RNA recognition motif (RRM) found in vertebrate fused in Ewing's sarcoma protein (FUS), TATA-binding protein-associated factor 15 (TAF15) and similar proteins; This subgroup corresponds to the RRM of FUS and TAF15. FUS (TLS or Pigpen or hnRNP P2), also termed 75 kDa DNA-pairing protein (POMp75), or oncoprotein TLS (Translocated in liposarcoma), is a member of the FET (previously TET) (FUS/TLS, EWS, TAF15) family of RNA- and DNA-binding proteins whose expression is altered in cancer. It is a multi-functional protein and has been implicated in pre-mRNA splicing, chromosome stability, cell spreading, and transcription. FUS was originally identified in human myxoid and round cell liposarcomas as an oncogenic fusion with the stress-induced DNA-binding transcription factor CHOP (CCAAT enhancer-binding homologous protein) and later as hnRNP P2, a component of hnRNP H complex assembled on pre-mRNA. It can form ternary complexes with hnRNP A1 and hnRNP C1/C2. Additional research indicates that FUS binds preferentially to GGUG-containing RNAs. In the presence of Mg2+, it can bind both single- and double-stranded DNA (ssDNA/dsDNA) and promote ATP-independent annealing of complementary ssDNA and D-loop formation in superhelical dsDNA. FUS has been shown to be recruited by single stranded noncoding RNAs to the regulatory regions of target genes such as cyclin D1, where it represses transcription by disrupting complex formation. TAF15 (TAFII68), also termed TATA-binding protein-associated factor 2N (TAF2N), or RNA-binding protein 56 (RBP56), originally identified as a TAF in the general transcription initiation TFIID complex, is a novel RNA/ssDNA-binding protein with homology to the proto-oncoproteins FUS and EWS (also termed EWSR1), belonging to the FET family as well. TAF15 likely functions in RNA polymerase II (RNAP II) transcription by interacting with TFIID and subunits of RNAP II itself. TAF15 is also associated with U1 snRNA, chromatin and RNA, in a complex distinct from the Sm-containing U1 snRNP that functions in splicing. Like other members in the FET family, both FUS and TAF15 contain an N-terminal Ser, Gly, Gln and Tyr-rich region composed of multiple copies of a degenerate hexapeptide repeat motif. The C-terminal region consists of a conserved nuclear import and retention signal (C-NLS), a C2/C2 zinc-finger motif, a conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and at least 1 arginine-glycine-glycine (RGG)-repeat region.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 232 DNNTIFVQGLGEGVSTDQVGEFFKQIGIIKTNKKTGKPMINLYTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGN 311
Cdd:cd12535   1 DNNTIFVQGLGEDVTIDSVADYFKQIGIIKTNKKTGKPMINLYTDKETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGN 80

                ....*.
gi 21327701 312 IIKVSF 317
Cdd:cd12535  81 PIKVSF 86

serine-rich protein; This serine-rich protein belongs to a family with large size (over 1000 amino acids), which a highly serine-rich central region that averages over 300 aa in length. Species encoding members of this family of proteins tend to be anaerobic bacteria, including Gram-positive bacteria of the human gut microbiome and Chloroflexi from marine sediments.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701     2 SDSGSYGQSGG----------EQQSYSTyGNPGSQGYGqASQSYSGYGQttdsSYGQNYSGYSSYGQSQS-GYSQSYGGY 70
Cdd:NF033849  382 SRSSSSGVSGGfsggiagggvTSEGLGA-SQGGSEGWG-SGDSVQSVSQ----SYGSSSSTGTSSGHSDSsSHSTSSGQA 455

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 21327701    71 ENQKQS-SYSQQPYNNQGQQQ-NMESSGSQGGRAPSYDQpDYGQQDSYDQQSGYDQ 124
Cdd:NF033849  456 DSVSQGtSWSEGTGTSQGQSVgTSESWSTSQSETDSVGD-STGTSESVSQGDGRST 510

RNA recognition motif (RRM) found in vertebrate fused in Ewing's sarcoma protein (FUS), TATA-binding protein-associated factor 15 (TAF15) and similar proteins; This subgroup corresponds to the RRM of FUS and TAF15. FUS (TLS or Pigpen or hnRNP P2), also termed 75 kDa DNA-pairing protein (POMp75), or oncoprotein TLS (Translocated in liposarcoma), is a member of the FET (previously TET) (FUS/TLS, EWS, TAF15) family of RNA- and DNA-binding proteins whose expression is altered in cancer. It is a multi-functional protein and has been implicated in pre-mRNA splicing, chromosome stability, cell spreading, and transcription. FUS was originally identified in human myxoid and round cell liposarcomas as an oncogenic fusion with the stress-induced DNA-binding transcription factor CHOP (CCAAT enhancer-binding homologous protein) and later as hnRNP P2, a component of hnRNP H complex assembled on pre-mRNA. It can form ternary complexes with hnRNP A1 and hnRNP C1/C2. Additional research indicates that FUS binds preferentially to GGUG-containing RNAs. In the presence of Mg2+, it can bind both single- and double-stranded DNA (ssDNA/dsDNA) and promote ATP-independent annealing of complementary ssDNA and D-loop formation in superhelical dsDNA. FUS has been shown to be recruited by single stranded noncoding RNAs to the regulatory regions of target genes such as cyclin D1, where it represses transcription by disrupting complex formation. TAF15 (TAFII68), also termed TATA-binding protein-associated factor 2N (TAF2N), or RNA-binding protein 56 (RBP56), originally identified as a TAF in the general transcription initiation TFIID complex, is a novel RNA/ssDNA-binding protein with homology to the proto-oncoproteins FUS and EWS (also termed EWSR1), belonging to the FET family as well. TAF15 likely functions in RNA polymerase II (RNAP II) transcription by interacting with TFIID and subunits of RNAP II itself. TAF15 is also associated with U1 snRNA, chromatin and RNA, in a complex distinct from the Sm-containing U1 snRNP that functions in splicing. Like other members in the FET family, both FUS and TAF15 contain an N-terminal Ser, Gly, Gln and Tyr-rich region composed of multiple copies of a degenerate hexapeptide repeat motif. The C-terminal region consists of a conserved nuclear import and retention signal (C-NLS), a C2/C2 zinc-finger motif, a conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and at least 1 arginine-glycine-glycine (RGG)-repeat region.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 232 DNNTIFVQGLGEGVSTDQVGEFFKQIGIIKTNKKTGKPMINLYTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGN 311
Cdd:cd12535   1 DNNTIFVQGLGEDVTIDSVADYFKQIGIIKTNKKTGKPMINLYTDKETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGN 80

                ....*.
gi 21327701 312 IIKVSF 317
Cdd:cd12535  81 PIKVSF 86

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 233 NNTIFVQGLGEGVSTDQVGEFFKQIGIIKTnkktgkpmINLYTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNI 312
Cdd:COG0724   1 SMKIYVGNLPYSVTEEDLRELFSEYGEVTS--------VKLITDRETGRSRGFGFVEMPDDEEAQAAIEALNGAELMGRT 72

                        90
                ....*....|.
gi 21327701 313 IKVSFATRRPE 323
Cdd:COG0724  73 LKVNEARPREE 83

Zn-finger in Ran binding protein and others;

                          10        20        30
                  ....*....|....*....|....*....|.
gi 21327701   354 KSGDWVCPnpSCGNMNFARRNSCNQCNEPRP 384
Cdd:pfam00641   1 REGDWDCS--KCLVQNFATSTKCVACQAPKP 29

glycine-rich RNA-binding protein 4; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701  236 IFVQGLGEGVSTDQVGEFFKQIGIIKTNKktgkpminLYTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNIIKV 315
Cdd:PLN03134  37 LFIGGLSWGTDDASLRDAFAHFGDVVDAK--------VIVDRETGRSRGFGFVNFNDEGAATAAISEMDGKELNGRHIRV 108

                 ....*..
gi 21327701  316 SFATRRP 322
Cdd:PLN03134 109 NPANDRP 115

serine-rich protein; This serine-rich protein belongs to a family with large size (over 1000 amino acids), which a highly serine-rich central region that averages over 300 aa in length. Species encoding members of this family of proteins tend to be anaerobic bacteria, including Gram-positive bacteria of the human gut microbiome and Chloroflexi from marine sediments.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701     2 SDSGSYGQSGG----------EQQSYSTyGNPGSQGYGqASQSYSGYGQttdsSYGQNYSGYSSYGQSQS-GYSQSYGGY 70
Cdd:NF033849  382 SRSSSSGVSGGfsggiagggvTSEGLGA-SQGGSEGWG-SGDSVQSVSQ----SYGSSSSTGTSSGHSDSsSHSTSSGQA 455

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 21327701    71 ENQKQS-SYSQQPYNNQGQQQ-NMESSGSQGGRAPSYDQpDYGQQDSYDQQSGYDQ 124
Cdd:NF033849  456 DSVSQGtSWSEGTGTSQGQSVgTSESWSTSQSETDSVGD-STGTSESVSQGDGRST 510

RNA recognition motif (RRM) found in vertebrate fused in Ewing's sarcoma protein (FUS), TATA-binding protein-associated factor 15 (TAF15) and similar proteins; This subgroup corresponds to the RRM of FUS and TAF15. FUS (TLS or Pigpen or hnRNP P2), also termed 75 kDa DNA-pairing protein (POMp75), or oncoprotein TLS (Translocated in liposarcoma), is a member of the FET (previously TET) (FUS/TLS, EWS, TAF15) family of RNA- and DNA-binding proteins whose expression is altered in cancer. It is a multi-functional protein and has been implicated in pre-mRNA splicing, chromosome stability, cell spreading, and transcription. FUS was originally identified in human myxoid and round cell liposarcomas as an oncogenic fusion with the stress-induced DNA-binding transcription factor CHOP (CCAAT enhancer-binding homologous protein) and later as hnRNP P2, a component of hnRNP H complex assembled on pre-mRNA. It can form ternary complexes with hnRNP A1 and hnRNP C1/C2. Additional research indicates that FUS binds preferentially to GGUG-containing RNAs. In the presence of Mg2+, it can bind both single- and double-stranded DNA (ssDNA/dsDNA) and promote ATP-independent annealing of complementary ssDNA and D-loop formation in superhelical dsDNA. FUS has been shown to be recruited by single stranded noncoding RNAs to the regulatory regions of target genes such as cyclin D1, where it represses transcription by disrupting complex formation. TAF15 (TAFII68), also termed TATA-binding protein-associated factor 2N (TAF2N), or RNA-binding protein 56 (RBP56), originally identified as a TAF in the general transcription initiation TFIID complex, is a novel RNA/ssDNA-binding protein with homology to the proto-oncoproteins FUS and EWS (also termed EWSR1), belonging to the FET family as well. TAF15 likely functions in RNA polymerase II (RNAP II) transcription by interacting with TFIID and subunits of RNAP II itself. TAF15 is also associated with U1 snRNA, chromatin and RNA, in a complex distinct from the Sm-containing U1 snRNP that functions in splicing. Like other members in the FET family, both FUS and TAF15 contain an N-terminal Ser, Gly, Gln and Tyr-rich region composed of multiple copies of a degenerate hexapeptide repeat motif. The C-terminal region consists of a conserved nuclear import and retention signal (C-NLS), a C2/C2 zinc-finger motif, a conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and at least 1 arginine-glycine-glycine (RGG)-repeat region.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 232 DNNTIFVQGLGEGVSTDQVGEFFKQIGIIKTNKKTGKPMINLYTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGN 311
Cdd:cd12535   1 DNNTIFVQGLGEDVTIDSVADYFKQIGIIKTNKKTGKPMINLYTDKETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGN 80

                ....*.
gi 21327701 312 IIKVSF 317
Cdd:cd12535  81 PIKVSF 86

RNA recognition motif (RRM) found in Drosophila melanogaster RNA-binding protein cabeza and similar proteins; This subgroup corresponds to the RRM in cabeza, also termed P19, or sarcoma-associated RNA-binding fly homolog (SARFH). It is a putative homolog of human RNA-binding proteins FUS (also termed TLS or Pigpen or hnRNP P2), EWS (also termed EWSR1), TAF15 (also termed hTAFII68 or TAF2N or RPB56), and belongs to the of the FET (previously TET) (FUS/TLS, EWS, TAF15) family of RNA- and DNA-binding proteins whose expression is altered in cancer. It is a nuclear RNA binding protein that may play an important role in the regulation of RNA metabolism during fly development. Cabeza contains one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 236 IFVQGLGEGVSTDQVGEFFKQIGIIKTNKKTGKPMINLYTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNIIKV 315
Cdd:cd12534   1 VFVSNLPPNTTEQDLAEHFGSIGIIKIDKKTGKPKIWLYKDKDTGEPKGEATVTYDDPHAASAAIEWFNNKDFMGNTIKV 80

                ...
gi 21327701 316 SFA 318
Cdd:cd12534  81 SLA 83

RNA recognition motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701    235 TIFVQGLGEGVSTDQVGEFFKQIGIIKTnkktgkpmINLYTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNIIK 314
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVES--------VRLVRDKETGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLK 72

                   .
gi 21327701    315 V 315
Cdd:smart00360  73 V 73

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 236 IFVQGLGEGVSTDQVGEFFKQIGIIKTnkktgkpmINLYTDKDtGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNIIKV 315
Cdd:cd00590   1 LFVGNLPPDTTEEDLRELFSKFGEVVS--------VRIVRDRD-GKSKGFAFVEFESPEDAEKALEALNGTELGGRPLKV 71

                .
gi 21327701 316 S 316
Cdd:cd00590  72 S 72

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 21327701   236 IFVQGLGEGVSTDQVGEFFKQIGIIKTnkktgkpmINLYTDkDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNIIK 314
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKS--------IRLVRD-ETGRSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

RNA recognition motif 1 (RRM1) found in yeast nucleolar protein 4 (Nop4p) and similar proteins; This subgroup corresponds to the RRM1 of Nop4p (also known as Nop77p), encoded by YPL043W from Saccharomyces cerevisiae. It is an essential nucleolar protein involved in processing and maturation of 27S pre-rRNA and biogenesis of 60S ribosomal subunits. Nop4p has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 235 TIFVQGLGEGVSTDQVGEFFKQIGIIKtnkktgKPMInlYTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNIIK 314
Cdd:cd12674   2 TLFVRNLPFDVTLESLTDFFSDIGPVK------HAVV--VTDPETKKSRGYGFVSFSTHDDAEEALAKLKNRKLSGHILK 73

                ....*..
gi 21327701 315 VSFATRR 321
Cdd:cd12674  74 LDFAKPR 80

RNA recognition motif (RRM) found in RNA-binding protein RBM8A, RBM8B nd similar proteins; This subfamily corresponds to the RRM of RBM8, also termed binder of OVCA1-1 (BOV-1), or RNA-binding protein Y14, which is one of the components of the exon-exon junction complex (EJC). It has two isoforms, RBM8A and RBM8B, both of which are identical except that RBM8B is 16 amino acids shorter at its N-terminus. RBM8, together with other EJC components (such as Magoh, Aly/REF, RNPS1, Srm160, and Upf3), plays critical roles in postsplicing processing, including nuclear export and cytoplasmic localization of the mRNA, and the nonsense-mediated mRNA decay (NMD) surveillance process. RBM8 binds to mRNA 20-24 nucleotides upstream of a spliced exon-exon junction. It is also involved in spliced mRNA nuclear export, and the process of nonsense-mediated decay of mRNAs with premature stop codons. RBM8 forms a specific heterodimer complex with the EJC protein Magoh which then associates with Aly/REF, RNPS1, DEK, and SRm160 on the spliced mRNA, and inhibits ATP turnover by eIF4AIII, thereby trapping the EJC core onto RNA. RBM8 contains an N-terminal putative bipartite nuclear localization signal, one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), in the central region, and a C-terminal serine-arginine rich region (SR domain) and glycine-arginine rich region (RG domain).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 236 IFVQGLGEGVSTDQVGEFFKQIGIIKTnkktgkpmINLYTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNIIKV 315
Cdd:cd12324   9 IFVTGVHEEAQEEDIHDKFAEFGEIKN--------LHLNLDRRTGFVKGYALVEYETKKEAQAAIEGLNGKELLGQTISV 80

                ....*..
gi 21327701 316 SFATRRP 322
Cdd:cd12324  81 DWAFVKG 87

RNA recognition motif in type II polyadenylate-binding proteins; This subfamily corresponds to the RRM of type II polyadenylate-binding proteins (PABPs), including polyadenylate-binding protein 2 (PABP-2 or PABPN1), embryonic polyadenylate-binding protein 2 (ePABP-2 or PABPN1L) and similar proteins. PABPs are highly conserved proteins that bind to the poly(A) tail present at the 3' ends of most eukaryotic mRNAs. They have been implicated in the regulation of poly(A) tail length during the polyadenylation reaction, translation initiation, mRNA stabilization by influencing the rate of deadenylation and inhibition of mRNA decapping. ePABP-2 is predominantly located in the cytoplasm and PABP-2 is located in the nucleus. In contrast to the type I PABPs containing four copies of RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), the type II PABPs contains a single highly-conserved RRM. This subfamily also includes Saccharomyces cerevisiae RBP29 (SGN1, YIR001C) gene encoding cytoplasmic mRNA-binding protein Rbp29 that binds preferentially to poly(A). Although not essential for cell viability, Rbp29 plays a role in modulating the expression of cytoplasmic mRNA. Like other type II PABPs, Rbp29 contains one RRM only.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 236 IFVQGLGEGVSTDQVGEFFKQIGIIktNKktgkpmINLYTDKDTGKPKGEATVSFDDPPSAKAAIDwFDGKEFHGNIIKV 315
Cdd:cd12306   2 IYVGNVDYGTTPEELQAHFKSCGTI--NR------VTILCDKFTGQPKGFAYIEFVDKSSVENALL-LNESEFRGRQIKV 72

                .
gi 21327701 316 S 316
Cdd:cd12306  73 T 73

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 236 IFVQGLGEGVSTDQVGEFFKQIGIIKTnkktgkpmINLYTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNIIKV 315
Cdd:cd12347   1 LYVGGLAEEVDEKVLHAAFIPFGDIVD--------IQIPLDYETEKHRGFAFVEFEEAEDAAAAIDNMNESELFGRTIRV 72

                ...
gi 21327701 316 SFA 318
Cdd:cd12347  73 NLA 75

RNA recognition motif (RRM) found in eukaryotic translation initiation factor 3 subunit G (eIF-3G) and similar proteins; This subfamily corresponds to the RRM of eIF-3G and similar proteins. eIF-3G, also termed eIF-3 subunit 4, or eIF-3-delta, or eIF3-p42, or eIF3-p44, is the RNA-binding subunit of eIF3, a large multisubunit complex that plays a central role in the initiation of translation by binding to the 40 S ribosomal subunit and promoting the binding of methionyl-tRNAi and mRNA. eIF-3G binds 18 S rRNA and beta-globin mRNA, and therefore appears to be a nonspecific RNA-binding protein. eIF-3G is one of the cytosolic targets and interacts with mature apoptosis-inducing factor (AIF). eIF-3G contains one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). This family also includes yeast eIF3-p33, a homolog of vertebrate eIF-3G, plays an important role in the initiation phase of protein synthesis in yeast. It binds both, mRNA and rRNA, fragments due to an RRM near its C-terminus.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 235 TIFVQGLGEGVSTDQVGEFFKQIGIIktnkktgkPMINLYTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNIIK 314
Cdd:cd12408   1 TIRVTNLSEDATEEDLRELFRPFGPI--------SRVYLAKDKETGQSKGFAFVTFETREDAERAIEKLNGFGYDNLILS 72

                ....
gi 21327701 315 VSFA 318
Cdd:cd12408  73 VEWA 76

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 235 TIFVQGLGEGVSTDQVGEFFKQIGIIKTnkktgkpmINLYTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNIIK 314
Cdd:cd21608   1 KLYVGNLSWDTTEDDLRDLFSEFGEVES--------AKVITDRETGRSRGFGFVTFSTAEAAEAAIDALNGKELDGRSIV 72

                ....
gi 21327701 315 VSFA 318
Cdd:cd21608  73 VNEA 76

RNA recognition motif 2 (RRM2) found in yeast protein gar2 and similar proteins; This subfamily corresponds to the RRM2 of yeast protein gar2, a novel nucleolar protein required for 18S rRNA and 40S ribosomal subunit accumulation. It shares similar domain architecture with nucleolin from vertebrates and NSR1 from Saccharomyces cerevisiae. The highly phosphorylated N-terminal domain of gar2 is made up of highly acidic regions separated from each other by basic sequences, and contains multiple phosphorylation sites. The central domain of gar2 contains two closely adjacent N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The C-terminal RGG (or GAR) domain of gar2 is rich in glycine, arginine and phenylalanine residues.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 236 IFVQGLGEGVSTDQVGEFFKQIGIIKTnkktgkpmINLYTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNIIKV 315
Cdd:cd12448   1 LFVGNLPFSATQDALYEAFSQHGSIVS--------VRLPTDRETGQPKGFGYVDFSTIDSAEAAIDALGGEYIDGRPIRL 72

                .
gi 21327701 316 S 316
Cdd:cd12448  73 D 73

RNA recognition motif 3 (RRM3) found found in type I polyadenylate-binding proteins; This subfamily corresponds to the RRM3 of type I poly(A)-binding proteins (PABPs), highly conserved proteins that bind to the poly(A) tail present at the 3' ends of most eukaryotic mRNAs. They have been implicated in the regulation of poly(A) tail length during the polyadenylation reaction, translation initiation, mRNA stabilization by influencing the rate of deadenylation and inhibition of mRNA decapping. The family represents type I polyadenylate-binding proteins (PABPs), including polyadenylate-binding protein 1 (PABP-1 or PABPC1), polyadenylate-binding protein 3 (PABP-3 or PABPC3), polyadenylate-binding protein 4 (PABP-4 or APP-1 or iPABP), polyadenylate-binding protein 5 (PABP-5 or PABPC5), polyadenylate-binding protein 1-like (PABP-1-like or PABPC1L), polyadenylate-binding protein 1-like 2 (PABPC1L2 or RBM32), polyadenylate-binding protein 4-like (PABP-4-like or PABPC4L), yeast polyadenylate-binding protein, cytoplasmic and nuclear (PABP or ACBP-67), and similar proteins. PABP-1 is an ubiquitously expressed multifunctional protein that may play a role in 3' end formation of mRNA, translation initiation, mRNA stabilization, protection of poly(A) from nuclease activity, mRNA deadenylation, inhibition of mRNA decapping, and mRNP maturation. Although PABP-1 is thought to be a cytoplasmic protein, it is also found in the nucleus. PABP-1 may be involved in nucleocytoplasmic trafficking and utilization of mRNP particles. PABP-1 contains four copies of RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), a less well conserved linker region, and a proline-rich C-terminal conserved domain (CTD). PABP-3 is a testis-specific poly(A)-binding protein specifically expressed in round spermatids. It is mainly found in mammalian and may play an important role in the testis-specific regulation of mRNA homeostasis. PABP-3 shows significant sequence similarity to PABP-1. However, it binds to poly(A) with a lower affinity than PABP-1. PABP-1 possesses an A-rich sequence in its 5'-UTR and allows binding of PABP and blockage of translation of its own mRNA. In contrast, PABP-3 lacks the A-rich sequence in its 5'-UTR. PABP-4 is an inducible poly(A)-binding protein (iPABP) that is primarily localized to the cytoplasm. It shows significant sequence similarity to PABP-1 as well. The RNA binding properties of PABP-1 and PABP-4 appear to be identical. PABP-5 is encoded by PABPC5 gene within the X-specific subinterval, and expressed in fetal brain and in a range of adult tissues in mammalian, such as ovary and testis. It may play an important role in germ cell development. Moreover, unlike other PABPs, PABP-5 contains only four RRMs, but lacks both the linker region and the CTD. PABP-1-like and PABP-1-like 2 are the orthologs of PABP-1. PABP-4-like is the ortholog of PABP-5. Their cellular functions remain unclear. The family also includes the yeast PABP, a conserved poly(A) binding protein containing poly(A) tails that can be attached to the 3'-ends of mRNAs. The yeast PABP and its homologs may play important roles in the initiation of translation and in mRNA decay. Like vertebrate PABP-1, the yeast PABP contains four RRMs, a linker region, and a proline-rich CTD as well. The first two RRMs are mainly responsible for specific binding to poly(A). The proline-rich region may be involved in protein-protein interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 236 IFVQGLGEGVSTDQVGEFFKQIGIIKTNKktgkpminLYTDkDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNIIKV 315
Cdd:cd12380   4 VYVKNFGEDVDDDELKELFEKYGKITSAK--------VMKD-DSGKSKGFGFVNFENHEAAQKAVEELNGKELNGKKLYV 74

                ...
gi 21327701 316 SFA 318
Cdd:cd12380  75 GRA 77

RNA recognition motif 1 (RRM1) found in Saccharomyces cerevisiae protein HRB1, G-strand-binding protein 2 (GBP2) and similar proteins; The family includes Saccharomyces cerevisiae protein HRB1 (also called protein TOM34) and GBP2, both of which are SR-like mRNA-binding proteins which shuttle from the nucleus to the cytoplasm when bound to the mature mRNA molecules. They act as quality control factors for spliced mRNAs. GBP2, also called RAP1 localization factor 6, is a single-strand telomeric DNA-binding protein that binds single-stranded telomeric sequences of the type (TG[1-3])n in vitro. It also binds to RNA. GBP2 influences the localization of RAP1 in the nuclei and plays a role in modulating telomere length. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the first RRM motif.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 233 NNTIFVQGLGEGVSTDQVGEFFKQIG-IIKTNKKTGKpminlytdkdtGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGN 311
Cdd:cd21605   1 ENSIFVGNLPFDCTWEDLKDHFSQVGeVIRADIVTSR-----------GRHRGMGTVEFTNKEDVDRAISKFDHTMFMGR 69

                ....
gi 21327701 312 IIKV 315
Cdd:cd21605  70 EIFV 73

RNA recognition motif 1 (RRM1) found in nucleolin-like proteins mainly from plants; This subfamily corresponds to the RRM1 of a group of plant nucleolin-like proteins, including nucleolin 1 (also termed protein nucleolin like 1) and nucleolin 2 (also termed protein nucleolin like 2, or protein parallel like 1). They play roles in the regulation of ribosome synthesis and in the growth and development of plants. Like yeast nucleolin, nucleolin-like proteins possess two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 235 TIFVQGLGEGVSTDQVGEFFKQIGIIKTnkktgkpmINLYTDKDTGKPKGEATVSFDDPPSAKAAIDwFDGKEFHGNIIK 314
Cdd:cd12450   1 TLFVGNLSWSATQDDLENFFSDCGEVVD--------VRIAMDRDDGRSKGFGHVEFASAESAQKALE-KSGQDLGGREIR 71

                ....*..
gi 21327701 315 VSFATRR 321
Cdd:cd12450  72 LDLANER 78

Zinc finger domain; Zinc finger domain in Ran-binding proteins (RanBPs), and other proteins. In RanBPs, this domain binds RanGDP.

                           10        20
                   ....*....|....*....|....*..
gi 21327701    356 GDWVCPnpSCGNMNFARRNSCNQCNEP 382
Cdd:smart00547   1 GDWECP--ACTFLNFASRSKCFACGAP 25

RNA recognition motif (RRM) found in Saccharomyces cerevisiae nucleolar protein 6 (Nop6) and similar proteins; This subfamily corresponds to the RRM of Nop6, also known as Ydl213c, a component of 90S pre-ribosomal particles in yeast S. cerevisiae. It is enriched in the nucleolus and is required for 40S ribosomal subunit biogenesis. Nop6 is a non-essential putative RNA-binding protein with two N-terminal putative nuclear localisation sequences (NLS-1 and NLS-2) and an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). It binds to the pre-rRNA early during transcription and plays an essential role in pre-rRNA processing.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 234 NTIFVQGLGEGVSTDQVGEFFKQIGIIKTnkktgkpmINLYTDKDTGKPKGEATVSFDDPPSAKAAIDwFDGKEFHGNII 313
Cdd:cd12400   1 YILFVGNLPYDTTAEDLKEHFKKAGEPPS--------VRLLTDKKTGKSKGCAFVEFDNQKALQKALK-LHHTSLGGRKI 71

                ..
gi 21327701 314 KV 315
Cdd:cd12400  72 NV 73

RNA recognition motif 1 (RRM1) found in yeast nucleolar protein 3 (Npl3p) and similar proteins; This subfamily corresponds to the RRM1 of Npl3p, also termed mitochondrial targeting suppressor 1 protein, or nuclear polyadenylated RNA-binding protein 1. Npl3p is a major yeast RNA-binding protein that competes with 3'-end processing factors, such as Rna15, for binding to the nascent RNA, protecting the transcript from premature termination and coordinating transcription termination and the packaging of the fully processed transcript for export. It specifically recognizes a class of G/U-rich RNAs. Npl3p is a multi-domain protein containing two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), separated by a short linker and a C-terminal domain rich in glycine, arginine and serine residues.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 236 IFVQGLGEGVSTDQVGEFFKQIGIIKTNKktgkpMINlytdkdtgkPKGEATVSFDDPPSAKAAIDWFDGKEFHGNIIKV 315
Cdd:cd12340   2 LFVRPFPPDTSESAIREIFSPYGPVKEVK-----MLS---------DSNFAFVEFEELEDAIRAKDSVHGRVLNNEPLYV 67

                ..
gi 21327701 316 SF 317
Cdd:cd12340  68 TY 69

RNA recognition motif (RRM) found in AZoospermia (DAZ) autosomal homologs, DAZL (DAZ-like) and BOULE; This subfamily corresponds to the RRM domain of two Deleted in AZoospermia (DAZ) autosomal homologs, DAZL (DAZ-like) and BOULE. BOULE is the founder member of the family and DAZL arose from BOULE in an ancestor of vertebrates. The DAZ gene subsequently originated from a duplication transposition of the DAZL gene. Invertebrates contain a single DAZ homolog, BOULE, while vertebrates, other than catarrhine primates, possess both BOULE and DAZL genes. The catarrhine primates possess BOULE, DAZL, and DAZ genes. The family members encode closely related RNA-binding proteins that are required for fertility in numerous organisms. These proteins contain an RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a varying number of copies of a DAZ motif, believed to mediate protein-protein interactions. DAZL and BOULE contain a single copy of the DAZ motif, while DAZ proteins can contain 8-24 copies of this repeat. Although their specific biochemical functions remain to be investigated, DAZL proteins may interact with poly(A)-binding proteins (PABPs), and act as translational activators of specific mRNAs during gametogenesis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 234 NTIFVQGLGEGVSTDQVGEFFKQIGIIKTNKktgkpMINlytDKDtGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNII 313
Cdd:cd12412   3 NRIFVGGIDWDTTEEELREFFSKFGKVKDVK-----IIK---DRA-GVSKGYGFVTFETQEDAEKIQKWGANLVFKGKKL 73

                ....*...
gi 21327701 314 KVSFATRR 321
Cdd:cd12412  74 NVGPAIRK 81

RNA recognition motif in negative elongation factor E (NELF-E) and similar proteins; This subfamily corresponds to the RRM of NELF-E, also termed RNA-binding protein RD. NELF-E is the RNA-binding subunit of cellular negative transcription elongation factor NELF (negative elongation factor) involved in transcriptional regulation of HIV-1 by binding to the stem of the viral transactivation-response element (TAR) RNA which is synthesized by cellular RNA polymerase II at the viral long terminal repeat. NELF is a heterotetrameric protein consisting of NELF A, B, C or the splice variant D, and E. NELF-E contains an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). It plays a role in the control of HIV transcription by binding to TAR RNA. In addition, NELF-E is associated with the NELF-B subunit, probably via a leucine zipper motif.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 234 NTIFVQGlgEGVSTDQVGEFFKQIGIIktnkktgkpmINLYTDKdtgkPKGEATVSFDDPPSAKAAIDWFDGKEFHGNII 313
Cdd:cd12305   5 NTVYVSG--YGITEDVLKKAFSPFGNI----------INISMEI----EKNCAFVTFEKMESADQAIAELNGTTVEGVQL 68

                ....*..
gi 21327701 314 KVSFATR 320
Cdd:cd12305  69 KVSIARR 75

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A0 (hnRNP A0) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP A0, a low abundance hnRNP protein that has been implicated in mRNA stability in mammalian cells. It has been identified as the substrate for MAPKAP-K2 and may be involved in the lipopolysaccharide (LPS)-induced post-transcriptional regulation of tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase 2 (COX-2) and macrophage inflammatory protein 2 (MIP-2). hnRNP A0 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long glycine-rich region at the C-terminus.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 21327701 236 IFVQGLGEGVSTDQVGEFFKQIGIIKTnkktgkpmINLYTDKDTGKPKGEATVSFDDPPSA-KAAI 300
Cdd:cd12579   2 LFVGGLKGDVGEGDLVEHFSQFGTVEK--------VEVIADKDTGKKRGFGFVYFEDHDSAdKAAV 59

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 235 TIFVQGLGEGVSTDQVGEFFKQIGIIKTNKktgkpminLYTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNIIK 314
Cdd:cd12671   8 SVFVGNIPYEATEEQLKDIFSEVGPVVSFR--------LVYDRETGKPKGYGFCEYQDQETALSAMRNLNGYELNGRALR 79

                ....*.
gi 21327701 315 VSFATR 320
Cdd:cd12671  80 VDNAAS 85

RNA recognition motif (RRM) found in the Aly/REF family; This subfamily corresponds to the RRM of Aly/REF family which includes THO complex subunit 4 (THOC4, also termed Aly/REF), S6K1 Aly/REF-like target (SKAR, also termed PDIP3 or PDIP46) and similar proteins. THOC4 is an mRNA transporter protein with a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). It is involved in RNA transportation from the nucleus, and was initially identified as a transcription coactivator of LEF-1 and AML-1 for the TCRalpha enhancer function. In addition, THOC4 specifically binds to rhesus (RH) promoter in erythroid, and might be a novel transcription cofactor for erythroid-specific genes. SKAR shows high sequence homology with THOC4 and possesses one RRM as well. SKAR is widely expressed and localizes to the nucleus. It may be a critical player in the function of S6K1 in cell and organism growth control by binding the activated, hyperphosphorylated form of S6K1 but not S6K2. Furthermore, SKAR functions as a protein partner of the p50 subunit of DNA polymerase delta. In addition, SKAR may have particular importance in pancreatic beta cell size determination and insulin secretion.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 235 TIFVQGLGEGVSTDQVGEFFKQIGiiktnkktgkPMINLYTDKD-TGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNII 313
Cdd:cd12418   2 RVRVSNLHPDVTEEDLRELFGRVG----------PVKSVKINYDrSGRSTGTAYVVFERPEDAEKAIKQFDGVLLDGQPM 71

                ..
gi 21327701 314 KV 315
Cdd:cd12418  72 KV 73

RNA recognition motif 3 (RRM3) found in CELF/Bruno-like family of RNA binding proteins CELF1, CELF2, CELF3, CELF4, CELF5, CELF6 and similar proteins; This subgroup corresponds to the RRM3 of the CUGBP1 and ETR-3-like factors (CELF) or BRUNOL (Bruno-like) proteins, a family of structurally related RNA-binding proteins involved in the regulation of pre-mRNA splicing in the nucleus and in the control of mRNA translation and deadenylation in the cytoplasm. The family contains six members: CELF-1 (also termed BRUNOL-2, or CUG-BP1, or NAPOR, or EDEN-BP), CELF-2 (also termed BRUNOL-3, or ETR-3, or CUG-BP2, or NAPOR-2), CELF-3 (also termed BRUNOL-1, or TNRC4, or ETR-1, or CAGH4, or ER DA4), CELF-4 (also termed BRUNOL-4), CELF-5 (also termed BRUNOL-5), CELF-6 (also termed BRUNOL-6). They all contain three highly conserved RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C-terminus of the protein. The low sequence conservation of the linker region is highly suggestive of a large variety in the co-factors that associate with the various CELF family members. Based on both sequence similarity and function, the CELF family can be divided into two subfamilies, the first containing CELFs 1 and 2, and the second containing CELFs 3, 4, 5, and 6. The different CELF proteins may act through different sites on at least some substrates. Furthermore, CELF proteins may interact with each other in varying combinations to influence alternative splicing in different contexts.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 21327701 274 YTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNIIKVS 316
Cdd:cd12362  31 FVDKNTGRSKGFGFVSYDNPLSAQAAIKAMNGFQVGGKRLKVQ 73

RNA recognition motif (RRM) found in U1 small nuclear ribonucleoprotein 70 kDa (U1-70K) and similar proteins; This subfamily corresponds to the RRM of U1-70K, also termed snRNP70, a key component of the U1 snRNP complex, which is one of the key factors facilitating the splicing of pre-mRNA via interaction at the 5' splice site, and is involved in regulation of polyadenylation of some viral and cellular genes, enhancing or inhibiting efficient poly(A) site usage. U1-70K plays an essential role in targeting the U1 snRNP to the 5' splice site through protein-protein interactions with regulatory RNA-binding splicing factors, such as the RS protein ASF/SF2. Moreover, U1-70K protein can specifically bind to stem-loop I of the U1 small nuclear RNA (U1 snRNA) contained in the U1 snRNP complex. It also mediates the binding of U1C, another U1-specific protein, to the U1 snRNP complex. U1-70K contains a conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by an adjacent glycine-rich region at the N-terminal half, and two serine/arginine-rich (SR) domains at the C-terminal half. The RRM is responsible for the binding of stem-loop I of U1 snRNA molecule. Additionally, the most prominent immunodominant region that can be recognized by auto-antibodies from autoimmune patients may be located within the RRM. The SR domains are involved in protein-protein interaction with SR proteins that mediate 5' splice site recognition. For instance, the first SR domain is necessary and sufficient for ASF/SF2 Binding. The family also includes Drosophila U1-70K that is an essential splicing factor required for viability in flies, but its SR domain is dispensable. The yeast U1-70k doesn't contain easily recognizable SR domains and shows low sequence similarity in the RRM region with other U1-70k proteins and therefore not included in this family. The RRM domain is dispensable for yeast U1-70K function.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21327701 234 NTIFVQGLGEGVSTDQVGEFFKQIGIIKTnkktgkpmINLYTDKDTGKPKGEATVSFDDPPSAKAAIDWFDGKEFHGNII 313
Cdd:cd12236   2 KTLFVARLSYDTTESKLRREFEKYGPIKR--------VRLVRDKKTGKSRGYAFIEFEHERDMKAAYKHADGKKIDGRRV 73

                ....
gi 21327701 314 KVSF 317
Cdd:cd12236  74 LVDV 77

RNA recognition motif 2 in La autoantigen (La or SS-B or LARP3), La-related protein 7 (LARP7 or PIP7S) and similar proteins; This subfamily corresponds to the RRM2 of La and LARP7. La is a highly abundant nuclear phosphoprotein and well conserved in eukaryotes. It specifically binds the 3'-terminal UUU-OH motif of nascent RNA polymerase III transcripts and protects them from exonucleolytic degradation by 3' exonucleases. In addition, La can directly facilitate the translation and/or metabolism of many UUU-3' OH-lacking cellular and viral mRNAs, through binding internal RNA sequences within the untranslated regions of target mRNAs. LARP7 is an oligopyrimidine-binding protein that binds to the highly conserved 3'-terminal U-rich stretch (3' -UUU-OH) of 7SK RNA. It is a stable component of the 7SK small nuclear ribonucleoprotein (7SK snRNP), intimately associates with all the nuclear 7SK and is required for 7SK stability. LARP7 also acts as a negative transcriptional regulator of cellular and viral polymerase II genes, acting by means of the 7SK snRNP system. LARP7 plays an essential role in the inhibition of positive transcription elongation factor b (P-TEFb)-dependent transcription, which has been linked to the global control of cell growth and tumorigenesis. Both La and LARP7 contain an N-terminal La motif (LAM), followed by two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 21327701 233 NNTIFVQGLGEGVSTDQVGEFFKQIGIIKtnkktgkpminlYTDKDTGKPKGEatVSFDDPPSAKAAIDWFDGKE 307
Cdd:cd12292   1 GLILKITGIGPSVSRDDLKELFKQFGEVE------------YVDFTPGDDEGH--VRFKTSEAAQKARDAYTGKL 61