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 1621574559  41 TFSQEVFTELQEKYGEIEEMNVCDNLGDHLVGNVYVKFRREEDGERAVAELSNRWFNGQAVH 102
Cdd:cd12538    38 EFYEDVFVELEEKYGEIEEMNVCDNLGDHLVGNVYVKFRREEDAEKAVNDLNNRWFNGQPIY 99

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1621574559  41 TFSQEVFTELQEKYGEIEEMNVCDNLGDHLVGNVYVKFRREEDGERAVAELSNRWFNGQAVH 102
Cdd:cd12538    38 EFYEDVFVELEEKYGEIEEMNVCDNLGDHLVGNVYVKFRREEDAEKAVNDLNNRWFNGQPIY 99

Zinc finger C-x8-C-x5-C-x3-H type (and similar);

                          10        20
                  ....*....|....*....|....*..
gi 1621574559  13 KDKVNCSFYFKIGVCRHGDRCSRLHNK 39
Cdd:pfam00642   1 YKTELCRFFLRTGYCKYGDRCKFAHGQ 27

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1621574559  32 RCSRLHN--------KPTFSQEVFTELQE---KYGEIEEMNVCDNLGDhlvGNVYVKFRREEDGERAVAELSNRWFNGQA 100
Cdd:TIGR01622 400 RCLVLSNmfdpateeEPNWDKEIEDDVREecsKYGGVVHIYVDDKNSA---GDIYLKFDSVQAAEAAIKALNGRYFGGKM 476

                  .
gi 1621574559 101 V 101
Cdd:TIGR01622 477 I 477

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1621574559  41 TFSQEVFTELQEKYGEIEEMNVCDNLGDHLVGNVYVKFRREEDGERAVAELSNRWFNGQAVH 102
Cdd:cd12538    38 EFYEDVFVELEEKYGEIEEMNVCDNLGDHLVGNVYVKFRREEDAEKAVNDLNNRWFNGQPIY 99

RNA recognition motif (RRM) found in splicing factor U2AF 35 kDa subunit B (U2AF35B); This subgroup corresponds to the RRM of U2AF35B, also termed zinc finger CCCH domain-containing protein 60 (C3H60), 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. Members in this family are mainly found in plant. They show high sequence homology to vertebrates U2AF35 that 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. U2AF35B 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 domain. 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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1621574559  42 FSQEVFTELQeKYGEIEEMNVCDNLGDHLVGNVYVKFRREEDGERAVAELSNRWFNGQ 99
Cdd:cd12539    38 FYEDVFEELS-KFGEVEALNVCDNLGDHMVGNVYVKFRDEEHAAAALKALQGRFYAGR 94

RNA recognition motif (RRM) found in U2 small nuclear ribonucleoprotein auxiliary factor 35 kDa subunit-related protein 1 (U2AFBPL) and similar proteins; This subgroup corresponds to the RRM of U2AFBPL, a human homolog of the imprinted mouse gene U2afbp-rs, which encodes a U2 small nuclear ribonucleoprotein auxiliary factor 35 kDa subunit-related protein 1 (U2AFBPL), also termed CCCH type zinc finger, RNA-binding motif and serine/arginine rich protein 1 (U2AF1RS1), or U2 small nuclear RNA auxiliary factor 1-like 1 (U2AF1L1). Although the biological role of U2AFBPL remains unclear, it shows high sequence homology to splicing factor U2AF 35 kDa subunit (U2AF35 or U2AF1) that 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. Like U2AF35, U2AFBPL 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 domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1621574559  42 FSQEVFTELqEKYGEIEEMNVCDNLGDHLVGNVYVKFRREEDGERAVAELSNRWFNGQAVH 102
Cdd:cd12540    41 FYEDVLPEF-KKFGKVVQFKVCCNSEPHLRGNVYVQYQSEEEALKAFTSFNGRWYAGKQLQ 100

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1621574559  43 SQEVFTELQE-------KYGEIEEMNVCDNLGDhlvGNVYVKFRREEDGERAVAELSNRWFNGQAV 101
Cdd:cd12285    17 EDNWDDEIKEdvieecsKYGPVLHIYVDKNSPQ---GNVYVKFKTIEAAQKCVQAMNGRWFDGRQI 79

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1621574559  39 KPTFSQEVFTELQ---EKYGEIEEMNVCDnlgDHLVGNVYVKFRREEDGERAVAELSNRWFNGQAVH 102
Cdd:cd12282    18 DPELINEIKEDLReecEKFGQVKKVVVFD---RHPDGVASVKFKEPEEADKCIQALNGRWFAGRKLE 81

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 1621574559  40 PTFSQEVFTELQEKYGEIEEMNVCDNLGDHLVGNVYVKFRREEDGERAVAELSNRWFNGQAVH 102
Cdd:pfam00076   8 PDTTEEDLKDLFSKFGPIKSIRLVRDETGRSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1621574559  49 ELQEKYGEIEEMNVCDNLGdhlvgnvYVKFRREEDGERAVAELSNRWFNGQAVH 102
Cdd:cd12343    18 ALFEKYGKVTECDIVKNYA-------FVHMEKEEDAEDAIKALNGYEFMGSRIN 64

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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1621574559  51 QEKYGEIEEmnvcdnlGDHLVgNVYVKFRREEDGERAVAELSNRWFNGQAV 101
Cdd:cd12648    40 QEKQGEEED-------AEIIV-KIFVEFSMPSEAEKAIQALNGRWFGGRKV 82

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1621574559  32 RCSRLHN--------KPTFSQEVFTELQE---KYGEIEEMNVCDNLGDhlvGNVYVKFRREEDGERAVAELSNRWFNGQA 100
Cdd:TIGR01622 400 RCLVLSNmfdpateeEPNWDKEIEDDVREecsKYGGVVHIYVDDKNSA---GDIYLKFDSVQAAEAAIKALNGRYFGGKM 476

                  .
gi 1621574559 101 V 101
Cdd:TIGR01622 477 I 477

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
                  ....*....|....*....|....*....|.
gi 1621574559  72 GNVYVKFRREEDGERAVAELSNRWFNGQAVH 102
Cdd:cd12413    42 GFGYVTFALAEDAQRALEEVKGKKFGGRKIK 72