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 578836633  500 SVCSTTLWVGQLDKRTTQQDVASLLEEFGPIESINMIPPRGCAYIVMVHRQDAYRALQKLSRGNYKVNQKSIKIAWALNK 579
Cdd:cd12461     1 SVCSTTLWVGQLDKRTTQQDVASLLEEFGQIESINMIPPRGCAYIVMVHRQDAYRALQKLSRGNYKVNQKSIKIAWALNK 80

                  .
gi 578836633  580 G 580
Cdd:cd12461    81 G 81

transcription termination factor Rho; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578836633  958 RNDNRQQFNSGRDQERFGRRSFGNRVEN-DRERYGNRNDDRDNSNRDRREWGRRSPDRDRHRDLEERNRRS 1027
Cdd:PRK12678  196 RGRDGDDRDRRDRREQGDRREERGRRDGgDRRGRRRRRDRRDARGDDNREDRGDRDGDDGEGRGGRRGRRF 266

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 578836633  500 SVCSTTLWVGQLDKRTTQQDVASLLEEFGPIESINMIPPRGCAYIVMVHRQDAYRALQKLSRGNYKVNQKSIKIAWALNK 579
Cdd:cd12461     1 SVCSTTLWVGQLDKRTTQQDVASLLEEFGQIESINMIPPRGCAYIVMVHRQDAYRALQKLSRGNYKVNQKSIKIAWALNK 80

                  .
gi 578836633  580 G 580
Cdd:cd12461    81 G 81

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 578836633     6 AFNQELFSLMDmkppiSRAKMILITKAAIKAIKLYKHVVQIVEKFIKKCKPEYKVPGLYVIDSIVRQSRHQFGTDkdvFG 85
Cdd:pfam04818    2 ALEKKLSSLNN-----SQESIQTLSKWILFHRKHAKAIVEVWEKYLKKAKPEKKLHLLYLANDVLQNSRKKGKSE---FA 73

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 578836633    86 PRFSKNITATFQYLYL-CPSEDKSKIVRVLNLWQKNGVFKIEII 128
Cdd:pfam04818   74 DAFEPVLPEAFASAYKkCDEKLKKKLERLLNIWEERNVFSPEVI 117

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 578836633   506 LWVGQLDKRTTQQDVASLLEEFGPIESINMIP-----PRGCAYIVMVHRQDAYRALQKLSrgNYKVNQKSIK 572
Cdd:pfam00076    1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRdetgrSKGFAFVEFEDEEDAEKAIEALN--GKELGGRELK 70

DNA polymerase III subunits gamma and tau; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578836633  133 DMAAGTSNAAPVAENVTNNEGSPPPPVKVSSEPPTQATPNSVPAV-PQLPSSDAFAAVAQLFQTTQGQQLQQILQTFQQP 211
Cdd:PRK07994  369 EVPPQSAAPAASAQATAAPTAAVAPPQAPAVPPPPASAPQQAPAVpLPETTSQLLAARQQLQRAQGATKAKKSEPAAASR 448

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 578836633  212 PKPQSPALDNAVMAQVQAITAQLKTTPTQPSEQKAAFPPPEQKT--AFDKKLLDRFDYDDEPE----AVEESKKED 281
Cdd:PRK07994  449 ARPVNSALERLASVRPAPSALEKAPAKKEAYRWKATNPVEVKKEpvATPKALKKALEHEKTPElaakLAAEAIERD 524

splicing factor, CC1-like family; This model represents a subfamily of RNA splicing factors including the Pad-1 protein (N. crassa), CAPER (M. musculus) and CC1.3 (H.sapiens). These proteins are characterized by an N-terminal arginine-rich, low complexity domain followed by three (or in the case of 4 H. sapiens paralogs, two) RNA recognition domains (rrm: pfam00706). These splicing factors are closely related to the U2AF splicing factor family (TIGR01642). A homologous gene from Plasmodium falciparum was identified in the course of the analysis of that genome at TIGR and was included in the seed.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578836633   969 RDQERFGRRSFGNRVENDRERYGNRNDDRDNSNRDRREwgrRSPDRDRHRD--------LEERNRRSSGHRDRERDSRDR 1040
Cdd:TIGR01622    3 RDRERERLRDSSSAGDRDRRRDKGRERSRDRSRDRERS---RSRRRDRHRDrdyyrgreRRSRSRRPNRRYRPREKRRRR 79

                           90       100
                   ....*....|....*....|...
gi 578836633  1041 ESRREKE---EARGKEKPEVTDR 1060
Cdd:TIGR01622   80 GDSYRRRrddRRSRREKPRARDG 102

CID (CTD-Interacting Domain) of SR-related and CTD-associated factor 8 and similar proteins; This subfamily includes SR-related and CTD-associated factors 8 (SCAF8) and 4 (SCAF4), and similar proteins. SCAF4 is also called Splicing factor arginine serine rich 15 (SFRS15). Members may play roles in mRNA processing. Both SCAF4 and SCAF8 contains a CTD-interacting domain (CID) at the amino terminus and a Ser/Arg-rich domain followed by an RNA recognition motif. 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 578836633    6 AFNQELFSLMDMKPPISRAKMILITKAAIKAIKLYKHVVQIVEKFIKKCKPEYKVPGLYVIDSIVRQSRHQFGTDKDVFG 85
Cdd:cd16983     2 EFNKELSSLLDSKPPVSKSKINAITKLAIKAIKFYKHVVQSVEKFIQKCKPEYKLPGLYVIDSIIRQSRHQYGKEKDVYA 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 578836633   86 PRFSKNITATFQYLYLCPSEDKSKIVRVLNLWQKNGVFKIEIIQPLLDMA 135
Cdd:cd16983    82 PRFAKNLSKTFLNLLKCPEKDKPKVKRVLNLWQKNGVFPKEIIQPLLDAA 131

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 578836633  500 SVCSTTLWVGQLDKRTTQQDVASLLEEFGPIESINMIPPRGCAYIVMVHRQDAYRALQKLSRGNYKVNQKSIKIAWALNK 579
Cdd:cd12461     1 SVCSTTLWVGQLDKRTTQQDVASLLEEFGQIESINMIPPRGCAYIVMVHRQDAYRALQKLSRGNYKVNQKSIKIAWALNK 80

                  .
gi 578836633  580 G 580
Cdd:cd12461    81 G 81

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 578836633  502 CSTTLWVGQLDKRTTQQDVASLLEEFGPIESINMIPPRGCAYIVMVHRQDAYRALQKLSrgNYKVNQKSIKIAWALNKG 580
Cdd:cd12227     1 CSTTLWVGHLSKKVTQEELKNLFEEYGEIQSIDMIPPRGCAYVCMKTRQDAHRALQKLK--NHKLRGKSIKIAWAPNKG 77

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578836633      6 AFNQELFSLMdmkppISRAKMILITKAAIKAIKLYKHVVQIVEKFIKKCKPEYKVPGLYVIDSIVRQSRHQFGTD-KDVF 84
Cdd:smart00582    1 AFEQKLESLN-----NSQESIQTLTKWAIEHASHAKEIVELWEKYIKKAPVPRKLPLLYLLDSIVQNSKRKYGSEfGDEL 75

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|
gi 578836633     85 GPRFSKNITATFQYlylCPSEDKSKIVRVLNLWQKNGVFKIEIIQPLLDM 134
Cdd:smart00582   76 GPVFQDALRRVLGA---APEELKKKIRRLLNIWEERGIFPPEVLRPLREK 122

CID (CTD-Interacting Domain) of Nrd1 and similar proteins; This subfamily includes Saccharomyces cerevisiae protein Nrd1, Schizosaccharomyces pombe Rpb7-binding protein Seb1, and similar proteins. Nrd1 cooperates with Nab3 and Sen1, also called the Nrd1-Nab3-Sen1 (NNS) complex, to terminate the transcription by RNA polymerase (Pol) II (RNAPII) of many noncoding RNAs (ncRNAs), including small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), and cryptic unstable transcripts (CUTs). Schizosaccharomyces pombe Seb1 does not function in an NNS-like termination pathway but promotes polyadenylation site selection of coding and noncoding genes. It cotranscriptionally controls alternative polyadenylation. CID binds tightly to the carboxy-terminal domain (CTD) of RNAP II. Nrd1 CID preferentially interacts with CTD phosphorylated at Ser5. 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 578836633    7 FNQELFSLMDMKPP-ISRAKMILITKAAIKAIKLYKHVVQIVEKFIKKCKPEYKVPGLYVIDSIVRQSRHQ---FGTDKD 82
Cdd:cd16984     3 FEATLKSLQALKPPgVSGSKIKKLTDIAVDNVQSESQIVSKLYRYFKKAPPTHKLGVLYVVDSVVRAWIDQakkNGQSID 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 578836633   83 VFGP---------RFSKNITATFQ-YLYLCPSEDKSKIVRVLNLWQKNGVFKIEIIQPL 131
Cdd:cd16984    83 SSAPdgtfaagvyKITELIESLMNdAIQSAPEDQKEKIKKLVDIWEKGNTFPAEMLNSI 141

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578836633   33 AIKAIKLYKHVVQIVEKFIKKCKPEYKVPGLYVIDSIVRqsrhqfgTDKDVFGPRFSKNITATFQYLY-LCPSEDKSKIV 111
Cdd:cd16982    26 AEENIQAAQAIVEAIEERIRKVPPEQKLPALYLLDSIVK-------NVGGPYTSLFSPNLVDLFLDAYrLVDEKTRKKLE 98

                  ....*.
gi 578836633  112 RVLNLW 117
Cdd:cd16982    99 KLLNTW 104

RNA recognition motif 3 (RRM3) found in yeast negative growth regulatory protein NGR1 (RBP1), yeast protein NAM8 and similar proteins; This subfamily corresponds to the RRM3 of NGR1 and NAM8. NGR1, also termed RNA-binding protein RBP1, is a putative glucose-repressible protein that binds both RNA and single-stranded DNA (ssDNA) in yeast. It may function in regulating cell growth in early log phase, possibly through its participation in RNA metabolism. NGR1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a glutamine-rich stretch that may be involved in transcriptional activity. In addition, NGR1 has an asparagine-rich region near the carboxyl terminus which also harbors a methionine-rich region. The family also includes protein NAM8, which is a putative RNA-binding protein that acts as a suppressor of mitochondrial splicing deficiencies when overexpressed in yeast. It may be a non-essential component of the mitochondrial splicing machinery. Like NGR1, NAM8 contains two RRMs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 578836633  504 TTLWVGQLDKRTTQQDVASLLEEFGPIESINMIPPRGCAYIVMVHRQDAYRALQKLSrgNYKVNQKSIKIAW 575
Cdd:cd12346     2 TTVFVGGLDPNVTEEDLRVLFGPFGEIVYVKIPPGKGCGFVQFVNRASAEAAIQKLQ--GTPIGGSRIRLSW 71

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578836633   40 YKH---VVQIVEKFIKK--CKPEYKVPGLYVIDSIVRQSRHQfgtDKDVFGPRFSKNITATFQYLYL-CPSEDKSKIVRV 113
Cdd:cd17003    29 YRHadeIAEIWSDYLLKssVNSRRKLLLIYLANDVVQQAKAK---KKTEFIDAFSKVLPEVLEKIYPsLPSDIKKKIKRV 105

                          90
                  ....*....|....*...
gi 578836633  114 LNLWQKNGVFKIEIIQPL 131
Cdd:cd17003   106 VNVWKQRQIFSKDVIDDI 123

RNA recognition motif 2 (RRM2) and 4 (RRM4) found in RNA-binding protein MRN1 and similar proteins; This subgroup corresponds to the RRM2 and RRM4 of MRN1, also termed multicopy suppressor of RSC-NHP6 synthetic lethality protein 1, or post-transcriptional regulator of 69 kDa, and is an 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 578836633  503 STTLWVGQLDKRTTQQDVASLLEEFGPIESINMIPPRGCAYIVMVHRQDAYRALQKLSRGNYKVNQKSI 571
Cdd:cd12262     3 SRNVYVGNLDDSLTEEEIRGILEKYGEIESIKILKEKNCAFVNYLNIANAIKAVQELPIKNPKFKKVRI 71

RNA recognition motif (RRM) found in eukaryotic RNA-binding protein 18 and similar proteins; This subfamily corresponds to the RRM of RBM18, a putative RNA-binding protein containing a well-conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The biological role of RBM18 remains unclear.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578836633  506 LWVGQLDKRTTQQDVASLLEEFGPIESINMI---------PPRGCAYIVMVHRQDAYRALQKLsrgNYK-VNQKSIKIAW 575
Cdd:cd12355     2 LWIGNLDPRLTEYHLLKLLSKYGKIKKFDFLfhktgplkgQPRGYCFVTFETKEEAEKAIECL---NGKlALGKKLVVRW 78

                  .
gi 578836633  576 A 576
Cdd:cd12355    79 A 79

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 578836633  506 LWVGQLDKRTTQQDVASLLEEFGPIESINMI------PPRGCAYIVMVHRQDAYRALQKL 559
Cdd:cd12361     2 LFVGMIPKTASEEDVRPLFEQFGNIEEVQILrdkqtgQSKGCAFVTFSTREEALRAIEAL 61

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 578836633  505 TLWVGQLDKRTTQQDVASLLEEFGPIESINMI------PPRGCAYIVMVHRQD---AYRA 555
Cdd:cd12236     3 TLFVARLSYDTTESKLRREFEKYGPIKRVRLVrdkktgKSRGYAFIEFEHERDmkaAYKH 62

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 578836633  505 TLWVGQLDKRTTQQDVASLLEEFGPIESINmIP-------PRGCAYIVMVHRQDAYRALQKLSRGNYK 565
Cdd:cd12408     1 TIRVTNLSEDATEEDLRELFRPFGPISRVY-LAkdketgqSKGFAFVTFETREDAERAIEKLNGFGYD 67

CID (CTD-Interacting Domain) of Regulation of nuclear pre-mRNA domain-containing proteins; This family is composed of Regulation of nuclear pre-mRNA domain-containing proteins 1A (RPRD1A), 1B (RPRD1B), 2 (RPRD2), yeast Rtt103, and similar proteins. RPRD1A, RPRD1B, and RPRD2 are CID (CTD-Interacting Domain) containing proteins that co-purify with RNA polymerase (Pol) II (RNAP II) and three other RNAP II-associated proteins, RPAP2, GRINL1A and RECQL5, but not with the Mediator complex. Yeast transcription termination factor Rtt103 is a CID containing protein that functions in DNA damage response. CID binds tightly to the carboxy-terminal domain (CTD) of 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 578836633   38 KLYKHVVQIVEKFIKKCKPEYKVPGLYVIDSIVRQSRHQFGTDkdvFGPRFSKNITATFQYLYLCPSED-KSKIVRVLNL 116
Cdd:cd16981    30 KHAKQIVKIWLKELKKAKPERKLTLLYLANDVLQNSRRKGAPE---FVEAFKKVLPEALALVRSEGDESvRKKVLRVLNI 106

                          90
                  ....*....|....*...
gi 578836633  117 WQKNGVFKIEIIQPLLDM 134
Cdd:cd16981   107 WEERNVFGSEFLAELRAI 124

CID (CTD-Interacting Domain) of Regulation of nuclear pre-mRNA domain-containing protein 1A; Regulation of nuclear pre-mRNA domain-containing protein 1A (RPRD1A) is also called Cyclin-dependent kinase inhibitor 2B-related protein or p15INK4B-related protein (P15RS). RPRD1A is a CID (CTD-Interacting Domain) containing protein that co-purifies with RNA polymerase (Pol) II (RNAP II) and three other RNAP II-associated proteins, RPAP2, GRINL1A and RECQL5, but not with the Mediator complex. CID binds tightly to the carboxy-terminal domain (CTD) of 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. RPRD1A form homodimers and heterodimers with RPRD1B through their coiled-coil domains. Both RPRD1A and RPRD1B associate directly with RPAP2 phosphatase and serve as CTD scaffolds to coordinate the dephosphorylation of phospho-S5 by RPAP2. 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 578836633   41 KH---VVQIVEKFIKKCKPEYKVPGLYVIDSIVRQSRHQfgtdkdvfGPRFSKN----ITATFQYLYLCPSED-KSKIVR 112
Cdd:cd17011    32 KHsrpIVTVWERELRKAKPNRKLTFLYLANDVIQNSKRK--------GPEFTKDfapvIVEAFKHVSSETDEScKKHLGR 103

                          90
                  ....*....|....*....
gi 578836633  113 VLNLWQKNGVFKIEIIQPL 131
Cdd:cd17011   104 VLSIWEERSVYENDVLEQL 122

DNA polymerase III subunits gamma and tau; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578836633  133 DMAAGTSNAAPVAENVTNNEGSPPPPVKVSSEPPTQATPNSVPAV-PQLPSSDAFAAVAQLFQTTQGQQLQQILQTFQQP 211
Cdd:PRK07994  369 EVPPQSAAPAASAQATAAPTAAVAPPQAPAVPPPPASAPQQAPAVpLPETTSQLLAARQQLQRAQGATKAKKSEPAAASR 448

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 578836633  212 PKPQSPALDNAVMAQVQAITAQLKTTPTQPSEQKAAFPPPEQKT--AFDKKLLDRFDYDDEPE----AVEESKKED 281
Cdd:PRK07994  449 ARPVNSALERLASVRPAPSALEKAPAKKEAYRWKATNPVEVKKEpvATPKALKKALEHEKTPElaakLAAEAIERD 524

RNA recognition motif (RRM) found in transformer-2 protein homolog TRA2-alpha, TRA2-beta and similar proteins; This subfamily corresponds to the RRM of two mammalian homologs of Drosophila transformer-2 (Tra2), TRA2-alpha, TRA2-beta (also termed SFRS10), and similar proteins found in eukaryotes. TRA2-alpha is a 40-kDa serine/arginine-rich (SR) protein that specifically binds to gonadotropin-releasing hormone (GnRH) exonic splicing enhancer on exon 4 (ESE4) and is necessary for enhanced GnRH pre-mRNA splicing. It strongly stimulates GnRH intron A excision in a dose-dependent manner. In addition, TRA2-alpha can interact with either 9G8 or SRp30c, which may also be crucial for ESE-dependent GnRH pre-mRNA splicing. TRA2-beta is a serine/arginine-rich (SR) protein that controls the pre-mRNA alternative splicing of the calcitonin/calcitonin gene-related peptide (CGRP), the survival motor neuron 1 (SMN1) protein and the tau protein. Both, TRA2-alpha and TRA2-beta, contains a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), flanked by the N- and C-terminal arginine/serine (RS)-rich regions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 578836633  503 STTLWVGQLDKRTTQQDVASLLEEFGPIESINMI------PPRGCAYIVMVHRQDAYRALQKL 559
Cdd:cd12363     1 SRCLGVFGLSLYTTERDLREVFSRYGPIEKVQVVydqqtgRSRGFGFVYFESVEDAKEAKERL 63

RNA recognition motif 2 (RRM2) found in RNA-binding protein MRN1 and similar proteins; This subgroup corresponds to the RRM2 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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 578836633  503 STTLWVGQLDKRTTQQDVASLLEEFGPIESINMIPPRGCAYIVMVHRQDAYRALQKLS 560
Cdd:cd12523     3 SRNVYLGNLPESITEEELREDLEKFGPIDQIKIVKEKNIAFVHFLSIANAIKVVTTLP 60

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 578836633  503 STTLWVGQLDKRTTQQDVASLLEeFGPIESINMIPPRGCAYIVMVHRQDAYRALQKLSRGNYKVNQKSIKIAW 575
Cdd:cd12520     1 SRTVYLGNLPPNTTVKELLSHVR-SGPIENVRILPEKNCAFISFLDPSAATAFHSDAILKRLSIKGVELKIGW 72

RNA recognition motif 1 (RRM1) found in the Hu proteins family, Drosophila sex-lethal (SXL), and similar proteins; This subfamily corresponds to the RRM1 of Hu proteins and SXL. The Hu proteins family 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 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. 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. This family also includes the sex-lethal protein (SXL) from Drosophila melanogaster. SXL governs sexual differentiation and X chromosome dosage compensation in flies. It induces female-specific alternative splicing of the transformer (tra) pre-mRNA by binding to the tra uridine-rich polypyrimidine tract at the non-sex-specific 3' splice site during the sex-determination process. SXL binds to its own pre-mRNA and promotes female-specific alternative splicing. It contains an N-terminal Gly/Asn-rich domain that may be responsible for the protein-protein interaction, and tandem RRMs that show high preference to bind single-stranded, uridine-rich target RNA transcripts.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 578836633  506 LWVGQLDKRTTQQDVASLLEEFGPIESINMIPPR------GCAYIVMVHRQDAYRALQKLSrgNYKVNQKSIKIAWA 576
Cdd:cd12375     2 LIVNYLPQSMTQEELRSLFGAIGPIESCKLVRDKitgqslGYGFVNYRDPNDARKAINTLN--GLDLENKRLKVSYA 76

RNA recognition motif 1 (RRM1) found in CUGBP Elav-like family member CELF-3, CELF-4, CELF-5, CELF-6 and similar proteins; This subfamily corresponds to the RRM1 of CELF-3, CELF-4, CELF-5, CELF-6, all of which belong to the CUGBP1 and ETR-3-like factors (CELF) or BRUNOL (Bruno-like) family of RNA-binding proteins that display dual nuclear and cytoplasmic localizations and have been implicated in the regulation of pre-mRNA splicing and in the control of mRNA translation and deadenylation. CELF-3, expressed in brain and testis only, is also known as bruno-like protein 1 (BRUNOL-1), or CAG repeat protein 4, or CUG-BP- and ETR-3-like factor 3, or embryonic lethal abnormal vision (ELAV)-type RNA-binding protein 1 (ETR-1), or expanded repeat domain protein CAG/CTG 4, or trinucleotide repeat-containing gene 4 protein (TNRC4). It plays an important role in the pathogenesis of tauopathies. CELF-3 contains 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 effect of CELF-3 on tau splicing is mediated mainly by the RNA-binding activity of RRM2. The divergent linker region might mediate the interaction of CELF-3 with other proteins regulating its activity or involved in target recognition. CELF-4, highly expressed throughout the brain and in glandular tissues, moderately expressed in heart, skeletal muscle, and liver, is also known as bruno-like protein 4 (BRUNOL-4), or CUG-BP- and ETR-3-like factor 4. Like CELF-3, CELF-4 also contain three highly conserved RRMs. The splicing activation or repression activity of CELF-4 on some specific substrates is mediated by its RRM1/RRM2. On the other hand, both RRM1 and RRM2 of CELF-4 can activate cardiac troponin T (cTNT) exon 5 inclusion. CELF-5, expressed in brain, is also known as bruno-like protein 5 (BRUNOL-5), or CUG-BP- and ETR-3-like factor 5. Although its biological role remains unclear, CELF-5 shares same domain architecture with CELF-3. CELF-6, strongly expressed in kidney, brain, and testis, is also known as bruno-like protein 6 (BRUNOL-6), or CUG-BP- and ETR-3-like factor 6. It activates exon inclusion of a cardiac troponin T minigene in transient transfection assays in an muscle-specific splicing enhancer (MSE)-dependent manner and can activate inclusion via multiple copies of a single element, MSE2. CELF-6 also promotes skipping of exon 11 of insulin receptor, a known target of CELF activity that is expressed in kidney. In additiona to three highly conserved RRMs, CELF-6 also possesses numerous potential phosphorylation sites, a potential nuclear localization signal (NLS) at the C terminus, and an alanine-rich region within the divergent linker region.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 578836633  503 STTLWVGQLDKRTTQQDVASLLEEFGPIESINMIPPR------GCAYIVMVHRQDAYRA 555
Cdd:cd12632     5 AIKLFIGQIPRNLEEKDLRPLFEQFGKIYELTVLKDKytgmhkGCAFLTYCARESALKA 63

RNA recognition motif 4 (RRM4) found in RNA-binding protein 19 (RBM19) and RNA recognition motif 3 (RRM3) found in multiple RNA-binding domain-containing protein 1 (MRD1); This subfamily corresponds to the RRM4 of RBM19 and the RRM3 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 homologues 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). MRD1 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 578836633  504 TTLWVGQLDKRTTQQDVASLLEEFGPIESINMIPPRGCAYIVMVHRQDAYRALQKLSRGNYK 565
Cdd:cd12317     1 TVILVKNLPFGATEEELRELFEKFGTLGRLLLPPSRTIALVEFLEPQDARRAFKKLAYKRFK 62

RNA recognition motif 1 (RRM1) found in type I polyadenylate-binding proteins; This subfamily corresponds to the RRM1 of type I poly(A)-binding proteins (PABPs), highly conserved proteins that bind to the poly(A) tail present at the 3' ends of most eukaryotic mRNAs. They have been implicated in the regulation of poly(A) tail length during the polyadenylation reaction, translation initiation, mRNA stabilization by influencing the rate of deadenylation and inhibition of mRNA decapping. The family represents type I polyadenylate-binding proteins (PABPs), including polyadenylate-binding protein 1 (PABP-1 or PABPC1), polyadenylate-binding protein 3 (PABP-3 or PABPC3), polyadenylate-binding protein 4 (PABP-4 or APP-1 or iPABP), polyadenylate-binding protein 5 (PABP-5 or PABPC5), polyadenylate-binding protein 1-like (PABP-1-like or PABPC1L), polyadenylate-binding protein 1-like 2 (PABPC1L2 or RBM32), polyadenylate-binding protein 4-like (PABP-4-like or PABPC4L), yeast polyadenylate-binding protein, cytoplasmic and nuclear (PABP or ACBP-67), and similar proteins. PABP-1 is a ubiquitously expressed multifunctional protein that may play a role in 3' end formation of mRNA, translation initiation, mRNA stabilization, protection of poly(A) from nuclease activity, mRNA deadenylation, inhibition of mRNA decapping, and mRNP maturation. Although PABP-1 is thought to be a cytoplasmic protein, it is also found in the nucleus. PABP-1 may be involved in nucleocytoplasmic trafficking and utilization of mRNP particles. PABP-1 contains four copies of RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), a less well conserved linker region, and a proline-rich C-terminal conserved domain (CTD). PABP-3 is a testis-specific poly(A)-binding protein specifically expressed in round spermatids. It is mainly found in mammalian and may play an important role in the testis-specific regulation of mRNA homeostasis. PABP-3 shows significant sequence similarity to PABP-1. However, it binds to poly(A) with a lower affinity than PABP-1. Moreover, PABP-1 possesses an A-rich sequence in its 5'-UTR and allows binding of PABP and blockage of translation of its own mRNA. In contrast, PABP-3 lacks the A-rich sequence in its 5'-UTR. PABP-4 is an inducible poly(A)-binding protein (iPABP) that is primarily localized to the cytoplasm. It shows significant sequence similarity to PABP-1 as well. The RNA binding properties of PABP-1 and PABP-4 appear to be identical. PABP-5 is encoded by PABPC5 gene within the X-specific subinterval, and expressed in fetal brain and in a range of adult tissues in mammals, such as ovary and testis. It may play an important role in germ cell development. Moreover, unlike other PABPs, PABP-5 contains only four RRMs, but lacks both the linker region and the CTD. PABP-1-like and PABP-1-like 2 are the orthologs of PABP-1. PABP-4-like is the ortholog of PABP-5. Their cellular functions remain unclear. The family also includes yeast PABP, a conserved poly(A) binding protein containing poly(A) tails that can be attached to the 3'-ends of mRNAs. The yeast PABP and its homologs may play important roles in the initiation of translation and in mRNA decay. Like vertebrate PABP-1, the yeast PABP contains four RRMs, a linker region, and a proline-rich CTD as well. The first two RRMs are mainly responsible for specific binding to poly(A). The proline-rich region may be involved in protein-protein interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578836633  506 LWVGQLDKRTTQqdvASLLEEF---GPIESI----NMIPPR--GCAYIVMVHRQDAYRALQKLsrgNYK-VNQKSIKIAW 575
Cdd:cd12378     2 LYVGDLHPDVTE---AMLYEKFspaGPVLSIrvcrDAVTRRslGYAYVNFQQPADAERALDTL---NFDvIKGKPIRIMW 75

                  .
gi 578836633  576 A 576
Cdd:cd12378    76 S 76

CID (CTD-Interacting Domain) of Regulation of nuclear pre-mRNA domain-containing protein 1B; Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B) is also called Cell cycle-related and expression-elevated protein in tumor (CREPT). RPRD1B is a CID (CTD-Interacting Domain) containing protein that co-purifies with RNA polymerase (Pol) II (RNAP II) and three other RNAP II-associated proteins, RPAP2, GRINL1A and RECQL5, but not with the Mediator complex. CID binds tightly to the carboxy-terminal domain (CTD) of 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. RPRD1B form homodimers and heterodimers with RPRD1A through their coiled-coil domains. Both RPRD1A and RPRD1B associate directly with RPAP2 phosphatase and serve as CTD scaffolds to coordinate the dephosphorylation of phospho-S5 by RPAP2. RPRD1B is highly expressed during tumorigenesis and in endometrial cancer, has been shown to promote tumor growth by accelerating the cell cycle. 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 578836633   41 KHVVQIV---EKFIKKCKPEYKVPGLYVIDSIVRQSRHQfgtdkdvfGPRFSKNITATFQYLYLCPSED-----KSKIVR 112
Cdd:cd17012    33 KHAGPIVsvwHRELRKAKSSRKLTFLYLANDVIQNSKRK--------GPEFTREFESVLVDAFSHVAREadegcKKPLER 104

                          90
                  ....*....|....*....
gi 578836633  113 VLNLWQKNGVFKIEIIQPL 131
Cdd:cd17012   105 LLNIWQERSVYGGDFIQQL 123

RNA recognition motif (RRM) found in Arabidopsis thaliana arginine/serine-rich-splicing factor RSp31 and similar proteins from plants; This subfamily corresponds to the RRM1in a family that represents a novel group of arginine/serine (RS) or serine/arginine (SR) splicing factors existing in plants, such as A. thaliana RSp31, RSp35, RSp41 and similar proteins. Like vertebrate RS splicing factors, these proteins function as plant splicing factors and play crucial roles in constitutive and alternative splicing in plants. They all contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), at their N-terminus, and an RS domain at their C-terminus.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578836633  506 LWVGQLDKRTTQQDVASLLEEFGPIESINMipPRGCAYIVMVHRQDAYRALQKLSRGNYKVNQKSIKIAWA 576
Cdd:cd12234     3 VFCGNFEYDARQSEIERLFGKYGRVDRVDM--KSGYAFVYMEDERDAEDAIRGLDNFEFGRQRRRLRVEWT 71

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578836633  505 TLWVGQLDKRTTQQDVASLLEEFGPIESINMIP-----PRGCAYIVMVHRQDAYRALQKLSrgNYKVNQKSIKIA 574
Cdd:cd12392     4 KLFVKGLPFSCTKEELEELFKQHGTVKDVRLVTyrngkPKGLAYVEYENEADASQAVLKTD--GTEIKDHTISVA 76

RNA recognition motif 2 (RRM2) found in plant flowering time control protein FCA and similar proteins; This subgroup corresponds to the RRM2 of FCA, a gene controlling flowering time in Arabidopsis, which encodes a flowering time control protein that functions in the posttranscriptional regulation of transcripts involved in the flowering process. The flowering time control protein FCA contains two RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNP (ribonucleoprotein domains), and a WW protein interaction domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 578836633  506 LWVGQLDKRTTQQDVASLLEEFGPIESINMIPPR------GCAYIVMVHRQDAYRALQKLSrGNYK 565
Cdd:cd12637     2 LFVGSLPKTATEQEVRDLFEAYGEVEEVYLMKDPvtqqgtGCAFVKFAYKEEALAAIRSLN-GTVT 66

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 578836633  506 LWVGQLDKRTTQQDVASLLEEFGPIESINMIppRGCAYIVMVHRQDAYRALQKLSrgNYKVNQKSIKI 573
Cdd:cd12343     2 IFVGNLPDAATSEELRALFEKYGKVTECDIV--KNYAFVHMEKEEDAEDAIKALN--GYEFMGSRINV 65

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor SRSF10, SRSF12 and similar proteins; This subfamily corresponds to the RRM of SRSF10 and SRSF12. SRSF10, also termed 40 kDa SR-repressor protein (SRrp40), or FUS-interacting serine-arginine-rich protein 1 (FUSIP1), or splicing factor SRp38, or splicing factor, arginine/serine-rich 13A (SFRS13A), or TLS-associated protein with Ser-Arg repeats (TASR). It is a serine-arginine (SR) protein that acts as a potent and general splicing repressor when dephosphorylated. It mediates global inhibition of splicing both in M phase of the cell cycle and in response to heat shock. SRSF10 emerges as a modulator of cholesterol homeostasis through the regulation of low-density lipoprotein receptor (LDLR) splicing efficiency. It also regulates cardiac-specific alternative splicing of triadin pre-mRNA and is required for proper Ca2+ handling during embryonic heart development. In contrast, the phosphorylated SRSF10 functions as a sequence-specific splicing activator in the presence of a nuclear cofactor. It activates distal alternative 5' splice site of adenovirus E1A pre-mRNA in vivo. Moreover, SRSF10 strengthens pre-mRNA recognition by U1 and U2 snRNPs. SRSF10 localizes to the nuclear speckles and can shuttle between nucleus and cytoplasm. SRSF12, also termed 35 kDa SR repressor protein (SRrp35), or splicing factor, arginine/serine-rich 13B (SFRS13B), or splicing factor, arginine/serine-rich 19 (SFRS19), is a serine/arginine (SR) protein-like alternative splicing regulator that antagonizes authentic SR proteins in the modulation of alternative 5' splice site choice. For instance, it activates distal alternative 5' splice site of the adenovirus E1A pre-mRNA in vivo. Both, SRSF10 and SRSF12, contain a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C-terminal RS domain rich in serine-arginine dipeptides.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578836633  504 TTLWVGQLDKRTTQQDVASLLEEFGPIESInMIP-------PRGCAYIVMVHRQDAYRALQKLSRGNykVNQKSIKIAWA 576
Cdd:cd12312     1 TSLFVRNVADDTRPDDLRREFGRYGPIVDV-YIPldfytrrPRGFAYIQFEDVRDAEDALYYLDRTR--FLGREIEIQFA 77

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 578836633  506 LWVGQLDKRTTQQDVASLLEEFGPIESINMIP------PRGCAYIVMVHRQDAYRALQKL 559
Cdd:cd12284     1 LYVGSLHFNITEDMLRGIFEPFGKIEFVQLQKdpetgrSKGYGFIQFRDAEDAKKALEQL 60

RNA recognition motif 1 (RRM1) and 2 (RRM2) found in the matrin 3 family of nuclear proteins; This subfamily corresponds to the RRM of the matrin 3 family of nuclear proteins consisting of Matrin 3 (MATR3), nuclear protein 220 (NP220) and similar proteins. MATR3 is a highly conserved inner nuclear matrix protein that has been implicated in various biological processes. NP220 is a large nucleoplasmic DNA-binding protein that binds to cytidine-rich sequences, such as CCCCC (G/C), in double-stranded DNA (dsDNA). Both, Matrin 3 and NP220, contain two RNA recognition motif (RRM), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a Cys2-His2 zinc finger-like motif at the C-terminal region.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 578836633  516 TQQDVASLLEEFGPIESINMIPPRGCAYIVMVHRQDAYRALQKLSRGNYKVNQKSIKIA 574
Cdd:cd12436    14 SEEDVLKLAEPFGKVNNVLLIRSKREAFIEMETAEDAQAMLSYCKTKPITIKGKKVKVS 72