RNA recognition motif (RRM) found in eukaryotic translation initiation factor 4B (eIF-4B) and similar proteins; This subfamily corresponds to the RRM of eIF-4B, a multi-domain RNA-binding protein that has been primarily implicated in promoting the binding of 40S ribosomal subunits to mRNA during translation initiation. It contains two RNA-binding domains; the N-terminal well-conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), binds the 18S rRNA of the 40S ribosomal subunit and the C-terminal basic domain (BD), including two arginine-rich motifs (ARMs), binds mRNA during initiation, and is primarily responsible for the stimulation of the helicase activity of eIF-4A. eIF-4B also contains a DRYG domain (a region rich in Asp, Arg, Tyr, and Gly amino acids) in the middle, which is responsible for both, self-association of eIF-4B and binding to the p170 subunit of eIF3. Additional research indicates that eIF-4B can interact with the poly(A) binding protein (PABP) in mammalian cells, which can stimulate both, the eIF-4B-mediated activation of the helicase activity of eIF-4A and binding of poly(A) by PABP. eIF-4B has also been shown to interact specifically with the internal ribosome entry sites (IRES) of several picornaviruses which facilitate cap-independent translation initiation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 205371761  94 PPYTAFLGNLPYDVTEESIKEFFRGLNISAVRLPREPsNPERLKGFGYAEFEDLDSLLSALSLNEESLGNRRIRVDVADQ 173
Cdd:cd12402    1 PPYTAYLGNLPYDVTEDDIEDFFRGLNISSVRLPREN-GPGRLRGFGYVEFEDRESLIQALSLNEESLKNRRIRVDVAGQ 79

                 ..
gi 205371761 174 AQ 175
Cdd:cd12402   80 AQ 81

transcription termination factor Rho; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 205371761 158 EESLGNRRIRVDVADQAQDKDRDDRSFGRDRNRDSDKTDTDwRARPATDSFDDYPPRRGDDSFGDKYR---DRYDSDRYR 234
Cdd:PRK12678 166 EEERDERRRRGDREDRQAEAERGERGRREERGRDGDDRDRR-DRREQGDRREERGRRDGGDRRGRRRRrdrRDARGDDNR 244

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 205371761 235 DGYRDGYRDGPRRDMDRYGGRDRYDDRGSRDYDRGYDSR 273
Cdd:PRK12678 245 EDRGDRDGDDGEGRGGRRGRRFRDRDRRGRRGGDGGNER 283

RNA recognition motif (RRM) found in eukaryotic translation initiation factor 4B (eIF-4B) and similar proteins; This subfamily corresponds to the RRM of eIF-4B, a multi-domain RNA-binding protein that has been primarily implicated in promoting the binding of 40S ribosomal subunits to mRNA during translation initiation. It contains two RNA-binding domains; the N-terminal well-conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), binds the 18S rRNA of the 40S ribosomal subunit and the C-terminal basic domain (BD), including two arginine-rich motifs (ARMs), binds mRNA during initiation, and is primarily responsible for the stimulation of the helicase activity of eIF-4A. eIF-4B also contains a DRYG domain (a region rich in Asp, Arg, Tyr, and Gly amino acids) in the middle, which is responsible for both, self-association of eIF-4B and binding to the p170 subunit of eIF3. Additional research indicates that eIF-4B can interact with the poly(A) binding protein (PABP) in mammalian cells, which can stimulate both, the eIF-4B-mediated activation of the helicase activity of eIF-4A and binding of poly(A) by PABP. eIF-4B has also been shown to interact specifically with the internal ribosome entry sites (IRES) of several picornaviruses which facilitate cap-independent translation initiation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 205371761  94 PPYTAFLGNLPYDVTEESIKEFFRGLNISAVRLPREPsNPERLKGFGYAEFEDLDSLLSALSLNEESLGNRRIRVDVADQ 173
Cdd:cd12402    1 PPYTAYLGNLPYDVTEDDIEDFFRGLNISSVRLPREN-GPGRLRGFGYVEFEDRESLIQALSLNEESLKNRRIRVDVAGQ 79

                 ..
gi 205371761 174 AQ 175
Cdd:cd12402   80 AQ 81

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 205371761   99 FLGNLPYDVTEESIKEFFRGLN-ISAVRLPRepSNPERLKGFGYAEFEDLDSLLS-ALSLNEESLGNRRIR 167
Cdd:pfam00076   2 FVGNLPPDTTEEDLKDLFSKFGpIKSIRLVR--DETGRSKGFAFVEFEDEEDAEKaIEALNGKELGGRELK 70

DNA topoisomerase 2-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 205371761  372 REREVEERLQKEQEKLQRQLDEPKLERRPRERHP-SWRSEETQERERSRTGSESSQTGTSTTSSRNARRRESEKSLENET 450
Cdd:PTZ00108 1150 KEIAKEQRLKSKTKGKASKLRKPKLKKKEKKKKKsSADKSKKASVVGNSKRVDSDEKRKLDDKPDNKKSNSSGSDQEDDE 1229

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 205371761  451 LNKEEDCHSPTSKPPKPDQPLKVMPAPPPKENAWVKRSS----NPPARSQSSDTEQQSPTSGGGKVAPAQPSEEGPGRKD 526
Cdd:PTZ00108 1230 EQKTKPKKSSVKRLKSKKNNSSKSSEDNDEFSSDDLSKEgkpkNAPKRVSAVQYSPPPPSKRPDGESNGGSKPSSPTKKK 1309

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 205371761  527 ENKVDgmnAPKGQTGNSSRGPGDGGNRDHWKESDRKDGKKDQDSRSAPEPKKPEEnpaSKFSSASKYAALSVDGEDENEG 606
Cdd:PTZ00108 1310 VKKRL---EGSLAALKKKKKSEKKTARKKKSKTRVKQASASQSSRLLRRPRKKKS---DSSSEDDDDSEVDDSEDEDDED 1383

                  ..
gi 205371761  607 ED 608
Cdd:PTZ00108 1384 DE 1385

RNA recognition motif (RRM) found in eukaryotic translation initiation factor 4B (eIF-4B) and similar proteins; This subfamily corresponds to the RRM of eIF-4B, a multi-domain RNA-binding protein that has been primarily implicated in promoting the binding of 40S ribosomal subunits to mRNA during translation initiation. It contains two RNA-binding domains; the N-terminal well-conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), binds the 18S rRNA of the 40S ribosomal subunit and the C-terminal basic domain (BD), including two arginine-rich motifs (ARMs), binds mRNA during initiation, and is primarily responsible for the stimulation of the helicase activity of eIF-4A. eIF-4B also contains a DRYG domain (a region rich in Asp, Arg, Tyr, and Gly amino acids) in the middle, which is responsible for both, self-association of eIF-4B and binding to the p170 subunit of eIF3. Additional research indicates that eIF-4B can interact with the poly(A) binding protein (PABP) in mammalian cells, which can stimulate both, the eIF-4B-mediated activation of the helicase activity of eIF-4A and binding of poly(A) by PABP. eIF-4B has also been shown to interact specifically with the internal ribosome entry sites (IRES) of several picornaviruses which facilitate cap-independent translation initiation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 205371761  94 PPYTAFLGNLPYDVTEESIKEFFRGLNISAVRLPREPsNPERLKGFGYAEFEDLDSLLSALSLNEESLGNRRIRVDVADQ 173
Cdd:cd12402    1 PPYTAYLGNLPYDVTEDDIEDFFRGLNISSVRLPREN-GPGRLRGFGYVEFEDRESLIQALSLNEESLKNRRIRVDVAGQ 79

                 ..
gi 205371761 174 AQ 175
Cdd:cd12402   80 AQ 81

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 205371761  96 YTAFLGNLPYDVTEESIKEFFRGL-NISAVRLPREPSNpERLKGFGYAEFEDLDSLLSALSLNEESLGNRRIRV 168
Cdd:cd12400    1 YILFVGNLPYDTTAEDLKEHFKKAgEPPSVRLLTDKKT-GKSKGCAFVEFDNQKALQKALKLHHTSLGGRKINV 73

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 205371761    97 TAFLGNLPYDVTEESIKEFFRGL-NISAVRLPREPsNPERLKGFGYAEFEDLDSLLS-ALSLNEESLGNRRIRV 168
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFgKVESVRLVRDK-ETGKSKGFAFVEFESEEDAEKaLEALNGKELDGRPLKV 73

RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain); The RRM motif is probably diagnostic of an RNA binding protein. RRMs are found in a variety of RNA binding proteins, including various hnRNP proteins, proteins implicated in regulation of alternative splicing, and protein components of snRNPs. The motif also appears in a few single stranded DNA binding proteins. The RRM structure consists of four strands and two helices arranged in an alpha/beta sandwich, with a third helix present during RNA binding in some cases The C-terminal beta strand (4th strand) and final helix are hard to align and have been omitted in the SEED alignment The LA proteins have an N terminal rrm which is included in the seed. There is a second region towards the C terminus that has some features characteriztic of a rrm but does not appear to have the important structural core of a rrm. The LA proteins are one of the main autoantigens in Systemic lupus erythematosus (SLE), an autoimmune disease.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 205371761   99 FLGNLPYDVTEESIKEFFRGLN-ISAVRLPRepSNPERLKGFGYAEFEDLDSLLS-ALSLNEESLGNRRIR 167
Cdd:pfam00076   2 FVGNLPPDTTEEDLKDLFSKFGpIKSIRLVR--DETGRSKGFAFVEFEDEEDAEKaIEALNGKELGGRELK 70

RNA recognition motif (RRM) found in cleavage stimulation factor subunit 2 (CSTF2), yeast ortholog mRNA 3'-end-processing protein RNA15 and similar proteins; This subfamily corresponds to the RRM domain of CSTF2, its tau variant and eukaryotic homologs. CSTF2, also termed cleavage stimulation factor 64 kDa subunit (CstF64), is the vertebrate conterpart of yeast mRNA 3'-end-processing protein RNA15. It is expressed in all somatic tissues and is one of three cleavage stimulatory factor (CstF) subunits required for polyadenylation. CstF64 contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a CstF77-binding domain, a repeated MEARA helical region and a conserved C-terminal domain reported to bind the transcription factor PC-4. During polyadenylation, CstF interacts with the pre-mRNA through the RRM of CstF64 at U- or GU-rich sequences within 10 to 30 nucleotides downstream of the cleavage site. CSTF2T, also termed tauCstF64, is a paralog of the X-linked cleavage stimulation factor CstF64 protein that supports polyadenylation in most somatic cells. It is expressed during meiosis and subsequent haploid differentiation in a more limited set of tissues and cell types, largely in meiotic and postmeiotic male germ cells, and to a lesser extent in brain. The loss of CSTF2T will cause male infertility, as it is necessary for spermatogenesis and fertilization. Moreover, CSTF2T is required for expression of genes involved in morphological differentiation of spermatids, as well as for genes having products that function during interaction of motile spermatozoa with eggs. It promotes germ cell-specific patterns of polyadenylation by using its RRM to bind to different sequence elements downstream of polyadenylation sites than does CstF64. The family also includes yeast ortholog mRNA 3'-end-processing protein RNA15 and similar proteins. RNA15 is a core subunit of cleavage factor IA (CFIA), an essential transcriptional 3'-end processing factor from Saccharomyces cerevisiae. RNA recognition by CFIA is mediated by an N-terminal RRM, which is contained in the RNA15 subunit of the complex. The RRM of RNA15 has a strong preference for GU-rich RNAs, mediated by a binding pocket that is entirely conserved in both yeast and vertebrate RNA15 orthologs.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 205371761  96 YTAFLGNLPYDVTEESIKEFFRGL-NISAVRLPREPSNpERLKGFGYAEFEDLDSLLSALSL-NEESLGNRRIRVDVA 171
Cdd:cd12398    1 RSVFVGNIPYDATEEQLKEIFSEVgPVVSFRLVTDRET-GKPKGYGFCEFRDAETALSAVRNlNGYELNGRPLRVDFA 77

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 205371761  97 TAFLGNLPYDVTEESIKEFFRGL-NISAVRLPREPSNpERLKGFGYAEFEDLDSLLSALSLNEESLGNRRIRVDVADQ 173
Cdd:cd12450    1 TLFVGNLSWSATQDDLENFFSDCgEVVDVRIAMDRDD-GRSKGFGHVEFASAESAQKALEKSGQDLGGREIRLDLANE 77

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 205371761  99 FLGNLPYDVTEESIKEFFRGL-NISAVRLPREPSNpERLKGFGYAEFEDLDSLLSALSL-NEESLGNRRIRVDVAdqaqd 176
Cdd:COG0724    5 YVGNLPYSVTEEDLRELFSEYgEVTSVKLITDRET-GRSRGFGFVEMPDDEEAQAAIEAlNGAELMGRTLKVNEA----- 78

                 ....*..
gi 205371761 177 KDRDDRS 183
Cdd:COG0724   79 RPREERP 85

RNA recognition motif (RRM) found in cleavage stimulation factor subunit 2 (CSTF2), cleavage stimulation factor subunit 2 tau variant (CSTF2T) and similar proteins; This subgroup corresponds to the RRM domain of CSTF2, its tau variant and eukaryotic homologs. CSTF2, also termed cleavage stimulation factor 64 kDa subunit (CstF64), is the vertebrate conterpart of yeast mRNA 3'-end-processing protein RNA15. It is expressed in all somatic tissues and is one of three cleavage stimulatory factor (CstF) subunits required for polyadenylation. CstF64 contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a CstF77-binding domain, a repeated MEARA helical region and a conserved C-terminal domain reported to bind the transcription factor PC-4. During polyadenylation, CstF interacts with the pre-mRNA through the RRM of CstF64 at U- or GU-rich sequences within 10 to 30 nucleotides downstream of the cleavage site. CSTF2T, also termed tauCstF64, is a paralog of the X-linked cleavage stimulation factor CstF64 protein that supports polyadenylation in most somatic cells. It is expressed during meiosis and subsequent haploid differentiation in a more limited set of tissues and cell types, largely in meiotic and postmeiotic male germ cells, and to a lesser extent in brain. The loss of CSTF2T will cause male infertility, as it is necessary for spermatogenesis and fertilization. Moreover, CSTF2T is required for expression of genes involved in morphological differentiation of spermatids, as well as for genes having products that function during interaction of motile spermatozoa with eggs. It promotes germ cell-specific patterns of polyadenylation by using its RRM to bind to different sequence elements downstream of polyadenylation sites than does CstF64.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 205371761  97 TAFLGNLPYDVTEESIKEFFRGLN-ISAVRL--PREPSNPerlKGFGYAEFEDLDSLLSALSL-NEESLGNRRIRVDVA 171
Cdd:cd12671    8 SVFVGNIPYEATEEQLKDIFSEVGpVVSFRLvyDRETGKP---KGYGFCEYQDQETALSAMRNlNGYELNGRALRVDNA 83

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 205371761  99 FLGNLPYDVTEESIKEFFRGLN-ISAVRLP--REPSNPerlKGFGYAEFEDLDSLLSA-LSLNEESLGNRRIRVDVA 171
Cdd:cd12399    2 YVGNLPYSASEEQLKSLFGQFGaVFDVKLPmdRETKRP---RGFGFVELQEEESAEKAiAKLDGTDFMGRTIRVNEA 75

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 205371761  99 FLGNLPYDVTEESIKEFFRGL-NISAVRLPREPsNPERLKGFGYAEFEDLDSLLSALSLNEESLGNRRIRV 168
Cdd:cd12306    3 YVGNVDYGTTPEELQAHFKSCgTINRVTILCDK-FTGQPKGFAYIEFVDKSSVENALLLNESEFRGRQIKV 72

RNA recognition motif 5 (RRM5) found in RNA-binding protein 19 (RBM19 or RBD-1) and similar proteins; This subfamily corresponds to the RRM5 of RBM19 and RRM4 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).

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 205371761  97 TAFLGNLPYDVTEESIKEFFRGLN-ISAVRLPR--EPSNPERLKGFGYAEFE 145
Cdd:cd12318    2 TLFVKNLNFKTTEEALKKHFEKCGpIRSVTIAKkkDPKGPLLSMGYGFVEFK 53

RNA recognition motif 1 (RRM1) found in yeast regulator of rDNA transcription protein 5 (RRT5) and similar proteins; This subfamily corresponds to the RRM1 of the lineage specific family containing a group of uncharacterized yeast regulators of rDNA transcription protein 5 (RRT5), which may play roles in the modulation of rDNA transcription. RRT5 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 205371761 102 NLPYDVTEESIKEFFRGLNISAVRLPREP-----SNPERLKGFGYAEFEDLDSLLSALSL-NEESLGNRRIRV 168
Cdd:cd12409    6 NLSYSTTEEELEELLKDYKPVSVLIPSYTvrgfrSRKHRPLGIAYAEFSSVEEAEKVVKDlNGKVFKGRKLFV 78

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 205371761  99 FLGNLPYDVTEESIKEFFRGL-NISAVRLPREpSNPERLKGFGYAEFEDLDSLLSA-LSLNEESLGNRRIRVDVADQ 173
Cdd:cd12449    4 FVGGLSFDTNEQSLEEVFSKYgQISEVVVVKD-RETQRSRGFGFVTFENPDDAKDAmMAMNGKSLDGRQIRVDQAGK 79

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein (hnRNP) H protein family; This subfamily corresponds to the RRM2 of hnRNP H protein family which includes hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H'), hnRNP F and hnRNP H3 (also termed hnRNP 2H9). They represent a group of nuclear RNA binding proteins that are involved in pre-mRNA processing, having similar RNA binding affinities and specifically recognizing the sequence GGGA. They can either stimulate or repress splicing upon binding to a GGG motif. hnRNP H binds to the RNA substrate in the presence or absence of these proteins, whereas hnRNP F binds to the nuclear mRNA only in the presence of cap-binding proteins. Furthermore, hnRNP H and hnRNP H2 are almost identical; both have been found to bind nuclear-matrix proteins. hnRNP H activates exon inclusion by binding G-rich intronic elements downstream of the 5' splice site in the transcripts of c-src, human immunodeficiency virus type 1 (HIV-1), Bcl-X, GRIN1, and myelin. It silences exons when bound to exonic elements in the transcripts of beta-tropomyosin, HIV-1, and alpha-tropomyosin. hnRNP H2 has been implicated in pre-mRNA 3' end formation. hnRNP H3 may be involved in the splicing arrest induced by heat shock. Most family members contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), except for hnRNP H3, in which the RRM1 is absent. RRM1 and RRM2 are responsible for the binding to the RNA at DGGGD motifs, and they play an important role in efficiently silencing the exon. Members in this family can regulate the alternative splicing of the fibroblast growth factor receptor 2 (FGFR2) transcripts, and function as silencers of FGFR2 exon IIIc through an interaction with the exonic GGG motifs. The lack of RRM1 could account for the reduced silencing activity within hnRNP H3. In addition, the family members have an extensive glycine-rich region near the C-terminus, which may allow them to homo- or heterodimerize. The family also includes a cytoplasmic poly(A)+ mRNA binding protein, GRSF-1, which interacts with RNA in a G-rich element-dependent manner. It may function in RNA packaging, stabilization of RNA secondary structure, or other macromolecular interactions. GRSF-1 also contains three potential RRMs responsible for the RNA binding, and two auxiliary domains (an acidic alpha-helical domain and an N-terminal alanine-rich region) that may play a role in protein-protein interactions and provide binding specificity.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 205371761 100 LGNLPYDVTEESIKEFFRGLNI--SAVRLPREPSNpeRLKGFGYAEFEDLDSLLSALSLNEESLGNRRIRV 168
Cdd:cd12504    5 LRGLPYGCTKEEIAQFFSGLEIvpNGITLPMDRRG--RSTGEAFVQFASQEIAEQALGKHKEKIGHRYIEI 73

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

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 205371761  99 FLGNLPYDVTEESIKEFFRGL-NISAVRLPREPSnPERLKGFGYAEFEDLDSLLSA-LSLNEESLGNRRIRVDVA 171
Cdd:cd12371    4 YVASVHPDLSEDDIKSVFEAFgKIKSCSLAPDPE-TGKHKGYGFIEYENPQSAQDAiASMNLFDLGGQYLRVGRA 77

RNA recognition motif 2 (RRM2) found in vertebrate nucleolin; This subfamily corresponds to the RRM2 of ubiquitously expressed protein nucleolin, also termed protein C23, a multifunctional major nucleolar phosphoprotein that has been implicated in various metabolic processes, such as ribosome biogenesis, cytokinesis, nucleogenesis, cell proliferation and growth, cytoplasmic-nucleolar transport of ribosomal components, transcriptional repression, replication, signal transduction, inducing chromatin decondensation, etc. Nucleolin exhibits intrinsic self-cleaving, DNA helicase, RNA helicase and DNA-dependent ATPase activities. It can be phosphorylated by many protein kinases, such as the major mitotic kinase Cdc2, casein kinase 2 (CK2), and protein kinase C-zeta. Nucleolin shares similar domain architecture with gar2 from Schizosaccharomyces pombe and NSR1 from Saccharomyces cerevisiae. The highly phosphorylated N-terminal domain of nucleolin is made up of highly acidic regions separated from each other by basic sequences, and contains multiple phosphorylation sites. The central domain of nucleolin contains four closely adjacent N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), which suggests that nucleolin is potentially able to interact with multiple RNA targets. The C-terminal RGG (or GAR) domain of nucleolin is rich in glycine, arginine and phenylalanine residues, and contains high levels of NG,NG-dimethylarginines.RRM2, together with RRM1, binds specifically to RNA stem-loops containing the sequence (U/G)CCCG(A/G) in the loop.

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                 ....*....|....*....|....*....|....*....|....*....
gi 205371761  97 TAFLGNLPYDVTEESIKEFFRglNISAVRLPrePSNPERLKGFGYAEFE 145
Cdd:cd12404    5 TLFVKNLPYSTTQDELKEVFE--DAVDIRIP--MGRDGRSKGIAYIEFK 49

RNA recognition motif 1 (RRM1) found in Schizosaccharomyces pombe mRNA export factor Crp79 and similar proteins; Crp79, also called meiotic expression up-regulated protein 5 (Mug5), or polyadenylate-binding protein crp79, or PABP, or poly(A)-binding protein, is an auxiliary mRNA export factor that binds the poly(A) tail of mRNA and is involved in the export of mRNA from the nucleus to the cytoplasm. 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 205371761  97 TAFLGNLPYDVTEESIKEFFRGL-NISAVRLPREPSN-PERLKGFGYAEFEDLDSLLSA-LSLNEESLGNRRIRV 168
Cdd:cd21619    3 TIYVGNIDMTINEDALEKIFSRYgQVESVRRPPIHTDkADRTTGFGFIKYTDAESAERAmQQADGILLGRRRLVV 77

RNA recognition motif 3 (RRM3) found in RNA-binding protein 12 (RBM12) and similar proteins; This subfamily corresponds to the RRM3 of RBM12. RBM12, also termed SH3/WW domain anchor protein in the nucleus (SWAN), is ubiquitously expressed. It contains five distinct RNA binding motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two proline-rich regions, and several putative transmembrane domains. The biological role of RBM12 remains unclear.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 205371761  87 RSRLPKSPPYTAFLGNLPYDVTEESIKEFFRGLNI--SAVRLPREPSNpeRLKGFGYAEFEDLDSLLSALSLNEESLGNR 164
Cdd:cd12512    1 RSRSPHEKGFCVYLKGLPYEAENKHVIEFFKKLDIveDSIYIAYGPNG--RATGEGFVEFRNEIDYKAALCRHKQYMGNR 78

                 ....
gi 205371761 165 RIRV 168
Cdd:cd12512   79 FIQV 82

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein hnRNP H, hnRNP H2, hnRNP F and similar proteins; This subgroup corresponds to the RRM2 of hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H') and hnRNP F. These represent a group of nuclear RNA binding proteins that play important roles in the regulation of alternative splicing decisions. hnRNP H and hnRNP F are two closely related proteins, both of which bind to the RNA sequence DGGGD. They are present in a complex with the tissue-specific splicing factor Fox2, and regulate the alternative splicing of the fibroblast growth factor receptor 2 (FGFR2) transcripts. The presence of Fox 2 can allows hnRNP H and hnRNP F to better compete with the SR protein ASF/SF2 for binding to FGFR2 exon IIIc. Thus, hnRNP H and hnRNP F can function as potent silencers of FGFR2 exon IIIc inclusion through an interaction with the exonic GGG motifs. Furthermore, hnRNP H and hnRNP H2 are almost identical; both have been found to bind nuclear-matrix proteins. hnRNP H activates exon inclusion by binding G-rich intronic elements downstream of the 5' splice site in the transcripts of c-src, human immunodeficiency virus type 1 (HIV-1), Bcl-X, GRIN1, and myelin. It silences exons when bound to exonic elements in the transcripts of beta-tropomyosin, HIV-1, and alpha-tropomyosin. hnRNP H2 has been implicated in pre-mRNA 3' end formation. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 are responsible for the binding to the RNA at DGGGD motifs, and they play an important role in efficiently silencing the exon. In addition, the family members have an extensive glycine-rich region near the C-terminus, which may allow them to homo- or heterodimerize.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 205371761 100 LGNLPYDVTEESIKEFFRGLNI--SAVRLPREPSNpeRLKGFGYAEFEDLDSLLSALSLNEESLGNRRIRVDVADQAQ 175
Cdd:cd12731   13 LRGLPFGCSKEEIVQFFSGLEIvpNGITLPVDFQG--RSTGEAFVQFASQEIAEKALKKHKERIGHRYIEIFKSSRAE 88

RNA recognition motif (RRM) found in ras GTPase-activating protein-binding protein G3BP1, G3BP2 and similar proteins; This subfamily corresponds to the RRM domain in the G3BP family of RNA-binding and SH3 domain-binding proteins. G3BP acts at the level of RNA metabolism in response to cell signaling, possibly as RNA transcript stabilizing factors or an RNase. Members include G3BP1, G3BP2 and similar proteins. These proteins associate directly with the SH3 domain of GTPase-activating protein (GAP), which functions as an inhibitor of Ras. They all contain an N-terminal nuclear transfer factor 2 (NTF2)-like domain, an acidic domain, a domain containing PXXP motif(s), an RNA recognition motif (RRM), and an Arg-Gly-rich region (RGG-rich region, or arginine methylation motif).

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                 ....*....|....*....|....*....|....*....|....*...
gi 205371761  99 FLGNLPYDVTEESIKEFF-RGLNISAVRLPREPSNpERLKGFGYAEFE 145
Cdd:cd12229    7 FVGNLPHDITEDELKEFFsRFGNVLELRINSKGGG-GRLPNFGFVVFD 53

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A/B (hnRNP A/B) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP A/B, also termed APOBEC1-binding protein 1 (ABBP-1), an RNA unwinding protein with a high affinity for G- followed by U-rich regions. hnRNP A/B has also been identified as an APOBEC1-binding protein that interacts with apolipoprotein B (apoB) mRNA transcripts around the editing site and thus plays an important role in apoB mRNA editing. hnRNP A/B contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long C-terminal glycine-rich domain that contains a potential ATP/GTP binding loop.

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 205371761  92 KSPPYTAFLGNLPYDVTEESIKEFFRGL-NISAVRLPREPSNPERlKGFGYAEFE 145
Cdd:cd12584    1 KDPVKKIFVGGLNPETTEEKIREYFGEFgEIEAIELPMDPKTNKR-RGFVFITFK 54

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 205371761  98 AFLGNLPYDVTEESIKEFFRGLN-ISAVRLPREPSNPeRLKGFGYAEFEDLDSLLSALSLNEESLGNRRIRV 168
Cdd:cd12271    1 VYVGGIPYYSTEAEIRSYFSSCGeVRSVDLMRFPDSG-NFRGIAFITFKTEEAAKRALALDGEMLGNRFLKV 71

RNA recognition motif;

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                  ....*....|....*....|....*....|....*....|....*....|
gi 205371761   99 FLGNLPYDVTEESIKEFFRGLNISAVRLPREPSNPER---LKGFGYAEFE 145
Cdd:pfam16367   5 FVGGLPWDITEAELTATFGRFGPLLVDWPGKPESPSYfpdVKGYVFLVFE 54