RNA recognition motif (RRM) found in vertebrate Ewing Sarcoma Protein (EWS); This subgroup corresponds to the RRM of EWS, also termed Ewing sarcoma breakpoint region 1 protein, 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 multifunctional protein and may play roles in transcription and RNA processing. EWS is involved in transcriptional regulation by interacting with the preinitiation complex TFIID and the RNA polymerase II (RNAPII) complexes. It is also associated with splicing factors, such as the U1 snRNP protein U1C, suggesting its implication in pre-mRNA splicing. Additionally, EWS has been shown to regulate DNA damage-induced alternative splicing (AS). Like other members in the FET family, EWS contains 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. EWS specifically binds to poly G and poly U RNA. It also binds to the proximal-element DNA of the macrophage-specific promoter of the CSF-1 receptor gene.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 367 SAVYVQGLNDSVTLDDLADFFKQCGVVKMNKRTGQPMIHIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKL 446
Cdd:cd12533    1 STIYVQGLNENVTLEELADFFKHCGVVKINKRTGQPMINIYTDKETGKPKGDATVSYEDPPAAKAAVEWFDGKDFQGNKL 80

                 ....
gi 672076595 447 KVSL 450
Cdd:cd12533   81 KVSM 84

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595  53 TQAQSTATYGQTAYA-TSYGQPPTVEGTSTGYTtPTAPQAYSQpVQGYGTGAYDTTTATVTTTQASYAAQSAYGTQPAYP 131
Cdd:PRK12438 852 STSPSSSTFPQLSRVlVSVREPRTEGGVRVGYA-PTLAEALDQ-VFGPGTGRVATAPGGDAASAPPPGAGPPAPPQAVPP 929

                         90
                 ....*....|....*.
gi 672076595 132 AYGQQPAATAPTRPQD 147
Cdd:PRK12438 930 PRTTQPPAAPPRGPDV 945

RNA recognition motif (RRM) found in vertebrate Ewing Sarcoma Protein (EWS); This subgroup corresponds to the RRM of EWS, also termed Ewing sarcoma breakpoint region 1 protein, 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 multifunctional protein and may play roles in transcription and RNA processing. EWS is involved in transcriptional regulation by interacting with the preinitiation complex TFIID and the RNA polymerase II (RNAPII) complexes. It is also associated with splicing factors, such as the U1 snRNP protein U1C, suggesting its implication in pre-mRNA splicing. Additionally, EWS has been shown to regulate DNA damage-induced alternative splicing (AS). Like other members in the FET family, EWS contains 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. EWS specifically binds to poly G and poly U RNA. It also binds to the proximal-element DNA of the macrophage-specific promoter of the CSF-1 receptor gene.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 367 SAVYVQGLNDSVTLDDLADFFKQCGVVKMNKRTGQPMIHIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKL 446
Cdd:cd12533    1 STIYVQGLNENVTLEELADFFKHCGVVKINKRTGQPMINIYTDKETGKPKGDATVSYEDPPAAKAAVEWFDGKDFQGNKL 80

                 ....
gi 672076595 447 KVSL 450
Cdd:cd12533   81 KVSM 84

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 370 YVQGLNDSVTLDDLADFFKQCGVVKMnkrtgqpmIHIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKLKVS 449
Cdd:COG0724    5 YVGNLPYSVTEEDLRELFSEYGEVTS--------VKLITDRETGRSRGFGFVEMPDDEEAQAAIEALNGAELMGRTLKVN 76

                 ....*..
gi 672076595 450 LARKKPP 456
Cdd:COG0724   77 EARPREE 83

Zn-finger in Ran binding protein and others;

                          10        20        30
                  ....*....|....*....|....*....|
gi 672076595  524 RAGDWQCPnpGCGNQNFAWRTECNQCKAPK 553
Cdd:pfam00641   1 REGDWDCS--KCLVQNFATSTKCVACQAPK 28

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595  369 VYVQGLNDSVTLDDLADFFKQCGVVKMNKrtgqpmihIYLDkETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKLKV 448
Cdd:TIGR01628 288 LYVKNLDDTVTDEKLRELFSECGEITSAK--------VMLD-EKGVSRGFGFVCFSNPEEANRAVTEMHGRMLGGKPLYV 358

                  ....*.
gi 672076595  449 SLARKK 454
Cdd:TIGR01628 359 ALAQRK 364

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595  53 TQAQSTATYGQTAYA-TSYGQPPTVEGTSTGYTtPTAPQAYSQpVQGYGTGAYDTTTATVTTTQASYAAQSAYGTQPAYP 131
Cdd:PRK12438 852 STSPSSSTFPQLSRVlVSVREPRTEGGVRVGYA-PTLAEALDQ-VFGPGTGRVATAPGGDAASAPPPGAGPPAPPQAVPP 929

                         90
                 ....*....|....*.
gi 672076595 132 AYGQQPAATAPTRPQD 147
Cdd:PRK12438 930 PRTTQPPAAPPRGPDV 945

RNA recognition motif (RRM) found in vertebrate Ewing Sarcoma Protein (EWS); This subgroup corresponds to the RRM of EWS, also termed Ewing sarcoma breakpoint region 1 protein, 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 multifunctional protein and may play roles in transcription and RNA processing. EWS is involved in transcriptional regulation by interacting with the preinitiation complex TFIID and the RNA polymerase II (RNAPII) complexes. It is also associated with splicing factors, such as the U1 snRNP protein U1C, suggesting its implication in pre-mRNA splicing. Additionally, EWS has been shown to regulate DNA damage-induced alternative splicing (AS). Like other members in the FET family, EWS contains 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. EWS specifically binds to poly G and poly U RNA. It also binds to the proximal-element DNA of the macrophage-specific promoter of the CSF-1 receptor gene.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 367 SAVYVQGLNDSVTLDDLADFFKQCGVVKMNKRTGQPMIHIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKL 446
Cdd:cd12533    1 STIYVQGLNENVTLEELADFFKHCGVVKINKRTGQPMINIYTDKETGKPKGDATVSYEDPPAAKAAVEWFDGKDFQGNKL 80

                 ....
gi 672076595 447 KVSL 450
Cdd:cd12533   81 KVSM 84

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 672076595 365 DNSAVYVQGLNDSVTLDDLADFFKQCGVVKMNKRTGQPMIHIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGS 444
Cdd:cd12535    1 DNNTIFVQGLGEDVTIDSVADYFKQIGIIKTNKKTGKPMINLYTDKETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGN 80

                 ....*.
gi 672076595 445 KLKVSL 450
Cdd:cd12535   81 PIKVSF 86

RNA recognition motif 1 (RRM1) found in HIV Tat-specific factor 1 (Tat-SF1) and similar proteins; This subfamily corresponds to the RRM1 of Tat-SF1 and CUS2. Tat-SF1 is the cofactor for stimulation of transcriptional elongation by human immunodeficiency virus-type 1 (HIV-1) Tat. It is a substrate of an associated cellular kinase. Tat-SF1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a highly acidic carboxyl-terminal half. The family also includes CUS2, a yeast homolog of human Tat-SF1. CUS2 interacts with U2 RNA in splicing extracts and functions as a splicing factor that aids assembly of the splicing-competent U2 snRNP in vivo. CUS2 also associates with PRP11 that is a subunit of the conserved splicing factor SF3a. Like Tat-SF1, CUS2 contains two RRMs as well.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 366 NSAVYVQGLNDSVTLDDLADFFKQCGVVKMNKRTGQPMIHIYLDKEtGKPKGDATVSYEDPPTAKAAVEWFDGKD-FQGS 444
Cdd:cd12281    1 NTNVYVSGLPLDITVEEFVELFSKCGIIMEDPETGEPKIKLYRDEN-GNLKGDALCCYLKEESVELALQLLDGTEiGRGY 79

                 ....*...
gi 672076595 445 KLKVSLAR 452
Cdd:cd12281   80 KIHVERAK 87

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 370 YVQGLNDSVTLDDLADFFKQCGVVKMnkrtgqpmIHIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKLKVS 449
Cdd:COG0724    5 YVGNLPYSVTEEDLRELFSEYGEVTS--------VKLITDRETGRSRGFGFVEMPDDEEAQAAIEALNGAELMGRTLKVN 76

                 ....*..
gi 672076595 450 LARKKPP 456
Cdd:COG0724   77 EARPREE 83

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 369 VYVQGLNDSVTLDDLADFFKQCGVVKMnkrtgqpmIHIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKLKV 448
Cdd:cd12398    3 VFVGNIPYDATEEQLKEIFSEVGPVVS--------FRLVTDRETGKPKGYGFCEFRDAETALSAVRNLNGYELNGRPLRV 74

                 ...
gi 672076595 449 SLA 451
Cdd:cd12398   75 DFA 77

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595  369 VYVQGLNDSVTLDDLADFFKQCGVVKmnkrtgqpmiHIYL-DKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKLK 447
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIK----------SIRLvRDETGRSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

RNA recognition motif 3 (RRM3) found in RNA-binding protein 19 (RBM19) and RNA recognition motif 2 found in multiple RNA-binding domain-containing protein 1 (MRD1); This subfamily corresponds to the RRM3 of RBM19 and RRM2 of MRD1. RBM19, also termed RNA-binding domain-1 (RBD-1), is a nucleolar protein conserved in eukaryotes involved in ribosome biogenesis by processing rRNA and is essential for preimplantation development. It has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). MRD1 is encoded by a novel yeast gene MRD1 (multiple RNA-binding domain). It is well conserved in yeast and its homologs exist in all eukaryotes. MRD1 is present in the nucleolus and the nucleoplasm. It interacts with the 35 S precursor rRNA (pre-rRNA) and U3 small nucleolar RNAs (snoRNAs). It is essential for the initial processing at the A0-A2 cleavage sites in the 35 S pre-rRNA. MRD1 contains 5 conserved RRMs, which may play an important structural role in organizing specific rRNA processing events.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 369 VYVQGLNDSVTLDDLADFFKQCGVVKMnkrtgqpmIHIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKLKV 448
Cdd:cd12316    2 LFVRNLPFTATEDELRELFEAFGKISE--------VHIPLDKQTKRSKGFAFVLFVIPEDAVKAYQELDGSIFQGRLLHV 73

RNA recognition motif (RRM) found in Helicobacter pylori HP0827 protein and similar proteins; This subfamily corresponds to the RRM of H. pylori HP0827, a putative ssDNA-binding protein 12rnp2 precursor, containing one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The ssDNA binding may be important in activation of HP0827.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 369 VYVQGLNDSVTLDDLADFFKQCGVVKMnkrtgqpmIHIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKLKV 448
Cdd:cd12399    1 LYVGNLPYSASEEQLKSLFGQFGAVFD--------VKLPMDRETKRPRGFGFVELQEEESAEKAIAKLDGTDFMGRTIRV 72

                 ...
gi 672076595 449 SLA 451
Cdd:cd12399   73 NEA 75

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 672076595 369 VYVQGLNDSVTLDDLADFFKQCGVVKmnkrtgqpMIHIYLDKETGKPKGDATVSYEDPPTAKAAVEwFDGKDFQGSKLKV 448
Cdd:cd12450    2 LFVGNLSWSATQDDLENFFSDCGEVV--------DVRIAMDRDDGRSKGFGHVEFASAESAQKALE-KSGQDLGGREIRL 72

                 ....*.
gi 672076595 449 SLARKK 454
Cdd:cd12450   73 DLANER 78

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 672076595 369 VYVQGLNDSVTLDDLADFFKQCGVVkmNKRTgqpmihIYLDKETGKPKGDATVSYEDPPTAKAAVEwFDGKDFQGSKLKV 448
Cdd:cd12306    2 IYVGNVDYGTTPEELQAHFKSCGTI--NRVT------ILCDKFTGQPKGFAYIEFVDKSSVENALL-LNESEFRGRQIKV 72

                 .
gi 672076595 449 S 449
Cdd:cd12306   73 T 73

RNA recognition motif 3 (RRM3) 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 third RRM motif.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 366 NSAVYVQGLNDSVTLDDLADFFKQCGVVKMNKrtgqpmihIYLDkETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSK 445
Cdd:cd21607    2 NNTIYCSNLPLSTAESDLYDLFETIGKVNNAE--------LKYD-ETGDPTGSAVVEYENLDDADVCISKLNNYNYGGCD 72

                 ....*..
gi 672076595 446 LKVSLAR 452
Cdd:cd21607   73 LKISYAK 79

RNA recognition motif (RRM) found in ist3 family; This subfamily corresponds to the RRM of the ist3 family that includes fungal U2 small nuclear ribonucleoprotein (snRNP) component increased sodium tolerance protein 3 (ist3), X-linked 2 RNA-binding motif proteins (RBMX2) found in Metazoa and plants, and similar proteins. Gene IST3 encoding ist3, also termed U2 snRNP protein SNU17 (Snu17p), is a novel yeast Saccharomyces cerevisiae protein required for the first catalytic step of splicing and for progression of spliceosome assembly. It binds specifically to the U2 snRNP and is an intrinsic component of prespliceosomes and spliceosomes. Yeast ist3 contains an atypical RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). In the yeast pre-mRNA retention and splicing complex, the atypical RRM of ist3 functions as a scaffold that organizes the other two constituents, Bud13p (bud site selection 13) and Pml1p (pre-mRNA leakage 1). Fission yeast Schizosaccharomyces pombe gene cwf29 encoding ist3, also termed cell cycle control protein cwf29, is an RNA-binding protein complexed with cdc5 protein 29. It also contains one RRM. The biological function of RBMX2 remains unclear. It shows high sequence similarity to yeast ist3 protein and harbors one RRM as well.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 361 DEDSDNSAVYVQGLNDSVTLDDLADFFKQCGVVkmnkrtgqpmIHIYL--DKETGKPKGDATVSYEDPPTAKAAVEWFDG 438
Cdd:cd12411    4 DEYKDSAYIYIGGLPYELTEGDILCVFSQYGEI----------VDINLvrDKKTGKSKGFAFLAYEDQRSTILAVDNLNG 73

                         90
                 ....*....|
gi 672076595 439 KDFQGSKLKV 448
Cdd:cd12411   74 IKLLGRTIRV 83

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 672076595 367 SAVYVQGLNDSVTLDDLADFFKQCGVVKmnkrtgQPMIhiYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKL 446
Cdd:cd12674    1 TTLFVRNLPFDVTLESLTDFFSDIGPVK------HAVV--VTDPETKKSRGYGFVSFSTHDDAEEALAKLKNRKLSGHIL 72

                 ....*...
gi 672076595 447 KVSLARKK 454
Cdd:cd12674   73 KLDFAKPR 80

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

                           10        20
                   ....*....|....*....|....*..
gi 672076595   526 GDWQCPnpGCGNQNFAWRTECNQCKAP 552
Cdd:smart00547   1 GDWECP--ACTFLNFASRSKCFACGAP 25

RNA recognition motif (RRM) found in pre-mRNA cleavage factor Im 68 kDa subunit (CFIm68 or CPSF6), pre-mRNA cleavage factor Im 59 kDa subunit (CFIm59 or CPSF7), and similar proteins; This subfamily corresponds to the RRM of cleavage factor Im (CFIm) subunits. Cleavage factor Im (CFIm) is a highly conserved component of the eukaryotic mRNA 3' processing machinery that functions in UGUA-mediated poly(A) site recognition, the regulation of alternative poly(A) site selection, mRNA export, and mRNA splicing. It is a complex composed of a small 25 kDa (CFIm25) subunit and a larger 59/68/72 kDa subunit. Two separate genes, CPSF6 and CPSF7, code for two isoforms of the large subunit, CFIm68 and CFIm59. Structurally related CFIm68 and CFIm59, also termed cleavage and polyadenylation specificity factor subunit 6 (CPSF7), or cleavage and polyadenylation specificity factor 59 kDa subunit (CPSF59), are functionally redundant. Both contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a central proline-rich region, and a C-terminal RS-like domain. Their N-terminal RRM mediates the interaction with CFIm25, and also serves to enhance RNA binding and facilitate RNA looping.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 369 VYVQGLNDSVTLDDLADFFKQCGVVKMNKrtgqpmIHIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKLKV 448
Cdd:cd12372    1 LYVGNLQWWTTDEDLEGACASFGVVDVKE------IKFFEHKANGKSKGYAYVEFASPAAAAAVKEKLEKREFNGRPCVV 74

                 ..
gi 672076595 449 SL 450
Cdd:cd12372   75 TP 76

RNA recognition motif (RRM) found in cold inducible RNA binding protein (CIRBP), RNA binding motif protein 3 (RBM3) and similar proteins; This subfamily corresponds to the RRM domain of two structurally related heterogenous nuclear ribonucleoproteins, CIRBP (also termed CIRP or A18 hnRNP) and RBM3 (also termed RNPL), both of which belong to a highly conserved cold shock proteins family. The cold shock proteins can be induced after exposure to a moderate cold-shock and other cellular stresses such as UV radiation and hypoxia. CIRBP and RBM3 may function in posttranscriptional regulation of gene expression by binding to different transcripts, thus allowing the cell to response rapidly to environmental signals. However, the kinetics and degree of cold induction are different between CIRBP and RBM3. Tissue distribution of their expression is different. CIRBP and RBM3 may be differentially regulated under physiological and stress conditions and may play distinct roles in cold responses of cells. CIRBP, also termed glycine-rich RNA-binding protein CIRP, is localized in the nucleus and mediates the cold-induced suppression of cell cycle progression. CIRBP also binds DNA and possibly serves as a chaperone that assists in the folding/unfolding, assembly/disassembly and transport of various proteins. RBM3 may enhance global protein synthesis and the formation of active polysomes while reducing the levels of ribonucleoprotein complexes containing microRNAs. RBM3 may also serve to prevent the loss of muscle mass by its ability to decrease cell death. Furthermore, RBM3 may be essential for cell proliferation and mitosis. Both, CIRBP and RBM3, contain an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), that is involved in RNA binding, and C-terminal glycine-rich domain (RGG motif) that probably enhances RNA-binding via protein-protein and/or protein-RNA interactions. Like CIRBP, RBM3 can also bind to both RNA and DNA via its RRM domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 369 VYVQGLNDSVTLDDLADFFKQCGVVKMnkrtgqpmIHIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKLKV 448
Cdd:cd12449    3 LFVGGLSFDTNEQSLEEVFSKYGQISE--------VVVVKDRETQRSRGFGFVTFENPDDAKDAMMAMNGKSLDGRQIRV 74

                 ....*.
gi 672076595 449 SLARKK 454
Cdd:cd12449   75 DQAGKS 80

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595  369 VYVQGLNDSVTLDDLADFFKQCGVVKMNKrtgqpmihIYLDkETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKLKV 448
Cdd:TIGR01628 288 LYVKNLDDTVTDEKLRELFSECGEITSAK--------VMLD-EKGVSRGFGFVCFSNPEEANRAVTEMHGRMLGGKPLYV 358

                  ....*.
gi 672076595  449 SLARKK 454
Cdd:TIGR01628 359 ALAQRK 364

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 369 VYVQGLNDSVTLDDLADFFKQCGVVKMNKrtgqpmihIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKLKV 448
Cdd:cd12362    1 LFVYHLPNEFTDQDLYQLFAPFGNVVSAK--------VFVDKNTGRSKGFGFVSYDNPLSAQAAIKAMNGFQVGGKRLKV 72

                 .
gi 672076595 449 S 449
Cdd:cd12362   73 Q 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 672076595 369 VYVQGLNDSVTLDDLADFFKQCGVVKMnkrtgqpmIHIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKLKV 448
Cdd:cd12347    1 LYVGGLAEEVDEKVLHAAFIPFGDIVD--------IQIPLDYETEKHRGFAFVEFEEAEDAAAAIDNMNESELFGRTIRV 72

                 ...
gi 672076595 449 SLA 451
Cdd:cd12347   73 NLA 75

RNA recognition motif 3 (RRM3) found in RNA-binding protein 28 (RBM28) and similar proteins; This subfamily corresponds to the RRM3 of RBM28 and Nop4p. RBM28 is a specific nucleolar component of the spliceosomal small nuclear ribonucleoproteins (snRNPs), possibly coordinating their transition through the nucleolus. It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), and may play a role in the maturation of both small nuclear and ribosomal RNAs. RBM28 has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an extremely acidic region between RRM2 and RRM3. The family also includes nucleolar protein 4 (Nop4p or 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 also contains four RRMs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 369 VYVQGLNDSVTLDDLADFFKQCGVVKMNKrtgqpmihIYLDKETGKPKGDATVSYEDPPTAKAAVE------WFDGKDFQ 442
Cdd:cd12415    3 VFIRNLSFDTTEEDLKEFFSKFGEVKYAR--------IVLDKDTGHSKGTAFVQFKTKESADKCIEaandesEDGGLVLD 74

                 ....*....
gi 672076595 443 GSKLKVSLA 451
Cdd:cd12415   75 GRKLIVSLA 83

RNA recognition motif (RRM) found in heterogeneous nuclear ribonucleoprotein G (hnRNP G), Y chromosome RNA recognition motif 1 (hRBMY), testis-specific heterogeneous nuclear ribonucleoprotein G-T (hnRNP G-T) and similar proteins; This subfamily corresponds to the RRM domain of hnRNP G, also termed glycoprotein p43 or RBMX, an RNA-binding motif protein located on the X chromosome. It is expressed ubiquitously and has been implicated in the splicing control of several pre-mRNAs. Moreover, hnRNP G may function as a regulator of transcription for SREBP-1c and GnRH1. Research has shown that hnRNP G may also act as a tumor-suppressor since it upregulates the Txnip gene and promotes the fidelity of DNA end-joining activity. In addition, hnRNP G appears to play a critical role in proper neural development of zebrafish and frog embryos. The family also includes several paralogs of hnRNP G, such as hRBMY and hnRNP G-T (also termed RNA-binding motif protein, X-linked-like-2). Both, hRBMY and hnRNP G-T, are exclusively expressed in testis and critical for male fertility. Like hnRNP G, hRBMY and hnRNP G-T interact with factors implicated in the regulation of pre-mRNA splicing, such as hTra2-beta1 and T-STAR. Although members in this family share a high conserved N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), they appear to recognize different RNA targets. For instance, hRBMY interacts specifically with a stem-loop structure in which the loop is formed by the sequence CA/UCAA. In contrast, hnRNP G associates with single stranded RNA sequences containing a CCA/C motif. In addition to the RRM, hnRNP G contains a nascent transcripts targeting domain (NTD) in the middle region and a novel auxiliary RNA-binding domain (RBD) in its C-terminal region. The C-terminal RBD exhibits distinct RNA binding specificity, and would play a critical role in the regulation of alternative splicing by hnRNP G.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 672076595 409 DKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKLKVSLARK 453
Cdd:cd12382   36 DRETNKSRGFAFVTFESPADAKDAARDMNGKELDGKAIKVEQATK 80

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 672076595 364 SDNSA--VYVQGLNDSVTLDDLADFFKQCGVVKMNKrtgqpmihIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDF 441
Cdd:cd12671    2 SDRSLrsVFVGNIPYEATEEQLKDIFSEVGPVVSFR--------LVYDRETGKPKGYGFCEYQDQETALSAMRNLNGYEL 73

                         90
                 ....*....|
gi 672076595 442 QGSKLKVSLA 451
Cdd:cd12671   74 NGRALRVDNA 83

RNA recognition motif 2 (RRM2) found in splicing regulatory glutamine/lysine-rich protein 1 (SREK1) and similar proteins; This subfamily corresponds to the RRM2 of SREK1, also termed serine/arginine-rich-splicing regulatory protein 86-kDa (SRrp86), or splicing factor arginine/serine-rich 12 (SFRS12), or splicing regulatory protein 508 amino acid (SRrp508). SREK1 belongs to a family of proteins containing regions rich in serine-arginine dipeptides (SR proteins family), which is involved in bridge-complex formation and splicing by mediating protein-protein interactions across either introns or exons. It is a unique SR family member and it may play a crucial role in determining tissue specific patterns of alternative splicing. SREK1 can alter splice site selection by both positively and negatively modulating the activity of other SR proteins. For instance, SREK1 can activate SRp20 and repress SC35 in a dose-dependent manner both in vitro and in vivo. In addition, SREK1 contains two (some contain only one) RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and two serine-arginine (SR)-rich domains (SR domains) separated by an unusual glutamic acid-lysine (EK) rich region. The RRM and SR domains are highly conserved among other members of the SR superfamily. However, the EK domain is unique to SREK1. It plays a modulatory role controlling SR domain function by involvement in the inhibition of both constitutive and alternative splicing and in the selection of splice-site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 369 VYVQGLNDSVTLDDLADFFKQCGVVKMNKRTGQPmihiyldketGKPKGDATVSYEDPPTAKAAVEwFDGKDFQGSKLKV 448
Cdd:cd12260    7 VYVGNLDPSTTADQLLEFFSQAGEVKYVRMAGDE----------TQPTRYAFVEFAEQTSVINALK-LNGKMFGGRPLKV 75

RNA recognition motif 1 (RRM1) found in Arabidopsis thaliana phragmoplastin interacting protein 1 (PHIP1) and similar proteins; This subfamily corresponds to the RRM1 of PHIP1. A. thaliana PHIP1 and its homologs represent a novel class of plant-specific RNA-binding proteins that may play a unique role in the polarized mRNA transport to the vicinity of the cell plate. The family members consist of multiple functional domains, including a lysine-rich domain (KRD domain) that contains three nuclear localization motifs (KKKR/NK), two RNA recognition motifs (RRMs), and three CCHC-type zinc fingers. PHIP1 is a peripheral membrane protein and is localized at the cell plate during cytokinesis in plants. In addition to phragmoplastin, PHIP1 interacts with two Arabidopsis small GTP-binding proteins, Rop1 and Ran2. However, PHIP1 interacted only with the GTP-bound form of Rop1 but not the GDP-bound form. It also binds specifically to Ran2 mRNA.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 369 VYVQGLNDSVTLDDLADFFKQCGVVKMnkrtgqpmIHIYLDKETGKPKGDATVSYEDPPTAKAAVEWfDGKDFQGSKLKV 448
Cdd:cd12271    1 VYVGGIPYYSTEAEIRSYFSSCGEVRS--------VDLMRFPDSGNFRGIAFITFKTEEAAKRALAL-DGEMLGNRFLKV 71

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor SRSF10, SRSF12 and similar proteins; This subfamily corresponds to the RRM of SRSF10 and SRSF12. SRSF10, also termed 40 kDa SR-repressor protein (SRrp40), or FUS-interacting serine-arginine-rich protein 1 (FUSIP1), or splicing factor SRp38, or splicing factor, arginine/serine-rich 13A (SFRS13A), or TLS-associated protein with Ser-Arg repeats (TASR). It is a serine-arginine (SR) protein that acts as a potent and general splicing repressor when dephosphorylated. It mediates global inhibition of splicing both in M phase of the cell cycle and in response to heat shock. SRSF10 emerges as a modulator of cholesterol homeostasis through the regulation of low-density lipoprotein receptor (LDLR) splicing efficiency. It also regulates cardiac-specific alternative splicing of triadin pre-mRNA and is required for proper Ca2+ handling during embryonic heart development. In contrast, the phosphorylated SRSF10 functions as a sequence-specific splicing activator in the presence of a nuclear cofactor. It activates distal alternative 5' splice site of adenovirus E1A pre-mRNA in vivo. Moreover, SRSF10 strengthens pre-mRNA recognition by U1 and U2 snRNPs. SRSF10 localizes to the nuclear speckles and can shuttle between nucleus and cytoplasm. SRSF12, also termed 35 kDa SR repressor protein (SRrp35), or splicing factor, arginine/serine-rich 13B (SFRS13B), or splicing factor, arginine/serine-rich 19 (SFRS19), is a serine/arginine (SR) protein-like alternative splicing regulator that antagonizes authentic SR proteins in the modulation of alternative 5' splice site choice. For instance, it activates distal alternative 5' splice site of the adenovirus E1A pre-mRNA in vivo. Both, SRSF10 and SRSF12, contain a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C-terminal RS domain rich in serine-arginine dipeptides.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 367 SAVYVQGLNDSVTLDDLADFFKQCGVVKMnkrtgqpmIHIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKL 446
Cdd:cd12312    1 TSLFVRNVADDTRPDDLRREFGRYGPIVD--------VYIPLDFYTRRPRGFAYIQFEDVRDAEDALYYLDRTRFLGREI 72

                         90
                 ....*....|..
gi 672076595 447 KVSLA---RKKP 455
Cdd:cd12312   73 EIQFAqgdRKTP 84

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor 3 (SRSF3) and similar proteins; This subfamily corresponds to the RRM of two serine/arginine (SR) proteins, serine/arginine-rich splicing factor 3 (SRSF3) and serine/arginine-rich splicing factor 7 (SRSF7). SRSF3, also termed pre-mRNA-splicing factor SRp20, modulates alternative splicing by interacting with RNA cis-elements in a concentration- and cell differentiation-dependent manner. It is also involved in termination of transcription, alternative RNA polyadenylation, RNA export, and protein translation. SRSF3 is critical for cell proliferation, and tumor induction and maintenance. It can shuttle between the nucleus and cytoplasm. SRSF7, also termed splicing factor 9G8, plays a crucial role in both constitutive splicing and alternative splicing of many pre-mRNAs. Its localization and functions are tightly regulated by phosphorylation. SRSF7 is predominantly present in the nuclear and can shuttle between nucleus and cytoplasm. It cooperates with the export protein, Tap/NXF1, helps mRNA export to the cytoplasm, and enhances the expression of unspliced mRNA. Moreover, SRSF7 inhibits tau E10 inclusion through directly interacting with the proximal downstream intron of E10, a clustering region for frontotemporal dementia with Parkinsonism (FTDP) mutations. Both SRSF3 and SRSF7 contain a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal RS domain rich in serine-arginine dipeptides. The RRM domain is involved in RNA binding, and the RS domain has been implicated in protein shuttling and protein-protein interactions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076595 369 VYVQGLNDSVTLDDLADFFKQCGVVKmnkrtgqpmiHIYLDKetgKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKLKV 448
Cdd:cd12373    2 VYVGNLGPRVTKRELEDAFEKYGPLR----------NVWVAR---NPPGFAFVEFEDPRDAEDAVRALDGRRICGSRVRV 68

                 ....
gi 672076595 449 SLAR 452
Cdd:cd12373   69 ELSR 72

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 672076595 365 DNSaVYVQGLNDSVTLDDLADFFKQCG-VVKMNkrtgqpmihIYLDKetGKPKGDATVSYEDPPTAKAAVEWFDGKDFQG 443
Cdd:cd21605    1 ENS-IFVGNLPFDCTWEDLKDHFSQVGeVIRAD---------IVTSR--GRHRGMGTVEFTNKEDVDRAISKFDHTMFMG 68

                 ....*
gi 672076595 444 SKLKV 448
Cdd:cd21605   69 REIFV 73