5-formyltetrahydrofolate cyclo-ligase family; 5-formyltetrahydrofolate cyclo-ligase or methenyl-THF synthetase EC:6.3.3.2 catalyzes the interchange of 5-formyltetrahydrofolate (5-FTHF) to 5-10-methenyltetrahydrofolate, this requires ATP and Mg2+. 5-FTHF is used in chemotherapy where it is clinically known as Leucovorin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116875838    9 KQDIREQI---WGYMESQNLADFPRPVHHRIPNFKGSylacQNIKDLDVFartqeVKVDPDKPLEGVRLLVLQSKKTLLV 85
Cdd:pfam01812   1 KQELRKQLlarRRALSEEERAAQSEALHQRLISLPEY----QKAKRVAAY-----VSVGGEIDTRELIDLLLEEGKRVLL 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116875838   86 PTPRLRTGLFN--KITPPPGATKDILRKCATSQGVRNYSVPIGLDsrvLVDLVVVGSVAVSEKGWRIGKGEGYADLEYAM 163
Cdd:pfam01812  72 PVPRPGSGHLDmvRFTPYYPEDSLPRGAWGLKEPVEEELRELALG---QLDLVLVPGVAFDRQGYRLGRGGGYYDRYLAR 148

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 116875838  164 MVSMGAvsKETPVVTIVHDCQVVDIPeelVEEHDITVDYILTP 206
Cdd:pfam01812 149 LQGHGA--KPYTVGLAFDEQLVERLP---VEPHDVPVDEVVTE 186

5-formyltetrahydrofolate cyclo-ligase family; 5-formyltetrahydrofolate cyclo-ligase or methenyl-THF synthetase EC:6.3.3.2 catalyzes the interchange of 5-formyltetrahydrofolate (5-FTHF) to 5-10-methenyltetrahydrofolate, this requires ATP and Mg2+. 5-FTHF is used in chemotherapy where it is clinically known as Leucovorin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116875838    9 KQDIREQI---WGYMESQNLADFPRPVHHRIPNFKGSylacQNIKDLDVFartqeVKVDPDKPLEGVRLLVLQSKKTLLV 85
Cdd:pfam01812   1 KQELRKQLlarRRALSEEERAAQSEALHQRLISLPEY----QKAKRVAAY-----VSVGGEIDTRELIDLLLEEGKRVLL 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116875838   86 PTPRLRTGLFN--KITPPPGATKDILRKCATSQGVRNYSVPIGLDsrvLVDLVVVGSVAVSEKGWRIGKGEGYADLEYAM 163
Cdd:pfam01812  72 PVPRPGSGHLDmvRFTPYYPEDSLPRGAWGLKEPVEEELRELALG---QLDLVLVPGVAFDRQGYRLGRGGGYYDRYLAR 148

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 116875838  164 MVSMGAvsKETPVVTIVHDCQVVDIPeelVEEHDITVDYILTP 206
Cdd:pfam01812 149 LQGHGA--KPYTVGLAFDEQLVERLP---VEPHDVPVDEVVTE 186

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 116875838   77 LQSKKTLLVP--TPRLRTGLFNKITPPpgatKDILRKcatsqGVRNYSVPIGLDSRVL----VDLVVVGSVAVSEKGWRI 150
Cdd:TIGR02727  63 LKEGKRVALPkvDPDGKEMLFFRIWSP----EQLLTK-----GPFGILEPVGDLEEPVppdeIDLIIVPGVAFDRRGYRL 133

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 116875838  151 GKGEGYADLEYAMMvsmgavskETPVVTIVHDCQVVD-IPeelVEEHDITVDYILTP 206
Cdd:TIGR02727 134 GYGGGYYDRFLARL--------KGITIGLAFDFQLVDeLP---REPHDVPVDAIITE 179

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 116875838  307 VYVGNLPGDARVSDLKRALRELGSV-----PLRLTWQgPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLR 372
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIksirlVRDETGR-SKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116875838 308 YVGNLPGDARVSDLKRALRELGSV------PLRLTwQGPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLRVALARQQRD 381
Cdd:COG0724    5 YVGNLPYSVTEEDLRELFSEYGEVtsvkliTDRET-GRSRGFGFVEMPDDEEAQAAIEALNGAELMGRTLKVNEARPREE 83

                 .
gi 116875838 382 K 382
Cdd:COG0724   84 R 84

5-formyltetrahydrofolate cyclo-ligase family; 5-formyltetrahydrofolate cyclo-ligase or methenyl-THF synthetase EC:6.3.3.2 catalyzes the interchange of 5-formyltetrahydrofolate (5-FTHF) to 5-10-methenyltetrahydrofolate, this requires ATP and Mg2+. 5-FTHF is used in chemotherapy where it is clinically known as Leucovorin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116875838    9 KQDIREQI---WGYMESQNLADFPRPVHHRIPNFKGSylacQNIKDLDVFartqeVKVDPDKPLEGVRLLVLQSKKTLLV 85
Cdd:pfam01812   1 KQELRKQLlarRRALSEEERAAQSEALHQRLISLPEY----QKAKRVAAY-----VSVGGEIDTRELIDLLLEEGKRVLL 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116875838   86 PTPRLRTGLFN--KITPPPGATKDILRKCATSQGVRNYSVPIGLDsrvLVDLVVVGSVAVSEKGWRIGKGEGYADLEYAM 163
Cdd:pfam01812  72 PVPRPGSGHLDmvRFTPYYPEDSLPRGAWGLKEPVEEELRELALG---QLDLVLVPGVAFDRQGYRLGRGGGYYDRYLAR 148

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 116875838  164 MVSMGAvsKETPVVTIVHDCQVVDIPeelVEEHDITVDYILTP 206
Cdd:pfam01812 149 LQGHGA--KPYTVGLAFDEQLVERLP---VEPHDVPVDEVVTE 186

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 116875838   77 LQSKKTLLVP--TPRLRTGLFNKITPPpgatKDILRKcatsqGVRNYSVPIGLDSRVL----VDLVVVGSVAVSEKGWRI 150
Cdd:TIGR02727  63 LKEGKRVALPkvDPDGKEMLFFRIWSP----EQLLTK-----GPFGILEPVGDLEEPVppdeIDLIIVPGVAFDRRGYRL 133

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 116875838  151 GKGEGYADLEYAMMvsmgavskETPVVTIVHDCQVVD-IPeelVEEHDITVDYILTP 206
Cdd:TIGR02727 134 GYGGGYYDRFLARL--------KGITIGLAFDFQLVDeLP---REPHDVPVDAIITE 179

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 116875838   307 VYVGNLPGDARVSDLKRALRELGSV-----PLRLTWQGPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLRV 373
Cdd:smart00360   2 LFVGNLPPDTTEEELRELFSKFGKVesvrlVRDKETGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 116875838  307 VYVGNLPGDARVSDLKRALRELGSV-----PLRLTWQgPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLR 372
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIksirlVRDETGR-SKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

5-formyltetrahydrofolate cyclo-ligase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116875838 133 VDLVVVGSVAVSEKGWRIGKGEGYADleyAMMVSMGAVSKET-----PVVTIVHDCQVVDIPEELVEEHDITVDYILTPT 207
Cdd:PLN02812 132 LDLLLLPGLAFDRSGRRLGRGGGYYD---TFLSKYQELAKEKgwkqpLLVALSYSPQILDEGSVPVDETDVLVDALVTPS 208

                 ...
gi 116875838 208 RVI 210
Cdd:PLN02812 209 GVI 211

RNA recognition motif (RRM) found in vertebrate serine/arginine-rich splicing factor 3 (SRSF3); This subgroup corresponds to the RRM of SRSF3, also termed pre-mRNA-splicing factor SRp20, a splicing regulatory serine/arginine (SR) protein that 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. SRSF3 can shuttle between the nucleus and cytoplasm. It contains 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 116875838 302 PLAADVYVGNLPGDARVSDLKRALRELGsvPLRLTW--QGPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLRVALARQQ 379
Cdd:cd12645    2 PLDCKVYVGNLGNNGNKTELERAFGYYG--PLRSVWvaRNPPGFAFVEFEDPRDAADAVRELDGRTLCGCRVRVELSNGE 79

                 .
gi 116875838 380 R 380
Cdd:cd12645   80 K 80

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 116875838 307 VYVGNLPGDARVSDLKRALRELGSVpLRLTWQGPRRR---AFLHYPDSAAAQQAVSCLQGLRLGTDTLRVAL 375
Cdd:cd12338    2 IYVGNLPGDIRERDIEDLFYKYGPI-LAIDLKNRRRGppfAFVEFEDPRDAEDAIRGRDGYDFDGYRLRVEF 72

RNA recognition motif (RRM) found in cleavage stimulation factor subunit 2 (CSTF2), cleavage stimulation factor subunit 2 tau variant (CSTF2T) and similar proteins; This subgroup 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 116875838 307 VYVGNLPGDARVSDLKRALRELGSV-PLRLTWQ----GPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLRV 373
Cdd:cd12671    9 VFVGNIPYEATEEQLKDIFSEVGPVvSFRLVYDretgKPKGYGFCEYQDQETALSAMRNLNGYELNGRALRV 80

5-formyltetrahydrofolate cyclo-ligase family protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 116875838 133 VDLVVVGSVAVSEKGWRIGKGEGYADLEYAMMVSMGAvskeTPVvTIVHDCQVVD-IPeelVEEHDITVDYILTPTRV 209
Cdd:PRK10333 110 LDVLITPLVAFDEYGQRLGMGGGFYDRTLQNWQHYKT----QPV-GYAHDCQLVEkLP---VEEWDIPLPAVVTPSKV 179

RNA recognition motif 3 (RRM3) found in the Spen (split end) protein family; This subfamily corresponds to the RRM3 domain in the Spen (split end) protein family which includes RNA binding motif protein 15 (RBM15), putative RNA binding motif protein 15B (RBM15B) and similar proteins found in Metazoa. RBM15, also termed one-twenty two protein 1 (OTT1), conserved in eukaryotes, is a novel mRNA export factor and is a novel component of the NXF1 pathway. It binds to NXF1 and serves as receptor for the RNA export element RTE. It also possess mRNA export activity and can facilitate the access of DEAD-box protein DBP5 to mRNA at the nuclear pore complex (NPC). RNA-binding protein 15B (RBM15B), also termed one twenty-two 3 (OTT3), is a paralog of RBM15 and therefore has post-transcriptional regulatory activity. It is a nuclear protein sharing with RBM15 the association with the splicing factor compartment and the nuclear envelope as well as the binding to mRNA export factors NXF1 and Aly/REF. Members in this family belong to the Spen (split end) protein family, which shares a domain architecture comprising of three N-terminal RNA recognition motifs (RRMs), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal SPOC (Spen paralog and ortholog C-terminal) domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 116875838 307 VYVGNLPGDARVSDLKRALRELGSvPLRLTWQGPRRRAFLHYPDSAAAQQAVSCLQGLRLGTDTLRV 373
Cdd:cd12310    1 LWVGGLGPWTSLAELEREFDRFGA-IRKIDYRKGDDYAYILYESLDAAQAAVRALRGFPLGGPDRRL 66

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

                         10        20        30
                 ....*....|....*....|....*....|...
gi 116875838 344 AFLHYPDSAAAQQAVSCLQGLRLGTDTLRVALA 376
Cdd:cd12650   45 GFVNYVDPSDAEKAINTLNGLRLQNKTIKVSYA 77