RNA recognition motif (RRM) found in Saccharomyces cerevisiae protein Nrd1, Schizosaccharomyces pombe Rpb7-binding protein seb1 and similar proteins; This subfamily corresponds to the RRM of Nrd1 and Seb1. Nrd1 is a novel heterogeneous nuclear ribonucleoprotein (hnRNP)-like RNA-binding protein encoded by gene NRD1 (for nuclear pre-mRNA down-regulation) from yeast S. cerevisiae. It is implicated in 3' end formation of small nucleolar and small nuclear RNAs transcribed by polymerase II, and plays a critical role in pre-mRNA metabolism. Nrd1 contains an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a short arginine-, serine-, and glutamate-rich segment similar to the regions rich in RE and RS dipeptides (RE/RS domains) in many metazoan splicing factors, and a proline- and glutamine-rich C-terminal domain (P+Q domain) similar to domains found in several yeast hnRNPs. Disruption of NRD1 gene is lethal to yeast cells. Its N-terminal domain is sufficient for viability, which may facilitate interactions with RNA polymerase II where Nrd1 may function as an auxiliary factor. By contrast, the RRM, RE/RS domains, and P+Q domain are dispensable. Seb1 is an RNA-binding protein encoded by gene seb1 (for seven binding) from fission yeast S. pombe. It is essential for cell viability and bound directly to Rpb7 subunit of RNA polymerase II. Seb1 is involved in processing of polymerase II transcripts. It also contains one RRM motif and a region rich in arginine-serine dipeptides (RS domain).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 6324078  336 VYSRTLFIGGVPLNMKEWDLANVLKPFAEVQSVILNNSRKHAFVKVYSRHEAENVLQNFNK--DGALPLRTRWGVGFGP 412
Cdd:cd12331   1 VYSRTLFIGGVTLNMKEWDLRSVFKRFGEVQSVILNNSRRHAFVKMYSRHEAENALQAMEKvpDGDLPLRTRWGVGFGP 79

RNA recognition motif (RRM) found in Saccharomyces cerevisiae protein Nrd1, Schizosaccharomyces pombe Rpb7-binding protein seb1 and similar proteins; This subfamily corresponds to the RRM of Nrd1 and Seb1. Nrd1 is a novel heterogeneous nuclear ribonucleoprotein (hnRNP)-like RNA-binding protein encoded by gene NRD1 (for nuclear pre-mRNA down-regulation) from yeast S. cerevisiae. It is implicated in 3' end formation of small nucleolar and small nuclear RNAs transcribed by polymerase II, and plays a critical role in pre-mRNA metabolism. Nrd1 contains an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a short arginine-, serine-, and glutamate-rich segment similar to the regions rich in RE and RS dipeptides (RE/RS domains) in many metazoan splicing factors, and a proline- and glutamine-rich C-terminal domain (P+Q domain) similar to domains found in several yeast hnRNPs. Disruption of NRD1 gene is lethal to yeast cells. Its N-terminal domain is sufficient for viability, which may facilitate interactions with RNA polymerase II where Nrd1 may function as an auxiliary factor. By contrast, the RRM, RE/RS domains, and P+Q domain are dispensable. Seb1 is an RNA-binding protein encoded by gene seb1 (for seven binding) from fission yeast S. pombe. It is essential for cell viability and bound directly to Rpb7 subunit of RNA polymerase II. Seb1 is involved in processing of polymerase II transcripts. It also contains one RRM motif and a region rich in arginine-serine dipeptides (RS domain).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 6324078  336 VYSRTLFIGGVPLNMKEWDLANVLKPFAEVQSVILNNSRKHAFVKVYSRHEAENVLQNFNK--DGALPLRTRWGVGFGP 412
Cdd:cd12331   1 VYSRTLFIGGVTLNMKEWDLRSVFKRFGEVQSVILNNSRRHAFVKMYSRHEAENALQAMEKvpDGDLPLRTRWGVGFGP 79

CID domain; This domain binds to the phosphorylated C-terminal domain (CTD) of RNA polymerase II. This domain is known as the CTD-interacting domain (CID).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324078      5 DDFQNFVATLESFKDlksgisgsRIKKLTTYALDHIDIESKIISLIIDYSRLCPDSHKLGSLYIIDSIgrayLDETRSNS 84
Cdd:pfam04818   1 EALEKKLSSLNNSQE--------SIQTLSKWILFHRKHAKAIVEVWEKYLKKAKPEKKLHLLYLANDV----LQNSRKKG 68

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 6324078     85 NSSSnkpgtcahaINTLGEVIQELLSDAIAKSNQDHKEKIRMLLDIWDRSGLFQKSYL 142
Cdd:pfam04818  69 KSEF---------ADAFEPVLPEAFASAYKKCDEKLKKKLERLLNIWEERNVFSPEVI 117

CID (CTD-Interacting Domain) family; The CTD-Interacting Domain (CID) is present in several eukaryotic RNA-processing factors including yeast proteins, Pcf11 and Nrd1, and vertebrate proteins, CTD-associated factors 8 (SCAF8) and Regulation of nuclear pre-mRNA domain-containing proteins (such as RPRD1 and RPRD2). Pcf11 is a conserved and essential subunit of the yeast cleavage factor IA, which is required for polyadenylation-dependent 3'-RNA processing and transcription termination. Nrd1 is implicated in polyadenylation-independent 3'-RNA processing. CID binds tightly to the carboxy-terminal domain (CTD) of RNA polymerase (Pol) II (RNAP II). During transcription, RNAP II synthesizes eukaryotic messenger RNA. Transcription is coupled to RNA processing through the CTD, which consists of up to 52 repeats of the sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. CID contains eight alpha-helices in a right-handed superhelical arrangement, which closely resembles that of the VHS domains and ARM (Armadillo) repeat proteins, except for its two amino-terminal helices.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324078    8 QNFVATLESFKDLksgiSGSRIKKLTTYALDHIDIESKIISLIIDYSRLCPDSHKLGSLYIIDSIGRAYLDEtrsnsnss 87
Cdd:cd03562   1 KAFNSKLEELSDL----SQQSITTLTKWAIHHIKHSRPIVTVIEREIRKCKPNRKLTFLYLIDSIIRNSKRK-------- 68

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6324078   88 snkpgtCAHAINTLGEVIQELLSDAIAKSNQDHKEKIRMLLDIWDRSGLFQKSYLNAIRSK 148
Cdd:cd03562  69 ------GPEFTKDFSPVIVELFKHVYSETDEDCKKKLGRVLSIWEERNVFENSVLEQLKQA 123

domain present in proteins, which are involved in regulation of nuclear pre-mRNA;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324078       9 NFVATLESFKdlksgISGSRIKKLTTYALDHIDIESKIISLIIDYSRLCPDSHKLGSLYIIDSIGRAYLDEtrsnsnsss 88
Cdd:smart00582   1 AFEQKLESLN-----NSQESIQTLTKWAIEHASHAKEIVELWEKYIKKAPVPRKLPLLYLLDSIVQNSKRK--------- 66

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6324078      89 nkpgTCAHAINTLGEVIQELLSDAIAKSNQDHKEKIRMLLDIWDRSGLFQKSYLNAIRSKCF 150
Cdd:smart00582  67 ----YGSEFGDELGPVFQDALRRVLGAAPEELKKKIRRLLNIWEERGIFPPEVLRPLREKLN 124

CID domain; This domain binds to the phosphorylated C-terminal domain (CTD) of RNA polymerase II. This domain is known as the CTD-interacting domain (CID).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324078      5 DDFQNFVATLESFKDlksgisgsRIKKLTTYALDHIDIESKIISLIIDYSRLCPDSHKLGSLYIIDSIgrayLDETRSNS 84
Cdd:pfam04818   1 EALEKKLSSLNNSQE--------SIQTLSKWILFHRKHAKAIVEVWEKYLKKAKPEKKLHLLYLANDV----LQNSRKKG 68

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 6324078     85 NSSSnkpgtcahaINTLGEVIQELLSDAIAKSNQDHKEKIRMLLDIWDRSGLFQKSYL 142
Cdd:pfam04818  69 KSEF---------ADAFEPVLPEAFASAYKKCDEKLKKKLERLLNIWEERNVFSPEVI 117

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
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324078  341 LFIGGVPLNMKEWDLANVLKPFAEVQSVIL-----NNSRKHAFVKVYSRHEAENVLQNFN 395
Cdd:cd00590   1 LFVGNLPPDTTEEDLRELFSKFGEVVSVRIvrdrdGKSKGFAFVEFESPEDAEKALEALN 60

RNA recognition motif 1 (RRM1) and 2 (RRM2) found in CELF/Bruno-like family of RNA binding proteins and plant flowering time control protein FCA; This subfamily corresponds to the RRM1 and RRM2 domains of the CUGBP1 and ETR-3-like factors (CELF) as well as plant flowering time control protein FCA. CELF, also termed BRUNOL (Bruno-like) proteins, is a family of structurally related RNA-binding proteins involved in regulation of pre-mRNA splicing in the nucleus, and control of mRNA translation and deadenylation in the cytoplasm. The family contains six members: CELF-1 (also known as BRUNOL-2, CUG-BP1, NAPOR, EDEN-BP), CELF-2 (also known as BRUNOL-3, ETR-3, CUG-BP2, NAPOR-2), CELF-3 (also known as BRUNOL-1, TNRC4, ETR-1, CAGH4, ER DA4), CELF-4 (BRUNOL-4), CELF-5 (BRUNOL-5) and CELF-6 (BRUNOL-6). They all contain three highly conserved RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C-terminus of the protein. The low sequence conservation of the linker region is highly suggestive of a large variety in the co-factors that associate with the various CELF family members. Based on both, sequence similarity and function, the CELF family can be divided into two subfamilies, the first containing CELFs 1 and 2, and the second containing CELFs 3, 4, 5, and 6. The different CELF proteins may act through different sites on at least some substrates. Furthermore, CELF proteins may interact with each other in varying combinations to influence alternative splicing in different contexts. This subfamily also includes plant flowering time control protein FCA that functions in the posttranscriptional regulation of transcripts involved in the flowering process. FCA contains two RRMs, and a WW protein interaction domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6324078  341 LFIGGVPLNMKEWDLANVLKPFAEVQSV-IL-----NNSRKHAFVKVYSRHEAENVLQNFN 395
Cdd:cd12361   2 LFVGMIPKTASEEDVRPLFEQFGNIEEVqILrdkqtGQSKGCAFVTFSTREEALRAIEALH 62

RNA recognition motif (RRM) found in Pre-mRNA-splicing factor RBM22 and similar proteins; This subgroup corresponds to the RRM of RBM22 (also known as RNA-binding motif protein 22, or Zinc finger CCCH domain-containing protein 16), a newly discovered RNA-binding motif protein which belongs to the SLT11 gene family. SLT11 gene encoding protein (Slt11p) is a splicing factor in yeast, which is required for spliceosome assembly. Slt11p has two distinct biochemical properties: RNA-annealing and RNA-binding activities. RBM22 is the homolog of SLT11 in vertebrate. It has been reported to be involved in pre-splicesome assembly and to interact with the Ca2+-signaling protein ALG-2. It also plays an important role in embryogenesis. RBM22 contains a conserved RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a zinc finger of the unusual type C-x8-C-x5-C-x3-H, and a C-terminus that is unusually rich in the amino acids Gly and Pro, including sequences of tetraprolines.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6324078  339 RTLFIGGVPLNMKEWDLANVLKPFAEVQSVILNNSRKHAFVKVYSRHEAENVLQN-FNK--DGALPLRTRWG 407
Cdd:cd12224   2 TTLYVGGLGDKITEKDLRDHFYQFGEIRSITVVARQQCAFVQFTTRQAAERAAERtFNKliIKGRRLKVKWG 73

CID (CTD-Interacting Domain) of Pcf11; Pcf11 is conserved across eukaryotes. The best studied protein is Saccharomyces cerevisiae Pcf11, also called protein 1 of CF I, an essential subunit of the cleavage factor IA (CFIA) complex which is required for polyadenylation-dependent pre-mRNA 3'-end processing and RNA polymerase (Pol) II (RNAP II) transcription termination. Human Pcf11, also referred to as pre-mRNA cleavage complex 2 protein Pcf11, has been shown to enhance degradation of RNAP II-associated nascent RNA and transcriptional termination. The family also includes plant PCFS4 (Pcf11-similar-4 protein or Polyadenylation and cleavage factor homolog 4) and Caenorhabditis elegans Polyadenylation and cleavage factor homolog 11. CID binds tightly to the carboxy-terminal domain (CTD) of RNAP II. Pcf11 CID preferentially interacts with CTD phosphorylated at Ser2. During transcription, RNAP II synthesizes eukaryotic messenger RNA. Transcription is coupled to RNA processing through the CTD, which consists of up to 52 repeats of the sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. CID contains eight alpha-helices in a right-handed superhelical arrangement, which closely resembles that of the VHS domains and ARM (Armadillo) repeat proteins, except for its two amino-terminal helices.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 6324078   29 IKKLTTYALDHIDIESKIISLIIDYSRLCPDSHKLGSLYIIDSI 72
Cdd:cd16982  19 INNLTMLAEENIQAAQAIVEAIEERIRKVPPEQKLPALYLLDSI 62

RNA recognition motif 2 (RRM2) found in vertebrate RNA-binding motif, single-stranded-interacting protein 3 (RBMS3); This subgroup corresponds to the RRM2 of RBMS3, a new member of the c-myc gene single-strand binding proteins (MSSP) family of DNA regulators. Unlike other MSSP proteins, RBMS3 is not a transcriptional regulator. It 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. RBMS3 contain two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and its C-terminal region is acidic and enriched in prolines, glutamines and threonines.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324078  341 LFIGGVPLNMKEWDLANVLKPFAEVQSV-ILNN----SRKHAFVKVYSRHEAENVLQNFN 395
Cdd:cd12475   4 LYISNLPISMDEQELENMLKPFGHVISTrILRDangvSRGVGFARMESTEKCEVVIQHFN 63

CID (CTD-Interacting Domain) of yeast transcription termination factor Rtt103 and similar proteins; Yeast transcription termination factor Rtt103 is a CID (CTD-Interacting Domain) containing protein that functions in DNA damage response. It associates with sites of DNA breaks and is essential for recovery from DNA double strand breaks in the chromosome. CID binds tightly to the carboxy-terminal domain (CTD) of RNA polymerase (Pol) II (RNAP II). Rtt103 CID preferentially interacts with CTD phosphorylated at Ser2. During transcription, RNAP II synthesizes eukaryotic messenger RNA. Transcription is coupled to RNA processing through the CTD, which consists of up to 52 repeats of the sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. CID contains eight alpha-helices in a right-handed superhelical arrangement, which closely resembles that of the VHS domains and ARM (Armadillo) repeat proteins, except for its two amino-terminal helices.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 6324078   98 INTLGEVIQELLSDAIAKSNQDHKEKIRMLLDIWDRSGLFQKSYLNAIRSK 148
Cdd:cd17003  76 IDAFSKVLPEVLEKIYPSLPSDIKKKIKRVVNVWKQRQIFSKDVIDDIEER 126

RNA recognition motif 1 (RRM1) found in the p54nrb/PSF/PSP1 family; This subfamily corresponds to the RRM1 of the p54nrb/PSF/PSP1 family, including 54 kDa nuclear RNA- and DNA-binding protein (p54nrb or NonO or NMT55), polypyrimidine tract-binding protein (PTB)-associated-splicing factor (PSF or POMp100), paraspeckle protein 1 (PSP1 or PSPC1), which are ubiquitously expressed and are conserved in vertebrates. p54nrb is a multi-functional protein involved in numerous nuclear processes including transcriptional regulation, splicing, DNA unwinding, nuclear retention of hyperedited double-stranded RNA, viral RNA processing, control of cell proliferation, and circadian rhythm maintenance. PSF is also a multi-functional protein that binds RNA, single-stranded DNA (ssDNA), double-stranded DNA (dsDNA) and many factors, and mediates diverse activities in the cell. PSP1 is a novel nucleolar factor that accumulates within a new nucleoplasmic compartment, termed paraspeckles, and diffusely distributes in the nucleoplasm. The cellular function of PSP1 remains unknown currently. This subfamily also includes some p54nrb/PSF/PSP1 homologs from invertebrate species, such as the Drosophila melanogaster gene no-ontransient A (nonA) encoding puff-specific protein Bj6 (also termed NONA) and Chironomus tentans hrp65 gene encoding protein Hrp65. D. melanogaster NONA is involved in eye development and behavior, and may play a role in circadian rhythm maintenance, similar to vertebrate p54nrb. C. tentans Hrp65 is a component of nuclear fibers associated with ribonucleoprotein particles in transit from the gene to the nuclear pore. All family members contain a DBHS domain (for Drosophila behavior, human splicing), which comprises two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a charged protein-protein interaction module. PSF has an additional large N-terminal domain that differentiates it from other family members.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 6324078  341 LFIGGVPLNMKEWDLANVLKPFAEVQSVILNNSRKHAFVKVYSRHEAE 388
Cdd:cd12332   4 LFVGNLPNDITEEEFKELFQKYGEVSEVFLNKGKGFGFIRLDTRANAE 51

RNA recognition motif (RRM) found in vertebrate RNA-binding protein with multiple splicing (RBP-MS); This subfamily corresponds to the RRM of RBP-MS, also termed heart and RRM expressed sequence (hermes), an RNA-binding proteins found in various vertebrate species. It contains an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). RBP-MS physically interacts with Smad2, Smad3 and Smad4 and plays a role in regulation of Smad-mediated transcriptional activity. In addition, RBP-MS may be involved in regulation of mRNA translation and localization during Xenopus laevis development.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6324078  339 RTLFIGGVPLNMKEWDLANVLKPFAEVQSVILNNSRKH--AFVKVYSRHEAE---NVLQNFNKDGALPLRTR 405
Cdd:cd12682   2 RTLFVSGLPLDIKPRELYLLFRPFKGYEGSLIKLTSKQpvGFVSFDSRSEAEaakNALNGIRFDPEIPQTLR 73

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6324078  340 TLFIGGVPLNMKEWDLANVLKPFAEVQSVILNNSRKHAFVKvYSRHEAENV----LQNFNKDGAlPLRTRWG 407
Cdd:cd12354   2 TVYVGNITKGLTEALLQQTFSPFGQILEVRVFPDKGYAFIR-FDSHEAATHaivsVNGTIINGQ-AVKCSWG 71

RNA recognition motif (RRM) found in SR-related and CTD-associated factor 4 (SCAF4), SR-related and CTD-associated factor 8 (SCAF8) and similar proteins; This subfamily corresponds to the RRM in a new class of SCAFs (SR-like CTD-associated factors), including SCAF4, SCAF8 and similar proteins. The biological role of SCAF4 remains unclear, but it shows high sequence similarity to SCAF8 (also termed CDC5L complex-associated protein 7, or RNA-binding motif protein 16, or CTD-binding SR-like protein RA8). SCAF8 is a nuclear matrix protein that interacts specifically with a highly serine-phosphorylated form of the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II (pol II). The pol II CTD plays a role in coupling transcription and pre-mRNA processing. In addition, SCAF8 co-localizes primarily with transcription sites that are enriched in nuclear matrix fraction, which is known to contain proteins involved in pre-mRNA processing. Thus, SCAF8 may play a direct role in coupling with both, transcription and pre-mRNA processing, processes. SCAF8 and SCAF4 both contain a conserved N-terminal CTD-interacting domain (CID), an atypical RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNPs (ribonucleoprotein domain), and serine/arginine-rich motifs.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 6324078  338 SRTLFIGGVPLNMKEWDLANVLKPFAEVQSVILNNSRKHAFVKVYSRHEAENVLQ 392
Cdd:cd12227   2 STTLWVGHLSKKVTQEELKNLFEEYGEIQSIDMIPPRGCAYVCMKTRQDAHRALQ 56

RNA recognition motif 1 (RRM1) found in vertebrate paraspeckle protein 1 (PSP1); This subgroup corresponds to the RRM1 of PSPC1, also termed paraspeckle component 1 (PSPC1), a novel nucleolar factor that accumulates within a new nucleoplasmic compartment, termed paraspeckles, and diffusely distributes in the nucleoplasm. It is ubiquitously expressed and highly conserved in vertebrates. Its cellular function remains unknown currently, however, PSPC1 forms a novel heterodimer with the nuclear protein p54nrb, also known as non-POU domain-containing octamer-binding protein (NonO), which localizes to paraspeckles in an RNA-dependent manner. PSPC1 contains two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), at the N-terminus.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324078  341 LFIGGVPLNMKEWDLANVLKPFAEVQSVILNNSRKHAFVKVYSRHEAEnvLQNFNKDGAL----PLRTRW 406
Cdd:cd12586   4 LFVGNLPTDITEEDFKRLFERYGEPSEVFINRDRGFGFIRLESRTLAE--IAKAELDGTIlksrPLRIRF 71

RNA recognition motif (RRM) found in SR-related and CTD-associated factor 4 (SCAF4) and similar proteins; The CD corresponds to the RRM of SCAF4 (also termed splicing factor, arginine/serine-rich 15 or SFR15, or CTD-binding SR-like protein RA4) that belongs to a new class of SCAFs (SR-like CTD-associated factors). Although its biological function remains unclear, SCAF4 shows high sequence similarity to SCAF8 that interacts specifically with a highly serine-phosphorylated form of the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II (pol II) and may play a direct role in coupling with both, transcription and pre-mRNA processing, processes. SCAF4 and SCAF8 both contain a conserved N-terminal CTD-interacting domain (CID), an atypical RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and serine/arginine-rich motifs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324078  336 VYSRTLFIGGVPLNMKEWDLANVLKPFAEVQSVILNNSRKHAFVKVYSRHEAENVLQNFNKDG----ALPLRTRWGVGFG 411
Cdd:cd12461   2 VCSTTLWVGQLDKRTTQQDVASLLEEFGQIESINMIPPRGCAYIVMVHRQDAYRALQKLSRGNykvnQKSIKIAWALNKG 81

RNA recognition motif 2 (RRM2) found in the Hu proteins family; This subfamily corresponds to the RRM2 of Hu proteins family which represents a group of RNA-binding proteins involved in diverse biological processes. Since the Hu proteins share high homology with the Drosophila embryonic lethal abnormal vision (ELAV) protein, the Hu family is sometimes referred to as the ELAV family. Drosophila ELAV is exclusively expressed in neurons and is required for the correct differentiation and survival of neurons in flies. The neuronal members of the Hu family include Hu-antigen B (HuB or ELAV-2 or Hel-N1), Hu-antigen C (HuC or ELAV-3 or PLE21), and Hu-antigen D (HuD or ELAV-4), which play important roles in neuronal differentiation, plasticity and memory. HuB is also expressed in gonads. Hu-antigen R (HuR or ELAV-1 or HuA) is the ubiquitously expressed Hu family member. It has a variety of biological functions mostly related to the regulation of cellular response to DNA damage and other types of stress. Moreover, HuR has an anti-apoptotic function during early cell stress response. It binds to mRNAs and enhances the expression of several anti-apoptotic proteins, such as p21waf1, p53, and prothymosin alpha. HuR also has pro-apoptotic function by promoting apoptosis when cell death is unavoidable. Furthermore, HuR may be important in muscle differentiation, adipogenesis, suppression of inflammatory response and modulation of gene expression in response to chronic ethanol exposure and amino acid starvation. Hu proteins perform their cytoplasmic and nuclear molecular functions by coordinately regulating functionally related mRNAs. In the cytoplasm, Hu proteins recognize and bind to AU-rich RNA elements (AREs) in the 3' untranslated regions (UTRs) of certain target mRNAs, such as GAP-43, vascular epithelial growth factor (VEGF), the glucose transporter GLUT1, eotaxin and c-fos, and stabilize those ARE-containing mRNAs. They also bind and regulate the translation of some target mRNAs, such as neurofilament M, GLUT1, and p27. In the nucleus, Hu proteins function as regulators of polyadenylation and alternative splicing. Each Hu protein contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 may cooperate in binding to an ARE. RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions.

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gi 6324078  341 LFIGGVPLNMKEWDLANVLKPFAE-VQSVILNN-----SRKHAFVKVYSRHEAENVLQNFNK 396
Cdd:cd12652   3 LYVSGLPKTMTQKELEQLFSQFGRiITSRILCDnvtglSRGVGFIRFDKRVEAERAIKALNG 64