Nuclear transport factor 2 (NTF2) domain plays an important role in the trafficking of macromolecules, ions and small molecules between the cytoplasm and nucleus. This bi-directional transport of macromolecules across the nuclear envelope requires many soluble factors that includes GDP-binding protein Ran (RanGDP). RanGDP is required for both import and export of proteins and poly(A) RNA. RanGDP also has been implicated in cell cycle control, specifically in mitotic spindle assembly. In interphase cells, RanGDP is predominately nuclear and thought to be GTP bound, but it is also present in the cytoplasm, probably in the GDP-bound state. NTF2 mediates the nuclear import of RanGDP. NTF2 binds to both RanGDP and FxFG repeat-containing nucleoporins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646615  12 SPQSVGREFVRQYYTLLNKAPNHLHRFYNHNSSYIHGESKLVVGQREIHNRIQQLNFNDCHAKISQVDAQATLGNGVVVQ 91
Cdd:cd00780   1 SAEDVAKAFVQQYYSIFDNNREGLHRLYGDTSMLSREGMKQVTGRDAIVEKLSSLPFQKTKHKITTVDSQPTPSGGVIVM 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 24646615  92 VTGELSNDGQPMRRFTQTFVLAAQsPKKYYVHNDIFRYQD 131
Cdd:cd00780  81 VTGSLKLDEQPPRKFSQTFVLAPQ-NGGYFVLNDIFRFVD 119

Nuclear transport factor 2 (NTF2) domain plays an important role in the trafficking of macromolecules, ions and small molecules between the cytoplasm and nucleus. This bi-directional transport of macromolecules across the nuclear envelope requires many soluble factors that includes GDP-binding protein Ran (RanGDP). RanGDP is required for both import and export of proteins and poly(A) RNA. RanGDP also has been implicated in cell cycle control, specifically in mitotic spindle assembly. In interphase cells, RanGDP is predominately nuclear and thought to be GTP bound, but it is also present in the cytoplasm, probably in the GDP-bound state. NTF2 mediates the nuclear import of RanGDP. NTF2 binds to both RanGDP and FxFG repeat-containing nucleoporins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646615  12 SPQSVGREFVRQYYTLLNKAPNHLHRFYNHNSSYIHGESKLVVGQREIHNRIQQLNFNDCHAKISQVDAQATLGNGVVVQ 91
Cdd:cd00780   1 SAEDVAKAFVQQYYSIFDNNREGLHRLYGDTSMLSREGMKQVTGRDAIVEKLSSLPFQKTKHKITTVDSQPTPSGGVIVM 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 24646615  92 VTGELSNDGQPMRRFTQTFVLAAQsPKKYYVHNDIFRYQD 131
Cdd:cd00780  81 VTGSLKLDEQPPRKFSQTFVLAPQ-NGGYFVLNDIFRFVD 119

RNA recognition motif (RRM) found in ras GTPase-activating protein-binding protein G3BP1, G3BP2 and similar proteins; This subfamily corresponds to the RRM domain in the G3BP family of RNA-binding and SH3 domain-binding proteins. G3BP acts at the level of RNA metabolism in response to cell signaling, possibly as RNA transcript stabilizing factors or an RNase. Members include G3BP1, G3BP2 and similar proteins. These proteins associate directly with the SH3 domain of GTPase-activating protein (GAP), which functions as an inhibitor of Ras. They all contain an N-terminal nuclear transfer factor 2 (NTF2)-like domain, an acidic domain, a domain containing PXXP motif(s), an RNA recognition motif (RRM), and an Arg-Gly-rich region (RGG-rich region, or arginine methylation motif).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646615 490 GDNQQLFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKVPPgmrsplNYGFITYDDPEAVQKCLANCPLYFpensP 569
Cdd:cd12229   1 PDNHQLFVGNLPHDITEDELKEFFSRFGNVLELRINSKGGGGRLP------NFGFVVFDDPEAVQKILANKPIMF----R 70

                        90
                ....*....|.
gi 24646615 570 DGQKLNVEEKK 580
Cdd:cd12229  71 GEHRLNVEEKK 81

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24646615   495 LFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKvppgmrsPLNYGFITYDDPEAVQKCLANCP 561
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRDETGR-------SKGFAFVEFEDEEDAEKAIEALN 60

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 24646615   481 RRSSNTQQFGDnqqLFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKVppgmrspLNYGFITYDDPEAVQKCLANC 560
Cdd:TIGR01628 170 REAAPLKKFTN---LYVKNLDPSVNEDKLRELFAKFGEITSAAVMKDGSGRS-------RGFAFVNFEKHEDAAKAVEEM 239

                          90       100       110
                  ....*....|....*....|....*....|...
gi 24646615   561 PLYFPENSPDGQKLNVEEKKPRVRndmvpRQQI 593
Cdd:TIGR01628 240 NGKKIGLAKEGKKLYVGRAQKRAE-----REAE 267

Nuclear transport factor 2 (NTF2) domain plays an important role in the trafficking of macromolecules, ions and small molecules between the cytoplasm and nucleus. This bi-directional transport of macromolecules across the nuclear envelope requires many soluble factors that includes GDP-binding protein Ran (RanGDP). RanGDP is required for both import and export of proteins and poly(A) RNA. RanGDP also has been implicated in cell cycle control, specifically in mitotic spindle assembly. In interphase cells, RanGDP is predominately nuclear and thought to be GTP bound, but it is also present in the cytoplasm, probably in the GDP-bound state. NTF2 mediates the nuclear import of RanGDP. NTF2 binds to both RanGDP and FxFG repeat-containing nucleoporins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646615  12 SPQSVGREFVRQYYTLLNKAPNHLHRFYNHNSSYIHGESKLVVGQREIHNRIQQLNFNDCHAKISQVDAQATLGNGVVVQ 91
Cdd:cd00780   1 SAEDVAKAFVQQYYSIFDNNREGLHRLYGDTSMLSREGMKQVTGRDAIVEKLSSLPFQKTKHKITTVDSQPTPSGGVIVM 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 24646615  92 VTGELSNDGQPMRRFTQTFVLAAQsPKKYYVHNDIFRYQD 131
Cdd:cd00780  81 VTGSLKLDEQPPRKFSQTFVLAPQ-NGGYFVLNDIFRFVD 119

RNA recognition motif (RRM) found in ras GTPase-activating protein-binding protein G3BP1, G3BP2 and similar proteins; This subfamily corresponds to the RRM domain in the G3BP family of RNA-binding and SH3 domain-binding proteins. G3BP acts at the level of RNA metabolism in response to cell signaling, possibly as RNA transcript stabilizing factors or an RNase. Members include G3BP1, G3BP2 and similar proteins. These proteins associate directly with the SH3 domain of GTPase-activating protein (GAP), which functions as an inhibitor of Ras. They all contain an N-terminal nuclear transfer factor 2 (NTF2)-like domain, an acidic domain, a domain containing PXXP motif(s), an RNA recognition motif (RRM), and an Arg-Gly-rich region (RGG-rich region, or arginine methylation motif).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646615 490 GDNQQLFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKVPPgmrsplNYGFITYDDPEAVQKCLANCPLYFpensP 569
Cdd:cd12229   1 PDNHQLFVGNLPHDITEDELKEFFSRFGNVLELRINSKGGGGRLP------NFGFVVFDDPEAVQKILANKPIMF----R 70

                        90
                ....*....|.
gi 24646615 570 DGQKLNVEEKK 580
Cdd:cd12229  71 GEHRLNVEEKK 81

RNA recognition motif (RRM) found in ras GTPase-activating protein-binding protein 2 (G3BP2) and similar proteins; This subgroup corresponds to the RRM of G3BP2, also termed GAP SH3 domain-binding protein 2, a cytoplasmic protein that interacts with both IkappaBalpha and IkappaBalpha/NF-kappaB complexes, indicating that G3BP2 may play a role in the control of nucleocytoplasmic distribution of IkappaBalpha and cytoplasmic anchoring of the IkappaBalpha/NF-kappaB complex. G3BP2 contains an N-terminal nuclear transfer factor 2 (NTF2)-like domain, an acidic domain, a domain containing five PXXP motifs, an RNA recognition motif (RRM domain), and an Arg-Gly-rich region (RGG-rich region, or arginine methylation motif). It binds to the SH3 domain of RasGAP, a multi-functional protein controlling Ras activity, through its N-terminal NTF2-like domain. The acidic domain is sufficient for the interaction of G3BP2 with the IkappaBalpha cytoplasmic retention sequence. Furthermore, G3BP2 might influence stability or translational efficiency of particular mRNAs by binding to RNA-containing structures within the cytoplasm through its RNA-binding domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646615 488 QFGDNQQLFLGNIPHHASEDDLREIFSRFGNVLELRILSKA-GNKVPpgmrsplNYGFITYDDPEAVQKCLANCPLYFPE 566
Cdd:cd12464   1 RYPDSHQLFVGNLPHDIDENELKEFFMSFGNVVELRINTKGvGGKLP-------NFGFVVFDDSDPVQRILNAKPIMFRG 73

                        90
                ....*....|....
gi 24646615 567 NSpdgqKLNVEEKK 580
Cdd:cd12464  74 EV----RLNVEEKK 83

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 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKvppgmrsPLNYGFITYDDPEAVQKCLANcplyFPENSPDGQKL 574
Cdd:cd00590   1 LFVGNLPPDTTEEDLRELFSKFGEVVSVRIVRDRDGK-------SKGFAFVEFESPEDAEKALEA----LNGTELGGRPL 69

                ...
gi 24646615 575 NVE 577
Cdd:cd00590  70 KVS 72

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 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRIL-SKAGnkVPPGmrsplnYGFITYDDPEAVQKCLANCP-LYFpenspDGQ 572
Cdd:cd12412   5 IFVGGIDWDTTEEELREFFSKFGKVKDVKIIkDRAG--VSKG------YGFVTFETQEDAEKIQKWGAnLVF-----KGK 71

                ....
gi 24646615 573 KLNV 576
Cdd:cd12412  72 KLNV 75

RNA recognition motif (RRM) found in Saccharomyces cerevisiae nucleolar protein 6 (Nop6) and similar proteins; This subfamily corresponds to the RRM of Nop6, also known as Ydl213c, a component of 90S pre-ribosomal particles in yeast S. cerevisiae. It is enriched in the nucleolus and is required for 40S ribosomal subunit biogenesis. Nop6 is a non-essential putative RNA-binding protein with two N-terminal putative nuclear localisation sequences (NLS-1 and NLS-2) and an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). It binds to the pre-rRNA early during transcription and plays an essential role in pre-rRNA processing.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKVPPGmrsplnYGFITYDDPEAVQKCLAncplyFPENSPDGQKL 574
Cdd:cd12400   3 LFVGNLPYDTTAEDLKEHFKKAGEPPSVRLLTDKKTGKSKG------CAFVEFDNQKALQKALK-----LHHTSLGGRKI 71

                ...
gi 24646615 575 NVE 577
Cdd:cd12400  72 NVE 74

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKVPPGmrsplnYGFITYDDPEAVQKCLAN 559
Cdd:cd12316   2 LFVRNLPFTATEDELRELFEAFGKISEVHIPLDKQTKRSKG------FAFVLFVIPEDAVKAYQE 60

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 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKVPPGMrsplnyGFITYDDPEAVQKCL--ANCPLYFPENSPDGQ 572
Cdd:cd12415   3 VFIRNLSFDTTEEDLKEFFSKFGEVKYARIVLDKDTGHSKGT------AFVQFKTKESADKCIeaANDESEDGGLVLDGR 76

                ....
gi 24646615 573 KLNV 576
Cdd:cd12415  77 KLIV 80

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24646615 494 QLFLGNIPHHASEDDLREIFSRFGNVLELRILS--KAGnkvppgmRSPlNYGFITYDDPEAVQKCLANC 560
Cdd:cd21608   1 KLYVGNLSWDTTEDDLRDLFSEFGEVESAKVITdrETG-------RSR-GFGFVTFSTAEAAEAAIDAL 61

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRI-------LSKaGnkvppgmrsplnYGFITYDDPEAVQKCLA---NCPLyf 564
Cdd:COG0724   4 IYVGNLPYSVTEEDLRELFSEYGEVTSVKLitdretgRSR-G------------FGFVEMPDDEEAQAAIEalnGAEL-- 68

                        90
                ....*....|....*...
gi 24646615 565 penspDGQKLNVEEKKPR 582
Cdd:COG0724  69 -----MGRTLKVNEARPR 81

RNA recognition motif 2 (RRM2) found in yeast nuclear polyadenylated RNA-binding protein 4 (Hrp1p or Nab4p) and similar proteins; This subfamily corresponds to the RRM1 of Hrp1p and similar proteins. Hrp1p or Nab4p, also termed cleavage factor IB (CFIB), is a sequence-specific trans-acting factor that is essential for mRNA 3'-end formation in yeast Saccharomyces cerevisiae. It can be UV cross-linked to RNA and specifically recognizes the (UA)6 RNA element required for both, the cleavage and poly(A) addition steps. Moreover, Hrp1p can shuttle between the nucleus and the cytoplasm, and play an additional role in the export of mRNAs to the cytoplasm. Hrp1p also interacts with Rna15p and Rna14p, two components of CF1A. In addition, Hrp1p functions as a factor directly involved in modulating the activity of the nonsense-mediated mRNA decay (NMD) pathway; it binds specifically to a downstream sequence element (DSE)-containing RNA and interacts with Upf1p, a component of the surveillance complex, further triggering the NMD pathway. Hrp1p contains two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an arginine-glycine-rich region harboring repeats of the sequence RGGF/Y.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646615 494 QLFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKVPPGmrsplnYGFITYDDPEAVQKCLANCPLYFpenspDGQK 573
Cdd:cd12330   1 KIFVGGLAPDVTEEEFKEYFEQFGTVVDAVVMLDHDTGRSRG------FGFVTFDSESAVEKVLSKGFHEL-----GGKK 69

                ....*....
gi 24646615 574 LNVEEKKPR 582
Cdd:cd12330  70 VEVKRATPK 78

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein R (hnRNP R) and similar proteins; This subfamily corresponds to the RRM1 in hnRNP R, hnRNP Q, APOBEC-1 complementation factor (ACF), and dead end protein homolog 1 (DND1). hnRNP R is a ubiquitously expressed nuclear RNA-binding protein that specifically binds mRNAs with a preference for poly(U) stretches. It has been implicated in mRNA processing and mRNA transport, and also acts as a regulator to modify binding to ribosomes and RNA translation. hnRNP Q is also a ubiquitously expressed nuclear RNA-binding protein. It has been identified as a component of the spliceosome complex, as well as a component of the apobec-1 editosome, and has been implicated in the regulation of specific mRNA transport. ACF is an RNA-binding subunit of a core complex that interacts with apoB mRNA to facilitate C to U RNA editing. It may also act as an apoB mRNA recognition factor and chaperone, and play a key role in cell growth and differentiation. DND1 is essential for maintaining viable germ cells in vertebrates. It interacts with the 3'-untranslated region (3'-UTR) of multiple messenger RNAs (mRNAs) and prevents micro-RNA (miRNA) mediated repression of mRNA. This family also includes two functionally unknown RNA-binding proteins, RBM46 and RBM47. All members in this family, except for DND1, contain three conserved RNA recognition motifs (RRMs); DND1 harbors only two RRMs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646615 494 QLFLGNIPHHASEDDLREIFSRFGNVLELRIlskagnkvppgMRSPLN----YGFITYDDPEAVQKCLANCPLYfpENSP 569
Cdd:cd12249   3 EVFVGKIPRDVFEDELVPLFEKCGKIYELRL-----------MMDFSGlnrgYAFVTYTNKEAAQRAVKTLNNY--EIRP 69

                ....*...
gi 24646615 570 dGQKLNVE 577
Cdd:cd12249  70 -GKLLGVC 76

RNA recognition motif (RRM) found in eukaryotic RNA-binding protein 25 and similar proteins; This subfamily corresponds to the RRM of RBM25, also termed Arg/Glu/Asp-rich protein of 120 kDa (RED120), or protein S164, or RNA-binding region-containing protein 7, an evolutionary-conserved splicing coactivator SRm160 (SR-related nuclear matrix protein of 160 kDa, )-interacting protein. RBM25 belongs to a family of RNA-binding proteins containing a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), at the N-terminus, a RE/RD-rich (ER) central region, and a C-terminal proline-tryptophan-isoleucine (PWI) motif. It localizes to the nuclear speckles and associates with multiple splicing components, including splicing cofactors SRm160/300, U snRNAs, assembled splicing complexes, and spliced mRNAs. It may play an important role in pre-mRNA processing by coupling splicing with mRNA 3'-end formation. Additional research indicates that RBM25 is one of the RNA-binding regulators that direct the alternative splicing of apoptotic factors. It can activate proapoptotic Bcl-xS 5'ss by binding to the exonic splicing enhancer, CGGGCA, and stabilize the pre-mRNA-U1 snRNP through interaction with hLuc7A, a U1 snRNP-associated factor.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKvppgmrsPLNYGFITYDDPEAVQKCL 557
Cdd:cd12446   3 VFVGNIPDDVSDDFIRQLLEKCGKVLSWKRVQDPSGK-------LKAFGFCEFEDPEGALRAL 58

RNA recognition motif 1 (RRM1) found in RNA-binding protein Musashi homolog Musashi-1, Musashi-2 and similar proteins; This subfamily corresponds to the RRM1 in Musashi-1 and Musashi-2. Musashi-1 (also termed Msi1) is a neural RNA-binding protein putatively expressed in central nervous system (CNS) stem cells and neural progenitor cells, and associated with asymmetric divisions in neural progenitor cells. It is evolutionarily conserved from invertebrates to vertebrates. Musashi-1 is a homolog of Drosophila Musashi and Xenopus laevis nervous system-specific RNP protein-1 (Nrp-1). It has been implicated in the maintenance of the stem-cell state, differentiation, and tumorigenesis. It translationally regulates the expression of a mammalian numb gene by binding to the 3'-untranslated region of mRNA of Numb, encoding a membrane-associated inhibitor of Notch signaling, and further influences neural development. Moreover, Musashi-1 represses translation by interacting with the poly(A)-binding protein and competes for binding of the eukaryotic initiation factor-4G (eIF-4G). Musashi-2 (also termed Msi2) has been identified as a regulator of the hematopoietic stem cell (HSC) compartment and of leukemic stem cells after transplantation of cells with loss and gain of function of the gene. It influences proliferation and differentiation of HSCs and myeloid progenitors, and further modulates normal hematopoiesis and promotes aggressive myeloid leukemia. Both, Musashi-1 and Musashi-2, contain two conserved N-terminal tandem RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), along with other domains of unknown function.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24646615 494 QLFLGNIPHHASEDDLREIFSRFGNVLELRIlskagnkvppgMRSPLN-----YGFITYDDPEAVQKCLANCP 561
Cdd:cd12576   1 KMFIGGLSWQTTPEGLREYFSKFGEITECMV-----------MRDPTTkrsrgFGFVTFSDPASVDKVLAQGP 62

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

                        10        20        30
                ....*....|....*....|....*....|.
gi 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRIL 525
Cdd:cd12361   2 LFVGMIPKTASEEDVRPLFEQFGNIEEVQIL 32

RNA recognition motif 1 (RRM1) and 2 (RRM2) found in RRM-containing coactivator activator/modulator (CoAA) and similar proteins; This subfamily corresponds to the RRM in CoAA (also known as RBM14 or PSP2) and RNA-binding protein 4 (RBM4). CoAA is a heterogeneous nuclear ribonucleoprotein (hnRNP)-like protein identified as a nuclear receptor coactivator. It mediates transcriptional coactivation and RNA splicing effects in a promoter-preferential manner, and is enhanced by thyroid hormone receptor-binding protein (TRBP). CoAA contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a TRBP-interacting domain. RBM4 is a ubiquitously expressed splicing factor with two isoforms, RBM4A (also known as Lark homolog) and RBM4B (also known as RBM30), which are very similar in structure and sequence. RBM4 may also function as a translational regulator of stress-associated mRNAs as well as play a role in micro-RNA-mediated gene regulation. RBM4 contains two N-terminal RRMs, a CCHC-type zinc finger, and three alanine-rich regions within their C-terminal regions. This family also includes Drosophila RNA-binding protein lark (Dlark), a homolog of human RBM4. It plays an important role in embryonic development and in the circadian regulation of adult eclosion. Dlark shares high sequence similarity with RBM4 at the N-terminal region. However, Dlark has three proline-rich segments instead of three alanine-rich segments within the C-terminal region.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRILSkagnkvppgmrsplNYGFITYDDPEAVQKCLANCplyfpENSP-DGQK 573
Cdd:cd12343   2 IFVGNLPDAATSEELRALFEKYGKVTECDIVK--------------NYAFVHMEKEEDAEDAIKAL-----NGYEfMGSR 62

                ....
gi 24646615 574 LNVE 577
Cdd:cd12343  63 INVE 66

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKVPPGmrsplnYGFITYDDPEAVQKCL 557
Cdd:cd12448   1 LFVGNLPFSATQDALYEAFSQHGSIVSVRLPTDRETGQPKG------FGYVDFSTIDSAEAAI 57

RNA recognition motif in nucleolar protein interacting with the FHA domain of pKI-67 (NIFK) and similar proteins; This subgroup corresponds to the RRM of NIFK and Nop15p. NIFK, also termed MKI67 FHA domain-interacting nucleolar phosphoprotein, or nucleolar phosphoprotein Nopp34, is a putative RNA-binding protein interacting with the forkhead associated (FHA) domain of pKi-67 antigen in a mitosis-specific and phosphorylation-dependent manner. It is nucleolar in interphase but associates with condensed mitotic chromosomes. This family also includes Saccharomyces cerevisiae YNL110C gene encoding ribosome biogenesis protein 15 (Nop15p), also termed nucleolar protein 15. Both, NIFK and Nop15p, contain an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRIL--SKAGNkvppgmrsPLNYGFITYDDPE 551
Cdd:cd12307   2 VYIGHLPHGFYEPELRKYFSQFGTVTRLRLSrsKKTGK--------SKGYAFVEFEDPE 52

RNA recognition motif 1 (RRM1) found in Schizosaccharomyces pombe meiotically up-regulated gene 28 protein (Mug28) and similar proteins; Mug28 is a meiosis-specific protein that regulates spore wall formation. 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646615 492 NQQLFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKVpPGMRSPLNYGFITYDDPEAVQKCL--ANCPLYfpensp 569
Cdd:cd21620   1 ERSLYVGNLPQTCQSEDLIILFEPYGNVCGAHIASRKKVKV-SWVKPSKLFAFVEFETKEAATTAIvlLNGITY------ 73

                ....*...
gi 24646615 570 DGQKLNVE 577
Cdd:cd21620  74 MGCQLKVE 81

RNA recognition motif 2 (RRM2) found in yeast multiple RNA-binding domain-containing protein 1 (MRD1) and similar proteins; This subgroup corresponds to the RRM2 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). It is essential for the initial processing at the A0-A2 cleavage sites in the 35 S pre-rRNA. MRD1 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24646615 491 DNQQLFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKVPPGmrsplnYGFITYDDPE-AVQ 554
Cdd:cd12566   1 ETGRLFLRNLPYSTKEDDLQKLFSKFGEVSEVHVPIDKKTKKSKG------FAYVLFLDPEdAVQ 59

RNA recognition motif 3 (RRM3) found in RNA-binding protein 19 (RBM19) and similar proteins; This subgroup corresponds to the RRM3 of RBM19, also termed RNA-binding domain-1 (RBD-1), which is a nucleolar protein conserved in eukaryotes. It is involved in ribosome biogenesis by processing rRNA. In addition, it is essential for preimplantation development. RBM19 has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24646615 494 QLFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKVPPGmrsplnYGFITYDDPEAVQKCLA 558
Cdd:cd12567   4 RLFVRNLPYTCTEEDLEKLFSKYGPLSEVHFPIDSLTKKPKG------FAFVTYMIPEHAVKAYA 62

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein A/B (hnRNP A/B) and similar proteins; This subgroup corresponds to the RRM1 of hnRNP A/B, also termed APOBEC1-binding protein 1 (ABBP-1), which is an RNA unwinding protein with a high affinity for G- followed by U-rich regions. hnRNP A/B has also been identified as an APOBEC1-binding protein that interacts with apolipoprotein B (apoB) mRNA transcripts around the editing site and thus plays an important role in apoB mRNA editing. hnRNP A/B contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long C-terminal glycine-rich domain that contains a potential ATP/GTP binding loop.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24646615 491 DNQQLFLGNIPHHASEDDLREIFSRFGNVLELRIlskagnKVPPGMRSPLNYGFITYDDPEAVQKCLA 558
Cdd:cd12757   3 DAGKMFVGGLSWDTSKKDLKDYFTKFGEVVDCTI------KMDPNTGRSRGFGFILFKDAASVDKVLE 64

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 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKvppgMRsplNYGFITYDDPEAVQKCLAncplYFPENSPDGQKL 574
Cdd:cd12565   3 IIVKNLPKYVTEKRLKEHFSKKGEITDVKVMRTKDGK----SR---RFGFIGFKSEEEAQKAVK----YFNKTFIDTSKI 71

                ...
gi 24646615 575 NVE 577
Cdd:cd12565  72 SVE 74

RNA recognition motif (RRM) found in cold inducible RNA binding protein (CIRBP), RNA binding motif protein 3 (RBM3) and similar proteins; This subfamily corresponds to the RRM domain of two structurally related heterogenous nuclear ribonucleoproteins, CIRBP (also termed CIRP or A18 hnRNP) and RBM3 (also termed RNPL), both of which belong to a highly conserved cold shock proteins family. The cold shock proteins can be induced after exposure to a moderate cold-shock and other cellular stresses such as UV radiation and hypoxia. CIRBP and RBM3 may function in posttranscriptional regulation of gene expression by binding to different transcripts, thus allowing the cell to response rapidly to environmental signals. However, the kinetics and degree of cold induction are different between CIRBP and RBM3. Tissue distribution of their expression is different. CIRBP and RBM3 may be differentially regulated under physiological and stress conditions and may play distinct roles in cold responses of cells. CIRBP, also termed glycine-rich RNA-binding protein CIRP, is localized in the nucleus and mediates the cold-induced suppression of cell cycle progression. CIRBP also binds DNA and possibly serves as a chaperone that assists in the folding/unfolding, assembly/disassembly and transport of various proteins. RBM3 may enhance global protein synthesis and the formation of active polysomes while reducing the levels of ribonucleoprotein complexes containing microRNAs. RBM3 may also serve to prevent the loss of muscle mass by its ability to decrease cell death. Furthermore, RBM3 may be essential for cell proliferation and mitosis. Both, CIRBP and RBM3, contain an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), that is involved in RNA binding, and C-terminal glycine-rich domain (RGG motif) that probably enhances RNA-binding via protein-protein and/or protein-RNA interactions. Like CIRBP, RBM3 can also bind to both RNA and DNA via its RRM domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646615 494 QLFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKVPPGmrsplnYGFITYDDPEAVQKCLancpLYFPENSPDGQK 573
Cdd:cd12449   2 KLFVGGLSFDTNEQSLEEVFSKYGQISEVVVVKDRETQRSRG------FGFVTFENPDDAKDAM----MAMNGKSLDGRQ 71

                ....*..
gi 24646615 574 LNVEEKK 580
Cdd:cd12449  72 IRVDQAG 78

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRIlskagNKVPPGMRSPlNYGFITYDDPEAVQKCLAN 559
Cdd:cd12284   1 LYVGSLHFNITEDMLRGIFEPFGKIEFVQL-----QKDPETGRSK-GYGFIQFRDAEDAKKALEQ 59

RNA recognition motif 1 (RRM1) found in vertebrate RNA-binding protein 4 (RBM4); This subgroup corresponds to the RRM1 of RBM4, a ubiquitously expressed splicing factor that has two isoforms, RBM4A (also known as Lark homolog) and RBM4B (also known as RBM30), which are very similar in structure and sequence. RBM4 may function as a translational regulator of stress-associated mRNAs and also plays a role in micro-RNA-mediated gene regulation. RBM4 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), a CCHC-type zinc finger, and three alanine-rich regions within their C-terminal regions. The C-terminal region may be crucial for nuclear localization and protein-protein interaction. The RRMs, in combination with the C-terminal region, are responsible for the splicing function of RBM4.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646615 494 QLFLGNIPHHASEDDLREIFSRFGNVLELRILSkagnkvppgmrsplNYGFITYDDPEAVQKCLANCPLYFPENSPdgqk 573
Cdd:cd12606   2 KLFIGNLPREATEEEIRSLFEQYGKVTECDIIK--------------NYGFVHMEDKSAADEAIRNLHHYKLHGVA---- 63

                ....
gi 24646615 574 LNVE 577
Cdd:cd12606  64 INVE 67

RNA recognition motif 1 (RRM1) found in yeast nuclear polyadenylated RNA-binding protein 4 (Hrp1p or Nab4p) and similar proteins; This subfamily corresponds to the RRM1 of Hrp1p and similar proteins. Hrp1p or Nab4p, also termed cleavage factor IB (CFIB), is a sequence-specific trans-acting factor that is essential for mRNA 3'-end formation in yeast Saccharomyces cerevisiae. It can be UV cross-linked to RNA and specifically recognizes the (UA)6 RNA element required for both, the cleavage and poly(A) addition, steps. Moreover, Hrp1p can shuttle between the nucleus and the cytoplasm, and play an additional role in the export of mRNAs to the cytoplasm. Hrp1p also interacts with Rna15p and Rna14p, two components of CF1A. In addition, Hrp1p functions as a factor directly involved in modulating the activity of the nonsense-mediated mRNA decay (NMD) pathway. It binds specifically to a downstream sequence element (DSE)-containing RNA and interacts with Upf1p, a component of the surveillance complex, further triggering the NMD pathway. Hrp1p contains two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an arginine-glycine-rich region harboring repeats of the sequence RGGF/Y.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRILskagnKVPPGMRSPlNYGFITYDDPEAVQKCLANcplyfpENSPDGQKL 574
Cdd:cd12577   1 MFIGGLNWDTTEEGLRDYFSQFGTVVDCTIM-----KDSATGRSR-GFGFLTFEDPSSVNEVMKK------EHVLDGKII 68

                ....*...
gi 24646615 575 NVEEKKPR 582
Cdd:cd12577  69 DPKRAIPR 76

RNA recognition motif (RRM) found in heterogeneous nuclear ribonucleoprotein C (hnRNP C)-related proteins; This subfamily corresponds to the RRM in the hnRNP C-related protein family, including hnRNP C proteins, Raly, and Raly-like protein (RALYL). hnRNP C proteins, C1 and C2, are produced by a single coding sequence. They are the major constituents of the heterogeneous nuclear RNA (hnRNA) ribonucleoprotein (hnRNP) complex in vertebrates. They bind hnRNA tightly, suggesting a central role in the formation of the ubiquitous hnRNP complex; they are involved in the packaging of the hnRNA in the nucleus and in processing of pre-mRNA such as splicing and 3'-end formation. Raly, also termed autoantigen p542, is an RNA-binding protein that may play a critical role in embryonic development. The biological role of RALYL remains unclear. It shows high sequence homology with hnRNP C proteins and Raly. Members of this family are characterized by an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal auxiliary domain. The Raly proteins contain a glycine/serine-rich stretch within the C-terminal regions, which is absent in the hnRNP C proteins. Thus, the Raly proteins represent a newly identified class of evolutionarily conserved autoepitopes.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 24646615 495 LFLGNIP-HHASEDDLREIFSRFGNVLELRILSkagnkvppgmrsplNYGFITYDDPE 551
Cdd:cd12341   3 IFVGNLPtDQMTKEDLEEIFSKYGKILGISLHK--------------GYGFVQFDNEE 46

RNA recognition motif 1 (RRM1) found in CUGBP Elav-like family member CELF-3, CELF-4, CELF-5, CELF-6 and similar proteins; This subfamily corresponds to the RRM1 of CELF-3, CELF-4, CELF-5, CELF-6, all of which belong to the CUGBP1 and ETR-3-like factors (CELF) or BRUNOL (Bruno-like) family of RNA-binding proteins that display dual nuclear and cytoplasmic localizations and have been implicated in the regulation of pre-mRNA splicing and in the control of mRNA translation and deadenylation. CELF-3, expressed in brain and testis only, is also known as bruno-like protein 1 (BRUNOL-1), or CAG repeat protein 4, or CUG-BP- and ETR-3-like factor 3, or embryonic lethal abnormal vision (ELAV)-type RNA-binding protein 1 (ETR-1), or expanded repeat domain protein CAG/CTG 4, or trinucleotide repeat-containing gene 4 protein (TNRC4). It plays an important role in the pathogenesis of tauopathies. CELF-3 contains three highly conserved RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C-terminus of the protein.The effect of CELF-3 on tau splicing is mediated mainly by the RNA-binding activity of RRM2. The divergent linker region might mediate the interaction of CELF-3 with other proteins regulating its activity or involved in target recognition. CELF-4, highly expressed throughout the brain and in glandular tissues, moderately expressed in heart, skeletal muscle, and liver, is also known as bruno-like protein 4 (BRUNOL-4), or CUG-BP- and ETR-3-like factor 4. Like CELF-3, CELF-4 also contain three highly conserved RRMs. The splicing activation or repression activity of CELF-4 on some specific substrates is mediated by its RRM1/RRM2. On the other hand, both RRM1 and RRM2 of CELF-4 can activate cardiac troponin T (cTNT) exon 5 inclusion. CELF-5, expressed in brain, is also known as bruno-like protein 5 (BRUNOL-5), or CUG-BP- and ETR-3-like factor 5. Although its biological role remains unclear, CELF-5 shares same domain architecture with CELF-3. CELF-6, strongly expressed in kidney, brain, and testis, is also known as bruno-like protein 6 (BRUNOL-6), or CUG-BP- and ETR-3-like factor 6. It activates exon inclusion of a cardiac troponin T minigene in transient transfection assays in an muscle-specific splicing enhancer (MSE)-dependent manner and can activate inclusion via multiple copies of a single element, MSE2. CELF-6 also promotes skipping of exon 11 of insulin receptor, a known target of CELF activity that is expressed in kidney. In additiona to three highly conserved RRMs, CELF-6 also possesses numerous potential phosphorylation sites, a potential nuclear localization signal (NLS) at the C terminus, and an alanine-rich region within the divergent linker region.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24646615 491 DNQQLFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKVPPGMrsplnyGFITYDDPEAVQKC 556
Cdd:cd12632   4 DAIKLFIGQIPRNLEEKDLRPLFEQFGKIYELTVLKDKYTGMHKGC------AFLTYCARESALKA 63

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 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRILSKAGNKVPPGmrsplnYGFITYDDPEAVQKCLANCPLYfpenSPDGQKL 574
Cdd:cd12362   1 LFVYHLPNEFTDQDLYQLFAPFGNVVSAKVFVDKNTGRSKG------FGFVSYDNPLSAQAAIKAMNGF----QVGGKRL 70

                ...
gi 24646615 575 NVE 577
Cdd:cd12362  71 KVQ 73

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins; This subfamily corresponds to the RRM1 in hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins. hnRNP D0 is a UUAG-specific nuclear RNA binding protein that may be involved in pre-mRNA splicing and telomere elongation. hnRNP A/B is an RNA unwinding protein with a high affinity for G- followed by U-rich regions. hnRNP A/B has also been identified as an APOBEC1-binding protein that interacts with apolipoprotein B (apoB) mRNA transcripts around the editing site and thus plays an important role in apoB mRNA editing. hnRNP DL (or hnRNP D-like) is a dual functional protein that possesses DNA- and RNA-binding properties. It has been implicated in mRNA biogenesis at the transcriptional and post-transcriptional levels. All members in this family contain two putative RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glycine- and tyrosine-rich C-terminus.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24646615 495 LFLGNIPHHASEDDLREIFSRFGNVLELRIlskagnKVPPGMRSPLNYGFITYDDPEAVQKCL 557
Cdd:cd12575   1 MFIGGLSWDTSKKDLKDYFSKFGEVVDCTI------KLDPVTGRSRGFGFVLFKDAESVDKVL 57