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 283135201 282 DNNTIFVQGLGENVTIESVADYFKQIGIIKTNKKTGQPMINLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGN 361
Cdd:cd12535    1 DNNTIFVQGLGEDVTIDSVADYFKQIGIIKTNKKTGKPMINLYTDKETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGN 80

                 ....*.
gi 283135201 362 PIKVSF 367
Cdd:cd12535   81 PIKVSF 86

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 283135201 282 DNNTIFVQGLGENVTIESVADYFKQIGIIKTNKKTGQPMINLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGN 361
Cdd:cd12535    1 DNNTIFVQGLGEDVTIDSVADYFKQIGIIKTNKKTGKPMINLYTDKETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGN 80

                 ....*.
gi 283135201 362 PIKVSF 367
Cdd:cd12535   81 PIKVSF 86

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135201 283 NNTIFVQGLGENVTIESVADYFKQIGIIKTnkktgqpmINLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNP 362
Cdd:COG0724    1 SMKIYVGNLPYSVTEEDLRELFSEYGEVTS--------VKLITDRETGRSRGFGFVEMPDDEEAQAAIEALNGAELMGRT 72

                         90
                 ....*....|.
gi 283135201 363 IKVSFATRRAD 373
Cdd:COG0724   73 LKVNEARPREE 83

Zn-finger in Ran binding protein and others;

                          10        20
                  ....*....|....*....|....*...
gi 283135201  421 RAGDWKCPnpTCENMNFSWRNECNQCKA 448
Cdd:pfam00641   1 REGDWDCS--KCLVQNFATSTKCVACQA 26

U2 snRNP auxilliary factor, large subunit, splicing factor; These splicing factors consist of an N-terminal arginine-rich low complexity domain followed by three tandem RNA recognition motifs (pfam00076). The well-characterized members of this family are auxilliary components of the U2 small nuclear ribonuclearprotein splicing factor (U2AF). These proteins are closely related to the CC1-like subfamily of splicing factors (TIGR01622). Members of this subfamily are found in plants, metazoa and fungi.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135201  284 NTIFVQGLGENVTIESVADYFKQIGIIKTnkktgqpmINLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPI 363
Cdd:TIGR01642 296 DRIYIGNLPLYLGEDQIKELLESFGDLKA--------FNLIKDIATGLSKGYAFCEYKDPSVTDVAIAALNGKDTGDNKL 367

                  ....*.
gi 283135201  364 KVSFAT 369
Cdd:TIGR01642 368 HVQRAC 373

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 283135201 282 DNNTIFVQGLGENVTIESVADYFKQIGIIKTNKKTGQPMINLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGN 361
Cdd:cd12535    1 DNNTIFVQGLGEDVTIDSVADYFKQIGIIKTNKKTGKPMINLYTDKETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGN 80

                 ....*.
gi 283135201 362 PIKVSF 367
Cdd:cd12535   81 PIKVSF 86

RNA recognition motif (RRM) found in the FET family of RNA-binding proteins; This subfamily corresponds to the RRM of FET (previously TET) (FUS/TLS, EWS, TAF15) family of RNA-binding proteins. This ubiquitously expressed family of similarly structured proteins predominantly localizing to the nuclear, includes FUS (also known as TLS or Pigpen or hnRNP P2), EWS (also known as EWSR1), TAF15 (also known as hTAFII68 or TAF2N or RPB56), and Drosophila Cabeza (also known as SARFH). The corresponding coding genes of these proteins are involved in deleterious genomic rearrangements with transcription factor genes in a variety of human sarcomas and acute leukemias. All FET proteins interact with each other and are therefore likely to be part of the very same protein complexes, which suggests a general bridging role for FET proteins coupling RNA transcription, processing, transport, and DNA repair. The FET proteins contain multiple copies of a degenerate hexapeptide repeat motif at the N-terminus. The C-terminal region consists of a conserved nuclear import and retention signal (C-NLS), a putative zinc-finger domain, and a conserved RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), which is flanked by 3 arginine-glycine-glycine (RGG) boxes. FUS and EWS might have similar sequence specificity; both bind preferentially to GGUG-containing RNAs. FUS has also been shown to bind strongly to human telomeric RNA and to small low-copy-number RNAs tethered to the promoter of cyclin D1. To date, nothing is known about the RNA binding specificity of TAF15.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135201 286 IFVQGLGENVTIESVADYFKQIGIIKTNKKTGQPMINLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPIKV 365
Cdd:cd12280    1 IFVSGLPPDVTIDELADLFGQIGIIKRYKDTWPPKIKIYTDKETGKPKGEATLTYEDPSAAKAAIEWFNGKEFRGNKIKV 80

                 ..
gi 283135201 366 SF 367
Cdd:cd12280   81 SL 82

RNA recognition motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135201   285 TIFVQGLGENVTIESVADYFKQIGIIKTnkktgqpmINLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPIK 364
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVES--------VRLVRDKETGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLK 72

                   .
gi 283135201   365 V 365
Cdd:smart00360  73 V 73

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135201 283 NNTIFVQGLGENVTIESVADYFKQIGIIKTnkktgqpmINLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNP 362
Cdd:COG0724    1 SMKIYVGNLPYSVTEEDLRELFSEYGEVTS--------VKLITDRETGRSRGFGFVEMPDDEEAQAAIEALNGAELMGRT 72

                         90
                 ....*....|.
gi 283135201 363 IKVSFATRRAD 373
Cdd:COG0724   73 LKVNEARPREE 83

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 283135201  286 IFVQGLGENVTIESVADYFKQIGIIKTnkktgqpmINLYTDrETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPIK 364
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 283135201 285 TIFVQGLGENVTIESVADYFKQIGIIKtnkktgQPMInlYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPIK 364
Cdd:cd12674    2 TLFVRNLPFDVTLESLTDFFSDIGPVK------HAVV--VTDPETKKSRGYGFVSFSTHDDAEEALAKLKNRKLSGHILK 73

                 ....*..
gi 283135201 365 VSFATRR 371
Cdd:cd12674   74 LDFAKPR 80

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 283135201 286 IFVQGLGENVTIESVADYFKQIGIIKTnkktgqpmINLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPIKV 365
Cdd:cd12448    1 LFVGNLPFSATQDALYEAFSQHGSIVS--------VRLPTDRETGQPKGFGYVDFSTIDSAEAAIDALGGEYIDGRPIRL 72

                 .
gi 283135201 366 S 366
Cdd:cd12448   73 D 73

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 283135201 284 NTIFVQGLGENVTIESVADYFKQIGiiktnkktgqPMIN--LYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGN 361
Cdd:cd12398    1 RSVFVGNIPYDATEEQLKEIFSEVG----------PVVSfrLVTDRETGKPKGYGFCEFRDAETALSAVRNLNGYELNGR 70

                 ....*..
gi 283135201 362 PIKVSFA 368
Cdd:cd12398   71 PLRVDFA 77

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A subfamily; This subfamily corresponds to the RRM2 of hnRNP A0, hnRNP A1, hnRNP A2/B1, hnRNP A3 and similar proteins. hnRNP A0 is 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 A1 is an abundant eukaryotic nuclear RNA-binding protein that may modulate splice site selection in pre-mRNA splicing. hnRNP A2/B1 is an RNA trafficking response element-binding protein that interacts with the hnRNP A2 response element (A2RE). Many mRNAs, such as myelin basic protein (MBP), myelin-associated oligodendrocytic basic protein (MOBP), carboxyanhydrase II (CAII), microtubule-associated protein tau, and amyloid precursor protein (APP) are trafficked by hnRNP A2/B1. hnRNP A3 is also a RNA trafficking response element-binding protein that participates in the trafficking of A2RE-containing RNA. The hnRNP A subfamily is characterized by 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 283135201 286 IFVQGLGENVTIESVADYFKQIGIIKTnkktgqpmINLYTDRETGKLKGEATVSFDDPPSAKAAI 350
Cdd:cd12328    2 LFVGGLKEDVEEEDLREYFSQFGKVES--------VEIVTDKETGKKRGFAFVTFDDHDSVDKIV 58

RNA recognition motif 2 (RRM2) found in squamous cell carcinoma antigen recognized by T-cells 3 (SART3) and similar proteins; This subfamily corresponds to the RRM2 of SART3, also termed Tat-interacting protein of 110 kDa (Tip110), is an RNA-binding protein expressed in the nucleus of the majority of proliferating cells, including normal cells and malignant cells, but not in normal tissues except for the testes and fetal liver. It is involved in the regulation of mRNA splicing probably via its complex formation with RNA-binding protein with a serine-rich domain (RNPS1), a pre-mRNA-splicing factor. SART3 has also been identified as a nuclear Tat-interacting protein that regulates Tat transactivation activity through direct interaction and functions as an important cellular factor for HIV-1 gene expression and viral replication. In addition, SART3 is required for U6 snRNP targeting to Cajal bodies. It binds specifically and directly to the U6 snRNA, interacts transiently with the U6 and U4/U6 snRNPs, and promotes the reassembly of U4/U6 snRNPs after splicing in vitro. SART3 contains an N-terminal half-a-tetratricopeptide repeat (HAT)-rich domain, a nuclearlocalization signal (NLS) domain, and two C-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135201 282 DNNTIFVQGLGENVTIESVADYFKQIGIIKTnkktgqpmINLYTDReTGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGN 361
Cdd:cd12392    1 EKNKLFVKGLPFSCTKEELEELFKQHGTVKD--------VRLVTYR-NGKPKGLAYVEYENEADASQAVLKTDGTEIKDH 71

                 ....*
gi 283135201 362 PIKVS 366
Cdd:cd12392   72 TISVA 76

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 283135201 286 IFVQGLGENVTIESVADYFKQIGIIktNKktgqpmINLYTDRETGKLKGEATVSFDDPPSAKAAIDwFDGKEFSGNPIKV 365
Cdd:cd12306    2 IYVGNVDYGTTPEELQAHFKSCGTI--NR------VTILCDKFTGQPKGFAYIEFVDKSSVENALL-LNESEFRGRQIKV 72

                 .
gi 283135201 366 S 366
Cdd:cd12306   73 T 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 283135201 285 TIFVQGLGENVTIESVADYFKQIGIIKTnkktgqpmINLYTDRETGKLKGEATVSFDDPPSAKAAIDwFDGKEFSGNPIK 364
Cdd:cd12450    1 TLFVGNLSWSATQDDLENFFSDCGEVVD--------VRIAMDRDDGRSKGFGHVEFASAESAQKALE-KSGQDLGGREIR 71

                 ....*..
gi 283135201 365 VSFATRR 371
Cdd:cd12450   72 LDLANER 78

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 283135201 286 IFVQGLGENVTIESVADYFKQIGIIkTNKKTgqPMinlytDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPIKV 365
Cdd:cd12399    1 LYVGNLPYSASEEQLKSLFGQFGAV-FDVKL--PM-----DRETKRPRGFGFVELQEEESAEKAIAKLDGTDFMGRTIRV 72

                 ...
gi 283135201 366 SFA 368
Cdd:cd12399   73 NEA 75

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 283135201 284 NTIFVQGLGENVTIESVADYFKQIGIIKTNKktgqpMINlytDREtGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPI 363
Cdd:cd12412    3 NRIFVGGIDWDTTEEELREFFSKFGKVKDVK-----IIK---DRA-GVSKGYGFVTFETQEDAEKIQKWGANLVFKGKKL 73

                 ....*...
gi 283135201 364 KVSFATRR 371
Cdd:cd12412   74 NVGPAIRK 81

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 283135201 323 LYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPIKVSFATR 370
Cdd:cd12382   33 LMKDRETNKSRGFAFVTFESPADAKDAARDMNGKELDGKAIKVEQATK 80

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 283135201 284 NTIFVQGLGenVTIESVADYFKQIGIIktnkktgqpmINLYTDREtgklKGEATVSFDDPPSAKAAIDWFDGKEFSGNPI 363
Cdd:cd12305    5 NTVYVSGYG--ITEDVLKKAFSPFGNI----------INISMEIE----KNCAFVTFEKMESADQAIAELNGTTVEGVQL 68

                 ....*..
gi 283135201 364 KVSFATR 370
Cdd:cd12305   69 KVSIARR 75

RNA recognition motif 2 (RRM2) found in vertebrate RNA-binding protein RBM23, RBM39 and similar proteins; This subfamily corresponds to the RRM2 of RBM39 (also termed HCC1), a nuclear autoantigen that contains an N-terminal arginine/serine rich (RS) motif and three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). An octapeptide sequence called the RS-ERK motif is repeated six times in the RS region of RBM39. Although the cellular function of RBM23 remains unclear, it shows high sequence homology to RBM39 and contains two RRMs. It may possibly function as a pre-mRNA splicing factor.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 283135201 321 INLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPIKVSFATRR 371
Cdd:cd12284   28 VQLQKDPETGRSKGYGFIQFRDAEDAKKALEQLNGFELAGRPMKVGHVTER 78

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
                 ....*....|....*....|....*....|....*....|....*..
gi 283135201 321 INLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPIKVSF 367
Cdd:cd12372   30 IKFFEHKANGKSKGYAYVEFASPAAAAAVKEKLEKREFNGRPCVVTP 76

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 283135201 278 QDNSDNNTIFVQGLGENVTIESVADYFKQIGIIKTnkktgqpmINLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKE 357
Cdd:cd12411    4 DEYKDSAYIYIGGLPYELTEGDILCVFSQYGEIVD--------INLVRDKKTGKSKGFAFLAYEDQRSTILAVDNLNGIK 75

                 ....*...
gi 283135201 358 FSGNPIKV 365
Cdd:cd12411   76 LLGRTIRV 83

RNA recognition motif 2 (RRM2) found in nucleolin-like proteins mainly from plants; This subfamily corresponds to the RRM2 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 283135201 285 TIFVQG----LGENVTIESVADYFKQIGIIKTnkktgqpmINLYTDRETGKLKGEATVSFDDPPSAKAAIDwFDGKEFSG 360
Cdd:cd12451    1 TIFVKGfdasLGEDTIRDELREHFGECGEVTN--------VRIPTDRETGELKGFAYIEFSTKEAKEKALE-LNGSDIAG 71

                 ....*...
gi 283135201 361 NPIKVSFA 368
Cdd:cd12451   72 GNLVVDEA 79

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 283135201 285 TIFVQGLGENVTIESVADYFKQIGIIKTNKktgqpminLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPIK 364
Cdd:cd12671    8 SVFVGNIPYEATEEQLKDIFSEVGPVVSFR--------LVYDRETGKPKGYGFCEYQDQETALSAMRNLNGYELNGRALR 79

                 ....*.
gi 283135201 365 VSFATR 370
Cdd:cd12671   80 VDNAAS 85

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 283135201 286 IFVQGLGENVTIESVADYFKQIGIIKTnkktgqpmINLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPIKV 365
Cdd:cd12449    3 LFVGGLSFDTNEQSLEEVFSKYGQISE--------VVVVKDRETQRSRGFGFVTFENPDDAKDAMMAMNGKSLDGRQIRV 74

                 ...
gi 283135201 366 SFA 368
Cdd:cd12449   75 DQA 77

RNA recognition motif (RRM) found in eukaryotic RNA-binding protein RBM24, RBM38 and similar proteins; This subfamily corresponds to the RRM of RBM24 and RBM38 from vertebrate, SUPpressor family member SUP-12 from Caenorhabditis elegans and similar proteins. Both, RBM24 and RBM38, are preferentially expressed in cardiac and skeletal muscle tissues. They regulate myogenic differentiation by controlling the cell cycle in a p21-dependent or -independent manner. RBM24, also termed RNA-binding region-containing protein 6, interacts with the 3'-untranslated region (UTR) of myogenin mRNA and regulates its stability in C2C12 cells. RBM38, also termed CLL-associated antigen KW-5, or HSRNASEB, or RNA-binding region-containing protein 1(RNPC1), or ssDNA-binding protein SEB4, is a direct target of the p53 family. It is required for maintaining the stability of the basal and stress-induced p21 mRNA by binding to their 3'-UTRs. It also binds the AU-/U-rich elements in p63 3'-UTR and regulates p63 mRNA stability and activity. SUP-12 is a novel tissue-specific splicing factor that controls muscle-specific splicing of the ADF/cofilin pre-mRNA in C. elegans. All family members contain a conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135201 286 IFVQGLGENVTIESVADYFKQIGIIKTNKktgqpminLYTDRETGKLKGEATVSFDDPPSAKAAIDwfdgkefSGNPIkv 365
Cdd:cd12384    3 IFVGGLPYHTTDDSLREYFEQFGEIEEAV--------VITDRQTGKSRGYGFVTMADREAAERACK-------DPNPI-- 65

                         90
                 ....*....|
gi 283135201 366 sFATRRADFN 375
Cdd:cd12384   66 -IDGRKANVN 74

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 283135201 283 NNTIFVQGLGENVTIESVADYFKQIGIIKTNKktgqpminLYTDrETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNP 362
Cdd:cd21607    2 NNTIYCSNLPLSTAESDLYDLFETIGKVNNAE--------LKYD-ETGDPTGSAVVEYENLDDADVCISKLNNYNYGGCD 72

                 ....*..
gi 283135201 363 IKVSFAT 369
Cdd:cd21607   73 LKISYAK 79

RNA recognition motif 2 (RRM2) found in yeast nuclear polyadenylated RNA-binding protein 4 (Hrp1p or Nab4p) and similar proteins; This subfamily corresponds to the RRM1 of Hrp1p and similar proteins. Hrp1p or Nab4p, also termed cleavage factor IB (CFIB), is a sequence-specific trans-acting factor that is essential for mRNA 3'-end formation in yeast Saccharomyces cerevisiae. It can be UV cross-linked to RNA and specifically recognizes the (UA)6 RNA element required for both, the cleavage and poly(A) addition steps. Moreover, Hrp1p can shuttle between the nucleus and the cytoplasm, and play an additional role in the export of mRNAs to the cytoplasm. Hrp1p also interacts with Rna15p and Rna14p, two components of CF1A. In addition, Hrp1p functions as a factor directly involved in modulating the activity of the nonsense-mediated mRNA decay (NMD) pathway; it binds specifically to a downstream sequence element (DSE)-containing RNA and interacts with Upf1p, a component of the surveillance complex, further triggering the NMD pathway. Hrp1p contains two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an arginine-glycine-rich region harboring repeats of the sequence RGGF/Y.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135201 286 IFVQGLGENVTIESVADYFKQIGIIktnkKTGQPMInlytDRETGKLKGEATVSFDDPPSAKAAIDwFDGKEFSGNPIKV 365
Cdd:cd12330    2 IFVGGLAPDVTEEEFKEYFEQFGTV----VDAVVML----DHDTGRSRGFGFVTFDSESAVEKVLS-KGFHELGGKKVEV 72

                 ....*.
gi 283135201 366 SFATRR 371
Cdd:cd12330   73 KRATPK 78

RNA recognition motif (RRM) found in yeast RNA annealing protein YRA1 (Yra1p), yeast mRNA export protein mlo3 and similar proteins; This subfamily corresponds to the RRM of Yra1p and mlo3. Yra1p is an essential nuclear RNA-binding protein encoded by Saccharomyces cerevisiae YRA1 gene. It belongs to the evolutionarily conserved REF (RNA and export factor binding proteins) family of hnRNP-like proteins. Yra1p possesses potent RNA annealing activity and interacts with a number of proteins involved in nuclear transport and RNA processing. It binds to the mRNA export factor Mex67p/TAP and couples transcription to export in yeast. Yra1p is associated with Pse1p and Kap123p, two members of the beta-importin family, further mediating transport of Yra1p into the nucleus. In addition, the co-transcriptional loading of Yra1p is required for autoregulation. Yra1p consists of two highly conserved N- and C-terminal boxes and a central RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). This subfamily includes RNA-annealing protein mlo3, also termed mRNA export protein mlo3, which has been identified in fission yeast as a protein that causes defects in chromosome segregation when overexpressed. It shows high sequence similarity with Yra1p.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135201 286 IFVQGLGENVTIESVADYFK-QIGIIKTnkktgqpMINLYTdrETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGN-PI 363
Cdd:cd12267    3 VIVSNLPKDVTEAQIREYFVsQIGPIKR-------VLLSYN--EGGKSTGIANITFKRAGDATKAYDKFNGRLDDGNrKM 73

                 ..
gi 283135201 364 KV 365
Cdd:cd12267   74 KV 75

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A3 (hnRNP A3) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP A3, a novel RNA trafficking response element-binding protein that interacts with the hnRNP A2 response element (A2RE) independently of hnRNP A2 and participates in the trafficking of A2RE-containing RNA. hnRNP A3 can shuttle between the nucleus and the cytoplasm. It 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
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 283135201 286 IFVQGLGENVTIESVADYFKQIGIIKTnkktgqpmINLYTDRETGKLKGEATVSFDD 342
Cdd:cd12582    3 IFVGGIKEDTEEYHLRDYFEKYGKIET--------IEVMEDRQSGKKRGFAFVTFDD 51

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP A2/B1, an RNA trafficking response element-binding protein that interacts with the hnRNP A2 response element (A2RE). Many mRNAs, such as myelin basic protein (MBP), myelin-associated oligodendrocytic basic protein (MOBP), carboxyanhydrase II (CAII), microtubule-associated protein tau, and amyloid precursor protein (APP) are trafficked by hnRNP A2/B1. hnRNP A2/B1 also functions as a splicing factor that regulates alternative splicing of the tumor suppressors, such as BIN1, WWOX, the antiapoptotic proteins c-FLIP and caspase-9B, the insulin receptor (IR), and the RON proto-oncogene among others. Overexpression of hnRNP A2/B1 has been described in many cancers. It functions as a nuclear matrix protein involving in RNA synthesis and the regulation of cellular migration through alternatively splicing pre-mRNA. It may play a role in tumor cell differentiation. hnRNP A2/B1 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
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 283135201 286 IFVQGLGENVTIESVADYFKQIGIIKTnkktgqpmINLYTDRETGKLKGEATVSFDD 342
Cdd:cd12581    3 LFVGGIKEDTEEHHLRDYFEEYGKIDT--------IEIITDRQSGKKRGFGFVTFDD 51

RNA recognition motif in fission yeast Schizosaccharomyces pombe SET domain-containing protein 1 (spSet1p) and similar proteins; This subfamily corresponds to the RRM of spSet1p, also termed H3 lysine-4 specific histone-lysine N-methyltransferase, or COMPASS component SET1, or lysine N-methyltransferase 2, or Set1 complex component, is encoded by SET1 from the fission yeast S. pombe. It is essential for the H3 lysine-4 methylation. in vivo, and plays an important role in telomere maintenance and DNA repair in an ATM kinase Rad3-dependent pathway. spSet1p is the homology counterpart of Saccharomyces cerevisiae Set1p (scSet1p). However, it is more closely related to Set1 found in mammalian. Moreover, unlike scSet1p, spSet1p is not required for heterochromatin assembly in fission yeast. spSet1p contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a conserved SET domain that may play a role in DNA repair and telomere function.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135201 286 IFVQGLGENVTIESVADYFKQIGIIKTnkktgqpmINLYTDRETGKLKGEATVSFDDPP--------SAKAAIDWFDGKE 357
Cdd:cd12303    1 IVITGLSPLTTSNQILLHFRPHGEIEA--------SDLKLDPRTGQSIGICWVRFAGPYlrlsnaaeSAKRAVSGQNGYR 72

                         90
                 ....*....|
gi 283135201 358 FSGNPIKVSF 367
Cdd:cd12303   73 IGGATIRVFL 82