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 672040273 514 RKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESKSYFPPKGYAFLLFQEESSVQALIDACLEEDGKLYLCVSSPTI 593
Cdd:cd12724    1 RKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESKSYFPPKGYAFLLFQDERSVQALIDACIEEDDKLYLCVSSPTI 80

                         90
                 ....*....|..
gi 672040273 594 KDKPVQIRPWNL 605
Cdd:cd12724   81 KDKPVQIRPWNL 92

Cytoplasmic polyadenylation element-binding protein ZZ domain; This ZZ-type zinc finger domain binds zinc via two conserved histidines in the C-terminal part of the domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 672040273  697 VEVKPYVLDDqMCDECQGTRcggkfAPFFCANVTCLQYYCEYCWASIHSRAGREFHKPLVKE 758
Cdd:pfam16366   1 VQIDPYLEDS-LCSECNGQP-----GPYFCRDLSCFKYYCRSCWQWQHSRDRLRNHKPLVRN 56

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 672040273 514 RKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESKSYFPPKGYAFLLFQEESSVQALIDACLEEDGKLYLCVSSPTI 593
Cdd:cd12724    1 RKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESKSYFPPKGYAFLLFQDERSVQALIDACIEEDDKLYLCVSSPTI 80

                         90
                 ....*....|..
gi 672040273 594 KDKPVQIRPWNL 605
Cdd:cd12724   81 KDKPVQIRPWNL 92

RNA recognition motif;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672040273  513 SRKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESKSYFPP-KGYAFLLFQEESSVQALIDACLEEDGKLYLCVSSP 591
Cdd:pfam16367   1 SRKVFVGGLPWDITEAELTATFGRFGPLLVDWPGKPESPSYFPDvKGYVFLVFEDEKSVQALLDACTQEDGKYYLKLSSP 80

                          90
                  ....*....|.
gi 672040273  592 TIKDKPVQIRP 602
Cdd:pfam16367  81 RMKDKPVQIRP 91

RNA recognition motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 672040273   515 KVFVGGLPPDIDEDEITASFRRFGPLV-VDWPHKAESKSyfpPKGYAFLLFQEESSVQALIDAC 577
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVEsVRLVRDKETGK---SKGFAFVEFESEEDAEKALEAL 61

B-box-type 1 zinc finger (Bbox1); The B-box-type zinc finger is a short zinc binding domain of around 40 amino acid residues in length. It has been found in transcription factors, ribonucleoproteins and proto-oncoproteins, such as in TRIM (tripartite motif) proteins that consist of an N-terminal RING finger (originally called an A-box), followed by 1-2 B-box domains and a coiled-coil domain (also called RBCC for Ring, B-box, Coiled-Coil). The B-box-type zinc finger often presents in combination with other motifs, like RING zinc finger, NHL motif, coiled-coil or RFP domain, in functionally unrelated proteins, most likely mediating protein-protein interactions. Based on different consensus sequences and the spacing of the 7-8 zinc-binding residues, the B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2). This family corresponds to the type 1 B-box (Bbox1).

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 672040273 708 MCDECQGTRcggkfAPFFCanVTCLQYYCEYCWASIHSR 746
Cdd:cd19757    1 LCDECEERE-----ATVYC--LECEEFLCDDCSDAIHRR 32

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 672040273 514 RKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESKSYFPPKGYAFLLFQEESSVQALIDACLEEDGKLYLCVSSPTI 593
Cdd:cd12724    1 RKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESKSYFPPKGYAFLLFQDERSVQALIDACIEEDDKLYLCVSSPTI 80

                         90
                 ....*....|..
gi 672040273 594 KDKPVQIRPWNL 605
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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672040273 622 KTIFVGGVPRPLRAVELAMIMDRLYGGVCYAGIDTDPELKYPKGAGRVAFSNQQSYIAAISARFVQLQHNDIDKRVEVKP 701
Cdd:cd12726    1 KTIFVGGVPRPLRAVELAMIMDRLYGGVCYAGIDTDPELKYPKGAGRVAFSNQQSYIAAISARFVQLQHGDIDKRVEVKP 80

                 .
gi 672040273 702 Y 702
Cdd:cd12726   81 Y 81

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672040273 622 KTIFVGGVPRPLRAVELAMIMDRLYGGVCYAGIDTDPELKYPKGAGRVAFSNQQSYIAAISARFVQLQHNDIDKRVEVKP 701
Cdd:cd12445    1 RTVFVGGLPLPLTAAELAAILERLYGGVCYVEIDTDEFYLYPTGCARVTFNNEQSYIKAVSEVFVELPFGTINKRVRIRP 80

                 .
gi 672040273 702 Y 702
Cdd:cd12445   81 Y 81

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672040273 619 DPRKTIFVGGVPRPLRAVELAMIMDRLYGGVCYAGIDTDpELKYPKGAGRVAFSNQQSYIAAISARFVQLQHNDIDKRVE 698
Cdd:cd12725    1 DPSKTVFVGALHGMLNAEGLANIMNDLFGGVVYAGIDTD-KHKYPIGSGRVTFNNQRSYMKAVNAAFVEIKTPKFTKKVQ 79

                 ....
gi 672040273 699 VKPY 702
Cdd:cd12725   80 IDPY 83

RNA recognition motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 672040273   515 KVFVGGLPPDIDEDEITASFRRFGPLV-VDWPHKAESKSyfpPKGYAFLLFQEESSVQALIDAC 577
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVEsVRLVRDKETGK---SKGFAFVEFESEEDAEKALEAL 61

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 672040273  516 VFVGGLPPDIDEDEITASFRRFGPLV-VDWPHKAESKSyfppKGYAFLLFQEESSVQALIDACleeDGKLY 585
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKsIRLVRDETGRS----KGFAFVEFEDEEDAEKAIEAL---NGKEL 64

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 672040273 513 SRKVFVGGLPPDIDEDEITASFRRFGPLV-VDWPHKAESKSyfpPKGYAFLLFQEESSV 570
Cdd:cd12327    2 SKKVFVGGIPHNCGETELRDYFKRYGVVTeVVMMYDAEKQR---SRGFGFITFEDEQSV 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 672040273 513 SRKVFVGGLPPDIDEDEITASFRRFGPLV-VDWPHKAESKsyfPPKGYAFLLFQEESSVQALIDAC 577
Cdd:cd12229    3 NHQLFVGNLPHDITEDELKEFFSRFGNVLeLRINSKGGGG---RLPNFGFVVFDDPEAVQKILANK 65

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 672040273 515 KVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAesksyfPPkGYAFLLFQEESSVQaliDACLEEDGKlYLC 587
Cdd:cd12373    1 KVYVGNLGPRVTKRELEDAFEKYGPLRNVWVARN------PP-GFAFVEFEDPRDAE---DAVRALDGR-RIC 62

RNA recognition motif (RRM) found in cyclophilin-33 (Cyp33) and similar proteins; This subfamily corresponds to the RRM of Cyp33, also termed peptidyl-prolyl cis-trans isomerase E (PPIase E), or cyclophilin E, or rotamase E. Cyp33 is a nuclear RNA-binding cyclophilin with an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal PPIase domain. Cyp33 possesses RNA-binding activity and preferentially binds to polyribonucleotide polyA and polyU, but hardly to polyG and polyC. It binds specifically to mRNA, which can stimulate its PPIase activity. Moreover, Cyp33 interacts with the third plant homeodomain (PHD3) zinc finger cassette of the mixed lineage leukemia (MLL) proto-oncoprotein and a poly-A RNA sequence through its RRM domain. It further mediates downregulation of the expression of MLL target genes HOXC8, HOXA9, CDKN1B, and C-MYC, in a proline isomerase-dependent manner. Cyp33 also possesses a PPIase activity that catalyzes cis-trans isomerization of the peptide bond preceding a proline, which has been implicated in the stimulation of folding and conformational changes in folded and unfolded proteins. The PPIase activity can be inhibited by the immunosuppressive drug cyclosporin A.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 672040273 516 VFVGGLPPDIDEDEITASFRRFGPLV-VDWPHKAESKSYfppKGYAFLLFQEESSVQALID 575
Cdd:cd12347    1 LYVGGLAEEVDEKVLHAAFIPFGDIVdIQIPLDYETEKH---RGFAFVEFEEAEDAAAAID 58

RNA recognition motif 2 (RRM2) found in granule-associated RNA binding proteins (p40-TIA-1 and TIAR), and yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1; This subfamily corresponds to the RRM3 of TIA-1, TIAR, and PUB1. Nucleolysin TIA-1 isoform p40 (p40-TIA-1 or TIA-1) and nucleolysin TIA-1-related protein (TIAR) are granule-associated RNA binding proteins involved in inducing apoptosis in cytotoxic lymphocyte (CTL) target cells. They share high sequence similarity and are expressed in a wide variety of cell types. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis.TIAR is mainly localized in the nucleus of hematopoietic and nonhematopoietic cells. It is translocated from the nucleus to the cytoplasm in response to exogenous triggers of apoptosis. Both TIA-1 and TIAR bind specifically to poly(A) but not to poly(C) homopolymers. They are composed of three N-terminal highly homologous RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. TIA-1 and TIAR interact with RNAs containing short stretches of uridylates and their RRM2 can mediate the specific binding to uridylate-rich RNAs. The C-terminal auxiliary domain may be responsible for interacting with other proteins. In addition, TIA-1 and TIAR share a potential serine protease-cleavage site (Phe-Val-Arg) localized at the junction between their RNA binding domains and their C-terminal auxiliary domains. This subfamily also includes a yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1, termed ARS consensus-binding protein ACBP-60, or poly uridylate-binding protein, or poly(U)-binding protein, which has been identified as both a heterogeneous nuclear RNA-binding protein (hnRNP) and a cytoplasmic mRNA-binding protein (mRNP). It may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm. PUB1 is distributed in both, the nucleus and the cytoplasm, and binds to poly(A)+ RNA (mRNA or pre-mRNA). Although it is one of the major cellular proteins cross-linked by UV light to polyadenylated RNAs in vivo, PUB1 is nonessential for cell growth in yeast. PUB1 also binds to T-rich single stranded DNA (ssDNA); however, there is no strong evidence implicating PUB1 in the mechanism of DNA replication. PUB1 contains three RRMs, and a GAR motif (glycine and arginine rich stretch) that is located between RRM2 and RRM3.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 672040273 516 VFVGGLPPDIDEDEITASFRRFGPLvvdwphkAESKsYFPPKGYAFLLFQ-EESSVQALI 574
Cdd:cd12354    3 VYVGNITKGLTEALLQQTFSPFGQI-------LEVR-VFPDKGYAFIRFDsHEAATHAIV 54

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein D-like (hnRNP DL) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP DL (or hnRNP D-like), also termed AU-rich element RNA-binding factor, or JKT41-binding protein (protein laAUF1 or JKTBP), 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 672040273 515 KVFVGGLPPDIDEDEITASFRRFGPLV-VDWPHKAESKSYfppKGYAFLLFQEESSVQALID 575
Cdd:cd12585    1 KVFVGGLSPDTSEEQIKEYFGAFGEIEnIELPMDTKTNER---RGFCFITYTDEEPVQKLLE 59

RNA recognition motif 1 (RRM1) found in serine/arginine-rich splicing factor 1 (SRSF1) and similar proteins; This subgroup corresponds to the RRM1 in three serine/arginine (SR) proteins: serine/arginine-rich splicing factor 1 (SRSF1 or ASF-1), serine/arginine-rich splicing factor 9 (SRSF9 or SRp30C), and plant pre-mRNA-splicing factor SF2 (SR1). SRSF1 is a shuttling SR protein involved in constitutive and alternative splicing, nonsense-mediated mRNA decay (NMD), mRNA export and translation. It also functions as a splicing-factor oncoprotein that regulates apoptosis and proliferation to promote mammary epithelial cell transformation. SRSF9 has been implicated in the activity of many elements that control splice site selection, the alternative splicing of the glucocorticoid receptor beta in neutrophils and in the gonadotropin-releasing hormone pre-mRNA. It can also interact with other proteins implicated in alternative splicing, including YB-1, rSLM-1, rSLM-2, E4-ORF4, Nop30, and p32. Both, SRSF1 and SRSF9, contain two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal RS domains rich in serine-arginine dipeptides. In contrast, SF2 contains two N-terminal RRMs and a C-terminal PSK domain rich in proline, serine and lysine residues.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 672040273 515 KVFVGGLPPDIDEDEITASFRRFGPLVvdwphKAESKSYFPPKGYAFLLFQEESSVQaliDACLEEDG 582
Cdd:cd12338    1 RIYVGNLPGDIRERDIEDLFYKYGPIL-----AIDLKNRRRGPPFAFVEFEDPRDAE---DAIRGRDG 60

RNA recognition motif 2 (RRM2) found in Nicotiana sylvestris chloroplastic 33 kDa ribonucleoprotein (NsCP33) and similar proteins; The family includes NsCP33, Arabidopsis thaliana chloroplastic 31 kDa ribonucleoprotein (CP31A) and mitochondrial glycine-rich RNA-binding protein 2 (AtGR-RBP2). NsCP33 may be involved in splicing and/or processing of chloroplast RNA's. AtCP31A, also called RNA-binding protein 1/2/3 (AtRBP33), or RNA-binding protein CP31A, or RNA-binding protein RNP-T, or RNA-binding protein cp31, is required for specific RNA editing events in chloroplasts and stabilizes specific chloroplast mRNAs, as well as for normal chloroplast development under cold stress conditions by stabilizing transcripts of numerous mRNAs under these conditions. CP31A may modulate telomere replication through RNA binding domains. AtGR-RBP2, also called AtRBG2, or glycine-rich protein 2 (AtGRP2), or mitochondrial RNA-binding protein 1a (At-mRBP1a), plays a role in RNA transcription or processing during stress. It binds RNAs and DNAs sequence with a preference to single-stranded nucleic acids. AtGR-RBP2 displays strong affinity to poly(U) sequence. It exerts cold and freezing tolerance, probably by exhibiting an RNA chaperone activity during the cold and freezing adaptation process. Some members in this family contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the second RRM motif.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 672040273 515 KVFVGGLPPDIDEDEITASFRRFG-----PLVVDwphKAESKSyfppKGYAFLLFQEESSVQALIDAC 577
Cdd:cd21608    1 KLYVGNLSWDTTEDDLRDLFSEFGevesaKVITD---RETGRS----RGFGFVTFSTAEAAEAAIDAL 61

RNA recognition motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 672040273   623 TIFVGGVPRPLRAVELAMIMDRlYGGVCYAGIDTDPELKYPKGAGRVAFSNQQSYIAAISA 683
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSK-FGKVESVRLVRDKETGKSKGFAFVEFESEEDAEKALEA 60

RNA recognition motif 1 (RRM1) found in the c-myc gene single-strand binding proteins (MSSP) family; This subfamily corresponds to the RRM1 of c-myc gene single-strand binding proteins (MSSP) family, including single-stranded DNA-binding protein MSSP-1 (also termed RBMS1 or SCR2) and MSSP-2 (also termed RBMS2 or SCR3). All MSSP family members contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), both of which are responsible for the specific DNA binding activity. Both, MSSP-1 and -2, have been identified as protein factors binding to a putative DNA replication origin/transcriptional enhancer sequence present upstream from the human c-myc gene in both single- and double-stranded forms. Thus, they have been implied in regulating DNA replication, transcription, apoptosis induction, and cell-cycle movement, via the interaction with c-MYC, the product of protooncogene c-myc. Moreover, the family includes a new member termed RNA-binding motif, single-stranded-interacting protein 3 (RBMS3), which is not a transcriptional regulator. RBMS3 binds with high affinity to A/U-rich stretches of RNA, and to A/T-rich DNA sequences, and functions as a regulator of cytoplasmic activity. In addition, a putative meiosis-specific RNA-binding protein termed sporulation-specific protein 5 (SPO5, or meiotic RNA-binding protein 1, or meiotically up-regulated gene 12 protein), encoded by Schizosaccharomyces pombe Spo5/Mug12 gene, is also included in this family. SPO5 is a novel meiosis I regulator that may function in the vicinity of the Mei2 dot.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 672040273 514 RKVFVGGLPPDIDEDEITASFRRFGPLVvdwPHKA--ESKSYfPPKGYAFLLFQEESSVQALIDA 576
Cdd:cd12243    1 TNVYIRGLPPNTTDEDLLLLCQSFGKII---STKAiiDKQTN-KCKGYGFVDFDSPEAALKAIEG 61

RNA recognition motif 1 (RRM1) found in RNA-binding protein MRN1 and similar proteins; This subgroup corresponds to the RRM1 of MRN1, also termed multicopy suppressor of RSC-NHP6 synthetic lethality protein 1, or post-transcriptional regulator of 69 kDa,which is a RNA-binding protein found in yeast. Although its specific biological role remains unclear, MRN1 might be involved in translational regulation. Members in this family contain four copies of conserved RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 672040273 513 SRKVFVGGLPPDIDEDEITaSFRRFGPLvvdwphkaESKSYFPPKGYAFLLFQEESSVQALI-DACLE 579
Cdd:cd12520    1 SRTVYLGNLPPNTTVKELL-SHVRSGPI--------ENVRILPEKNCAFISFLDPSAATAFHsDAILK 59

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A subfamily; This subfamily corresponds to the RRM2 of hnRNP A0, hnRNP A1, hnRNP A2/B1, hnRNP A3 and similar proteins. hnRNP A0 is a low abundance hnRNP protein that has been implicated in mRNA stability in mammalian cells. It has been identified as the substrate for MAPKAP-K2 and may be involved in the lipopolysaccharide (LPS)-induced post-transcriptional regulation of tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase 2 (COX-2) and macrophage inflammatory protein 2 (MIP-2). hnRNP A1 is an abundant eukaryotic nuclear RNA-binding protein that may modulate splice site selection in pre-mRNA splicing. hnRNP A2/B1 is an RNA trafficking response element-binding protein that interacts with the hnRNP A2 response element (A2RE). Many mRNAs, such as myelin basic protein (MBP), myelin-associated oligodendrocytic basic protein (MOBP), carboxyanhydrase II (CAII), microtubule-associated protein tau, and amyloid precursor protein (APP) are trafficked by hnRNP A2/B1. hnRNP A3 is also a RNA trafficking response element-binding protein that participates in the trafficking of A2RE-containing RNA. The hnRNP A subfamily is characterized by two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long glycine-rich region at the C-terminus.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 672040273 515 KVFVGGLPPDIDEDEITASFRRFGP-----LVVDwphKAESKsyfpPKGYAFLLFQEESSV 570
Cdd:cd12328    1 KLFVGGLKEDVEEEDLREYFSQFGKvesveIVTD---KETGK----KRGFAFVTFDDHDSV 54

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 672040273 514 RKVFVGGLPPDIDEDEITASFRRFGPLV-VDWPHKAESKSyfpPKGYAFLLFQ-EESSVQA 572
Cdd:cd12398    1 RSVFVGNIPYDATEEQLKEIFSEVGPVVsFRLVTDRETGK---PKGYGFCEFRdAETALSA 58

RNA recognition motif 2 (RRM2) found in granule-associated RNA binding proteins p40-TIA-1 and TIAR; This subfamily corresponds to the RRM2 of nucleolysin TIA-1 isoform p40 (p40-TIA-1 or TIA-1) and nucleolysin TIA-1-related protein (TIAR), both of which are granule-associated RNA binding proteins involved in inducing apoptosis in cytotoxic lymphocyte (CTL) target cells. TIA-1 and TIAR share high sequence similarity. They are expressed in a wide variety of cell types. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis. TIAR is mainly localized in the nucleus of hematopoietic and nonhematopoietic cells. It is translocated from the nucleus to the cytoplasm in response to exogenous triggers of apoptosis. Both, TIA-1 and TIAR, bind specifically to poly(A) but not to poly(C) homopolymers. They are composed of three N-terminal highly homologous RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. TIA-1 and TIAR interact with RNAs containing short stretches of uridylates and their RRM2 can mediate the specific binding to uridylate-rich RNAs. The C-terminal auxiliary domain may be responsible for interacting with other proteins. In addition, TIA-1 and TIAR share a potential serine protease-cleavage site (Phe-Val-Arg) localized at the junction between their RNA binding domains and their C-terminal auxiliary domains.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 672040273 515 KVFVGGLPPDIDEDEITASFRRFGPL----VVDWPHKAESksyfppKGYAFLLFQEESSVQALI 574
Cdd:cd12353    1 HIFVGDLSPEIETEDLKEAFAPFGEIsdarVVKDTQTGKS------KGYGFVSFVKKEDAENAI 58

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 672040273 513 SRKVFVGGLPPDIDEDEITASFRRFGPL-----VVDwphKAESKSyfppKGYAFLLFQEESSVqaliDACLEEDGKLYlc 587
Cdd:cd12676    1 GRTLFVRNLPFDATEDELYSHFSQFGPLkyarvVKD---PATGRS----KGTAFVKFKNKEDA----DNCLSAAPEAQ-- 67

                         90       100
                 ....*....|....*....|....*..
gi 672040273 588 VSSPTIKDKPVQIRPWNLSdSDFVMDG 614
Cdd:cd12676   68 STSLLEKYSLEQDITDDVS-AKFTLDG 93

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 672040273 514 RKVFVGGLPPDIDEDEITASFRRFGPlVVDwphkaesksYFPPK---GYAFLLFQEESSVQALI 574
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 672040273 515 KVFVGGLPPDIDEDEITASFRRFGPlVVDWPHKAESKSYfPPKGYAFLLFQEESSVQALIDacLEE---DGKL 584
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 672040273 515 KVFVGGLPPDIDEDEITASFRRFGPLVvdwphKAESKSYFPPKGYAFLLFQEESSVQaliDACLEEDG 582
Cdd:cd12599    1 RVYVGNLPMDIREREVEDLFSKYGPVV-----SIDLKIPPRPPAYAFVEFEDARDAE---DAIRGRDG 60

RNA recognition motif 1 (RRM1) found in (U)-binding-splicing factor PUF60 and similar proteins; This subfamily corresponds to the RRM1 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 672040273 515 KVFVGGLPPDIDEDEITASFRRFGPLvvdwphKAESKSYFPP----KGYAFLLFQ 565
Cdd:cd12370    2 RVYVGSIYFELGEDTIRQAFAPFGPI------KSIDMSWDPVtmkhKGFAFVEYE 50

Cell division protein DedD (periplasmic protein involved in septation) [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 672040273  96 EPGAAEAPSTPLSSETPKPEDSSAVPALSPASAPPAP 132
Cdd:COG3147    8 APAAAAAPAAPAAAAAPAPAAAAAAAAPKPAAKPAAP 44

RNA recognition motif 1 (RRM1) found in vertebrate heterogeneous nuclear ribonucleoprotein R (hnRNP R); This subgroup corresponds to the RRM1 of hnRNP R, which is a ubiquitously expressed nuclear RNA-binding protein that specifically binds mRNAs with a preference for poly(U) stretches. Upon binding of RNA, hnRNP R forms oligomers, most probably dimers. hnRNP R has been implicated in mRNA processing and mRNA transport, and also acts as a regulator to modify binding to ribosomes and RNA translation. It is predominantly located in axons of motor neurons and to a much lower degree in sensory axons. In axons of motor neurons, it also functions as a cytosolic protein and interacts with wild type of survival motor neuron (SMN) proteins directly, further providing a molecular link between SMN and the spliceosome. Moreover, hnRNP R plays an important role in neural differentiation and development, and in retinal development and light-elicited cellular activities. hnRNP R contains an acidic auxiliary N-terminal region, followed by two well defined and one degenerated RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal RGG motif; it binds RNA through its RRM domains.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 672040273 515 KVFVGGLPPDIDEDEITASFRRFGP-----LVVDwPHKAESksyfppKGYAFLLFQEESSVQALIDAC 577
Cdd:cd12482    3 EVFVGKIPRDLYEDELVPLFEKAGPiwdlrLMMD-PLSGQN------RGYAFITFCNKEAAQEAVKLC 63

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 672040273 646 YGGVCYAGIDTDPELKYPKGAGRVAFSNQQSYIAAISArfvqLQHNDIDKR 696
Cdd:cd12448   22 HGSIVSVRLPTDRETGQPKGFGYVDFSTIDSAEAAIDA----LGGEYIDGR 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 672040273 515 KVFVGGLPPDIDEDEITASFRRFGPL----VVdwphkaesksyfppKGYAFLLFQEESSVQALIDA 576
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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 672040273 517 FVGGLPPDIDEDEITASFRRFGP-----LVVDwphKAESKsyfpPKGYAFLLFQEESSVQALIDACleeDGK 583
Cdd:cd12236    5 FVARLSYDTTESKLRREFEKYGPikrvrLVRD---KKTGK----SRGYAFIEFEHERDMKAAYKHA---DGK 66

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 672040273 624 IFVGGVPRPLRAVELAMIMDRlYGGVCYAGIDTDPELKyPKGAGRVAFSNQQSYIAAISArfvqLQHNDID-KRVEVK 700
Cdd:cd00590    1 LFVGNLPPDTTEEDLRELFSK-FGEVVSVRIVRDRDGK-SKGFAFVEFESPEDAEKALEA----LNGTELGgRPLKVS 72

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 672040273 514 RKVFVGGLPPDIDEDEITASFRRFGPL-VVDWPHKAESKSYFPPKGYAFLLFQEESSVQalidACLEEDGKlylcvsspT 592
Cdd:cd12298    1 REIRVRNLDFELDEEALRGIFEKFGEIeSINIPKKQKNRKGRHNNGFAFVTFEDADSAE----SALQLNGT--------L 68

                 ....*...
gi 672040273 593 IKDKPVQI 600
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.

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gi 672040273 516 VFVGGLPPDIDEDEITASFRRFGP-----LVVDwphKAESKSyfppKGYAFLLFQEESS 569
Cdd:cd12411   12 IYIGGLPYELTEGDILCVFSQYGEivdinLVRD---KKTGKS----KGFAFLAYEDQRS 63

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

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gi 672040273 521 LPPDIDEDEITASFRRFGP-----LVVDwphKAESKSyfppKGYAFLLFQEESSVQALIDA 576
Cdd:cd12408    7 LSEDATEEDLRELFRPFGPisrvyLAKD---KETGQS----KGFAFVTFETREDAERAIEK 60

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

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gi 672040273 515 KVFVGGLPPDIDEDEITASFRRFGPLV-VDWPHKAESKSyfpPKGYAFLLFQEESSVQAlidACLEEDGKLY 585
Cdd:cd12316    1 RLFVRNLPFTATEDELRELFEAFGKISeVHIPLDKQTKR---SKGFAFVLFVIPEDAVK---AYQELDGSIF 66