TCRalpha enhancer function. In addition, THOC4 specifically binds to rhesus (RH) promoter in erythroid, and might be a novel transcription cofactor for erythroid-specific genes. SKAR shows high sequence homology with THOC4 and possesses one RRM as well. SKAR is widely expressed and localizes to the nucleus. It may be a critical player in the function of S6K1 in cell and organism growth control by binding the activated, hyperphosphorylated form of S6K1 but not S6K2. Furthermore, SKAR functions as a protein partner of the p50 subunit of DNA polymerase delta. In addition, SKAR may have particular importance in pancreatic beta cell size determination and insulin secretion.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 23296313  12 IYIKHINEKIKKEELKRslycLFSQFGRLLDV--VALKTPKLRGQAWVVFTEVTAASNAVRQMQNFPFYDKPMRIQ 85
Cdd:cd12418   3 VRVSNLHPDVTEEDLRE----LFGRVGPVKSVkiNYDRSGRSTGTAYVVFERPEDAEKAIKQFDGVLLDGQPMKVE 74

RNA recognition motif 2 (RRM2) found in CUGBP Elav-like family member CELF-1, CELF-2 and similar proteins; This subgroup corresponds to the RRM2 of CELF-1 (also termed BRUNOL-2, or CUG-BP1, or EDEN-BP), CELF-2 (also termed BRUNOL-3, or ETR-3, or CUG-BP2, or NAPOR), both of which belong to the CUGBP1 and ETR-3-like factors (CELF) or BRUNOL (Bruno-like) family of RNA-binding proteins that have been implicated in the regulation of pre-mRNA splicing and in the control of mRNA translation and deadenylation. CELF-1 is strongly expressed in all adult and fetal tissues tested. Human CELF-1 is a nuclear and cytoplasmic RNA-binding protein that regulates multiple aspects of nuclear and cytoplasmic mRNA processing, with implications for onset of type 1 myotonic dystrophy (DM1), a neuromuscular disease associated with an unstable CUG triplet expansion in the 3'-UTR (3'-untranslated region) of the DMPK (myotonic dystrophy protein kinase) gene; it preferentially targets UGU-rich mRNA elements. It has been shown to bind to a Bruno response element, a cis-element involved in translational control of oskar mRNA in Drosophila, and share sequence similarity to Bruno, the Drosophila protein that mediates this process. The Xenopus homolog embryo deadenylation element-binding protein (EDEN-BP) mediates sequence-specific deadenylation of Eg5 mRNA. It binds specifically to the EDEN motif in the 3'-untranslated regions of maternal mRNAs and targets these mRNAs for deadenylation and translational repression. CELF-1 contains 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 two N-terminal RRMs of EDEN-BP are necessary for the interaction with EDEN as well as a part of the linker region (between RRM2 and RRM3). Oligomerization of EDEN-BP is required for specific mRNA deadenylation and binding. CELF-2 is expressed in all tissues at some level, but highest in brain, heart, and thymus. It has been implicated in the regulation of nuclear and cytoplasmic RNA processing events, including alternative splicing, RNA editing, stability and translation. CELF-2 shares high sequence identity with CELF-1, but shows different binding specificity; it preferentially binds to sequences with UG repeats and UGUU motifs. It has been shown to bind to a Bruno response element, a cis-element involved in translational control of oskar mRNA in Drosophila, and share sequence similarity to Bruno, the Drosophila protein that mediates this process. It also binds to the 3'-UTR of cyclooxygenase-2 messages, affecting both translation and mRNA stability, and binds to apoB mRNA, regulating its C to U editing. CELF-2 also contains three highly conserved RRMs. It binds to RNA via the first two RRMs, which are also important for localization in the cytoplasm. The splicing activation or repression activity of CELF-2 on some specific substrates is mediated by RRM1/RRM2. Both, RRM1 and RRM2 of CELF-2, can activate cardiac troponin T (cTNT) exon 5 inclusion. In addition, CELF-2 possesses a typical arginine and lysine-rich nuclear localization signal (NLS) in the C-terminus, within RRM3.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23296313   9 NQSIYIKHINEKIKKEELKrslyCLFSQFGRLLDVVALKTPK--LRGQAWVVFTEVTAASNAVRQM---QNFPFYDKPMR 83
Cdd:cd12634   1 DRKLFIGMVSKKCNENDIR----VMFSPFGQIEECRILRGPDglSRGCAFVTFSTRAMAQNAIKAMhqsQTMEGCSSPIV 76

                ....
gi 23296313  84 IQYA 87
Cdd:cd12634  77 VKFA 80

RNA recognition motif 6 (RRM6) found in RNA-binding protein 19 (RBM19 or RBD-1) and RNA recognition motif 5 (RRM5) found in multiple RNA-binding domain-containing protein 1 (MRD1); This subfamily corresponds to the RRM6 of RBM19 and RRM5 of MRD1. RBM19, also termed RNA-binding domain-1 (RBD-1), is a nucleolar protein conserved in eukaryotes. It is 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). MRD1 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). It is essential for the initial processing at the A0-A2 cleavage sites in the 35 S pre-rRNA. MRD1 contains 5 conserved RRMs, which may play an important structural role in organizing specific rRNA processing events.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 23296313 155 NILFIHNLPIETNSMMLQLLFEQYPGFKEIRMiEAKP-----GIAFVEY--EDDVQSsmAMQALQG 213
Cdd:cd12320   1 TKLIVKNVPFEATRKEIRELFSPFGQLKSVRL-PKKFdgshrGFAFVEFvtKQEAQN--AMEALKS 63

RNA recognition motif (RRM) found in Saccharomyces cerevisiae nucleolar protein 6 (Nop6) and similar proteins; This subfamily corresponds to the RRM of Nop6, also known as Ydl213c, a component of 90S pre-ribosomal particles in yeast S. cerevisiae. It is enriched in the nucleolus and is required for 40S ribosomal subunit biogenesis. Nop6 is a non-essential putative RNA-binding protein with two N-terminal putative nuclear localisation sequences (NLS-1 and NLS-2) and an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). It binds to the pre-rRNA early during transcription and plays an essential role in pre-rRNA processing.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 23296313 155 NILFIHNLPIETNSMMLQLLFEQYPGFKEIRMI----EAKP-GIAFVEYEDDVQSSMAMQ----ALQGFKI 216
Cdd:cd12400   1 YILFVGNLPYDTTAEDLKEHFKKAGEPPSVRLLtdkkTGKSkGCAFVEFDNQKALQKALKlhhtSLGGRKI 71

RNA recognition motif 6 (RRM6) found in RNA-binding protein 19 (RBM19 or RBD-1) and RNA recognition motif 5 (RRM5) found in multiple RNA-binding domain-containing protein 1 (MRD1); This subfamily corresponds to the RRM6 of RBM19 and RRM5 of MRD1. RBM19, also termed RNA-binding domain-1 (RBD-1), is a nucleolar protein conserved in eukaryotes. It is 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). MRD1 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). It is essential for the initial processing at the A0-A2 cleavage sites in the 35 S pre-rRNA. MRD1 contains 5 conserved RRMs, which may play an important structural role in organizing specific rRNA processing events.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23296313  12 IYIKHINEKIKKEELKRslycLFSQFGRlldVVALKTPK-----LRGQAWVVFTEVTAASNAVRQMQNFPFYDKPMRIQY 86
Cdd:cd12320   3 LIVKNVPFEATRKEIRE----LFSPFGQ---LKSVRLPKkfdgsHRGFAFVEFVTKQEAQNAMEALKSTHLYGRHLVLEY 75

                .
gi 23296313  87 A 87
Cdd:cd12320  76 A 76

RNA recognition motif (RRM) found in cleavage stimulation factor subunit 2 (CSTF2), yeast ortholog mRNA 3'-end-processing protein RNA15 and similar proteins; This subfamily 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. The family also includes yeast ortholog mRNA 3'-end-processing protein RNA15 and similar proteins. RNA15 is a core subunit of cleavage factor IA (CFIA), an essential transcriptional 3'-end processing factor from Saccharomyces cerevisiae. RNA recognition by CFIA is mediated by an N-terminal RRM, which is contained in the RNA15 subunit of the complex. The RRM of RNA15 has a strong preference for GU-rich RNAs, mediated by a binding pocket that is entirely conserved in both yeast and vertebrate RNA15 orthologs.

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gi 23296313 155 NILFIHNLPIETNSMMLQLLFEQYPGFKEIRMIE----AKP-GIAFVEYEDDVQSSMAMQALQGFKI 216
Cdd:cd12398   1 RSVFVGNIPYDATEEQLKEIFSEVGPVVSFRLVTdretGKPkGYGFCEFRDAETALSAVRNLNGYEL 67

RNA recognition motif (RRM) found in THO complex subunit 4 (THOC4) and similar proteins; This subgroup corresponds to the RRM of THOC4, also termed transcriptional coactivator Aly/REF, or ally of AML-1 and LEF-1, or bZIP-enhancing factor BEF, an mRNA transporter protein with a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). It is involved in RNA transportation from the nucleus. THOC4 was initially identified as a transcription coactivator of LEF-1 and AML-1 for the TCRalpha enhancer function. In addition, THOC4 specifically binds to rhesus (RH) promoter in erythroid. It might be a novel transcription cofactor for erythroid-specific genes.

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gi 23296313  33 LFSQFGRLLD--VVALKTPKLRGQAWVVFTEVTAASNAVRQMQNFPFYDKPMRIQ 85
Cdd:cd12680  20 LFAEFGTLKKaaVHYDRSGRSLGTAEVVFERRADALKAMKQYNGVPLDGRPMKIQ 74