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 677361180    8 TKLLGLQEFKAAKTV----KINPDAPQKNARFLTLEARKTLLVPTPRLRTGLFN--KIVPPSRATKEILRICATSQGIKE 81
Cdd:pfam01812  29 QRLISLPEYQKAKRVaayvSVGGEIDTRELIDLLLEEGKRVLLPVPRPGSGHLDmvRFTPYYPEDSLPRGAWGLKEPVEE 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677361180   82 YSVPVGLdgkARVDLVVVGSVAVSEKGWRIGKGEGYADMEYAMMVSMGAvqEDTPVVTIVHDCQVVDIAeelLDDHDLTV 161
Cdd:pfam01812 109 ELRELAL---GQLDLVLVPGVAFDRQGYRLGRGGGYYDRYLARLQGHGA--KPYTVGLAFDEQLVERLP---VEPHDVPV 180

                  ....*.
gi 677361180  162 DYILTP 167
Cdd:pfam01812 181 DEVVTE 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 677361180    8 TKLLGLQEFKAAKTV----KINPDAPQKNARFLTLEARKTLLVPTPRLRTGLFN--KIVPPSRATKEILRICATSQGIKE 81
Cdd:pfam01812  29 QRLISLPEYQKAKRVaayvSVGGEIDTRELIDLLLEEGKRVLLPVPRPGSGHLDmvRFTPYYPEDSLPRGAWGLKEPVEE 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677361180   82 YSVPVGLdgkARVDLVVVGSVAVSEKGWRIGKGEGYADMEYAMMVSMGAvqEDTPVVTIVHDCQVVDIAeelLDDHDLTV 161
Cdd:pfam01812 109 ELRELAL---GQLDLVLVPGVAFDRQGYRLGRGGGYYDRYLARLQGHGA--KPYTVGLAFDEQLVERLP---VEPHDVPV 180

                  ....*.
gi 677361180  162 DYILTP 167
Cdd:pfam01812 181 DEVVTE 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 677361180    1 QGASHAATKLLGLQEFKAAKTV------KINPDApqknaRFLTLEAR---KTLLVP--TPRLRTGLFNKIVPPSratkEI 69
Cdd:TIGR02727  22 AASSAIAKRLLALIEWKNAKTIalylplRGEVDT-----RPLIEQLLkegKRVALPkvDPDGKEMLFFRIWSPE----QL 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677361180   70 LRicATSQGIKEYSVPV-GLDGKARVDLVVVGSVAVSEKGWRIGKGEGYADMEYAMMvsmgavqeDTPVVTIVHDCQVVD 148
Cdd:TIGR02727  93 LT--KGPFGILEPVGDLeEPVPPDEIDLIIVPGVAFDRRGYRLGYGGGYYDRFLARL--------KGITIGLAFDFQLVD 162

                         170
                  ....*....|....*....
gi 677361180  149 iaEELLDDHDLTVDYILTP 167
Cdd:TIGR02727 163 --ELPREPHDVPVDAIITE 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 677361180  243 VYVGNIPPSVRVSELKSALREF----HATPLRLNWQGAQHRAFLDYKDKATAESAVSSLKGLSLGGNTLR 308
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFgpikSIRLVRDETGRSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677361180 242 TVYVGNIPPSVRVSELKSALREFhatplrlnwqGAQHR---------------AFLDYKDKATAESAVSSLKGLSLGGNT 306
Cdd:COG0724    3 KIYVGNLPYSVTEEDLRELFSEY----------GEVTSvklitdretgrsrgfGFVEMPDDEEAQAAIEALNGAELMGRT 72

                 ....*..
gi 677361180 307 LRVELAK 313
Cdd:COG0724   73 LKVNEAR 79

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 677361180    8 TKLLGLQEFKAAKTV----KINPDAPQKNARFLTLEARKTLLVPTPRLRTGLFN--KIVPPSRATKEILRICATSQGIKE 81
Cdd:pfam01812  29 QRLISLPEYQKAKRVaayvSVGGEIDTRELIDLLLEEGKRVLLPVPRPGSGHLDmvRFTPYYPEDSLPRGAWGLKEPVEE 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677361180   82 YSVPVGLdgkARVDLVVVGSVAVSEKGWRIGKGEGYADMEYAMMVSMGAvqEDTPVVTIVHDCQVVDIAeelLDDHDLTV 161
Cdd:pfam01812 109 ELRELAL---GQLDLVLVPGVAFDRQGYRLGRGGGYYDRYLARLQGHGA--KPYTVGLAFDEQLVERLP---VEPHDVPV 180

                  ....*.
gi 677361180  162 DYILTP 167
Cdd:pfam01812 181 DEVVTE 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 677361180 243 VYVGNIPPSVRVSELKSALREF----HATPLRLNWQGAQHRAFLDYKDKATAESAVSSLKGLSLGGNTLRVE 310
Cdd:cd00590    1 LFVGNLPPDTTEEDLRELFSKFgevvSVRIVRDRDGKSKGFAFVEFESPEDAEKALEALNGTELGGRPLKVS 72

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 677361180 243 VYVGNIPPSVRVSELKSALREFhaTPLRLNWQgAQHR---AFLDYKDKATAESAVSSLKGLSLGGNTLRVELAKN 314
Cdd:cd12373    2 VYVGNLGPRVTKRELEDAFEKY--GPLRNVWV-ARNPpgfAFVEFEDPRDAEDAVRALDGRRICGSRVRVELSRG 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 677361180  243 VYVGNIPPSVRVSELKSALREF----HATPLRLNWQGAQHRAFLDYKDKATAESAVSSLKGLSLGGNTLR 308
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFgpikSIRLVRDETGRSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

5-formyltetrahydrofolate cyclo-ligase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677361180  85 PVGLDGKAR---------VDLVVVGSVAVSEKGWRIGKGEGYAD---MEYAMMVsmGAVQEDTP-VVTIVHDCQVVDIAE 151
Cdd:PLN02812 114 PVDADGNPRedvlqapepLDLLLLPGLAFDRSGRRLGRGGGYYDtflSKYQELA--KEKGWKQPlLVALSYSPQILDEGS 191

                         90       100
                 ....*....|....*....|
gi 677361180 152 ELLDDHDLTVDYILTPTRTI 171
Cdd:PLN02812 192 VPVDETDVLVDALVTPSGVI 211

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 677361180 243 VYVGNIPPSVRVSELKSALREF-HATPLRLN---WQGAQHRAFLDYKDKATA-ESAVSSLKGLSLGGNTLRVELAK 313
Cdd:cd12226    2 LFVGGLSPSITEDDLERRFSRFgTVSDVEIIrkkDAPDRGFAYIDLRTSEAAlQKCLSTLNGVKWKGSRLKIQLAK 77

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 677361180 242 TVYVGNIPPSVRVSELKSALREF---HATPLRLNWQGAQHrAFLDYKDKATAESAVSSLKGLSLGGNTLRVEL 311
Cdd:cd12338    1 RIYVGNLPGDIRERDIEDLFYKYgpiLAIDLKNRRRGPPF-AFVEFEDPRDAEDAIRGRDGYDFDGYRLRVEF 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 677361180 242 TVYVGNIPPSVRVSELKSALREfhATP---LRLNWQGAQHR----AFLDYKDKATAESAVSSLKGLSLGGNTLRVELA 312
Cdd:cd12671    8 SVFVGNIPYEATEEQLKDIFSE--VGPvvsFRLVYDRETGKpkgyGFCEYQDQETALSAMRNLNGYELNGRALRVDNA 83

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 677361180 242 TVYVGNIPPSVRVSELKSALREF---HATPLRLNWQGAQHR--AFLDYKDKATAESAVSSLKGLSLGGNTLRVELA 312
Cdd:cd21608    1 KLYVGNLSWDTTEDDLRDLFSEFgevESAKVITDRETGRSRgfGFVTFSTAEAAEAAIDALNGKELDGRSIVVNEA 76

RNA recognition motif 2 (RRM2) found in (U)-binding-splicing factor PUF60 and similar proteins; This subfamily corresponds to the RRM2 of PUF60, also termed FUSE-binding protein-interacting repressor (FBP-interacting repressor or FIR), or Ro-binding protein 1 (RoBP1), or Siah-binding protein 1 (Siah-BP1). PUF60 is an essential splicing factor that functions as a poly-U RNA-binding protein required to reconstitute splicing in depleted nuclear extracts. Its function is enhanced through interaction with U2 auxiliary factor U2AF65. PUF60 also controls human c-myc gene expression by binding and inhibiting the transcription factor far upstream sequence element (FUSE)-binding-protein (FBP), an activator of c-myc promoters. PUF60 contains two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbors another RRM and binds to tryptophan-containing linear peptide motifs (UHM ligand motifs, ULMs) in several nuclear proteins. Research indicates that PUF60 binds FUSE as a dimer, and only the first two RRM domains participate in the single-stranded DNA recognition.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 677361180 243 VYVGNIPPSVRVSELKSALREF---HATPLRLNWQGAQHRA--FLDYKDKATAESAVSSLKGLSLGGNTLRV 309
Cdd:cd12371    3 IYVASVHPDLSEDDIKSVFEAFgkiKSCSLAPDPETGKHKGygFIEYENPQSAQDAIASMNLFDLGGQYLRV 74

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 677361180 242 TVYVGNIPPSV---RVSELKSAlrEFHATPLRLNWQGAQHR-AFLDYKDKATAESAVSsLKGLSLGGNTLRVELAK 313
Cdd:cd12225    2 TIHVGGIDGSLsedELADYFSN--CGEVTQVRLCGDRVHTRfAWVEFATDASALSALN-LDGTTLGGHPLRVSPSK 74

RNA recognition motif (RRM) found in cyclophilin-33 (Cyp33) and similar proteins; This subfamily corresponds to the RRM of Cyp33, also termed peptidyl-prolyl cis-trans isomerase E (PPIase E), or cyclophilin E, or rotamase E. Cyp33 is a nuclear RNA-binding cyclophilin with an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal PPIase domain. Cyp33 possesses RNA-binding activity and preferentially binds to polyribonucleotide polyA and polyU, but hardly to polyG and polyC. It binds specifically to mRNA, which can stimulate its PPIase activity. Moreover, Cyp33 interacts with the third plant homeodomain (PHD3) zinc finger cassette of the mixed lineage leukemia (MLL) proto-oncoprotein and a poly-A RNA sequence through its RRM domain. It further mediates downregulation of the expression of MLL target genes HOXC8, HOXA9, CDKN1B, and C-MYC, in a proline isomerase-dependent manner. Cyp33 also possesses a PPIase activity that catalyzes cis-trans isomerization of the peptide bond preceding a proline, which has been implicated in the stimulation of folding and conformational changes in folded and unfolded proteins. The PPIase activity can be inhibited by the immunosuppressive drug cyclosporin A.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 677361180 243 VYVGNIPPSVRVSELKSALREF---HATPLRLNWQGAQHR--AFLDYKDKATAESAVSSLKGLSLGGNTLRVELA 312
Cdd:cd12347    1 LYVGGLAEEVDEKVLHAAFIPFgdiVDIQIPLDYETEKHRgfAFVEFEEAEDAAAAIDNMNESELFGRTIRVNLA 75

RNA recognition motif (RRM) found in RNA-binding protein 44 (RBM44) and similar proteins; This subgroup corresponds to the RRM of RBM44, a novel germ cell intercellular bridge protein that is localized in the cytoplasm and intercellular bridges from pachytene to secondary spermatocyte stages. RBM44 interacts with itself and testis-expressed gene 14 (TEX14). Unlike TEX14, RBM44 does not function in the formation of stable intercellular bridges. It carries an RNA recognition motif (RRM) that could potentially bind a multitude of RNA sequences in the cytoplasm and help to shuttle them through the intercellular bridge, facilitating their dispersion into the interconnected neighboring cells.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 677361180 243 VYVGNIPPSVRVSELKSALREFHATPLRLNWQGAQHR-AFLDYKDKATAESAVSSLKGLSLGGNTLRVELAK 313
Cdd:cd12248    4 VHVGNLAPSVSEEDLLMHFEKYHVSKISIQKLSMNYRyASLTFDDASDAQAAVKEMNGKDISGRKVKVRYVK 75

RNA recognition motif 2 (RRM2) found in granule-associated RNA binding proteins (p40-TIA-1 and TIAR), and yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1; This subfamily corresponds to the RRM3 of TIA-1, TIAR, and PUB1. Nucleolysin TIA-1 isoform p40 (p40-TIA-1 or TIA-1) and nucleolysin TIA-1-related protein (TIAR) are granule-associated RNA binding proteins involved in inducing apoptosis in cytotoxic lymphocyte (CTL) target cells. They share high sequence similarity and are expressed in a wide variety of cell types. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis.TIAR is mainly localized in the nucleus of hematopoietic and nonhematopoietic cells. It is translocated from the nucleus to the cytoplasm in response to exogenous triggers of apoptosis. Both TIA-1 and TIAR bind specifically to poly(A) but not to poly(C) homopolymers. They are composed of three N-terminal highly homologous RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. TIA-1 and TIAR interact with RNAs containing short stretches of uridylates and their RRM2 can mediate the specific binding to uridylate-rich RNAs. The C-terminal auxiliary domain may be responsible for interacting with other proteins. In addition, TIA-1 and TIAR share a potential serine protease-cleavage site (Phe-Val-Arg) localized at the junction between their RNA binding domains and their C-terminal auxiliary domains. This subfamily also includes a yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1, termed ARS consensus-binding protein ACBP-60, or poly uridylate-binding protein, or poly(U)-binding protein, which has been identified as both a heterogeneous nuclear RNA-binding protein (hnRNP) and a cytoplasmic mRNA-binding protein (mRNP). It may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm. PUB1 is distributed in both, the nucleus and the cytoplasm, and binds to poly(A)+ RNA (mRNA or pre-mRNA). Although it is one of the major cellular proteins cross-linked by UV light to polyadenylated RNAs in vivo, PUB1 is nonessential for cell growth in yeast. PUB1 also binds to T-rich single stranded DNA (ssDNA); however, there is no strong evidence implicating PUB1 in the mechanism of DNA replication. PUB1 contains three RRMs, and a GAR motif (glycine and arginine rich stretch) that is located between RRM2 and RRM3.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 677361180 241 TTVYVGNIPPSVRVSELKSALREF-HATPLRLNWQGAQhrAFLDYKDKATAESAVSSLKGLSLGGNTLR 308
Cdd:cd12354    1 TTVYVGNITKGLTEALLQQTFSPFgQILEVRVFPDKGY--AFIRFDSHEAATHAIVSVNGTIINGQAVK 67

RNA recognition motif 1 (RRM1) found in the VICKZ family proteins; Thid subfamily corresponds to the RRM1 of IGF2BPs (or IMPs) found in the VICKZ family that have been implicated in the post-transcriptional regulation of several different RNAs and in subcytoplasmic localization of mRNAs during embryogenesis. IGF2BPs are composed of two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and four hnRNP K homology (KH) domains.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 677361180 244 YVGNIPPSVRVSELKSALREfHATPLR---LNWQGAqhrAFLDYKDKATAESAVSSLKGLSLGGNTLRVELA 312
Cdd:cd12358    2 YIGNLSSDVNESDLRQLFEE-HKIPVSsvlVKKGGY---AFVDCPDQSWADKAIEKLNGKILQGKVIEVEHS 69

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 677361180 243 VYVGNIPPSVRVSELKSALREFHAtPLRLNWQGAQHRAFLDYKDKATAESAVSSLKGLSLGGN--TLRVELAK 313
Cdd:cd12310    1 LWVGGLGPWTSLAELEREFDRFGA-IRKIDYRKGDDYAYILYESLDAAQAAVRALRGFPLGGPdrRLRVDFAD 72

RNA recognition motif 1 (RRM1) found in (U)-binding-splicing factor PUF60 and similar proteins; This subfamily corresponds to the RRM1 of PUF60, also termed FUSE-binding protein-interacting repressor (FBP-interacting repressor or FIR), or Ro-binding protein 1 (RoBP1), or Siah-binding protein 1 (Siah-BP1). PUF60 is an essential splicing factor that functions as a poly-U RNA-binding protein required to reconstitute splicing in depleted nuclear extracts. Its function is enhanced through interaction with U2 auxiliary factor U2AF65. PUF60 also controls human c-myc gene expression by binding and inhibiting the transcription factor far upstream sequence element (FUSE)-binding-protein (FBP), an activator of c-myc promoters. PUF60 contains two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbors another RRM and binds to tryptophan-containing linear peptide motifs (UHM ligand motifs, ULMs) in several nuclear proteins. Research indicates that PUF60 binds FUSE as a dimer, and only the first two RRM domains participate in the single-stranded DNA recognition.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 677361180 243 VYVGNIPPSVRVSELKSALREFhaTPLR---LNWQGAQHR----AFLDYKDKATAESAVSSLKGLSLGGNTLRV 309
Cdd:cd12370    3 VYVGSIYFELGEDTIRQAFAPF--GPIKsidMSWDPVTMKhkgfAFVEYEVPEAAQLALEQMNGVMLGGRNIKV 74

RNA recognition motif 1 (RRM1) found in vertebrate serine/arginine-rich splicing factor 9 (SRSF9); This subgroup corresponds to the RRM1 of SRSF9, also termed pre-mRNA-splicing factor SRp30C. SRSF9 is an essential splicing regulatory serine/arginine (SR) protein that 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. SRSF9 can also interact with other proteins implicated in alternative splicing, including YB-1, rSLM-1, rSLM-2, E4-ORF4, Nop30, and p32. SRSF9 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by an unusually short C-terminal RS domains rich in serine-arginine dipeptides.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 677361180 243 VYVGNIPPSVRVSELKSALREF---HATPLRlNWQGAQHRAFLDYKDKATAESAVSSLKGLSLGGNTLRVE 310
Cdd:cd12598    2 IYVGNLPSDVREKDLEDLFYKYgriRDIELK-NRRGLVPFAFVRFEDPRDAEDAVFGRNGYDFGQCRLRVE 71

RNA recognition motif (RRM) found in tRNA (uracil-5-)-methyltransferase homolog A (TRMT2A) and similar proteins; This subfamily corresponds to the RRM of TRMT2A, also known as HpaII tiny fragments locus 9c protein (HTF9C), a novel cell cycle regulated protein. It is an independent biologic factor expressed in tumors associated with clinical outcome in HER2 expressing breast cancer. The function of TRMT2A remains unclear although by sequence homology it has a RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), related to RNA methyltransferases.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 677361180 245 VGNIPPSVRVSELKSALREFHATPLRLNWQGAQHRAFLDYKDKATAESAVSSLKGLSLGGNTLRVELAK 313
Cdd:cd12439   10 IKNLPKYIGFGQLKKFLQKLGLKPHKIKLIGRQTFAFVTFRNEEDRDKALKVLNGHKWKGKVLSAKLAK 78