U1 small nuclear ribonucleoprotein of 70kDa MW N terminal; This domain is found in eukaryotes. This domain is about 90 amino acids in length. This domain is found associated with pfam00076. This domain is part of U1 snRNP, which is the pre-mRNA binding protein of the penta-snRNP spliceosome complex. It extends over a distance of 180 A from its RNA binding domain, wraps around the core domain of U1 snRNP consisting of the seven Sm proteins and finally contacts U1-C, which is crucial for 5'-splice-site recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2368596618   6 SKYPDDVSRLFKPRPPLSYKRPTDYPYAKRQTnPNITGVANLLSTSLKHYMEEFPEGSPNNHLQRYEDIKLSKIKNAQLL 85
Cdd:pfam12220   1 SKLPPNLLALFAPRPPLPYLPPLDYPPEKRKT-APITGVAAYLSEFEEEEEPPPPPGTETKEEKRERKRKEKKEKQEEKL 79

                          90
                  ....*....|..
gi 2368596618  86 DRRLQNWNPNVD 97
Cdd:pfam12220  80 EEGLEEWDPNED 91

U1 small nuclear ribonucleoprotein of 70kDa MW N terminal; This domain is found in eukaryotes. This domain is about 90 amino acids in length. This domain is found associated with pfam00076. This domain is part of U1 snRNP, which is the pre-mRNA binding protein of the penta-snRNP spliceosome complex. It extends over a distance of 180 A from its RNA binding domain, wraps around the core domain of U1 snRNP consisting of the seven Sm proteins and finally contacts U1-C, which is crucial for 5'-splice-site recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2368596618   6 SKYPDDVSRLFKPRPPLSYKRPTDYPYAKRQTnPNITGVANLLSTSLKHYMEEFPEGSPNNHLQRYEDIKLSKIKNAQLL 85
Cdd:pfam12220   1 SKLPPNLLALFAPRPPLPYLPPLDYPPEKRKT-APITGVAAYLSEFEEEEEPPPPPGTETKEEKRERKRKEKKEKQEEKL 79

                          90
                  ....*....|..
gi 2368596618  86 DRRLQNWNPNVD 97
Cdd:pfam12220  80 EEGLEEWDPNED 91

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2368596618 108 TIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDP 158
Cdd:COG0724     3 KIYVGNLPYSVTEEDLRELFSEYGEVTSVKLITDRETGRSRGFGFVEMPDD 53

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2368596618  78 KIKNAQLLDRRLQNWNPNVDPHIKDTDPYRTIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKD 157
Cdd:TIGR01622 186 IVQLSEAEKNRAARAATETSGHHPNSIPFHRLYVGNLHFNITEQDLRQIFEPFGEIEFVQLQKDPETGRSKGYGFIQFRD 265

                  ....*..
gi 2368596618 158 PISSKMA 164
Cdd:TIGR01622 266 AEQAKEA 272

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2368596618 106 YRTIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMAFKEIGvhrGIQIKDRICIVDI 185
Cdd:cd12236     1 FKTLFVARLSYDTTESKLRREFEKYGPIKRVRLVRDKKTGKSRGYAFIEFEHERDMKAAYKHAD---GKKIDGRRVLVDV 77

                          90
                  ....*....|.
gi 2368596618 186 ERGRTVKYFKP 196
Cdd:cd12236    78 ERGRTVKGWKP 88

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2368596618  108 TIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMAFKEigvHRGIQIKDRICIV 183
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRDKETGKSKGFAFVEFESEEDAEKALEA---LNGKELDGRPLKV 73

RNA recognition motif (RRM) found in U11/U12 small nuclear ribonucleoprotein 35 kDa protein (U11/U12-35K) and similar proteins; This subfamily corresponds to the RRM of U11/U12-35K, also termed protein HM-1, or U1 snRNP-binding protein homolog, and is one of the components of the U11/U12 snRNP, which is a subunit of the minor (U12-dependent) spliceosome required for splicing U12-type nuclear pre-mRNA introns. U11/U12-35K is highly conserved among bilateria and plants, but lacks in some organisms, such as Saccharomyces cerevisiae and Caenorhabditis elegans. Moreover, U11/U12-35K shows significant sequence homology to U1 snRNP-specific 70 kDa protein (U1-70K or snRNP70). It contains a conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by an adjacent glycine-rich region, and Arg-Asp and Arg-Glu dipeptide repeats rich domain, making U11/U12-35K a possible functional analog of U1-70K. It may facilitate 5' splice site recognition in the minor spliceosome and play a role in exon bridging, interacting with components of the major spliceosome bound to the pyrimidine tract of an upstream U2-type intron. The family corresponds to the RRM of U11/U12-35K that may directly contact the U11 or U12 snRNA through the RRM domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2368596618 103 TDPYRTIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMAFKEigVHRGIqIKDRICI 182
Cdd:cd12237     1 GDPRLTLFVGRLSLQTTEEKLKEVFSRYGDIRRLRLVRDIVTGFSKRYAFIEYKEERDALHAYRD--AKKLV-IDQYEIF 77

                          90
                  ....*....|....
gi 2368596618 183 VDIERGRTVKYFKP 196
Cdd:cd12237    78 VDFECERTLPGWIP 91

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2368596618 107 RTIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMAFKE---IGVHRGIQIKDRICIV 183
Cdd:cd12415     1 KTVFIRNLSFDTTEEDLKEFFSKFGEVKYARIVLDKDTGHSKGTAFVQFKTKESADKCIEAandESEDGGLVLDGRKLIV 80

                  .
gi 2368596618 184 D 184
Cdd:cd12415    81 S 81

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        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2368596618 109 IFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMAFKEI 168
Cdd:cd12382     4 LFIGGLNTETNEKALEAVFGKYGRIVEVLLMKDRETNKSRGFAFVTFESPADAKDAARDM 63

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2368596618 108 TIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDP 158
Cdd:COG0724     3 KIYVGNLPYSVTEEDLRELFSEYGEVTSVKLITDRETGRSRGFGFVEMPDD 53

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 2368596618 107 RTIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMAFKEIgvhRGIQIKDRICIVD 184
Cdd:cd12398     1 RSVFVGNIPYDATEEQLKEIFSEVGPVVSFRLVTDRETGKPKGYGFCEFRDAETALSAVRNL---NGYELNGRPLRVD 75

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 2368596618 109 IFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDP 158
Cdd:cd12325     1 LFVGGLSWETTEESLREYFSKYGEVVDCVVMKDPATGRSRGFGFVTFKDP 50

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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2368596618 108 TIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDP 158
Cdd:cd21608     1 KLYVGNLSWDTTEDDLRDLFSEFGEVESAKVITDRETGRSRGFGFVTFSTA 51

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2368596618 109 IFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMAFKEIGvhrGIQIKDRI 180
Cdd:cd12316     2 LFVRNLPFTATEDELRELFEAFGKISEVHIPLDKQTKRSKGFAFVLFVIPEDAVKAYQELD---GSIFQGRL 70

RNA recognition motif 1 (RRM1) found in TAR DNA-binding protein 43 (TDP-43) and similar proteins; This subfamily corresponds to the RRM1 of TDP-43 (also termed TARDBP), a ubiquitously expressed pathogenic protein whose normal function and abnormal aggregation are directly linked to the genetic disease cystic fibrosis, and two neurodegenerative disorders: frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). TDP-43 binds both DNA and RNA, and has been implicated in transcriptional repression, pre-mRNA splicing and translational regulation. TDP-43 is a dimeric protein with two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal glycine-rich domain. The RRMs are responsible for DNA and RNA binding; they bind to TAR DNA and RNA sequences with UG-repeats. The glycine-rich domain can interact with the hnRNP family proteins to form the hnRNP-rich complex involved in splicing inhibition. It is also essential for the cystic fibrosis transmembrane conductance regulator (CFTR) exon 9-skipping activity.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2368596618 114 LPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMAFKEigVHRgiqIKDRICIVDI 185
Cdd:cd12321     7 LPWKTTEQDLKEYFSTFGEVLMVQVKKDPKTGRSKGFGFVRFASYETQVKVLSQ--RHM---IDGRWCDVKL 73

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 2368596618 108 TIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKiTQKSKGYAFIVFKD 157
Cdd:cd12412     4 RIFVGGIDWDTTEEELREFFSKFGKVKDVKIIKDR-AGVSKGYGFVTFET 52

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2368596618 109 IFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMA----FKEIGVHR 172
Cdd:cd12579     2 LFVGGLKGDVGEGDLVEHFSQFGTVEKVEVIADKDTGKKRGFGFVYFEDHDSADKAavvkFHSINGHR 69

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 2368596618 109 IFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDP 158
Cdd:cd12328     2 LFVGGLKEDVEEEDLREYFSQFGKVESVEIVTDKETGKKRGFAFVTFDDH 51

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 2368596618 109 IFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMAF 165
Cdd:cd12284     1 LYVGSLHFNITEDMLRGIFEPFGKIEFVQLQKDPETGRSKGYGFIQFRDAEDAKKAL 57

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2368596618 109 IFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMAFKEIG 169
Cdd:cd12353     2 IFVGDLSPEIETEDLKEAFAPFGEISDARVVKDTQTGKSKGYGFVSFVKKEDAENAIQGMN 62

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2368596618 110 FIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKdpiSSKMAFKEI----------GVHRGIQIK 177
Cdd:cd12361     3 FVGMIPKTASEEDVRPLFEQFGNIEEVQILRDKQTGQSKGCAFVTFS---TREEALRAIealhnkktmpGCSSPLQVK 77

RNA recognition motif 2 (RRM2) found in yeast nucleolar protein 12 (Nop12p) and similar proteins; This subgroup corresponds to the RRM2 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 is 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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2368596618 109 IFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMA 164
Cdd:cd12670     2 VFVGNLAFEAEEEGLWRYFGKCGAIESVRIVRDPKTNVGKGFAYVQFKDENAVEKA 57

RNA recognition motif 2 (RRM2) found in U2 large nuclear ribonucleoprotein auxiliary factor U2AF 65 kDa subunit (U2AF65) and similar proteins; This subfamily corresponds to the RRM2 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2368596618 109 IFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMAfkeIGVHRGIQIKDRICIV 183
Cdd:cd12231     3 LFIGGLPNYLNEDQVKELLQSFGKLKAFNLVKDSATGLSKGYAFCEYVDDNVTDQA---IAGLNGMQLGDKKLLV 74

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2368596618 108 TIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMAFK 166
Cdd:cd12272     1 TVYIGNLAWDIDEDDLRELFAECCEITNVRLHTDKETGEFKGYGHVEFADEESLDAALK 59

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins; This subfamily corresponds to the RRM2 of hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins. hnRNP D0, 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. It 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 memembers in this family contain two putative RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glycine- and tyrosine-rich C-terminus.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 2368596618 109 IFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKD 157
Cdd:cd12329     2 IFVGGLSPETTEEKIREYFGKFGNIVEIELPMDKKTNKRRGFCFITFDS 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2368596618 109 IFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPIS 160
Cdd:cd12576     2 MFIGGLSWQTTPEGLREYFSKFGEITECMVMRDPTTKRSRGFGFVTFSDPAS 53

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP A2/B1, 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 A2/B1 also functions as a splicing factor that regulates alternative splicing of the tumor suppressors, such as BIN1, WWOX, the antiapoptotic proteins c-FLIP and caspase-9B, the insulin receptor (IR), and the RON proto-oncogene among others. Overexpression of hnRNP A2/B1 has been described in many cancers. It functions as a nuclear matrix protein involving in RNA synthesis and the regulation of cellular migration through alternatively splicing pre-mRNA. It may play a role in tumor cell differentiation. hnRNP A2/B1 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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2368596618 107 RTIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKD 157
Cdd:cd12581     1 KKLFVGGIKEDTEEHHLRDYFEEYGKIDTIEIITDRQSGKKRGFGFVTFDD 51

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2368596618 111 IGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMAfkeIGVHRGIQIKDR 179
Cdd:cd12375     4 VNYLPQSMTQEELRSLFGAIGPIESCKLVRDKITGQSLGYGFVNYRDPNDARKA---INTLNGLDLENK 69

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein D-like (hnRNP D-like or hnRNP DL) and similar proteins; This subgroup corresponds to the RRM1 of hnRNP DL (or hnRNP D-like), also termed AU-rich element RNA-binding factor, or JKT41-binding protein (protein laAUF1 or JKTBP), which 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. hnRNP DL binds single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) in a non-sequencespecific manner, and interacts with poly(G) and poly(A) tenaciously. It contains two putative two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glycine- and tyrosine-rich C-terminus.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2368596618 109 IFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPIS 160
Cdd:cd12758     2 MFIGGLSWDTSKKDLTEYLSRFGEVVDCTIKTDPVTGRSRGFGFVLFKDAAS 53

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins; This subfamily corresponds to the RRM1 in 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 family contain two putative RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glycine- and tyrosine-rich C-terminus.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2368596618 109 IFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPIS 160
Cdd:cd12575     1 MFIGGLSWDTSKKDLKDYFSKFGEVVDCTIKLDPVTGRSRGFGFVLFKDAES 52

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2368596618 104 DPYRTIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFK--DPI 159
Cdd:cd12584     2 DPVKKIFVGGLNPETTEEKIREYFGEFGEIEAIELPMDPKTNKRRGFVFITFKeeDPV 59

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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2368596618 107 RTIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKD 157
Cdd:cd12582     1 KKIFVGGIKEDTEEYHLRDYFEKYGKIETIEVMEDRQSGKKRGFAFVTFDD 51

RNA recognition motif (RRM) found in cyclophilin-33 (Cyp33) and similar proteins; This subfamily corresponds to the RRM of Cyp33, also termed peptidyl-prolyl cis-trans isomerase E (PPIase E), or cyclophilin E, or rotamase E. Cyp33 is a nuclear RNA-binding cyclophilin with an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal PPIase domain. Cyp33 possesses RNA-binding activity and preferentially binds to polyribonucleotide polyA and polyU, but hardly to polyG and polyC. It binds specifically to mRNA, which can stimulate its PPIase activity. Moreover, Cyp33 interacts with the third plant homeodomain (PHD3) zinc finger cassette of the mixed lineage leukemia (MLL) proto-oncoprotein and a poly-A RNA sequence through its RRM domain. It further mediates downregulation of the expression of MLL target genes HOXC8, HOXA9, CDKN1B, and C-MYC, in a proline isomerase-dependent manner. Cyp33 also possesses a PPIase activity that catalyzes cis-trans isomerization of the peptide bond preceding a proline, which has been implicated in the stimulation of folding and conformational changes in folded and unfolded proteins. The PPIase activity can be inhibited by the immunosuppressive drug cyclosporin A.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2368596618 109 IFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMA 164
Cdd:cd12347     1 LYVGGLAEEVDEKVLHAAFIPFGDIVDIQIPLDYETEKHRGFAFVEFEEAEDAAAA 56

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2368596618 108 TIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPISSKMAFKEIgvhRGIQIKDRICIVDIER 187
Cdd:cd12413     1 TLFVRNLPYDTTDEQLEELFSDVGPVKRCFVVKDKGKDKCRGFGYVTFALAEDAQRALEEV---KGKKFGGRKIKVELAK 77

                  ..
gi 2368596618 188 GR 189
Cdd:cd12413    78 KK 79

RNA recognition motif (RRM) found in vertebrate deleted in azoospermia-like (DAZL) proteins; This subgroup corresponds to the RRM of DAZL, also termed SPGY-like-autosomal, encoded by the autosomal homolog of DAZ gene, DAZL. It is ancestral to the deleted in azoospermia (DAZ) protein. DAZL is germ-cell-specific RNA-binding protein that contains a RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a DAZ motif, a protein-protein interaction domain. Although their specific biochemical functions remain to be investigated, DAZL proteins may interact with poly(A)-binding proteins (PABPs), and act as translational activators of specific mRNAs during gametogenesis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2368596618 108 TIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKiTQKSKGYAFIVFKDP------ISSKMAFK 166
Cdd:cd12672     7 TVFVGGIDIRMDENEIRSFFARYGSVKEVKIITDR-TGVSKGYGFVSFYDDvdiqkiVESQINFH 70

RNA recognition motif 1 (RRM1) found in vertebrate Hu-antigen B (HuB); This subgroup corresponds to the RRM1 of HuB, also termed ELAV-like protein 2 (ELAV-2), or ELAV-like neuronal protein 1, or nervous system-specific RNA-binding protein Hel-N1 (Hel-N1), one of the neuronal members of the Hu family. The neuronal Hu proteins play important roles in neuronal differentiation, plasticity and memory. HuB is also expressed in gonads and is up-regulated during neuronal differentiation of embryonic carcinoma P19 cells. Like other Hu proteins, HuB contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 may cooperate in binding to an AU-rich RNA element (ARE). RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2368596618 104 DPYRTIFIGRLPYDLDEIELQKYFVKFGEIEKIRIVKDKITQKSKGYAFIVFKDPissKMAFKEIGVHRGIQIKDRICIV 183
Cdd:cd12771     2 DSKTNLIVNYLPQNMTQEELKSLFGSIGEIESCKLVRDKITGQSLGYGFVNYIEP---KDAEKAINTLNGLRLQTKTIKV 78

                  ....
gi 2368596618 184 DIER 187
Cdd:cd12771    79 SYAR 82