RNA recognition motif (RRM) found in Drosophila melanogaster RNA-binding protein cabeza and similar proteins; This subgroup corresponds to the RRM in cabeza, also termed P19, or sarcoma-associated RNA-binding fly homolog (SARFH). It is a putative homolog of human RNA-binding proteins FUS (also termed TLS or Pigpen or hnRNP P2), EWS (also termed EWSR1), TAF15 (also termed hTAFII68 or TAF2N or RPB56), and belongs to the of the FET (previously TET) (FUS/TLS, EWS, TAF15) family of RNA- and DNA-binding proteins whose expression is altered in cancer. It is a nuclear RNA binding protein that may play an important role in the regulation of RNA metabolism during fly development. Cabeza contains one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  78 IFVSGMDPSTTEQDIETHFGAIGIIKKDKRTMKPKIWLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIKV 157
Cdd:cd12534    1 VFVSNLPPNTTEQDLAEHFGSIGIIKIDKKTGKPKIWLYKDKDTGEPKGEATVTYDDPHAASAAIEWFNNKDFMGNTIKV 80

                 ...
gi 442616561 158 SLA 160
Cdd:cd12534   81 SLA 83

RNA recognition motif (RRM) found in Drosophila melanogaster RNA-binding protein cabeza and similar proteins; This subgroup corresponds to the RRM in cabeza, also termed P19, or sarcoma-associated RNA-binding fly homolog (SARFH). It is a putative homolog of human RNA-binding proteins FUS (also termed TLS or Pigpen or hnRNP P2), EWS (also termed EWSR1), TAF15 (also termed hTAFII68 or TAF2N or RPB56), and belongs to the of the FET (previously TET) (FUS/TLS, EWS, TAF15) family of RNA- and DNA-binding proteins whose expression is altered in cancer. It is a nuclear RNA binding protein that may play an important role in the regulation of RNA metabolism during fly development. Cabeza contains one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  78 IFVSGMDPSTTEQDIETHFGAIGIIKKDKRTMKPKIWLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIKV 157
Cdd:cd12534    1 VFVSNLPPNTTEQDLAEHFGSIGIIKIDKKTGKPKIWLYKDKDTGEPKGEATVTYDDPHAASAAIEWFNNKDFMGNTIKV 80

                 ...
gi 442616561 158 SLA 160
Cdd:cd12534   81 SLA 83

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  77 TIFVSGMDPSTTEQDIETHFGAIGIIKKDKrtmkpkiwLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIK 156
Cdd:COG0724    3 KIYVGNLPYSVTEEDLRELFSEYGEVTSVK--------LITDRETGRSRGFGFVEMPDDEEAQAAIEALNGAELMGRTLK 74

                 ....*
gi 442616561 157 VSLAQ 161
Cdd:COG0724   75 VNEAR 79

Zn-finger in Ran binding protein and others;

                          10        20        30
                  ....*....|....*....|....*....|
gi 442616561  231 RDGDWKCNSCNNTNFAWRNECNRCKTPKGD 260
Cdd:pfam00641   1 REGDWDCSKCLVQNFATSTKCVACQAPKPD 30

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561   69 NDMITQEDTIFVSGMDPSTTEQDIETHFGAIGIIKKDKRTMKpkiwlyknkETGASKGEATVTYDDTNAAQSAIEWFDGR 148
Cdd:TIGR01628 279 RKMKAQGVNLYVKNLDDTVTDEKLRELFSECGEITSAKVMLD---------EKGVSRGFGFVCFSNPEEANRAVTEMHGR 349

                          90
                  ....*....|....*
gi 442616561  149 DFNGNAIKVSLAQRQ 163
Cdd:TIGR01628 350 MLGGKPLYVALAQRK 364

RNA recognition motif (RRM) found in Drosophila melanogaster RNA-binding protein cabeza and similar proteins; This subgroup corresponds to the RRM in cabeza, also termed P19, or sarcoma-associated RNA-binding fly homolog (SARFH). It is a putative homolog of human RNA-binding proteins FUS (also termed TLS or Pigpen or hnRNP P2), EWS (also termed EWSR1), TAF15 (also termed hTAFII68 or TAF2N or RPB56), and belongs to the of the FET (previously TET) (FUS/TLS, EWS, TAF15) family of RNA- and DNA-binding proteins whose expression is altered in cancer. It is a nuclear RNA binding protein that may play an important role in the regulation of RNA metabolism during fly development. Cabeza contains one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  78 IFVSGMDPSTTEQDIETHFGAIGIIKKDKRTMKPKIWLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIKV 157
Cdd:cd12534    1 VFVSNLPPNTTEQDLAEHFGSIGIIKIDKKTGKPKIWLYKDKDTGEPKGEATVTYDDPHAASAAIEWFNNKDFMGNTIKV 80

                 ...
gi 442616561 158 SLA 160
Cdd:cd12534   81 SLA 83

RNA recognition motif (RRM) found in vertebrate fused in Ewing's sarcoma protein (FUS), TATA-binding protein-associated factor 15 (TAF15) and similar proteins; This subgroup corresponds to the RRM of FUS and TAF15. FUS (TLS or Pigpen or hnRNP P2), also termed 75 kDa DNA-pairing protein (POMp75), or oncoprotein TLS (Translocated in liposarcoma), is a member of the FET (previously TET) (FUS/TLS, EWS, TAF15) family of RNA- and DNA-binding proteins whose expression is altered in cancer. It is a multi-functional protein and has been implicated in pre-mRNA splicing, chromosome stability, cell spreading, and transcription. FUS was originally identified in human myxoid and round cell liposarcomas as an oncogenic fusion with the stress-induced DNA-binding transcription factor CHOP (CCAAT enhancer-binding homologous protein) and later as hnRNP P2, a component of hnRNP H complex assembled on pre-mRNA. It can form ternary complexes with hnRNP A1 and hnRNP C1/C2. Additional research indicates that FUS binds preferentially to GGUG-containing RNAs. In the presence of Mg2+, it can bind both single- and double-stranded DNA (ssDNA/dsDNA) and promote ATP-independent annealing of complementary ssDNA and D-loop formation in superhelical dsDNA. FUS has been shown to be recruited by single stranded noncoding RNAs to the regulatory regions of target genes such as cyclin D1, where it represses transcription by disrupting complex formation. TAF15 (TAFII68), also termed TATA-binding protein-associated factor 2N (TAF2N), or RNA-binding protein 56 (RBP56), originally identified as a TAF in the general transcription initiation TFIID complex, is a novel RNA/ssDNA-binding protein with homology to the proto-oncoproteins FUS and EWS (also termed EWSR1), belonging to the FET family as well. TAF15 likely functions in RNA polymerase II (RNAP II) transcription by interacting with TFIID and subunits of RNAP II itself. TAF15 is also associated with U1 snRNA, chromatin and RNA, in a complex distinct from the Sm-containing U1 snRNP that functions in splicing. Like other members in the FET family, both FUS and TAF15 contain an N-terminal Ser, Gly, Gln and Tyr-rich region composed of multiple copies of a degenerate hexapeptide repeat motif. The C-terminal region consists of a conserved nuclear import and retention signal (C-NLS), a C2/C2 zinc-finger motif, a conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and at least 1 arginine-glycine-glycine (RGG)-repeat region.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  76 DTIFVSGMDPSTTEQDIETHFGAIGIIKKDKRTMKPKIWLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAI 155
Cdd:cd12535    3 NTIFVQGLGEDVTIDSVADYFKQIGIIKTNKKTGKPMINLYTDKETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPI 82

                 ....
gi 442616561 156 KVSL 159
Cdd:cd12535   83 KVSF 86

RNA recognition motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561    77 TIFVSGMDPSTTEQDIETHFGAIGIIKKdkrtmkpkIWLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIK 156
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVES--------VRLVRDKETGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLK 72

                   .
gi 442616561   157 V 157
Cdd:smart00360  73 V 73

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  78 IFVSGMDPSTTEQDIETHFGAIGIIKKdkrtmkpkIWLYKNKEtGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIKV 157
Cdd:cd00590    1 LFVGNLPPDTTEEDLRELFSKFGEVVS--------VRIVRDRD-GKSKGFAFVEFESPEDAEKALEALNGTELGGRPLKV 71

                 .
gi 442616561 158 S 158
Cdd:cd00590   72 S 72

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 442616561   78 IFVSGMDPSTTEQDIETHFGAIGIIKKdkrtmkpkIWLyKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIK 156
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKS--------IRL-VRDETGRSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  77 TIFVSGMDPSTTEQDIETHFGAIGIIKKDKrtmkpkiwLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIK 156
Cdd:cd21608    1 KLYVGNLSWDTTEDDLRDLFSEFGEVESAK--------VITDRETGRSRGFGFVTFSTAEAAEAAIDALNGKELDGRSIV 72

                 ....
gi 442616561 157 VSLA 160
Cdd:cd21608   73 VNEA 76

RNA recognition motif (RRM) found in AZoospermia (DAZ) autosomal homologs, DAZL (DAZ-like) and BOULE; This subfamily corresponds to the RRM domain of two Deleted in AZoospermia (DAZ) autosomal homologs, DAZL (DAZ-like) and BOULE. BOULE is the founder member of the family and DAZL arose from BOULE in an ancestor of vertebrates. The DAZ gene subsequently originated from a duplication transposition of the DAZL gene. Invertebrates contain a single DAZ homolog, BOULE, while vertebrates, other than catarrhine primates, possess both BOULE and DAZL genes. The catarrhine primates possess BOULE, DAZL, and DAZ genes. The family members encode closely related RNA-binding proteins that are required for fertility in numerous organisms. These proteins contain an RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a varying number of copies of a DAZ motif, believed to mediate protein-protein interactions. DAZL and BOULE contain a single copy of the DAZ motif, while DAZ proteins can contain 8-24 copies of this repeat. Although their specific biochemical functions remain to be investigated, DAZL proteins may interact with poly(A)-binding proteins (PABPs), and act as translational activators of specific mRNAs during gametogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  76 DTIFVSGMDPSTTEQDIETHFGAIGIIKKDKrtmkpkiwLYKNKEtGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAI 155
Cdd:cd12412    3 NRIFVGGIDWDTTEEELREFFSKFGKVKDVK--------IIKDRA-GVSKGYGFVTFETQEDAEKIQKWGANLVFKGKKL 73

                 ....*...
gi 442616561 156 KVSLAQRQ 163
Cdd:cd12412   74 NVGPAIRK 81

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  77 TIFVSGMDPSTTEQDIETHFGAIGIIkKDKRtmkpkIWLYKNketGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIK 156
Cdd:cd12392    4 KLFVKGLPFSCTKEELEELFKQHGTV-KDVR-----LVTYRN---GKPKGLAYVEYENEADASQAVLKTDGTEIKDHTIS 74

                 ...
gi 442616561 157 VSL 159
Cdd:cd12392   75 VAI 77

RNA recognition motif (RRM) found in cleavage stimulation factor subunit 2 (CSTF2), yeast ortholog mRNA 3'-end-processing protein RNA15 and similar proteins; This subfamily corresponds to the RRM domain of CSTF2, its tau variant and eukaryotic homologs. CSTF2, also termed cleavage stimulation factor 64 kDa subunit (CstF64), is the vertebrate conterpart of yeast mRNA 3'-end-processing protein RNA15. It is expressed in all somatic tissues and is one of three cleavage stimulatory factor (CstF) subunits required for polyadenylation. CstF64 contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a CstF77-binding domain, a repeated MEARA helical region and a conserved C-terminal domain reported to bind the transcription factor PC-4. During polyadenylation, CstF interacts with the pre-mRNA through the RRM of CstF64 at U- or GU-rich sequences within 10 to 30 nucleotides downstream of the cleavage site. CSTF2T, also termed tauCstF64, is a paralog of the X-linked cleavage stimulation factor CstF64 protein that supports polyadenylation in most somatic cells. It is expressed during meiosis and subsequent haploid differentiation in a more limited set of tissues and cell types, largely in meiotic and postmeiotic male germ cells, and to a lesser extent in brain. The loss of CSTF2T will cause male infertility, as it is necessary for spermatogenesis and fertilization. Moreover, CSTF2T is required for expression of genes involved in morphological differentiation of spermatids, as well as for genes having products that function during interaction of motile spermatozoa with eggs. It promotes germ cell-specific patterns of polyadenylation by using its RRM to bind to different sequence elements downstream of polyadenylation sites than does CstF64. The family also includes yeast ortholog mRNA 3'-end-processing protein RNA15 and similar proteins. RNA15 is a core subunit of cleavage factor IA (CFIA), an essential transcriptional 3'-end processing factor from Saccharomyces cerevisiae. RNA recognition by CFIA is mediated by an N-terminal RRM, which is contained in the RNA15 subunit of the complex. The RRM of RNA15 has a strong preference for GU-rich RNAs, mediated by a binding pocket that is entirely conserved in both yeast and vertebrate RNA15 orthologs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  77 TIFVSGMDPSTTEQDIETHFGAIGIIKKDKrtmkpkiwLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIK 156
Cdd:cd12398    2 SVFVGNIPYDATEEQLKEIFSEVGPVVSFR--------LVTDRETGKPKGYGFCEFRDAETALSAVRNLNGYELNGRPLR 73

                 ....
gi 442616561 157 VSLA 160
Cdd:cd12398   74 VDFA 77

RNA recognition motif in type II polyadenylate-binding proteins; This subfamily corresponds to the RRM of type II polyadenylate-binding proteins (PABPs), including polyadenylate-binding protein 2 (PABP-2 or PABPN1), embryonic polyadenylate-binding protein 2 (ePABP-2 or PABPN1L) and similar proteins. PABPs are 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. ePABP-2 is predominantly located in the cytoplasm and PABP-2 is located in the nucleus. In contrast to the type I PABPs containing four copies of RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), the type II PABPs contains a single highly-conserved RRM. This subfamily also includes Saccharomyces cerevisiae RBP29 (SGN1, YIR001C) gene encoding cytoplasmic mRNA-binding protein Rbp29 that binds preferentially to poly(A). Although not essential for cell viability, Rbp29 plays a role in modulating the expression of cytoplasmic mRNA. Like other type II PABPs, Rbp29 contains one RRM only.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  78 IFVSGMDPSTTEQDIETHFGAIGIIKkdkrtmkpKIWLYKNKETGASKGEATVTYDDTNAAQSAIEwFDGRDFNGNAIKV 157
Cdd:cd12306    2 IYVGNVDYGTTPEELQAHFKSCGTIN--------RVTILCDKFTGQPKGFAYIEFVDKSSVENALL-LNESEFRGRQIKV 72

                 .
gi 442616561 158 S 158
Cdd:cd12306   73 T 73

RNA recognition motif (RRM) found in Helicobacter pylori HP0827 protein and similar proteins; This subfamily corresponds to the RRM of H. pylori HP0827, a putative ssDNA-binding protein 12rnp2 precursor, containing one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The ssDNA binding may be important in activation of HP0827.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  78 IFVSGMDPSTTEQDIETHFGAIGIIKKDKRTMkpkiwlykNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIKV 157
Cdd:cd12399    1 LYVGNLPYSASEEQLKSLFGQFGAVFDVKLPM--------DRETKRPRGFGFVELQEEESAEKAIAKLDGTDFMGRTIRV 72

                 ...
gi 442616561 158 SLA 160
Cdd:cd12399   73 NEA 75

RNA recognition motif (RRM) found in heterogeneous nuclear ribonucleoprotein G (hnRNP G), Y chromosome RNA recognition motif 1 (hRBMY), testis-specific heterogeneous nuclear ribonucleoprotein G-T (hnRNP G-T) and similar proteins; This subfamily corresponds to the RRM domain of hnRNP G, also termed glycoprotein p43 or RBMX, an RNA-binding motif protein located on the X chromosome. It is expressed ubiquitously and has been implicated in the splicing control of several pre-mRNAs. Moreover, hnRNP G may function as a regulator of transcription for SREBP-1c and GnRH1. Research has shown that hnRNP G may also act as a tumor-suppressor since it upregulates the Txnip gene and promotes the fidelity of DNA end-joining activity. In addition, hnRNP G appears to play a critical role in proper neural development of zebrafish and frog embryos. The family also includes several paralogs of hnRNP G, such as hRBMY and hnRNP G-T (also termed RNA-binding motif protein, X-linked-like-2). Both, hRBMY and hnRNP G-T, are exclusively expressed in testis and critical for male fertility. Like hnRNP G, hRBMY and hnRNP G-T interact with factors implicated in the regulation of pre-mRNA splicing, such as hTra2-beta1 and T-STAR. Although members in this family share a high conserved N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), they appear to recognize different RNA targets. For instance, hRBMY interacts specifically with a stem-loop structure in which the loop is formed by the sequence CA/UCAA. In contrast, hnRNP G associates with single stranded RNA sequences containing a CCA/C motif. In addition to the RRM, hnRNP G contains a nascent transcripts targeting domain (NTD) in the middle region and a novel auxiliary RNA-binding domain (RBD) in its C-terminal region. The C-terminal RBD exhibits distinct RNA binding specificity, and would play a critical role in the regulation of alternative splicing by hnRNP G.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  78 IFVSGMDPSTTEQDIETHFGAIGIIKKdkrtmkpkIWLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIKV 157
Cdd:cd12382    4 LFIGGLNTETNEKALEAVFGKYGRIVE--------VLLMKDRETNKSRGFAFVTFESPADAKDAARDMNGKELDGKAIKV 75

                 ....*
gi 442616561 158 SLAQR 162
Cdd:cd12382   76 EQATK 80

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  77 TIFVSGMDPSTTEQDIETHFGAIGIIKkdkrtmkpKIWLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIK 156
Cdd:cd12236    3 TLFVARLSYDTTESKLRREFEKYGPIK--------RVRLVRDKKTGKSRGYAFIEFEHERDMKAAYKHADGKKIDGRRVL 74

                 .
gi 442616561 157 V 157
Cdd:cd12236   75 V 75

RNA recognition motif 2 (RRM2) found in nucleolin-like proteins mainly from plants; This subfamily corresponds to the RRM2 of a group of plant nucleolin-like proteins, including nucleolin 1 (also termed protein nucleolin like 1) and nucleolin 2 (also termed protein nucleolin like 2, or protein parallel like 1). They play roles in the regulation of ribosome synthesis and in the growth and development of plants. Like yeast nucleolin, nucleolin-like proteins possess two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  77 TIFVSGMDPS----TTEQDIETHFGAIGIIKkdkrtmkpKIWLYKNKETGASKGEATVTYDDTNAAQSAIEwFDGRDFNG 152
Cdd:cd12451    1 TIFVKGFDASlgedTIRDELREHFGECGEVT--------NVRIPTDRETGELKGFAYIEFSTKEAKEKALE-LNGSDIAG 71

                 ....*...
gi 442616561 153 NAIKVSLA 160
Cdd:cd12451   72 GNLVVDEA 79

RNA recognition motif 3 (RRM3) found in Saccharomyces cerevisiae protein HRB1, G-strand-binding protein 2 (GBP2) and similar proteins; The family includes Saccharomyces cerevisiae protein HRB1 (also called protein TOM34) and GBP2, both of which are SR-like mRNA-binding proteins which shuttle from the nucleus to the cytoplasm when bound to the mature mRNA molecules. They act as quality control factors for spliced mRNAs. GBP2, also called RAP1 localization factor 6, is a single-strand telomeric DNA-binding protein that binds single-stranded telomeric sequences of the type (TG[1-3])n in vitro. It also binds to RNA. GBP2 influences the localization of RAP1 in the nuclei and plays a role in modulating telomere length. 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 third RRM motif.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  77 TIFVSGMDPSTTEQDIETHFGAIGIIKKDKrtmkpkiwlYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIK 156
Cdd:cd21607    4 TIYCSNLPLSTAESDLYDLFETIGKVNNAE---------LKYDETGDPTGSAVVEYENLDDADVCISKLNNYNYGGCDLK 74

                 ....*
gi 442616561 157 VSLAQ 161
Cdd:cd21607   75 ISYAK 79

Zinc finger domain; Zinc finger domain in Ran-binding proteins (RanBPs), and other proteins. In RanBPs, this domain binds RanGDP.

                           10        20
                   ....*....|....*....|....*
gi 442616561   233 GDWKCNSCNNTNFAWRNECNRCKTP 257
Cdd:smart00547   1 GDWECPACTFLNFASRSKCFACGAP 25

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  78 IFVSGMDPSTTEQDIETHFGAIGIIKKdkrtmkpkIWLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIKV 157
Cdd:cd12347    1 LYVGGLAEEVDEKVLHAAFIPFGDIVD--------IQIPLDYETEKHRGFAFVEFEEAEDAAAAIDNMNESELFGRTIRV 72

                 ...
gi 442616561 158 SLA 160
Cdd:cd12347   73 NLA 75

RNA recognition motif 1 (RRM1) found in yeast nucleolar protein 4 (Nop4p) and similar proteins; This subgroup corresponds to the RRM1 of Nop4p (also known as Nop77p), encoded by YPL043W from Saccharomyces cerevisiae. It is an essential nucleolar protein involved in processing and maturation of 27S pre-rRNA and biogenesis of 60S ribosomal subunits. Nop4p has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  77 TIFVSGMDPSTTEQDIETHFGAIGIIKKdkrtmkpkIWLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIK 156
Cdd:cd12674    2 TLFVRNLPFDVTLESLTDFFSDIGPVKH--------AVVVTDPETKKSRGYGFVSFSTHDDAEEALAKLKNRKLSGHILK 73

                 ....*..
gi 442616561 157 VSLAQRQ 163
Cdd:cd12674   74 LDFAKPR 80

RNA recognition motif 2 (RRM2) found in Arabidopsis thaliana phragmoplastin interacting protein 1 (PHIP1) and similar proteins; The CD corresponds to the RRM2 of PHIP1. A. thaliana PHIP1 and its homologs represent a novel class of plant-specific RNA-binding proteins that may play a unique role in the polarized mRNA transport to the vicinity of the cell plate. The family members consist of multiple functional domains, including a lysine-rich domain (KRD domain) that contains three nuclear localization motifs (KKKR/NK), two RNA recognition motifs (RRMs), and three CCHC-type zinc fingers. PHIP1 is a peripheral membrane protein and is localized at the cell plate during cytokinesis in plants. In addition to phragmoplastin, PHIP1 interacts with two Arabidopsis small GTP-binding proteins, Rop1 and Ran2. However, PHIP1 interacted only with the GTP-bound form of Rop1 but not the GDP-bound form. It also binds specifically to Ran2 mRNA.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  77 TIFVSGMDPSTTEQDIETHFGAIGIIKKdkrtmkpkIWLYKNKETGASKGEATVTYDDTNAAQSAIEwFDGRDFNGNAIK 156
Cdd:cd12272    1 TVYIGNLAWDIDEDDLRELFAECCEITN--------VRLHTDKETGEFKGYGHVEFADEESLDAALK-LAGTKLCGRPIR 71

                 ..
gi 442616561 157 VS 158
Cdd:cd12272   72 VD 73

RNA recognition motif 1 (RRM1) found in yeast multiple RNA-binding domain-containing protein 1 (MRD1) and similar proteins; This subgroup corresponds to the RRM1 of MRD1 which is encoded by a novel yeast gene MRD1 (multiple RNA-binding domain). It is well-conserved in yeast and its homologs exist in all eukaryotes. MRD1 is present in the nucleolus and the nucleoplasm. It interacts with the 35 S precursor rRNA (pre-rRNA) and U3 small nucleolar RNAs (snoRNAs). MRD1 is essential for the initial processing at the A0-A2 cleavage sites in the 35 S pre-rRNA. It contains 5 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), which may play an important structural role in organizing specific rRNA processing events.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  78 IFVSGMDPSTTEQDIETHFGAIGIIKkDKRTMKpkiwlyknKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIKV 157
Cdd:cd12565    3 IIVKNLPKYVTEKRLKEHFSKKGEIT-DVKVMR--------TKDGKSRRFGFIGFKSEEEAQKAVKYFNKTFIDTSKISV 73

                 ...
gi 442616561 158 SLA 160
Cdd:cd12565   74 EFA 76

RNA recognition motif 2 (RRM2) found in yeast nucleolar protein 13 (Nop13p) and similar proteins; This subfamily corresponds to the RRM2 of Nop13p encoded by YNL175c from Saccharomyces cerevisiae. It shares high sequence similarity with nucleolar protein 12 (Nop12p). Both Nop12p and Nop13p are not essential for growth. However, unlike Nop12p that is localized to the nucleolus, Nop13p localizes primarily to the nucleolus but is also present in the nucleoplasm to a lesser extent. Nop13p contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  78 IFVSGMDPSTTEQDIETHFGAIGIIKkdkrtmkpKIWLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIKV 157
Cdd:cd12397    1 LFVGNLSFETTEEDLRKHFAPAGKIR--------KVRMATFEDSGKCKGFAFVDFKEIESATNAVKGPINHSLNGRDLRV 72

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  78 IFVSGMDPSTTEQDIETHFGAIGIIKKdkrtmkpkIWLYKNKETGASKGEATVTYDDTNAAQSAIEWfDGRDFNGNAIKV 157
Cdd:cd12271    1 VYVGGIPYYSTEAEIRSYFSSCGEVRS--------VDLMRFPDSGNFRGIAFITFKTEEAAKRALAL-DGEMLGNRFLKV 71

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 442616561  86 STTEQDIETHFGAIGIIKKDKrtmkpkiwLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIKVSLA 160
Cdd:cd12375   10 SMTQEELRSLFGAIGPIESCK--------LVRDKITGQSLGYGFVNYRDPNDARKAINTLNGLDLENKRLKVSYA 76

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561   69 NDMITQEDTIFVSGMDPSTTEQDIETHFGAIGIIKKDKRTMKpkiwlyknkETGASKGEATVTYDDTNAAQSAIEWFDGR 148
Cdd:TIGR01628 279 RKMKAQGVNLYVKNLDDTVTDEKLRELFSECGEITSAKVMLD---------EKGVSRGFGFVCFSNPEEANRAVTEMHGR 349

                          90
                  ....*....|....*
gi 442616561  149 DFNGNAIKVSLAQRQ 163
Cdd:TIGR01628 350 MLGGKPLYVALAQRK 364

glycine-rich RNA-binding protein 4; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  78 IFVSGMDPSTTEQDIETHFGAIGIIKKDKrtmkpkiwLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIKV 157
Cdd:PLN03134  37 LFIGGLSWGTDDASLRDAFAHFGDVVDAK--------VIVDRETGRSRGFGFVNFNDEGAATAAISEMDGKELNGRHIRV 108

                 ...
gi 442616561 158 SLA 160
Cdd:PLN03134 109 NPA 111

RNA recognition motif 3 (RRM3) found in CELF/Bruno-like family of RNA binding proteins CELF1, CELF2, CELF3, CELF4, CELF5, CELF6 and similar proteins; This subgroup corresponds to the RRM3 of the CUGBP1 and ETR-3-like factors (CELF) or BRUNOL (Bruno-like) proteins, a family of structurally related RNA-binding proteins involved in the regulation of pre-mRNA splicing in the nucleus and in the control of mRNA translation and deadenylation in the cytoplasm. The family contains six members: CELF-1 (also termed BRUNOL-2, or CUG-BP1, or NAPOR, or EDEN-BP), CELF-2 (also termed BRUNOL-3, or ETR-3, or CUG-BP2, or NAPOR-2), CELF-3 (also termed BRUNOL-1, or TNRC4, or ETR-1, or CAGH4, or ER DA4), CELF-4 (also termed BRUNOL-4), CELF-5 (also termed BRUNOL-5), CELF-6 (also termed 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  78 IFVSGMDPSTTEQDIETHFGAIGIIkkdkrtMKPKIwlYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIKV 157
Cdd:cd12362    1 LFVYHLPNEFTDQDLYQLFAPFGNV------VSAKV--FVDKNTGRSKGFGFVSYDNPLSAQAAIKAMNGFQVGGKRLKV 72

                 .
gi 442616561 158 S 158
Cdd:cd12362   73 Q 73

RNA recognition motif 1 (RRM1) found in granule-associated RNA binding proteins p40-TIA-1 and TIAR; This subfamily corresponds to the RRM1 of nucleolysin TIA-1 isoform p40 (p40-TIA-1 or TIA-1) and nucleolysin TIA-1-related protein (TIAR), both of which are granule-associated RNA binding proteins involved in inducing apoptosis in cytotoxic lymphocyte (CTL) target cells. TIA-1 and TIAR share high sequence similarity. They are expressed in a wide variety of cell types. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis.TIAR is mainly localized in the nucleus of hematopoietic and nonhematopoietic cells. It is translocated from the nucleus to the cytoplasm in response to exogenous triggers of apoptosis. Both, TIA-1 and TIAR, bind specifically to poly(A) but not to poly(C) homopolymers. They are composed of three N-terminal highly homologous RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. TIA-1 and TIAR interact with RNAs containing short stretches of uridylates and their RRM2 can mediate the specific binding to uridylate-rich RNAs. The C-terminal auxiliary domain may be responsible for interacting with other proteins. In addition, TIA-1 and TIAR share a potential serine protease-cleavage site (Phe-Val-Arg) localized at the junction between their RNA binding domains and their C-terminal auxiliary domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  78 IFVSGMDPSTTEQDIETHFGAIGIIKKDKRTMkpkiwlyknkETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIKV 157
Cdd:cd12352    1 LYVGNLDRQVTEDLILQLFSQIGPCKSCKMIT----------EHGGNDPYCFVEFYEHNHAAAALQAMNGRKILGKEVKV 70

                 ...
gi 442616561 158 SLA 160
Cdd:cd12352   71 NWA 73

RNA recognition motif 3 (RRM3) found in RNA-binding protein 28 (RBM28) and similar proteins; This subfamily corresponds to the RRM3 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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616561  77 TIFVSGMDPSTTEQDIETHFGAIGIIKKDKrtmkpkiwLYKNKETGASKGEATVTYDDTNAAQSAIE-----------WF 145
Cdd:cd12415    2 TVFIRNLSFDTTEEDLKEFFSKFGEVKYAR--------IVLDKDTGHSKGTAFVQFKTKESADKCIEaandesedgglVL 73

                         90
                 ....*....|....*
gi 442616561 146 DGRDfngnaIKVSLA 160
Cdd:cd12415   74 DGRK-----LIVSLA 83

RNA recognition motif 1 (RRM1) found in RNA-binding protein 45 (RBM45) and similar proteins; This subfamily corresponds to the RRM1 of RBM45, also termed developmentally-regulated RNA-binding protein 1 (DRB1), a new member of RNA recognition motif (RRM)-type neural RNA-binding proteins, which expresses under spatiotemporal control. It is encoded by gene drb1 that is expressed in neurons, not in glial cells. RBM45 predominantly localizes in cytoplasm of cultured cells and specifically binds to poly(C) RNA. It could play an important role during neurogenesis. RBM45 carries four RRMs, also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 442616561  86 STTEQDIETHFGAIGIIKKdkrtmkpkIWLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNA--IKVSLA 160
Cdd:cd12366   13 SVTEDDLREAFSPFGEIQD--------IWVVKDKQTKESKGIAYVKFAKSSQAARAMEEMHGKCLGDDTkpIKVLIA 81

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 442616561  85 PSTTEQDIETHFGAIGIIKKDKrtmkpkiwLYKNKETGASKGEATVTYDDTNAAQSAIEWFDGRDFNGNAIKVSLA 160
Cdd:cd12650   10 QNMTQDEIRSLFSSIGEIESCK--------LIRDKVTGQSLGYGFVNYVDPSDAEKAINTLNGLRLQNKTIKVSYA 77