RNA recognition motif (RRM) found in SRA stem-loop-interacting RNA-binding protein (SLIRP) and similar proteins; This subfamily corresponds to the RRM of SLIRP, a widely expressed small steroid receptor RNA activator (SRA) binding protein, which binds to STR7, a functional substructure of SRA. SLIRP is localized predominantly to the mitochondria and plays a key role in modulating several nuclear receptor (NR) pathways. It functions as a co-repressor to repress SRA-mediated nuclear receptor coactivation. It modulates SHARP- and SKIP-mediated co-regulation of NR activity. SLIRP contains an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), which is required for SLIRP's corepression activities.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 283046784  21 AFVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHIIDGVKIHVQ 92
Cdd:cd12242    2 LFVSNLPWTTGSSELKEYFSQFGKVKRCNLPFDKETGFHKGFGFVSFENEDGLRNALQKQKHIFEGNKVSVQ 73

RNA recognition motif (RRM) found in SRA stem-loop-interacting RNA-binding protein (SLIRP) and similar proteins; This subfamily corresponds to the RRM of SLIRP, a widely expressed small steroid receptor RNA activator (SRA) binding protein, which binds to STR7, a functional substructure of SRA. SLIRP is localized predominantly to the mitochondria and plays a key role in modulating several nuclear receptor (NR) pathways. It functions as a co-repressor to repress SRA-mediated nuclear receptor coactivation. It modulates SHARP- and SKIP-mediated co-regulation of NR activity. SLIRP contains an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), which is required for SLIRP's corepression activities.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 283046784  21 AFVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHIIDGVKIHVQ 92
Cdd:cd12242    2 LFVSNLPWTTGSSELKEYFSQFGKVKRCNLPFDKETGFHKGFGFVSFENEDGLRNALQKQKHIFEGNKVSVQ 73

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQ 79
Cdd:COG0724    5 YVGNLPYSVTEEDLRELFSEYGEVTSVKLITDRETGRSRGFGFVEMPDDEEAQAAIEA 62

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 283046784   34 ELREHFAQFGHVRRCTVPFDkETGFHRGMGWVQFSSQEELQNALQQEH-HIIDGVKIHVQ-AQR 95
Cdd:TIGR01628 301 KLRELFSECGEITSAKVMLD-EKGVSRGFGFVCFSNPEEANRAVTEMHgRMLGGKPLYVAlAQR 363

RNA recognition motif (RRM) found in SRA stem-loop-interacting RNA-binding protein (SLIRP) and similar proteins; This subfamily corresponds to the RRM of SLIRP, a widely expressed small steroid receptor RNA activator (SRA) binding protein, which binds to STR7, a functional substructure of SRA. SLIRP is localized predominantly to the mitochondria and plays a key role in modulating several nuclear receptor (NR) pathways. It functions as a co-repressor to repress SRA-mediated nuclear receptor coactivation. It modulates SHARP- and SKIP-mediated co-regulation of NR activity. SLIRP contains an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), which is required for SLIRP's corepression activities.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 283046784  21 AFVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHIIDGVKIHVQ 92
Cdd:cd12242    2 LFVSNLPWTTGSSELKEYFSQFGKVKRCNLPFDKETGFHKGFGFVSFENEDGLRNALQKQKHIFEGNKVSVQ 73

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKEtGFHRGMGWVQFSSQEELQNALQQEHH-IIDGVKIHVQ 92
Cdd:cd00590    2 FVGNLPPDTTEEDLRELFSKFGEVVSVRIVRDRD-GKSKGFAFVEFESPEDAEKALEALNGtELGGRPLKVS 72

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQ 79
Cdd:COG0724    5 YVGNLPYSVTEEDLRELFSEYGEVTSVKLITDRETGRSRGFGFVEMPDDEEAQAAIEA 62

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHI-IDGVKIHVQ 92
Cdd:cd12413    3 FVRNLPYDTTDEQLEELFSDVGPVKRCFVVKDKGKDKCRGFGYVTFALAEDAQRALEEVKGKkFGGRKIKVE 74

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHIIDGVKI 89
Cdd:cd12576    3 FIGGLSWQTTPEGLREYFSKFGEITECMVMRDPTTKRSRGFGFVTFSDPASVDKVLAQGPHELDGKKI 70

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHIIDGVKI 89
Cdd:cd12757    8 FVGGLSWDTSKKDLKDYFTKFGEVVDCTIKMDPNTGRSRGFGFILFKDAASVDKVLEQKEHRLDGRVI 75

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 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHH-IIDGVKIHV 91
Cdd:cd12316    3 FVRNLPFTATEDELRELFEAFGKISEVHIPLDKQTKRSKGFAFVLFVIPEDAVKAYQELDGsIFQGRLLHV 73

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQ 79
Cdd:cd12415    4 FIRNLSFDTTEEDLKEFFSKFGEVKYARIVLDKDTGHSKGTAFVQFKTKESADKCIEA 61

RNA recognition motif (RRM) found in AZoospermia (DAZ) autosomal homologs, DAZL (DAZ-like) and BOULE; This subfamily corresponds to the RRM domain of two Deleted in AZoospermia (DAZ) autosomal homologs, DAZL (DAZ-like) and BOULE. BOULE is the founder member of the family and DAZL arose from BOULE in an ancestor of vertebrates. The DAZ gene subsequently originated from a duplication transposition of the DAZL gene. Invertebrates contain a single DAZ homolog, BOULE, while vertebrates, other than catarrhine primates, possess both BOULE and DAZL genes. The catarrhine primates possess BOULE, DAZL, and DAZ genes. The family members encode closely related RNA-binding proteins that are required for fertility in numerous organisms. These proteins contain an RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a varying number of copies of a DAZ motif, believed to mediate protein-protein interactions. DAZL and BOULE contain a single copy of the DAZ motif, while DAZ proteins can contain 8-24 copies of this repeat. Although their specific biochemical functions remain to be investigated, DAZL proteins may interact with poly(A)-binding proteins (PABPs), and act as translational activators of specific mRNAs during gametogenesis.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKEtGFHRGMGWVQFSSQEELQNALQ-QEHHIIDGVKIHV 91
Cdd:cd12412    6 FVGGIDWDTTEEELREFFSKFGKVKDVKIIKDRA-GVSKGYGFVTFETQEDAEKIQKwGANLVFKGKKLNV 75

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 283046784   22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDkETGFHRGMGWVQFSSQEELQNALQQEHHI-IDGVKIH 90
Cdd:pfam00076   2 FVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRD-ETGRSKGFAFVEFEDEEDAEKAIEALNGKeLGGRELK 70

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 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHIIDGVKIHVQ 92
Cdd:cd12330    3 FVGGLAPDVTEEEFKEYFEQFGTVVDAVVMLDHDTGRSRGFGFVTFDSESAVEKVLSKGFHELGGKKVEVK 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 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHIIDGVKIHV 91
Cdd:cd12306    3 YVGNVDYGTTPEELQAHFKSCGTINRVTILCDKFTGQPKGFAYIEFVDKSSVENALLLNESEFRGRQIKV 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).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHIIDGVKIHVQAQRAK 97
Cdd:cd12450    3 FVGNLSWSATQDDLENFFSDCGEVVDVRIAMDRDDGRSKGFGHVEFASAESAQKALEKSGQDLGGREIRLDLANER 78

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHIIDGVKIhvQAQRAK 97
Cdd:cd12758    3 FIGGLSWDTSKKDLTEYLSRFGEVVDCTIKTDPVTGRSRGFGFVLFKDAASVDKVLELKEHKLDGKLI--DPKRAK 76

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDketgfHRGMGWVQFSSQEELQNALQQEhHIIDGVKIHV 91
Cdd:cd12322    4 FVGRCTEDMTEDDLRQYFSQFGEVTDVFIPKP-----FRAFAFVTFADDEVAQSLCGED-HIIKGVSVHI 67

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQ--EHHIID 85
Cdd:cd21615   22 FVGRLDYSLTELELQKKFSKFGEIEKIRIVRDKETGKSRGYAFIVFKSESDAKNAFKEgnGLRGLK 87

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 283046784  23 VRKIPWTAAASELREHFAQFGHVRRCTVPfDKETGFHRGMGWVQFSSQEELQNALQ 78
Cdd:cd12320    5 VKNVPFEATRKEIRELFSPFGQLKSVRLP-KKFDGSHRGFAFVEFVTKQEAQNAME 59

RNA recognition motif 1 (RRM1) 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHiIDGVKI 89
Cdd:cd12577    2 FIGGLNWDTTEEGLRDYFSQFGTVVDCTIMKDSATGRSRGFGFLTFEDPSSVNEVMKKEHV-LDGKII 68

RNA recognition motif 2 (RRM2) found in RNA-binding protein Musashi homologs Musashi-1, Musashi-2 and similar proteins; This subfamily corresponds to the RRM2.in Musashi-1 (also termed Msi1), 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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHIIDGVKIHVQ 92
Cdd:cd12323    3 FVGGLSANTTEDDVKKYFSQFGKVEDAMLMFDKQTNRHRGFGFVTFESEDVVDKVCEIHFHEINNKMVECK 73

RNA recognition motif 3 in fungal pre-messenger RNA splicing protein 24 (Prp24) and similar proteins; This subfamily corresponds to the RRM3 of Prp24, also termed U4/U6 snRNA-associated-splicing factor PRP24 (U4/U6 snRNP), an RNA-binding protein with four well conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). It facilitates U6 RNA base-pairing with U4 RNA during spliceosome assembly. Prp24 specifically binds free U6 RNA primarily with RRMs 1 and 2 and facilitates pairing of U6 RNA bases with U4 RNA bases. Additionally, it may also be involved in dissociation of the U4/U6 complex during spliceosome activation.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHR---GMGWVQFSSQEELQNALQQEHHIIDGVKIHV 91
Cdd:cd12298    4 RVRNLDFELDEEALRGIFEKFGEIESINIPKKQKNRKGRhnnGFAFVTFEDADSAESALQLNGTLLDNRKISV 76

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein A subfamily; This subfamily corresponds to the RRM1 in 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 283046784  35 LREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHIIDGVKihVQAQRA 96
Cdd:cd12578   16 LRNHFEQWGEITDVVVMKDPATKRSRGFGFVTYSSASEVDAAMNARPHKVDGRV--VEPKRA 75

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 283046784  22 FVRKIPWTAAASELREHFAQFGHVRrcTVPFDKETGFHrgmGWVQFSSQEELQNALQQEHHIIDGVKIHVQAQ 94
Cdd:cd12279    6 FVSGFKRGTSELELSDYFQAFGPVA--SVVMDKDKGVY---AIVEMDSTETVEKVLSQPQHCLNGQRLRVKPR 73

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKetGFHRGMGWVQFSSQEELQNALQQEHH 82
Cdd:cd21605    5 FVGNLPFDCTWEDLKDHFSQVGEVIRADIVTSR--GRHRGMGTVEFTNKEDVDRAISKFDH 63

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEH-HIIDGVKIHVQ 92
Cdd:cd12362    2 FVYHLPNEFTDQDLYQLFAPFGNVVSAKVFVDKNTGRSKGFGFVSYDNPLSAQAAIKAMNgFQVGGKRLKVQ 73

glycine-rich RNA-binding protein 4; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQ 79
Cdd:PLN03134  38 FIGGLSWGTDDASLRDAFAHFGDVVDAKVIVDRETGRSRGFGFVNFNDEGAATAAISE 95

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor SRSF10, SRSF12 and similar proteins; This subfamily corresponds to the RRM of SRSF10 and SRSF12. SRSF10, also termed 40 kDa SR-repressor protein (SRrp40), or FUS-interacting serine-arginine-rich protein 1 (FUSIP1), or splicing factor SRp38, or splicing factor, arginine/serine-rich 13A (SFRS13A), or TLS-associated protein with Ser-Arg repeats (TASR). It is a serine-arginine (SR) protein that acts as a potent and general splicing repressor when dephosphorylated. It mediates global inhibition of splicing both in M phase of the cell cycle and in response to heat shock. SRSF10 emerges as a modulator of cholesterol homeostasis through the regulation of low-density lipoprotein receptor (LDLR) splicing efficiency. It also regulates cardiac-specific alternative splicing of triadin pre-mRNA and is required for proper Ca2+ handling during embryonic heart development. In contrast, the phosphorylated SRSF10 functions as a sequence-specific splicing activator in the presence of a nuclear cofactor. It activates distal alternative 5' splice site of adenovirus E1A pre-mRNA in vivo. Moreover, SRSF10 strengthens pre-mRNA recognition by U1 and U2 snRNPs. SRSF10 localizes to the nuclear speckles and can shuttle between nucleus and cytoplasm. SRSF12, also termed 35 kDa SR repressor protein (SRrp35), or splicing factor, arginine/serine-rich 13B (SFRS13B), or splicing factor, arginine/serine-rich 19 (SFRS19), is a serine/arginine (SR) protein-like alternative splicing regulator that antagonizes authentic SR proteins in the modulation of alternative 5' splice site choice. For instance, it activates distal alternative 5' splice site of the adenovirus E1A pre-mRNA in vivo. Both, SRSF10 and SRSF12, contain a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C-terminal RS domain rich in serine-arginine dipeptides.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHI-IDGVKIHVQ 92
Cdd:cd12312    4 FVRNVADDTRPDDLRREFGRYGPIVDVYIPLDFYTRRPRGFAYIQFEDVRDAEDALYYLDRTrFLGREIEIQ 75

RNA recognition motif 4 (RRM4) found in type I polyadenylate-binding proteins; This subfamily corresponds to the RRM4 of type I poly(A)-binding proteins (PABPs), highly conserved proteins that bind to the poly(A) tail present at the 3' ends of most eukaryotic mRNAs. They have been implicated in theThe CD corresponds to the RRM. regulation of poly(A) tail length during the polyadenylation reaction, translation initiation, mRNA stabilization by influencing the rate of deadenylation and inhibition of mRNA decapping. The family represents type I polyadenylate-binding proteins (PABPs), including polyadenylate-binding protein 1 (PABP-1 or PABPC1), polyadenylate-binding protein 3 (PABP-3 or PABPC3), polyadenylate-binding protein 4 (PABP-4 or APP-1 or iPABP), polyadenylate-binding protein 5 (PABP-5 or PABPC5), polyadenylate-binding protein 1-like (PABP-1-like or PABPC1L), polyadenylate-binding protein 1-like 2 (PABPC1L2 or RBM32), polyadenylate-binding protein 4-like (PABP-4-like or PABPC4L), yeast polyadenylate-binding protein, cytoplasmic and nuclear (PABP or ACBP-67), and similar proteins. PABP-1 is an ubiquitously expressed multifunctional protein that may play a role in 3' end formation of mRNA, translation initiation, mRNA stabilization, protection of poly(A) from nuclease activity, mRNA deadenylation, inhibition of mRNA decapping, and mRNP maturation. Although PABP-1 is thought to be a cytoplasmic protein, it is also found in the nucleus. PABP-1 may be involved in nucleocytoplasmic trafficking and utilization of mRNP particles. PABP-1 contains four copies of RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), a less well conserved linker region, and a proline-rich C-terminal conserved domain (CTD). PABP-3 is a testis-specific poly(A)-binding protein specifically expressed in round spermatids. It is mainly found in mammalian and may play an important role in the testis-specific regulation of mRNA homeostasis. PABP-3 shows significant sequence similarity to PABP-1. However, it binds to poly(A) with a lower affinity than PABP-1. Moreover, PABP-1 possesses an A-rich sequence in its 5'-UTR and allows binding of PABP and blockage of translation of its own mRNA. In contrast, PABP-3 lacks the A-rich sequence in its 5'-UTR. PABP-4 is an inducible poly(A)-binding protein (iPABP) that is primarily localized to the cytoplasm. It shows significant sequence similarity to PABP-1 as well. The RNA binding properties of PABP-1 and PABP-4 appear to be identical. PABP-5 is encoded by PABPC5 gene within the X-specific subinterval, and expressed in fetal brain and in a range of adult tissues in mammalian, such as ovary and testis. It may play an important role in germ cell development. Moreover, unlike other PABPs, PABP-5 contains only four RRMs, but lacks both the linker region and the CTD. PABP-1-like and PABP-1-like 2 are the orthologs of PABP-1. PABP-4-like is the ortholog of PABP-5. Their cellular functions remain unclear. The family also includes the yeast PABP, a conserved poly(A) binding protein containing poly(A) tails that can be attached to the 3'-ends of mRNAs. The yeast PABP and its homologs may play important roles in the initiation of translation and in mRNA decay. Like vertebrate PABP-1, the yeast PABP contains four RRMs, a linker region, and a proline-rich CTD as well. The first two RRMs are mainly responsible for specific binding to poly(A). The proline-rich region may be involved in protein-protein interactions.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 283046784  34 ELREHFAQFGHVRRCTVPFDkETGFHRGMGWVQFSSQEELQNALQQEH-HIIDGVKIHVQ-AQR 95
Cdd:cd12381   17 KLREEFSPFGTITSAKVMTD-EGGRSKGFGFVCFSSPEEATKAVTEMNgRIIGGKPLYVAlAQR 79

RNA recognition motif 2 (RRM2) found in RNA-binding protein 28 (RBM28) and similar proteins; This subfamily corresponds to the RRM2 of RBM28 and Nop4p. RBM28 is a specific nucleolar component of the spliceosomal small nuclear ribonucleoproteins (snRNPs), possibly coordinating their transition through the nucleolus. It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), and may play a role in the maturation of both small nuclear and ribosomal RNAs. RBM28 has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an extremely acidic region between RRM2 and RRM3. The family also includes nucleolar protein 4 (Nop4p or Nop77p) encoded by YPL043W from Saccharomyces cerevisiae. It is an essential nucleolar protein involved in processing and maturation of 27S pre-rRNA and biogenesis of 60S ribosomal subunits. Nop4p also contains four RRMs.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 283046784  23 VRKIPWTAAASELREHFAQFGHVRRCTVPfDKETGFHRGMGWVQFSSQEELQNALQ 78
Cdd:cd12414    4 VRNLPFKCTEDDLKKLFSKFGKVLEVTIP-KKPDGKLRGFAFVQFTNVADAAKAIK 58

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 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHH-IIDGVKIHVQAQRAKALH 100
Cdd:cd12237    8 FVGRLSLQTTEEKLKEVFSRYGDIRRLRLVRDIVTGFSKRYAFIEYKEERDALHAYRDAKKlVIDQYEIFVDFECERTLP 87

                 .
gi 283046784 101 G 101
Cdd:cd12237   88 G 88

RNA recognition motif 1 (RRM1) found in RNA-binding protein Musashi homolog 1 (Musashi-1) and similar proteins; This subgroup corresponds to the RRM1 of Musashi-1. The mammalian MSI1 gene encoding 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. Musashi-1 is evolutionarily conserved from invertebrates to vertebrates. It is a homolog of Drosophila Musashi and Xenopus laevis nervous system-specific RNP protein-1 (Nrp-1). Musashi-1 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, it represses translation by interacting with the poly(A)-binding protein and competes for binding of the eukaryotic initiation factor-4G (eIF-4G). Musashi-1 contains 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHIIDGVKI 89
Cdd:cd12759    4 FIGGLSWQTTQEGLREYFGQFGEVKECLVMRDPLTKRSRGFGFVTFMDQAGVDKVLAQSRHELDSKTI 71

RNA recognition motif 1 (RRM1) found in vertebrate RNA-binding protein 26 (RBM26) and similar proteins; This subfamily corresponds to the RRM1 of RBM26, and the RRM of RBM27. RBM26, also known as cutaneous T-cell lymphoma (CTCL) tumor antigen se70-2, represents a cutaneous lymphoma (CL)-associated antigen. It contains two RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The RRMs may play some functional roles in RNA-binding or protein-protein interactions. RBM27 contains only one RRM; its biological function remains unclear.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 283046784  22 FVRKIPWTA-AASELREHFAQFGHVRRCTVPFDKETGFhrgmgwVQFSSQEELQNALQ 78
Cdd:cd12257    5 EVRNIPPELnNITKLREHFSKFGTIVNIQVNYNPESAL------VQFSTSEEANKAYR 56

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKEtGFHRGMGWVQFSSQEELQNALQQEHH-IIDGVKIHVQ 92
Cdd:cd12565    4 IVKNLPKYVTEKRLKEHFSKKGEITDVKVMRTKD-GKSRRFGFIGFKSEEEAQKAVKYFNKtFIDTSKISVE 74

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 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEHHIIDGVKIHVQ 92
Cdd:cd12395    3 FVGNLPFDIEEEELRKHFEDCGDVEAVRIVRDRETGIGKGFGYVLFKDKDSVDLALKLNGSKLRGRKLRVK 73

RNA recognition motif 2 (RRM2) found in RNA-binding protein 45 (RBM45) and similar proteins; This subfamily corresponds to the RRM2 of RBM45, also termed developmentally-regulated RNA-binding protein 1 (DRB1), a new member of RNA recognition motif (RRM)-type neural RNA-binding proteins, which expresses under spatiotemporal control. It is encoded by gene drb1 that is expressed in neurons, not in glial cells. RBM45 predominantly localizes in cytoplasm of cultured cells and specifically binds to poly(C) RNA. It could play an important role during neurogenesis. RBM45 carries four RRMs, also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 283046784  26 IPWTAAASELREHFAQFGHVRRCTVPFDKETGFHRGMGWVQF 67
Cdd:cd12367    8 IPKSYTEEDLREKFKEFGDIEYCSIVKDKNTGESKGFGYVKF 49

RNA recognition motif 1 (RRM1) found in RNA-binding protein 19 (RBM19) and similar proteins; This subgroup corresponds to the RRM1 of RBM19, also termed RNA-binding domain-1 (RBD-1), a nucleolar protein conserved in eukaryotes. It is involved in ribosome biogenesis by processing rRNA. In addition, it is essential for preimplantation development. RBM19 has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 283046784  23 VRKIPWTAAASELREHFAQFGHVRRCTVPFDKETGFhRGMGWVQFSSQEELQNALQQEHH-IIDGVKIHVQ 92
Cdd:cd12564    5 VKNLPSSITEDRLRKLFSAFGTITDVQLKYTKDGKF-RRFGFVGFKSEEEAQKALKHFNNsFIDTSRITVE 74

RNA recognition motif 1 (RRM1) found in squamous cell carcinoma antigen recognized by T-cells 3 (SART3) and similar proteins; This subfamily corresponds to the RRM1 of SART3, also termed Tat-interacting protein of 110 kDa (Tip110), an RNA-binding protein expressed in the nucleus of the majority of proliferating cells, including normal cells and malignant cells, but not in normal tissues except for the testes and fetal liver. It is involved in the regulation of mRNA splicing probably via its complex formation with RNA-binding protein with a serine-rich domain (RNPS1), a pre-mRNA-splicing factor. SART3 has also been identified as a nuclear Tat-interacting protein that regulates Tat transactivation activity through direct interaction and functions as an important cellular factor for HIV-1 gene expression and viral replication. In addition, SART3 is required for U6 snRNP targeting to Cajal bodies. It binds specifically and directly to the U6 snRNA, interacts transiently with the U6 and U4/U6 snRNPs, and promotes the reassembly of U4/U6 snRNPs after splicing in vitro. SART3 contains an N-terminal half-a-tetratricopeptide repeat (HAT)-rich domain, a nuclearlocalization signal (NLS) domain, and two C-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 283046784  22 FVRKIPWTAAASELREHFAQFGHVRRCTVPFDKeTGFHRGMGWVQFSSQEELQNALQQEHHIIDG 86
Cdd:cd12391    3 FVSNLDYSVPEDKIREIFSGCGEITDVRLVKNY-KGKSKGYCYVEFKDEESAQKALKLDRQPVEG 66

RNA recognition motif (RRM) found in cold inducible RNA binding protein (CIRBP), RNA binding motif protein 3 (RBM3) and similar proteins; This subfamily corresponds to the RRM domain of two structurally related heterogenous nuclear ribonucleoproteins, CIRBP (also termed CIRP or A18 hnRNP) and RBM3 (also termed RNPL), both of which belong to a highly conserved cold shock proteins family. The cold shock proteins can be induced after exposure to a moderate cold-shock and other cellular stresses such as UV radiation and hypoxia. CIRBP and RBM3 may function in posttranscriptional regulation of gene expression by binding to different transcripts, thus allowing the cell to response rapidly to environmental signals. However, the kinetics and degree of cold induction are different between CIRBP and RBM3. Tissue distribution of their expression is different. CIRBP and RBM3 may be differentially regulated under physiological and stress conditions and may play distinct roles in cold responses of cells. CIRBP, also termed glycine-rich RNA-binding protein CIRP, is localized in the nucleus and mediates the cold-induced suppression of cell cycle progression. CIRBP also binds DNA and possibly serves as a chaperone that assists in the folding/unfolding, assembly/disassembly and transport of various proteins. RBM3 may enhance global protein synthesis and the formation of active polysomes while reducing the levels of ribonucleoprotein complexes containing microRNAs. RBM3 may also serve to prevent the loss of muscle mass by its ability to decrease cell death. Furthermore, RBM3 may be essential for cell proliferation and mitosis. Both, CIRBP and RBM3, contain an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), that is involved in RNA binding, and C-terminal glycine-rich domain (RGG motif) that probably enhances RNA-binding via protein-protein and/or protein-RNA interactions. Like CIRBP, RBM3 can also bind to both RNA and DNA via its RRM domain.

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gi 283046784  35 LREHFAQFGHVRRCTVPFDKETGFHRGMGWVQFSSQEELQNALQQEH-HIIDGVKIHV 91
Cdd:cd12449   17 LEEVFSKYGQISEVVVVKDRETQRSRGFGFVTFENPDDAKDAMMAMNgKSLDGRQIRV 74