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
                  ....*....|....*....|....*....|..
gi 1063739542   1 MEDERDAEDAIRALDRFEYGRTGRRLRVEWTK 32
Cdd:cd12234    41 MEDERDAEDAIRGLDNFEFGRQRRRLRVEWTK 72

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063739542   56 TLFVINFDaQNTRTRDLERHFEPYGKIVNVRIRRN--------FAFIQYEAQEDATRALDATNSSKLMDKVISV 121
Cdd:smart00360   1 TLFVGNLP-PDTTEEELRELFSKFGKVESVRLVRDketgkskgFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

RNA recognition motif (RRM) found in Arabidopsis thaliana arginine/serine-rich-splicing factor RSp31 and similar proteins from plants; This subfamily corresponds to the RRM1in a family that represents a novel group of arginine/serine (RS) or serine/arginine (SR) splicing factors existing in plants, such as A. thaliana RSp31, RSp35, RSp41 and similar proteins. Like vertebrate RS splicing factors, these proteins function as plant splicing factors and play crucial roles in constitutive and alternative splicing in plants. They all contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), at their N-terminus, and an RS domain at their C-terminus.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1063739542   1 MEDERDAEDAIRALDRFEYGRTGRRLRVEWTK 32
Cdd:cd12234    41 MEDERDAEDAIRGLDNFEFGRQRRRLRVEWTK 72

ELAV/HuD family splicing factor; This model describes the ELAV/HuD subfamily of splicing factors found in metazoa. HuD stands for the human paraneoplastic encephalomyelitis antigen D of which there are 4 variants in human. ELAV stnds for the Drosophila Embryonic lethal abnormal visual protein. ELAV-like splicing factors are also known in human as HuB (ELAV-like protein 2), HuC (ELAV-like protein 3, Paraneoplastic cerebellar degeneration-associated antigen) and HuR (ELAV-like protein 1). These genes are most closely related to the sex-lethal subfamily of splicing factors found in Dipteran insects (TIGR01659). These proteins contain 3 RNA-recognition motifs (rrm: pfam00076).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063739542  70 RDLERHFEPYGKIVNVRI--------RRNFAFIQYEAQEDATRALDATNSSKLMD--KVISVEYAVKDDDSRGNGYSPER 139
Cdd:TIGR01661 104 HELESIFSPFGQIITSRIlsdnvtglSKGVGFIRFDKRDEADRAIKTLNGTTPSGctEPITVKFANNPSSSNSKGLLSQL 183

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1063739542 140 RRDRSPDRRRRSpspyrreRGSPDYGRGASPVAHKRERTSPDYGR 184
Cdd:TIGR01661 184 EAVQNPQTTRVP-------LSTILTAAGIGPMHHAAARFRPSAGD 221

RNA recognition motif (RRM) found in fission yeast pre-mRNA-splicing factor Srp1p, Arabidopsis thaliana arginine/serine-rich-splicing factor RSp31 and similar proteins; This subfamily corresponds to the RRM of Srp1p and RRM2 of plant SR splicing factors. Srp1p is encoded by gene srp1 from fission yeast Schizosaccharomyces pombe. It plays a role in the pre-mRNA splicing process, but is not essential for growth. Srp1p is closely related to the SR protein family found in Metazoa. It contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a glycine hinge and a RS domain in the middle, and a C-terminal domain. The family also includes a novel group of arginine/serine (RS) or serine/arginine (SR) splicing factors existing in plants, such as A. thaliana RSp31, RSp35, RSp41 and similar proteins. Like vertebrate RS splicing factors, these proteins function as plant splicing factors and play crucial roles in constitutive and alternative splicing in plants. They all contain two RRMs at their N-terminus and an RS domain at their C-terminus.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063739542  56 TLFVINFDAQNTRTRDLERHFEPYGKIVNVRIRRNFAFIQYEAQEDATRALDATNSSKLMDKVISVEYA 124
Cdd:cd12233     1 TLFVVGFDPGTTREEDIEKLFEPFGPLVRCDIRKTFAFVEFEDSEDATKALEALHGSRIDGSVLTVEFV 69

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 1063739542  57 LFVINFDaQNTRTRDLERHFEPYGKIVNVRI-------RRNFAFIQYEAQEDATRALDATNSSKLMDKVISVE 122
Cdd:cd00590     1 LFVGNLP-PDTTEEDLRELFSKFGEVVSVRIvrdrdgkSKGFAFVEFESPEDAEKALEALNGTELGGRPLKVS 72

RNA recognition motif 1 (RRM1) and 2 (RRM2) found in RRM-containing coactivator activator/modulator (CoAA) and similar proteins; This subfamily corresponds to the RRM in CoAA (also known as RBM14 or PSP2) and RNA-binding protein 4 (RBM4). CoAA is a heterogeneous nuclear ribonucleoprotein (hnRNP)-like protein identified as a nuclear receptor coactivator. It mediates transcriptional coactivation and RNA splicing effects in a promoter-preferential manner, and is enhanced by thyroid hormone receptor-binding protein (TRBP). CoAA contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a TRBP-interacting domain. RBM4 is a ubiquitously expressed splicing factor with two isoforms, RBM4A (also known as Lark homolog) and RBM4B (also known as RBM30), which are very similar in structure and sequence. RBM4 may also function as a translational regulator of stress-associated mRNAs as well as play a role in micro-RNA-mediated gene regulation. RBM4 contains two N-terminal RRMs, a CCHC-type zinc finger, and three alanine-rich regions within their C-terminal regions. This family also includes Drosophila RNA-binding protein lark (Dlark), a homolog of human RBM4. It plays an important role in embryonic development and in the circadian regulation of adult eclosion. Dlark shares high sequence similarity with RBM4 at the N-terminal region. However, Dlark has three proline-rich segments instead of three alanine-rich segments within the C-terminal region.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063739542  57 LFVINFDAqNTRTRDLERHFEPYGKIVNVRIRRNFAFIQYEAQEDATRALDATNSSKLMDKVISVE 122
Cdd:cd12343     2 IFVGNLPD-AATSEELRALFEKYGKVTECDIVKNYAFVHMEKEEDAEDAIKALNGYEFMGSRINVE 66

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063739542  71 DLERHFEPYGKIVNVRIRRN-------FAFIQYEAQEDATRALDATNSSKLMDKVISVEYAV 125
Cdd:cd12414    15 DLKKLFSKFGKVLEVTIPKKpdgklrgFAFVQFTNVADAAKAIKGMNGKKIKGRPVAVDWAV 76

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063739542  72 LERHFEPYGKIVNVRI--------RRNFAFIQYEAQEDATRALDATNSSKLMDKVISVEYA 124
Cdd:cd12347    15 LHAAFIPFGDIVDIQIpldyetekHRGFAFVEFEEAEDAAAAIDNMNESELFGRTIRVNLA 75

RNA recognition motif 2 (RRM2) found in squamous cell carcinoma antigen recognized by T-cells 3 (SART3) and similar proteins; This subfamily corresponds to the RRM2 of SART3, also termed Tat-interacting protein of 110 kDa (Tip110), is an RNA-binding protein expressed in the nucleus of the majority of proliferating cells, including normal cells and malignant cells, but not in normal tissues except for the testes and fetal liver. It is involved in the regulation of mRNA splicing probably via its complex formation with RNA-binding protein with a serine-rich domain (RNPS1), a pre-mRNA-splicing factor. SART3 has also been identified as a nuclear Tat-interacting protein that regulates Tat transactivation activity through direct interaction and functions as an important cellular factor for HIV-1 gene expression and viral replication. In addition, SART3 is required for U6 snRNP targeting to Cajal bodies. It binds specifically and directly to the U6 snRNA, interacts transiently with the U6 and U4/U6 snRNPs, and promotes the reassembly of U4/U6 snRNPs after splicing in vitro. SART3 contains an N-terminal half-a-tetratricopeptide repeat (HAT)-rich domain, a nuclearlocalization signal (NLS) domain, and two C-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063739542  55 KTLFVINFDAQNTRTrDLERHFEPYGKIVNVRI--RRN-----FAFIQYEAQEDATRALDATNSSKLMDKVISV 121
Cdd:cd12392     3 NKLFVKGLPFSCTKE-ELEELFKQHGTVKDVRLvtYRNgkpkgLAYVEYENEADASQAVLKTDGTEIKDHTISV 75

RNA recognition motif (RRM) found in yeast nuclear polyadenylated RNA-binding protein 3 (Nab3p) and similar proteins; This subfamily corresponds to the RRM of Nab3p, an acidic nuclear polyadenylated RNA-binding protein encoded by Saccharomyces cerevisiae NAB3 gene that is essential for cell viability. Nab3p is predominantly localized within the nucleoplasm and essential for growth in yeast. It may play an important role in packaging pre-mRNAs into ribonucleoprotein structures amenable to efficient nuclear RNA processing. Nab3p contains an N-terminal aspartic/glutamic acid-rich region, a central RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal region rich in glutamine and proline residues.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063739542  57 LFVINFDAQNTRTRDLERHFEPYGKIVNVRIRRNFAFIQYEAQEDATRALDATNSSKLMDKVISVE 122
Cdd:cd12342     2 LFIGNLPTKRVSKEDLFRIFSPYGHLMQIVIKNAFGFVQFDSPQSCRNAIECEQGEMNRGKKLHLE 67

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063739542  71 DLERHFEPYGKIVNVRIRRN--------FAFIQYEAQEDATRALDATNSSKLMDKVISVE 122
Cdd:cd12362    14 DLYQLFAPFGNVVSAKVFVDkntgrskgFGFVSYDNPLSAQAAIKAMNGFQVGGKRLKVQ 73

RNA recognition motif (RRM) found in eukaryotic RNA-binding protein 18 and similar proteins; This subfamily corresponds to the RRM of RBM18, a putative RNA-binding protein containing a well-conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The biological role of RBM18 remains unclear.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063739542  57 LFVINFDAQNTRtRDLERHFEPYGKIVNVRI-----------RRNFAFIQYEAQEDATRALDATNSSKLMDKVISVEYA 124
Cdd:cd12355     2 LWIGNLDPRLTE-YHLLKLLSKYGKIKKFDFlfhktgplkgqPRGYCFVTFETKEEAEKAIECLNGKLALGKKLVVRWA 79

RNA recognition motif 1 (RRM1) found in vertebrate RRM-containing coactivator activator/modulator (CoAA); This subgroup corresponds to the RRM1 of CoAA, also termed RNA-binding protein 14 (RBM14), or paraspeckle protein 2 (PSP2), or synaptotagmin-interacting protein (SYT-interacting protein), a heterogeneous nuclear ribonucleoprotein (hnRNP)-like protein identified as a nuclear receptor coactivator. It mediates transcriptional coactivation and RNA splicing effects in a promoter-preferential manner and is enhanced by thyroid hormone receptor-binding protein (TRBP). CoAA contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a TRBP-interacting domain. It stimulates transcription through its interactions with coactivators, such as TRBP and CREB-binding protein CBP/p300, via the TRBP-interacting domain and interaction with an RNA-containing complex, such as DNA-dependent protein kinase-poly(ADP-ribose) polymerase complexes, via the RRMs.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063739542  57 LFVINFDaQNTRTRDLERHFEPYGKIVNVRIRRNFAFIQYEAQEDATRALDATNSSKLMDKVISVE 122
Cdd:cd12608     3 IFVGNVD-EDTSQEELSALFEPYGAVLSCAVMKQFAFVHMRGEAAADRAIRELNGRELHGRALVVE 67

RNA recognition motif (RRM) found in transformer-2 protein homolog TRA2-alpha, TRA2-beta and similar proteins; This subfamily corresponds to the RRM of two mammalian homologs of Drosophila transformer-2 (Tra2), TRA2-alpha, TRA2-beta (also termed SFRS10), and similar proteins found in eukaryotes. TRA2-alpha is a 40-kDa serine/arginine-rich (SR) protein that specifically binds to gonadotropin-releasing hormone (GnRH) exonic splicing enhancer on exon 4 (ESE4) and is necessary for enhanced GnRH pre-mRNA splicing. It strongly stimulates GnRH intron A excision in a dose-dependent manner. In addition, TRA2-alpha can interact with either 9G8 or SRp30c, which may also be crucial for ESE-dependent GnRH pre-mRNA splicing. TRA2-beta is a serine/arginine-rich (SR) protein that controls the pre-mRNA alternative splicing of the calcitonin/calcitonin gene-related peptide (CGRP), the survival motor neuron 1 (SMN1) protein and the tau protein. Both, TRA2-alpha and TRA2-beta, contains a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), flanked by the N- and C-terminal arginine/serine (RS)-rich regions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063739542  66 NTRTRDLERHFEPYGKIVNVRI--------RRNFAFIQYEAQEDATRALDATNSSKLMDKVISVEYAV 125
Cdd:cd12363    12 YTTERDLREVFSRYGPIEKVQVvydqqtgrSRGFGFVYFESVEDAKEAKERLNGQEIDGRRIRVDYSI 79

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063739542  72 LERHFEPYGKIVNVRI--------RRNFAFIQYEAQEDATRALDATNSSKLMDKVISVEYAVK 126
Cdd:cd12382    18 LEAVFGKYGRIVEVLLmkdretnkSRGFAFVTFESPADAKDAARDMNGKELDGKAIKVEQATK 80

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 1063739542  57 LFV--INFDaqnTRTRDLERHFEPYGKIVNVRI--------RRNFAFIQYEAQEDATRALDATNSSKLMDKVISVEYAVK 126
Cdd:cd12449     3 LFVggLSFD---TNEQSLEEVFSKYGQISEVVVvkdretqrSRGFGFVTFENPDDAKDAMMAMNGKSLDGRQIRVDQAGK 79

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063739542  55 KTLFV--INFDaqnTRTRDLERHFEPYGKIVNVRIRRN--------FAFIQYEAQEDATRALDATNSSKLMDKVISVEY 123
Cdd:cd12236     2 KTLFVarLSYD---TTESKLRREFEKYGPIKRVRLVRDkktgksrgYAFIEFEHERDMKAAYKHADGKKIDGRRVLVDV 77

RNA recognition motif (RRM) found in the scaffold attachment factor (SAFB) family; This subfamily corresponds to the RRM domain of the SAFB family, including scaffold attachment factor B1 (SAFB1), scaffold attachment factor B2 (SAFB2), SAFB-like transcriptional modulator (SLTM), and similar proteins, which are ubiquitously expressed. SAFB1, SAFB2 and SLTM have been implicated in many diverse cellular processes including cell growth and transformation, stress response, and apoptosis. They share high sequence similarities and all contain a scaffold attachment factor-box (SAF-box, also known as SAP domain) DNA-binding motif, an RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a region rich in glutamine and arginine residues. SAFB1 is a nuclear protein with a distribution similar to that of SLTM, but unlike that of SAFB2, which is also found in the cytoplasm. To a large extent, SAFB1 and SLTM might share similar functions, such as the inhibition of an oestrogen reporter gene. The additional cytoplasmic localization of SAFB2 implies that it could play additional roles in the cytoplasmic compartment which are distinct from the nuclear functions shared with SAFB1 and SLTM.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063739542  57 LFVINFDAqNTRTRDLERHFEPYGKIVNVRI--------RRNFAFIQYEAQEDATRALDATNSSKLMDKVISVE 122
Cdd:cd12417     2 LWISGLSD-TTKAADLKKIFSKYGKVVSAKVvtsartpgSRCYGYVTMASVEEADLCIKSLNKTELHGRVITVE 74

RNA recognition motif 3 (RRM3) found found in type I polyadenylate-binding proteins; This subfamily corresponds to the RRM3 of type I poly(A)-binding proteins (PABPs), highly conserved proteins that bind to the poly(A) tail present at the 3' ends of most eukaryotic mRNAs. They have been implicated in the regulation of poly(A) tail length during the polyadenylation reaction, translation initiation, mRNA stabilization by influencing the rate of deadenylation and inhibition of mRNA decapping. The family represents type I polyadenylate-binding proteins (PABPs), including polyadenylate-binding protein 1 (PABP-1 or PABPC1), polyadenylate-binding protein 3 (PABP-3 or PABPC3), polyadenylate-binding protein 4 (PABP-4 or APP-1 or iPABP), polyadenylate-binding protein 5 (PABP-5 or PABPC5), polyadenylate-binding protein 1-like (PABP-1-like or PABPC1L), polyadenylate-binding protein 1-like 2 (PABPC1L2 or RBM32), polyadenylate-binding protein 4-like (PABP-4-like or PABPC4L), yeast polyadenylate-binding protein, cytoplasmic and nuclear (PABP or ACBP-67), and similar proteins. PABP-1 is 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. 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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063739542  57 LFVINFDAQNTRTRdLERHFEPYGKIVNVRIRRN-------FAFIQYEAQEDATRALDATNSSKLMDKVISVEYAVK 126
Cdd:cd12380     4 VYVKNFGEDVDDDE-LKELFEKYGKITSAKVMKDdsgkskgFGFVNFENHEAAQKAVEELNGKELNGKKLYVGRAQK 79

RNA recognition motif 3 (RRM3) found in Schizosaccharomyces pombe mRNA export factor Crp79, meiotically up-regulated gene 28 protein (Mug28) and similar proteins; Crp79, also called meiotic expression up-regulated protein 5 (Mug5), or polyadenylate-binding protein crp79, or PABP, or poly(A)-binding protein, is an auxiliary mRNA export factor that binds the poly(A) tail of mRNA and is involved in the export of mRNA from the nucleus to the cytoplasm. Mug28 is a meiosis-specific protein that regulates spore wall formation. 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 three RRM motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063739542  57 LFVINFDAQN-TRTRDLERHFEPYGKIV--------NVRIRRNFAFIQYEAQEDATRALDATNSSKLMDKVISVEYAVKD 127
Cdd:cd21622     6 LFVKNLDDTViTNKEDLEQLFSPFGQIVssylatypGTGISKGFGFVAFSKPEDAAKAKETLNGVMVGRKRIFVSYAERK 85

                  ....
gi 1063739542 128 DDSR 131
Cdd:cd21622    86 EDRE 89

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 1063739542  55 KTLFVINFDAQNTRTRDLERHFEPYGKIVNVRIR--RNFAFIQYEAQEDATRALDAT 109
Cdd:cd12257     2 TTLEVRNIPPELNNITKLREHFSKFGTIVNIQVNynPESALVQFSTSEEANKAYRSP 58

RNA recognition motif (RRM) found in RNA-binding protein RBM8A, RBM8B nd similar proteins; This subfamily corresponds to the RRM of RBM8, also termed binder of OVCA1-1 (BOV-1), or RNA-binding protein Y14, which is one of the components of the exon-exon junction complex (EJC). It has two isoforms, RBM8A and RBM8B, both of which are identical except that RBM8B is 16 amino acids shorter at its N-terminus. RBM8, together with other EJC components (such as Magoh, Aly/REF, RNPS1, Srm160, and Upf3), plays critical roles in postsplicing processing, including nuclear export and cytoplasmic localization of the mRNA, and the nonsense-mediated mRNA decay (NMD) surveillance process. RBM8 binds to mRNA 20-24 nucleotides upstream of a spliced exon-exon junction. It is also involved in spliced mRNA nuclear export, and the process of nonsense-mediated decay of mRNAs with premature stop codons. RBM8 forms a specific heterodimer complex with the EJC protein Magoh which then associates with Aly/REF, RNPS1, DEK, and SRm160 on the spliced mRNA, and inhibits ATP turnover by eIF4AIII, thereby trapping the EJC core onto RNA. RBM8 contains an N-terminal putative bipartite nuclear localization signal, one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), in the central region, and a C-terminal serine-arginine rich region (SR domain) and glycine-arginine rich region (RG domain).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063739542  71 DLERHFEPYGKIVNVRI---RRN-----FAFIQYEAQEDATRALDATNSSKLMDKVISVEYA 124
Cdd:cd12324    22 DIHDKFAEFGEIKNLHLnldRRTgfvkgYALVEYETKKEAQAAIEGLNGKELLGQTISVDWA 83

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063739542  55 KTLFVINFDAQNTRtRDLERHFEPYGKIVNVRI-------RRNFAFIQYEAQEDATRALDATNSSKLMDKVISVEYA 124
Cdd:cd12320     1 TKLIVKNVPFEATR-KEIRELFSPFGQLKSVRLpkkfdgsHRGFAFVEFVTKQEAQNAMEALKSTHLYGRHLVLEYA 76

RNA recognition motif 1 (RRM1) found in fission yeast pre-mRNA-splicing factor Srp1p and similar proteins; This subgroup corresponds to the RRM domain in Srp1p encoded by gene srp1 from fission yeast Schizosaccharomyces pombe. It plays a role in the pre-mRNA splicing process, but not essential for growth. Srp1p is closely related to the SR protein family found in metazoa. It contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a glycine hinge and a RS domain in the middle, and a C-terminal domain. Some family members also contain another RRM domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063739542  56 TLFVINFDAQnTRTRDLERHFEPYGKIVNVRI-------RRNFAFIQYEAQEDATRAL 106
Cdd:cd12467     1 TLYVTGFGAE-TRARDLAYEFERYGRLVRCDIppprtfqSRPFAFVEYESHRDAEDAY 57

RNA recognition motif 1 (RRM1) found in yeast meiotic activator RIM4 and similar proteins; This subfamily corresponds to the RRM1 of RIM4, also termed regulator of IME2 protein 4, a putative RNA binding protein that is expressed at elevated levels early in meiosis. It functions as a meiotic activator required for both the IME1- and IME2-dependent pathways of meiotic gene expression, as well as early events of meiosis, such as meiotic division and recombination, in Saccharomyces cerevisiae. RIM4 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The family also includes a putative RNA-binding protein termed multicopy suppressor of sporulation protein Msa1. It is a putative RNA-binding protein encoded by a novel gene, msa1, from the fission yeast Schizosaccharomyces pombe. Msa1 may be involved in the inhibition of sexual differentiation by controlling the expression of Ste11-regulated genes, possibly through the pheromone-signaling pathway. Like RIM4, Msa1 also contains two RRMs, both of which are essential for the function of Msa1.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063739542  57 LFVINFDAqnTRTRD-----LERHFEPYGKIVNVRIRRN-----FAFIQYEAQEDATRALDATNSSKLMDKVISVEYA 124
Cdd:cd12453     5 LFVASLSS--ARSDEelcaaVTNHFSKWGELLNVKVLKDwsnrpYAFVQYTNTEDAKNALVNGHNTLLDGRHLRVEKA 80

RNA recognition motif 1 (RRM1) found in Drosophila sex-lethal (SXL) and similar proteins; This subfamily corresponds to the RRM1 of SXL which governs sexual differentiation and X chromosome dosage compensation in Drosophila melanogaster. 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 also to its own pre-mRNA and promotes female-specific alternative splicing. SXL contains an N-terminal Gly/Asn-rich domain that may be responsible for the protein-protein interaction, and tandem RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), that show high preference to bind single-stranded, uridine-rich target RNA transcripts.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063739542  56 TLFVINFDAQNTRTRDLERHFEPYGKIVNVRIRRN--------FAFIQYEAQEDATRALDATNSSKLMDKVISVEYA 124
Cdd:cd12649     1 TNLIVNYLPQDLTDREFRALFRAIGPVNTCKIVRDkktgysygFGFVDFTSEEDAQRAIKTLNGLQLQNKRLKVAYA 77

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063739542  57 LFVINFDAQNTrTRDLERHFEPYGKIVNVRIRRN-------FAFIQYEAQEDATRALDATNSSKLMDKVISVEYAVKDDD 129
Cdd:TIGR01628 288 LYVKNLDDTVT-DEKLRELFSECGEITSAKVMLDekgvsrgFGFVCFSNPEEANRAVTEMHGRMLGGKPLYVALAQRKEQ 366

                  ..
gi 1063739542 130 SR 131
Cdd:TIGR01628 367 RR 368

RNA recognition motif 2 (RRM2) found in splicing factor 3B subunit 4 (SF3B4) and similar proteins; This subfamily corresponds to the RRM2 of SF3B4, also termed pre-mRNA-splicing factor SF3b 49 kDa (SF3b50), or spliceosome-associated protein 49 (SAP 49). SF3B4 is a component of the multiprotein complex splicing factor 3b (SF3B), an integral part of the U2 small nuclear ribonucleoprotein (snRNP) and the U11/U12 di-snRNP. SF3B is essential for the accurate excision of introns from pre-messenger RNA, and is involved in the recognition of the pre-mRNA's branch site within the major and minor spliceosomes. SF3B4 functions to tether U2 snRNP with pre-mRNA at the branch site during spliceosome assembly. It is an evolutionarily highly conserved protein with orthologs across diverse species. SF3B4 contains two closely adjacent N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). It binds directly to pre-mRNA and also interacts directly and highly specifically with another SF3B subunit called SAP 145.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063739542  57 LFVINFDAqNTRTRDLERHFEPYGKIV-NVRIRRN--------FAFIQYEAQEDATRALDATNSSKLMDKVISVEYAVKD 127
Cdd:cd12335     4 LFIGNLDP-EVDEKLLYDTFSAFGVILqTPKIMRDpdtgnskgFGFVSFDSFEASDAAIEAMNGQYLCNRPITVSYAFKK 82

                  .
gi 1063739542 128 D 128
Cdd:cd12335    83 D 83

RNA recognition motif 1 (RRM1) found in La-related protein 7 (LARP7) and similar proteins; This subfamily corresponds to the RRM1 of LARP7, also termed La ribonucleoprotein domain family member 7, or P-TEFb-interaction protein for 7SK stability (PIP7S), an oligopyrimidine-binding protein that binds to the highly conserved 3'-terminal U-rich stretch (3' -UUU-OH) of 7SK RNA. LARP7 is a stable component of the 7SK small nuclear ribonucleoprotein (7SK snRNP). It intimately associates with all the nuclear 7SK and is required for 7SK stability. LARP7 also acts as a negative transcriptional regulator of cellular and viral polymerase II genes, acting by means of the 7SK snRNP system. It plays an essential role in the inhibition of positive transcription elongation factor b (P-TEFb)-dependent transcription, which has been linked to the global control of cell growth and tumorigenesis. LARP7 contains a La motif (LAM) and an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), at the N-terminal region, which mediates binding to the U-rich 3' terminus of 7SK RNA. LARP7 also carries another putative RRM domain at its C-terminus.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1063739542  71 DLERHFEPYGKIVNVRIRR--------NFAFIQYEAQEDATRALDATNSSKLM 115
Cdd:cd12290    15 WIEAVFSKYGEVVYVSIPRykstgdpkGFAFIEFETSESAQKAVKHFNSPPEA 67

RNA recognition motif 3 (RRM3) found in the Hu proteins family; This subfamily corresponds to the RRM3 of the Hu proteins family which represent 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 the 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063739542  56 TLFVINFdAQNTRTRDLERHFEPYGKIVNVRIRRN--------FAFIQYEAQEDATRALDATNSSKLMDKVISVEY 123
Cdd:cd12377     1 CIFVYNL-APDADESLLWQLFGPFGAVQNVKIIRDfttnkckgYGFVTMTNYDEAAVAIASLNGYRLGGRVLQVSF 75

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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1063739542  71 DLERHFEPYGKIVNVRIRRNF--------AFIQYEAQEDATRALDATNSSKLMD 116
Cdd:cd12361    15 DVRPLFEQFGNIEEVQILRDKqtgqskgcAFVTFSTREEALRAIEALHNKKTMP 68

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063739542  55 KTLFVINFDAQnTRTRDLERHFEPYGKIVNVRIR----------RNFAFIQYEAQEDATRALDATNSSKLMDKVISV 121
Cdd:cd21619     2 NTIYVGNIDMT-INEDALEKIFSRYGQVESVRRPpihtdkadrtTGFGFIKYTDAESAERAMQQADGILLGRRRLVV 77

RNA recognition motif 3 (RRM3) found in yeast negative growth regulatory protein NGR1 (RBP1), yeast protein NAM8 and similar proteins; This subfamily corresponds to the RRM3 of NGR1 and NAM8. NGR1, also termed RNA-binding protein RBP1, is a putative glucose-repressible protein that binds both RNA and single-stranded DNA (ssDNA) in yeast. It may function in regulating cell growth in early log phase, possibly through its participation in RNA metabolism. NGR1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a glutamine-rich stretch that may be involved in transcriptional activity. In addition, NGR1 has an asparagine-rich region near the carboxyl terminus which also harbors a methionine-rich region. The family also includes protein NAM8, which is a putative RNA-binding protein that acts as a suppressor of mitochondrial splicing deficiencies when overexpressed in yeast. It may be a non-essential component of the mitochondrial splicing machinery. Like NGR1, NAM8 contains two RRMs.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1063739542  56 TLFVINFDAqNTRTRDLERHFEPYGKIVNVRIR--RNFAFIQYEAQEDATRALDATN 110
Cdd:cd12346     3 TVFVGGLDP-NVTEEDLRVLFGPFGEIVYVKIPpgKGCGFVQFVNRASAEAAIQKLQ 58

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063739542  57 LFVINFDAQNTRTRdLERHFEPYGKIVNVRIRRN-------FAFIQYEAQEDATRALDATNSSKL----MDKVISVEYAV 125
Cdd:TIGR01628 181 LYVKNLDPSVNEDK-LRELFAKFGEITSAAVMKDgsgrsrgFAFVNFEKHEDAAKAVEEMNGKKIglakEGKKLYVGRAQ 259

                  ....
gi 1063739542 126 KDDD 129
Cdd:TIGR01628 260 KRAE 263

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1063739542  55 KTLFVINFDaQNTRTRDLERHFEPYGKIVNVRIRR-----NFAFIQYEAQEDATRAL 106
Cdd:cd12350     3 RTLFIGNLE-KTTTYGDLRNIFERFGEIIDIDIKKqngnpQYAFLQYCDIASVVKAI 58

RNA recognition motif 2 (RRM2) found in yeast nucleolar protein 4 (Nop4p) and similar proteins; This subgroup corresponds to the RRM2 of Nop4p (also known as 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 has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063739542  72 LERHFEPYGKIVNVRIRRN-------FAFIQYEAQEDATRALDATNSSKLMDKVISVEYAVKDD 128
Cdd:cd12675    18 LKKLFGRYGKVVEATIPRKkggklsgFAFVTMKGRKNAEEALESVNGLEIDGRPVAVDWAVSKN 81

RNA recognition motif (RRM) found in scaffold attachment factor B1 (SAFB1), scaffold attachment factor B2 (SAFB2), and similar proteins; This subgroup corresponds to RRM of SAFB1, also termed scaffold attachment factor B (SAF-B), heat-shock protein 27 estrogen response element ERE and TATA-box-binding protein (HET), or heterogeneous nuclear ribonucleoprotein hnRNP A1- associated protein (HAP), a large multi-domain protein with well-described functions in transcriptional repression, RNA splicing and metabolism, and a proposed role in chromatin organization. Based on the numerous functions, SAFB1 has been implicated in many diverse cellular processes including cell growth and transformation, stress response, and apoptosis. SAFB1 specifically binds to AT-rich scaffold or matrix attachment region DNA elements (S/MAR DNA) by using its N-terminal scaffold attachment factor-box (SAF-box, also known as SAP domain), a homeodomain-like DNA binding motif. The central region of SAFB1 is composed of an RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a nuclear localization signal (NLS). The C-terminus of SAFB1 contains Glu/Arg- and Gly-rich regions that might be involved in protein-protein interaction. Additional studies indicate that the C-terminal region contains a potent and transferable transcriptional repression domain. Another family member is SAFB2, a homolog of SAFB1. Both SAFB1 and SAFB2 are ubiquitously coexpressed and share very high sequence similarity, suggesting that they might function in a similar manner. However, unlike SAFB1, exclusively existing in the nucleus, SAFB2 is also present in the cytoplasm. The additional cytoplasmic localization of SAFB2 implies that it could play additional roles in the cytoplasmic compartment which are distinct from the nuclear functions shared with SAFB1.

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gi 1063739542  64 AQNTRTRDLERHFEPYGKIVNVRIRRN--------FAFIQYEAQEDATRALDATNSSKLMDKVISVE 122
Cdd:cd12679    10 SSTTRATDLKNLFSKYGKVVGAKVVTNarspgarcYGFVTMSTSEEATKCISHLHRTELHGRMISVE 76

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.

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gi 1063739542  57 LFVINFDAQNTRTRdLERHFEPYGKIVNVRIRRN-------FAFIQYEAQEDATRALDATNSSKLMDKVISVEYA 124
Cdd:cd12381     4 LYVKNLDDTIDDEK-LREEFSPFGTITSAKVMTDeggrskgFGFVCFSSPEEATKAVTEMNGRIIGGKPLYVALA 77