RNA recognition motif 1 (RRM1) found in vertebrate RNA-binding protein 5 (RBM5); This subgroup corresponds to the RRM1 of RBM5, also termed protein G15, or putative tumor suppressor LUCA15, or renal carcinoma antigen NY-REN-9, a known modulator of apoptosis. It may also act as a tumor suppressor or an RNA splicing factor. RBM5 shows high sequence similarity to RNA-binding protein 6 (RBM6 or NY-LU-12 or g16 or DEF-3). Both, RBM5 and RBM6, specifically bind poly(G) RNA. They contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two C2H2-type zinc fingers, a nuclear localization signal, and a G-patch/D111 domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630610  93 DERESKTIMLRGLPITITESDIREMMESFEGPQPADVRLMKRKTGVSRGFAFVEFYHLQDATSWMEANQKKLVIQGKHIA 172
Cdd:cd12752     1 DEKESKTIMLRGLPINITENDIRELIESFEGPQPADVRLMKRKTGVSRGFAFVEFYHLQDATSWMEANQKKLVIQGKTIA 80

                  ....*..
gi 1034630610 173 MHYSNPR 179
Cdd:cd12752    81 MHYSNPR 87

OCRE domain; The OCRE (OCtamer REpeat) domain contains 5 repeats of an 8-residue motif, which were shown to form beta-strands. Based on the architectures of proteins containing OCRE domains, a role in RNA metabolism and/or signalling has been proposed.

                          10        20
                  ....*....|....*....|....*....
gi 1034630610 349 PGSPYYYNSLTQQYLYWDGEKETYVPAAE 377
Cdd:cd16168    28 PNSQYYYNSLTQQYLYWDGEKQTYLPAAE 56

RNA recognition motif 1 (RRM1) found in vertebrate RNA-binding protein 5 (RBM5); This subgroup corresponds to the RRM1 of RBM5, also termed protein G15, or putative tumor suppressor LUCA15, or renal carcinoma antigen NY-REN-9, a known modulator of apoptosis. It may also act as a tumor suppressor or an RNA splicing factor. RBM5 shows high sequence similarity to RNA-binding protein 6 (RBM6 or NY-LU-12 or g16 or DEF-3). Both, RBM5 and RBM6, specifically bind poly(G) RNA. They contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two C2H2-type zinc fingers, a nuclear localization signal, and a G-patch/D111 domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630610  93 DERESKTIMLRGLPITITESDIREMMESFEGPQPADVRLMKRKTGVSRGFAFVEFYHLQDATSWMEANQKKLVIQGKHIA 172
Cdd:cd12752     1 DEKESKTIMLRGLPINITENDIRELIESFEGPQPADVRLMKRKTGVSRGFAFVEFYHLQDATSWMEANQKKLVIQGKTIA 80

                  ....*..
gi 1034630610 173 MHYSNPR 179
Cdd:cd12752    81 MHYSNPR 87

glycine rich nucleic binding domain; A predicted glycine rich nucleic binding domain found in the splicing factor 45, SON DNA binding protein and D-type Retrovirus- polyproteins.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1034630610  608 IDHSNIGNKMLQAMGWREGSGLGRKCQGITAPIEAQVRLKGAGLGAK 654
Cdd:smart00443   1 ISTSNIGAKLLRKMGWKEGQGLGKNEQGIVEPISAEIKKDRKGLGAV 47

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034630610   99 TIMLRGLPITITESDIREMMESFeGPqPADVRLMK-RKTGVSRGFAFVEFYHLQDATSWMEANQKKlVIQGKHI 171
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKF-GK-VESVRLVRdKETGKSKGFAFVEFESEEDAEKALEALNGK-ELDGRPL 71

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034630610 100 IMLRGLPITITESDIREMMESFEGPQpaDVRLMKRKTGVSRGFAFVEFYHLQDAT 154
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIK--SIRLVRDETGRSKGFAFVEFEDEEDAE 53

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 1034630610  61 ERERERR--------NSDRSEDGYHSDGDYGEHDYRHDIS----DERESKTIMLRGLPITITESDIREMMEsfEGPQPAD 128
Cdd:TIGR01622  66 PNRRYRPrekrrrrgDSYRRRRDDRRSRREKPRARDGTPEplteDERDRRTVFVQQLAARARERDLYEFFS--KVGKVRD 143

                          90       100
                  ....*....|....*....|.
gi 1034630610 129 VRLMK-RKTGVSRGFAFVEFY 148
Cdd:TIGR01622 144 VQIIKdRNSRRSKGVGYVEFY 164

RNA recognition motif 1 (RRM1) found in vertebrate RNA-binding protein 5 (RBM5); This subgroup corresponds to the RRM1 of RBM5, also termed protein G15, or putative tumor suppressor LUCA15, or renal carcinoma antigen NY-REN-9, a known modulator of apoptosis. It may also act as a tumor suppressor or an RNA splicing factor. RBM5 shows high sequence similarity to RNA-binding protein 6 (RBM6 or NY-LU-12 or g16 or DEF-3). Both, RBM5 and RBM6, specifically bind poly(G) RNA. They contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two C2H2-type zinc fingers, a nuclear localization signal, and a G-patch/D111 domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630610  93 DERESKTIMLRGLPITITESDIREMMESFEGPQPADVRLMKRKTGVSRGFAFVEFYHLQDATSWMEANQKKLVIQGKHIA 172
Cdd:cd12752     1 DEKESKTIMLRGLPINITENDIRELIESFEGPQPADVRLMKRKTGVSRGFAFVEFYHLQDATSWMEANQKKLVIQGKTIA 80

                  ....*..
gi 1034630610 173 MHYSNPR 179
Cdd:cd12752    81 MHYSNPR 87

RNA recognition motif 1 (RRM1) found in vertebrate RNA-binding protein 10 (RBM10); This subgroup corresponds to the RRM1 of RBM10, also termed G patch domain-containing protein 9, or RNA-binding protein S1-1 (S1-1), a paralog of putative tumor suppressor RNA-binding protein 5 (RBM5 or LUCA15 or H37). It may play an important role in mRNA generation, processing and degradation in several cell types. The rat homolog of human RBM10 is protein S1-1, a hypothetical RNA binding protein with poly(G) and poly(U) binding capabilities. RBM10 is structurally related to RBM5 and RNA-binding protein 6 (RBM6 or NY-LU-12 or g16 or DEF-3). It contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two C2H2-type zinc fingers, and a G-patch/D111 domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630610  97 SKTIMLRGLPITITESDIREMMESfEGPQPADVRLMKRK-TGVSRGFAFVEFYHLQDATSWMEANQKKLVIQGKHIAMHY 175
Cdd:cd12753     1 SNIIMLRMLPQSATENDIRGQLQA-HGVQPREVRLMRNKsSGQSRGFAFVEFNHLQDATRWMEANQHSLTILGQKVSMHY 79

                  ....*
gi 1034630610 176 SNPRP 180
Cdd:cd12753    80 SDPKP 84

G-patch domain; This domain is found in a number of RNA binding proteins, and is also found in proteins that contain RNA binding domains. This suggests that this domain may have an RNA binding function. This domain has seven highly conserved glycines.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1034630610 610 HSNIGNKMLQAMGWREGSGLGRKCQGITAPIEAQVRLKGAGLGAK 654
Cdd:pfam01585   1 TSNIGFKLLQKMGWKEGQGLGKNEQGIAEPIEAKIKKDRRGLGAE 45

RNA recognition motif 2 (RRM2) found in vertebrate RNA-binding protein 5 (RBM5); This subgroup corresponds to the RRM2 of RBM5, also termed protein G15, or putative tumor suppressor LUCA15, or renal carcinoma antigen NY-REN-9, a known modulator of apoptosis. It may also act as a tumor suppressor or an RNA splicing factor. RBM5 shows high sequence similarity to RNA-binding protein 6 (RBM6 or NY-LU-12 or g16 or DEF-3). Both, RBM5 and RBM6, specifically bind poly(G) RNA. They contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two C2H2-type zinc fingers, a nuclear localization signal, and a G-patch/D111 domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630610  97 SKTIMLRGL-PITITESdIREMMESFEGPQPADVRLMKRK-TGVSRGFAFVEfyhlqdatswmeanqkklviqgkhiamh 174
Cdd:cd12755     2 SDTIILRNIaPHTVVDS-IMTALSPYASLAVNNIRLIKDKqTQQNRGFAFVQ---------------------------- 52

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630610 175 ysnprpkfedwlcnktlnrkcllepqsrfslwITTVIDASQLLQILQSLHPPLKIDGKTIGVDFAK 240
Cdd:cd12755    53 --------------------------------LSSALEASQLLQILQSLHPPLKIDGKTIGVDFAK 86

RNA recognition motif 2 (RRM2) found in RNA-binding protein 5 (RBM5) and similar proteins; This subgroup corresponds to the RRM2 of RNA-binding protein 5 (RBM5 or LUCA15 or H37), RNA-binding protein 10 (RBM10 or S1-1) and similar proteins. RBM5 is a known modulator of apoptosis. It may also act as a tumor suppressor or an RNA splicing factor; it specifically binds poly(G) RNA. RBM10, a paralog of RBM5, may play an important role in mRNA generation, processing and degradation in several cell types. The rat homolog of human RBM10 is protein S1-1, a hypothetical RNA binding protein with poly(G) and poly(U) binding capabilities. Both, RBM5 and RBM10, contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two C2H2-type zinc fingers, and a G-patch/D111 domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630610  99 TIMLRGL-PITITESdIREMMESFEGPQPADVRLMKRK-TGVSRGFAFVEfyhlqdatswmeanqkklviqgkhiamhys 176
Cdd:cd12562     4 TIILRNInPHTTVDS-ILGALAPYAVLSSSNVRLIKDKqTQLNRGFAFVQ------------------------------ 52

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034630610 177 nprpkfedwlcnktlnrkcllepqsrfslwITTVIDASQLLQILQSLHPPLKIDGKTIGVDFAK 240
Cdd:cd12562    53 ------------------------------LSSPIEASQLLQILQSLHPPLTIDGKTINVDFAK 86

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034630610   99 TIMLRGLPITITESDIREMMESFeGPqPADVRLMK-RKTGVSRGFAFVEFYHLQDATSWMEANQKKlVIQGKHI 171
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKF-GK-VESVRLVRdKETGKSKGFAFVEFESEEDAEKALEALNGK-ELDGRPL 71

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034630610 100 IMLRGLPITITESDIREMMESFEGPQpaDVRLMKRKTGVSRGFAFVEFYHLQDATSWMEANQKKlVIQGKHI 171
Cdd:cd00590     1 LFVGNLPPDTTEEDLRELFSKFGEVV--SVRIVRDRDGKSKGFAFVEFESPEDAEKALEALNGT-ELGGRPL 69

RNA recognition motif 1 (RRM1) found in vertebrate RNA-binding protein 6 (RBM6); This subfamily corresponds to the RRM1 of RBM6, also termed lung cancer antigen NY-LU-12, or protein G16, or RNA-binding protein DEF-3, which has been predicted to be a nuclear factor based on its nuclear localization signal. It shows high sequence similarity to RNA-binding protein 5 (RBM5 or LUCA15 or NY-REN-9). Both, RBM6 and RBM5, specifically bind poly(G) RNA. They contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two C2H2-type zinc fingers, a nuclear localization signal, and a G-patch/D111 domain. In contrast to RBM5, RBM6 has two additional unique domains: the decamer repeat occurring more than 20 times, and the POZ (poxvirus and zinc finger) domain. The POZ domain may be involved in protein-protein interactions and inhibit binding of target sequences by zinc fingers.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630610  98 KTIMLRGLPITITESDIremMESFEGPQPADVRLMKRK---TGVSRGFAFVEFYHLQDATSWMEANQKKLVIQGKHIAMH 174
Cdd:cd12314     1 NLIRLIGVPETATKEQI---LNAFRVPDGMPVKNLKLKnyvPGYDYDYVCVEFSLLEDAIGCMEANQGTLKIGTKEVTLE 77

                  .
gi 1034630610 175 Y 175
Cdd:cd12314    78 Y 78

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034630610  97 SKTIMLRGLPITITESDIREMMESFeGpQPADVRLMK-RKTGVSRGFAFVEF 147
Cdd:COG0724     1 SMKIYVGNLPYSVTEEDLRELFSEY-G-EVTSVKLITdRETGRSRGFGFVEM 50

RNA recognition motif 6 (RRM6) found in RNA-binding protein 19 (RBM19 or RBD-1) and RNA recognition motif 5 (RRM5) found in multiple RNA-binding domain-containing protein 1 (MRD1); This subfamily corresponds to the RRM6 of RBM19 and RRM5 of MRD1. RBM19, also termed RNA-binding domain-1 (RBD-1), is a nucleolar protein conserved in eukaryotes. It is involved in ribosome biogenesis by processing rRNA and is essential for preimplantation development. It has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). MRD1 is encoded by a novel yeast gene MRD1 (multiple RNA-binding domain). It is well-conserved in yeast and its homologs exist in all eukaryotes. MRD1 is present in the nucleolus and the nucleoplasm. It interacts with the 35 S precursor rRNA (pre-rRNA) and U3 small nucleolar RNAs (snoRNAs). It is essential for the initial processing at the A0-A2 cleavage sites in the 35 S pre-rRNA. MRD1 contains 5 conserved RRMs, which may play an important structural role in organizing specific rRNA processing events.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630610  98 KTIMLRGLPITITESDIREMMESFEgpQPADVRLMKRKTGVSRGFAFVEFYHLQDATSWMEANQ------KKLVIQ 167
Cdd:cd12320     1 TKLIVKNVPFEATRKEIRELFSPFG--QLKSVRLPKKFDGSHRGFAFVEFVTKQEAQNAMEALKsthlygRHLVLE 74

RNA recognition motif 1 (RRM1) found in plant Mei2-like proteins; This subgroup corresponds to the RRM1 of Mei2-like proteins that represent an ancient eukaryotic RNA-binding proteins family. Their corresponding Mei2-like genes appear to have arisen early in eukaryote evolution, been lost from some lineages such as Saccharomyces cerevisiae and metazoans, and diversified in the plant lineage. The plant Mei2-like genes may function in cell fate specification during development, rather than as stimulators of meiosis. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The C-terminal RRM (RRM3) is unique to Mei2-like proteins and it is highly conserved between plants and fungi. Up to date, the intracellular localization, RNA target(s), cellular interactions and phosphorylation states of Mei2-like proteins in plants remain unclear.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630610  97 SKTIMLRGLPITITESDIREMMESFegpqpADVRLMkRKTGVSRGFAFVEFYHLQDATSWMEANQKKLvIQGKHIAMHYS 176
Cdd:cd12524     1 SRTLFVRNINSSVEDEELRALFEQF-----GEIRTL-YTACKHRGFIMVSYYDIRAAQSAKRALQGTE-LGGRKLDIHFS 73

                  ...
gi 1034630610 177 NPR 179
Cdd:cd12524    74 IPK 76

RNA recognition motif 2 (RRM2) found in vertebrate nucleolin; This subfamily corresponds to the RRM2 of ubiquitously expressed protein nucleolin, also termed protein C23, a multifunctional major nucleolar phosphoprotein that has been implicated in various metabolic processes, such as ribosome biogenesis, cytokinesis, nucleogenesis, cell proliferation and growth, cytoplasmic-nucleolar transport of ribosomal components, transcriptional repression, replication, signal transduction, inducing chromatin decondensation, etc. Nucleolin exhibits intrinsic self-cleaving, DNA helicase, RNA helicase and DNA-dependent ATPase activities. It can be phosphorylated by many protein kinases, such as the major mitotic kinase Cdc2, casein kinase 2 (CK2), and protein kinase C-zeta. Nucleolin shares similar domain architecture with gar2 from Schizosaccharomyces pombe and NSR1 from Saccharomyces cerevisiae. The highly phosphorylated N-terminal domain of nucleolin is made up of highly acidic regions separated from each other by basic sequences, and contains multiple phosphorylation sites. The central domain of nucleolin contains four closely adjacent N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), which suggests that nucleolin is potentially able to interact with multiple RNA targets. The C-terminal RGG (or GAR) domain of nucleolin is rich in glycine, arginine and phenylalanine residues, and contains high levels of NG,NG-dimethylarginines.RRM2, together with RRM1, binds specifically to RNA stem-loops containing the sequence (U/G)CCCG(A/G) in the loop.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630610  95 RESKTIMLRGLPITITESDIREMMEsfegpQPADVRLMKRKTGVSRGFAFVEFYHLQDATSWMEANQkKLVIQGKHIAMH 174
Cdd:cd12404     1 RDARTLFVKNLPYSTTQDELKEVFE-----DAVDIRIPMGRDGRSKGIAYIEFKSEAEAEKALEEKQ-GTEVDGRSIVVD 74

                  .
gi 1034630610 175 Y 175
Cdd:cd12404    75 Y 75

RNA recognition motif 4 (RRM4) found in RNA-binding protein RBM12, RBM12B and similar proteins; This subfamily corresponds to the RRM4 of RBM12 and RBM12B. RBM12, also termed SH3/WW domain anchor protein in the nucleus (SWAN), is ubiquitously expressed. It contains five distinct RNA binding motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two proline-rich regions, and several putative transmembrane domains. RBM12B show high sequence semilarity with RBM12. It contains five distinct RRMs as well. The biological roles of both RBM12 and RBM12B remain unclear.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034630610 100 IMLRGLPITITESDIREMMESFeGPQPADVRLMKRKTGVSRGFAFVEFYHLQDATSWMEANQKKL 164
Cdd:cd12514     2 IRITNLPYDATPVDIQRFFEDH-GVRPEDVHLLRNKKGRGNGEALVTFKSEGDAREVLKLNGKKL 65

RNA recognition motif (RRM) found in eukaryotic translation initiation factor 3 subunit G (eIF-3G) and similar proteins; This subfamily corresponds to the RRM of eIF-3G and similar proteins. eIF-3G, also termed eIF-3 subunit 4, or eIF-3-delta, or eIF3-p42, or eIF3-p44, is the RNA-binding subunit of eIF3, a large multisubunit complex that plays a central role in the initiation of translation by binding to the 40 S ribosomal subunit and promoting the binding of methionyl-tRNAi and mRNA. eIF-3G binds 18 S rRNA and beta-globin mRNA, and therefore appears to be a nonspecific RNA-binding protein. eIF-3G is one of the cytosolic targets and interacts with mature apoptosis-inducing factor (AIF). eIF-3G contains one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). This family also includes yeast eIF3-p33, a homolog of vertebrate eIF-3G, plays an important role in the initiation phase of protein synthesis in yeast. It binds both, mRNA and rRNA, fragments due to an RRM near its C-terminus.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630610  99 TIMLRGLPITITESDIREMMESFeGPQPAdVRLMK-RKTGVSRGFAFVEFYHLQDA 153
Cdd:cd12408     1 TIRVTNLSEDATEEDLRELFRPF-GPISR-VYLAKdKETGQSKGFAFVTFETREDA 54

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 1034630610  96 ESKTIMLRGLPITITESDIREMMESFeGPQpADVRLMKRKTGVSRGFAFVEFYHLQDA-TSWMEANqkKLVIQGKHIAMH 174
Cdd:cd12392     1 EKNKLFVKGLPFSCTKEELEELFKQH-GTV-KDVRLVTYRNGKPKGLAYVEYENEADAsQAVLKTD--GTEIKDHTISVA 76

                  ....
gi 1034630610 175 YSNP 178
Cdd:cd12392    77 ISNP 80

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034630610 100 IMLRGLPITITESDIREMMESFEGPQpaDVRLMKRKTGVSRGFAFVEFYHLQDATSWMEA-NQKKlvIQGKHIA 172
Cdd:cd12414     2 LIVRNLPFKCTEDDLKKLFSKFGKVL--EVTIPKKPDGKLRGFAFVQFTNVADAAKAIKGmNGKK--IKGRPVA 71

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034630610 105 LPITITESDIREMMESFeGPQpADVRLMKRK-TGVSRGFAFVEFYHLQDATSWMEA--NQKKL 164
Cdd:cd12361     7 IPKTASEEDVRPLFEQF-GNI-EEVQILRDKqTGQSKGCAFVTFSTREEALRAIEAlhNKKTM 67

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 1034630610  99 TIMLRGLPITITESDIREMMESFeGpQPADVRLMKRKTGVSRGFAFVEFYHLQDATSwMEANQKKLVIQGK 169
Cdd:cd12412     4 RIFVGGIDWDTTEEELREFFSKF-G-KVKDVKIIKDRAGVSKGYGFVTFETQEDAEK-IQKWGANLVFKGK 71

RNA recognition motif 2 (RRM2) found in RNA-binding protein 12 (RBM12) and similar proteins; This subgroup corresponds to the RRM2 of RBM12, also termed SH3/WW domain anchor protein in the nucleus (SWAN), which is ubiquitously expressed. It contains five distinct RNA binding motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two proline-rich regions, and several putative transmembrane domains. The biological role of RBM12 remains unclear.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034630610 100 IMLRGLPITITESDIREMmesFEGPQPADVRLMKRKTGVSRGFAFVEFYHLQDATSWMEANqKKLVIQ 167
Cdd:cd12747     4 VHLHGMPFSATEADVRDF---FHGLRIDAIHMLKDHLGRNNGNALVKFYSPQDTFEALKRN-RMMMGQ 67

RNA recognition motif 1 (RRM1) found in RNA-binding protein 19 (RBM19), yeast multiple RNA-binding domain-containing protein 1 (MRD1) and similar proteins; This subfamily corresponds to the RRM1 of RBM19 and MRD1. RBM19, also termed RNA-binding domain-1 (RBD-1), is a nucleolar protein conserved in eukaryotes. It is involved in ribosome biogenesis by processing rRNA and is essential for preimplantation development. It has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). MRD1 is encoded by a novel yeast gene MRD1 (multiple RNA-binding domain). It is well-conserved in yeast and its homologs exist in all eukaryotes. MRD1 is present in the nucleolus and the nucleoplasm. It interacts with the 35 S precursor rRNA (pre-rRNA) and U3 small nucleolar RNAs (snoRNAs). It is essential for the initial processing at the A0-A2 cleavage sites in the 35 S pre-rRNA. MRD1 contains 5 conserved RRMs, which may play an important structural role in organizing specific rRNA processing events.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034630610 100 IMLRGLPITITESDIREMMESFEGPQP---ADVRLMKRKTGVSRGFAFVEFYHLQDATSWME 158
Cdd:cd12315     3 LIVKNLPLSLDEDQFRRLFSQKCKDIGltiTDCKLLTKSGGVSRRFGFVGFKDEEDAQKAKE 64

RNA recognition motif 1 (RRM1) found in squamous cell carcinoma antigen recognized by T-cells 3 (SART3) and similar proteins; This subfamily corresponds to the RRM1 of SART3, also termed Tat-interacting protein of 110 kDa (Tip110), 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
                  ....*....|....*....|....*....|....*....|....*....
gi 1034630610  99 TIMLRGLPITITESDIREMMESFEgpQPADVRLMKRKTGVSRGFAFVEF 147
Cdd:cd12391     1 TVFVSNLDYSVPEDKIREIFSGCG--EITDVRLVKNYKGKSKGYCYVEF 47

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034630610 104 GLPITITESDIREMMESFEgpQPADVRLMK-RKTGVSRGFAFVEFYHLQDAtswmeanqkKLVIQGKHI 171
Cdd:cd12321     6 GLPWKTTEQDLKEYFSTFG--EVLMVQVKKdPKTGRSKGFGFVRFASYETQ---------VKVLSQRHM 63

RNA recognition motif 1 (RRM1) found in Drosophila sex-lethal (SXL) and similar proteins; This subfamily corresponds to the RRM1 of SXL which governs sexual differentiation and X chromosome dosage compensation in Drosophila melanogaster. It induces female-specific alternative splicing of the transformer (tra) pre-mRNA by binding to the tra uridine-rich polypyrimidine tract at the non-sex-specific 3' splice site during the sex-determination process. SXL binds also to its own pre-mRNA and promotes female-specific alternative splicing. SXL contains an N-terminal Gly/Asn-rich domain that may be responsible for the protein-protein interaction, and tandem RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), that show high preference to bind single-stranded, uridine-rich target RNA transcripts.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034630610 105 LPITITESDIREMMESFeGPQPADVRLMKRKTGVSRGFAFVEFYHLQDATSWMEA-NQkkLVIQGKHIAMHYSNP 178
Cdd:cd12649     8 LPQDLTDREFRALFRAI-GPVNTCKIVRDKKTGYSYGFGFVDFTSEEDAQRAIKTlNG--LQLQNKRLKVAYARP 79

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 1034630610  96 ESKTIMLRGLPITITESDIREMMESFEgpQPADVRL-MKRKTGVSRGFAFVEFYHLQDATSWMEANQKKlVIQGK--HI 171
Cdd:cd12566     1 ETGRLFLRNLPYSTKEDDLQKLFSKFG--EVSEVHVpIDKKTKKSKGFAYVLFLDPEDAVQAYNELDGK-VFQGRliHI 76

RNA recognition motif 3 (RRM3) found in yeast nucleolar protein 4 (Nop4p) and similar proteins; This subgroup corresponds to the RRM3 of Nop4p (also known as Nop77p), encoded by YPL043W from Saccharomyces cerevisiae. It is an essential nucleolar protein involved in processing and maturation of 27S pre-rRNA and biogenesis of 60S ribosomal subunits. Nop4p has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034630610  97 SKTIMLRGLPITITESDIREMMESFEGPQPADVrLMKRKTGVSRGFAFVEFYHLQDA 153
Cdd:cd12676     1 GRTLFVRNLPFDATEDELYSHFSQFGPLKYARV-VKDPATGRSKGTAFVKFKNKEDA 56

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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630610  98 KTIMLRGLPITITESDIREMMESFeGPQpADVRLMK-RKTGVSRGFAFVEFYHLQD 152
Cdd:cd12236     2 KTLFVARLSYDTTESKLRREFEKY-GPI-KRVRLVRdKKTGKSRGYAFIEFEHERD 55

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor SRSF2, SRSF8 and similar proteins; This subfamily corresponds to the RRM of SRSF2 and SRSF8. SRSF2, also termed protein PR264, or splicing component, 35 kDa (splicing factor SC35 or SC-35), is a prototypical SR protein that plays important roles in the alternative splicing of pre-mRNA. It is also involved in transcription elongation by directly or indirectly mediating the recruitment of elongation factors to the C-terminal domain of polymerase II. SRSF2 is exclusively localized in the nucleus and is restricted to nuclear processes. It contains a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C-terminal RS domain rich in serine-arginine dipeptides. The RRM is responsible for the specific recognition of 5'-SSNG-3' (S=C/G) RNA. In the regulation of alternative splicing events, it specifically binds to cis-regulatory elements on the pre-mRNA. The RS domain modulates SRSF2 activity through phosphorylation, directly contacts RNA, and promotes protein-protein interactions with the spliceosome. SRSF8, also termed SRP46 or SFRS2B, is a novel mammalian SR splicing factor encoded by a PR264/SC35 functional retropseudogene. SRSF8 is localized in the nucleus and does not display the same activity as PR264/SC35. It functions as an essential splicing factor in complementing a HeLa cell S100 extract deficient in SR proteins. Like SRSF2, SRSF8 contains a single N-terminal RRM and a C-terminal RS domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034630610 104 GLPITITESDIREMMESFEgpQPADVRLMK-RKTGVSRGFAFVEFYHLQDATSWMEANQKKlVIQGKHI 171
Cdd:cd12311     5 NLTYRTTPDDLRRVFEKYG--EVGDVYIPRdRYTRESRGFAFVRFYDKRDAEDAIDAMDGA-ELDGREL 70

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630610  98 KTIMLRGLPITITESDIREMMESFeGPQPADVRLMKRKTGVSRGFAFVEFYHLQDATSWM-EANQKKLviQGKHIAMHYS 176
Cdd:cd12674     1 TTLFVRNLPFDVTLESLTDFFSDI-GPVKHAVVVTDPETKKSRGYGFVSFSTHDDAEEALaKLKNRKL--SGHILKLDFA 77

                  ...
gi 1034630610 177 NPR 179
Cdd:cd12674    78 KPR 80

OCRE domain; The OCtamer REpeat (OCRE) has been annotated as a 42-residue sequence motif with 12 tyrosine residues in the spliceosome trans-regulatory elements RBM5 and RBM10 (RBM [RNA-binding motif]), which are known to regulate alternative splicing of Fas and Bcl-x pre-mRNA transcripts. The structure of the domain consists of an anti-parallel arrangement of six beta strands.

                          10        20
                  ....*....|....*....|....*..
gi 1034630610 349 PGSPYYYNSLTQQYLYWDGEKETYVPA 375
Cdd:pfam17780  25 PNTGLYYDPATGKYYTYDEETKSYVPH 51

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034630610 105 LPITITESDIREMMESFEGPQpaDVRLM-KRKTGVSRGFAFVEF 147
Cdd:cd12400     8 LPYDTTAEDLKEHFKKAGEPP--SVRLLtDKKTGKSKGCAFVEF 49

RNA recognition motif 1 (RRM1) found in the Hu proteins family, Drosophila sex-lethal (SXL), and similar proteins; This subfamily corresponds to the RRM1 of Hu proteins and SXL. The Hu proteins family represents a group of RNA-binding proteins involved in diverse biological processes. Since the Hu proteins share high homology with the Drosophila embryonic lethal abnormal vision (ELAV) protein, the Hu family is sometimes referred to as the ELAV family. Drosophila ELAV is exclusively expressed in neurons and is required for the correct differentiation and survival of neurons in flies. The neuronal members of the Hu family include Hu-antigen B (HuB or ELAV-2 or Hel-N1), Hu-antigen C (HuC or ELAV-3 or PLE21), and Hu-antigen D (HuD or ELAV-4), which play important roles in neuronal differentiation, plasticity and memory. HuB is also expressed in gonads. Hu-antigen R (HuR or ELAV-1 or HuA) is ubiquitously expressed Hu family member. It has a variety of biological functions mostly related to the regulation of cellular response to DNA damage and other types of stress. Hu proteins perform their cytoplasmic and nuclear molecular functions by coordinately regulating functionally related mRNAs. In the cytoplasm, Hu proteins recognize and bind to AU-rich RNA elements (AREs) in the 3' untranslated regions (UTRs) of certain target mRNAs, such as GAP-43, vascular epithelial growth factor (VEGF), the glucose transporter GLUT1, eotaxin and c-fos, and stabilize those ARE-containing mRNAs. They also bind and regulate the translation of some target mRNAs, such as neurofilament M, GLUT1, and p27. In the nucleus, Hu proteins function as regulators of polyadenylation and alternative splicing. Each Hu protein contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 may cooperate in binding to an ARE. RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions. This family also includes the sex-lethal protein (SXL) from Drosophila melanogaster. SXL governs sexual differentiation and X chromosome dosage compensation in flies. It induces female-specific alternative splicing of the transformer (tra) pre-mRNA by binding to the tra uridine-rich polypyrimidine tract at the non-sex-specific 3' splice site during the sex-determination process. SXL binds to its own pre-mRNA and promotes female-specific alternative splicing. It contains an N-terminal Gly/Asn-rich domain that may be responsible for the protein-protein interaction, and tandem RRMs that show high preference to bind single-stranded, uridine-rich target RNA transcripts.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034630610 105 LPITITESDIREMMESFeGPQPAdVRLMK-RKTGVSRGFAFVEFYHLQDATSWMEAnQKKLVIQGKHIAMHYS 176
Cdd:cd12375     7 LPQSMTQEELRSLFGAI-GPIES-CKLVRdKITGQSLGYGFVNYRDPNDARKAINT-LNGLDLENKRLKVSYA 76

RNA recognition motif (RRM) found in polypyrimidine tract-binding protein 1 (PTB or hnRNP I), heterogeneous nuclear ribonucleoprotein L (hnRNP-L), and similar proteins; This subfamily corresponds to the RRM1 of the majority of family members that include polypyrimidine tract-binding protein 1 (PTB or hnRNP I), polypyrimidine tract-binding protein 2 (PTBP2 or nPTB), regulator of differentiation 1 (Rod1), heterogeneous nuclear ribonucleoprotein L (hnRNP-L), heterogeneous nuclear ribonucleoprotein L-like (hnRNP-LL), polypyrimidine tract-binding protein homolog 3 (PTBPH3), polypyrimidine tract-binding protein homolog 1 and 2 (PTBPH1 and PTBPH2), and similar proteins. PTB is an important negative regulator of alternative splicing in mammalian cells and also functions at several other aspects of mRNA metabolism, including mRNA localization, stabilization, polyadenylation, and translation. PTBP2 is highly homologous to PTB and is perhaps specific to the vertebrates. Unlike PTB, PTBP2 is enriched in the brain and in some neural cell lines. It binds more stably to the downstream control sequence (DCS) RNA than PTB does but is a weaker repressor of splicing in vitro. PTBP2 also greatly enhances the binding of two other proteins, heterogeneous nuclear ribonucleoprotein (hnRNP) H and KH-type splicing-regulatory protein (KSRP), to the DCS RNA. The binding properties of PTBP2 and its reduced inhibitory activity on splicing imply roles in controlling the assembly of other splicing-regulatory proteins. Rod1 is a mammalian polypyrimidine tract binding protein (PTB) homolog of a regulator of differentiation in the fission yeast Schizosaccharomyces pombe, where the nrd1 gene encodes an RNA binding protein negatively regulates the onset of differentiation. ROD1 is predominantly expressed in hematopoietic cells or organs. It might play a role controlling differentiation in mammals. hnRNP-L is a higher eukaryotic specific subunit of human KMT3a (also known as HYPB or hSet2) complex required for histone H3 Lys-36 trimethylation activity. It plays both, nuclear and cytoplasmic, roles in mRNA export of intronless genes, IRES-mediated translation, mRNA stability, and splicing. hnRNP-LL protein plays a critical and unique role in the signal-induced regulation of CD45 and acts as a global regulator of alternative splicing in activated T cells. The family also includes polypyrimidine tract binding protein homolog 3 (PTBPH3) found in plant. Although its biological roles remain unclear, PTBPH3 shows significant sequence similarity to other family members, all of which contain four RNA recognition motifs (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain). Although their biological roles remain unclear, both PTBPH1 and PTBPH2 show significant sequence similarity to PTB. However, in contrast to PTB, they have three RRMs. In addition, this family also includes RNA-binding motif protein 20 (RBM20) that is an alternative splicing regulator associated with dilated cardiomyopathy (DCM) and contains only one RRM.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034630610 100 IMLRGLPITITESDIREMMESFegPQPADVRLMKRKtgvsrGFAFVEFYHLQDATSWME-ANQKKLVIQGKHIAMHYSN 177
Cdd:cd12421     2 VHIRNLPPDATEADLVALGLPF--GKVTNVLLLKGK-----NQALVEMEDVESASSMVNyYTTVPPLIRGRPVYVQYSN 73

RNA recognition motif 3 (RRM3) found in RNA-binding protein 28 (RBM28) and similar proteins; This subfamily corresponds to the RRM3 of RBM28 and Nop4p. RBM28 is a specific nucleolar component of the spliceosomal small nuclear ribonucleoproteins (snRNPs), possibly coordinating their transition through the nucleolus. It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), and may play a role in the maturation of both small nuclear and ribosomal RNAs. RBM28 has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an extremely acidic region between RRM2 and RRM3. The family also includes nucleolar protein 4 (Nop4p or Nop77p) encoded by YPL043W from Saccharomyces cerevisiae. It is an essential nucleolar protein involved in processing and maturation of 27S pre-rRNA and biogenesis of 60S ribosomal subunits. Nop4p also contains four RRMs.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1034630610  98 KTIMLRGLPITITESDIREMMESFegpqpADVRL----MKRKTGVSRGFAFVEF 147
Cdd:cd12415     1 KTVFIRNLSFDTTEEDLKEFFSKF-----GEVKYarivLDKDTGHSKGTAFVQF 49

RNA recognition motif 1 (RRM1) found in RNA-binding protein 28 (RBM28) and similar proteins; This subfamily corresponds to the RRM1 of RBM28 and Nop4p. RBM28 is a specific nucleolar component of the spliceosomal small nuclear ribonucleoproteins (snRNPs), possibly coordinating their transition through the nucleolus. It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), and may play a role in the maturation of both small nuclear and ribosomal RNAs. RBM28 has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an extremely acidic region between RRM2 and RRM3. The family also includes nucleolar protein 4 (Nop4p or Nop77p) encoded by YPL043W from Saccharomyces cerevisiae. It is an essential nucleolar protein involved in processing and maturation of 27S pre-rRNA and biogenesis of 60S ribosomal subunits. Nop4p also contains four RRMs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630610  99 TIMLRGLPITITESDIREMMESFeGPqpadVR---LMKRK-TGVSRGFAFVEFYHLQDATSWMEANQKKLViQGKHIAMH 174
Cdd:cd12413     1 TLFVRNLPYDTTDEQLEELFSDV-GP----VKrcfVVKDKgKDKCRGFGYVTFALAEDAQRALEEVKGKKF-GGRKIKVE 74

                  ....*
gi 1034630610 175 YSNPR 179
Cdd:cd12413    75 LAKKK 79

RNA recognition motif 2 (RRM2) found in RNA-binding protein 34 (RBM34) and similar proteins; This subfamily corresponds to the RRM2 of RBM34, a putative RNA-binding protein containing two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). Although the function of RBM34 remains unclear currently, its RRM domains may participate in mRNA processing. RBM34 may act as an mRNA processing-related protein.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034630610 105 LPITITESDIREMmesFEGPQP-ADVRLMK-RKTGVSRGFAFVEFYHLQDATSWMEANQKKL 164
Cdd:cd12395     7 LPFDIEEEELRKH---FEDCGDvEAVRIVRdRETGIGKGFGYVLFKDKDSVDLALKLNGSKL 65

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 1034630610  61 ERERERR--------NSDRSEDGYHSDGDYGEHDYRHDIS----DERESKTIMLRGLPITITESDIREMMEsfEGPQPAD 128
Cdd:TIGR01622  66 PNRRYRPrekrrrrgDSYRRRRDDRRSRREKPRARDGTPEplteDERDRRTVFVQQLAARARERDLYEFFS--KVGKVRD 143