RNA recognition motif (RRM) found in vertebrate methenyltetrahydrofolate synthetase domain-containing proteins; This subfamily corresponds to methenyltetrahydrofolate synthetase domain (MTHFSD), a putative RNA-binding protein found in various vertebrate species. It contains an N-terminal 5-formyltetrahydrofolate cyclo-ligase domain and a C-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The biological role of MTHFSD remains unclear.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767990410 287 DVYVGNLPGDARVSDLKRALRELGSVPLRLTWQGPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLRVALAR 358
Cdd:cd12270    1 TVYVGNIPRSVRVSDLKSALRERGINPLRITWQGARGKAFLHYSDMADADSAVSSLQGLRIGGNTLTVELAK 72

RNA recognition motif (RRM) found in vertebrate methenyltetrahydrofolate synthetase domain-containing proteins; This subfamily corresponds to methenyltetrahydrofolate synthetase domain (MTHFSD), a putative RNA-binding protein found in various vertebrate species. It contains an N-terminal 5-formyltetrahydrofolate cyclo-ligase domain and a C-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The biological role of MTHFSD remains unclear.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767990410 287 DVYVGNLPGDARVSDLKRALRELGSVPLRLTWQGPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLRVALAR 358
Cdd:cd12270    1 TVYVGNIPRSVRVSDLKSALRERGINPLRITWQGARGKAFLHYSDMADADSAVSSLQGLRIGGNTLTVELAK 72

5-formyltetrahydrofolate cyclo-ligase [Coenzyme transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767990410 114 VDLVVVGSVAVSEKGWRIGKGEGYAD--LEyammvsmgAVSKETPVVTIVHDCQVVD-IPeelVEEHDITVDYILTPTRV 190
Cdd:COG0212  118 IDLVLVPLLAFDRRGYRLGYGGGYYDrtLA--------RLRPRPLTIGLAFDCQLVDeLP---VEPHDVPLDAIVTEKGV 186

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767990410   288 VYVGNLPGDARVSDLKRALRELGSV-----PLRLTWQGPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLRV 354
Cdd:smart00360   2 LFVGNLPPDTTEEELRELFSKFGKVesvrlVRDKETGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

5-formyltetrahydrofolate cyclo-ligase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767990410 114 VDLVVVGSVAVSEKGWRIGKGEGYADleyAMMVSMGAVSKET-----PVVTIVHDCQVVDIPEELVEEHDITVDYILTPT 188
Cdd:PLN02812 132 LDLLLLPGLAFDRSGRRLGRGGGYYD---TFLSKYQELAKEKgwkqpLLVALSYSPQILDEGSVPVDETDVLVDALVTPS 208

                 ...
gi 767990410 189 RVI 191
Cdd:PLN02812 209 GVI 211

RNA recognition motif (RRM) found in vertebrate methenyltetrahydrofolate synthetase domain-containing proteins; This subfamily corresponds to methenyltetrahydrofolate synthetase domain (MTHFSD), a putative RNA-binding protein found in various vertebrate species. It contains an N-terminal 5-formyltetrahydrofolate cyclo-ligase domain and a C-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The biological role of MTHFSD remains unclear.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767990410 287 DVYVGNLPGDARVSDLKRALRELGSVPLRLTWQGPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLRVALAR 358
Cdd:cd12270    1 TVYVGNIPRSVRVSDLKSALRERGINPLRITWQGARGKAFLHYSDMADADSAVSSLQGLRIGGNTLTVELAK 72

5-formyltetrahydrofolate cyclo-ligase [Coenzyme transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767990410 114 VDLVVVGSVAVSEKGWRIGKGEGYAD--LEyammvsmgAVSKETPVVTIVHDCQVVD-IPeelVEEHDITVDYILTPTRV 190
Cdd:COG0212  118 IDLVLVPLLAFDRRGYRLGYGGGYYDrtLA--------RLRPRPLTIGLAFDCQLVDeLP---VEPHDVPLDAIVTEKGV 186

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767990410 288 VYVGNLPGDARVSDLKRALRELGSV----PLRLTWQGPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLRV 354
Cdd:cd00590    1 LFVGNLPPDTTEEDLRELFSKFGEVvsvrIVRDRDGKSKGFAFVEFESPEDAEKALEALNGTELGGRPLKV 71

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767990410 288 VYVGNLPGDARVSDLKRALRELGsvPLRLTW--QGPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLRVALAR 358
Cdd:cd12373    2 VYVGNLGPRVTKRELEDAFEKYG--PLRNVWvaRNPPGFAFVEFEDPRDAEDAVRALDGRRICGSRVRVELSR 72

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767990410 288 VYVGNLPGDARVSDLKRALRELGSV-PLRL-----TWQgPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLRVALA 357
Cdd:cd12398    3 VFVGNIPYDATEEQLKEIFSEVGPVvSFRLvtdreTGK-PKGYGFCEFRDAETALSAVRNLNGYELNGRPLRVDFA 77

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767990410 289 YVGNLPGDARVSDLKRALRELGSV------PLRLTwQGPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLRVALARQQRD 362
Cdd:COG0724    5 YVGNLPYSVTEEDLRELFSEYGEVtsvkliTDRET-GRSRGFGFVEMPDDEEAQAAIEALNGAELMGRTLKVNEARPREE 83

                 .
gi 767990410 363 K 363
Cdd:COG0724   84 R 84

RNA recognition motif 1 (RRM1) found in serine/arginine-rich splicing factor 1 (SRSF1) and similar proteins; This subgroup corresponds to the RRM1 in three serine/arginine (SR) proteins: serine/arginine-rich splicing factor 1 (SRSF1 or ASF-1), serine/arginine-rich splicing factor 9 (SRSF9 or SRp30C), and plant pre-mRNA-splicing factor SF2 (SR1). SRSF1 is a shuttling SR protein involved in constitutive and alternative splicing, nonsense-mediated mRNA decay (NMD), mRNA export and translation. It also functions as a splicing-factor oncoprotein that regulates apoptosis and proliferation to promote mammary epithelial cell transformation. SRSF9 has been implicated in the activity of many elements that control splice site selection, the alternative splicing of the glucocorticoid receptor beta in neutrophils and in the gonadotropin-releasing hormone pre-mRNA. It can also interact with other proteins implicated in alternative splicing, including YB-1, rSLM-1, rSLM-2, E4-ORF4, Nop30, and p32. Both, SRSF1 and SRSF9, contain two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal RS domains rich in serine-arginine dipeptides. In contrast, SF2 contains two N-terminal RRMs and a C-terminal PSK domain rich in proline, serine and lysine residues.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767990410 288 VYVGNLPGDARVSDLKRALRELGSVpLRLTWQGPRRR---AFLHYPDSAAAQQAVSCLQGLRLGTDTLRVAL 356
Cdd:cd12338    2 IYVGNLPGDIRERDIEDLFYKYGPI-LAIDLKNRRRGppfAFVEFEDPRDAEDAIRGRDGYDFDGYRLRVEF 72

RNA recognition motif (RRM) found in nucleolar protein 8 (NOL8) and similar proteins; This model corresponds to the RRM of NOL8 (also termed Nop132) encoded by a novel NOL8 gene that is up-regulated in the majority of diffuse-type, but not intestinal-type, gastric cancers. Thus, NOL8 may be a good molecular target for treatment of diffuse-type gastric cancer. Also, NOL8 is a phosphorylated protein that contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), suggesting NOL8 is likely to function as a novel RNA-binding protein. It may be involved in regulation of gene expression at the post-transcriptional level or in ribosome biogenesis in cancer cells.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767990410 288 VYVGNLPGDARVSDLKRALRELGSV-PLRL---TWQGPRRRAFLHY-PDSAAAQQAVSCLQGLRLGTDTLRVALAR 358
Cdd:cd12226    2 LFVGGLSPSITEDDLERRFSRFGTVsDVEIirkKDAPDRGFAYIDLrTSEAALQKCLSTLNGVKWKGSRLKIQLAK 77

RNA recognition motif (RRM) found in vertebrate serine/arginine-rich splicing factor 7 (SRSF7); This subgroup corresponds to the RRM of SRSF7, also termed splicing factor 9G8, is a splicing regulatory serine/arginine (SR) protein that plays a crucial role in both constitutive splicing and alternative splicing of many pre-mRNAs. Its localization and functions are tightly regulated by phosphorylation. SRSF7 is predominantly present in the nuclear and can shuttle between nucleus and cytoplasm. It cooperates with the export protein, Tap/NXF1, helps mRNA export to the cytoplasm, and enhances the expression of unspliced mRNA. SRSF7 inhibits tau E10 inclusion through directly interacting with the proximal downstream intron of E10, a clustering region for frontotemporal dementia with Parkinsonism (FTDP) mutations. SRSF7 contains a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a CCHC-type zinc knuckle motif in its median region, and a C-terminal RS domain rich in serine-arginine dipeptides. The RRM domain is involved in RNA binding, and the RS domain has been implicated in protein shuttling and protein-protein interactions.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767990410 288 VYVGNLPGDARVSDLKRALRELGsvPLRLTW--QGPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLRVALA 357
Cdd:cd12646    2 VYVGNLGTGAGKGELERAFSYYG--PLRTVWiaRNPPGFAFVEFEDPRDAEDAVRGLDGKVICGSRVRVELS 71

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767990410 288 VYVGNLPGDARVSDLKRALRELG---SVPL---RLTwqGpRRR--AFLHYPDSAAAQQAVSCLQGLRLGTDTLRVALA 357
Cdd:cd21608    2 LYVGNLSWDTTEDDLRDLFSEFGeveSAKVitdRET--G-RSRgfGFVTFSTAEAAEAAIDALNGKELDGRSIVVNEA 76

RNA recognition motif 1 (RRM1) found in vertebrate Hu-antigen D (HuD); This subgroup corresponds to the RRM1 of HuD, also termed ELAV-like protein 4 (ELAV-4), or paraneoplastic encephalomyelitis antigen HuD, one of the neuronal members of the Hu family. The neuronal Hu proteins play important roles in neuronal differentiation, plasticity and memory. HuD has been implicated in various aspects of neuronal function, such as the commitment and differentiation of neuronal precursors as well as synaptic remodeling in mature neurons. HuD also functions as an important regulator of mRNA expression in neurons by interacting with AU-rich RNA element (ARE) and stabilizing multiple transcripts. Moreover, HuD regulates the nuclear processing/stability of N-myc pre-mRNA in neuroblastoma cells, as well as the neurite elongation and morphological differentiation. HuD specifically binds poly(A) RNA. Like other Hu proteins, HuD contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 may cooperate in binding to an ARE. RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 767990410 325 AFLHYPDSAAAQQAVSCLQGLRLGTDTLRVALAR 358
Cdd:cd12770   46 GFVNYIDPKDAEKAINTLNGLRLQTKTIKVSYAR 79