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 795187749   10 KQDIREQI---WDHMESQNLADFPRPVHHRIPNFKGSylacQNIKDLDVFartqeVKVDPDKPLEGVRLLALQSNKTLLV 86
Cdd:pfam01812   1 KQELRKQLlarRRALSEEERAAQSEALHQRLISLPEY----QKAKRVAAY-----VSVGGEIDTRELIDLLLEEGKRVLL 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 795187749   87 PTPRLRTGLFN--KITPPPGATKDILRKCATSQGVRNYSVPIGLDsrvLVDLVVVGSVAVSEKGWRIGKGEGYADLEYAM 164
Cdd:pfam01812  72 PVPRPGSGHLDmvRFTPYYPEDSLPRGAWGLKEPVEEELRELALG---QLDLVLVPGVAFDRQGYRLGRGGGYYDRYLAR 148

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 795187749  165 MVSMGAvsTETPVVTIVHDCQVVDIPeelLEEHDITVDYILTP 207
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 795187749   10 KQDIREQI---WDHMESQNLADFPRPVHHRIPNFKGSylacQNIKDLDVFartqeVKVDPDKPLEGVRLLALQSNKTLLV 86
Cdd:pfam01812   1 KQELRKQLlarRRALSEEERAAQSEALHQRLISLPEY----QKAKRVAAY-----VSVGGEIDTRELIDLLLEEGKRVLL 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 795187749   87 PTPRLRTGLFN--KITPPPGATKDILRKCATSQGVRNYSVPIGLDsrvLVDLVVVGSVAVSEKGWRIGKGEGYADLEYAM 164
Cdd:pfam01812  72 PVPRPGSGHLDmvRFTPYYPEDSLPRGAWGLKEPVEEELRELALG---QLDLVLVPGVAFDRQGYRLGRGGGYYDRYLAR 148

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 795187749  165 MVSMGAvsTETPVVTIVHDCQVVDIPeelLEEHDITVDYILTP 207
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 795187749   77 ALQSNKTLLVP--TPRLRTGLFNKITPPpgatKDILRKcatsqGVRNYSVPIGLDSRVL----VDLVVVGSVAVSEKGWR 150
Cdd:TIGR02727  62 LLKEGKRVALPkvDPDGKEMLFFRIWSP----EQLLTK-----GPFGILEPVGDLEEPVppdeIDLIIVPGVAFDRRGYR 132

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 795187749  151 IGKGEGYADLEYAMMvsmgavstETPVVTIVHDCQVVD-IPEellEEHDITVDYILTP 207
Cdd:TIGR02727 133 LGYGGGYYDRFLARL--------KGITIGLAFDFQLVDeLPR---EPHDVPVDAIITE 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 795187749  309 YVGNLPRDARVSDLKRALRELGSV-----PLRLTWQgPRRRAFLRYPDSAAAQQAVSCLQGLRLGTDTLR 373
Cdd:pfam00076   2 FVGNLPPDTTEEDLKDLFSKFGPIksirlVRDETGR-SKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

5-formyltetrahydrofolate cyclo-ligase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 795187749 134 VDLVVVGSVAVSEKGWRIGKGEGYADLEYAMMVSMGAVSTETP--VVTIVHDCQVVDIPEELLEEHDITVDYILTPTRVI 211
Cdd:PLN02812 132 LDLLLLPGLAFDRSGRRLGRGGGYYDTFLSKYQELAKEKGWKQplLVALSYSPQILDEGSVPVDETDVLVDALVTPSGVI 211

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 795187749   10 KQDIREQI---WDHMESQNLADFPRPVHHRIPNFKGSylacQNIKDLDVFartqeVKVDPDKPLEGVRLLALQSNKTLLV 86
Cdd:pfam01812   1 KQELRKQLlarRRALSEEERAAQSEALHQRLISLPEY----QKAKRVAAY-----VSVGGEIDTRELIDLLLEEGKRVLL 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 795187749   87 PTPRLRTGLFN--KITPPPGATKDILRKCATSQGVRNYSVPIGLDsrvLVDLVVVGSVAVSEKGWRIGKGEGYADLEYAM 164
Cdd:pfam01812  72 PVPRPGSGHLDmvRFTPYYPEDSLPRGAWGLKEPVEEELRELALG---QLDLVLVPGVAFDRQGYRLGRGGGYYDRYLAR 148

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 795187749  165 MVSMGAvsTETPVVTIVHDCQVVDIPeelLEEHDITVDYILTP 207
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 795187749   77 ALQSNKTLLVP--TPRLRTGLFNKITPPpgatKDILRKcatsqGVRNYSVPIGLDSRVL----VDLVVVGSVAVSEKGWR 150
Cdd:TIGR02727  62 LLKEGKRVALPkvDPDGKEMLFFRIWSP----EQLLTK-----GPFGILEPVGDLEEPVppdeIDLIIVPGVAFDRRGYR 132

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 795187749  151 IGKGEGYADLEYAMMvsmgavstETPVVTIVHDCQVVD-IPEellEEHDITVDYILTP 207
Cdd:TIGR02727 133 LGYGGGYYDRFLARL--------KGITIGLAFDFQLVDeLPR---EPHDVPVDAIITE 179

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 795187749   309 YVGNLPRDARVSDLKRALRELGSV-----PLRLTWQGPRRRAFLRYPDSAAAQQAVSCLQGLRLGTDTLRV 374
Cdd:smart00360   3 FVGNLPPDTTEEELRELFSKFGKVesvrlVRDKETGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

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 795187749 309 YVGNLPRDARVSDLKRALRELGsvPLRLTW--QGPRRRAFLRYPDSAAAQQAVSCLQGLRLGTDTLRVALAR 378
Cdd:cd12373    3 YVGNLGPRVTKRELEDAFEKYG--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 795187749 309 YVGNLPRDARVSDLKRALRELGSV-PLRL-----TWQgPRRRAFLRYPDSAAAQQAVSCLQGLRLGTDTLRVALA 377
Cdd:cd12398    4 FVGNIPYDATEEQLKEIFSEVGPVvSFRLvtdreTGK-PKGYGFCEFRDAETALSAVRNLNGYELNGRPLRVDFA 77

5-formyltetrahydrofolate cyclo-ligase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 795187749 134 VDLVVVGSVAVSEKGWRIGKGEGYADLEYAMMVSMGAVSTETP--VVTIVHDCQVVDIPEELLEEHDITVDYILTPTRVI 211
Cdd:PLN02812 132 LDLLLLPGLAFDRSGRRLGRGGGYYDTFLSKYQELAKEKGWKQplLVALSYSPQILDEGSVPVDETDVLVDALVTPSGVI 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 795187749 303 PLAADAYVGNLPRDARVSDLKRALRELGsvPLRLTW--QGPRRRAFLRYPDSAAAQQAVSCLQGLRLGTDTLRVALARQQ 380
Cdd:cd12645    2 PLDCKVYVGNLGNNGNKTELERAFGYYG--PLRSVWvaRNPPGFAFVEFEDPRDAADAVRELDGRTLCGCRVRVELSNGE 79

                 .
gi 795187749 381 R 381
Cdd:cd12645   80 K 80

RNA recognition motif 2 (RRM2) found in Drosophila sex-lethal (SXL) and similar proteins; This subfamily corresponds to the RRM2 of the sex-lethal protein (SXL) which governs sexual differentiation and X chromosome dosage compensation in Drosophila melanogaster. It induces female-specific alternative splicing of the transformer (tra) pre-mRNA by binding to the tra uridine-rich polypyrimidine tract at the non-sex-specific 3' splice site during the sex-determination process. SXL binds also to its own pre-mRNA and promotes female-specific alternative splicing. SXL contains an N-terminal Gly/Asn-rich domain that may be responsible for the protein-protein interaction, and tandem RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), that show high preference to bind single-stranded, uridine-rich target RNA transcripts.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 795187749 306 ADAYVGNLPRDARVSDLKRALRELGSVP----LRLTWQG-PRRRAFLRYPDSAAAQQAVSCLQGLRL--GTDTLRVALA 377
Cdd:cd12651    3 TNLYVTNLPRTITEDELDTIFGAYGNIVqknlLRDKLTGrPRGVAFVRYDKREEAQAAISALNGTIPegGTQPLSVRLA 81

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 795187749 308 AYVGNLPRDARVSDLKRALRELGSVPLRL----TWQGPRRRAFLRYPDSAAAQQAVScLQGLRLGTDTLRVALARQQR 381
Cdd:cd12402    5 AYLGNLPYDVTEDDIEDFFRGLNISSVRLprenGPGRLRGFGYVEFEDRESLIQALS-LNEESLKNRRIRVDVAGQAQ 81

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 795187749 309 YVGNLPRDARVSDLKRALRELG---SVPL---RLTwqGpRRR--AFLRYPDSAAAQQAVSCLQGLRLGTDTLRVALA 377
Cdd:cd21608    3 YVGNLSWDTTEDDLRDLFSEFGeveSAKVitdRET--G-RSRgfGFVTFSTAEAAEAAIDALNGKELDGRSIVVNEA 76

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 795187749 309 YVGNLPRDARVSDLKRALRELGsvPLRLTW--QGPRRRAFLRYPDSAAAQQAVSCLQGLRLGTDTLRVALA 377
Cdd:cd12646    3 YVGNLGTGAGKGELERAFSYYG--PLRTVWiaRNPPGFAFVEFEDPRDAEDAVRGLDGKVICGSRVRVELS 71