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 2017833120 302 VYIGDIPSTTRVSELKSILRSRDAFPLQLTWQGAQRRAFLNYSDPAHAQVVLEKLEGLNIGGHPVRVEMAR 372
Cdd:cd12270     2 VYVGNIPRSVRVSDLKSALRERGINPLRITWQGARGKAFLHYSDMADADSAVSSLQGLRIGGNTLTVELAK 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 2017833120 302 VYIGDIPSTTRVSELKSILRSRDAFPLQLTWQGAQRRAFLNYSDPAHAQVVLEKLEGLNIGGHPVRVEMAR 372
Cdd:cd12270     2 VYVGNIPRSVRVSDLKSALRERGINPLRITWQGARGKAFLHYSDMADADSAVSSLQGLRIGGNTLTVELAK 72

5,10-methenyltetrahydrofolate synthetase; This enzyme, 5,10-methenyltetrahydrofolate synthetase, is also called 5-formyltetrahydrofolate cycloligase. Function of bacterial proteins in this family was inferred originally from the known activity of eukaryotic homologs. Recently, activity was shown explicitly for the member from Mycoplasma pneumonia. Members of this family from alpha- and gamma-proteobacteria, designated ygfA, are often found in an operon with 6S structural RNA, and show a similar pattern of high expression during stationary phase. The function may be to deplete folate to slow 1-carbon biosynthetic metabolism. [Central intermediary metabolism, One-carbon metabolism]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2017833120  92 PTPRLRSGLFNkITPPPGATKEvlricatsqgvrnysvPLGLDaavQVDLIVVGSVAVSEKGWRIGKGEGFADMEYAMMV 171
Cdd:TIGR02727  89 PEQLLTKGPFG-ILEPVGDLEE----------------PVPPD---EIDLIIVPGVAFDRRGYRLGYGGGYYDRFLARLK 148

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2017833120 172 AmgavtdqtIVVTVVHDCQVLD-IPEEllgDHDLTVDYILTP 212
Cdd:TIGR02727 149 G--------ITIGLAFDFQLVDeLPRE---PHDVPVDAIITE 179

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2017833120  302 VYIGDIPSTTRVSELKSILR-----SRDAFPLQLTWQGAQRRAFLNYSDPAHAQVVLEKLEGLNIGGHPVRV 368
Cdd:smart00360   2 LFVGNLPPDTTEEELRELFSkfgkvESVRLVRDKETGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

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 2017833120 302 VYIGDIPSTTRVSELKSILRSRDAFPLQLTWQGAQRRAFLNYSDPAHAQVVLEKLEGLNIGGHPVRVEMAR 372
Cdd:cd12270     2 VYVGNIPRSVRVSDLKSALRERGINPLRITWQGARGKAFLHYSDMADADSAVSSLQGLRIGGNTLTVELAK 72

5,10-methenyltetrahydrofolate synthetase; This enzyme, 5,10-methenyltetrahydrofolate synthetase, is also called 5-formyltetrahydrofolate cycloligase. Function of bacterial proteins in this family was inferred originally from the known activity of eukaryotic homologs. Recently, activity was shown explicitly for the member from Mycoplasma pneumonia. Members of this family from alpha- and gamma-proteobacteria, designated ygfA, are often found in an operon with 6S structural RNA, and show a similar pattern of high expression during stationary phase. The function may be to deplete folate to slow 1-carbon biosynthetic metabolism. [Central intermediary metabolism, One-carbon metabolism]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2017833120  92 PTPRLRSGLFNkITPPPGATKEvlricatsqgvrnysvPLGLDaavQVDLIVVGSVAVSEKGWRIGKGEGFADMEYAMMV 171
Cdd:TIGR02727  89 PEQLLTKGPFG-ILEPVGDLEE----------------PVPPD---EIDLIIVPGVAFDRRGYRLGYGGGYYDRFLARLK 148

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2017833120 172 AmgavtdqtIVVTVVHDCQVLD-IPEEllgDHDLTVDYILTP 212
Cdd:TIGR02727 149 G--------ITIGLAFDFQLVDeLPRE---PHDVPVDAIITE 179

5-formyltetrahydrofolate cyclo-ligase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2017833120 133 LDAAVQVDLIVVGSVAVSEKGWRIGKGEGFAD---MEYAMMvAMGAVTDQTIVVTVVHDCQVLDIPEELLGDHDLTVDYI 209
Cdd:PLN02812  126 LQAPEPLDLLLLPGLAFDRSGRRLGRGGGYYDtflSKYQEL-AKEKGWKQPLLVALSYSPQILDEGSVPVDETDVLVDAL 204

                  ....*..
gi 2017833120 210 LTPTRVI 216
Cdd:PLN02812  205 VTPSGVI 211

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2017833120 302 VYIGDIPSTTRVSELksilrsRDAF----PLQLTWqgAQRR----AFLNYSDPAHAQVVLEKLEGLNIGGHPVRVEMARG 373
Cdd:cd12373     2 VYVGNLGPRVTKREL------EDAFekygPLRNVW--VARNppgfAFVEFEDPRDAEDAVRALDGRRICGSRVRVELSRG 73

RNA recognition motif (RRM) found in yeast RNA-binding protein PIN4, fission yeast RNA-binding post-transcriptional regulators cip1, cip2 and similar proteins; This subfamily corresponds to the RRM in PIN4, also termed psi inducibility protein 4 or modifier of damage tolerance Mdt1, a novel phosphothreonine (pThr)-containing protein that specifically interacts with the pThr-binding site of the Rad53 FHA1 domain. It is encoded by gene MDT1 (YBL051C) from yeast Saccharomyces cerevisiae. PIN4 is involved in normal G2/M cell cycle progression in the absence of DNA damage and functions as a novel target of checkpoint-dependent cell cycle arrest pathways. It contains an N-terminal RRM, a nuclear localization signal, a coiled coil, and a total of 15 SQ/TQ motifs. cip1 (Csx1-interacting protein 1) and cip2 (Csx1-interacting protein 2) are novel cytoplasmic RRM-containing proteins that counteract Csx1 function during oxidative stress. They are not essential for viability in fission yeast Schizosaccharomyces pombe. Both cip1 and cip2 contain one RRM. Like PIN4, Cip2 also possesses an R3H motif that may function in sequence-specific binding to single-stranded nucleic acids.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 2017833120 339 AFLNYSDPAHAQVVLEKLEGLNIGGHPVRVEMAR 372
Cdd:cd12253    46 AFANFRSPEEAQTVVEALNGYEISGRRLRVEYKR 79