N-terminal SNARE complex binding domain of the complexin family of SNARE regulators; Complexins (CPXs) are small, cytosolic proteins that bind to the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex to regulate synaptic vesicle exocytosis. There are four CPX isoforms: complexin I/synaphin-2, complexin II/synaphin-1, complexin III and complexin IV. CPXs I and II are highly homologous hydrophilic proteins that are enriched in neurons where they colocalize with syntaxin and SNAP25. They regulate the sequential interactions of alpha-SNAP and synaptotagmins with the SNAP receptor during exocytosis. CPXs III and IV are the only CPX isoforms present in retinal ribbon synapses. In addition, CPXs III and IV carry an extension with a functional CAAX-box farnesylation site that is absent in CPXs I and II. Their C-terminal farnesylation regulates their synaptic targeting and modulatory function in transmitter release. They may contribute to the unique release efficacy of retinal sensory neurons. CPXs III and IV can functionally replace CPXs I and II. Most of the invertebrate CPXs are more similar to CPXs I and II than to CPXs III and IV. This model corresponds to the N-terminal region of CPX that is responsible for SNARE complex binding.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1237937874 641 SYEEYQHERLKREEYRRE-YEKRESERAKQRERQRQK 676
Cdd:cd22740     2 EEEEYQEALREEEEERDAkHAQMKAERAAMRQHIRDK 38

RNA recognition motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1237937874  683 VIYVGKIRPDTTRTELRDRFEVFGEIEECTV-----NLRDDGYGFITYRYTCDAFAALE--NGYTL 741
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLvrdkeTGKSKGFAFVEFESEEDAEKALEalNGKEL 66

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937874 658 EYEKRESERAKQRERQRQKAIEERRVIYVGKIRPDTTRTELRDRFEVFGEIEECTVNL-----RDDGYGFITYRYTCDAF 732
Cdd:TIGR01622 191 EAEKNRAARAATETSGHHPNSIPFHRLYVGNLHFNITEQDLRQIFEPFGEIEFVQLQKdpetgRSKGYGFIQFRDAEQAK 270

                          90
                  ....*....|.
gi 1237937874 733 AALE--NGYTL 741
Cdd:TIGR01622 271 EALEkmNGFEL 281

N-terminal SNARE complex binding domain of the complexin family of SNARE regulators; Complexins (CPXs) are small, cytosolic proteins that bind to the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex to regulate synaptic vesicle exocytosis. There are four CPX isoforms: complexin I/synaphin-2, complexin II/synaphin-1, complexin III and complexin IV. CPXs I and II are highly homologous hydrophilic proteins that are enriched in neurons where they colocalize with syntaxin and SNAP25. They regulate the sequential interactions of alpha-SNAP and synaptotagmins with the SNAP receptor during exocytosis. CPXs III and IV are the only CPX isoforms present in retinal ribbon synapses. In addition, CPXs III and IV carry an extension with a functional CAAX-box farnesylation site that is absent in CPXs I and II. Their C-terminal farnesylation regulates their synaptic targeting and modulatory function in transmitter release. They may contribute to the unique release efficacy of retinal sensory neurons. CPXs III and IV can functionally replace CPXs I and II. Most of the invertebrate CPXs are more similar to CPXs I and II than to CPXs III and IV. This model corresponds to the N-terminal region of CPX that is responsible for SNARE complex binding.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1237937874 641 SYEEYQHERLKREEYRRE-YEKRESERAKQRERQRQK 676
Cdd:cd22740     2 EEEEYQEALREEEEERDAkHAQMKAERAAMRQHIRDK 38

RNA recognition motif (RRM) found in the peroxisome proliferator-activated receptor gamma coactivator 1A (PGC-1alpha) family of regulated coactivators; This subfamily corresponds to the RRM of PGC-1alpha, PGC-1beta, and PGC-1-related coactivator (PRC), which serve as mediators between environmental or endogenous signals and the transcriptional machinery governing mitochondrial biogenesis. They play an important integrative role in the control of respiratory gene expression through interacting with a number of transcription factors, such as NRF-1, NRF-2, ERR, CREB and YY1. All family members are multi-domain proteins containing the N-terminal activation domain, an LXXLL coactivator signature, a tetrapeptide motif (DHDY) responsible for HCF binding, and an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). In contrast to PGC-1alpha and PRC, PGC-1beta possesses two glutamic/aspartic acid-rich acidic domains, but lacks most of the arginine/serine (SR)-rich domain that is responsible for the regulation of RNA processing.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937874 680 ERRVIYVGKIRPDTTRTELRDRFEVFGEIEECTVNLRDDG--YGFITYRYTCDAFAALENGYTLRRSNETDFELYFCGRK 757
Cdd:cd12357     1 ERRVVYVGKLEQDTTRSELRRRFEVFGEIEECTVHFRERGdkYGFVTYRYSEDAFLALENGHDLRKRNEPMFDLSFGGRR 80

                          90
                  ....*....|.
gi 1237937874 758 QFFKSNYADLD 768
Cdd:cd12357    81 AFCKSSYADLD 91

RNA recognition motif (RRM) found in peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC-1-beta) and similar proteins; This subfamily corresponds to the RRM of PGC-1beta, also termed PPAR-gamma coactivator 1-beta, or PPARGC-1-beta, or PGC-1-related estrogen receptor alpha coactivator, which is one of the members of PGC-1 transcriptional coactivators family, including PGC-1alpha and PGC-1-related coactivator (PRC). PGC-1beta plays a nonredundant role in controlling mitochondrial oxidative energy metabolism and affects both, insulin sensitivity and mitochondrial biogenesis, and functions in a number of oxidative tissues. It is involved in maintaining baseline mitochondrial function and cardiac contractile function following pressure overload hypertrophy by preserving glucose metabolism and preventing oxidative stress. PGC-1beta induces hypertriglyceridemia in response to dietary fats through activating hepatic lipogenesis and lipoprotein secretion. It can stimulate apolipoprotein C3 (APOC3) expression, further mediating hypolipidemic effect of nicotinic acid. PGC-1beta also drives nuclear respiratory factor 1 (NRF-1) target gene expression and NRF-1 and estrogen related receptor alpha (ERRalpha)-dependent mitochondrial biogenesis. The modulation of the expression of PGC-1beta can trigger ERRalpha-induced adipogenesis. PGC-1beta is also a potent regulator inducing angiogenesis in skeletal muscle. The transcriptional activity of PGC-1beta can be increased through binding to host cell factor (HCF), a cellular protein involved in herpes simplex virus (HSV) infection and cell cycle regulation. PGC-1beta is a multi-domain protein containing an N-terminal activation domain, an LXXLL coactivator signature, a tetrapeptide motif (DHDY) responsible for HCF binding, two glutamic/aspartic acid-rich acidic domains, and an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). In contrast to PGC-1alpha, PGC-1beta lacks most of the arginine/serine (SR)-rich domain that is responsible for the regulation of RNA processing.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937874 675 QKAIEERRVIYVGKIRPDTTRTELRDRFEVFGEIEECTV---NLRDDGYGFITYRYTCDAFAALENGYTLRRSNETDFEL 751
Cdd:cd12356     1 EKAIGEGRVVYIRNLSSSMSSNELKRRFEVFGEITECCVlsrSNRGEKYGFITYRDSEHAALSLQKGASLRKRNEPSFQL 80

                          90
                  ....*....|....*..
gi 1237937874 752 YFCGRKQFFKSNYADLD 768
Cdd:cd12356    81 SYGGLRHFFWTRYTDLD 97

RNA recognition motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1237937874  683 VIYVGKIRPDTTRTELRDRFEVFGEIEECTV-----NLRDDGYGFITYRYTCDAFAALE--NGYTL 741
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLvrdkeTGKSKGFAFVEFESEEDAEKALEalNGKEL 66

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECT-VNLRD---DGYGFITYRYTCDAFAALENGytlrrsnetdFELYFCGRK 757
Cdd:cd12412     5 IFVGGIDWDTTEEELREFFSKFGKVKDVKiIKDRAgvsKGYGFVTFETQEDAEKIQKWG----------ANLVFKGKK 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECTV----NLRDDGYGFITYRYTCDAFAALE--NGYTLR 742
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLvrdeTGRSKGFAFVEFEDEEDAEKAIEalNGKELG 65

RNA recognition motif (RRM) found in eukaryotic RNA-binding protein RBM24, RBM38 and similar proteins; This subfamily corresponds to the RRM of RBM24 and RBM38 from vertebrate, SUPpressor family member SUP-12 from Caenorhabditis elegans and similar proteins. Both, RBM24 and RBM38, are preferentially expressed in cardiac and skeletal muscle tissues. They regulate myogenic differentiation by controlling the cell cycle in a p21-dependent or -independent manner. RBM24, also termed RNA-binding region-containing protein 6, interacts with the 3'-untranslated region (UTR) of myogenin mRNA and regulates its stability in C2C12 cells. RBM38, also termed CLL-associated antigen KW-5, or HSRNASEB, or RNA-binding region-containing protein 1(RNPC1), or ssDNA-binding protein SEB4, is a direct target of the p53 family. It is required for maintaining the stability of the basal and stress-induced p21 mRNA by binding to their 3'-UTRs. It also binds the AU-/U-rich elements in p63 3'-UTR and regulates p63 mRNA stability and activity. SUP-12 is a novel tissue-specific splicing factor that controls muscle-specific splicing of the ADF/cofilin pre-mRNA in C. elegans. All family members contain a conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECTV-----NLRDDGYGFITYRYTCDAFAALEN 737
Cdd:cd12384     3 IFVGGLPYHTTDDSLREYFEQFGEIEEAVVitdrqTGKSRGYGFVTMADREAAERACKD 61

RNA recognition motif 2 (RRM2) found in yeast meiotic activator RIM4 and similar proteins; This subfamily corresponds to the RRM2 of RIM4, also termed regulator of IME2 protein 4, a putative RNA binding protein that is expressed at elevated levels early in meiosis. It functions as a meiotic activator required for both the IME1- and IME2-dependent pathways of meiotic gene expression, as well as early events of meiosis, such as meiotic division and recombination, in Saccharomyces cerevisiae. RIM4 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The family also includes a putative RNA-binding protein termed multicopy suppressor of sporulation protein Msa1. It is a putative RNA-binding protein encoded by a novel gene, msa1, from the fission yeast Schizosaccharomyces pombe. Msa1 may be involved in the inhibition of sexual differentiation by controlling the expression of Ste11-regulated genes, possibly through the pheromone-signaling pathway. Like RIM4, Msa1 also contains two RRMs, both of which are essential for the function of Msa1.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1237937874 680 ERRVIYVGKIRPDTTRTELRDRFEVFGEIEECTVNLRDD---GYGFITYRYTCDAFAALEN 737
Cdd:cd12454     2 DKLSIFVGQLDPKTTDSELFRRFSKYGKIVDCKLIKRPEpvnAFAFLRFESEEAAEAAVEE 62

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECTV-----NLRDDGYGFITYRYTCDAFAALEN-------GYTLR 742
Cdd:cd12347     1 LYVGGLAEEVDEKVLHAAFIPFGDIVDIQIpldyeTEKHRGFAFVEFEEAEDAAAAIDNmneselfGRTIR 71

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECTVNlRDDGYGFITYRYTCDAFAA 734
Cdd:cd12332     4 LFVGNLPNDITEEEFKELFQKYGEVSEVFLN-KGKGFGFIRLDTRANAEAA 53

RNA recognition motif 2 (RRM2) found in CUGBP Elav-like family member CELF-3, CELF-4, CELF-5, CELF-6 and similar proteins; This subgroup corresponds to the RRM2 of CELF-3, CELF-4, CELF-5, and 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, being 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, being 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 a 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 addition 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 1237937874 682 RVIYVGKIRPDTTRTELRDRFEVFGEIEECTVnLRD-DGY----GFITYRYTCDAFAALEN 737
Cdd:cd12635     2 RKLFVGMLGKQQSEDDVRRLFEPFGSIEECTI-LRGpDGNskgcAFVKFSSHAEAQAAINA 61

RNA recognition motif 2 (RRM2) found in (U)-binding-splicing factor PUF60 and similar proteins; This subfamily corresponds to the RRM2 of PUF60, also termed FUSE-binding protein-interacting repressor (FBP-interacting repressor or FIR), or Ro-binding protein 1 (RoBP1), or Siah-binding protein 1 (Siah-BP1). PUF60 is an essential splicing factor that functions as a poly-U RNA-binding protein required to reconstitute splicing in depleted nuclear extracts. Its function is enhanced through interaction with U2 auxiliary factor U2AF65. PUF60 also controls human c-myc gene expression by binding and inhibiting the transcription factor far upstream sequence element (FUSE)-binding-protein (FBP), an activator of c-myc promoters. PUF60 contains two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbors another RRM and binds to tryptophan-containing linear peptide motifs (UHM ligand motifs, ULMs) in several nuclear proteins. Research indicates that PUF60 binds FUSE as a dimer, and only the first two RRM domains participate in the single-stranded DNA recognition.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECTVNL-----RDDGYGFITYRYTCDAFAALE--NGYTL 741
Cdd:cd12371     3 IYVASVHPDLSEDDIKSVFEAFGKIKSCSLAPdpetgKHKGYGFIEYENPQSAQDAIAsmNLFDL 67

RNA recognition motif 2 (RRM2) found in granule-associated RNA binding proteins (p40-TIA-1 and TIAR), and yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1; This subfamily corresponds to the RRM3 of TIA-1, TIAR, and PUB1. Nucleolysin TIA-1 isoform p40 (p40-TIA-1 or TIA-1) and nucleolysin TIA-1-related protein (TIAR) are granule-associated RNA binding proteins involved in inducing apoptosis in cytotoxic lymphocyte (CTL) target cells. They share high sequence similarity and are expressed in a wide variety of cell types. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis.TIAR is mainly localized in the nucleus of hematopoietic and nonhematopoietic cells. It is translocated from the nucleus to the cytoplasm in response to exogenous triggers of apoptosis. Both TIA-1 and TIAR bind specifically to poly(A) but not to poly(C) homopolymers. They are composed of three N-terminal highly homologous RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. TIA-1 and TIAR interact with RNAs containing short stretches of uridylates and their RRM2 can mediate the specific binding to uridylate-rich RNAs. The C-terminal auxiliary domain may be responsible for interacting with other proteins. In addition, TIA-1 and TIAR share a potential serine protease-cleavage site (Phe-Val-Arg) localized at the junction between their RNA binding domains and their C-terminal auxiliary domains. This subfamily also includes a yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1, termed ARS consensus-binding protein ACBP-60, or poly uridylate-binding protein, or poly(U)-binding protein, which has been identified as both a heterogeneous nuclear RNA-binding protein (hnRNP) and a cytoplasmic mRNA-binding protein (mRNP). It may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm. PUB1 is distributed in both, the nucleus and the cytoplasm, and binds to poly(A)+ RNA (mRNA or pre-mRNA). Although it is one of the major cellular proteins cross-linked by UV light to polyadenylated RNAs in vivo, PUB1 is nonessential for cell growth in yeast. PUB1 also binds to T-rich single stranded DNA (ssDNA); however, there is no strong evidence implicating PUB1 in the mechanism of DNA replication. PUB1 contains three RRMs, and a GAR motif (glycine and arginine rich stretch) that is located between RRM2 and RRM3.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECTVNlRDDGYGFITY 725
Cdd:cd12354     3 VYVGNITKGLTEALLQQTFSPFGQILEVRVF-PDKGYAFIRF 43

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
                  ....*....|....*....|....*....|....*....|....*....
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECTVnLRDD------GYGFITYR 726
Cdd:cd12576     2 MFIGGLSWQTTPEGLREYFSKFGEITECMV-MRDPttkrsrGFGFVTFS 49

RNA recognition motif 3 (RRM3) found found in type I polyadenylate-binding proteins; This subfamily corresponds to the RRM3 of type I poly(A)-binding proteins (PABPs), highly conserved proteins that bind to the poly(A) tail present at the 3' ends of most eukaryotic mRNAs. They have been implicated in the regulation of poly(A) tail length during the polyadenylation reaction, translation initiation, mRNA stabilization by influencing the rate of deadenylation and inhibition of mRNA decapping. The family represents type I polyadenylate-binding proteins (PABPs), including polyadenylate-binding protein 1 (PABP-1 or PABPC1), polyadenylate-binding protein 3 (PABP-3 or PABPC3), polyadenylate-binding protein 4 (PABP-4 or APP-1 or iPABP), polyadenylate-binding protein 5 (PABP-5 or PABPC5), polyadenylate-binding protein 1-like (PABP-1-like or PABPC1L), polyadenylate-binding protein 1-like 2 (PABPC1L2 or RBM32), polyadenylate-binding protein 4-like (PABP-4-like or PABPC4L), yeast polyadenylate-binding protein, cytoplasmic and nuclear (PABP or ACBP-67), and similar proteins. PABP-1 is an ubiquitously expressed multifunctional protein that may play a role in 3' end formation of mRNA, translation initiation, mRNA stabilization, protection of poly(A) from nuclease activity, mRNA deadenylation, inhibition of mRNA decapping, and mRNP maturation. Although PABP-1 is thought to be a cytoplasmic protein, it is also found in the nucleus. PABP-1 may be involved in nucleocytoplasmic trafficking and utilization of mRNP particles. PABP-1 contains four copies of RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), a less well conserved linker region, and a proline-rich C-terminal conserved domain (CTD). PABP-3 is a testis-specific poly(A)-binding protein specifically expressed in round spermatids. It is mainly found in mammalian and may play an important role in the testis-specific regulation of mRNA homeostasis. PABP-3 shows significant sequence similarity to PABP-1. However, it binds to poly(A) with a lower affinity than PABP-1. PABP-1 possesses an A-rich sequence in its 5'-UTR and allows binding of PABP and blockage of translation of its own mRNA. In contrast, PABP-3 lacks the A-rich sequence in its 5'-UTR. PABP-4 is an inducible poly(A)-binding protein (iPABP) that is primarily localized to the cytoplasm. It shows significant sequence similarity to PABP-1 as well. The RNA binding properties of PABP-1 and PABP-4 appear to be identical. PABP-5 is encoded by PABPC5 gene within the X-specific subinterval, and expressed in fetal brain and in a range of adult tissues in mammalian, such as ovary and testis. It may play an important role in germ cell development. Moreover, unlike other PABPs, PABP-5 contains only four RRMs, but lacks both the linker region and the CTD. PABP-1-like and PABP-1-like 2 are the orthologs of PABP-1. PABP-4-like is the ortholog of PABP-5. Their cellular functions remain unclear. The family also includes the yeast PABP, a conserved poly(A) binding protein containing poly(A) tails that can be attached to the 3'-ends of mRNAs. The yeast PABP and its homologs may play important roles in the initiation of translation and in mRNA decay. Like vertebrate PABP-1, the yeast PABP contains four RRMs, a linker region, and a proline-rich CTD as well. The first two RRMs are mainly responsible for specific binding to poly(A). The proline-rich region may be involved in protein-protein interactions.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECTVnLRDD-----GYGFITYRYTCDAFAALENgytlrrSNETDF---ELYfCG 755
Cdd:cd12380     4 VYVKNFGEDVDDDELKELFEKYGKITSAKV-MKDDsgkskGFGFVNFENHEAAQKAVEE------LNGKELngkKLY-VG 75

                  ...
gi 1237937874 756 RKQ 758
Cdd:cd12380    76 RAQ 78

RNA recognition motif (RRM) found in nucleolar protein 8 (NOL8) and similar proteins; This model corresponds to the RRM of NOL8 (also termed Nop132) encoded by a novel NOL8 gene that is up-regulated in the majority of diffuse-type, but not intestinal-type, gastric cancers. Thus, NOL8 may be a good molecular target for treatment of diffuse-type gastric cancer. Also, NOL8 is a phosphorylated protein that contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), suggesting NOL8 is likely to function as a novel RNA-binding protein. It may be involved in regulation of gene expression at the post-transcriptional level or in ribosome biogenesis in cancer cells.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1237937874 683 VIYVGKIRPDTTRTELRDRFEVFGEIEECTVNLRDD----GYGFITYRYTCDAFA 733
Cdd:cd12226     1 RLFVGGLSPSITEDDLERRFSRFGTVSDVEIIRKKDapdrGFAYIDLRTSEAALQ 55

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein D0 (hnRNP D0) and similar proteins; This subgroup corresponds to the RRM1 of hnRNP D0, also termed AU-rich element RNA-binding protein 1, which is a UUAG-specific nuclear RNA binding protein that may be involved in pre-mRNA splicing and telomere elongation. hnRNP D0 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), in the middle and an RGG box rich in glycine and arginine residues in the C-terminal part. Each of RRMs can bind solely to the UUAG sequence specifically.

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                  ....*....|....*....|....*....|....*....|....*...
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECTVNL-----RDDGYGFITYR 726
Cdd:cd12756     1 MFIGGLSWDTTKKDLKDYFSKFGEVVDCTLKLdpitgRSRGFGFVLFK 48

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937874 658 EYEKRESERAKQRERQRQKAIEERRVIYVGKIRPDTTRTELRDRFEVFGEIEECTVNL-----RDDGYGFITYRYTCDAF 732
Cdd:TIGR01622 191 EAEKNRAARAATETSGHHPNSIPFHRLYVGNLHFNITEQDLRQIFEPFGEIEFVQLQKdpetgRSKGYGFIQFRDAEQAK 270

                          90
                  ....*....|.
gi 1237937874 733 AALE--NGYTL 741
Cdd:TIGR01622 271 EALEkmNGFEL 281

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein A subfamily; This subfamily corresponds to the RRM1 in hnRNP A0, hnRNP A1, hnRNP A2/B1, hnRNP A3 and similar proteins. hnRNP A0 is a low abundance hnRNP protein that has been implicated in mRNA stability in mammalian cells. It has been identified as the substrate for MAPKAP-K2 and may be involved in the lipopolysaccharide (LPS)-induced post-transcriptional regulation of tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase 2 (COX-2) and macrophage inflammatory protein 2 (MIP-2). hnRNP A1 is an abundant eukaryotic nuclear RNA-binding protein that may modulate splice site selection in pre-mRNA splicing. hnRNP A2/B1 is an RNA trafficking response element-binding protein that interacts with the hnRNP A2 response element (A2RE). Many mRNAs, such as myelin basic protein (MBP), myelin-associated oligodendrocytic basic protein (MOBP), carboxyanhydrase II (CAII), microtubule-associated protein tau, and amyloid precursor protein (APP) are trafficked by hnRNP A2/B1. hnRNP A3 is also a RNA trafficking response element-binding protein that participates in the trafficking of A2RE-containing RNA. The hnRNP A subfamily is characterized by two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long glycine-rich region at the C-terminus.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECTV-----NLRDDGYGFITY 725
Cdd:cd12578     2 LFIGGLSYETTDDSLRNHFEQWGEITDVVVmkdpaTKRSRGFGFVTY 48

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor 3 (SRSF3) and similar proteins; This subfamily corresponds to the RRM of two serine/arginine (SR) proteins, serine/arginine-rich splicing factor 3 (SRSF3) and serine/arginine-rich splicing factor 7 (SRSF7). SRSF3, also termed pre-mRNA-splicing factor SRp20, modulates alternative splicing by interacting with RNA cis-elements in a concentration- and cell differentiation-dependent manner. It is also involved in termination of transcription, alternative RNA polyadenylation, RNA export, and protein translation. SRSF3 is critical for cell proliferation, and tumor induction and maintenance. It can shuttle between the nucleus and cytoplasm. SRSF7, also termed splicing factor 9G8, plays a crucial role in both constitutive splicing and alternative splicing of many pre-mRNAs. Its localization and functions are tightly regulated by phosphorylation. SRSF7 is predominantly present in the nuclear and can shuttle between nucleus and cytoplasm. It cooperates with the export protein, Tap/NXF1, helps mRNA export to the cytoplasm, and enhances the expression of unspliced mRNA. Moreover, SRSF7 inhibits tau E10 inclusion through directly interacting with the proximal downstream intron of E10, a clustering region for frontotemporal dementia with Parkinsonism (FTDP) mutations. Both SRSF3 and SRSF7 contain a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal RS domain rich in serine-arginine dipeptides. The RRM domain is involved in RNA binding, and the RS domain has been implicated in protein shuttling and protein-protein interactions.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECTVNLRDDGYGFITYRYTCDA 731
Cdd:cd12373     2 VYVGNLGPRVTKRELEDAFEKYGPLRNVWVARNPPGFAFVEFEDPRDA 49

RNA recognition motif 1 (RRM1) found in (U)-binding-splicing factor PUF60 and similar proteins; This subfamily corresponds to the RRM1 of PUF60, also termed FUSE-binding protein-interacting repressor (FBP-interacting repressor or FIR), or Ro-binding protein 1 (RoBP1), or Siah-binding protein 1 (Siah-BP1). PUF60 is an essential splicing factor that functions as a poly-U RNA-binding protein required to reconstitute splicing in depleted nuclear extracts. Its function is enhanced through interaction with U2 auxiliary factor U2AF65. PUF60 also controls human c-myc gene expression by binding and inhibiting the transcription factor far upstream sequence element (FUSE)-binding-protein (FBP), an activator of c-myc promoters. PUF60 contains two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbors another RRM and binds to tryptophan-containing linear peptide motifs (UHM ligand motifs, ULMs) in several nuclear proteins. Research indicates that PUF60 binds FUSE as a dimer, and only the first two RRM domains participate in the single-stranded DNA recognition.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEEC-----TVNLRDDGYGFITYRYTCDAFAALE--NGYTL 741
Cdd:cd12370     3 VYVGSIYFELGEDTIRQAFAPFGPIKSIdmswdPVTMKHKGFAFVEYEVPEAAQLALEqmNGVML 67

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A subfamily; This subfamily corresponds to the RRM2 of hnRNP A0, hnRNP A1, hnRNP A2/B1, hnRNP A3 and similar proteins. hnRNP A0 is a low abundance hnRNP protein that has been implicated in mRNA stability in mammalian cells. It has been identified as the substrate for MAPKAP-K2 and may be involved in the lipopolysaccharide (LPS)-induced post-transcriptional regulation of tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase 2 (COX-2) and macrophage inflammatory protein 2 (MIP-2). hnRNP A1 is an abundant eukaryotic nuclear RNA-binding protein that may modulate splice site selection in pre-mRNA splicing. hnRNP A2/B1 is an RNA trafficking response element-binding protein that interacts with the hnRNP A2 response element (A2RE). Many mRNAs, such as myelin basic protein (MBP), myelin-associated oligodendrocytic basic protein (MOBP), carboxyanhydrase II (CAII), microtubule-associated protein tau, and amyloid precursor protein (APP) are trafficked by hnRNP A2/B1. hnRNP A3 is also a RNA trafficking response element-binding protein that participates in the trafficking of A2RE-containing RNA. The hnRNP A subfamily is characterized by two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long glycine-rich region at the C-terminus.

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                  ....*....|....*....|....*....|....*....|....*..
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECTVNL-----RDDGYGFITY 725
Cdd:cd12328     2 LFVGGLKEDVEEEDLREYFSQFGKVESVEIVTdketgKKRGFAFVTF 48

poly-U binding splicing factor, half-pint family; The proteins represented by this model contain three RNA recognition motifs (rrm: pfam00076) and have been characterized as poly-pyrimidine tract binding proteins associated with RNA splicing factors. In the case of PUF60 (GP|6176532), in complex with p54, and in the presence of U2AF, facilitates association of U2 snRNP with pre-mRNA.

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                  ....*....|....*....|....*....|....*....|....*...
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECTVnLRD------DGYGFITY 725
Cdd:TIGR01645 207 IYVASVHPDLSETDIKSVFEAFGEIVKCQL-ARAptgrghKGYGFIEY 253

RNA recognition motif (RRM) found in U11/U12 small nuclear ribonucleoprotein 35 kDa protein (U11/U12-35K) and similar proteins; This subfamily corresponds to the RRM of U11/U12-35K, also termed protein HM-1, or U1 snRNP-binding protein homolog, and is one of the components of the U11/U12 snRNP, which is a subunit of the minor (U12-dependent) spliceosome required for splicing U12-type nuclear pre-mRNA introns. U11/U12-35K is highly conserved among bilateria and plants, but lacks in some organisms, such as Saccharomyces cerevisiae and Caenorhabditis elegans. Moreover, U11/U12-35K shows significant sequence homology to U1 snRNP-specific 70 kDa protein (U1-70K or snRNP70). It contains a conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by an adjacent glycine-rich region, and Arg-Asp and Arg-Glu dipeptide repeats rich domain, making U11/U12-35K a possible functional analog of U1-70K. It may facilitate 5' splice site recognition in the minor spliceosome and play a role in exon bridging, interacting with components of the major spliceosome bound to the pyrimidine tract of an upstream U2-type intron. The family corresponds to the RRM of U11/U12-35K that may directly contact the U11 or U12 snRNA through the RRM domain.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1237937874 681 RRVIYVGKIRPDTTRTELRDRFEVFGEIEECTVnLRD------DGYGFITYRYTCDAFAALENGYTL 741
Cdd:cd12237     4 RLTLFVGRLSLQTTEEKLKEVFSRYGDIRRLRL-VRDivtgfsKRYAFIEYKEERDALHAYRDAKKL 69

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1237937874 692 DTTRTELRDRFEVFGEIEECTVnLRDD------GYGFITYRYTCDAFAALE--NGYTLR 742
Cdd:cd12375    10 SMTQEELRSLFGAIGPIESCKL-VRDKitgqslGYGFVNYRDPNDARKAINtlNGLDLE 67

RNA recognition motif 2 (RRM2) found in RNA-binding protein Musashi homologs Musashi-1, Musashi-2 and similar proteins; This subfamily corresponds to the RRM2.in Musashi-1 (also termed Msi1), 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.

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                  ....*....|....*....|....*....|....*....|....*...
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEEC------TVNlRDDGYGFITY 725
Cdd:cd12323     2 IFVGGLSANTTEDDVKKYFSQFGKVEDAmlmfdkQTN-RHRGFGFVTF 48

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and similar proteins; This subgroup corresponds to the RRM1 of hnRNP A1, also termed helix-destabilizing protein, or single-strand RNA-binding protein, or hnRNP core protein A1, and is an abundant eukaryotic nuclear RNA-binding protein that may modulate splice site selection in pre-mRNA splicing. hnRNP A1 has been characterized as a splicing silencer, often acting in opposition to an activating hnRNP H. It silences exons when bound to exonic elements in the alternatively spliced transcripts of c-src, HIV, GRIN1, and beta-tropomyosin. hnRNP A1 can shuttle between the nucleus and the cytoplasm. Thus, it may be involved in transport of cellular RNAs, including the packaging of pre-mRNA into hnRNP particles and transport of poly A+ mRNA from the nucleus to the cytoplasm. The cytoplasmic hnRNP A1 has high affinity with AU-rich elements, whereas the nuclear hnRNP A1 has high affinity with a polypyrimidine stretch bordered by AG at the 3' ends of introns. hnRNP A1 is also involved in the replication of an RNA virus, such as mouse hepatitis virus (MHV), through an interaction with the transcription-regulatory region of viral RNA. hnRNP A1, together with the scaffold protein septin 6, serves as host protein to form a complex with NS5b and viral RNA, and further plays important roles in the replication of Hepatitis C virus (HCV). hnRNP A1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long glycine-rich region at the C-terminus. The RRMs of hnRNP A1 play an important role in silencing the exon and the glycine-rich domain is responsible for protein-protein interactions.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937874 682 RVIYVGKIRPDTTRTELRDRFEVFGEIEECTV-----NLRDDGYGFITYRYTCDAFAALE 736
Cdd:cd12761     3 RKLFIGGLSFETTDESLRSHFEQWGTLTDCVVmrdpnTKRSRGFGFVTYATVEEVDAAMN 62

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins; This subfamily corresponds to the RRM2 of hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins. hnRNP D0, 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. It 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 memembers 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.

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                  ....*....|....*....|....*....|....*....|....*..
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEEC-----TVNLRDDGYGFITY 725
Cdd:cd12329     2 IFVGGLSPETTEEKIREYFGKFGNIVEIelpmdKKTNKRRGFCFITF 48

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein D-like (hnRNP D-like or hnRNP DL) and similar proteins; This subgroup corresponds to the RRM1 of hnRNP DL (or hnRNP D-like), also termed AU-rich element RNA-binding factor, or JKT41-binding protein (protein laAUF1 or JKTBP), which 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. hnRNP DL binds single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) in a non-sequencespecific manner, and interacts with poly(G) and poly(A) tenaciously. It contains two putative two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glycine- and tyrosine-rich C-terminus.

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                  ....*....|....*....|....*....|....*....|....*...
gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECTVNL-----RDDGYGFITYR 726
Cdd:cd12758     2 MFIGGLSWDTSKKDLTEYLSRFGEVVDCTIKTdpvtgRSRGFGFVLFK 49

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1237937874 684 IYVGKIRPD-TTRTELRDRFEVFGEIEECTVNlrdDGYGFITYRYTCDAFAAL--ENG 738
Cdd:cd12341     3 IFVGNLPTDqMTKEDLEEIFSKYGKILGISLH---KGYGFVQFDNEEDARAAVagENG 57

RNA recognition motif 1 (RRM1) found in vertebrate 54 kDa nuclear RNA- and DNA-binding protein (p54nrb); This subgroup corresponds to the RRM1 of p54nrb, also termed non-POU domain-containing octamer-binding protein (NonO), or 55 kDa nuclear protein (NMT55), or DNA-binding p52/p100 complex 52 kDa subunit. p54nrb is a multifunctional protein involved in numerous nuclear processes including transcriptional regulation, splicing, DNA unwinding, nuclear retention of hyperedited double-stranded RNA, viral RNA processing, control of cell proliferation, and circadian rhythm maintenance. It is ubiquitously expressed and highly conserved in vertebrates. p54nrb binds both, single- and double-stranded RNA and DNA, and also possesses inherent carbonic anhydrase activity. It forms a heterodimer with paraspeckle component 1 (PSPC1 or PSP1), localizing to paraspeckles in an RNA-dependent manneras well as with polypyrimidine tract-binding protein-associated-splicing factor (PSF). p54nrb contains two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), at the N-terminus.

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gi 1237937874 681 RRVIYVGKIRPDTTRTELRDRFEVFGEIEECTVNlRDDGYGFI 723
Cdd:cd12588     1 RSRLFVGNLPPDITEEEMRKLFEKYGKAGEVFIH-KDKGFGFI 42

N-terminal SNARE complex binding domain of the complexin family of SNARE regulators; Complexins (CPXs) are small, cytosolic proteins that bind to the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex to regulate synaptic vesicle exocytosis. There are four CPX isoforms: complexin I/synaphin-2, complexin II/synaphin-1, complexin III and complexin IV. CPXs I and II are highly homologous hydrophilic proteins that are enriched in neurons where they colocalize with syntaxin and SNAP25. They regulate the sequential interactions of alpha-SNAP and synaptotagmins with the SNAP receptor during exocytosis. CPXs III and IV are the only CPX isoforms present in retinal ribbon synapses. In addition, CPXs III and IV carry an extension with a functional CAAX-box farnesylation site that is absent in CPXs I and II. Their C-terminal farnesylation regulates their synaptic targeting and modulatory function in transmitter release. They may contribute to the unique release efficacy of retinal sensory neurons. CPXs III and IV can functionally replace CPXs I and II. Most of the invertebrate CPXs are more similar to CPXs I and II than to CPXs III and IV. This model corresponds to the N-terminal region of CPX that is responsible for SNARE complex binding.

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gi 1237937874 641 SYEEYQHERLKREEYRRE-YEKRESERAKQRERQRQK 676
Cdd:cd22740     2 EEEEYQEALREEEEERDAkHAQMKAERAAMRQHIRDK 38

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

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gi 1237937874 682 RVIYVGKI-----RPDTTRTELRDRFEVFGEIEECTVnLRDDGYGFITYRYTCDA-FA 733
Cdd:cd12360     2 RTLYVGGIkaasnKLAQIEEILRRHFGEWGEIERIRV-LPSKGIAFVRYKNRANAeFA 58

RNA recognition motif 2 (RRM2) found in Deleted in azoospermia-associated protein 1 (DAZAP1) and similar proteins; This subfamily corresponds to the RRM2 of DAZAP1 or DAZ-associated protein 1, also termed proline-rich RNA binding protein (Prrp), a multi-functional ubiquitous RNA-binding protein expressed most abundantly in the testis and essential for normal cell growth, development, and spermatogenesis. DAZAP1 is a shuttling protein whose acetylated is predominantly nuclear and the nonacetylated form is in cytoplasm. DAZAP1 also functions as a translational regulator that activates translation in an mRNA-specific manner. DAZAP1 was initially identified as a binding partner of Deleted in Azoospermia (DAZ). It also interacts with numerous hnRNPs, including hnRNP U, hnRNP U like-1, hnRNPA1, hnRNPA/B, and hnRNP D, suggesting DAZAP1 might associate and cooperate with hnRNP particles to regulate adenylate-uridylate-rich elements (AU-rich element or ARE)-containing mRNAs. DAZAP1 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal proline-rich domain.

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gi 1237937874 684 IYVGKIRPDTTRTELRDRFEVFGEIEECTV-----NLRDDGYGFITY 725
Cdd:cd12327     5 VFVGGIPHNCGETELRDYFKRYGVVTEVVMmydaeKQRSRGFGFITF 51

RNA recognition motif 1 (RRM1) found in TAR DNA-binding protein 43 (TDP-43) and similar proteins; This subfamily corresponds to the RRM1 of TDP-43 (also termed TARDBP), a ubiquitously expressed pathogenic protein whose normal function and abnormal aggregation are directly linked to the genetic disease cystic fibrosis, and two neurodegenerative disorders: frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). TDP-43 binds both DNA and RNA, and has been implicated in transcriptional repression, pre-mRNA splicing and translational regulation. TDP-43 is a dimeric protein with two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal glycine-rich domain. The RRMs are responsible for DNA and RNA binding; they bind to TAR DNA and RNA sequences with UG-repeats. The glycine-rich domain can interact with the hnRNP family proteins to form the hnRNP-rich complex involved in splicing inhibition. It is also essential for the cystic fibrosis transmembrane conductance regulator (CFTR) exon 9-skipping activity.

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gi 1237937874 692 DTTRTELRDRFEVFGEIEECTVNL-----RDDGYGFITY 725
Cdd:cd12321    10 KTTEQDLKEYFSTFGEVLMVQVKKdpktgRSKGFGFVRF 48