RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1021311761   67 TVYVGNLnSQTTTADQLLEFFKQVGEVKFVRMAGDET--QPTRFAFVEFADQNSVPRAL-AFNGVMFGDRPLKI 137
Cdd:smart00360   1 TLFVGNL-PPDTTEEELRELFSKFGKVESVRLVRDKEtgKSKGFAFVEFESEEDAEKALeALNGKELDGRPLKV 73

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1021311761  68 VYVGNLNsQTTTADQLLEFFKQVGEVKFVRMAGDET-QPTRFAFVEFADQNSVPRAL-AFNGVMFGDRPLK 136
Cdd:pfam00076   1 LFVGNLP-PDTTEEDLKDLFSKFGPIKSIRLVRDETgRSKGFAFVEFEDEEDAEKAIeALNGKELGGRELK 70

nucleic acid binding protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1021311761  66 RTVYVGNLnSQTTTADQLLEFFKQVGEVKFVRMAGDeTQPTRFAFVEFADQNSVPRALAFNGVMFGDRPLKINHSNNAIV 145
Cdd:PLN03120    5 RTVKVSNV-SLKATERDIKEFFSFSGDIEYVEMQSE-NERSQIAYVTFKDPQGAETALLLSGATIVDQSVTITPAEDYQL 82

                          90       100
                  ....*....|....*....|....*....
gi 1021311761 146 KPPEMTPQAAAKELEEVMKRVREAQSFIS 174
Cdd:PLN03120   83 PPEALAPLSSNSPASGAESAVKKAEDVVS 111

RNA recognition motif 1 (RRM1) found in Arabidopsis thaliana CTC-interacting domain protein CID8, CID9, CID10, CID11, CID12, CID 13 and similar proteins; This subgroup corresponds to the RRM1 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1021311761  64 IRRTVYVGNLNSQTTTAdQLLEFFKQVGEVKFVRMAGDETQPTRFAFVEFADQNSVPRALAFNGVMFGDRPLKINHSNNA 143
Cdd:cd12459     1 IRRTVYVSDIDQQVTEE-QLAALFSNCGQVVDCRICGDPNSVLRFAFIEFTDEEGARAALSLSGTMLGFYPVRVLPSKTA 79

                  .
gi 1021311761 144 I 144
Cdd:cd12459    80 I 80

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1021311761  66 RTVYVGNLNSQTTTADqLLEFFKQVGEVKFVRMAGDETQpTRFAFVEFADQNSVPRALAFNGVMFGDRPLKINHSNNA 143
Cdd:cd12225     1 RTIHVGGIDGSLSEDE-LADYFSNCGEVTQVRLCGDRVH-TRFAWVEFATDASALSALNLDGTTLGGHPLRVSPSKTA 76

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1021311761   67 TVYVGNLnSQTTTADQLLEFFKQVGEVKFVRMAGDET--QPTRFAFVEFADQNSVPRAL-AFNGVMFGDRPLKI 137
Cdd:smart00360   1 TLFVGNL-PPDTTEEELRELFSKFGKVESVRLVRDKEtgKSKGFAFVEFESEEDAEKALeALNGKELDGRPLKV 73

RNA recognition motif in type II polyadenylate-binding proteins; This subfamily corresponds to the RRM of type II polyadenylate-binding proteins (PABPs), including polyadenylate-binding protein 2 (PABP-2 or PABPN1), embryonic polyadenylate-binding protein 2 (ePABP-2 or PABPN1L) and similar proteins. PABPs are 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. ePABP-2 is predominantly located in the cytoplasm and PABP-2 is located in the nucleus. In contrast to the type I PABPs containing four copies of RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), the type II PABPs contains a single highly-conserved RRM. This subfamily also includes Saccharomyces cerevisiae RBP29 (SGN1, YIR001C) gene encoding cytoplasmic mRNA-binding protein Rbp29 that binds preferentially to poly(A). Although not essential for cell viability, Rbp29 plays a role in modulating the expression of cytoplasmic mRNA. Like other type II PABPs, Rbp29 contains one RRM only.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1021311761  68 VYVGNLNsQTTTADQLLEFFKQVGEVKFVRMAGDET--QPTRFAFVEFADQNSVPRALAFNGVMFGDRPLKI 137
Cdd:cd12306     2 IYVGNVD-YGTTPEELQAHFKSCGTINRVTILCDKFtgQPKGFAYIEFVDKSSVENALLLNESEFRGRQIKV 72

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1021311761  67 TVYVGNLNSQTTTADqLLEFFKQVGEVKFVRMAGDetQPTR----FAFVEFADQNSVPRALAFNGVMFGDRPLKI 137
Cdd:cd12283     1 TVFVMQLSLKARERD-LYEFFSKAGKVRDVRLIMD--RNSRrskgVAYVEFYDVESVPLALALTGQRLLGQPIMV 72

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1021311761  67 TVYVGNLNSQTTTADqLLEFFKQVgEVKFVRMAGD-ETQPTR-FAFVEFADQNSVPRALAFNGVMFGDRPLKINHSNN 142
Cdd:cd12401     7 TAYVGNLPFNTVQGD-LDAIFKDL-KVRSVRLVRDrETDKFKgFCYVEFEDLESLKEALEYDGALFEDRPLRVDIAEG 82

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1021311761  66 RTVYVGNLnSQTTTADQLLEFFKQVGEVKFVRMAGD-ET-QPTRFAFVEFADQNSVPRAL-AFNGVMFGDRPLKINHS 140
Cdd:cd12398     1 RSVFVGNI-PYDATEEQLKEIFSEVGPVVSFRLVTDrETgKPKGYGFCEFRDAETALSAVrNLNGYELNGRPLRVDFA 77

RNA recognition motif (RRM) found in nuclear cap-binding protein subunit 2 (CBP20) and similar proteins; This subfamily corresponds to the RRM of CBP20, also termed nuclear cap-binding protein subunit 2 (NCBP2), or cell proliferation-inducing gene 55 protein, or NCBP-interacting protein 1 (NIP1). CBP20 is the small subunit of the nuclear cap binding complex (CBC), which is a conserved eukaryotic heterodimeric protein complex binding to 5'-capped polymerase II transcripts and plays a central role in the maturation of pre-mRNA and uracil-rich small nuclear RNA (U snRNA). CBP20 is most likely responsible for the binding of capped RNA. It contains an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and interacts with the second and third domains of CBP80, the large subunit of CBC.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1021311761  68 VYVGNLnSQTTTADQLLEFFKQVGEVKFVRMAGDETQ--PTRFAFVEFADQNSVPRALAF-NGVMFGDRPLKI 137
Cdd:cd12240     1 LYVGNL-SFYTTEEQIYELFSKCGDIKRIIMGLDKFKktPCGFCFVEYYSREDAENAVKYlNGTKLDDRIIRV 72

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1021311761  67 TVYVGNLnSQTTTADQLLEFFKQVGEVKFVRMAGD-ETQPTR-FAFVEFADQNSVPRALAFNGVMFGDRPLKIN 138
Cdd:cd12272     1 TVYIGNL-AWDIDEDDLRELFAECCEITNVRLHTDkETGEFKgYGHVEFADEESLDAALKLAGTKLCGRPIRVD 73

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1021311761  67 TVYVGNLnSQTTTADQLLEFFKQVGEVKFVRMAGDETQPTR-FAFVEFADQNSVPRALAFNGVMFGDRPL 135
Cdd:cd12391     1 TVFVSNL-DYSVPEDKIREIFSGCGEITDVRLVKNYKGKSKgYCYVEFKDEESAQKALKLDRQPVEGRPM 69

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1021311761  67 TVYVGNLnSQTTTADQLLEFFKQVGEVKFVRMAGD-ETQPTR-FAFVEFADQNSVPRALAF-NGVMFGDRPLKIN 138
Cdd:cd21608     1 KLYVGNL-SWDTTEDDLRDLFSEFGEVESAKVITDrETGRSRgFGFVTFSTAEAAEAAIDAlNGKELDGRSIVVN 74

RNA recognition motif (RRM) found in vertebrate RNA-binding protein 7 (RBM7); This subfamily corresponds to the RRM of RBM7, a 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. RBM7 interacts with splicing factors SAP145 (the spliceosomal splicing factor 3b subunit 2) and SRp20. It 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. RBM7 contains 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1021311761  66 RTVYVGNLNSQTTTaDQLLEFFKQVGEVKFVRMAGD-ETQPTRFAFVEFADQNSVPRALA-FNGVMFGDRPLKI 137
Cdd:cd12592     2 RTLFVGNLDTKVTE-ELLFELFLQAGPVIKVKIPKDkDGKPKQFAFVNFKHEVSVPYAMNlLNGIKLYGRPLKI 74

RNA recognition motif (RRM) found in eukaryotic translation initiation factor 4B (eIF-4B) and similar proteins; This subfamily corresponds to the RRM of eIF-4B, a multi-domain RNA-binding protein that has been primarily implicated in promoting the binding of 40S ribosomal subunits to mRNA during translation initiation. It contains two RNA-binding domains; the N-terminal well-conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), binds the 18S rRNA of the 40S ribosomal subunit and the C-terminal basic domain (BD), including two arginine-rich motifs (ARMs), binds mRNA during initiation, and is primarily responsible for the stimulation of the helicase activity of eIF-4A. eIF-4B also contains a DRYG domain (a region rich in Asp, Arg, Tyr, and Gly amino acids) in the middle, which is responsible for both, self-association of eIF-4B and binding to the p170 subunit of eIF3. Additional research indicates that eIF-4B can interact with the poly(A) binding protein (PABP) in mammalian cells, which can stimulate both, the eIF-4B-mediated activation of the helicase activity of eIF-4A and binding of poly(A) by PABP. eIF-4B has also been shown to interact specifically with the internal ribosome entry sites (IRES) of several picornaviruses which facilitate cap-independent translation initiation.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1021311761  67 TVYVGNLnSQTTTADQLLEFFKQVGeVKFVRMAGDETQ--PTRFAFVEFADQNSVPRALAFNGVMFGDRPLKINHSNNA 143
Cdd:cd12402     4 TAYLGNL-PYDVTEDDIEDFFRGLN-ISSVRLPRENGPgrLRGFGYVEFEDRESLIQALSLNEESLKNRRIRVDVAGQA 80

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1021311761  67 TVYVGNLNSQTTtADQLLEFFKQVGEVKFVRMAGDE--TQPTRFAFVEFADQNSVPRALAFNGVMFGDRPLKIN 138
Cdd:cd12550     1 SVYVGNVDYGAT-AEELEAHFHGCGSVNRVTILCDKfsGHPKGFAYIEFADKESVRTALALDESLFRGRQIKVM 73

RNA recognition motif 1 (RRM1) found in U2 large nuclear ribonucleoprotein auxiliary factor U2AF 65 kDa subunit (U2AF65) and similar proteins; The subfamily corresponds to the RRM1 of U2AF65 and dU2AF50. U2AF65, also termed U2AF2, is the large subunit of U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor (U2AF), which has been implicated in the recruitment of U2 snRNP to pre-mRNAs and is a highly conserved heterodimer composed of large and small subunits. U2AF65 specifically recognizes the intron polypyrimidine tract upstream of the 3' splice site and promotes binding of U2 snRNP to the pre-mRNA branchpoint. U2AF65 also plays an important role in the nuclear export of mRNA. It facilitates the formation of a messenger ribonucleoprotein export complex, containing both the NXF1 receptor and the RNA substrate. Moreover, U2AF65 interacts directly and specifically with expanded CAG RNA, and serves as an adaptor to link expanded CAG RNA to NXF1 for RNA export. U2AF65 contains an N-terminal RS domain rich in arginine and serine, followed by a proline-rich segment and three C-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The N-terminal RS domain stabilizes the interaction of U2 snRNP with the branch point (BP) by contacting the branch region, and further promotes base pair interactions between U2 snRNA and the BP. The proline-rich segment mediates protein-protein interactions with the RRM domain of the small U2AF subunit (U2AF35 or U2AF1). The RRM1 and RRM2 are sufficient for specific RNA binding, while RRM3 is responsible for protein-protein interactions. The family also includes Splicing factor U2AF 50 kDa subunit (dU2AF50), the Drosophila ortholog of U2AF65. dU2AF50 functions as an essential pre-mRNA splicing factor in flies. It associates with intronless mRNAs and plays a significant and unexpected role in the nuclear export of a large number of intronless mRNAs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1021311761  66 RTVYVGNLNsQTTTADQLLEFFKQVgevkfVRMAGDETQP------------TRFAFVEFADQNSVPRALAFNGVMFGDR 133
Cdd:cd12230     2 RRLYVGNIP-PGITEEELMDFFNQA-----MRAAGLTQAPgnpvlavqinpdKNFAFVEFRSVEETTAALALDGIIFKGQ 75

                  ....
gi 1021311761 134 PLKI 137
Cdd:cd12230    76 PLKI 79

RNA recognition motif 3 (RRM3) found in ribonucleoprotein PTB-binding raver-1, raver-2 and similar proteins; This subfamily corresponds to the RRM3 of raver-1 and raver-2. Raver-1 is a ubiquitously expressed heterogeneous nuclear ribonucleoprotein (hnRNP) that serves as a co-repressor of the nucleoplasmic splicing repressor polypyrimidine tract-binding protein (PTB)-directed splicing of select mRNAs. It shuttles between the cytoplasm and the nucleus and can accumulate in the perinucleolar compartment, a dynamic nuclear substructure that harbors PTB. Raver-1 also modulates focal adhesion assembly by binding to the cytoskeletal proteins, including alpha-actinin, vinculin, and metavinculin (an alternatively spliced isoform of vinculin) at adhesion complexes, particularly in differentiated muscle tissue. Raver-2 is a novel member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. It shows high sequence homology to raver-1. Raver-2 exerts a spatio-temporal expression pattern during embryogenesis and is mainly limited to differentiated neurons and glia cells. Although it displays nucleo-cytoplasmic shuttling in heterokaryons, raver2 localizes to the nucleus in glia cells and neurons. Raver-2 can interact with PTB and may participate in PTB-mediated RNA-processing. However, there is no evidence indicating that raver-2 can bind to cytoplasmic proteins. Both, raver-1 and raver-2, contain three N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two putative nuclear localization signals (NLS) at the N- and C-termini, a central leucine-rich region, and a C-terminal region harboring two [SG][IL]LGxxP motifs. They binds to RNA through the RRMs. In addition, the two [SG][IL]LGxxP motifs serve as the PTB-binding motifs in raver1. However, raver-2 interacts with PTB through the SLLGEPP motif only.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1021311761  66 RTVYVGNLNSQTTTADQLLEFFKQVGEVKFVRMAGDETQPTRFAFVEFADQNSVPRA-LAFNGVMFGDRPLKI 137
Cdd:cd12390     3 KCLFVDRLPKDFRDGSELRKLFSQVGKPTFCQLAMGNGVPRGFAFVEFASAEDAEEAqQLLNGHDLQGSPIRV 75

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 1021311761  65 RRTVYVGNLNSQTTTADqLLEFFKQVGEVKFVRMAGDET--QPTRFAFVEFADQNSVPRALAFNGVMFGDRPLKINHS 140
Cdd:TIGR01622 114 RRTVFVQQLAARARERD-LYEFFSKVGKVRDVQIIKDRNsrRSKGVGYVEFYDVDSVQAALALTGQKLLGIPVIVQLS 190

RNA recognition motif 1 (RRM1) found in Schizosaccharomyces pombe mRNA export factor Crp79 and similar proteins; Crp79, also called meiotic expression up-regulated protein 5 (Mug5), or polyadenylate-binding protein crp79, or PABP, or poly(A)-binding protein, is an auxiliary mRNA export factor that binds the poly(A) tail of mRNA and is involved in the export of mRNA from the nucleus to the cytoplasm. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the first RRM motif.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1021311761  66 RTVYVGNLNSqTTTADQLLEFFKQVGEVKFVRMAGDET----QPTRFAFVEFADQNSVPRAL-AFNGVMFGDRPLKI 137
Cdd:cd21619     2 NTIYVGNIDM-TINEDALEKIFSRYGQVESVRRPPIHTdkadRTTGFGFIKYTDAESAERAMqQADGILLGRRRLVV 77

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1021311761  66 RTVYVGNLnSQTTTADQLLEFFKQVGEV-KFVRMAGDETQPTRFAFVEFADQNSVPRAL-AFNGVMFGDRPLKIN 138
Cdd:cd12446     1 TTVFVGNI-PDDVSDDFIRQLLEKCGKVlSWKRVQDPSGKLKAFGFCEFEDPEGALRALrLLNGLELGGKKLLVK 74

RNA recognition motif in vertebrate type II embryonic polyadenylate-binding protein 2 (ePABP-2); This subgroup corresponds to the RRM of ePABP-2, also termed embryonic poly(A)-binding protein 2, or poly(A)-binding protein nuclear-like 1 (PABPN1L). ePABP-2 is a novel embryonic-specific cytoplasmic type II poly(A)-binding protein that is expressed during the early stages of vertebrate development and in adult ovarian tissue. It may play an important role in the poly(A) metabolism of stored mRNAs during early vertebrate development. ePABP-2 shows significant sequence similarity to the ubiquitously expressed nuclear polyadenylate-binding protein 2 (PABP-2 or PABPN1). Like PABP-2, ePABP-2 contains one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), which is responsible for the poly(A) binding. In addition, it possesses an acidic N-terminal domain predicted to form a coiled-coil and an arginine-rich C-terminal domain.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1021311761  67 TVYVGNLNsQTTTADQLLEFFKQVGEVKFVRMAGDE--TQPTRFAFVEFADQNSVPRALAFNGVMFGDRPLKI 137
Cdd:cd12551     1 SVYVGNVD-YGSTADELEAHFNGCGPINRVTILCDKfsGHPKGYAYIEFATRSSVQAAVALDESSFRGRVIKV 72

RNA recognition motif 1 (RRM1) found in the U1A/U2B"/SNF protein family; This subfamily corresponds to the RRM1 of U1A/U2B"/SNF protein family which contains Drosophila sex determination protein SNF and its two mammalian counterparts, U1 small nuclear ribonucleoprotein A (U1 snRNP A or U1-A or U1A) and U2 small nuclear ribonucleoprotein B" (U2 snRNP B" or U2B"), all of which consist of two RNA recognition motifs (RRMs), connected by a variable, flexible linker. SNF is an RNA-binding protein found in the U1 and U2 snRNPs of Drosophila where it is essential in sex determination and possesses a novel dual RNA binding specificity. SNF binds with high affinity to both Drosophila U1 snRNA stem-loop II (SLII) and U2 snRNA stem-loop IV (SLIV). It can also bind to poly(U) RNA tracts flanking the alternatively spliced Sex-lethal (Sxl) exon, as does Drosophila Sex-lethal protein (SXL). U1A is an RNA-binding protein associated with the U1 snRNP, a small RNA-protein complex involved in pre-mRNA splicing. U1A binds with high affinity and specificity to stem-loop II (SLII) of U1 snRNA. It is predominantly a nuclear protein that shuttles between the nucleus and the cytoplasm independently of interactions with U1 snRNA. Moreover, U1A may be involved in RNA 3'-end processing, specifically cleavage, splicing and polyadenylation, through interacting with a large number of non-snRNP proteins. U2B", initially identified to bind to stem-loop IV (SLIV) at the 3' end of U2 snRNA, is a unique protein that comprises of the U2 snRNP. Additional research indicates U2B" binds to U1 snRNA stem-loop II (SLII) as well and shows no preference for SLIV or SLII on the basis of binding affinity. Moreover, U2B" does not require an auxiliary protein for binding to RNA, and its nuclear transport is independent of U2 snRNA binding.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1021311761  67 TVYVGNLNSQTTTAD---QLLEFFKQVGEV------KFVRMAGdetQptrfAFVEFADQNSVPRAL-AFNGVMFGDRPLK 136
Cdd:cd12246     1 TLYINNLNEKIKKDElkrSLYALFSQFGPVldivasKSLKMRG---Q----AFVVFKDVESATNALrALQGFPFYGKPMR 73

                  ....
gi 1021311761 137 INHS 140
Cdd:cd12246    74 IQYA 77

RNA recognition motif 1 (RRM1) found in Saccharomyces cerevisiae protein HRB1, G-strand-binding protein 2 (GBP2) and similar proteins; The family includes Saccharomyces cerevisiae protein HRB1 (also called protein TOM34) and GBP2, both of which are SR-like mRNA-binding proteins which shuttle from the nucleus to the cytoplasm when bound to the mature mRNA molecules. They act as quality control factors for spliced mRNAs. GBP2, also called RAP1 localization factor 6, is a single-strand telomeric DNA-binding protein that binds single-stranded telomeric sequences of the type (TG[1-3])n in vitro. It also binds to RNA. GBP2 influences the localization of RAP1 in the nuclei and plays a role in modulating telomere length. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the first RRM motif.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1021311761  67 TVYVGNLnSQTTTADQLLEFFKQVGEVkfVRmAGDETQPTR---FAFVEFADQNSVPRALA-FNGVMFGDR 133
Cdd:cd21605     3 SIFVGNL-PFDCTWEDLKDHFSQVGEV--IR-ADIVTSRGRhrgMGTVEFTNKEDVDRAISkFDHTMFMGR 69

RNA recognition motif 1 (RRM1) found in RNA-binding protein 34 (RBM34) and similar proteins; This subfamily corresponds to the RRM1 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1021311761  66 RTVYVGNLNSqTTTADQLLEFFKQVGEVKFVRMAG-------------------DETQPTRFAFVEFADQNSVPRALAFN 126
Cdd:cd12394     1 RTVFVGNLPV-TVKKKALKKLFKEFGKIESVRFRSvavanpklpkkvavikkkfHPKRDSMNAYVVFKEEESAQKALKLN 79

                          90
                  ....*....|.
gi 1021311761 127 GVMFGDRPLKI 137
Cdd:cd12394    80 GTEFEGHHIRV 90

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).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1021311761  65 RRTVYVGNLnSQTTTADQLLEFFKQVGEVKFVRMAGDET-QPTRFAFVEFADQNSVPRA-LAFNGVMFGDRPLKInhsnn 142
Cdd:cd12392     2 KNKLFVKGL-PFSCTKEELEELFKQHGTVKDVRLVTYRNgKPKGLAYVEYENEADASQAvLKTDGTEIKDHTISV----- 75

                  ....*.
gi 1021311761 143 AIVKPP 148
Cdd:cd12392    76 AISNPP 81

RNA recognition motif 3 (RRM3) found in SMART/HDAC1-associated repressor protein (SHARP) and similar proteins; This subfamily corresponds to the RRM3 of SHARP, also termed Msx2-interacting protein (MINT), or SPEN homolog, an estrogen-inducible transcriptional repressor that interacts directly with the nuclear receptor corepressor SMRT, histone deacetylases (HDACs) and components of the NuRD complex. SHARP recruits HDAC activity and binds to the steroid receptor RNA coactivator SRA through four conserved N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), further suppressing SRA-potentiated steroid receptor transcription activity. Thus, SHARP has the capacity to modulate both liganded and nonliganded nuclear receptors. SHARP also has been identified as a component of transcriptional repression complexes in Notch/RBP-Jkappa signaling pathways. In addition to the N-terminal RRMs, SHARP possesses a C-terminal SPOC domain (Spen paralog and ortholog C-terminal domain), which is highly conserved among Spen proteins.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1021311761  66 RTVYVGNLNSqTTTADQLLEFFKQVGEVKFVRMagdETQP--TRFAFVEFADQNSVPRAL-AFNGVMFGDRPLKI 137
Cdd:cd12350     3 RTLFIGNLEK-TTTYGDLRNIFERFGEIIDIDI---KKQNgnPQYAFLQYCDIASVVKAIkKMDGEYLGNNRLKL 73

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1021311761  68 VYVGNLnSQTTTADQLLEFFKQVGEV-KFVRMAGDETQPTR-FAFVEFADQNSVPRALAFNGVMFGDRPLKI 137
Cdd:cd12330     2 IFVGGL-APDVTEEEFKEYFEQFGTVvDAVVMLDHDTGRSRgFGFVTFDSESAVEKVLSKGFHELGGKKVEV 72

RNA recognition motif 3 (RRM3) found in Saccharomyces cerevisiae protein PES4, protein MIP6 and similar proteins; The family includes PES4 (also called DNA polymerase epsilon suppressor 4) and MIP6 (also called MEX67-interacting protein 6), both of which are predicted RNA binding proteins that may act as regulators of late translation, protection, and mRNA localization. MIP6 acts as a novel factor for nuclear mRNA export, binds to both poly(A)+ RNA and nuclear pores. It interacts with MEX67. Members in this family contain four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the third RRM motif.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1021311761  67 TVYVGNLNSqTTTADQLLEFFKQVGEVKFVRMAGDETQPTRFAFVEFADQNSVPRAL-AFNGVMFGDRPLKI 137
Cdd:cd21603     2 AIFVKNLPL-DTNNDEILDFFSKVGPIKSVFTSPKYKYNSLWAFVTYKKGSDTEKAIkLLNGTLFKGRTIEV 72

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor 11 (SRSF11), splicing regulatory glutamine/lysine-rich protein 1 (SREK1) and similar proteins; This subfamily corresponds to the RRM domain of SRSF11 (SRp54 or p54), SREK1 ( SFRS12 or SRrp86) and similar proteins, a group of proteins containing regions rich in serine-arginine dipeptides (SR protein family). These are involved in bridge-complex formation and splicing by mediating protein-protein interactions across either introns or exons. SR proteins have been identified as crucial regulators of alternative splicing. Different SR proteins display different substrate specificity, have distinct functions in alternative splicing of different pre-mRNAs, and can even negatively regulate splicing. All SR family members are characterized by the presence of one or two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and the C-terminal regions rich in serine and arginine dipeptides (SR domains). The RRM domain is responsible for RNA binding and specificity in both alternative and constitutive splicing. In contrast, SR domains are thought to be protein-protein interaction domains that are often interchangeable.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1021311761  68 VYVGNLnSQTTTADQLLEFFKQVGEVKFVRMAGDETQPT----RFAFVEFADQNSVPRALAFNGVMFGDRPLKI 137
Cdd:cd12259     2 VQVTNV-SPQATEEQMRTLFGFIGKIEELRLYPSEDDLApvlsKVCFVKYEDPEDVAVALHLTNTVFIDRALIV 74

RNA recognition motif 1 (RRM1) found in nucleolysin TIA-1 isoform p40 (p40-TIA-1) and similar proteins; This subgroup corresponds to the RRM1 of TIA-1, the 40-kDa isoform of T-cell-restricted intracellular antigen-1 (TIA-1) and a cytotoxic granule-associated RNA-binding protein mainly found in the granules of cytotoxic lymphocytes. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis, and functions as the granule component responsible for inducing apoptosis in cytolytic lymphocyte (CTL) targets. It is composed of three N-terminal highly homologous RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. TIA-1 interacts with RNAs containing short stretches of uridylates and its RRM2 can mediate the specific binding to uridylate-rich RNAs.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1021311761  67 TVYVGNLNSQTTTAdQLLEFFKQVGEVKFVRMAGDETQPTRFAFVEFADQNSVPRAL-AFNGVMFGDRPLKIN 138
Cdd:cd12615     1 TLYVGNLSRDVTEA-LILQLFSQIGPCKNCKMIMDTAGNDPYCFVEFHEHRHAAAALaAMNGRKIMGKEVKVN 72

RNA recognition motif 1 (RRM1) found in yeast regulator of rDNA transcription protein 5 (RRT5) and similar proteins; This subfamily corresponds to the RRM1 of the lineage specific family containing a group of uncharacterized yeast regulators of rDNA transcription protein 5 (RRT5), which may play roles in the modulation of rDNA transcription. RRT5 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1021311761  67 TVYVGNLNsQTTTADQLLEFFKQVGEVK------FVRMAGDETQ-PTRFAFVEFADQNSVPRAL-AFNGVMFGDRPLKI 137
Cdd:cd12409     1 RVYISNLS-YSTTEEELEELLKDYKPVSvlipsyTVRGFRSRKHrPLGIAYAEFSSVEEAEKVVkDLNGKVFKGRKLFV 78

RNA recognition motif (RRM) found in heterogeneous nuclear ribonucleoprotein (hnRNP) H protein family, epithelial splicing regulatory proteins (ESRPs), Drosophila RNA-binding protein Fusilli, RNA-binding protein 12 (RBM12) and similar proteins; The family includes RRM domains in the hnRNP H protein family, G-rich sequence factor 1 (GRSF-1), ESRPs (also termed RBM35), Drosophila Fusilli, RBM12 (also termed SWAN), RBM12B, RBM19 (also termed RBD-1) and similar proteins. The hnRNP H protein family includes hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H'), hnRNP F and hnRNP H3 (also termed hnRNP 2H9), which represent a group of nuclear RNA binding proteins that are involved in pre-mRNA processing. GRSF-1 is a cytoplasmic poly(A)+ mRNA binding protein which interacts with RNA in a G-rich element-dependent manner. It may function in RNA packaging, stabilization of RNA secondary structure, or other macromolecular interactions. ESRP1 (also termed RBM35A) and ESRP2 (also termed RBM35B) are epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of fibroblast growth factor receptor 2 (FGFR2), ENAH (also termed hMena), CD44 and CTNND1 (also termed p120-Catenin) transcripts. Fusilli shows high sequence homology to ESRPs. It can regulate endogenous FGFR2 splicing and functions as a splicing factor. The biological roles of both, RBM12 and RBM12B, remain unclear. RBM19 is a nucleolar protein conserved in eukaryotes. It is involved in ribosome biogenesis by processing rRNA. In addition, it is essential for preimplantation development. Members in this family contain 2~6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1021311761  67 TVYVGNLnSQTTTADQLLEFFK----QVGEVKFVRmaGDETQPTRFAFVEFADQNSVPRALAFNGVMFGDRPLKI 137
Cdd:cd12254     1 VVRLRGL-PFSATEEDIRDFFSgldiPPDGIHIVY--DDDGRPTGEAYVEFASEEDAQRALRRHKGKMGGRYIEV 72

RNA recognition motif 2 (RRM2) found in TAR DNA-binding protein 43 (TDP-43) and similar proteins; This subfamily corresponds to the RRM2 of TDP-43 (also termed TARDBP), a ubiquitously expressed pathogenic protein whose normal function and abnormal aggregation are directly linked to the genetic disease cystic fibrosis, and two neurodegenerative disorders: frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). TDP-43 binds both DNA and RNA, and has been implicated in transcriptional repression, pre-mRNA splicing and translational regulation. TDP-43 is a dimeric protein with two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal glycine-rich domain. The RRMs are responsible for DNA and RNA binding; they bind to TAR DNA and RNA sequences with UG-repeats. The glycine-rich domain can interact with the hnRNP family proteins to form the hnRNP-rich complex involved in splicing inhibition. It is also essential for the cystic fibrosis transmembrane conductance regulator (CFTR) exon 9-skipping activity.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1021311761  66 RTVYVGNLNSqTTTADQLLEFFKQVGEVKFVRMAgdetQPTR-FAFVEFADQNSV 119
Cdd:cd12322     1 RKVFVGRCTE-DMTEDDLRQYFSQFGEVTDVFIP----KPFRaFAFVTFADDEVA 50

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1021311761  69 YVGNLnSQTTTADQLLEFFKQVGEVK-FVRMAGDETQPTR-FAFVEFADQNSVPRALA 124
Cdd:cd12576     3 FIGGL-SWQTTPEGLREYFSKFGEITeCMVMRDPTTKRSRgFGFVTFSDPASVDKVLA 59