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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831509925  44 TEILCLMNMVTEDELKADDEYEEILEDVRDECSKYGIVRSLEIPRP-YEDHPVPGVGKVFVEFASTSDCQRAQAALTGRK 122
Cdd:cd12232     1 SRVLCLLNMVTPEELEDDEEYEEILEDVKEECSKYGKVLSVVIPRPeAEGVDVPGVGKVFVEFEDVEDAQKAQKALAGRK 80

                  ....*....
gi 1831509925 123 FANRTVVTS 131
Cdd:cd12232    81 FDGRTVVAS 89

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831509925  69 EDVRDECSKYGIVRSLEIPRPYEDHPvPGVGkvFVEFASTSDCQRAQAALTGRKFANRTV 128
Cdd:pfam00076  13 EDLKDLFSKFGPIKSIRLVRDETGRS-KGFA--FVEFEDEEDAEKAIEALNGKELGGREL 69

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831509925  44 TEILCLMNMVTEDELKADDEYEEILEDVRDECSKYGIVRSLEIPRP-YEDHPVPGVGKVFVEFASTSDCQRAQAALTGRK 122
Cdd:cd12232     1 SRVLCLLNMVTPEELEDDEEYEEILEDVKEECSKYGKVLSVVIPRPeAEGVDVPGVGKVFVEFEDVEDAQKAQKALAGRK 80

                  ....*....
gi 1831509925 123 FANRTVVTS 131
Cdd:cd12232    81 FDGRTVVAS 89

RNA recognition motif 3 (RRM3) found in vertebrate RNA-binding protein 39 (RBM39) and similar proteins; This subfamily corresponds to the RRM3 of RBM39, also termed hepatocellular carcinoma protein 1, or RNA-binding region-containing protein 2, or splicing factor HCC1, ia nuclear autoantigen that contains an N-terminal arginine/serine rich (RS) motif and three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). An octapeptide sequence called the RS-ERK motif is repeated six times in the RS region of RBM39. Based on the specific domain composition, RBM39 has been classified into a family of non-snRNP (small nuclear ribonucleoprotein) splicing factors that are usually not complexed to snRNAs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831509925  44 TEILCLMNMVTEDELKADDEYEEILEDVRDECSKYGIVRSLEIprpYEDHPvpgVGKVFVEFASTSDCQRAQAALTGRKF 123
Cdd:cd12285     1 SRCVILKNMFDPAEETEDNWDDEIKEDVIEECSKYGPVLHIYV---DKNSP---QGNVYVKFKTIEAAQKCVQAMNGRWF 74

                          90
                  ....*....|.
gi 1831509925 124 ANRTVVTSYYD 134
Cdd:cd12285    75 DGRQITAAYVP 85

RNA recognition motif 3 (RRM3) found in UHM domain of poly(U)-binding-splicing factor PUF60 and similar proteins; This subgroup corresponds to the RRM3 of PUF60, also termed FUSE-binding protein-interacting repressor (FBP-interacting repressor or FIR), or Ro-binding protein 1 (RoBP1), or Siah-binding protein 1 (Siah-BP1), an essential splicing factor that functions as a poly-U RNA-binding protein required to reconstitute splicing in depleted nuclear extracts. Its function is enhanced through interaction with U2 auxiliary factor U2AF65. PUF60 also controls human c-myc gene expression by binding and inhibiting the transcription factor far upstream sequence element (FUSE)-binding-protein (FBP), an activator of c-myc promoters. PUF60 contains two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbors another RRM and binds to tryptophan-containing linear peptide motifs (UHM ligand motifs, ULMs) in several nuclear proteins. The research indicates that PUF60 binds FUSE as a dimer, and only the first two RRM domains participate in the single-stranded DNA recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831509925  44 TEILCLMNMVTEDELkaDDEYEEileDVRDECSKYGIVRSLEI--PRPYEDHPVPGVGKVFVEFASTSDCQRAQAALTGR 121
Cdd:cd12648     1 SRVMVLRNMVGPEDI--DDDLEG---EVTEECGKFGAVNRVIIyqEKQGEEEDAEIIVKIFVEFSMPSEAEKAIQALNGR 75

                          90
                  ....*....|....*....
gi 1831509925 122 KFANRTVVTSYYDVDKYHN 140
Cdd:cd12648    76 WFGGRKVVAELYDQTRFDN 94

RNA recognition motif 2 (RRM2) found in HIV Tat-specific factor 1 (Tat-SF1) and similar proteins; This subfamily corresponds to the RRM2 of Tat-SF1 and CUS2. Tat-SF1 is the cofactor for stimulation of transcriptional elongation by human immunodeficiency virus-type 1 (HIV-1) Tat. It is a substrate of an associated cellular kinase. Tat-SF1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a highly acidic carboxyl-terminal half. The family also includes CUS2, a yeast homolog of human Tat-SF1. CUS2 interacts with U2 RNA in splicing extracts and functions as a splicing factor that aids assembly of the splicing-competent U2 snRNP in vivo. CUS2 also associates with PRP11 that is a subunit of the conserved splicing factor SF3a. Like Tat-SF1, CUS2 contains two RRMs as well.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831509925  46 ILCLMNMVTEDELKADDE-YEEILEDVRDECSKYGIVRSLEIprpYEDHPvPGVGKVFveFASTSDCQRAQAALTGRKFA 124
Cdd:cd12282     3 VVILKNMFHPKEFEEDPElINEIKEDLREECEKFGQVKKVVV---FDRHP-DGVASVK--FKEPEEADKCIQALNGRWFA 76

                          90
                  ....*....|
gi 1831509925 125 NRTVVTSYYD 134
Cdd:cd12282    77 GRKLEAETWD 86

RNA recognition motif (RRM) found in U2 small nuclear ribonucleoprotein auxiliary factor U2AF 35 kDa subunit (U2AF35) and similar proteins; This subfamily corresponds to the RRM in U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor (U2AF) which has been implicated in the recruitment of U2 snRNP to pre-mRNAs. It is a highly conserved heterodimer composed of large and small subunits; this family includes the small subunit of U2AF (U2AF35 or U2AF1) and U2AF 35 kDa subunit B (U2AF35B or C3H60). U2AF35 directly binds to the 3' splice site of the conserved AG dinucleotide and performs multiple functions in the splicing process in a substrate-specific manner. It promotes U2 snRNP binding to the branch-point sequences of introns through association with the large subunit of U2AF (U2AF65 or U2AF2). Although the biological role of U2AF35B remains unclear, it shows high sequence homolgy to U2AF35, which contains two N-terminal zinc fingers, a central RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal arginine/serine (SR) -rich segment interrupted by glycines. In contrast to U2AF35, U2AF35B has a plant-specific conserved C-terminal region containing SERE motif(s), which may have an important function specific to higher plants.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1831509925  54 TEDELKADDEYEEILEDVRDECSKYGIVRSLEIPRPYEDHPvpgVGKVFVEFASTSDCQRAQAALTGRKFANRTVVTSY 132
Cdd:cd12287    24 TLSEEEIQEHFDEFYEDVFLELSRFGEIEDLVVCSNLNDHL---LGNVYVKFESEEDAEAALQALNGRYYAGRPLYPEL 99

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831509925  69 EDVRDECSKYGIVRSLEIPRPYEDHPVpgvGKVFVEFASTSDCQRAQAALTGRKFANRTV 128
Cdd:cd00590    13 EDLRELFSKFGEVVSVRIVRDRDGKSK---GFAFVEFESPEDAEKALEALNGTELGGRPL 69

RNA recognition motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1831509925   69 EDVRDECSKYGIVRSLEIPRPYEDHPVPGVGkvFVEFASTSDCQRAQAALTGRKFANRTVV 129
Cdd:smart00360  14 EELRELFSKFGKVESVRLVRDKETGKSKGFA--FVEFESEEDAEKALEALNGKELDGRPLK 72

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831509925  69 EDVRDECSKYGIVRSLEIPRPYEDHPvPGVGkvFVEFASTSDCQRAQAALTGRKFANRTV 128
Cdd:pfam00076  13 EDLKDLFSKFGPIKSIRLVRDETGRS-KGFA--FVEFEDEEDAEKAIEALNGKELGGREL 69

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1831509925  69 EDVRDECSKYGIVRSLEIPRPyEDHPVPGVGkvFVEFASTSDCQRAQAALTGRKFANRTVV 129
Cdd:cd12414    14 DDLKKLFSKFGKVLEVTIPKK-PDGKLRGFA--FVQFTNVADAAKAIKGMNGKKIKGRPVA 71

RNA recognition motif (RRM) found in pre-mRNA cleavage factor Im 68 kDa subunit (CFIm68 or CPSF6), pre-mRNA cleavage factor Im 59 kDa subunit (CFIm59 or CPSF7), and similar proteins; This subfamily corresponds to the RRM of cleavage factor Im (CFIm) subunits. Cleavage factor Im (CFIm) is a highly conserved component of the eukaryotic mRNA 3' processing machinery that functions in UGUA-mediated poly(A) site recognition, the regulation of alternative poly(A) site selection, mRNA export, and mRNA splicing. It is a complex composed of a small 25 kDa (CFIm25) subunit and a larger 59/68/72 kDa subunit. Two separate genes, CPSF6 and CPSF7, code for two isoforms of the large subunit, CFIm68 and CFIm59. Structurally related CFIm68 and CFIm59, also termed cleavage and polyadenylation specificity factor subunit 6 (CPSF7), or cleavage and polyadenylation specificity factor 59 kDa subunit (CPSF59), are functionally redundant. Both contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a central proline-rich region, and a C-terminal RS-like domain. Their N-terminal RRM mediates the interaction with CFIm25, and also serves to enhance RNA binding and facilitate RNA looping.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1831509925  69 EDVRDECSKYGIVRSLEIPrpYEDHPVPGVGK--VFVEFASTSDCQRAQAALTGRKFANRTVVTSY 132
Cdd:cd12372    13 EDLEGACASFGVVDVKEIK--FFEHKANGKSKgyAYVEFASPAAAAAVKEKLEKREFNGRPCVVTP 76

RNA recognition motif 5 (RRM5) found in yeast multiple RNA-binding domain-containing protein 1 (MRD1) and similar proteins; This subgroup corresponds to the RRM5 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1831509925  64 YEEILEDVRDECSKYGIVRSLEIPRPYeDHPVPGVGkvFVEFASTSDCQRAQAALTGRKFANRTVVTSY 132
Cdd:cd12570    10 FEATKKDVRTLFSSYGQLKSVRVPKKF-DQSARGFA--FVEFSTAKEALNAMNALKDTHLLGRRLVLQY 75

RNA recognition motif (RRM) found in U2 small nuclear ribonucleoprotein auxiliary factor U2AF 35 kDa subunit (U2AF35); This subgroup corresponds to the RRM of U2AF35, also termed U2AF1, which is one of the small subunits of U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor (U2AF). It has been implicated in the recruitment of U2 snRNP to pre-mRNAs and is a highly conserved heterodimer composed of large and small subunits. U2AF35 directly binds to the 3' splice site of the conserved AG dinucleotide and performs multiple functions in the splicing process in a substrate-specific manner. It promotes U2 snRNP binding to the branch-point sequences of introns through association with the large subunit of U2AF, U2AF65 (also termed U2AF2). U2AF35 contains two N-terminal zinc fingers, a central RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal arginine/serine (SR)-rich segment interrupted by glycines. U2AF35 binds both U2AF65 and the pre-mRNA through its RRM domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1831509925  53 VTEDELKAddEYEEILEDVRDECS-KYGIVRSLEIPRPYEDHPVpgvGKVFVEFASTSDCQRAQAALTGRKFANRTV 128
Cdd:cd12538    27 VSDVELQE--HFDEFYEDVFVELEeKYGEIEEMNVCDNLGDHLV---GNVYVKFRREEDAEKAVNDLNNRWFNGQPI 98