RNA recognition motif (RRM) found in ras GTPase-activating protein-binding protein 1 (G3BP1) and similar proteins; This subgroup corresponds to the RRM of G3BP1, also termed ATP-dependent DNA helicase VIII (DH VIII), or GAP SH3 domain-binding protein 1, which has been identified as a phosphorylation-dependent endoribonuclease that interacts with the SH3 domain of RasGAP, a multi-functional protein controlling Ras activity. The acidic RasGAP binding domain of G3BP1 harbors an arsenite-regulated phosphorylation site and dominantly inhibits stress granule (SG) formation. G3BP1 also contains an N-terminal nuclear transfer factor 2 (NTF2)-like domain, an RNA recognition motif (RRM domain), and an Arg-Gly-rich region (RGG-rich region, or arginine methylation motif). The RRM domain and RGG-rich region are canonically associated with RNA binding. G3BP1 co-immunoprecipitates with mRNAs. It binds to and cleaves the 3'-untranslated region (3'-UTR) of the c-myc mRNA in a phosphorylation-dependent manner. Thus, G3BP1 may play a role in coupling extra-cellular stimuli to mRNA stability. It has been shown that G3BP1 is a novel Dishevelled-associated protein that is methylated upon Wnt3a stimulation and that arginine methylation of G3BP1 regulates both Ctnnb1 mRNA and canonical Wnt/beta-catenin signaling. Furthermore, G3BP1 can be associated with the 3'-UTR of beta-F1 mRNA in cytoplasmic RNA-granules, demonstrating that G3BP1 may specifically repress the translation of the transcript.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38327552 337 PDSHQLFIGNLPHEVDKSELKDFFQSYGNVVELRINSGGKLPNFGFVVFDDSEPVQKVLSNRPIMFRGEVRLNVEEKKTR 416
Cdd:cd12463   1 PDSHQLFVGNLPHDVDKSELKEFFQGYGNVVELRINSGGKLPNFGFVVFDDPEPVQKILSNRPIKFRGEVRLNVEEKKTR 80

Neuroendocrine-specific golgi protein P55 (NESP55); This family consists of several mammalian neuroendocrine-specific golgi protein P55 (NESP55) sequences. NESP55 is a novel member of the chromogranin family and is a soluble, acidic, heat-stable secretory protein that is expressed exclusively in endocrine and nervous tissues, although less widely than chromogranins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38327552   212 EEKPE--PVLE-ETAPEDAQKSSSPAPADIAQTVQEDLRTFSwasVTSKNLPPSGAVPVTGIP--PHVVKVPASQP---- 282
Cdd:pfam06390 137 ETEPDtaPTTEpETEPEDEPGPVVPKGATFHQSLTERLHALK---LQSADASPRRAPPSTQEPesAREGEEPERGPldkd 213

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 38327552   283 ------RPESKPESQIPPQR--PQRDQRVREQRINIPPQRGPRPIR 320
Cdd:pfam06390 214 prdpeeEEEEKEEEKQQPHRckPKKPARRRDPSPESPPKKGAIPIR 259

RNA recognition motif (RRM) found in ras GTPase-activating protein-binding protein 1 (G3BP1) and similar proteins; This subgroup corresponds to the RRM of G3BP1, also termed ATP-dependent DNA helicase VIII (DH VIII), or GAP SH3 domain-binding protein 1, which has been identified as a phosphorylation-dependent endoribonuclease that interacts with the SH3 domain of RasGAP, a multi-functional protein controlling Ras activity. The acidic RasGAP binding domain of G3BP1 harbors an arsenite-regulated phosphorylation site and dominantly inhibits stress granule (SG) formation. G3BP1 also contains an N-terminal nuclear transfer factor 2 (NTF2)-like domain, an RNA recognition motif (RRM domain), and an Arg-Gly-rich region (RGG-rich region, or arginine methylation motif). The RRM domain and RGG-rich region are canonically associated with RNA binding. G3BP1 co-immunoprecipitates with mRNAs. It binds to and cleaves the 3'-untranslated region (3'-UTR) of the c-myc mRNA in a phosphorylation-dependent manner. Thus, G3BP1 may play a role in coupling extra-cellular stimuli to mRNA stability. It has been shown that G3BP1 is a novel Dishevelled-associated protein that is methylated upon Wnt3a stimulation and that arginine methylation of G3BP1 regulates both Ctnnb1 mRNA and canonical Wnt/beta-catenin signaling. Furthermore, G3BP1 can be associated with the 3'-UTR of beta-F1 mRNA in cytoplasmic RNA-granules, demonstrating that G3BP1 may specifically repress the translation of the transcript.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38327552 337 PDSHQLFIGNLPHEVDKSELKDFFQSYGNVVELRINSGGKLPNFGFVVFDDSEPVQKVLSNRPIMFRGEVRLNVEEKKTR 416
Cdd:cd12463   1 PDSHQLFVGNLPHDVDKSELKEFFQGYGNVVELRINSGGKLPNFGFVVFDDPEPVQKILSNRPIKFRGEVRLNVEEKKTR 80

Nuclear transport factor 2 (NTF2) domain; This family includes the NTF2-like Delta-5-3-ketosteroid isomerase proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38327552    11 VGREFVRQYYTLLNQ-APDMLHRFYGKNSSYvhggLDSNGKpaDAVYGQKEIHRKVMSQNFTNCHTKIRHVDAH-ATLND 88
Cdd:pfam02136   1 VGNAFVQQYYAALDAhDPEGLHALYADDASM----LTPPGS--DPVVGLEAINEFFDSLPFTRIQHKITSVDSQpASLKD 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 38327552    89 GVVVQVMGLLSNNNQALRRFMQTFVLAPEGsvaNKFYVHNDIFRY 133
Cdd:pfam02136  75 GVLVMVTGELTVDDFPRRRFSQTFLLAPQR---GGYFVLNDIFRY 116

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 38327552   342 LFIGNLPHEVDKSELKDFFQSYGNVVELRI--NSGGKLPNFGFVVFDDSEPVQKVLSN 397
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLvrDETGRSKGFAFVEFEDEEDAEKAIEA 58

Neuroendocrine-specific golgi protein P55 (NESP55); This family consists of several mammalian neuroendocrine-specific golgi protein P55 (NESP55) sequences. NESP55 is a novel member of the chromogranin family and is a soluble, acidic, heat-stable secretory protein that is expressed exclusively in endocrine and nervous tissues, although less widely than chromogranins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38327552   212 EEKPE--PVLE-ETAPEDAQKSSSPAPADIAQTVQEDLRTFSwasVTSKNLPPSGAVPVTGIP--PHVVKVPASQP---- 282
Cdd:pfam06390 137 ETEPDtaPTTEpETEPEDEPGPVVPKGATFHQSLTERLHALK---LQSADASPRRAPPSTQEPesAREGEEPERGPldkd 213

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 38327552   283 ------RPESKPESQIPPQR--PQRDQRVREQRINIPPQRGPRPIR 320
Cdd:pfam06390 214 prdpeeEEEEKEEEKQQPHRckPKKPARRRDPSPESPPKKGAIPIR 259

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38327552   278 PASQPRPESKPESQIPPQRPQRDQRVREQRINiPPQRGPRPIREAGEQGDIEPRRMVRHP-DSHQLFIGNLPHEVDKSEL 356
Cdd:TIGR01622  53 YYRGRERRSRSRRPNRRYRPREKRRRRGDSYR-RRRDDRRSRREKPRARDGTPEPLTEDErDRRTVFVQQLAARARERDL 131

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 38327552   357 KDFFQSYGNVVELRI----NSgGKLPNFGFVVFDDSEPVQKVLS-------NRPIMFRGEvrlnvEEKKTRAAR 419
Cdd:TIGR01622 132 YEFFSKVGKVRDVQIikdrNS-RRSKGVGYVEFYDVDSVQAALAltgqkllGIPVIVQLS-----EAEKNRAAR 199

RNA recognition motif (RRM) found in ras GTPase-activating protein-binding protein 1 (G3BP1) and similar proteins; This subgroup corresponds to the RRM of G3BP1, also termed ATP-dependent DNA helicase VIII (DH VIII), or GAP SH3 domain-binding protein 1, which has been identified as a phosphorylation-dependent endoribonuclease that interacts with the SH3 domain of RasGAP, a multi-functional protein controlling Ras activity. The acidic RasGAP binding domain of G3BP1 harbors an arsenite-regulated phosphorylation site and dominantly inhibits stress granule (SG) formation. G3BP1 also contains an N-terminal nuclear transfer factor 2 (NTF2)-like domain, an RNA recognition motif (RRM domain), and an Arg-Gly-rich region (RGG-rich region, or arginine methylation motif). The RRM domain and RGG-rich region are canonically associated with RNA binding. G3BP1 co-immunoprecipitates with mRNAs. It binds to and cleaves the 3'-untranslated region (3'-UTR) of the c-myc mRNA in a phosphorylation-dependent manner. Thus, G3BP1 may play a role in coupling extra-cellular stimuli to mRNA stability. It has been shown that G3BP1 is a novel Dishevelled-associated protein that is methylated upon Wnt3a stimulation and that arginine methylation of G3BP1 regulates both Ctnnb1 mRNA and canonical Wnt/beta-catenin signaling. Furthermore, G3BP1 can be associated with the 3'-UTR of beta-F1 mRNA in cytoplasmic RNA-granules, demonstrating that G3BP1 may specifically repress the translation of the transcript.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38327552 337 PDSHQLFIGNLPHEVDKSELKDFFQSYGNVVELRINSGGKLPNFGFVVFDDSEPVQKVLSNRPIMFRGEVRLNVEEKKTR 416
Cdd:cd12463   1 PDSHQLFVGNLPHDVDKSELKEFFQGYGNVVELRINSGGKLPNFGFVVFDDPEPVQKILSNRPIKFRGEVRLNVEEKKTR 80

RNA recognition motif (RRM) found in ras GTPase-activating protein-binding protein G3BP1, G3BP2 and similar proteins; This subfamily corresponds to the RRM domain in the G3BP family of RNA-binding and SH3 domain-binding proteins. G3BP acts at the level of RNA metabolism in response to cell signaling, possibly as RNA transcript stabilizing factors or an RNase. Members include G3BP1, G3BP2 and similar proteins. These proteins associate directly with the SH3 domain of GTPase-activating protein (GAP), which functions as an inhibitor of Ras. They all contain an N-terminal nuclear transfer factor 2 (NTF2)-like domain, an acidic domain, a domain containing PXXP motif(s), an RNA recognition motif (RRM), and an Arg-Gly-rich region (RGG-rich region, or arginine methylation motif).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38327552 337 PDSHQLFIGNLPHEVDKSELKDFFQSYGNVVELRINS---GGKLPNFGFVVFDDSEPVQKVLSNRPIMFRGEVRLNVEEK 413
Cdd:cd12229   1 PDNHQLFVGNLPHDITEDELKEFFSRFGNVLELRINSkggGGRLPNFGFVVFDDPEAVQKILANKPIMFRGEHRLNVEEK 80

                .
gi 38327552 414 K 414
Cdd:cd12229  81 K 81

Nuclear transport factor 2 (NTF2) domain; This family includes the NTF2-like Delta-5-3-ketosteroid isomerase proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38327552    11 VGREFVRQYYTLLNQ-APDMLHRFYGKNSSYvhggLDSNGKpaDAVYGQKEIHRKVMSQNFTNCHTKIRHVDAH-ATLND 88
Cdd:pfam02136   1 VGNAFVQQYYAALDAhDPEGLHALYADDASM----LTPPGS--DPVVGLEAINEFFDSLPFTRIQHKITSVDSQpASLKD 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 38327552    89 GVVVQVMGLLSNNNQALRRFMQTFVLAPEGsvaNKFYVHNDIFRY 133
Cdd:pfam02136  75 GVLVMVTGELTVDDFPRRRFSQTFLLAPQR---GGYFVLNDIFRY 116

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVELRI--NSGGKLPNFGFVVFDDSEPVQKVLSN 397
Cdd:cd00590   1 LFVGNLPPDTTEEDLRELFSKFGEVVSVRIvrDRDGKSKGFAFVEFESPEDAEKALEA 58

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 38327552   342 LFIGNLPHEVDKSELKDFFQSYGNVVELRI--NSGGKLPNFGFVVFDDSEPVQKVLSN 397
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLvrDETGRSKGFAFVEFEDEEDAEKAIEA 58

RNA recognition motif (RRM) found in AZoospermia (DAZ) autosomal homologs, DAZL (DAZ-like) and BOULE; This subfamily corresponds to the RRM domain of two Deleted in AZoospermia (DAZ) autosomal homologs, DAZL (DAZ-like) and BOULE. BOULE is the founder member of the family and DAZL arose from BOULE in an ancestor of vertebrates. The DAZ gene subsequently originated from a duplication transposition of the DAZL gene. Invertebrates contain a single DAZ homolog, BOULE, while vertebrates, other than catarrhine primates, possess both BOULE and DAZL genes. The catarrhine primates possess BOULE, DAZL, and DAZ genes. The family members encode closely related RNA-binding proteins that are required for fertility in numerous organisms. These proteins contain an RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a varying number of copies of a DAZ motif, believed to mediate protein-protein interactions. DAZL and BOULE contain a single copy of the DAZ motif, while DAZ proteins can contain 8-24 copies of this repeat. Although their specific biochemical functions remain to be investigated, DAZL proteins may interact with poly(A)-binding proteins (PABPs), and act as translational activators of specific mRNAs during gametogenesis.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 38327552 340 HQLFIGNLPHEVDKSELKDFFQSYGNVVELRI--NSGGKLPNFGFVVFDDSEPVQKVLSNRP-IMFRGEvRLNV 410
Cdd:cd12412   3 NRIFVGGIDWDTTEEELREFFSKFGKVKDVKIikDRAGVSKGYGFVTFETQEDAEKIQKWGAnLVFKGK-KLNV 75

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A subfamily; This subfamily corresponds to the RRM2 of hnRNP A0, hnRNP A1, hnRNP A2/B1, hnRNP A3 and similar proteins. hnRNP A0 is a low abundance hnRNP protein that has been implicated in mRNA stability in mammalian cells. It has been identified as the substrate for MAPKAP-K2 and may be involved in the lipopolysaccharide (LPS)-induced post-transcriptional regulation of tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase 2 (COX-2) and macrophage inflammatory protein 2 (MIP-2). hnRNP A1 is an abundant eukaryotic nuclear RNA-binding protein that may modulate splice site selection in pre-mRNA splicing. hnRNP A2/B1 is an RNA trafficking response element-binding protein that interacts with the hnRNP A2 response element (A2RE). Many mRNAs, such as myelin basic protein (MBP), myelin-associated oligodendrocytic basic protein (MOBP), carboxyanhydrase II (CAII), microtubule-associated protein tau, and amyloid precursor protein (APP) are trafficked by hnRNP A2/B1. hnRNP A3 is also a RNA trafficking response element-binding protein that participates in the trafficking of A2RE-containing RNA. The hnRNP A subfamily is characterized by two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long glycine-rich region at the C-terminus.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVELRI---NSGGKLPNFGFVVFDDSEPVQKVLSNRPIMFRG---EVR 407
Cdd:cd12328   2 LFVGGLKEDVEEEDLREYFSQFGKVESVEIvtdKETGKKRGFAFVTFDDHDSVDKIVLQKYHTINGhrcEVK 73

RNA recognition motif 1 (RRM1) and 2 (RRM2) found in RRM-containing coactivator activator/modulator (CoAA) and similar proteins; This subfamily corresponds to the RRM in CoAA (also known as RBM14 or PSP2) and RNA-binding protein 4 (RBM4). CoAA is a heterogeneous nuclear ribonucleoprotein (hnRNP)-like protein identified as a nuclear receptor coactivator. It mediates transcriptional coactivation and RNA splicing effects in a promoter-preferential manner, and is enhanced by thyroid hormone receptor-binding protein (TRBP). CoAA contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a TRBP-interacting domain. RBM4 is a ubiquitously expressed splicing factor with two isoforms, RBM4A (also known as Lark homolog) and RBM4B (also known as RBM30), which are very similar in structure and sequence. RBM4 may also function as a translational regulator of stress-associated mRNAs as well as play a role in micro-RNA-mediated gene regulation. RBM4 contains two N-terminal RRMs, a CCHC-type zinc finger, and three alanine-rich regions within their C-terminal regions. This family also includes Drosophila RNA-binding protein lark (Dlark), a homolog of human RBM4. It plays an important role in embryonic development and in the circadian regulation of adult eclosion. Dlark shares high sequence similarity with RBM4 at the N-terminal region. However, Dlark has three proline-rich segments instead of three alanine-rich segments within the C-terminal region.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVELRInsggkLPNFGFVVFDDSEPVQ---KVLSNRPIMfrgEVRLNVE 411
Cdd:cd12343   2 IFVGNLPDAATSEELRALFEKYGKVTECDI-----VKNYAFVHMEKEEDAEdaiKALNGYEFM---GSRINVE 66

RNA recognition motif 2 (RRM2) found in RNA-binding protein 34 (RBM34) and similar proteins; This subfamily corresponds to the RRM2 of RBM34, a putative RNA-binding protein containing two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). Although the function of RBM34 remains unclear currently, its RRM domains may participate in mRNA processing. RBM34 may act as an mRNA processing-related protein.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 38327552 343 FIGNLPHEVDKSELKDFFQSYGNVVELRI----NSG-GKlpNFGFVVFDDSEPVQKVLSNRPIMFRG-EVR 407
Cdd:cd12395   3 FVGNLPFDIEEEELRKHFEDCGDVEAVRIvrdrETGiGK--GFGYVLFKDKDSVDLALKLNGSKLRGrKLR 71

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVELRI-------NSGGklpnFGFVVFDDSEPVQKV---LSNRPIMFRgevRLNVE 411
Cdd:COG0724   4 IYVGNLPYSVTEEDLRELFSEYGEVTSVKLitdretgRSRG----FGFVEMPDDEEAQAAieaLNGAELMGR---TLKVN 76

                ....*...
gi 38327552 412 EKKTRAAR 419
Cdd:COG0724  77 EARPREER 84

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
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVELRI---NSGGKLPNFGFVVFDDSEPVQKVLSN 397
Cdd:cd12362   1 LFVYHLPNEFTDQDLYQLFAPFGNVVSAKVfvdKNTGRSKGFGFVSYDNPLSAQAAIKA 59

RNA recognition motif 1 (RRM1) found in squamous cell carcinoma antigen recognized by T-cells 3 (SART3) and similar proteins; This subfamily corresponds to the RRM1 of SART3, also termed Tat-interacting protein of 110 kDa (Tip110), an RNA-binding protein expressed in the nucleus of the majority of proliferating cells, including normal cells and malignant cells, but not in normal tissues except for the testes and fetal liver. It is involved in the regulation of mRNA splicing probably via its complex formation with RNA-binding protein with a serine-rich domain (RNPS1), a pre-mRNA-splicing factor. SART3 has also been identified as a nuclear Tat-interacting protein that regulates Tat transactivation activity through direct interaction and functions as an important cellular factor for HIV-1 gene expression and viral replication. In addition, SART3 is required for U6 snRNP targeting to Cajal bodies. It binds specifically and directly to the U6 snRNA, interacts transiently with the U6 and U4/U6 snRNPs, and promotes the reassembly of U4/U6 snRNPs after splicing in vitro. SART3 contains an N-terminal half-a-tetratricopeptide repeat (HAT)-rich domain, a nuclearlocalization signal (NLS) domain, and two C-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 38327552 343 FIGNLPHEVDKSELKDFFQSYGNVVELRI--NSGGKLPNFGFVVFDDSEPVQKVLS-------NRPiMF 402
Cdd:cd12391   3 FVSNLDYSVPEDKIREIFSGCGEITDVRLvkNYKGKSKGYCYVEFKDEESAQKALKldrqpveGRP-MF 70

RNA recognition motif 2 (RRM2) found in yeast nuclear polyadenylated RNA-binding protein 4 (Hrp1p or Nab4p) and similar proteins; This subfamily corresponds to the RRM1 of Hrp1p and similar proteins. Hrp1p or Nab4p, also termed cleavage factor IB (CFIB), is a sequence-specific trans-acting factor that is essential for mRNA 3'-end formation in yeast Saccharomyces cerevisiae. It can be UV cross-linked to RNA and specifically recognizes the (UA)6 RNA element required for both, the cleavage and poly(A) addition steps. Moreover, Hrp1p can shuttle between the nucleus and the cytoplasm, and play an additional role in the export of mRNAs to the cytoplasm. Hrp1p also interacts with Rna15p and Rna14p, two components of CF1A. In addition, Hrp1p functions as a factor directly involved in modulating the activity of the nonsense-mediated mRNA decay (NMD) pathway; it binds specifically to a downstream sequence element (DSE)-containing RNA and interacts with Upf1p, a component of the surveillance complex, further triggering the NMD pathway. Hrp1p contains two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an arginine-glycine-rich region harboring repeats of the sequence RGGF/Y.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 38327552 341 QLFIGNLPHEVDKSELKDFFQSYGNVVELRI---NSGGKLPNFGFVVFDDSEPVQKVLSNRPIMFRGEvrlNVEEKK 414
Cdd:cd12330   1 KIFVGGLAPDVTEEEFKEYFEQFGTVVDAVVmldHDTGRSRGFGFVTFDSESAVEKVLSKGFHELGGK---KVEVKR 74

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins; This subfamily corresponds to the RRM2 of hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins. hnRNP D0, a UUAG-specific nuclear RNA binding protein that may be involved in pre-mRNA splicing and telomere elongation. hnRNP A/B is an RNA unwinding protein with a high affinity for G- followed by U-rich regions. It has also been identified as an APOBEC1-binding protein that interacts with apolipoprotein B (apoB) mRNA transcripts around the editing site and thus plays an important role in apoB mRNA editing. hnRNP DL (or hnRNP D-like) is a dual functional protein that possesses DNA- and RNA-binding properties. It has been implicated in mRNA biogenesis at the transcriptional and post-transcriptional levels. All memembers in this family contain two putative RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glycine- and tyrosine-rich C-terminus.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 38327552 341 QLFIGNLPHEVDKSELKDFFQSYGNVVELRI---NSGGKLPNFGFVVFDDSEPVQKVL 395
Cdd:cd12329   1 KIFVGGLSPETTEEKIREYFGKFGNIVEIELpmdKKTNKRRGFCFITFDSEEPVKKIL 58

RNA recognition motif 3 in fungal pre-messenger RNA splicing protein 24 (Prp24) and similar proteins; This subfamily corresponds to the RRM3 of Prp24, also termed U4/U6 snRNA-associated-splicing factor PRP24 (U4/U6 snRNP), an RNA-binding protein with four well conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). It facilitates U6 RNA base-pairing with U4 RNA during spliceosome assembly. Prp24 specifically binds free U6 RNA primarily with RRMs 1 and 2 and facilitates pairing of U6 RNA bases with U4 RNA bases. Additionally, it may also be involved in dissociation of the U4/U6 complex during spliceosome activation.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 38327552 341 QLFIGNLPHEVDKSELKDFFQSYGNVVELRI-----NSGGKLPN-FGFVVFDDSEPVQK-------VLSNRPI 400
Cdd:cd12298   2 EIRVRNLDFELDEEALRGIFEKFGEIESINIpkkqkNRKGRHNNgFAFVTFEDADSAESalqlngtLLDNRKI 74

RNA recognition motif 2 (RRM2) found in yeast nucleolar protein 13 (Nop13p) and similar proteins; This subfamily corresponds to the RRM2 of Nop13p encoded by YNL175c from Saccharomyces cerevisiae. It shares high sequence similarity with nucleolar protein 12 (Nop12p). Both Nop12p and Nop13p are not essential for growth. However, unlike Nop12p that is localized to the nucleolus, Nop13p localizes primarily to the nucleolus but is also present in the nucleoplasm to a lesser extent. Nop13p contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVELRINS---GGKLPNFGFVVFDDSEPVQKVLSNRPIMFRGEVRLNVE 411
Cdd:cd12397   1 LFVGNLSFETTEEDLRKHFAPAGKIRKVRMATfedSGKCKGFAFVDFKEIESATNAVKGPINHSLNGRDLRVE 73

RNA recognition motif (RRM) found in protein BOULE; This subgroup corresponds to the RRM of BOULE, the founder member of the human DAZ gene family. Invertebrates contain a single BOULE, while vertebrates, other than catarrhine primates, possess both BOULE and DAZL genes. The catarrhine primates possess BOULE, DAZL, and DAZ genes. BOULE encodes an RNA-binding protein containing an RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a single copy of the DAZ motif. Although its specific biochemical functions remains to be investigated, BOULE protein may interact with poly(A)-binding proteins (PABPs), and act as translational activators of specific mRNAs during gametogenesis.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 38327552 340 HQLFIGNLPHEVDKSELKDFFQSYGNVVELRI--NSGGKLPNFGFVVFDDSEPVQKVLSNRPIMFRGEVRLNV 410
Cdd:cd12673   3 NRIFVGGIDFKTNENDLRKFFAQYGSVKEVKIvnDRAGVSKGYGFITFETQEDAQKILQEAEKLNYKDKKLNI 75

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVELRI---NSGGKLPNFGFVVFDDSEPVQ---KVLSNRPIMFR 403
Cdd:cd12398   3 VFVGNIPYDATEEQLKEIFSEVGPVVSFRLvtdRETGKPKGYGFCEFRDAETALsavRNLNGYELNGR 70

RNA recognition motif (RRM) found in SRA stem-loop-interacting RNA-binding protein (SLIRP) and similar proteins; This subfamily corresponds to the RRM of SLIRP, a widely expressed small steroid receptor RNA activator (SRA) binding protein, which binds to STR7, a functional substructure of SRA. SLIRP is localized predominantly to the mitochondria and plays a key role in modulating several nuclear receptor (NR) pathways. It functions as a co-repressor to repress SRA-mediated nuclear receptor coactivation. It modulates SHARP- and SKIP-mediated co-regulation of NR activity. SLIRP contains an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), which is required for SLIRP's corepression activities.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVELRI---NSGGKLPNFGFVVFDDSEPVQKVLSNRPIMFRGE 405
Cdd:cd12242   2 LFVSNLPWTTGSSELKEYFSQFGKVKRCNLpfdKETGFHKGFGFVSFENEDGLRNALQKQKHIFEGN 68

RNA recognition motif 2 (RRM2) found in squamous cell carcinoma antigen recognized by T-cells 3 (SART3) and similar proteins; This subfamily corresponds to the RRM2 of SART3, also termed Tat-interacting protein of 110 kDa (Tip110), is an RNA-binding protein expressed in the nucleus of the majority of proliferating cells, including normal cells and malignant cells, but not in normal tissues except for the testes and fetal liver. It is involved in the regulation of mRNA splicing probably via its complex formation with RNA-binding protein with a serine-rich domain (RNPS1), a pre-mRNA-splicing factor. SART3 has also been identified as a nuclear Tat-interacting protein that regulates Tat transactivation activity through direct interaction and functions as an important cellular factor for HIV-1 gene expression and viral replication. In addition, SART3 is required for U6 snRNP targeting to Cajal bodies. It binds specifically and directly to the U6 snRNA, interacts transiently with the U6 and U4/U6 snRNPs, and promotes the reassembly of U4/U6 snRNPs after splicing in vitro. SART3 contains an N-terminal half-a-tetratricopeptide repeat (HAT)-rich domain, a nuclearlocalization signal (NLS) domain, and two C-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 38327552 338 DSHQLFIGNLPHEVDKSELKDFFQSYGNVVELRI--NSGGKLPNFGFVVF-DDSEPVQKVLSNRPIMFRGEV 406
Cdd:cd12392   1 EKNKLFVKGLPFSCTKEELEELFKQHGTVKDVRLvtYRNGKPKGLAYVEYeNEADASQAVLKTDGTEIKDHT 72

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein D-like (hnRNP DL) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP DL (or hnRNP D-like), also termed AU-rich element RNA-binding factor, or JKT41-binding protein (protein laAUF1 or JKTBP), is a dual functional protein that possesses DNA- and RNA-binding properties. It has been implicated in mRNA biogenesis at the transcriptional and post-transcriptional levels. hnRNP DL binds single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) in a non-sequencespecific manner, and interacts with poly(G) and poly(A) tenaciously. It contains two putative two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glycine- and tyrosine-rich C-terminus.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 38327552 341 QLFIGNLPHEVDKSELKDFFQSYGNV--VELRINSG-GKLPNFGFVVFDDSEPVQKVLSNR 398
Cdd:cd12585   1 KVFVGGLSPDTSEEQIKEYFGAFGEIenIELPMDTKtNERRGFCFITYTDEEPVQKLLESR 61

RNA recognition motif (RRM) found in eukaryotic translation initiation factor 4B (eIF-4B) and similar proteins; This subfamily corresponds to the RRM of eIF-4B, a multi-domain RNA-binding protein that has been primarily implicated in promoting the binding of 40S ribosomal subunits to mRNA during translation initiation. It contains two RNA-binding domains; the N-terminal well-conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), binds the 18S rRNA of the 40S ribosomal subunit and the C-terminal basic domain (BD), including two arginine-rich motifs (ARMs), binds mRNA during initiation, and is primarily responsible for the stimulation of the helicase activity of eIF-4A. eIF-4B also contains a DRYG domain (a region rich in Asp, Arg, Tyr, and Gly amino acids) in the middle, which is responsible for both, self-association of eIF-4B and binding to the p170 subunit of eIF3. Additional research indicates that eIF-4B can interact with the poly(A) binding protein (PABP) in mammalian cells, which can stimulate both, the eIF-4B-mediated activation of the helicase activity of eIF-4A and binding of poly(A) by PABP. eIF-4B has also been shown to interact specifically with the internal ribosome entry sites (IRES) of several picornaviruses which facilitate cap-independent translation initiation.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 38327552 343 FIGNLPHEVDKSELKDFFQSYgNVVELRI---NSGGKLPNFGFVVFDDSEPVQKVLS-------NRPI 400
Cdd:cd12402   6 YLGNLPYDVTEDDIEDFFRGL-NISSVRLpreNGPGRLRGFGYVEFEDRESLIQALSlneeslkNRRI 72

RNA recognition motif 1 (RRM1) found in TAR DNA-binding protein 43 (TDP-43) and similar proteins; This subfamily corresponds to the RRM1 of TDP-43 (also termed TARDBP), a ubiquitously expressed pathogenic protein whose normal function and abnormal aggregation are directly linked to the genetic disease cystic fibrosis, and two neurodegenerative disorders: frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). TDP-43 binds both DNA and RNA, and has been implicated in transcriptional repression, pre-mRNA splicing and translational regulation. TDP-43 is a dimeric protein with two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal glycine-rich domain. The RRMs are responsible for DNA and RNA binding; they bind to TAR DNA and RNA sequences with UG-repeats. The glycine-rich domain can interact with the hnRNP family proteins to form the hnRNP-rich complex involved in splicing inhibition. It is also essential for the cystic fibrosis transmembrane conductance regulator (CFTR) exon 9-skipping activity.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVELRIN---SGGKLPNFGFVVFDDSEPVQKVLSNR 398
Cdd:cd12321   2 LIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKkdpKTGRSKGFGFVRFASYETQVKVLSQR 61

RNA recognition motif 1 (RRM1) found in plant pre-mRNA-splicing factor SF2 and similar proteins; This subgroup corresponds to the RRM1 of SF2, also termed SR1 protein, a plant serine/arginine (SR)-rich phosphoprotein similar to the mammalian splicing factor SF2/ASF. It promotes splice site switching in mammalian nuclear extracts. SF2 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a C-terminal domain rich in proline, serine and lysine residues (PSK domain), a composition reminiscent of histones. This PSK domain harbors a putative phosphorylation site for the mitotic kinase cyclin/p34cdc2.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVELRINSGGKLPNFGFVVFDDSEPVQKVLSNRP-IMFRGEvRLNVE 411
Cdd:cd12599   2 VYVGNLPMDIREREVEDLFSKYGPVVSIDLKIPPRPPAYAFVEFEDARDAEDAIRGRDgYDFDGH-RLRVE 71

RNA recognition motif 2 (RRM2) found in chloroplastic plastid-specific 30S ribosomal protein 2 (PSRP-2) and similar proteins; PSRP-2, also called chloroplastic 30S ribosomal protein 2, or chloroplastic small ribosomal subunit protein cS22, is a component of the chloroplast ribosome (chloro-ribosome), a dedicated translation machinery responsible for the synthesis of chloroplast genome-encoded proteins, including proteins of the transcription and translation machinery and components of the photosynthetic apparatus. It binds single strand DNA (ssDNA) and RNA in vitro. It exhibits RNA chaperone activity and regulates negatively resistance responses to abiotic stresses during seed germination (e.g. salt, dehydration, and low temperature) and seedling growth (e.g. salt). PSRP-2 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the second RRM motif.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 38327552 340 HQLFIGNLPHEVDKSELKDFFQSYGNVVEL---RINSGGKLPNFGFVVFDDSEPVQKVLS--NRPIMFRGEVRLNV 410
Cdd:cd21610   3 YKVYVGNLAKTVTNELLKDFFSEKGKVLGAkvqRTPGTSKSNGFGFVSFSSEEDVEAAIQalNNSVLEGQKIRVNK 78

RNA recognition motif 1 and 2 (RRM1, RRM2) found in Arabidopsis thaliana CTC-interacting domain protein CID8, CID9, CID10, CID11, CID12, CID 13 and similar proteins; This subgroup corresponds to the RRM domains found in A. thaliana CID8, CID9, CID10, CID11, CID12, CID 13 and mainly their plant homologs. These highly related RNA-binding proteins contain an N-terminal PAM2 domain (PABP-interacting motif 2), two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a basic region that resembles a bipartite nuclear localization signal. The biological role of this family remains unclear.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVELRINSGGKLPNFGFVVFDDSEPVQKVLS 396
Cdd:cd12225   3 IHVGGIDGSLSEDELADYFSNCGEVTQVRLCGDRVHTRFAWVEFATDASALSALN 57

RNA recognition motif 3 (RRM3) found in RNA-binding protein 19 (RBM19) and RNA recognition motif 2 found in multiple RNA-binding domain-containing protein 1 (MRD1); This subfamily corresponds to the RRM3 of RBM19 and RRM2 of MRD1. RBM19, also termed RNA-binding domain-1 (RBD-1), is a nucleolar protein conserved in eukaryotes involved in ribosome biogenesis by processing rRNA and is essential for preimplantation development. It has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). 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
                ....*....|....*....|....*....|....*....|....*....|....*
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVELRI---NSGGKLPNFGFVVFDDSEPVQK 393
Cdd:cd12316   2 LFVRNLPFTATEDELRELFEAFGKISEVHIpldKQTKRSKGFAFVLFVIPEDAVK 56

RNA recognition motif 1 (RRM1) found in RNA-binding protein 19 (RBM19) and similar proteins; This subgroup corresponds to the RRM1 of RBM19, also termed RNA-binding domain-1 (RBD-1), a nucleolar protein conserved in eukaryotes. It is involved in ribosome biogenesis by processing rRNA. In addition, it is essential for preimplantation development. RBM19 has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNV--VELRINSGGKLPNFGFVVFDDSEPVQKVLSNRPIMFRGEVRLNVEE 412
Cdd:cd12564   3 LIVKNLPSSITEDRLRKLFSAFGTItdVQLKYTKDGKFRRFGFVGFKSEEEAQKALKHFNNSFIDTSRITVEE 75

RNA recognition motif 2 (RRM2) found in splicing factor 3B subunit 4 (SF3B4) and similar proteins; This subfamily corresponds to the RRM2 of SF3B4, also termed pre-mRNA-splicing factor SF3b 49 kDa (SF3b50), or spliceosome-associated protein 49 (SAP 49). SF3B4 is a component of the multiprotein complex splicing factor 3b (SF3B), 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 is involved in the recognition of the pre-mRNA's branch site within the major and minor spliceosomes. SF3B4 functions to tether U2 snRNP with pre-mRNA at the branch site during spliceosome assembly. It is an evolutionarily highly conserved protein with orthologs across diverse species. SF3B4 contains two closely adjacent N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). It binds directly to pre-mRNA and also interacts directly and highly specifically with another SF3B subunit called SAP 145.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVE----LRINSGGKLPNFGFVVFDDSEPVQ--------KVLSNRPI 400
Cdd:cd12335   4 LFIGNLDPEVDEKLLYDTFSAFGVILQtpkiMRDPDTGNSKGFGFVSFDSFEASDaaieamngQYLCNRPI 74

RNA recognition motif 2 (RRM2) found in yeast protein gar2 and similar proteins; This subfamily corresponds to the RRM2 of yeast protein gar2, a novel nucleolar protein required for 18S rRNA and 40S ribosomal subunit accumulation. It shares similar domain architecture with nucleolin from vertebrates and NSR1 from Saccharomyces cerevisiae. The highly phosphorylated N-terminal domain of gar2 is made up of highly acidic regions separated from each other by basic sequences, and contains multiple phosphorylation sites. The central domain of gar2 contains two closely adjacent N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The C-terminal RGG (or GAR) domain of gar2 is rich in glycine, arginine and phenylalanine residues.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVELRINSG---GKLPNFGFVVFDDSEPVQKV--------LSNRPI 400
Cdd:cd12448   1 LFVGNLPFSATQDALYEAFSQHGSIVSVRLPTDretGQPKGFGYVDFSTIDSAEAAidalggeyIDGRPI 70

RNA recognition motif 3 (RRM3) found in SMART/HDAC1-associated repressor protein (SHARP) and similar proteins; This subfamily corresponds to the RRM3 of SHARP, also termed Msx2-interacting protein (MINT), or SPEN homolog, 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
                ....*....|....*....|....*....|....*....|....*....|....
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVELRINSGGKLPNFGFVVFDDSEPVQKVL 395
Cdd:cd12350   5 LFIGNLEKTTTYGDLRNIFERFGEIIDIDIKKQNGNPQYAFLQYCDIASVVKAI 58

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 38327552 342 LFIGNLPHEVDKSELKDFFQSYGNVVELRI---NSGGKLPNFGFVVFDDSEPVQKVL 395
Cdd:cd12447   2 LFVGGLSWNVDDPWLKKEFEKYGGVISARVitdRGSGRSKGYGYVDFATPEAAQKAL 58