RNA recognition motif 1 (RRM1) found in cytoplasmic polyadenylation element-binding protein CPEB-2, CPEB-3, CPEB-4 and similar protiens; This subgroup corresponds to the RRM1 of the paralog proteins CPEB-2, CPEB-3 and CPEB-4, all well-conserved in both, vertebrates and invertebrates. Due to the high sequence similarity, members in this family may share similar expression patterns and functions. CPEB-2 is an RNA-binding protein that is abundantly expressed in testis and localized in cytoplasm in transfected HeLa cells. It preferentially binds to poly(U) RNA oligomers and may regulate the translation of stored mRNAs during spermiogenesis. Moreover, CPEB-2 impedes target RNA translation at elongation; it directly interacts with the elongation factor, eEF2, to reduce eEF2/ribosome-activated GTP hydrolysis in vitro and inhibit peptide elongation of CPEB2-bound RNA in vivo. CPEB-3 is a sequence-specific translational regulatory protein that regulates translation in a polyadenylation-independent manner. It functions as a translational repressor that governs the synthesis of the AMPA receptor GluR2 through binding GluR2 mRNA. It also represses translation of a reporter RNA in transfected neurons and stimulates translation in response to NMDA. CPEB-4 is an RNA-binding protein that mediates meiotic mRNA cytoplasmic polyadenylation and translation. It is essential for neuron survival and present on the endoplasmic reticulum (ER). It is accumulated in the nucleus upon ischemia or the depletion of ER calcium. CPEB-4 is overexpressed in a large variety of tumors and is associated with many mRNAs in cancer cells. All family members contain an N-terminal unstructured region, two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a Zn-finger motif. In addition, they do have conserved nuclear export signals that are not present in CPEB-1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2587669329 507 RKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESKSYFPPKGYAFLLFQEESSVQALIDACLEEDGKLYLCVSSPTI 586
Cdd:cd12724     1 RKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESKSYFPPKGYAFLLFQDERSVQALIDACIEEDDKLYLCVSSPTI 80

                          90
                  ....*....|..
gi 2587669329 587 KDKPVQIRPWNL 598
Cdd:cd12724    81 KDKPVQIRPWNL 92

RNA recognition motif 1 (RRM1) found in cytoplasmic polyadenylation element-binding protein CPEB-2, CPEB-3, CPEB-4 and similar protiens; This subgroup corresponds to the RRM1 of the paralog proteins CPEB-2, CPEB-3 and CPEB-4, all well-conserved in both, vertebrates and invertebrates. Due to the high sequence similarity, members in this family may share similar expression patterns and functions. CPEB-2 is an RNA-binding protein that is abundantly expressed in testis and localized in cytoplasm in transfected HeLa cells. It preferentially binds to poly(U) RNA oligomers and may regulate the translation of stored mRNAs during spermiogenesis. Moreover, CPEB-2 impedes target RNA translation at elongation; it directly interacts with the elongation factor, eEF2, to reduce eEF2/ribosome-activated GTP hydrolysis in vitro and inhibit peptide elongation of CPEB2-bound RNA in vivo. CPEB-3 is a sequence-specific translational regulatory protein that regulates translation in a polyadenylation-independent manner. It functions as a translational repressor that governs the synthesis of the AMPA receptor GluR2 through binding GluR2 mRNA. It also represses translation of a reporter RNA in transfected neurons and stimulates translation in response to NMDA. CPEB-4 is an RNA-binding protein that mediates meiotic mRNA cytoplasmic polyadenylation and translation. It is essential for neuron survival and present on the endoplasmic reticulum (ER). It is accumulated in the nucleus upon ischemia or the depletion of ER calcium. CPEB-4 is overexpressed in a large variety of tumors and is associated with many mRNAs in cancer cells. All family members contain an N-terminal unstructured region, two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a Zn-finger motif. In addition, they do have conserved nuclear export signals that are not present in CPEB-1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2587669329 507 RKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESKSYFPPKGYAFLLFQEESSVQALIDACLEEDGKLYLCVSSPTI 586
Cdd:cd12724     1 RKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESKSYFPPKGYAFLLFQDERSVQALIDACIEEDDKLYLCVSSPTI 80

                          90
                  ....*....|..
gi 2587669329 587 KDKPVQIRPWNL 598
Cdd:cd12724    81 KDKPVQIRPWNL 92

RNA recognition motif 2 (RRM2) found in cytoplasmic polyadenylation element-binding protein CPEB-2, CPEB-3, CPEB-4 and similar protiens; This subgroup corresponds to the RRM2 of the paralog proteins CPEB-2, CPEB-3 and CPEB-4, all well conserved in both, vertebrates and invertebrates. Due to the high sequence similarity, members in this family may share similar expression patterns and functions. CPEB-2 is an RNA-binding protein that is abundantly expressed in testis and localized in cytoplasm in transfected HeLa cells. It preferentially binds to poly(U) RNA oligomers and may regulate the translation of stored mRNAs during spermiogenesis. Moreover, CPEB-2 impedes target RNA translation at elongation; it directly interacts with the elongation factor, eEF2, to reduce eEF2/ribosome-activated GTP hydrolysis in vitro and inhibit peptide elongation of CPEB2-bound RNA in vivo. CPEB-3 is a sequence-specific translational regulatory protein that regulates translation in a polyadenylation-independent manner. It functions as a translational repressor that governs the synthesis of the AMPA receptor GluR2 through binding GluR2 mRNA. It also represses translation of a reporter RNA in transfected neurons and stimulates translation in response to NMDA. CPEB-4 is an RNA-binding protein that mediates meiotic mRNA cytoplasmic polyadenylation and translation. It is essential for neuron survival and present on the endoplasmic reticulum (ER). It is accumulated in the nucleus upon ischemia or the depletion of ER calcium. CPEB-4 is overexpressed in a large variety of tumors and is associated with many mRNAs in cancer cells. All family members contain an N-terminal unstructured region, two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a Zn-finger motif. In addition, they do have conserved nuclear export signals that are not present in CPEB-1.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2587669329 615 KTIFVGGVPRPLRAVELAMIMDRLYGGVCYAGIDTDPELKYPKGAGRVAFSNQQSYIAAISARFVQLQHNDIDKR 689
Cdd:cd12726     1 KTIFVGGVPRPLRAVELAMIMDRLYGGVCYAGIDTDPELKYPKGAGRVAFSNQQSYIAAISARFVQLQHGDIDKR 75

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2587669329  616 TIFVGGVPRPLRAVELAMIMDRlYGGVCYAGIDTDPELKYPKGAGRVAFSNQQSYIAAISArfvqLQHNDIDKRP 690
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSK-FGKVESVRLVRDKETGKSKGFAFVEFESEEDAEKALEA----LNGKELDGRP 70

RNA recognition motif 1 (RRM1) found in cytoplasmic polyadenylation element-binding protein CPEB-2, CPEB-3, CPEB-4 and similar protiens; This subgroup corresponds to the RRM1 of the paralog proteins CPEB-2, CPEB-3 and CPEB-4, all well-conserved in both, vertebrates and invertebrates. Due to the high sequence similarity, members in this family may share similar expression patterns and functions. CPEB-2 is an RNA-binding protein that is abundantly expressed in testis and localized in cytoplasm in transfected HeLa cells. It preferentially binds to poly(U) RNA oligomers and may regulate the translation of stored mRNAs during spermiogenesis. Moreover, CPEB-2 impedes target RNA translation at elongation; it directly interacts with the elongation factor, eEF2, to reduce eEF2/ribosome-activated GTP hydrolysis in vitro and inhibit peptide elongation of CPEB2-bound RNA in vivo. CPEB-3 is a sequence-specific translational regulatory protein that regulates translation in a polyadenylation-independent manner. It functions as a translational repressor that governs the synthesis of the AMPA receptor GluR2 through binding GluR2 mRNA. It also represses translation of a reporter RNA in transfected neurons and stimulates translation in response to NMDA. CPEB-4 is an RNA-binding protein that mediates meiotic mRNA cytoplasmic polyadenylation and translation. It is essential for neuron survival and present on the endoplasmic reticulum (ER). It is accumulated in the nucleus upon ischemia or the depletion of ER calcium. CPEB-4 is overexpressed in a large variety of tumors and is associated with many mRNAs in cancer cells. All family members contain an N-terminal unstructured region, two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a Zn-finger motif. In addition, they do have conserved nuclear export signals that are not present in CPEB-1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2587669329 507 RKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESKSYFPPKGYAFLLFQEESSVQALIDACLEEDGKLYLCVSSPTI 586
Cdd:cd12724     1 RKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESKSYFPPKGYAFLLFQDERSVQALIDACIEEDDKLYLCVSSPTI 80

                          90
                  ....*....|..
gi 2587669329 587 KDKPVQIRPWNL 598
Cdd:cd12724    81 KDKPVQIRPWNL 92

RNA recognition motif;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2587669329 506 SRKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESKSYFPP-KGYAFLLFQEESSVQALIDACLEEDGKLYLCVSSP 584
Cdd:pfam16367   1 SRKVFVGGLPWDITEAELTATFGRFGPLLVDWPGKPESPSYFPDvKGYVFLVFEDEKSVQALLDACTQEDGKYYLKLSSP 80

                          90
                  ....*....|.
gi 2587669329 585 TIKDKPVQIRP 595
Cdd:pfam16367  81 RMKDKPVQIRP 91

RNA recognition motif 2 (RRM2) found in cytoplasmic polyadenylation element-binding protein CPEB-1, CPEB-2, CPEB-3, CPEB-4 and similar protiens; This subfamily corresponds to the RRM2 of CPEB family of proteins that bind to defined groups of mRNAs and act as either translational repressors or activators to regulate their translation. CPEB proteins are well conserved in both, vertebrates and invertebrates. Based on sequence similarity, RNA-binding specificity, and functional regulation of translation, the CPEB proteins has been classified into two subfamilies. The first subfamily includes CPEB-1 and related proteins. CPEB-1 is an RNA-binding protein that interacts with the cytoplasmic polyadenylation element (CPE), a short U-rich motif in the 3' untranslated regions (UTRs) of certain mRNAs. It functions as a translational regulator that plays a major role in the control of maternal CPE-containing mRNA in oocytes, as well as of subsynaptic CPE-containing mRNA in neurons. Once phosphorylated and recruiting the polyadenylation complex, CPEB-1 may function as a translational activator stimulating polyadenylation and translation. Otherwise, it may function as a translational inhibitor when dephosphorylated and bound to a protein such as maskin or neuroguidin, which blocks translation initiation through interfering with the assembly of eIF-4E and eIF-4G. Although CPEB-1 is mainly located in cytoplasm, it can shuttle between nucleus and cytoplasm. The second subfamily includes CPEB-2, CPEB-3, CPEB-4, and related protiens. Due to the high sequence similarity, members in this subfamily may share similar expression patterns and functions. CPEB-2 is an RNA-binding protein that is abundantly expressed in testis and localized in cytoplasm in transfected HeLa cells. It preferentially binds to poly(U) RNA oligomers and may regulate the translation of stored mRNAs during spermiogenesis. Moreover, CPEB-2 impedes target RNA translation at elongation. It directly interacts with the elongation factor, eEF2, to reduce eEF2/ribosome-activated GTP hydrolysis in vitro and inhibit peptide elongation of CPEB2-bound RNA in vivo. CPEB-3 is a sequence-specific translational regulatory protein that regulates translation in a polyadenylation-independent manner. It functions as a translational repressor that governs the synthesis of the AMPA receptor GluR2 through binding GluR2 mRNA. It also represses translation of a reporter RNA in transfected neurons and stimulates translation in response to NMDA. CPEB-4 is an RNA-binding protein that mediates meiotic mRNA cytoplasmic polyadenylation and translation. It is essential for neuron survival and present on the endoplasmic reticulum (ER). It is accumulated in the nucleus upon ischemia or the depletion of ER calcium. CPEB-4 is overexpressed in a large variety of tumors and is associated with many mRNAs in cancer cells. All CPEB proteins are nucleus-cytoplasm shuttling proteins. They contain an N-terminal unstructured region, followed by two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a Zn-finger motif. CPEB-2, -3, and -4 have conserved nuclear export signals that are not present in CPEB-1.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2587669329 615 KTIFVGGVPRPLRAVELAMIMDRLYGGVCYAGIDTDPELKYPKGAGRVAFSNQQSYIAAISARFVQLQHNDIDKR 689
Cdd:cd12445     1 RTVFVGGLPLPLTAAELAAILERLYGGVCYVEIDTDEFYLYPTGCARVTFNNEQSYIKAVSEVFVELPFGTINKR 75

RNA recognition motif 2 (RRM2) found in cytoplasmic polyadenylation element-binding protein 1 (CPEB-1) and similar proteins; This subgroup corresponds to the RRM2 of CPEB-1 (also termed CPE-BP1 or CEBP), an RNA-binding protein that interacts with the cytoplasmic polyadenylation element (CPE), a short U-rich motif in the 3' untranslated regions (UTRs) of certain mRNAs. It functions as a translational regulator that plays a major role in the control of maternal CPE-containing mRNA in oocytes, as well as of subsynaptic CPE-containing mRNA in neurons. Once phosphorylated and recruiting the polyadenylation complex, CPEB-1 may function as a translational activator stimulating polyadenylation and translation. Otherwise, it may function as a translational inhibitor when dephosphorylated and bound to a protein such as maskin or neuroguidin, which blocks translation initiation through interfering with the assembly of eIF-4E and eIF-4G. Although CPEB-1 is mainly located in cytoplasm, it can shuttle between nucleus and cytoplasm. CPEB-1 contains an N-terminal unstructured region, two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a Zn-finger motif. Both of the RRMs and the Zn finger are required for CPEB-1 to bind CPE. The N-terminal regulatory region may be responsible for CPEB-1 interacting with other proteins.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2587669329 612 DPRKTIFVGGVPRPLRAVELAMIMDRLYGGVCYAGIDTDpELKYPKGAGRVAFSNQQSYIAAISARFVQL 681
Cdd:cd12725     1 DPSKTVFVGALHGMLNAEGLANIMNDLFGGVVYAGIDTD-KHKYPIGSGRVTFNNQRSYMKAVNAAFVEI 69

RNA recognition motif (RRM) superfamily; RRM, also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), is a highly abundant domain in eukaryotes found in proteins involved in post-transcriptional gene expression processes including mRNA and rRNA processing, RNA export, and RNA stability. This domain is 90 amino acids in length and consists of a four-stranded beta-sheet packed against two alpha-helices. RRM usually interacts with ssRNA, but is also known to interact with ssDNA as well as proteins. RRM binds a variable number of nucleotides, ranging from two to eight. The active site includes three aromatic side-chains located within the conserved RNP1 and RNP2 motifs of the domain. The RRM domain is found in a variety heterogeneous nuclear ribonucleoproteins (hnRNPs), proteins implicated in regulation of alternative splicing, and protein components of small nuclear ribonucleoproteins (snRNPs).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2587669329 509 VFVGGLPPDIDEDEITASFRRFGPLV-VDWPHKAESKSyfppKGYAFLLFQEESSVQALIDACleeDGKlylcvsspTIK 587
Cdd:cd00590     1 LFVGNLPPDTTEEDLRELFSKFGEVVsVRIVRDRDGKS----KGFAFVEFESPEDAEKALEAL---NGT--------ELG 65

                  ....*..
gi 2587669329 588 DKPVQIR 594
Cdd:cd00590    66 GRPLKVS 72

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 2587669329 508 KVFVGGLPPDIDEDEITASFRRFGPLV-----VDwphKAESKsyfpPKGYAFLLFQEESSVQALIDACLEEdgklylcvs 582
Cdd:cd12330     1 KIFVGGLAPDVTEEEFKEYFEQFGTVVdavvmLD---HDTGR----SRGFGFVTFDSESAVEKVLSKGFHE--------- 64

                          90
                  ....*....|...
gi 2587669329 583 sptIKDKPVQIRP 595
Cdd:cd12330    65 ---LGGKKVEVKR 74

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins; This subfamily corresponds to the RRM2 of hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins. hnRNP D0, a UUAG-specific nuclear RNA binding protein that may be involved in pre-mRNA splicing and telomere elongation. hnRNP A/B is an RNA unwinding protein with a high affinity for G- followed by U-rich regions. It 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 DL (or hnRNP D-like) is a dual functional protein that possesses DNA- and RNA-binding properties. It has been implicated in mRNA biogenesis at the transcriptional and post-transcriptional levels. All memembers in this family contain two putative RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glycine- and tyrosine-rich C-terminus.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2587669329 508 KVFVGGLPPDIDEDEITASFRRFGPLV-VDWP-HKAESKSyfppKGYAFLLFQEESSVQAL 566
Cdd:cd12329     1 KIFVGGLSPETTEEKIREYFGKFGNIVeIELPmDKKTNKR----RGFCFITFDSEEPVKKI 57

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).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2587669329 506 SRKVFVGGLPPDIDEDEITASFRRFGPLV-VDWPHKAESKsyfPPKGYAFLLFQEESSVQALIDAC 570
Cdd:cd12229     3 NHQLFVGNLPHDITEDELKEFFSRFGNVLeLRINSKGGGG---RLPNFGFVVFDDPEAVQKILANK 65

RNA recognition motif (RRM) found in U2-associated protein SR140 and similar proteins; This subgroup corresponds to the RRM of SR140 (also termed U2 snRNP-associated SURP motif-containing protein orU2SURP, or 140 kDa Ser/Arg-rich domain protein) which is a putative splicing factor mainly found in higher eukaryotes. Although it is initially identified as one of the 17S U2 snRNP-associated proteins, the molecular and physiological function of SR140 remains unclear. SR140 contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a SWAP/SURP domain that is found in a number of pre-mRNA splicing factors in the middle region, and a C-terminal arginine/serine-rich domain (RS domain).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2587669329 509 VFVGGLPPDIDEDEITASFRRFGPLV---VDWPHKAESKsyFPPKGYAFLLF 557
Cdd:cd12223     4 LYVGNLPPSVTEEVLLREFGRFGPLAsvkIMWPRTEEER--RRNRNCGFVAF 53

RNA recognition motif (RRM) found in nucleolar protein 8 (NOL8) and similar proteins; This model corresponds to the RRM of NOL8 (also termed Nop132) encoded by a novel NOL8 gene that is up-regulated in the majority of diffuse-type, but not intestinal-type, gastric cancers. Thus, NOL8 may be a good molecular target for treatment of diffuse-type gastric cancer. Also, NOL8 is a phosphorylated protein that contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), suggesting NOL8 is likely to function as a novel RNA-binding protein. It may be involved in regulation of gene expression at the post-transcriptional level or in ribosome biogenesis in cancer cells.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2587669329 509 VFVGGLPPDIDEDEITASFRRFGPLV-VDWPHkaesKSYFPPKGYAF--LLFQEESSVQAL 566
Cdd:cd12226     2 LFVGGLSPSITEDDLERRFSRFGTVSdVEIIR----KKDAPDRGFAYidLRTSEAALQKCL 58

RNA recognition motif (RRM) found in Saccharomyces cerevisiae U1 small nuclear ribonucleoprotein SNP1 and similar proteins; SNP1, also called U1 snRNP protein SNP1, or U1 small nuclear ribonucleoprotein 70 kDa homolog, or U1 70K, or U1 snRNP 70 kDa homolog, interacts with mRNA and is involved in nuclear mRNA splicing. It is a component of the spliceosome, where it is associated with snRNP U1 by binding stem loop I of U1 snRNA. Members in this family contain an N-terminal U1snRNP70 domain and an RNA recognition motif (RRM), also called RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2587669329 507 RKVFVGGLPPDIDEDEITASFRRFGP-----LVVDwphKAESKSyfppKGYAFLLFQEESSVQALIDAC 570
Cdd:cd21615    19 KTLFVGRLDYSLTELELQKKFSKFGEiekirIVRD---KETGKS----RGYAFIVFKSESDAKNAFKEG 80

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2587669329 507 RKVFVGGLPPDIDEDEITASFRRFGPL-VVDWPHKAESKSYfppKGYAFLLFQEESSVQALID 568
Cdd:cd12584     5 KKIFVGGLNPETTEEKIREYFGEFGEIeAIELPMDPKTNKR---RGFVFITFKEEDPVKKILE 64

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein D0 (hnRNP D0) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP D0, also termed AU-rich element RNA-binding protein 1, a UUAG-specific nuclear RNA binding protein that may be involved in pre-mRNA splicing and telomere elongation. hnRNP D0 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), in the middle and an RGG box rich in glycine and arginine residues in the C-terminal part. Each of RRMs can bind solely to the UUAG sequence specifically.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2587669329 508 KVFVGGLPPDIDEDEITASFRRFGPL-VVDWPHKAESKSYfppKGYAFLLFQEESSVQALID 568
Cdd:cd12583     1 KIFVGGLSPDTPEEKIREYFGAFGEVeSIELPMDNKTNKR---RGFCFITFKEEEPVKKIME 59

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2587669329  616 TIFVGGVPRPLRAVELAMIMDRlYGGVCYAGIDTDPELKYPKGAGRVAFSNQQSYIAAISArfvqLQHNDIDKRP 690
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSK-FGKVESVRLVRDKETGKSKGFAFVEFESEEDAEKALEA----LNGKELDGRP 70

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2587669329 508 KVFVGGLPPDIDEDEITASFRRFGPLvvdwpHKAE---SKSYFPPKGYAFLLFQEESSV 563
Cdd:cd12579     1 KLFVGGLKGDVGEGDLVEHFSQFGTV-----EKVEviaDKDTGKKRGFGFVYFEDHDSA 54

RNA recognition motif (RRM) found in heterogeneous nuclear ribonucleoprotein C (hnRNP C)-related proteins; This subfamily corresponds to the RRM in the hnRNP C-related protein family, including hnRNP C proteins, Raly, and Raly-like protein (RALYL). hnRNP C proteins, C1 and C2, are produced by a single coding sequence. They are the major constituents of the heterogeneous nuclear RNA (hnRNA) ribonucleoprotein (hnRNP) complex in vertebrates. They bind hnRNA tightly, suggesting a central role in the formation of the ubiquitous hnRNP complex; they are involved in the packaging of the hnRNA in the nucleus and in processing of pre-mRNA such as splicing and 3'-end formation. Raly, also termed autoantigen p542, is an RNA-binding protein that may play a critical role in embryonic development. The biological role of RALYL remains unclear. It shows high sequence homology with hnRNP C proteins and Raly. Members of this family are characterized by an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal auxiliary domain. The Raly proteins contain a glycine/serine-rich stretch within the C-terminal regions, which is absent in the hnRNP C proteins. Thus, the Raly proteins represent a newly identified class of evolutionarily conserved autoepitopes.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2587669329 507 RKVFVGGLPPD-IDEDEITASFRRFGplvvdwphKAESKSYFppKGYAFLLFQEESSVQAlidACLEEDGKLYL 579
Cdd:cd12341     1 SRIFVGNLPTDqMTKEDLEEIFSKYG--------KILGISLH--KGYGFVQFDNEEDARA---AVAGENGRTIK 61

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2587669329 509 VFVGGLPPDIDEDEITASFRRFGPLV-VDWPHKAESKSyfpPKGYAFLLFQEESSVQalidACLEEDG 575
Cdd:cd12271     1 VYVGGIPYYSTEAEIRSYFSSCGEVRsVDLMRFPDSGN---FRGIAFITFKTEEAAK----RALALDG 61

RNA recognition motif 1 (RRM1) found in La-related protein 7 (LARP7) and similar proteins; This subfamily corresponds to the RRM1 of LARP7, also termed La ribonucleoprotein domain family member 7, or P-TEFb-interaction protein for 7SK stability (PIP7S), an oligopyrimidine-binding protein that binds to the highly conserved 3'-terminal U-rich stretch (3' -UUU-OH) of 7SK RNA. LARP7 is a stable component of the 7SK small nuclear ribonucleoprotein (7SK snRNP). It intimately associates with all the nuclear 7SK and is required for 7SK stability. LARP7 also acts as a negative transcriptional regulator of cellular and viral polymerase II genes, acting by means of the 7SK snRNP system. It plays an essential role in the inhibition of positive transcription elongation factor b (P-TEFb)-dependent transcription, which has been linked to the global control of cell growth and tumorigenesis. LARP7 contains a La motif (LAM) and an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), at the N-terminal region, which mediates binding to the U-rich 3' terminus of 7SK RNA. LARP7 also carries another putative RRM domain at its C-terminus.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2587669329 509 VFVGGLPPDIDEDEITASFRRFGPLV-VDWPHKAESKSyfpPKGYAFLLFQEESSVQALIDA 569
Cdd:cd12290     2 VYVELLPKNATHEWIEAVFSKYGEVVyVSIPRYKSTGD---PKGFAFIEFETSESAQKAVKH 60

RNA recognition motif 3 (RRM3) found in yeast nucleolar protein 4 (Nop4p) and similar proteins; This subgroup corresponds to the RRM3 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 2587669329 506 SRKVFVGGLPPDIDEDEITASFRRFGPL-----VVDwphKAESKSyfppKGYAFLLFQEESSVqaliDACLEEDGKLYlc 580
Cdd:cd12676     1 GRTLFVRNLPFDATEDELYSHFSQFGPLkyarvVKD---PATGRS----KGTAFVKFKNKEDA----DNCLSAAPEAQ-- 67

                          90       100
                  ....*....|....*....|....*..
gi 2587669329 581 VSSPTIKDKPVQIRPWNLSdSDFVMDG 607
Cdd:cd12676    68 STSLLEKYSLEQDITDDVS-AKFTLDG 93

RNA recognition motif 2 (RRM2) found in U2 large nuclear ribonucleoprotein auxiliary factor U2AF 65 kDa subunit (U2AF65) and similar proteins; This subfamily corresponds to the RRM2 of U2AF65 and dU2AF50. U2AF65, also termed U2AF2, is the large subunit of U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor (U2AF), which has been implicated in the recruitment of U2 snRNP to pre-mRNAs and is a highly conserved heterodimer composed of large and small subunits. U2AF65 specifically recognizes the intron polypyrimidine tract upstream of the 3' splice site and promotes binding of U2 snRNP to the pre-mRNA branchpoint. U2AF65 also plays an important role in the nuclear export of mRNA. It facilitates the formation of a messenger ribonucleoprotein export complex, containing both the NXF1 receptor and the RNA substrate. Moreover, U2AF65 interacts directly and specifically with expanded CAG RNA, and serves as an adaptor to link expanded CAG RNA to NXF1 for RNA export. U2AF65 contains an N-terminal RS domain rich in arginine and serine, followed by a proline-rich segment and three C-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The N-terminal RS domain stabilizes the interaction of U2 snRNP with the branch point (BP) by contacting the branch region, and further promotes base pair interactions between U2 snRNA and the BP. The proline-rich segment mediates protein-protein interactions with the RRM domain of the small U2AF subunit (U2AF35 or U2AF1). The RRM1 and RRM2 are sufficient for specific RNA binding, while RRM3 is responsible for protein-protein interactions. The family also includes Splicing factor U2AF 50 kDa subunit (dU2AF50), the Drosophila ortholog of U2AF65. dU2AF50 functions as an essential pre-mRNA splicing factor in flies. It associates with intronless mRNAs and plays a significant and unexpected role in the nuclear export of a large number of intronless mRNAs.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2587669329 508 KVFVGGLPPDIDEDEITASFRRFGP-----LVVDwPHKAESksyfppKGYAFLLFQEES 561
Cdd:cd12231     2 KLFIGGLPNYLNEDQVKELLQSFGKlkafnLVKD-SATGLS------KGYAFCEYVDDN 53

RNA recognition motif 2 (RRM2) found in TAR DNA-binding protein 43 (TDP-43) and similar proteins; This subfamily corresponds to the RRM2 of TDP-43 (also termed TARDBP), a ubiquitously expressed pathogenic protein whose normal function and abnormal aggregation are directly linked to the genetic disease cystic fibrosis, and two neurodegenerative disorders: frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). TDP-43 binds both DNA and RNA, and has been implicated in transcriptional repression, pre-mRNA splicing and translational regulation. TDP-43 is a dimeric protein with two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal glycine-rich domain. The RRMs are responsible for DNA and RNA binding; they bind to TAR DNA and RNA sequences with UG-repeats. The glycine-rich domain can interact with the hnRNP family proteins to form the hnRNP-rich complex involved in splicing inhibition. It is also essential for the cystic fibrosis transmembrane conductance regulator (CFTR) exon 9-skipping activity.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2587669329 507 RKVFVGGLPPDIDEDEITASFRRFGPlVVDwphkaesksYFPPK---GYAFLLFQEESSVQALI 567
Cdd:cd12322     1 RKVFVGRCTEDMTEDDLRQYFSQFGE-VTD---------VFIPKpfrAFAFVTFADDEVAQSLC 54

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein D-like (hnRNP D-like or hnRNP DL) and similar proteins; This subgroup corresponds to the RRM1 of hnRNP DL (or hnRNP D-like), also termed AU-rich element RNA-binding factor, or JKT41-binding protein (protein laAUF1 or JKTBP), which is a dual functional protein that possesses DNA- and RNA-binding properties. It has been implicated in mRNA biogenesis at the transcriptional and post-transcriptional levels. hnRNP DL binds single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) in a non-sequencespecific manner, and interacts with poly(G) and poly(A) tenaciously. It contains two putative two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glycine- and tyrosine-rich C-terminus.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2587669329 508 KVFVGGLPPDIDEDEITASFRRFGPlVVDWPHKAESKSYfPPKGYAFLLFQEESSVQALIDacLEE---DGKL 577
Cdd:cd12758     1 KMFIGGLSWDTSKKDLTEYLSRFGE-VVDCTIKTDPVTG-RSRGFGFVLFKDAASVDKVLE--LKEhklDGKL 69

RNA recognition motif 1 (RRM1) found in plant pre-mRNA-splicing factor SF2 and similar proteins; This subgroup corresponds to the RRM1 of SF2, also termed SR1 protein, a plant serine/arginine (SR)-rich phosphoprotein similar to the mammalian splicing factor SF2/ASF. It promotes splice site switching in mammalian nuclear extracts. SF2 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a C-terminal domain rich in proline, serine and lysine residues (PSK domain), a composition reminiscent of histones. This PSK domain harbors a putative phosphorylation site for the mitotic kinase cyclin/p34cdc2.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2587669329 508 KVFVGGLPPDIDEDEITASFRRFGPLVvdwphKAESKSYFPPKGYAFLLFQEESSVQaliDACLEEDG 575
Cdd:cd12599     1 RVYVGNLPMDIREREVEDLFSKYGPVV-----SIDLKIPPRPPAYAFVEFEDARDAE---DAIRGRDG 60

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        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2587669329 508 KVFVGGLPPDIDEDEITASFRRFGPL--VVDWPHKAESKSyfppKGYAFLLFqeESSVQALiDACLEEDGK 576
Cdd:cd12382     3 KLFIGGLNTETNEKALEAVFGKYGRIveVLLMKDRETNKS----RGFAFVTF--ESPADAK-DAARDMNGK 66

RNA recognition motif 2 (RRM2) found in RNA-binding protein Musashi homologs Musashi-1, Musashi-2 and similar proteins; This subfamily corresponds to the RRM2.in Musashi-1 (also termed Msi1), a neural RNA-binding protein putatively expressed in central nervous system (CNS) stem cells and neural progenitor cells, and associated with asymmetric divisions in neural progenitor cells. It is evolutionarily conserved from invertebrates to vertebrates. Musashi-1 is a homolog of Drosophila Musashi and Xenopus laevis nervous system-specific RNP protein-1 (Nrp-1). It has been implicated in the maintenance of the stem-cell state, differentiation, and tumorigenesis. It translationally regulates the expression of a mammalian numb gene by binding to the 3'-untranslated region of mRNA of Numb, encoding a membrane-associated inhibitor of Notch signaling, and further influences neural development. Moreover, Musashi-1 represses translation by interacting with the poly(A)-binding protein and competes for binding of the eukaryotic initiation factor-4G (eIF-4G). Musashi-2 (also termed Msi2) has been identified as a regulator of the hematopoietic stem cell (HSC) compartment and of leukemic stem cells after transplantation of cells with loss and gain of function of the gene. It influences proliferation and differentiation of HSCs and myeloid progenitors, and further modulates normal hematopoiesis and promotes aggressive myeloid leukemia. Both, Musashi-1 and Musashi-2, contain two conserved N-terminal tandem RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), along with other domains of unknown function.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2587669329 508 KVFVGGLPPDIDEDEITASFRRFGP-----LVVDwphKAESKSyfppKGYAFLLFQEESSV 563
Cdd:cd12323     1 KIFVGGLSANTTEDDVKKYFSQFGKvedamLMFD---KQTNRH----RGFGFVTFESEDVV 54

RNA recognition motif (RRM) superfamily; RRM, also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), is a highly abundant domain in eukaryotes found in proteins involved in post-transcriptional gene expression processes including mRNA and rRNA processing, RNA export, and RNA stability. This domain is 90 amino acids in length and consists of a four-stranded beta-sheet packed against two alpha-helices. RRM usually interacts with ssRNA, but is also known to interact with ssDNA as well as proteins. RRM binds a variable number of nucleotides, ranging from two to eight. The active site includes three aromatic side-chains located within the conserved RNP1 and RNP2 motifs of the domain. The RRM domain is found in a variety heterogeneous nuclear ribonucleoproteins (hnRNPs), proteins implicated in regulation of alternative splicing, and protein components of small nuclear ribonucleoproteins (snRNPs).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2587669329 617 IFVGGVPRPLRAVELAMIMDRlYGGVCYAGIDTDPELKyPKGAGRVAFSNQQSYIAAISArfvqLQHNDIDKRP 690
Cdd:cd00590     1 LFVGNLPPDTTEEDLRELFSK-FGEVVSVRIVRDRDGK-SKGFAFVEFESPEDAEKALEA----LNGTELGGRP 68

RNA recognition motif 2 (RRM2) found in Deleted in azoospermia-associated protein 1 (DAZAP1) and similar proteins; This subfamily corresponds to the RRM2 of DAZAP1 or DAZ-associated protein 1, also termed proline-rich RNA binding protein (Prrp), a multi-functional ubiquitous RNA-binding protein expressed most abundantly in the testis and essential for normal cell growth, development, and spermatogenesis. DAZAP1 is a shuttling protein whose acetylated is predominantly nuclear and the nonacetylated form is in cytoplasm. DAZAP1 also functions as a translational regulator that activates translation in an mRNA-specific manner. DAZAP1 was initially identified as a binding partner of Deleted in Azoospermia (DAZ). It also interacts with numerous hnRNPs, including hnRNP U, hnRNP U like-1, hnRNPA1, hnRNPA/B, and hnRNP D, suggesting DAZAP1 might associate and cooperate with hnRNP particles to regulate adenylate-uridylate-rich elements (AU-rich element or ARE)-containing mRNAs. DAZAP1 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal proline-rich domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2587669329 615 KTIFVGGVPRPLRAVELAMIMDRlYGGVCYAGIDTDPELKYPKGAGRVAFSNQQSYIAAISARFVQL 681
Cdd:cd12327     3 KKVFVGGIPHNCGETELRDYFKR-YGVVTEVVMMYDAEKQRSRGFGFITFEDEQSVDQAVNMHFHDI 68

RNA recognition motif 1 (RRM1) and 2 (RRM2) found in RRM-containing coactivator activator/modulator (CoAA) and similar proteins; This subfamily corresponds to the RRM in CoAA (also known as RBM14 or PSP2) and RNA-binding protein 4 (RBM4). CoAA is a heterogeneous nuclear ribonucleoprotein (hnRNP)-like protein identified as a nuclear receptor coactivator. It mediates transcriptional coactivation and RNA splicing effects in a promoter-preferential manner, and is enhanced by thyroid hormone receptor-binding protein (TRBP). CoAA contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a TRBP-interacting domain. RBM4 is a ubiquitously expressed splicing factor with two isoforms, RBM4A (also known as Lark homolog) and RBM4B (also known as RBM30), which are very similar in structure and sequence. RBM4 may also function as a translational regulator of stress-associated mRNAs as well as play a role in micro-RNA-mediated gene regulation. RBM4 contains two N-terminal RRMs, a CCHC-type zinc finger, and three alanine-rich regions within their C-terminal regions. This family also includes Drosophila RNA-binding protein lark (Dlark), a homolog of human RBM4. It plays an important role in embryonic development and in the circadian regulation of adult eclosion. Dlark shares high sequence similarity with RBM4 at the N-terminal region. However, Dlark has three proline-rich segments instead of three alanine-rich segments within the C-terminal region.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2587669329 508 KVFVGGLPPDIDEDEITASFRRFGPL----VVdwphkaesksyfppKGYAFLLFQEESSVQALIDA 569
Cdd:cd12343     1 KIFVGNLPDAATSEELRALFEKYGKVtecdIV--------------KNYAFVHMEKEEDAEDAIKA 52

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2587669329 510 FVGGLPPDIDEDEITASFRRFGP-----LVVDwphKAESKsyfpPKGYAFLLFQEESSVQALIDACleeDGK 576
Cdd:cd12236     5 FVARLSYDTTESKLRREFEKYGPikrvrLVRD---KKTGK----SRGYAFIEFEHERDMKAAYKHA---DGK 66

RNA recognition motif 3 in fungal pre-messenger RNA splicing protein 24 (Prp24) and similar proteins; This subfamily corresponds to the RRM3 of Prp24, also termed U4/U6 snRNA-associated-splicing factor PRP24 (U4/U6 snRNP), an RNA-binding protein with four well conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). It facilitates U6 RNA base-pairing with U4 RNA during spliceosome assembly. Prp24 specifically binds free U6 RNA primarily with RRMs 1 and 2 and facilitates pairing of U6 RNA bases with U4 RNA bases. Additionally, it may also be involved in dissociation of the U4/U6 complex during spliceosome activation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2587669329 507 RKVFVGGLPPDIDEDEITASFRRFGPL-VVDWPHKAESKSYFPPKGYAFLLFQEESSVQalidACLEEDGKlylcvsspT 585
Cdd:cd12298     1 REIRVRNLDFELDEEALRGIFEKFGEIeSINIPKKQKNRKGRHNNGFAFVTFEDADSAE----SALQLNGT--------L 68

                  ....*...
gi 2587669329 586 IKDKPVQI 593
Cdd:cd12298    69 LDNRKISV 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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2587669329 509 VFVGGLPPDIDEDEITASFRRFGP-----LVVDwphKAESKSyfppKGYAFLLFQEESS 562
Cdd:cd12411    12 IYIGGLPYELTEGDILCVFSQYGEivdinLVRD---KKTGKS----KGFAFLAYEDQRS 63

RNA recognition motif (RRM) found in RNA-binding protein 7 (RBM7) and similar proteins; This subfamily corresponds to the RRM of RBM7, RBM11 and their eukaryotic homologous. RBM7 is an ubiquitously expressed pre-mRNA splicing factor that enhances messenger RNA (mRNA) splicing in a cell-specific manner or in a certain developmental process, such as spermatogenesis. It interacts with splicing factors SAP145 (the spliceosomal splicing factor 3b subunit 2) and SRp20, and may play a more specific role in meiosis entry and progression. Together with additional testis-specific RNA-binding proteins, RBM7 may regulate the splicing of specific pre-mRNA species that are important in the meiotic cell cycle. RBM11 is a novel tissue-specific splicing regulator that is selectively expressed in brain, cerebellum and testis, and to a lower extent in kidney. It is localized in the nucleoplasm and enriched in SRSF2-containing splicing speckles. It may play a role in the modulation of alternative splicing during neuron and germ cell differentiation. Both, RBM7 and RBM11, contain an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a region lacking known homology at the C-terminus. The RRM is responsible for RNA binding, whereas the C-terminal region permits nuclear localization and homodimerization.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2587669329 507 RKVFVGGLPPDIDEDEITASFRRFGPLV-VDWPHKAESKsyfpPKGYAFLLFQEESSV 563
Cdd:cd12336     2 RTLFVGNLDPRVTEEILYELFLQAGPLEgVKIPKDPNGK----PKNFAFVTFKHEVSV 55

RNA recognition motif (RRM) found in ras GTPase-activating protein-binding protein 2 (G3BP2) and similar proteins; This subgroup corresponds to the RRM of G3BP2, also termed GAP SH3 domain-binding protein 2, a cytoplasmic protein that interacts with both IkappaBalpha and IkappaBalpha/NF-kappaB complexes, indicating that G3BP2 may play a role in the control of nucleocytoplasmic distribution of IkappaBalpha and cytoplasmic anchoring of the IkappaBalpha/NF-kappaB complex. G3BP2 contains an N-terminal nuclear transfer factor 2 (NTF2)-like domain, an acidic domain, a domain containing five PXXP motifs, an RNA recognition motif (RRM domain), and an Arg-Gly-rich region (RGG-rich region, or arginine methylation motif). It binds to the SH3 domain of RasGAP, a multi-functional protein controlling Ras activity, through its N-terminal NTF2-like domain. The acidic domain is sufficient for the interaction of G3BP2 with the IkappaBalpha cytoplasmic retention sequence. Furthermore, G3BP2 might influence stability or translational efficiency of particular mRNAs by binding to RNA-containing structures within the cytoplasm through its RNA-binding domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2587669329 506 SRKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESKSYFPpkGYAFLLFQEESSVQALIDA 569
Cdd:cd12464     5 SHQLFVGNLPHDIDENELKEFFMSFGNVVELRINTKGVGGKLP--NFGFVVFDDSDPVQRILNA 66

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

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gi 2587669329 508 KVFVGGLPPDIDEDEITASFRRFGPLvvdwphkaESKSYFPPKGYAFLLFQEESSVQALIDAC---LEEDGKLY 578
Cdd:cd12340     1 RLFVRPFPPDTSESAIREIFSPYGPV--------KEVKMLSDSNFAFVEFEELEDAIRAKDSVhgrVLNNEPLY 66