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 665402454  396 CSTTLWVGHLSKLVYQEELSDTFGEYGDIVSIDQIVPRGCAFIVMNRRQDAHKAMQALKNHKLQGRAITISWAAGKG 472
Cdd:cd12227     1 CSTTLWVGHLSKKVTQEELKNLFEEYGEIQSIDMIPPRGCAYVCMKTRQDAHRALQKLKNHKLRGKSIKIAWAPNKG 77

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 665402454  396 CSTTLWVGHLSKLVYQEELSDTFGEYGDIVSIDQIVPRGCAFIVMNRRQDAHKAMQALKNHKLQGRAITISWAAGKG 472
Cdd:cd12227     1 CSTTLWVGHLSKKVTQEELKNLFEEYGEIQSIDMIPPRGCAYVCMKTRQDAHRALQKLKNHKLRGKSIKIAWAPNKG 77

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665402454      6 AFNNELSGLYDSRPPISKAkmaaiTKSAMRAIKLYKHVVQSVEKFILKCKPEYKVPGLYVIDSIVRQSRHQYGMD-KDLF 84
Cdd:smart00582    1 AFEQKLESLNNSQESIQTL-----TKWAIEHASHAKEIVELWEKYIKKAPVPRKLPLLYLLDSIVQNSKRKYGSEfGDEL 75

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|
gi 665402454     85 APRFQRNLTETFANLFRcapEDKSRIIRVLNLWQKNNVFKSEVIQPIFDL 134
Cdd:smart00582   76 GPVFQDALRRVLGAAPE---ELKKKIRRLLNIWEERGIFPPEVLRPLREK 122

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 665402454  397 STTLWVGHLSKLVYQEELSDTFGEYGDIVSIdQIV-------PRGCAFIVMNRRQDAHKAMQALKNHKLQGRAITISWA 468
Cdd:COG0724     1 SMKIYVGNLPYSVTEEDLRELFSEYGEVTSV-KLItdretgrSRGFGFVEMPDDEEAQAAIEALNGAELMGRTLKVNEA 78

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665402454 1093 SQSANSPPQEKLPAEnenfAKPADVTGDPLVAKSQTETSAACTPLYDELPP-----PAVPQTPTQPPKEPQGS-PPRPAP 1166
Cdd:PHA03247 2696 TSLADPPPPPPTPEP----APHALVSATPLPPGPAAARQASPALPAAPAPPavpagPATPGGPARPARPPTTAgPPAPAP 2771

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 665402454 1167 PVIETEAAPHEESVP--APPAELQTEAPSAEEPIAPAASADVVAEADP 1212
Cdd:PHA03247 2772 PAAPAAGPPRRLTRPavASLSESRESLPSPWDPADPPAAVLAPAAALP 2819

Androgen receptor;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665402454  1086 QKPGERASQSANS--PPQEKLPAENENFAKPADVTGDPLVAKSQTETSAACTPLYDELPPPA---------------VPQ 1148
Cdd:pfam02166   30 QNPGPRHPEAAGGaaPPGARLQHQQQQQQQVPQQPQQQESSPRQPQASVQPQQAGDDGSPPAhnrgpagylaleddeQPQ 109

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 665402454  1149 tPTQPPKEPQGSP-----PRPAPPVIETEAAPHEESVPAPPAELQTEAPSAEE---PIAPAASA------DVVAEA 1210
Cdd:pfam02166  110 -PSQAQPAAECCPengcvPEPGAAAAAGKGLPQQAVAPAAPDDDDSAAPSTLSllgPSFPGLSGcsadlkDILAEA 184

CCR4-NOT transcriptional regulation complex, NOT5 subunit [Transcription];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665402454 1033 EGNKAASETEPKPKNVETELGSTnTGAPAAATRVDTEEDWDQELQDyearMEAQKPGERAsQSANSPPQEKLPAEnENFA 1112
Cdd:COG5665   235 EWWGDPSLLATPPATPATEEKSS-QQPKSQPTSPSGGTTPPSTNQL----TTSNTPTSTA-KAQPQPPTKKQPAK-EPPS 307

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665402454 1113 KPADVTGDPLVAKSQTETSAACTPLYDELPPPAVPQTPTQP------PKEPQGSPPRPAPPVIET--------EAAPHEE 1178
Cdd:COG5665   308 DTASGNPSAPSVLINSDSPTSEDPATASVPTTEETTAFTTPssvpstPAEKDTPATDLATPVSPTppetsvdkKVSPDSA 387

                         170       180       190
                  ....*....|....*....|....*....|....
gi 665402454 1179 SVPAPPAElqtEAPSAEEPIAPAASADVVAEADP 1212
Cdd:COG5665   388 TSSTKSEK---EGGTASSPMPPNIAIGAKDDVDA 418

Kinetoplastid RNA Editing Protein A2 (KREPA2); The KREPA2 (TbMP63) protein is a component of the parasitic protozoan's KREPA RNA editing catalytic complex (RECC). Kinetoplastid RNA editing (KRE) proteins occur as pairs or sets of related proteins in multiple complexes. KREPA complex is composed of six components (KREPA1-6), which share a conserved C-terminal region containing an oligonucleotide-binding (OB)-fold-like domain. KREPAs are responsible for the site-specific insertion and deletion of U nucleotides in the kinetoplastid mitochondria pre-messenger RNA. Apart from the conserved C-terminal OB-fold domain, KREPA1, KREPA2, and KREPA3 contain two conserved C2H2 zinc-finger domains. KREPA2 and kinetoplastid RNA editing ligase 1 (KREL1) are specific for ligation post-U-deletion and are paralogous to KREL2 and KREPA1 that are specific for ligation post-U-insertion. KREPA2, is critical for RECC stability and KREL1 integration into the complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665402454 1105 PAENENFAKPADVTgDPLVAKSQTETSAACTPLYDelPPPAVPQTPTQPP--------KEPQGSPPRPAPPVIETEAAPH 1176
Cdd:cd23959   103 PDESLGPFRAARVP-NPFSASSSTQRETHKTAQVA--PPKAEPQTAPVTPfgqlpmfgQHPPPAKPLPAAAAAQQSSASP 179

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 665402454 1177 EE--------SVPAPP-AELQTEAPSAEEPIAPAASA 1204
Cdd:cd23959   180 GEvaspfasgTVSASPfATATDTAPSSGAPDGFPAEA 216

CID (CTD-Interacting Domain) of SR-related and CTD-associated factor 8; SR-related and CTD-associated factor 8 (SCAF8) is also called CDC5L complex-associated protein 7 (CCAP7) or RNA-binding motif protein 16 (RBM16). It may play a role in mRNA processing. 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 665402454    6 AFNNELSGLYDSRPPISKAKMAAITKSAMRAIKLYKHVVQSVEKFILKCKPEYKVPGLYVIDSIVRQSRHQYGMDKDLFA 85
Cdd:cd17004     2 TFNSELYSLNDYKPPISKAKMTQITKAAIKAIKFYKHVVQSVEKFIQKCKPEYKVPGLYVIDSIVRQSRHQFGQEKDVFA 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 665402454   86 PRFQRNLTETFANLFRCAPEDKSRIIRVLNLWQKNNVFKSEVIQPIFDLA 135
Cdd:cd17004    82 PRFSNNIISTFQNLYRCPGDDKSKIVRVLNLWQKNNVFKSEIIQPLLDMA 131

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 665402454  396 CSTTLWVGHLSKLVYQEELSDTFGEYGDIVSIDQIVPRGCAFIVMNRRQDAHKAMQALKNHKLQGRAITISWAAGKG 472
Cdd:cd12227     1 CSTTLWVGHLSKKVTQEELKNLFEEYGEIQSIDMIPPRGCAYVCMKTRQDAHRALQKLKNHKLRGKSIKIAWAPNKG 77

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 665402454     6 AFNNELSGLYDSrppisKAKMAAITKSAMRAIKLYKHVVQSVEKFILKCKPEYKVPGLYVIDSIVRQSRHQYGMDkdlFA 85
Cdd:pfam04818    2 ALEKKLSSLNNS-----QESIQTLSKWILFHRKHAKAIVEVWEKYLKKAKPEKKLHLLYLANDVLQNSRKKGKSE---FA 73

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 665402454    86 PRFQRNLTETFANLFRCAPED-KSRIIRVLNLWQKNNVFKSEVI 128
Cdd:pfam04818   74 DAFEPVLPEAFASAYKKCDEKlKKKLERLLNIWEERNVFSPEVI 117

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 665402454  394 SVCSTTLWVGHLSKLVYQEELSDTFGEYGDIVSIDQIVPRGCAFIVMNRRQDAHKAMQALK--NHKLQGRAITISWAAGK 471
Cdd:cd12461     1 SVCSTTLWVGQLDKRTTQQDVASLLEEFGQIESINMIPPRGCAYIVMVHRQDAYRALQKLSrgNYKVNQKSIKIAWALNK 80

                  .
gi 665402454  472 G 472
Cdd:cd12461    81 G 81

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 665402454    7 FNNELSGLYDSRPP-ISKAKMAAITKSAMRAIKLYKHVVQSVEKFILKCKPEYKVPGLYVIDSIVRQSRHQ---YGMDKD 82
Cdd:cd16984     3 FEATLKSLQALKPPgVSGSKIKKLTDIAVDNVQSESQIVSKLYRYFKKAPPTHKLGVLYVVDSVVRAWIDQakkNGQSID 82

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 665402454   83 LFAP---------RFQRNLTETFANLFRCAPED-KSRIIRVLNLWQKNNVFKSEVIQPIFD 133
Cdd:cd16984    83 SSAPdgtfaagvyKITELIESLMNDAIQSAPEDqKEKIKKLVDIWEKGNTFPAEMLNSIKQ 143

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 665402454    7 FNNELSGL-YDSRPPISkakmaAITKSAMRAIKLYKHVVQSVEKFILKCKPEYKVPGLYVIDSIVRQSRHQYgmdKDLFA 85
Cdd:cd16982     4 YRSALAELtFNSKPIIN-----NLTMLAEENIQAAQAIVEAIEERIRKVPPEQKLPALYLLDSIVKNVGGPY---TSLFS 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 665402454   86 PrfqrNLTETFANLFR-CAPEDKSRIIRVLNLW-----QKNNVFKSEVIQPI 131
Cdd:cd16982    76 P----NLVDLFLDAYRlVDEKTRKKLEKLLNTWktvfpNGKLLFPDEVLNKI 123

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 665402454  398 TTLWVGHLSKLVYQEELSDTFGEYGDIVSIDQIVPRGCAFIVMNRRQDAHKAMQALKNHKLQGRAITISW 467
Cdd:cd12346     2 TTVFVGGLDPNVTEEDLRVLFGPFGEIVYVKIPPGKGCGFVQFVNRASAEAAIQKLQGTPIGGSRIRLSW 71

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 665402454  398 TTLWVGHLSKLVYQEELSDTFGEYGDIVSIDQIVPRGCAFIVMNRRQDAHKAMQALKNhKL--QGRAITISWA 468
Cdd:cd12224     2 TTLYVGGLGDKITEKDLRDHFYQFGEIRSITVVARQQCAFVQFTTRQAAERAAERTFN-KLiiKGRRLKVKWG 73

RNA recognition motif 2 (RRM2) found in the Hu proteins family, Drosophila sex-lethal (SXL), and similar proteins; This subfamily corresponds to the RRM2 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 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. 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. Also included in this subfamily is 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 also to its own pre-mRNA and promotes female-specific alternative splicing. SXL 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 665402454  398 TTLWVGHLSKLVYQEELSDTFGEYGDIVS----IDQI--VPRGCAFIVMNRRQDAHKAMQALKNHKLQGRA--ITISWA 468
Cdd:cd12376     1 ANLYVSGLPKTMTQKELEQLFSQYGRIITsrilRDQLtgVSRGVGFIRFDKRIEAEEAIKGLNGQKPEGASepITVKFA 79

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 665402454  399 TLWVGHLSKLVYQEELSDTFGEYGDIVSIDQIV------PRGCAFIVMNRRQDAHKAMQALKNHKLQGRAITISWA 468
Cdd:cd21608     1 KLYVGNLSWDTTEDDLRDLFSEFGEVESAKVITdretgrSRGFGFVTFSTAEAAEAAIDALNGKELDGRSIVVNEA 76

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 665402454    6 AFNNELSGLYDSRPPISkakmaAITKSAMRAIKLYKHVVQSVEKFILK--CKPEYKVPGLYVIDSIVRQSRHQygmDKDL 83
Cdd:cd17003     3 QFISKLNALNETQESIV-----SISQWVLFHYRHADEIAEIWSDYLLKssVNSRRKLLLIYLANDVVQQAKAK---KKTE 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 665402454   84 FAPRFQRNLTETFANLFRCAPED-KSRIIRVLNLWQKNNVFKSEVIQPI 131
Cdd:cd17003    75 FIDAFSKVLPEVLEKIYPSLPSDiKKKIKRVVNVWKQRQIFSKDVIDDI 123

RNA recognition motif 2 (RRM2) found in Drosophila sex-lethal (SXL) and similar proteins; This subfamily corresponds to the RRM2 of the sex-lethal protein (SXL) which governs sexual differentiation and X chromosome dosage compensation in Drosophila melanogaster. 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 also to its own pre-mRNA and promotes female-specific alternative splicing. SXL contains an N-terminal Gly/Asn-rich domain that may be responsible for the protein-protein interaction, and tandem RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), that show high preference to bind single-stranded, uridine-rich target RNA transcripts.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 665402454  398 TTLWVGHLSKLVYQEELSDTFGEYGDIVSI----DQI--VPRGCAFIVMNRRQDAHKAMQALKNHKLQGRAITIS 466
Cdd:cd12651     3 TNLYVTNLPRTITEDELDTIFGAYGNIVQKnllrDKLtgRPRGVAFVRYDKREEAQAAISALNGTIPEGGTQPLS 77

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 665402454  398 TTLWVGHLSKLVYQEELSDTFGEYGDIVSIDQIVPRGCAFIVMNRRQDAHKAMQALKNHKLQGRAITISW 467
Cdd:cd12354     1 TTVYVGNITKGLTEALLQQTFSPFGQILEVRVFPDKGYAFIRFDSHEAATHAIVSVNGTIINGQAVKCSW 70

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 665402454   38 KLYKHVVQSVEKFILKCKPEYKVPGLYVIDSIVRQSRHQYGMDkdlFAPRFQRNLTETFANLFRCAPED-KSRIIRVLNL 116
Cdd:cd16981    30 KHAKQIVKIWLKELKKAKPERKLTLLYLANDVLQNSRRKGAPE---FVEAFKKVLPEALALVRSEGDESvRKKVLRVLNI 106

                          90
                  ....*....|..
gi 665402454  117 WQKNNVFKSEVI 128
Cdd:cd16981   107 WEERNVFGSEFL 118

RNA recognition motif (RRM) found in RNA-binding protein with serine-rich domain 1 (RNPS1) and similar proteins; This subfamily corresponds to the RRM of RNPS1 and its eukaryotic homologs. RNPS1, also termed RNA-binding protein prevalent during the S phase, or SR-related protein LDC2, was originally characterized as a general pre-mRNA splicing activator, which activates both constitutive and alternative splicing of pre-mRNA in vitro.It has been identified as a protein component of the splicing-dependent mRNP complex, or exon-exon junction complex (EJC), and is directly involved in mRNA surveillance. Furthermore, RNPS1 is a splicing regulator whose activator function is controlled in part by CK2 (casein kinase II) protein kinase phosphorylation. It can also function as a squamous-cell carcinoma antigen recognized by T cells-3 (SART3)-binding protein, and is involved in the regulation of mRNA splicing. RNPS1 contains an N-terminal serine-rich (S) domain, a central RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and the C-terminal arginine/serine/proline-rich (RS/P) domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 665402454  402 VGHLSKLVYQEELSDTFGEYGDIVSIDQIV------PRGCAFIVMNRRQDAHKAMQALKNHKLQGRAITIS 466
Cdd:cd12365     3 VGKLTRNVTKDHLKEIFSVYGTVKNVDLPIdrepnlPRGYAYVEFESPEDAEKAIKHMDGGQIDGQEVTVE 73

RNA recognition motif (RRM) found in yeast pre-mRNA-splicing factor Cwc2 and similar proteins; This subfamily corresponds to the RRM of yeast protein Cwc2, also termed Complexed with CEF1 protein 2, or PRP19-associated complex protein 40 (Ntc40), or synthetic lethal with CLF1 protein 3, one of the components of the Prp19-associated complex [nineteen complex (NTC)] that can bind to RNA. NTC is composed of the scaffold protein Prp19 and a number of associated splicing factors, and plays a crucial role in intron removal during premature mRNA splicing in eukaryotes. Cwc2 functions as an RNA-binding protein that can bind both small nuclear RNAs (snRNAs) and pre-mRNA in vitro. It interacts directly with the U6 snRNA to link the NTC to the spliceosome during pre-mRNA splicing. In the N-terminal half, Cwc2 contains a CCCH-type zinc finger (ZnF domain), a RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and an intervening loop, also termed RNA-binding loop or RB loop, between ZnF and RRM, all of which are necessary and sufficient for RNA binding. The ZnF is also responsible for mediating protein-protein interaction. The C-terminal flexible region of Cwc2 interacts with the WD40 domain of Prp19.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 665402454  399 TLWVGHL----SKLVYQEE-LSDTFGEYGDIVSIDQIVPRGCAFIVMNRRQDAHKAMQALKNHKLQGR-AITISWA 468
Cdd:cd12360     3 TLYVGGIkaasNKLAQIEEiLRRHFGEWGEIERIRVLPSKGIAFVRYKNRANAEFAKEAMADQSLDGGeVLNVRWA 78

RNA recognition motif 2 (RRM2) found in vertebrate Hu-antigen D (HuD); This subgroup corresponds to the RRM2 of HuD, also termed ELAV-like protein 4 (ELAV-4), or paraneoplastic encephalomyelitis antigen HuD, one of the neuronal members of the Hu family. The neuronal Hu proteins play important roles in neuronal differentiation, plasticity and memory. HuD has been implicated in various aspects of neuronal function, such as the commitment and differentiation of neuronal precursors as well as synaptic remodeling in mature neurons. HuD also functions as an important regulator of mRNA expression in neurons by interacting with AU-rich RNA element (ARE) and stabilizing multiple transcripts. Moreover, HuD regulates the nuclear processing/stability of N-myc pre-mRNA in neuroblastoma cells and also regulates the neurite elongation and morphological differentiation. HuD specifically binds poly(A) RNA. Like other Hu proteins, HuD 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665402454  394 SVCSTTLWVGHLSKLVYQEELSDTFGEYGDIVS----IDQI--VPRGCAFIVMNRRQDAHKAMQALKNHKLQGRA--ITI 465
Cdd:cd12774     2 SIRDANLYVSGLPKTMTQKELEQLFSQYGRIITsrilVDQVtgVSRGVGFIRFDKRIEAEEAIKGLNGQKPSGATepITV 81

                  ...
gi 665402454  466 SWA 468
Cdd:cd12774    82 KFA 84

RNA recognition motif 1 (RRM1) found in Schizosaccharomyces pombe mRNA export factor Crp79 and similar proteins; Crp79, also called meiotic expression up-regulated protein 5 (Mug5), or polyadenylate-binding protein crp79, or PABP, or poly(A)-binding protein, is an auxiliary mRNA export factor that binds the poly(A) tail of mRNA and is involved in the export of mRNA from the nucleus to the cytoplasm. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the first RRM motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 665402454  397 STTLWVGHLSKLVYQEELSDTFGEYGDIVSI-----DQIVP---RGCAFIVMNRRQDAHKAMQALKNHKLQGRAITI 465
Cdd:cd21619     1 SNTIYVGNIDMTINEDALEKIFSRYGQVESVrrppiHTDKAdrtTGFGFIKYTDAESAERAMQQADGILLGRRRLVV 77

RNA recognition motif 2 (RRM2) found in RNA-binding protein 28 (RBM28) and similar proteins; This subfamily corresponds to the RRM2 of RBM28 and Nop4p. RBM28 is a specific nucleolar component of the spliceosomal small nuclear ribonucleoproteins (snRNPs), possibly coordinating their transition through the nucleolus. It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), and may play a role in the maturation of both small nuclear and ribosomal RNAs. RBM28 has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an extremely acidic region between RRM2 and RRM3. The family also includes nucleolar protein 4 (Nop4p or 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 also contains four RRMs.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665402454  412 EELSDTFGEYGDIVSIdQIV------PRGCAFIVMNRRQDAHKAMQALKNHKLQGRAITISWA 468
Cdd:cd12414    14 DDLKKLFSKFGKVLEV-TIPkkpdgkLRGFAFVQFTNVADAAKAIKGMNGKKIKGRPVAVDWA 75

sex-lethal family splicing factor; This model describes the sex-lethal family of splicing factors found in Dipteran insects. The sex-lethal phenotype, however, may be limited to the Melanogasters and closely related species. In Drosophila the protein acts as an inhibitor of splicing. This subfamily is most closely related to the ELAV/HUD subfamily of splicing factors (TIGR01661).

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 665402454   394 SVCSTTLWVGHLSKLVYQEELSDTFGEYGDIVSIDQI------VPRGCAFIVMNRRQDAHKAMQALKN 455
Cdd:TIGR01659  190 SIKDTNLYVTNLPRTITDDQLDTIFGKYGQIVQKNILrdkltgTPRGVAFVRFNKREEAQEAISALNN 257

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 665402454  400 LWVGHLSKLVYQEELSDTFGEYGDIVSIDQIV---------PRGCAFIVMNRRQDAHKAMQALKNHKLQGRAITISWA 468
Cdd:cd12355     2 LWIGNLDPRLTEYHLLKLLSKYGKIKKFDFLFhktgplkgqPRGYCFVTFETKEEAEKAIECLNGKLALGKKLVVRWA 79

RNA recognition motif 2 (RRM2) found in vertebrate Hu-antigen B (HuB); This subgroup corresponds to the RRM2 of HuB, also termed ELAV-like protein 2 (ELAV-2), or ELAV-like neuronal protein 1, or nervous system-specific RNA-binding protein Hel-N1 (Hel-N1), one of the neuronal members of the Hu family. The neuronal Hu proteins play important roles in neuronal differentiation, plasticity and memory. HuB is also expressed in gonads. It is up-regulated during neuronal differentiation of embryonic carcinoma P19 cells. Like other Hu proteins, HuB 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 AU-rich RNA element (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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665402454  394 SVCSTTLWVGHLSKLVYQEELSDTFGEYGDIVS----IDQI--VPRGCAFIVMNRRQDAHKAMQALKNHKLQG--RAITI 465
Cdd:cd12775     2 SIRDANLYVSGLPKTMTQKELEQLFSQYGRIITsrilVDQVtgVSRGVGFIRFDKRIEAEEAIKGLNGQKPPGatEPITV 81

                  ...
gi 665402454  466 SWA 468
Cdd:cd12775    82 KFA 84