RNA recognition motif (RRM) found in speckle targeted PIP5K1A-regulated poly(A) polymerase (Star-PAP) and similar proteins; This subfamily corresponds to the RRM of Star-PAP, also termed RNA-binding motif protein 21 (RBM21), which is a ubiquitously expressed U6 snRNA-specific terminal uridylyltransferase (U6-TUTase) essential for cell proliferation. Although it belongs to the well-characterized poly(A) polymerase protein superfamily, Star-PAP is highly divergent from both, the poly(A) polymerase (PAP) and the terminal uridylyl transferase (TUTase), identified within the editing complexes of trypanosomes. Star-PAP predominantly localizes at nuclear speckles and catalyzes RNA-modifying nucleotidyl transferase reactions. It functions in mRNA biosynthesis and may be regulated by phosphoinositides. It binds to glutathione S-transferase (GST)-PIPKIalpha. Star-PAP preferentially uses ATP as a nucleotide substrate and possesses PAP activity that is stimulated by PtdIns4,5P2. It contains an N-terminal C2H2-type zinc finger motif followed by an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a split PAP domain linked by a proline-rich region, a PAP catalytic and core domain, a PAP-associated domain, an RS repeat, and a nuclear localization signal (NLS).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1543375474  54 GLRSVFVSGFPRDVDSAQLSEYFLAFGPVASVVMDKDKGVFAIVEMGDVGAREAVLSQSQHSLGGHRLRVRPRE 127
Cdd:cd12279     1 EERSVFVSGFKRGTSELELSDYFQAFGPVASVVMDKDKGVYAIVEMDSTETVEKVLSQPQHCLNGQRLRVKPRE 74

Zinc-finger of C2H2 type; This is a zinc-finger domain with the CxxCx(12)Hx(6)H motif, found in multiple copies in a wide range of proteins from plants to metazoans. Some member proteins, particularly those from plants, are annotated as being RNA-binding.

                          10        20
                  ....*....|....*....|....*
gi 1543375474  16 FRCCLCHVTTANRPSLDAHLGGRKH 40
Cdd:pfam12874   1 FYCELCNVTFNSESQLKSHLQGKKH 25

RNA recognition motif (RRM) found in speckle targeted PIP5K1A-regulated poly(A) polymerase (Star-PAP) and similar proteins; This subfamily corresponds to the RRM of Star-PAP, also termed RNA-binding motif protein 21 (RBM21), which is a ubiquitously expressed U6 snRNA-specific terminal uridylyltransferase (U6-TUTase) essential for cell proliferation. Although it belongs to the well-characterized poly(A) polymerase protein superfamily, Star-PAP is highly divergent from both, the poly(A) polymerase (PAP) and the terminal uridylyl transferase (TUTase), identified within the editing complexes of trypanosomes. Star-PAP predominantly localizes at nuclear speckles and catalyzes RNA-modifying nucleotidyl transferase reactions. It functions in mRNA biosynthesis and may be regulated by phosphoinositides. It binds to glutathione S-transferase (GST)-PIPKIalpha. Star-PAP preferentially uses ATP as a nucleotide substrate and possesses PAP activity that is stimulated by PtdIns4,5P2. It contains an N-terminal C2H2-type zinc finger motif followed by an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a split PAP domain linked by a proline-rich region, a PAP catalytic and core domain, a PAP-associated domain, an RS repeat, and a nuclear localization signal (NLS).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1543375474  54 GLRSVFVSGFPRDVDSAQLSEYFLAFGPVASVVMDKDKGVFAIVEMGDVGAREAVLSQSQHSLGGHRLRVRPRE 127
Cdd:cd12279     1 EERSVFVSGFKRGTSELELSDYFQAFGPVASVVMDKDKGVYAIVEMDSTETVEKVLSQPQHCLNGQRLRVKPRE 74

Nucleotidyltransferase (NT) domain of poly(A) polymerases and terminal uridylyl transferases; Poly(A) polymerases (PAPs) catalyze mRNA poly(A) tail synthesis, and terminal uridylyl transferases (TUTases) uridylate RNA. PAPs in this subgroup include human PAP alpha, mouse testis-specific cytoplasmic PAP beta, human nuclear PAP gamma, Saccharomyces cerevisiae PAP1, TRF4 and-5, Schizosaccharomyces pombe caffeine-induced death proteins -1, and -14, Caenorhabditis elegans Germ Line Development-2, and Chlamydomonas reinhardtii MUT68. This family also includes human U6 snRNA-specific TUTase1, and Trypanosoma brucei 3'-TUTase-1,-2, and 4. This family belongs to the Pol beta-like NT superfamily. In the majority of enzymes in this superfamily, two carboxylates, Dx[D/E], together with a third more distal carboxylate, coordinate two divalent metal cations involved in a two-metal ion mechanism of nucleotide addition. For the majority of proteins in this family, these carboxylate residues are conserved.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1543375474 341 LELVGSILRGCvPGVYRVQTVPSARRPVVKFCHRPSGLHGDVSLSNRLALHNSRFLSLCS 400
Cdd:cd05402    56 LRKLAKLLKKS-GEVVEVEPIINARVPIIKFVDKPTGIEVDISFNNLNGIRNTKLLRAYV 114

Cid1 family poly A polymerase; This domain is found in poly(A) polymerases and has been shown to have polynucleotide adenylyltransferase activity. Proteins in this family have been located to both the nucleus and the cytoplasm.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1543375474 490 PLSSLLAQFFSCVS-CWDLRGSLLSLREGQALPVAGgLPSNLWEGLRLGPLNLQDPFDLSH 549
Cdd:pfam03828   1 SLGELLIGFFEYYGrEFDYENVVISIRTGGILSKKE-KGWLRNEGRRPFLLCIEDPFDLDN 60

Zinc-finger of C2H2 type; This is a zinc-finger domain with the CxxCx(12)Hx(6)H motif, found in multiple copies in a wide range of proteins from plants to metazoans. Some member proteins, particularly those from plants, are annotated as being RNA-binding.

                          10        20
                  ....*....|....*....|....*
gi 1543375474  16 FRCCLCHVTTANRPSLDAHLGGRKH 40
Cdd:pfam12874   1 FYCELCNVTFNSESQLKSHLQGKKH 25

U1-like zinc finger; Family of C2H2-type zinc fingers, present in matrin, U1 small nuclear ribonucleoprotein C and other RNA-binding proteins.

                           10        20
                   ....*....|....*....|....*...
gi 1543375474   14 GGFRCCLCHVTTANRPSLDAHLGGRKHR 41
Cdd:smart00451   2 GGFYCKLCNVTFTDEISVEAHLKGKKHK 29

RNA recognition motif (RRM) found in speckle targeted PIP5K1A-regulated poly(A) polymerase (Star-PAP) and similar proteins; This subfamily corresponds to the RRM of Star-PAP, also termed RNA-binding motif protein 21 (RBM21), which is a ubiquitously expressed U6 snRNA-specific terminal uridylyltransferase (U6-TUTase) essential for cell proliferation. Although it belongs to the well-characterized poly(A) polymerase protein superfamily, Star-PAP is highly divergent from both, the poly(A) polymerase (PAP) and the terminal uridylyl transferase (TUTase), identified within the editing complexes of trypanosomes. Star-PAP predominantly localizes at nuclear speckles and catalyzes RNA-modifying nucleotidyl transferase reactions. It functions in mRNA biosynthesis and may be regulated by phosphoinositides. It binds to glutathione S-transferase (GST)-PIPKIalpha. Star-PAP preferentially uses ATP as a nucleotide substrate and possesses PAP activity that is stimulated by PtdIns4,5P2. It contains an N-terminal C2H2-type zinc finger motif followed by an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a split PAP domain linked by a proline-rich region, a PAP catalytic and core domain, a PAP-associated domain, an RS repeat, and a nuclear localization signal (NLS).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1543375474  54 GLRSVFVSGFPRDVDSAQLSEYFLAFGPVASVVMDKDKGVFAIVEMGDVGAREAVLSQSQHSLGGHRLRVRPRE 127
Cdd:cd12279     1 EERSVFVSGFKRGTSELELSDYFQAFGPVASVVMDKDKGVYAIVEMDSTETVEKVLSQPQHCLNGQRLRVKPRE 74

Nucleotidyltransferase (NT) domain of poly(A) polymerases and terminal uridylyl transferases; Poly(A) polymerases (PAPs) catalyze mRNA poly(A) tail synthesis, and terminal uridylyl transferases (TUTases) uridylate RNA. PAPs in this subgroup include human PAP alpha, mouse testis-specific cytoplasmic PAP beta, human nuclear PAP gamma, Saccharomyces cerevisiae PAP1, TRF4 and-5, Schizosaccharomyces pombe caffeine-induced death proteins -1, and -14, Caenorhabditis elegans Germ Line Development-2, and Chlamydomonas reinhardtii MUT68. This family also includes human U6 snRNA-specific TUTase1, and Trypanosoma brucei 3'-TUTase-1,-2, and 4. This family belongs to the Pol beta-like NT superfamily. In the majority of enzymes in this superfamily, two carboxylates, Dx[D/E], together with a third more distal carboxylate, coordinate two divalent metal cations involved in a two-metal ion mechanism of nucleotide addition. For the majority of proteins in this family, these carboxylate residues are conserved.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1543375474 341 LELVGSILRGCvPGVYRVQTVPSARRPVVKFCHRPSGLHGDVSLSNRLALHNSRFLSLCS 400
Cdd:cd05402    56 LRKLAKLLKKS-GEVVEVEPIINARVPIIKFVDKPTGIEVDISFNNLNGIRNTKLLRAYV 114

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1543375474   57 SVFVSGFPRDVDSAQLSEYFLAFGPVASVVMDKDKGV-----FAIVEMGDV-GAREAVLSQSQHSLGGHRLRV 123
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRDKETgkskgFAFVEFESEeDAEKALEALNGKELDGRPLKV 73

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 1543375474  58 VFVSGFPRDVDSAQLSEYFLAFGPV--ASVVMDKDKG---VFAIVEMGDVGAREAVLSQ-SQHSLGGHRLRVRP 125
Cdd:cd21608     2 LYVGNLSWDTTEDDLRDLFSEFGEVesAKVITDRETGrsrGFGFVTFSTAEAAEAAIDAlNGKELDGRSIVVNE 75

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1543375474  58 VFVSGFPRDVDSAQLSEYFLAFGPV--ASVVMDKDKGV---FAIVEMGDVGAREAVLSQSQHSLGGHRLRVRPREQK 129
Cdd:cd12330     2 IFVGGLAPDVTEEEFKEYFEQFGTVvdAVVMLDHDTGRsrgFGFVTFDSESAVEKVLSKGFHELGGKKVEVKRATPK 78

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 1543375474  56 RSVFVSGFPRDVDSAQLSEYFLAFGPVASV--VMDKDKG---VFAIVEMGDVG-AREAVLSQSQHSLGGHRLRV 123
Cdd:cd12398     1 RSVFVGNIPYDATEEQLKEIFSEVGPVVSFrlVTDRETGkpkGYGFCEFRDAEtALSAVRNLNGYELNGRPLRV 74

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A0 (hnRNP A0) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP A0, 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 A0 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1543375474  58 VFVSGFPRDVDSAQLSEYFLAFGPV--ASVVMDKDKGV---FAIVEMGDVGAREAVLSQSQHSLGGHRLRVRPREQKE 130
Cdd:cd12579     2 LFVGGLKGDVGEGDLVEHFSQFGTVekVEVIADKDTGKkrgFGFVYFEDHDSADKAAVVKFHSINGHRVEVKKAVPKE 79

RNA recognition motif 1 (RRM1) found in yeast nucleolar protein 3 (Npl3p) and similar proteins; This subfamily corresponds to the RRM1 of Npl3p, also termed mitochondrial targeting suppressor 1 protein, or nuclear polyadenylated RNA-binding protein 1. Npl3p is a major yeast RNA-binding protein that competes with 3'-end processing factors, such as Rna15, for binding to the nascent RNA, protecting the transcript from premature termination and coordinating transcription termination and the packaging of the fully processed transcript for export. It specifically recognizes a class of G/U-rich RNAs. Npl3p is a multi-domain protein containing two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), separated by a short linker and a C-terminal domain rich in glycine, arginine and serine residues.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1543375474  59 FVSGFPRDVDSAQLSEYFLAFGPVASVVMDKDKGvFAIVEM 99
Cdd:cd12340     3 FVRPFPPDTSESAIREIFSPYGPVKEVKMLSDSN-FAFVEF 42

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 1543375474  56 RSVFVSGFPRDVDSAQLSEYFLAFGPVASV--VMDKDKGVFAIVEMGDVGAREAVLSQSQHSLGGHRLRVRP 125
Cdd:cd12225     1 RTIHVGGIDGSLSEDELADYFSNCGEVTQVrlCGDRVHTRFAWVEFATDASALSALNLDGTTLGGHPLRVSP 72

RNA recognition motif 1 in La autoantigen (La or LARP3) and similar proteins; This subfamily corresponds to the RRM1 of La autoantigen, also termed Lupus La protein, or La ribonucleoprotein, or Sjoegren syndrome type B antigen (SS-B), a highly abundant nuclear phosphoprotein and well conserved in eukaryotes. It specifically binds the 3'-terminal UUU-OH motif of nascent RNA polymerase III transcripts and protects them from exonucleolytic degradation by 3' exonucleases. In addition, La can directly facilitate the translation and/or metabolism of many UUU-3' OH-lacking cellular and viral mRNAs, through binding internal RNA sequences within the untranslated regions of target mRNAs. La contains an N-terminal La motif (LAM), followed by two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). It also possesses a short basic motif (SBM) and a nuclear localization signal (NLS) at the C-terminus.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1543375474  57 SVFVSGFPRDVDSAQLSEYFLAFGPVASVVMDKDKG-------VFaiVEMGDVGAREAVLSQSQHSLGGHRLRV 123
Cdd:cd12291     1 TVYVKGFPLDATLDDIQEFFEKKGKVENVRMRRDLDskefkgsVF--VEFKTEEEAKKFLEKEKLKYKGKELTI 72

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A3 (hnRNP A3) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP A3, a novel RNA trafficking response element-binding protein that interacts with the hnRNP A2 response element (A2RE) independently of hnRNP A2 and participates in the trafficking of A2RE-containing RNA. hnRNP A3 can shuttle between the nucleus and the cytoplasm. It 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1543375474  56 RSVFVSGFPRDVDSAQLSEYFLAFGPVASVVMDKDKGV-----FAIVEMGDVGAREAVLSQSQHSLGGHRLRVR 124
Cdd:cd12582     1 KKIFVGGIKEDTEEYHLRDYFEKYGKIETIEVMEDRQSgkkrgFAFVTFDDHDTVDKIVVQKYHTINGHNCEVK 74

RNA recognition motif (RRM) found in cleavage stimulation factor subunit 2 (CSTF2), cleavage stimulation factor subunit 2 tau variant (CSTF2T) and similar proteins; This subgroup 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1543375474  55 LRSVFVSGFPRDVDSAQLSEYFLAFGPVAS--VVMDKDKGV---FAIVEMGDV-GAREAVLSQSQHSLGGHRLRV 123
Cdd:cd12671     6 LRSVFVGNIPYEATEEQLKDIFSEVGPVVSfrLVYDRETGKpkgYGFCEYQDQeTALSAMRNLNGYELNGRALRV 80

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP A1, also termed helix-destabilizing protein, or single-strand RNA-binding protein, or hnRNP core protein A1, 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. Moreover, hnRNP A1, together with the scaffold protein septin 6, serves as host proteins to form a complex with NS5b and viral RNA, and further play 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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1543375474  56 RSVFVSGFPRDVDSAQLSEYFLAFGPVASVVMDKDKGV-----FAIVEMGDVGAREAVLSQSQHSLGGHRLRVR 124
Cdd:cd12580     1 KKIFVGGIKEDTEEHHLRDYFEQYGKIEVIEIMTDRGSgkkrgFAFVTFDDHDSVDKIVIQKYHTVNGHNCEVR 74

RNA recognition motif (RRM) found in ras GTPase-activating protein-binding protein G3BP1, G3BP2 and similar proteins; This subfamily corresponds to the RRM domain in the G3BP family of RNA-binding and SH3 domain-binding proteins. G3BP acts at the level of RNA metabolism in response to cell signaling, possibly as RNA transcript stabilizing factors or an RNase. Members include G3BP1, G3BP2 and similar proteins. These proteins associate directly with the SH3 domain of GTPase-activating protein (GAP), which functions as an inhibitor of Ras. They all contain an N-terminal nuclear transfer factor 2 (NTF2)-like domain, an acidic domain, a domain containing PXXP motif(s), an RNA recognition motif (RRM), and an Arg-Gly-rich region (RGG-rich region, or arginine methylation motif).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1543375474  58 VFVSGFPRDVDSAQLSEYFLAFGPVASVVMDKDKGV-----FAIVEMGDVGAREAVLS-QSQHSLGGHRLRVRPR 126
Cdd:cd12229     6 LFVGNLPHDITEDELKEFFSRFGNVLELRINSKGGGgrlpnFGFVVFDDPEAVQKILAnKPIMFRGEHRLNVEEK 80

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1543375474  57 SVFVSGFPRDVDSAQLSEYFLAFGPVASV--VMDKDKGV---FAIVEMGDVGAREAVLSQSQHSLGGHRLRV 123
Cdd:cd12395     1 SVFVGNLPFDIEEEELRKHFEDCGDVEAVriVRDRETGIgkgFGYVLFKDKDSVDLALKLNGSKLRGRKLRV 72

Protein of unknown function (DUF3729); This family of proteins is found in viruses. Proteins in this family are typically between 145 and 1707 amino acids in length. The family is found in association with pfam01443, pfam01661, pfam05417, pfam01660, pfam00978. There is a single completely conserved residue L that may be functionally important.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1543375474 233 PKAPESPSLDSALASPLDPQALACTPASPPDSQPPASPQDSEALDFETPSSSLAPQTPDSALASETLASPQSLPPASP 310
Cdd:pfam12526  29 FSPPESAHPDPPPPVGDPRPPVVDTPPPVSAVWVLPPPSEPAAPEPDLVPPVTGPAGPPSPLAPPAPAQKPPLPPPRP 106

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1543375474  58 VFVSGFPRDVDSAQLSEYFLAFGPVASV-VMDKDKGvFAIVEMGDV-GAREAVLSQSQHSLGGHRLRV 123
Cdd:cd12373     2 VYVGNLGPRVTKRELEDAFEKYGPLRNVwVARNPPG-FAFVEFEDPrDAEDAVRALDGRRICGSRVRV 68

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein A/B (hnRNP A/B) and similar proteins; This subgroup corresponds to the RRM1 of hnRNP A/B, also termed APOBEC1-binding protein 1 (ABBP-1), which 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 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1543375474  58 VFVSGFPRDVDSAQLSEYFLAFGPVA--SVVMDKDKGV---FAIVEMGDVGAREAVLSQSQHSLGG 118
Cdd:cd12757     7 MFVGGLSWDTSKKDLKDYFTKFGEVVdcTIKMDPNTGRsrgFGFILFKDAASVDKVLEQKEHRLDG 72

RNA recognition motif (RRM) found in heterogeneous nuclear ribonucleoprotein G (hnRNP G), Y chromosome RNA recognition motif 1 (hRBMY), testis-specific heterogeneous nuclear ribonucleoprotein G-T (hnRNP G-T) and similar proteins; This subfamily corresponds to the RRM domain of hnRNP G, also termed glycoprotein p43 or RBMX, an RNA-binding motif protein located on the X chromosome. It is expressed ubiquitously and has been implicated in the splicing control of several pre-mRNAs. Moreover, hnRNP G may function as a regulator of transcription for SREBP-1c and GnRH1. Research has shown that hnRNP G may also act as a tumor-suppressor since it upregulates the Txnip gene and promotes the fidelity of DNA end-joining activity. In addition, hnRNP G appears to play a critical role in proper neural development of zebrafish and frog embryos. The family also includes several paralogs of hnRNP G, such as hRBMY and hnRNP G-T (also termed RNA-binding motif protein, X-linked-like-2). Both, hRBMY and hnRNP G-T, are exclusively expressed in testis and critical for male fertility. Like hnRNP G, hRBMY and hnRNP G-T interact with factors implicated in the regulation of pre-mRNA splicing, such as hTra2-beta1 and T-STAR. Although members in this family share a high conserved N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), they appear to recognize different RNA targets. For instance, hRBMY interacts specifically with a stem-loop structure in which the loop is formed by the sequence CA/UCAA. In contrast, hnRNP G associates with single stranded RNA sequences containing a CCA/C motif. In addition to the RRM, hnRNP G contains a nascent transcripts targeting domain (NTD) in the middle region and a novel auxiliary RNA-binding domain (RBD) in its C-terminal region. The C-terminal RBD exhibits distinct RNA binding specificity, and would play a critical role in the regulation of alternative splicing by hnRNP G.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1543375474  58 VFVSGFPRDVDSAQLSEYFLAFGPVASVVMDKDKG 92
Cdd:cd12382     4 LFIGGLNTETNEKALEAVFGKYGRIVEVLLMKDRE 38

RNA recognition motif 1 and 2 in poly [ADP-ribose] polymerase 10 (PARP-10) and similar proteins; This subgroup corresponds to the RRM1 and RRM2 of PARP-10, a novel oncoprotein c-Myc-interacting protein with poly(ADP-ribose) polymerase activity. It is localized to the nuclear and cytoplasmic compartments. In addition to the PARP activity, PARP-10 is also involved in the control of cell proliferation by inhibiting c-Myc- and E1A-mediated cotransformation of primary cells. PARP-10 may play a role in nuclear processes including the regulation of chromatin, gene transcription, and nuclear/cytoplasmic transport. It contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two overlapping C-terminal domains composed of a glycine-rich region and a region with homology to catalytic domains of PARP enzymes (PARP domain). In addition, PARP-10 contains two ubiquitin-interacting motifs (UIM).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1543375474  56 RSVFVSGFPRDVDSAQLSEYF-----LAFGPVASVVMDKDKgVFAIVEMGDVGAReaVLSQSQHSLGGHRLRVRP 125
Cdd:cd12547     1 GTLEVSGFSPDTSDELLELYFenkrrSGGGEVESIQRRGDK-AFITFEDPSVAER--VLARAEHVLNGATLTVKP 72

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1543375474  57 SVFVSGFPRDVDSAQLSEYFLAFGPVASV--VMDKDKGV---FAIVEMGDVGAREAVLSQSQHSLGGHRLRV 123
Cdd:cd12450     1 TLFVGNLSWSATQDDLENFFSDCGEVVDVriAMDRDDGRskgFGHVEFASAESAQKALEKSGQDLGGREIRL 72