RNA recognition motif (RRM) found in vertebrate RNA-binding protein Raly; This subgroup corresponds to the RRM of Raly, also termed autoantigen p542, or heterogeneous nuclear ribonucleoprotein C-like 2, or hnRNP core protein C-like 2, or hnRNP associated with lethal yellow protein homolog, an RNA-binding protein that may play a critical role in embryonic development. It is encoded by Raly, a ubiquitously expressed gene of unknown function. Raly shows a high degree of identity with the 5' sequences of p542 gene encoding autoantigen, which can cross-react with EBNA-1 of the Epstein Barr virus. Raly contains two distinct domains, an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal auxiliary domain that includes a unique glycine/serine-rich stretch.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958760761  20 NSRVFIGNLNTAVVKKSDVETIFSKYGRVAGCSVHKGYAFVQYANERHARAAVLGENGRVLAGQTLDINMAGEPKP 95
Cdd:cd12604     1 NSRVFIGNLNTAVVKKSDVETIFSKYGRVVGCSVHKGYAFVQYTNERHARAAVIGENGRVLAGQTLDINMAGEPKP 76

RNA recognition motif (RRM) found in vertebrate RNA-binding protein Raly; This subgroup corresponds to the RRM of Raly, also termed autoantigen p542, or heterogeneous nuclear ribonucleoprotein C-like 2, or hnRNP core protein C-like 2, or hnRNP associated with lethal yellow protein homolog, an RNA-binding protein that may play a critical role in embryonic development. It is encoded by Raly, a ubiquitously expressed gene of unknown function. Raly shows a high degree of identity with the 5' sequences of p542 gene encoding autoantigen, which can cross-react with EBNA-1 of the Epstein Barr virus. Raly contains two distinct domains, an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal auxiliary domain that includes a unique glycine/serine-rich stretch.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958760761  20 NSRVFIGNLNTAVVKKSDVETIFSKYGRVAGCSVHKGYAFVQYANERHARAAVLGENGRVLAGQTLDINMAGEPKP 95
Cdd:cd12604     1 NSRVFIGNLNTAVVKKSDVETIFSKYGRVVGCSVHKGYAFVQYTNERHARAAVIGENGRVLAGQTLDINMAGEPKP 76

RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain); The RRM motif is probably diagnostic of an RNA binding protein. RRMs are found in a variety of RNA binding proteins, including various hnRNP proteins, proteins implicated in regulation of alternative splicing, and protein components of snRNPs. The motif also appears in a few single stranded DNA binding proteins. The RRM structure consists of four strands and two helices arranged in an alpha/beta sandwich, with a third helix present during RNA binding in some cases The C-terminal beta strand (4th strand) and final helix are hard to align and have been omitted in the SEED alignment The LA proteins have an N terminal rrm which is included in the seed. There is a second region towards the C terminus that has some features characteriztic of a rrm but does not appear to have the important structural core of a rrm. The LA proteins are one of the main autoantigens in Systemic lupus erythematosus (SLE), an autoimmune disease.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958760761  23 VFIGNLNTAVvKKSDVETIFSKYGRVAGCSV-------HKGYAFVQYANERHARAAVLGENGRVLAGQTL 85
Cdd:pfam00076   1 LFVGNLPPDT-TEEDLKDLFSKFGPIKSIRLvrdetgrSKGFAFVEFEDEEDAEKAIEALNGKELGGREL 69

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958760761  15 DP---KSINSRVFIGNLNTAVVKKSDVETiFSKYGRVAGCSV-------HKGYAFVQYANERHARAAVLGENGRVLA 81
Cdd:TIGR01628  80 DPslrRSGVGNIFVKNLDKSVDNKALFDT-FSKFGNILSCKVatdengkSRGYGFVHFEKEESAKAAIQKVNGMLLN 155

RNA recognition motif (RRM) found in vertebrate RNA-binding protein Raly; This subgroup corresponds to the RRM of Raly, also termed autoantigen p542, or heterogeneous nuclear ribonucleoprotein C-like 2, or hnRNP core protein C-like 2, or hnRNP associated with lethal yellow protein homolog, an RNA-binding protein that may play a critical role in embryonic development. It is encoded by Raly, a ubiquitously expressed gene of unknown function. Raly shows a high degree of identity with the 5' sequences of p542 gene encoding autoantigen, which can cross-react with EBNA-1 of the Epstein Barr virus. Raly contains two distinct domains, an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal auxiliary domain that includes a unique glycine/serine-rich stretch.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958760761  20 NSRVFIGNLNTAVVKKSDVETIFSKYGRVAGCSVHKGYAFVQYANERHARAAVLGENGRVLAGQTLDINMAGEPKP 95
Cdd:cd12604     1 NSRVFIGNLNTAVVKKSDVETIFSKYGRVVGCSVHKGYAFVQYTNERHARAAVIGENGRVLAGQTLDINMAGEPKP 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958760761  21 SRVFIGNLNTAVVKKSDVETIFSKYGRVAGCSVHKGYAFVQYANERHARAAVLGENGRVLAGQTLDIN 88
Cdd:cd12341     1 SRIFVGNLPTDQMTKEDLEEIFSKYGKILGISLHKGYGFVQFDNEEDARAAVAGENGRTIKGQRLDIN 68

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958760761   22 RVFIGNLNTAVvKKSDVETIFSKYGRVAGCSV--------HKGYAFVQYANERHARAAVLGENGRVLAGQTLDI 87
Cdd:smart00360   1 TLFVGNLPPDT-TEEELRELFSKFGKVESVRLvrdketgkSKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain); The RRM motif is probably diagnostic of an RNA binding protein. RRMs are found in a variety of RNA binding proteins, including various hnRNP proteins, proteins implicated in regulation of alternative splicing, and protein components of snRNPs. The motif also appears in a few single stranded DNA binding proteins. The RRM structure consists of four strands and two helices arranged in an alpha/beta sandwich, with a third helix present during RNA binding in some cases The C-terminal beta strand (4th strand) and final helix are hard to align and have been omitted in the SEED alignment The LA proteins have an N terminal rrm which is included in the seed. There is a second region towards the C terminus that has some features characteriztic of a rrm but does not appear to have the important structural core of a rrm. The LA proteins are one of the main autoantigens in Systemic lupus erythematosus (SLE), an autoimmune disease.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958760761  23 VFIGNLNTAVvKKSDVETIFSKYGRVAGCSV-------HKGYAFVQYANERHARAAVLGENGRVLAGQTL 85
Cdd:pfam00076   1 LFVGNLPPDT-TEEDLKDLFSKFGPIKSIRLvrdetgrSKGFAFVEFEDEEDAEKAIEALNGKELGGREL 69

RNA recognition motif (RRM) found in yeast nuclear polyadenylated RNA-binding protein 3 (Nab3p) and similar proteins; This subfamily corresponds to the RRM of Nab3p, an acidic nuclear polyadenylated RNA-binding protein encoded by Saccharomyces cerevisiae NAB3 gene that is essential for cell viability. Nab3p is predominantly localized within the nucleoplasm and essential for growth in yeast. It may play an important role in packaging pre-mRNAs into ribonucleoprotein structures amenable to efficient nuclear RNA processing. Nab3p contains an N-terminal aspartic/glutamic acid-rich region, a central RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal region rich in glutamine and proline residues.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958760761  22 RVFIGNLNTAVVKKSDVETIFSKYGRVAGCSVHKGYAFVQYANERHARAAVLGENGRVLAGQTL 85
Cdd:cd12342     1 RLFIGNLPTKRVSKEDLFRIFSPYGHLMQIVIKNAFGFVQFDSPQSCRNAIECEQGEMNRGKKL 64

RNA recognition motif 2 (RRM2) found in vertebrate RRM-containing coactivator activator/modulator (CoAA); This subgroup corresponds to the RRM2 of CoAA, also termed RNA-binding protein 14 (RBM14), or paraspeckle protein 2 (PSP2), or synaptotagmin-interacting protein (SYT-interacting protein), 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. It stimulates transcription through its interactions with coactivators, such as TRBP and CREB-binding protein CBP/p300, via the TRBP-interacting domain and interaction with an RNA-containing complex, such as DNA-dependent protein kinase-poly(ADP-ribose) polymerase complexes, via the RRMs.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958760761  22 RVFIGNLnTAVVKKSDVETIFSKYGRVAGCSVHKGYAFVQYANERHARAAVLGENGRVLAGQTLDINM 89
Cdd:cd12609     2 KIFVGNV-SATCTSDELRGLFEEFGRVVECDKVKDYAFVHMEREEEALAAIEALNGKEVKGRRINVEL 68

RNA recognition motif 1 (RRM1) found in serine/arginine-rich splicing factor 4 (SRSF4) and similar proteins; This subfamily corresponds to the RRM1 in three serine/arginine (SR) proteins: serine/arginine-rich splicing factor 4 (SRSF4 or SRp75 or SFRS4), serine/arginine-rich splicing factor 5 (SRSF5 or SRp40 or SFRS5 or HRS), serine/arginine-rich splicing factor 6 (SRSF6 or SRp55). SRSF4 plays an important role in both, constitutive and alternative, splicing of many pre-mRNAs. It can shuttle between the nucleus and cytoplasm. SRSF5 regulates both alternative splicing and basal splicing. It is the only SR protein efficiently selected from nuclear extracts (NE) by the splicing enhancer (ESE) and essential for enhancer activation. SRSF6 preferentially interacts with a number of purine-rich splicing enhancers (ESEs) to activate splicing of the ESE-containing exon. It is the only protein from HeLa nuclear extract or purified SR proteins that specifically binds B element RNA after UV irradiation. SRSF6 may also recognize different types of RNA sites. Members in this family contain two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a C-terminal RS domains rich in serine-arginine dipeptides.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958760761  22 RVFIGNLNTAVVKKsDVETIFSKYGRVAGCSVHKGYAFVQYANERHARAAVLGENGRVLAGQTLDINMA 90
Cdd:cd12337     1 RVYIGRLPYRARER-DVERFFRGYGRIRDINLKNGFGFVEFEDPRDADDAVYELNGKELCGERVIVEHA 68

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 1958760761  21 SRVFIGNLNTAVVKKSdVETIFSKYGRVAGCSV--------HKGYAFVQYANERHARAAVLGENGRVLAGQTLDINMAGE 92
Cdd:cd12449     1 GKLFVGGLSFDTNEQS-LEEVFSKYGQISEVVVvkdretqrSRGFGFVTFENPDDAKDAMMAMNGKSLDGRQIRVDQAGK 79

RNA recognition motif 1 (RRM1) found in vertebrate serine/arginine-rich splicing factor 5 (SRSF5); This subgroup corresponds to the RRM1 of SRSF5, also termed delayed-early protein HRS, or pre-mRNA-splicing factor SRp40, or splicing factor, arginine/serine-rich 5 (SFRS5). SFSF5 is an essential splicing regulatory serine/arginine (SR) protein that regulates both alternative splicing and basal splicing. It is the only SR protein efficiently selected from nuclear extracts (NE) by the splicing enhancer (ESE) and it is necessary for enhancer activation. SRSF5 also functions as a factor required for insulin-regulated splice site selection for protein kinase C (PKC) betaII mRNA. It is involved in the regulation of PKCbetaII exon inclusion by insulin via its increased phosphorylation by a phosphatidylinositol 3-kinase (PI 3-kinase) signaling pathway. Moreover, SRSF5 can regulate alternative splicing in exon 9 of glucocorticoid receptor pre-mRNA in a dose-dependent manner. SRSF5 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a C-terminal RS domains rich in serine-arginine dipeptides. The specific RNA binding by SRSF5 requires the phosphorylation of its SR domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958760761  22 RVFIGNLNTAVVKKsDVETIFSKYGRVAGCSVHKGYAFVQYANERHARAAVLGENGRVLAGQTLDINMA 90
Cdd:cd12595     1 RVFIGRLNPAAREK-DVERFFKGYGRIRDIDLKRGFGFVEFEDPRDADDAVYELDGKELCNERVTIEHA 68

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958760761  21 SRVFIGNLNTAVvKKSDVETIFSKYGRVAGCSVH--KGYAFVQYANERHARAAVLGENGRVLAGQTL 85
Cdd:cd12332     2 CRLFVGNLPNDI-TEEEFKELFQKYGEVSEVFLNkgKGFGFIRLDTRANAEAAKAELDGTPRKGRQL 67

RNA recognition motif 1 (RRM1) found in vertebrate serine/arginine-rich splicing factor 6 (SRSF6); This subfamily corresponds to the RRM1 of SRSF6, also termed pre-mRNA-splicing factor SRp55, which is an essential splicing regulatory serine/arginine (SR) protein that preferentially interacts with a number of purine-rich splicing enhancers (ESEs) to activate splicing of the ESE-containing exon. It is the only protein from HeLa nuclear extract or purified SR proteins that specifically binds B element RNA after UV irradiation. SRSF6 may also recognize different types of RNA sites. For instance, it does not bind to the purine-rich sequence in the calcitonin-specific ESE, but binds to a region adjacent to the purine tract. Moreover, cellular levels of SRSF6 may control tissue-specific alternative splicing of the calcitonin/ calcitonin gene-related peptide (CGRP) pre-mRNA. SRSF6 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a C-terminal SR domains rich in serine-arginine dipeptides.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958760761  22 RVFIGNLNTAVVKKsDVETIFSKYGRVAGCSVHKGYAFVQYANERHARAAVLGENGRVLAGQTLDINMA 90
Cdd:cd12596     3 RVYIGRLSYHVREK-DIQRFFSGYGKLLEVDLKNGYGFVEFEDSRDADDAVYELNGKELCGERVIVEHA 70

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958760761  24 FIGNLNTAVVKKSdVETIFSKYGRVAGCSV---HKG---YAFVQYANERHARAAVLGENGRVLAGQTLDINMA 90
Cdd:cd12352     2 YVGNLDRQVTEDL-ILQLFSQIGPCKSCKMiteHGGndpYCFVEFYEHNHAAAALQAMNGRKILGKEVKVNWA 73

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958760761  23 VFIGNLNTAVVKKsDVETIFSKYGRVAGCSVH--KGYAFVQYANERHARAAVLGENGRVLAGQTL 85
Cdd:cd12354     3 VYVGNITKGLTEA-LLQQTFSPFGQILEVRVFpdKGYAFIRFDSHEAATHAIVSVNGTIINGQAV 66

RNA recognition motif (RRM) found in Zinc finger CCHC-type and RNA-binding motif-containing protein 1 (ZCRB1) and similar proteins; This subfamily corresponds to the RRM of ZCRB1, also termed MADP-1, or U11/U12 small nuclear ribonucleoprotein 31 kDa protein (U11/U12 snRNP 31 or U11/U12-31K), a novel multi-functional nuclear factor, which may be involved in morphine dependence, cold/heat stress, and hepatocarcinoma. It is located in the nucleoplasm, but outside the nucleolus. ZCRB1 is one of the components of U11/U12 snRNPs that bind to U12-type pre-mRNAs and form a di-snRNP complex, simultaneously recognizing the 5' splice site and branchpoint sequence. ZCRB1 is characterized by an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a CCHC-type Zinc finger motif. In addition, it contains core nucleocapsid motifs, and Lys- and Glu-rich domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958760761  21 SRVFIGNLNTAVVKkSDVETIFSKYGRVAGCSV--------HKGYAFVQYANERHARAAVLGENGRVLAGQTL 85
Cdd:cd12393     2 STVYVSNLPFSLTN-NDLHQIFSKYGKVVKVTIlkdketrkSKGVAFVLFLDRESAHNAVRAMNNKELFGRTL 73

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958760761  22 RVFIGNLNTAVvKKSDVETIFSKYGRVAGCSV--------HKGYAFVQYANERHARAAVLGENGRVLAGQTLDINMA 90
Cdd:cd12371     2 RIYVASVHPDL-SEDDIKSVFEAFGKIKSCSLapdpetgkHKGYGFIEYENPQSAQDAIASMNLFDLGGQYLRVGRA 77

RNA recognition motif 1 (RRM1) found in yeast meiotic activator RIM4 and similar proteins; This subfamily corresponds to the RRM1 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958760761  23 VFIGNLNTAvvkKSD------VETIFSKYGRVAGCSVHKG-----YAFVQYANERHARAAVLGENGRVLAGQTLDINMAg 91
Cdd:cd12453     5 LFVASLSSA---RSDeelcaaVTNHFSKWGELLNVKVLKDwsnrpYAFVQYTNTEDAKNALVNGHNTLLDGRHLRVEKA- 80

                  ....*.
gi 1958760761  92 epKPNR 97
Cdd:cd12453    81 --KVNR 84

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958760761  23 VFIGNLNTAVvKKSDVETIFSKYGRVAGCSVHKGYAFVQYANERHARAAVLG 74
Cdd:cd12234     3 VFCGNFEYDA-RQSEIERLFGKYGRVDRVDMKSGYAFVYMEDERDAEDAIRG 53

RNA recognition motif 1 (RRM1) found in nucleolin-like proteins mainly from plants; This subfamily corresponds to the RRM1 of a group of plant nucleolin-like proteins, including nucleolin 1 (also termed protein nucleolin like 1) and nucleolin 2 (also termed protein nucleolin like 2, or protein parallel like 1). They play roles in the regulation of ribosome synthesis and in the growth and development of plants. Like yeast nucleolin, nucleolin-like proteins possess two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958760761  23 VFIGNLNTAVvKKSDVETIFSKYGRVAGCSV--------HKGYAFVQYANERHARAAvLGENGRVLAGQTLDINMAGE 92
Cdd:cd12450     2 LFVGNLSWSA-TQDDLENFFSDCGEVVDVRIamdrddgrSKGFGHVEFASAESAQKA-LEKSGQDLGGREIRLDLANE 77

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958760761  20 NSRVFIGNLNTAVVKKsDVETIFSKYGRVAGCSV--HKGYAFVQYANERHARAAVLGENGRVLAGQTL 85
Cdd:cd12346     1 NTTVFVGGLDPNVTEE-DLRVLFGPFGEIVYVKIppGKGCGFVQFVNRASAEAAIQKLQGTPIGGSRI 67

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958760761  22 RVFIGNLNTAVvKKSDVETIFSKYGRV---------AGCSvhKGYAFVQYANERHARAAVLGENGRVLAGQTLDINMAGE 92
Cdd:cd12392     4 KLFVKGLPFSC-TKEELEELFKQHGTVkdvrlvtyrNGKP--KGLAYVEYENEADASQAVLKTDGTEIKDHTISVAISNP 80

                  .
gi 1958760761  93 P 93
Cdd:cd12392    81 P 81

RNA recognition motif (RRM) found in ist3 family; This subfamily corresponds to the RRM of the ist3 family that includes fungal U2 small nuclear ribonucleoprotein (snRNP) component increased sodium tolerance protein 3 (ist3), X-linked 2 RNA-binding motif proteins (RBMX2) found in Metazoa and plants, and similar proteins. Gene IST3 encoding ist3, also termed U2 snRNP protein SNU17 (Snu17p), is a novel yeast Saccharomyces cerevisiae protein required for the first catalytic step of splicing and for progression of spliceosome assembly. It binds specifically to the U2 snRNP and is an intrinsic component of prespliceosomes and spliceosomes. Yeast ist3 contains an atypical RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). In the yeast pre-mRNA retention and splicing complex, the atypical RRM of ist3 functions as a scaffold that organizes the other two constituents, Bud13p (bud site selection 13) and Pml1p (pre-mRNA leakage 1). Fission yeast Schizosaccharomyces pombe gene cwf29 encoding ist3, also termed cell cycle control protein cwf29, is an RNA-binding protein complexed with cdc5 protein 29. It also contains one RRM. The biological function of RBMX2 remains unclear. It shows high sequence similarity to yeast ist3 protein and harbors one RRM as well.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958760761  23 VFIGNLNTAVvKKSDVETIFSKYGRV--------AGCSVHKGYAFVQYANERHARAAVLGENGRVLAGQTL 85
Cdd:cd12411    12 IYIGGLPYEL-TEGDILCVFSQYGEIvdinlvrdKKTGKSKGFAFLAYEDQRSTILAVDNLNGIKLLGRTI 81

RNA recognition motif 3 (RRM3) found in Schizosaccharomyces pombe mRNA export factor Crp79, meiotically up-regulated gene 28 protein (Mug28) and similar proteins; Crp79, also called meiotic expression up-regulated protein 5 (Mug5), or polyadenylate-binding protein crp79, or PABP, or poly(A)-binding protein, is an auxiliary mRNA export factor that binds the poly(A) tail of mRNA and is involved in the export of mRNA from the nucleus to the cytoplasm. 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 three RRM motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958760761  15 DPKSinsrVFIGNLNTAVV-KKSDVETIFSKYGRVAGC--------SVHKGYAFVQYANERHARAAVLGENGRVLAGQTL 85
Cdd:cd21622     2 DPCN----LFVKNLDDTVItNKEDLEQLFSPFGQIVSSylatypgtGISKGFGFVAFSKPEDAAKAKETLNGVMVGRKRI 77

                          90
                  ....*....|....*.
gi 1958760761  86 DINMAgEPKPNRPKGL 101
Cdd:cd21622    78 FVSYA-ERKEDREKRL 92

RNA recognition motif 1 (RRM1) found in yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1 and similar proteins; This subgroup corresponds to the RRM1 of yeast protein PUB1, also termed ARS consensus-binding protein ACBP-60, or poly uridylate-binding protein, or poly(U)-binding protein. PUB1 has been identified as both, a heterogeneous nuclear RNA-binding protein (hnRNP) and a cytoplasmic mRNA-binding protein (mRNP), which may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm. It 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 RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a GAR motif (glycine and arginine rich stretch) that is located between RRM2 and RRM3.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958760761  23 VFIGNLNTAVVKKSdVETIFSKYGRVAGC-------SVHKGYAFVQYANERHARAAVLGENGRVLAGQTLDINMA 90
Cdd:cd12614     1 LYVGNLDPRVTEDL-LQEIFAVTGPVENCkiipdknSKGVNYGFVEYYDRRSAEIAIQTLNGRQIFGQEIKVNWA 74

RNA recognition motif 2 (RRM2) found in the VICKZ family proteins; This subfamily corresponds to the RRM2 of IGF-II mRNA-binding proteins (IGF2BPs or IMPs) in the VICKZ family that have been implicated in the post-transcriptional regulation of several different RNAs and in subcytoplasmic localization of mRNAs during embryogenesis. IGF2BPs are composed of two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and four hnRNP K homology (KH) domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958760761  21 SRVFIGNLNTAVvKKSDVETIFSKYGRVAGCSVHK-----GYAFVQYANERHARAAVLGENGRVLAGQTLDINM 89
Cdd:cd12359     1 RKIQIRNIPPHA-RWEDLDSLLSTYGTVENCEQVNtksetATVNVTYESPEQAQQAVNKLNGYQYEGSALKVSY 73

RNA recognition motif 2 (RRM2) found in RNA-binding protein 28 (RBM28) and similar proteins; This subfamily corresponds to the RRM2 of RBM28 and Nop4p. RBM28 is a specific nucleolar component of the spliceosomal small nuclear ribonucleoproteins (snRNPs), possibly coordinating their transition through the nucleolus. It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), and may play a role in the maturation of both small nuclear and ribosomal RNAs. RBM28 has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an extremely acidic region between RRM2 and RRM3. The family also includes nucleolar protein 4 (Nop4p or Nop77p) encoded by YPL043W from Saccharomyces cerevisiae. It is an essential nucleolar protein involved in processing and maturation of 27S pre-rRNA and biogenesis of 60S ribosomal subunits. Nop4p also contains four RRMs.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958760761  22 RVFIGNLnTAVVKKSDVETIFSKYGRVAGCSV-------HKGYAFVQYANERHARAAVLGENGRVLAG 82
Cdd:cd12414     1 RLIVRNL-PFKCTEDDLKKLFSKFGKVLEVTIpkkpdgkLRGFAFVQFTNVADAAKAIKGMNGKKIKG 67

RNA recognition motif 1 (RRM1) found in yeast protein gar2 and similar proteins; This subfamily corresponds to the RRM1 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958760761  23 VFIGNL----NTAVVKKSdvetiFSKYGRVAGCSV--------HKGYAFVQYANERHARAAVLGENGRVLAGQTLDINMA 90
Cdd:cd12447     2 LFVGGLswnvDDPWLKKE-----FEKYGGVISARVitdrgsgrSKGYGYVDFATPEAAQKALAAMSGKEIDGRQINVDFS 76

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958760761  21 SRVFIGNLNTAVvKKSDVETIFSKYGRVAgcSVH----------KGYAFVQYANERHARAAVLGENGRVLAGQTLDI 87
Cdd:cd12566     3 GRLFLRNLPYST-KEDDLQKLFSKFGEVS--EVHvpidkktkksKGFAYVLFLDPEDAVQAYNELDGKVFQGRLIHI 76

RNA recognition motif 2 (RRM2) found in the Spen (split end) protein family; This subfamily corresponds to the RRM2 domain in the Spen (split end) protein family which includes RNA binding motif protein 15 (RBM15), putative RNA binding motif protein 15B (RBM15B), and similar proteins found in Metazoa. RBM15, also termed one-twenty two protein 1 (OTT1), conserved in eukaryotes, is a novel mRNA export factor and component of the NXF1 pathway. It binds to NXF1 and serves as receptor for the RNA export element RTE. It also possess mRNA export activity and can facilitate the access of DEAD-box protein DBP5 to mRNA at the nuclear pore complex (NPC). RNA-binding protein 15B (RBM15B), also termed one twenty-two 3 (OTT3), is a paralog of RBM15 and therefore has post-transcriptional regulatory activity. It is a nuclear protein sharing with RBM15 the association with the splicing factor compartment and the nuclear envelope as well as the binding to mRNA export factors NXF1 and Aly/REF. Members in this family belong to the Spen (split end) protein family, which share a domain architecture comprising of three N-terminal RNA recognition motifs (RRMs), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal SPOC (Spen paralog and ortholog C-terminal) domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958760761  24 FIGNLNTAVvKKSDVETIFSKYGRVAGCSV-------HKGYAFVQYANERHARAAVLGENGRVL 80
Cdd:cd12309     6 FVGNLEITI-TEEELRRAFERYGVVEDVDIkrpprgqGNAYAFVKFLNLDMAHRAKVAMSGQYI 68

RNA recognition motif 2 (RRM2) found in granule-associated RNA binding proteins p40-TIA-1 and TIAR; This subfamily corresponds to the RRM2 of nucleolysin TIA-1 isoform p40 (p40-TIA-1 or TIA-1) and nucleolysin TIA-1-related protein (TIAR), both of which are granule-associated RNA binding proteins involved in inducing apoptosis in cytotoxic lymphocyte (CTL) target cells. TIA-1 and TIAR share high sequence similarity. They are expressed in a wide variety of cell types. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis. TIAR is mainly localized in the nucleus of hematopoietic and nonhematopoietic cells. It is translocated from the nucleus to the cytoplasm in response to exogenous triggers of apoptosis. Both, TIA-1 and TIAR, bind specifically to poly(A) but not to poly(C) homopolymers. They are composed of three N-terminal highly homologous RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. TIA-1 and TIAR interact with RNAs containing short stretches of uridylates and their RRM2 can mediate the specific binding to uridylate-rich RNAs. The C-terminal auxiliary domain may be responsible for interacting with other proteins. In addition, TIA-1 and TIAR share a potential serine protease-cleavage site (Phe-Val-Arg) localized at the junction between their RNA binding domains and their C-terminal auxiliary domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958760761  23 VFIGNLnTAVVKKSDVETIFSKYGRVAGCSV--------HKGYAFVQYANERHARAAVLGENGRVLAGQTLDIN 88
Cdd:cd12353     2 IFVGDL-SPEIETEDLKEAFAPFGEISDARVvkdtqtgkSKGYGFVSFVKKEDAENAIQGMNGQWLGGRNIRTN 74

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 1958760761   4 KIQTSNVTNKNDPKSINsrVFIGNLNTAVvKKSDVETIFSKYGRVAGCSV-------HKGYAFVQYANERHARAAVLGEN 76
Cdd:TIGR01628 271 KFEELQQERKMKAQGVN--LYVKNLDDTV-TDEKLRELFSECGEITSAKVmldekgvSRGFGFVCFSNPEEANRAVTEMH 347

                          90
                  ....*....|....
gi 1958760761  77 GRVLAGQTLDINMA 90
Cdd:TIGR01628 348 GRMLGGKPLYVALA 361

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958760761  24 FIGNLNTAVvKKSDVETIFSKYGRVAGCSV--------HKGYAFVQYANERHARAAVLGENGRVLAGQTL 85
Cdd:cd12236     5 FVARLSYDT-TESKLRREFEKYGPIKRVRLvrdkktgkSRGYAFIEFEHERDMKAAYKHADGKKIDGRRV 73

RNA recognition motif (RRM) found in S6K1 Aly/REF-like target (SKAR) and similar proteins; This subgroup corresponds to the RRM of SKAR, also termed polymerase delta-interacting protein 3 (PDIP3), 46 kDa DNA polymerase delta interaction protein (PDIP46), belonging to the Aly/REF family of RNA binding proteins that have been implicated in coupling transcription with pre-mRNA splicing and nucleo-cytoplasmic mRNA transport. SKAR is widely expressed and localizes to the nucleus. It may be a critical player in the function of S6K1 in cell and organism growth control by binding the activated, hyperphosphorylated form of S6K1 but not S6K2. Furthermore, SKAR functions as a protein partner of the p50 subunit of DNA polymerase delta. In addition, SKAR may have particular importance in pancreatic beta cell size determination and insulin secretion. SKAR contains a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958760761  22 RVFIGNLNTaVVKKSDVETIFSKYGRVAGCSVHK-GYAFVQYANERHARAAVLGENGRVLAGQTLDINM 89
Cdd:cd12681     2 RLTVSNLHP-SVTEDDIVELFSVIGALKRARLVRpGVAEVVYVRREDAITAIKKYNNRELDGQPMKCKL 69

RNA recognition motif 3 (RRM3) found in heterogeneous nuclear ribonucleoprotein R (hnRNP R) and similar proteins; This subfamily corresponds to the RRM3 in hnRNP R, hnRNP Q, and APOBEC-1 complementation factor (ACF). hnRNP R is a ubiquitously expressed nuclear RNA-binding protein that specifically bind mRNAs with a preference for poly(U) stretches and 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. This family also includes two functionally unknown RNA-binding proteins, RBM46 and RBM47. All members contain three conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958760761  23 VFIGNLNTAVVKKSdVETIFSKYGRVAGCSVHKGYAFVQYANERHARAAVLGENGRVLAGQTLDINMAgepKP 95
Cdd:cd12251     4 LYVRNLMLSTTEEK-LRELFSEYGKVERVKKIKDYAFVHFEERDDAVKAMEEMNGKELEGSEIEVSLA---KP 72

RNA recognition motif 2 (RRM2) found in nucleolysin TIA-1 isoform p40 (p40-TIA-1) and similar proteins; This subgroup corresponds to the RRM2 of p40-TIA-1, the 40-kDa isoform of T-cell-restricted intracellular antigen-1 (TIA-1), and a cytotoxic granule-associated RNA-binding protein mainly found in the granules of cytotoxic lymphocytes. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis, and function as the granule component responsible for inducing apoptosis in cytolytic lymphocyte (CTL) targets. It is 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 interacts with RNAs containing short stretches of uridylates and its RRM2 can mediate the specific binding to uridylate-rich RNAs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958760761  23 VFIGNLNTAVVKkSDVETIFSKYGRVAGCSV--------HKGYAFVQYANERHARAAVLGENGRVLAGQTLDIN 88
Cdd:cd12618     5 VFVGDLSPEITT-EDIKAAFAPFGRISDARVvkdmatgkSKGYGFVSFFNKWDAENAIQQMGGQWLGGRQIRTN 77

RNA recognition motif 3 (RRM3) found in vertebrate heterogeneous nuclear ribonucleoprotein R (hnRNP R); This subgroup corresponds to the RRM3 of hnRNP R. a ubiquitously expressed nuclear RNA-binding protein that specifically bind mRNAs with a preference for poly(U) stretches. Upon binding of RNA, hnRNP R forms oligomers, most probably dimers. hnRNP R has been implicated in mRNA processing and mRNA transport, and also acts as a regulator to modify binding to ribosomes and RNA translation. hnRNP R is predominantly located in axons of motor neurons and to a much lower degree in sensory axons. In axons of motor neurons, it also functions as a cytosolic protein and interacts with wild type of survival motor neuron (SMN) proteins directly, further providing a molecular link between SMN and the spliceosome. Moreover, hnRNP R plays an important role in neural differentiation and development, as well as in retinal development and light-elicited cellular activities. hnRNP R contains an acidic auxiliary N-terminal region, followed by two well-defined and one degenerated RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal RGG motif; hnRNP R binds RNA through its RRM domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958760761  23 VFIGNLNTAVVKKSdVETIFSKYGRVAGCSVHKGYAFVQYaNERHARAAVLGE-NGRVLAGQTLDINMA 90
Cdd:cd12494     4 LFVRNLATTVTEEI-LEKTFSQFGKLERVKKLKDYAFVHF-EDRDAAVKAMDEmNGKEVEGEEIEIVLA 70

RNA recognition motif (RRM) found in the scaffold attachment factor (SAFB) family; This subfamily corresponds to the RRM domain of the SAFB family, including scaffold attachment factor B1 (SAFB1), scaffold attachment factor B2 (SAFB2), SAFB-like transcriptional modulator (SLTM), and similar proteins, which are ubiquitously expressed. SAFB1, SAFB2 and SLTM have been implicated in many diverse cellular processes including cell growth and transformation, stress response, and apoptosis. They share high sequence similarities and all contain a scaffold attachment factor-box (SAF-box, also known as SAP domain) DNA-binding motif, an RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a region rich in glutamine and arginine residues. SAFB1 is a nuclear protein with a distribution similar to that of SLTM, but unlike that of SAFB2, which is also found in the cytoplasm. To a large extent, SAFB1 and SLTM might share similar functions, such as the inhibition of an oestrogen reporter gene. The additional cytoplasmic localization of SAFB2 implies that it could play additional roles in the cytoplasmic compartment which are distinct from the nuclear functions shared with SAFB1 and SLTM.

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gi 1958760761  24 FIGNLnTAVVKKSDVETIFSKYGRVAGCSV--------HKGYAFVQYANERHARAAVLGENGRVLAGQTL 85
Cdd:cd12417     3 WISGL-SDTTKAADLKKIFSKYGKVVSAKVvtsartpgSRCYGYVTMASVEEADLCIKSLNKTELHGRVI 71

RNA recognition motif 3 in fungal pre-messenger RNA splicing protein 24 (Prp24) and similar proteins; This subfamily corresponds to the RRM3 of Prp24, also termed U4/U6 snRNA-associated-splicing factor PRP24 (U4/U6 snRNP), an RNA-binding protein with four well conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). It facilitates U6 RNA base-pairing with U4 RNA during spliceosome assembly. Prp24 specifically binds free U6 RNA primarily with RRMs 1 and 2 and facilitates pairing of U6 RNA bases with U4 RNA bases. Additionally, it may also be involved in dissociation of the U4/U6 complex during spliceosome activation.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958760761  23 VFIGNLNTAVVKkSDVETIFSKYGRVAGCSVHK-----------GYAFVQYANERHARAAvLGENGRVLAGQTLDINM 89
Cdd:cd12298     3 IRVRNLDFELDE-EALRGIFEKFGEIESINIPKkqknrkgrhnnGFAFVTFEDADSAESA-LQLNGTLLDNRKISVSL 78