RNA recognition motif 1 (RRM1) found in yeast nucleolar protein 12 (Nop12p) and similar proteins; This subgroup corresponds to the RRM1 of Nop12p which is encoded by YOL041C from Saccharomyces cerevisiae. It is a novel nucleolar protein required for pre-25S rRNA processing and normal rates of cell growth at low temperatures. Nop12p shares high sequence similarity with nucleolar protein 13 (Nop13p). Both, Nop12p and Nop13p, are not essential for growth. However, unlike Nop13p that localizes primarily to the nucleolus but also present in the nucleoplasm to a lesser extent, Nop12p is localized to the nucleolus. Nop12p contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324532  148 RTVFIGNILSTVITSKKVYKEFKKLFgtnpiaeteesgnekeeesskksdNNEFAIESIRFRSISFDEALPRKVAFVQQK 227
Cdd:cd12669   1 RTIFVGNLPAEVVTSKSVYKNFKKLF------------------------NQFGKIQSIRFRSISFSDALPRKVAFIQKK 56

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 6324532  228 FHKSRDTINAYIVYKNKSaVRKICSNLNAVVFQDHHLRVDSVAHP 272
Cdd:cd12669  57 FHSSRDTVNAYIVFKEQS-SAKSALSLNGTVFMDRHLRVDSVAHP 100

RNA recognition motif 1 (RRM1) found in yeast nucleolar protein 12 (Nop12p) and similar proteins; This subgroup corresponds to the RRM1 of Nop12p which is encoded by YOL041C from Saccharomyces cerevisiae. It is a novel nucleolar protein required for pre-25S rRNA processing and normal rates of cell growth at low temperatures. Nop12p shares high sequence similarity with nucleolar protein 13 (Nop13p). Both, Nop12p and Nop13p, are not essential for growth. However, unlike Nop13p that localizes primarily to the nucleolus but also present in the nucleoplasm to a lesser extent, Nop12p is localized to the nucleolus. Nop12p contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324532  148 RTVFIGNILSTVITSKKVYKEFKKLFgtnpiaeteesgnekeeesskksdNNEFAIESIRFRSISFDEALPRKVAFVQQK 227
Cdd:cd12669   1 RTIFVGNLPAEVVTSKSVYKNFKKLF------------------------NQFGKIQSIRFRSISFSDALPRKVAFIQKK 56

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 6324532  228 FHKSRDTINAYIVYKNKSaVRKICSNLNAVVFQDHHLRVDSVAHP 272
Cdd:cd12669  57 FHSSRDTVNAYIVFKEQS-SAKSALSLNGTVFMDRHLRVDSVAHP 100

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324532     280 SIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKAL-LLNEKPMKSQK 348
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRDKETGKSKGFAFVEFESEEDAEKALeALNGKELDGRP 70

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6324532  280 SIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKA 336
Cdd:COG0724   3 KIYVGNLPYSVTEEDLRELFSEYGEVTSVKLITDRETGRSRGFGFVEMPDDEEAQAA 59

nucleic acid binding protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6324532   279 RSIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMgkgFAYVQFKDLQSVNKALLL 339
Cdd:PLN03120   5 RTVKVSNVSLKATERDIKEFFSFSGDIEYVEMQSENERSQ---IAYVTFKDPQGAETALLL 62

RNA recognition motif 1 (RRM1) found in yeast nucleolar protein 12 (Nop12p) and similar proteins; This subgroup corresponds to the RRM1 of Nop12p which is encoded by YOL041C from Saccharomyces cerevisiae. It is a novel nucleolar protein required for pre-25S rRNA processing and normal rates of cell growth at low temperatures. Nop12p shares high sequence similarity with nucleolar protein 13 (Nop13p). Both, Nop12p and Nop13p, are not essential for growth. However, unlike Nop13p that localizes primarily to the nucleolus but also present in the nucleoplasm to a lesser extent, Nop12p is localized to the nucleolus. Nop12p contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324532  148 RTVFIGNILSTVITSKKVYKEFKKLFgtnpiaeteesgnekeeesskksdNNEFAIESIRFRSISFDEALPRKVAFVQQK 227
Cdd:cd12669   1 RTIFVGNLPAEVVTSKSVYKNFKKLF------------------------NQFGKIQSIRFRSISFSDALPRKVAFIQKK 56

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 6324532  228 FHKSRDTINAYIVYKNKSaVRKICSNLNAVVFQDHHLRVDSVAHP 272
Cdd:cd12669  57 FHSSRDTVNAYIVFKEQS-SAKSALSLNGTVFMDRHLRVDSVAHP 100

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324532  280 SIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKALLLNEKPMksqkqedentkkptk 359
Cdd:cd12395   1 SVFVGNLPFDIEEEELRKHFEDCGDVEAVRIVRDRETGIGKGFGYVLFKDKDSVDLALKLNGSKL--------------- 65

                ....*...
gi 6324532  360 KARKLRVS 367
Cdd:cd12395  66 RGRKLRVK 73

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324532     280 SIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKAL-LLNEKPMKSQK 348
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRDKETGKSKGFAFVEFESEEDAEKALeALNGKELDGRP 70

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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 6324532  280 SIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMgKGFAYVQFKDLQSVNKALLLNEKPMK 345
Cdd:cd12391   1 TVFVSNLDYSVPEDKIREIFSGCGEITDVRLVKNYKGKS-KGYCYVEFKDEESAQKALKLDRQPVE 65

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6324532  281 IFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKAL 337
Cdd:cd12284   1 LYVGSLHFNITEDMLRGIFEPFGKIEFVQLQKDPETGRSKGYGFIQFRDAEDAKKAL 57

RNA recognition motif in type II polyadenylate-binding protein 2 (PABP-2) and similar proteins; This subgroup corresponds to the RRM of PABP-2, also termed poly(A)-binding protein 2, or nuclear poly(A)-binding protein 1 (PABPN1), or poly(A)-binding protein II (PABII), which is a ubiquitously expressed type II nuclear poly(A)-binding protein that directs the elongation of mRNA poly(A) tails during pre-mRNA processing. Although PABP-2 binds poly(A) with high affinity and specificity as type I poly(A)-binding proteins, it contains only one highly conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), which is responsible for the poly(A) binding. In addition, PABP-2 possesses an acidic N-terminal domain that is essential for the stimulation of PAP, and an arginine-rich C-terminal domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6324532  280 SIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKALLLNE 341
Cdd:cd12550   1 SVYVGNVDYGATAEELEAHFHGCGSVNRVTILCDKFSGHPKGFAYIEFADKESVRTALALDE 62

RNA recognition motif (RRM) found in Saccharomyces cerevisiae U1 small nuclear ribonucleoprotein SNP1 and similar proteins; SNP1, also called U1 snRNP protein SNP1, or U1 small nuclear ribonucleoprotein 70 kDa homolog, or U1 70K, or U1 snRNP 70 kDa homolog, interacts with mRNA and is involved in nuclear mRNA splicing. It is a component of the spliceosome, where it is associated with snRNP U1 by binding stem loop I of U1 snRNA. Members in this family contain an N-terminal U1snRNP70 domain and an RNA recognition motif (RRM), also called RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 6324532  271 HPAPHDKKRSIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKA 336
Cdd:cd21615  11 HIADGDPYKTLFVGRLDYSLTELELQKKFSKFGEIEKIRIVRDKETGKSRGYAFIVFKSESDAKNA 76

RNA recognition motif 1 (RRM1) found in vertebrate RNA-binding protein 39 (RBM39) and similar proteins; This subfamily corresponds to the RRM1 of RNA-binding protein 39 (RBM39), RNA-binding protein 23 (RBM23) and similar proteins. RBM39 (also termed HCC1) is a nuclear autoantigen that contains an N-terminal arginine/serine rich (RS) motif and three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). An octapeptide sequence called the RS-ERK motif is repeated six times in the RS region of RBM39. Although the cellular function of RBM23 remains unclear, it shows high sequence homology to RBM39 and contains two RRMs. It may possibly function as a pre-mRNA splicing factor.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 6324532  280 SIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKALLLNEKPMKSQ 347
Cdd:cd12283   1 TVFVMQLSLKARERDLYEFFSKAGKVRDVRLIMDRNSRRSKGVAYVEFYDVESVPLALALTGQRLLGQ 68

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 6324532    281 IFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSkTNMGKGFAYVQFKDLQSVNKAL 337
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRDE-TGRSKGFAFVEFEDEEDAEKAI 56

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6324532  280 SIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKA 336
Cdd:COG0724   3 KIYVGNLPYSVTEEDLRELFSEYGEVTSVKLITDRETGRSRGFGFVEMPDDEEAQAA 59

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 6324532  279 RSIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQS 332
Cdd:cd12398   1 RSVFVGNIPYDATEEQLKEIFSEVGPVVSFRLVTDRETGKPKGYGFCEFRDAET 54

RNA recognition motif (RRM) found in eukaryotic translation initiation factor 4H (eIF-4H) and similar proteins; This subfamily corresponds to the RRM of eIF-4H, also termed Williams-Beuren syndrome chromosomal region 1 protein, which, together with elf-4B/eIF-4G, serves as the accessory protein of RNA helicase eIF-4A. eIF-4H contains a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). It stimulates protein synthesis by enhancing the helicase activity of eIF-4A in the initiation step of mRNA translation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 6324532  282 FVGNLDFEEIEESLWKHFEPCgDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKALLLN 340
Cdd:cd12401   9 YVGNLPFNTVQGDLDAIFKDL-KVRSVRLVRDRETDKFKGFCYVEFEDLESLKEALEYD 66

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 6324532  279 RSIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKAL 337
Cdd:cd12415   1 KTVFIRNLSFDTTEEDLKEFFSKFGEVKYARIVLDKDTGHSKGTAFVQFKTKESADKCI 59

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324532  280 SIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKALLL 339
Cdd:cd12272   1 TVYIGNLAWDIDEDDLRELFAECCEITNVRLHTDKETGEFKGYGHVEFADEESLDAALKL 60

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein hnRNP A and hnRNP D subfamilies and similar proteins; This subfamily corresponds to the RRM1 in the hnRNP A subfamily which includes hnRNP A0, hnRNP A1, hnRNP A2/B1, hnRNP A3 and similar proteins. hnRNP A0 is a low abundance hnRNP protein that has been implicated in mRNA stability in mammalian cells. hnRNP A1 is an abundant eukaryotic nuclear RNA-binding protein that may modulate splice site selection in pre-mRNA splicing. hnRNP A2/B1 is an RNA trafficking response element-binding protein that interacts with the hnRNP A2 response element (A2RE). hnRNP A3 is also a RNA trafficking response element-binding protein that participates in the trafficking of A2RE-containing RNA. The hnRNP A subfamily is characterized by two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long glycine-rich region at the C-terminus. The hnRNP D subfamily includes hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins. hnRNP D0 is a UUAG-specific nuclear RNA binding protein that may be involved in pre-mRNA splicing and telomere elongation. hnRNP A/B is an RNA unwinding protein with a high affinity for G- followed by U-rich regions. hnRNP A/B has also been identified as an APOBEC1-binding protein that interacts with apolipoprotein B (apoB) mRNA transcripts around the editing site and thus, plays an important role in apoB mRNA editing. hnRNP DL (or hnRNP D-like) is a dual functional protein that possesses DNA- and RNA-binding properties. It has been implicated in mRNA biogenesis at the transcriptional and post-transcriptional levels. All members in this subfamily contain two putative RRMs and a glycine- and tyrosine-rich C-terminus. The family also contains DAZAP1 (Deleted in azoospermia-associated protein 1), RNA-binding protein Musashi homolog Musashi-1, Musashi-2 and similar proteins. They all harbor two RRMs.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6324532  281 IFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKAL 337
Cdd:cd12325   1 LFVGGLSWETTEESLREYFSKYGEVVDCVVMKDPATGRSRGFGFVTFKDPSSVDAVL 57

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6324532  281 IFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKAL 337
Cdd:cd12316   2 LFVRNLPFTATEDELRELFEAFGKISEVHIPLDKQTKRSKGFAFVLFVIPEDAVKAY 58

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 6324532  280 SIFVGNLDF----EEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKALLLN 340
Cdd:cd12451   1 TIFVKGFDAslgeDTIRDELREHFGECGEVTNVRIPTDRETGELKGFAYIEFSTKEAKEKALELN 65

RNA recognition motif (RRM) found in RNA-binding protein 7 (RBM7) and similar proteins; This subfamily corresponds to the RRM of RBM7, RBM11 and their eukaryotic homologous. RBM7 is an ubiquitously expressed pre-mRNA splicing factor that enhances messenger RNA (mRNA) splicing in a cell-specific manner or in a certain developmental process, such as spermatogenesis. It interacts with splicing factors SAP145 (the spliceosomal splicing factor 3b subunit 2) and SRp20, and may play a more specific role in meiosis entry and progression. Together with additional testis-specific RNA-binding proteins, RBM7 may regulate the splicing of specific pre-mRNA species that are important in the meiotic cell cycle. RBM11 is a novel tissue-specific splicing regulator that is selectively expressed in brain, cerebellum and testis, and to a lower extent in kidney. It is localized in the nucleoplasm and enriched in SRSF2-containing splicing speckles. It may play a role in the modulation of alternative splicing during neuron and germ cell differentiation. Both, RBM7 and RBM11, contain an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a region lacking known homology at the C-terminus. The RRM is responsible for RNA binding, whereas the C-terminal region permits nuclear localization and homodimerization.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 6324532  279 RSIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNmGKGFAYVQFKDLQSVNKAL-LLN 340
Cdd:cd12336   2 RTLFVGNLDPRVTEEILYELFLQAGPLEGVKIPKDPNGK-PKNFAFVTFKHEVSVPYAIqLLN 63

RNA recognition motif 1 (RRM1) found in type I polyadenylate-binding proteins; This subfamily corresponds to the RRM1 of type I poly(A)-binding proteins (PABPs), highly conserved proteins that bind to the poly(A) tail present at the 3' ends of most eukaryotic mRNAs. They have been implicated in the regulation of poly(A) tail length during the polyadenylation reaction, translation initiation, mRNA stabilization by influencing the rate of deadenylation and inhibition of mRNA decapping. The family represents type I polyadenylate-binding proteins (PABPs), including polyadenylate-binding protein 1 (PABP-1 or PABPC1), polyadenylate-binding protein 3 (PABP-3 or PABPC3), polyadenylate-binding protein 4 (PABP-4 or APP-1 or iPABP), polyadenylate-binding protein 5 (PABP-5 or PABPC5), polyadenylate-binding protein 1-like (PABP-1-like or PABPC1L), polyadenylate-binding protein 1-like 2 (PABPC1L2 or RBM32), polyadenylate-binding protein 4-like (PABP-4-like or PABPC4L), yeast polyadenylate-binding protein, cytoplasmic and nuclear (PABP or ACBP-67), and similar proteins. PABP-1 is a ubiquitously expressed multifunctional protein that may play a role in 3' end formation of mRNA, translation initiation, mRNA stabilization, protection of poly(A) from nuclease activity, mRNA deadenylation, inhibition of mRNA decapping, and mRNP maturation. Although PABP-1 is thought to be a cytoplasmic protein, it is also found in the nucleus. PABP-1 may be involved in nucleocytoplasmic trafficking and utilization of mRNP particles. PABP-1 contains four copies of RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), a less well conserved linker region, and a proline-rich C-terminal conserved domain (CTD). PABP-3 is a testis-specific poly(A)-binding protein specifically expressed in round spermatids. It is mainly found in mammalian and may play an important role in the testis-specific regulation of mRNA homeostasis. PABP-3 shows significant sequence similarity to PABP-1. However, it binds to poly(A) with a lower affinity than PABP-1. Moreover, PABP-1 possesses an A-rich sequence in its 5'-UTR and allows binding of PABP and blockage of translation of its own mRNA. In contrast, PABP-3 lacks the A-rich sequence in its 5'-UTR. PABP-4 is an inducible poly(A)-binding protein (iPABP) that is primarily localized to the cytoplasm. It shows significant sequence similarity to PABP-1 as well. The RNA binding properties of PABP-1 and PABP-4 appear to be identical. PABP-5 is encoded by PABPC5 gene within the X-specific subinterval, and expressed in fetal brain and in a range of adult tissues in mammals, such as ovary and testis. It may play an important role in germ cell development. Moreover, unlike other PABPs, PABP-5 contains only four RRMs, but lacks both the linker region and the CTD. PABP-1-like and PABP-1-like 2 are the orthologs of PABP-1. PABP-4-like is the ortholog of PABP-5. Their cellular functions remain unclear. The family also includes yeast PABP, a conserved poly(A) binding protein containing poly(A) tails that can be attached to the 3'-ends of mRNAs. The yeast PABP and its homologs may play important roles in the initiation of translation and in mRNA decay. Like vertebrate PABP-1, the yeast PABP contains four RRMs, a linker region, and a proline-rich CTD as well. The first two RRMs are mainly responsible for specific binding to poly(A). The proline-rich region may be involved in protein-protein interactions.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 6324532  280 SIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKAL------LLNEKP---MKSQK 348
Cdd:cd12378   1 SLYVGDLHPDVTEAMLYEKFSPAGPVLSIRVCRDAVTRRSLGYAYVNFQQPADAERALdtlnfdVIKGKPiriMWSQR 78

RNA recognition motif 2 (RRM2) found in splicing regulatory glutamine/lysine-rich protein 1 (SREK1) and similar proteins; This subfamily corresponds to the RRM2 of SREK1, also termed serine/arginine-rich-splicing regulatory protein 86-kDa (SRrp86), or splicing factor arginine/serine-rich 12 (SFRS12), or splicing regulatory protein 508 amino acid (SRrp508). SREK1 belongs to a family of proteins containing regions rich in serine-arginine dipeptides (SR proteins family), which is involved in bridge-complex formation and splicing by mediating protein-protein interactions across either introns or exons. It is a unique SR family member and it may play a crucial role in determining tissue specific patterns of alternative splicing. SREK1 can alter splice site selection by both positively and negatively modulating the activity of other SR proteins. For instance, SREK1 can activate SRp20 and repress SC35 in a dose-dependent manner both in vitro and in vivo. In addition, SREK1 contains two (some contain only one) RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and two serine-arginine (SR)-rich domains (SR domains) separated by an unusual glutamic acid-lysine (EK) rich region. The RRM and SR domains are highly conserved among other members of the SR superfamily. However, the EK domain is unique to SREK1. It plays a modulatory role controlling SR domain function by involvement in the inhibition of both constitutive and alternative splicing and in the selection of splice-site.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 6324532  278 KRSIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNmgKGFAYVQFKDLQSVNKALLLNEK 342
Cdd:cd12260   4 RRTVYVGNLDPSTTADQLLEFFSQAGEVKYVRMAGDETQP--TRYAFVEFAEQTSVINALKLNGK 66

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324532    268 SVAHPAPHDKKRsIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKAL 337
Cdd:TIGR01622 205 SGHHPNSIPFHR-LYVGNLHFNITEQDLRQIFEPFGEIEFVQLQKDPETGRSKGYGFIQFRDAEQAKEAL 273

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 6324532  280 SIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDsktnmgKGFAYVQFK 328
Cdd:cd12360   8 GIKAASNKLAQIEEILRRHFGEWGEIERIRVLPS------KGIAFVRYK 50

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 6324532  279 RSIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKAllLNEKPMK 345
Cdd:cd12761   3 RKLFIGGLSFETTDESLRSHFEQWGTLTDCVVMRDPNTKRSRGFGFVTYATVEEVDAA--MNARPHK 67

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 6324532  279 RSIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKA 336
Cdd:cd12236   2 KTLFVARLSYDTTESKLRREFEKYGPIKRVRLVRDKKTGKSRGYAFIEFEHERDMKAA 59

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
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6324532  275 HDKKRS---IFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQS 332
Cdd:cd12411   3 HDEYKDsayIYIGGLPYELTEGDILCVFSQYGEIVDINLVRDKKTGKSKGFAFLAYEDQRS 63

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A/B (hnRNP A/B) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP A/B, also termed APOBEC1-binding protein 1 (ABBP-1), an RNA unwinding protein with a high affinity for G- followed by U-rich regions. hnRNP A/B has also been identified as an APOBEC1-binding protein that interacts with apolipoprotein B (apoB) mRNA transcripts around the editing site and thus plays an important role in apoB mRNA editing. hnRNP A/B contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long C-terminal glycine-rich domain that contains a potential ATP/GTP binding loop.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6324532  276 DKKRSIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKAL 337
Cdd:cd12584   2 DPVKKIFVGGLNPETTEEKIREYFGEFGEIEAIELPMDPKTNKRRGFVFITFKEEDPVKKIL 63

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 6324532  281 IFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKALL 338
Cdd:cd12328   2 LFVGGLKEDVEEEDLREYFSQFGKVESVEIVTDKETGKKRGFAFVTFDDHDSVDKIVL 59

RNA recognition motif 1 (RRM1) found in Deleted in azoospermia-associated protein 1 (DAZAP1) and similar proteins; This subfamily corresponds to the RRM1 of DAZAP1 or DAZ-associated protein 1, also termed proline-rich RNA binding protein (Prrp), a multi-functional ubiquitous RNA-binding protein expressed most abundantly in the testis and essential for normal cell growth, development, and spermatogenesis. DAZAP1 is a shuttling protein whose acetylated form is predominantly nuclear and the nonacetylated form is in cytoplasm. It also functions as a translational regulator that activates translation in an mRNA-specific manner. DAZAP1 was initially identified as a binding partner of Deleted in Azoospermia (DAZ). It also interacts with numerous hnRNPs, including hnRNP U, hnRNP U like-1, hnRNPA1, hnRNPA/B, and hnRNP D, suggesting DAZAP1 might associate and cooperate with hnRNP particles to regulate adenylate-uridylate-rich elements (AU-rich element or ARE)-containing mRNAs. DAZAP1 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal proline-rich domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6324532  281 IFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKAL 337
Cdd:cd12574   2 LFVGGLDWSTTQETLRSYFSQYGEVVDCVIMKDKTTNQSRGFGFVKFKDPNCVGTVL 58

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
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 6324532  280 SIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKAL 337
Cdd:cd12447   1 TLFVGGLSWNVDDPWLKKEFEKYGGVISARVITDRGSGRSKGYGYVDFATPEAAQKAL 58

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6324532  281 IFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKAL 337
Cdd:cd12576   2 MFIGGLSWQTTPEGLREYFSKFGEITECMVMRDPTTKRSRGFGFVTFSDPASVDKVL 58

RNA recognition motif 1 and 2 (RRM1, RRM2) found in Arabidopsis thaliana CTC-interacting domain protein CID8, CID9, CID10, CID11, CID12, CID 13 and similar proteins; This subgroup corresponds to the RRM domains found in A. thaliana CID8, CID9, CID10, CID11, CID12, CID 13 and mainly their plant homologs. These highly related RNA-binding proteins contain an N-terminal PAM2 domain (PABP-interacting motif 2), two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a basic region that resembles a bipartite nuclear localization signal. The biological role of this family remains unclear.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6324532  279 RSIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMgkgFAYVQFKDLQSVNKALLLN 340
Cdd:cd12225   1 RTIHVGGIDGSLSEDELADYFSNCGEVTQVRLCGDRVHTR---FAWVEFATDASALSALNLD 59

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
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 6324532  280 SIFVGNLDFEEIEESLWKHFEPCGDIEYVRIirdsktNMGKGFAYVQFKDLQSVNKAL 337
Cdd:cd12346   3 TVFVGGLDPNVTEEDLRVLFGPFGEIVYVKI------PPGKGCGFVQFVNRASAEAAI 54

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 6324532    278 KRSIFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKALLLN-----EKPMKSQKQEDE 352
Cdd:TIGR01622 114 RRTVFVQQLAARARERDLYEFFSKVGKVRDVQIIKDRNSRRSKGVGYVEFYDVDSVQAALALTgqkllGIPVIVQLSEAE 193

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
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6324532  281 IFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDsKTNMGKGFAYVQFKDLQSVNKAL 337
Cdd:cd12412   5 IFVGGIDWDTTEEELREFFSKFGKVKDVKIIKD-RAGVSKGYGFVTFETQEDAEKIQ 60

RNA recognition motif 3 (RRM3) found in CELF/Bruno-like family of RNA binding proteins CELF1, CELF2, CELF3, CELF4, CELF5, CELF6 and similar proteins; This subgroup corresponds to the RRM3 of the CUGBP1 and ETR-3-like factors (CELF) or BRUNOL (Bruno-like) proteins, a family of structurally related RNA-binding proteins involved in the regulation of pre-mRNA splicing in the nucleus and in the control of mRNA translation and deadenylation in the cytoplasm. The family contains six members: CELF-1 (also termed BRUNOL-2, or CUG-BP1, or NAPOR, or EDEN-BP), CELF-2 (also termed BRUNOL-3, or ETR-3, or CUG-BP2, or NAPOR-2), CELF-3 (also termed BRUNOL-1, or TNRC4, or ETR-1, or CAGH4, or ER DA4), CELF-4 (also termed BRUNOL-4), CELF-5 (also termed BRUNOL-5), CELF-6 (also termed BRUNOL-6). They all contain three highly conserved RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C-terminus of the protein. The low sequence conservation of the linker region is highly suggestive of a large variety in the co-factors that associate with the various CELF family members. Based on both sequence similarity and function, the CELF family can be divided into two subfamilies, the first containing CELFs 1 and 2, and the second containing CELFs 3, 4, 5, and 6. The different CELF proteins may act through different sites on at least some substrates. Furthermore, CELF proteins may interact with each other in varying combinations to influence alternative splicing in different contexts.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 6324532  281 IFVGNLDFEEIEESLWKHFEPCGDIEYVRIIRDSKTNMGKGFAYVQFKDLQSVNKA 336
Cdd:cd12362   1 LFVYHLPNEFTDQDLYQLFAPFGNVVSAKVFVDKNTGRSKGFGFVSYDNPLSAQAA 56