RNA recognition motif (RRM) found in U2-associated protein SR140 and similar proteins; This subgroup corresponds to the RRM of SR140 (also termed U2 snRNP-associated SURP motif-containing protein orU2SURP, or 140 kDa Ser/Arg-rich domain protein) which is a putative splicing factor mainly found in higher eukaryotes. Although it is initially identified as one of the 17S U2 snRNP-associated proteins, the molecular and physiological function of SR140 remains unclear. SR140 contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a SWAP/SURP domain that is found in a number of pre-mRNA splicing factors in the middle region, and a C-terminal arginine/serine-rich domain (RS domain).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 995970143  272 TTNLYLGNINPQMNEEMLCQEFGRFGPLASVKIMWPRTDEERARERNCGFVAFMNRRDAERALKNLNGKMIMSFEMKLGW 351
Cdd:cd12223     1 TTNLYVGNLPPSVTEEVLLREFGRFGPLASVKIMWPRTEEERRRNRNCGFVAFMSRADAERAMRELNGKDVMGYELKLGW 80

                  ....
gi 995970143  352 GKAV 355
Cdd:cd12223    81 GKAV 84

cwf21 domain found in U2-associated protein SR140 and similar proteins; SR140, also called U2 snRNP-associated SURP motif-containing protein, U2SURP, or 140 kDa Ser/Arg-rich domain protein, is a putative splicing factor mainly found in higher eukaryotes. Although it was initially identified as a 17S U2 snRNP-associated protein, the molecular and physiological function of SR140 remains unclear. This model represents the cwf21 domain of SR140 and similar proteins. The cwf21 domain is involved in mRNA splicing; it binds directly to the spliceosomal protein Prp8.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 995970143  835 MSEEKRAKLREIELKVMKFQDELESGKRPKKPGQSFQEQVEHYRDKLLQ 883
Cdd:cd21370     1 IDEERRAKLREIELKVMKYQDELESGKRSRKPGESISEQVEQYRKKLLK 49

RNA recognition motif (RRM) found in U2-associated protein SR140 and similar proteins; This subgroup corresponds to the RRM of SR140 (also termed U2 snRNP-associated SURP motif-containing protein orU2SURP, or 140 kDa Ser/Arg-rich domain protein) which is a putative splicing factor mainly found in higher eukaryotes. Although it is initially identified as one of the 17S U2 snRNP-associated proteins, the molecular and physiological function of SR140 remains unclear. SR140 contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a SWAP/SURP domain that is found in a number of pre-mRNA splicing factors in the middle region, and a C-terminal arginine/serine-rich domain (RS domain).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 995970143  272 TTNLYLGNINPQMNEEMLCQEFGRFGPLASVKIMWPRTDEERARERNCGFVAFMNRRDAERALKNLNGKMIMSFEMKLGW 351
Cdd:cd12223     1 TTNLYVGNLPPSVTEEVLLREFGRFGPLASVKIMWPRTEEERRRNRNCGFVAFMSRADAERAMRELNGKDVMGYELKLGW 80

                  ....
gi 995970143  352 GKAV 355
Cdd:cd12223    81 GKAV 84

cwf21 domain found in U2-associated protein SR140 and similar proteins; SR140, also called U2 snRNP-associated SURP motif-containing protein, U2SURP, or 140 kDa Ser/Arg-rich domain protein, is a putative splicing factor mainly found in higher eukaryotes. Although it was initially identified as a 17S U2 snRNP-associated protein, the molecular and physiological function of SR140 remains unclear. This model represents the cwf21 domain of SR140 and similar proteins. The cwf21 domain is involved in mRNA splicing; it binds directly to the spliceosomal protein Prp8.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 995970143  835 MSEEKRAKLREIELKVMKFQDELESGKRPKKPGQSFQEQVEHYRDKLLQ 883
Cdd:cd21370     1 IDEERRAKLREIELKVMKYQDELESGKRSRKPGESISEQVEQYRKKLLK 49

RNA recognition motif;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 995970143    274 NLYLGNINPQMNEEMLCQEFGRFGPLASVKIMwprTDEERARERNCGFVAFMNRRDAERALKNLNGKMIMSFEMKL 349
Cdd:smart00360    1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLV---RDKETGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain); The RRM motif is probably diagnostic of an RNA binding protein. RRMs are found in a variety of RNA binding proteins, including various hnRNP proteins, proteins implicated in regulation of alternative splicing, and protein components of snRNPs. The motif also appears in a few single stranded DNA binding proteins. The RRM structure consists of four strands and two helices arranged in an alpha/beta sandwich, with a third helix present during RNA binding in some cases The C-terminal beta strand (4th strand) and final helix are hard to align and have been omitted in the SEED alignment The LA proteins have an N terminal rrm which is included in the seed. There is a second region towards the C terminus that has some features characteriztic of a rrm but does not appear to have the important structural core of a rrm. The LA proteins are one of the main autoantigens in Systemic lupus erythematosus (SLE), an autoimmune disease.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 995970143   275 LYLGNINPQMNEEMLCQEFGRFGPLASVKIMWPRTDeeraRERNCGFVAFMNRRDAERALKNLNGKMIMSFEMK 348
Cdd:pfam00076    1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRDETG----RSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 995970143   274 NLYLGNINPQMNEEMLCQEFGRFGPLASVKIMWprtdEERARERNCGFVAFMNRRDAERALKNLNGKMI 342
Cdd:TIGR01628  287 NLYVKNLDDTVTDEKLRELFSECGEITSAKVML----DEKGVSRGFGFVCFSNPEEANRAVTEMHGRML 351

CID (CTD-Interacting Domain) of Regulation of nuclear pre-mRNA domain-containing proteins; This family is composed of Regulation of nuclear pre-mRNA domain-containing proteins 1A (RPRD1A), 1B (RPRD1B), 2 (RPRD2), yeast Rtt103, and similar proteins. RPRD1A, RPRD1B, and RPRD2 are CID (CTD-Interacting Domain) containing proteins that co-purify with RNA polymerase (Pol) II (RNAP II) and three other RNAP II-associated proteins, RPAP2, GRINL1A and RECQL5, but not with the Mediator complex. Yeast transcription termination factor Rtt103 is a CID containing protein that functions in DNA damage response. CID binds tightly to the carboxy-terminal domain (CTD) of RNAP II. During transcription, RNAP II synthesizes eukaryotic messenger RNA. Transcription is coupled to RNA processing through the CTD, which consists of up to 52 repeats of the sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. CID contains eight alpha-helices in a right-handed superhelical arrangement, which closely resembles that of the VHS domains and ARM (Armadillo) repeat proteins, except for its two amino-terminal helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 995970143  538 RDKLEEILRGLTPRKNDIGDAMVFCLNNAEAAEEIVDCITESLsiLKTPLPKKIARLYLVSDVLYNSSAKvaNASYYRKF 617
Cdd:cd16981     1 EEALEKKLRSLNNTQQSIQTLSLWCLFHKKHAKQIVKIWLKEL--KKAKPERKLTLLYLANDVLQNSRRK--GAPEFVEA 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 995970143  618 FETKLCQIFSDLNATyrtiqghlQSENFKQRVMTCFRAWEDWAIYPEPFLIKLQNI 673
Cdd:cd16981    77 FKKVLPEALALVRSE--------GDESVRKKVLRVLNIWEERNVFGSEFLAELRAI 124

glycine-rich RNA-binding protein 4; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 995970143  272 TTNLYLGNINPQMNEEMLCQEFGRFGPLASVKIMwprTDEERARERNCGFVAFMNRRDAERALKNLNGK 340
Cdd:PLN03134   34 STKLFIGGLSWGTDDASLRDAFAHFGDVVDAKVI---VDRETGRSRGFGFVNFNDEGAATAAISEMDGK 99

RNA recognition motif (RRM) found in U2-associated protein SR140 and similar proteins; This subgroup corresponds to the RRM of SR140 (also termed U2 snRNP-associated SURP motif-containing protein orU2SURP, or 140 kDa Ser/Arg-rich domain protein) which is a putative splicing factor mainly found in higher eukaryotes. Although it is initially identified as one of the 17S U2 snRNP-associated proteins, the molecular and physiological function of SR140 remains unclear. SR140 contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a SWAP/SURP domain that is found in a number of pre-mRNA splicing factors in the middle region, and a C-terminal arginine/serine-rich domain (RS domain).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 995970143  272 TTNLYLGNINPQMNEEMLCQEFGRFGPLASVKIMWPRTDEERARERNCGFVAFMNRRDAERALKNLNGKMIMSFEMKLGW 351
Cdd:cd12223     1 TTNLYVGNLPPSVTEEVLLREFGRFGPLASVKIMWPRTEEERRRNRNCGFVAFMSRADAERAMRELNGKDVMGYELKLGW 80

                  ....
gi 995970143  352 GKAV 355
Cdd:cd12223    81 GKAV 84

cwf21 domain found in U2-associated protein SR140 and similar proteins; SR140, also called U2 snRNP-associated SURP motif-containing protein, U2SURP, or 140 kDa Ser/Arg-rich domain protein, is a putative splicing factor mainly found in higher eukaryotes. Although it was initially identified as a 17S U2 snRNP-associated protein, the molecular and physiological function of SR140 remains unclear. This model represents the cwf21 domain of SR140 and similar proteins. The cwf21 domain is involved in mRNA splicing; it binds directly to the spliceosomal protein Prp8.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 995970143  835 MSEEKRAKLREIELKVMKFQDELESGKRPKKPGQSFQEQVEHYRDKLLQ 883
Cdd:cd21370     1 IDEERRAKLREIELKVMKYQDELESGKRSRKPGESISEQVEQYRKKLLK 49

RNA recognition motif;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 995970143    274 NLYLGNINPQMNEEMLCQEFGRFGPLASVKIMwprTDEERARERNCGFVAFMNRRDAERALKNLNGKMIMSFEMKL 349
Cdd:smart00360    1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLV---RDKETGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 995970143  275 LYLGNINPQMNEEMLCQEFGRFGPLASVKIMWPRTDeeraRERNCGFVAFMNRRDAERALKNLNGKMIMSFEMKL 349
Cdd:cd00590     1 LFVGNLPPDTTEEDLRELFSKFGEVVSVRIVRDRDG----KSKGFAFVEFESPEDAEKALEALNGTELGGRPLKV 71

RNA recognition motif 1 (RRM1) found in granule-associated RNA binding proteins p40-TIA-1 and TIAR; This subfamily corresponds to the RRM1 of nucleolysin TIA-1 isoform p40 (p40-TIA-1 or TIA-1) and nucleolysin TIA-1-related protein (TIAR), both of which are granule-associated RNA binding proteins involved in inducing apoptosis in cytotoxic lymphocyte (CTL) target cells. TIA-1 and TIAR share high sequence similarity. They are expressed in a wide variety of cell types. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis.TIAR is mainly localized in the nucleus of hematopoietic and nonhematopoietic cells. It is translocated from the nucleus to the cytoplasm in response to exogenous triggers of apoptosis. Both, TIA-1 and TIAR, bind specifically to poly(A) but not to poly(C) homopolymers. They are composed of three N-terminal highly homologous RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. TIA-1 and TIAR interact with RNAs containing short stretches of uridylates and their RRM2 can mediate the specific binding to uridylate-rich RNAs. The C-terminal auxiliary domain may be responsible for interacting with other proteins. In addition, TIA-1 and TIAR share a potential serine protease-cleavage site (Phe-Val-Arg) localized at the junction between their RNA binding domains and their C-terminal auxiliary domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 995970143  275 LYLGNINPQMNEEMLCQEFGRFGPLASVKIMwprtdEERARERNCGFVAFMNRRDAERALKNLNGKMIMSFEMKLGW 351
Cdd:cd12352     1 LYVGNLDRQVTEDLILQLFSQIGPCKSCKMI-----TEHGGNDPYCFVEFYEHNHAAAALQAMNGRKILGKEVKVNW 72

RNA recognition motif 2 (RRM2) found in yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1 and similar proteins; This subgroup corresponds to the RRM2 of yeast protein PUB1, also termed ARS consensus-binding protein ACBP-60, or poly uridylate-binding protein, or poly(U)-binding protein. PUB1 has been identified as both, a heterogeneous nuclear RNA-binding protein (hnRNP) and a cytoplasmic mRNA-binding protein (mRNP), which may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm. It is distributed in both, the nucleus and the cytoplasm, and binds to poly(A)+ RNA (mRNA or pre-mRNA). Although it is one of the major cellular proteins cross-linked by UV light to polyadenylated RNAs in vivo, PUB1 is nonessential for cell growth in yeast. PUB1 also binds to T-rich single stranded DNA (ssDNA). However, there is no strong evidence implicating PUB1 in the mechanism of DNA replication. PUB1 contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a GAR motif (glycine and arginine rich stretch) that is located between RRM2 and RRM3.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 995970143  274 NLYLGNINPQMNEEMLCQEFGRFGPLASVKIMWprtDEERARERNCGFVAFMNRRDAERALKNLNGKMIMSFEMKLGW 351
Cdd:cd12619     3 NIFVGDLSPEVTDAALFNAFSDFPSCSDARVMW---DQKTGRSRGYGFVSFRSQQDAQNAINSMNGKWLGSRPIRCNW 77

cwf21 domain; The cwf21 domain is involved in mRNA splicing; it binds directly to the spliceosomal protein Prp8. Mutations in the cwf21 domain prevents its binding to Prp8. The domain is composed of two alpha helices. Proteins containing the cwf21 domain include complexed with CEF1 protein 21 (CWC21) from budding yeast, complexed with cdc5 protein 21 (CWF21) from fission yeast, as well as their orthologs, serine/arginine repetitive matrix proteins (SRRM2 and SRRM3) from vertebrates. This domain family also includes U2-associated protein SR140 from Eumetazoa, protein RRC1, and similar proteins from plants.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 995970143  835 MSEEKRAKLREIELKVMKFQDELESGKRpkKPGQSFQEQVEHYRDKLLQ 883
Cdd:cd21369     1 MDEEKRAKKREIELKVMELRDELEEQGR--KPEQQIQEKVEHYRDKLLQ 47

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 995970143  272 TTNLYLGNINPQMNEEMLCQEFGRFGPLASVKIMwprTDEERARERNCGFVAFMNRRDAERALKNLNGKMIM 343
Cdd:COG0724     1 SMKIYVGNLPYSVTEEDLRELFSEYGEVTSVKLI---TDRETGRSRGFGFVEMPDDEEAQAAIEALNGAELM 69

RNA recognition motif 2 (RRM2) found in vertebrate RNA-binding protein RBM23, RBM39 and similar proteins; This subfamily corresponds to the RRM2 of RBM39 (also termed HCC1), a nuclear autoantigen that contains an N-terminal arginine/serine rich (RS) motif and three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). An octapeptide sequence called the RS-ERK motif is repeated six times in the RS region of RBM39. Although the cellular function of RBM23 remains unclear, it shows high sequence homology to RBM39 and contains two RRMs. It may possibly function as a pre-mRNA splicing factor.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 995970143  275 LYLGNINPQMNEEMLCQEFGRFGPLASVKIMwprTDEERARERNCGFVAFMNRRDAERALKNLNGKMIMSFEMKLG 350
Cdd:cd12284     1 LYVGSLHFNITEDMLRGIFEPFGKIEFVQLQ---KDPETGRSKGYGFIQFRDAEDAKKALEQLNGFELAGRPMKVG 73

RNA recognition motif (RRM) found in Pre-mRNA-splicing factor RBM22 and similar proteins; This subgroup corresponds to the RRM of RBM22 (also known as RNA-binding motif protein 22, or Zinc finger CCCH domain-containing protein 16), a newly discovered RNA-binding motif protein which belongs to the SLT11 gene family. SLT11 gene encoding protein (Slt11p) is a splicing factor in yeast, which is required for spliceosome assembly. Slt11p has two distinct biochemical properties: RNA-annealing and RNA-binding activities. RBM22 is the homolog of SLT11 in vertebrate. It has been reported to be involved in pre-splicesome assembly and to interact with the Ca2+-signaling protein ALG-2. It also plays an important role in embryogenesis. RBM22 contains a conserved RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a zinc finger of the unusual type C-x8-C-x5-C-x3-H, and a C-terminus that is unusually rich in the amino acids Gly and Pro, including sequences of tetraprolines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 995970143  273 TNLYLGNINPQMNEEMLCQEFGRFGPLASVKImwprtdeerARERNCGFVAFMNRRDAERALKNLNGKMIMSFEM-KLGW 351
Cdd:cd12224     2 TTLYVGGLGDKITEKDLRDHFYQFGEIRSITV---------VARQQCAFVQFTTRQAAERAAERTFNKLIIKGRRlKVKW 72

                  ..
gi 995970143  352 GK 353
Cdd:cd12224    73 GR 74

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 995970143   274 NLYLGNINPQMNEEMLCQEFGRFGPLASVKIMWprtdEERARERNCGFVAFMNRRDAERALKNLNGKMI 342
Cdd:TIGR01628  287 NLYVKNLDDTVTDEKLRELFSECGEITSAKVML----DEKGVSRGFGFVCFSNPEEANRAVTEMHGRML 351

CID domain; This domain binds to the phosphorylated C-terminal domain (CTD) of RNA polymerase II. This domain is known as the CTD-interacting domain (CID).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 995970143   539 DKLEEILRGLTPRKNDIGDAMVFCLNNAEAAEEIVDCITESLsiLKTPLPKKIARLYLVSDVLYNSSAKvaNASYYRKFF 618
Cdd:pfam04818    1 EALEKKLSSLNNSQESIQTLSKWILFHRKHAKAIVEVWEKYL--KKAKPEKKLHLLYLANDVLQNSRKK--GKSEFADAF 76

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 995970143   619 ETKLCQIFSDLNATYrtiqghlqSENFKQRVMTCFRAWEDWAIYPEPFL 667
Cdd:pfam04818   77 EPVLPEAFASAYKKC--------DEKLKKKLERLLNIWEERNVFSPEVI 117

RNA recognition motif (RRM) found in heterogeneous nuclear ribonucleoprotein G (hnRNP G), Y chromosome RNA recognition motif 1 (hRBMY), testis-specific heterogeneous nuclear ribonucleoprotein G-T (hnRNP G-T) and similar proteins; This subfamily corresponds to the RRM domain of hnRNP G, also termed glycoprotein p43 or RBMX, an RNA-binding motif protein located on the X chromosome. It is expressed ubiquitously and has been implicated in the splicing control of several pre-mRNAs. Moreover, hnRNP G may function as a regulator of transcription for SREBP-1c and GnRH1. Research has shown that hnRNP G may also act as a tumor-suppressor since it upregulates the Txnip gene and promotes the fidelity of DNA end-joining activity. In addition, hnRNP G appears to play a critical role in proper neural development of zebrafish and frog embryos. The family also includes several paralogs of hnRNP G, such as hRBMY and hnRNP G-T (also termed RNA-binding motif protein, X-linked-like-2). Both, hRBMY and hnRNP G-T, are exclusively expressed in testis and critical for male fertility. Like hnRNP G, hRBMY and hnRNP G-T interact with factors implicated in the regulation of pre-mRNA splicing, such as hTra2-beta1 and T-STAR. Although members in this family share a high conserved N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), they appear to recognize different RNA targets. For instance, hRBMY interacts specifically with a stem-loop structure in which the loop is formed by the sequence CA/UCAA. In contrast, hnRNP G associates with single stranded RNA sequences containing a CCA/C motif. In addition to the RRM, hnRNP G contains a nascent transcripts targeting domain (NTD) in the middle region and a novel auxiliary RNA-binding domain (RBD) in its C-terminal region. The C-terminal RBD exhibits distinct RNA binding specificity, and would play a critical role in the regulation of alternative splicing by hnRNP G.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 995970143  273 TNLYLGNINPQMNEEMLCQEFGRFGPLASVKIMwprTDEERARERNCGFVAFMNRRDAERALKNLNGKMIM 343
Cdd:cd12382     2 GKLFIGGLNTETNEKALEAVFGKYGRIVEVLLM---KDRETNKSRGFAFVTFESPADAKDAARDMNGKELD 69

RNA recognition motif 2 (RRM2) found in granule-associated RNA binding proteins (p40-TIA-1 and TIAR), and yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1; This subfamily corresponds to the RRM3 of TIA-1, TIAR, and PUB1. Nucleolysin TIA-1 isoform p40 (p40-TIA-1 or TIA-1) and nucleolysin TIA-1-related protein (TIAR) are granule-associated RNA binding proteins involved in inducing apoptosis in cytotoxic lymphocyte (CTL) target cells. They share high sequence similarity and are expressed in a wide variety of cell types. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis.TIAR is mainly localized in the nucleus of hematopoietic and nonhematopoietic cells. It is translocated from the nucleus to the cytoplasm in response to exogenous triggers of apoptosis. Both TIA-1 and TIAR bind specifically to poly(A) but not to poly(C) homopolymers. They are composed of three N-terminal highly homologous RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. TIA-1 and TIAR interact with RNAs containing short stretches of uridylates and their RRM2 can mediate the specific binding to uridylate-rich RNAs. The C-terminal auxiliary domain may be responsible for interacting with other proteins. In addition, TIA-1 and TIAR share a potential serine protease-cleavage site (Phe-Val-Arg) localized at the junction between their RNA binding domains and their C-terminal auxiliary domains. This subfamily also includes a yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1, termed ARS consensus-binding protein ACBP-60, or poly uridylate-binding protein, or poly(U)-binding protein, which has been identified as both a heterogeneous nuclear RNA-binding protein (hnRNP) and a cytoplasmic mRNA-binding protein (mRNP). It may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm. PUB1 is distributed in both, the nucleus and the cytoplasm, and binds to poly(A)+ RNA (mRNA or pre-mRNA). Although it is one of the major cellular proteins cross-linked by UV light to polyadenylated RNAs in vivo, PUB1 is nonessential for cell growth in yeast. PUB1 also binds to T-rich single stranded DNA (ssDNA); however, there is no strong evidence implicating PUB1 in the mechanism of DNA replication. PUB1 contains three RRMs, and a GAR motif (glycine and arginine rich stretch) that is located between RRM2 and RRM3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 995970143  273 TNLYLGNINPQMNEEMLCQEFGRFGPLASVKIMwprtdeeraRERNCGFVAFMNRRDAERALKNLNGKMIMSFEMKLGWG 352
Cdd:cd12354     1 TTVYVGNITKGLTEALLQQTFSPFGQILEVRVF---------PDKGYAFIRFDSHEAATHAIVSVNGTIINGQAVKCSWG 71

RNA recognition motif (RRM) found in eukaryotic translation initiation factor 3 subunit G (eIF-3G) and similar proteins; This subfamily corresponds to the RRM of eIF-3G and similar proteins. eIF-3G, also termed eIF-3 subunit 4, or eIF-3-delta, or eIF3-p42, or eIF3-p44, is the RNA-binding subunit of eIF3, a large multisubunit complex that plays a central role in the initiation of translation by binding to the 40 S ribosomal subunit and promoting the binding of methionyl-tRNAi and mRNA. eIF-3G binds 18 S rRNA and beta-globin mRNA, and therefore appears to be a nonspecific RNA-binding protein. eIF-3G is one of the cytosolic targets and interacts with mature apoptosis-inducing factor (AIF). eIF-3G contains one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). This family also includes yeast eIF3-p33, a homolog of vertebrate eIF-3G, plays an important role in the initiation phase of protein synthesis in yeast. It binds both, mRNA and rRNA, fragments due to an RRM near its C-terminus.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 995970143  279 NINPQMNEEMLCQEFGRFGPLASVKIMwprTDEERARERNCGFVAFMNRRDAERALKNLNGKMIMSFEMKLGW 351
Cdd:cd12408     6 NLSEDATEEDLRELFRPFGPISRVYLA---KDKETGQSKGFAFVTFETREDAERAIEKLNGFGYDNLILSVEW 75

RNA recognition motif 2 (RRM2) found in vertebrate RNA binding motif protein 15 (RBM15); This subgroup corresponds to the RRM2 of RBM15, also termed one-twenty two protein 1 (OTT1), conserved in eukaryotes, a novel mRNA export factor and component of the NXF1 pathway. It binds to NXF1 and serves as receptor for the RNA export element RTE. It also possesses mRNA export activity and can facilitate the access of DEAD-box protein DBP5 to mRNA at the nuclear pore complex (NPC). RBM15 belongs to the Spen (split end) protein family, which contain three N-terminal RNA recognition motifs (RRMs), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal SPOC (Spen paralog and ortholog C-terminal) domain. This family also includes a RBM15-MKL1 (OTT-MAL) fusion protein that RBM15 is N-terminally fused to megakaryoblastic leukemia 1 protein (MKL1) at the C-terminus in a translocation involving chromosome 1 and 22, resulting in acute megakaryoblastic leukemia. The fusion protein could interact with the mRNA export machinery. Although it maintains the specific transactivator function of MKL1, the fusion protein cannot activate RTE-mediated mRNA expression and has lost the post-transcriptional activator function of RBM15. However, it has transdominant suppressor function contributing to its oncogenic properties.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 995970143  275 LYLGNINPQMNEEMLCQEFGRFGPLASVKIMWPrtdeERARERNCGFVAFMNRRDAERALKNLNGKMIMSFEMKLGWGKA 354
Cdd:cd12555    10 LFLGNLDITVTENDLRRAFDRFGVITEVDIKRP----GRGQTSTYGFLKFENLDMAHRAKLAMSGKVIGRNPIKIGYGKA 85

                  .
gi 995970143  355 V 355
Cdd:cd12555    86 T 86

RNA recognition motif 1 (RRM1) found in splicing factor 3B subunit 4 (SF3B4) and similar proteins; This subfamily corresponds to the RRM1 of SF3B4, also termed pre-mRNA-splicing factor SF3b 49 kDa (SF3b50), or spliceosome-associated protein 49 (SAP 49). SF3B4 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 995970143  275 LYLGNINPQMNEEMLCQEFGRFGPLASVKImwPRtDEERARERNCGFVAFMNRRDAERALKNLNG 339
Cdd:cd12334     1 VYVGNLDEKVTEELLWELFIQAGPVVNVHM--PK-DRVTQQHQGYGFVEFLSEEDADYAIKIMNM 62

RNA recognition motif 2 (RRM2) found in RNA-binding protein MRN1 and similar proteins; This subgroup corresponds to the RRM2 of MRN1, also termed multicopy suppressor of RSC-NHP6 synthetic lethality protein 1, or post-transcriptional regulator of 69 kDa, which is a RNA-binding protein found in yeast. Although its specific biological role remains unclear, MRN1 might be involved in translational regulation. Members in this family contain four copies of conserved RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 995970143  271 STTNLYLGNINPQMNEEMLCQEFGRFGPLASVKIMwprtdeeraRERNCGFVAFMNRRDAERALKNL 337
Cdd:cd12523     2 ASRNVYLGNLPESITEEELREDLEKFGPIDQIKIV---------KEKNIAFVHFLSIANAIKVVTTL 59

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 995970143  285 NEEMLCQEFGRFGPLASVKImwPRTDEERARerNCGFVAFMNRRDAERALKNLNGKMIM 343
Cdd:cd12414    12 TEDDLKKLFSKFGKVLEVTI--PKKPDGKLR--GFAFVQFTNVADAAKAIKGMNGKKIK 66

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 995970143  275 LYLGNINPQMNEEMLCQEFGRFGPLASVKIMwprTDEERARERNCGFVAFMNRRDAERALKNLNGKMI 342
Cdd:cd12449     3 LFVGGLSFDTNEQSLEEVFSKYGQISEVVVV---KDRETQRSRGFGFVTFENPDDAKDAMMAMNGKSL 67

RNA recognition motif 1 (RRM1) found in nucleolysin TIA-1 isoform p40 (p40-TIA-1) and similar proteins; This subgroup corresponds to the RRM1 of TIA-1, the 40-kDa isoform of T-cell-restricted intracellular antigen-1 (TIA-1) and a cytotoxic granule-associated RNA-binding protein mainly found in the granules of cytotoxic lymphocytes. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis, and functions as the granule component responsible for inducing apoptosis in cytolytic lymphocyte (CTL) targets. It is composed of three N-terminal highly homologous RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. TIA-1 interacts with RNAs containing short stretches of uridylates and its RRM2 can mediate the specific binding to uridylate-rich RNAs.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 995970143  275 LYLGNINPQMNEEMLCQEFGRFGPLASVKIMWprtdEERARERNCgFVAFMNRRDAERALKNLNGKMIMSFEMKLGWG 352
Cdd:cd12615     2 LYVGNLSRDVTEALILQLFSQIGPCKNCKMIM----DTAGNDPYC-FVEFHEHRHAAAALAAMNGRKIMGKEVKVNWA 74

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 995970143  274 NLYLGNINPQMNEEMLCQEFGRFGP-LASVKIMwprTDEERARERNCGFVAFMNRRDAERALKNLNGKMIMS 344
Cdd:cd12335     3 NLFIGNLDPEVDEKLLYDTFSAFGViLQTPKIM---RDPDTGNSKGFGFVSFDSFEASDAAIEAMNGQYLCN 71

RNA recognition motif 1 (RRM1) found in Saccharomyces cerevisiae protein PES4, protein MIP6 and similar proteins; The family includes PES4 (also called DNA polymerase epsilon suppressor 4) and MIP6 (also called MEX67-interacting protein 6), both of which are predicted RNA binding proteins that may act as regulators of late translation, protection, and mRNA localization. MIP6 acts as a novel factor for nuclear mRNA export, binds to both poly(A)+ RNA and nuclear pores. It interacts with MEX67. Members in this family contain four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the first RRM motif.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 995970143  273 TNLYLGNINPQMNEEMLCQEFGRFGPLASVKIMwprTDEERARERNCGFVAFMNRRDAERALKNLNGKMIMSFEMKL 349
Cdd:cd21601     1 TALFIGDLDKDVTEEMLRDIFSKYKSLVSVKIC---LDSETKKSLGYGYLNFSDKEDAEKAIEEFNYTPIFGKEVRI 74

RNA recognition motif 1 (RRM1) found in type I polyadenylate-binding proteins; This subfamily corresponds to the RRM1 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 a 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 mammals, 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 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 995970143  275 LYLGNINPQMNEEMLCQEFGRFGPLASVKIMwprTDEERARERNCGFVAFMNRRDAERALKNLNGKMIMSFEMKLGW 351
Cdd:cd12378     2 LYVGDLHPDVTEAMLYEKFSPAGPVLSIRVC---RDAVTRRSLGYAYVNFQQPADAERALDTLNFDVIKGKPIRIMW 75

RNA recognition motif 1 (RRM1) found in tRNA selenocysteine-associated protein 1 (SECp43) and similar proteins; This subfamily corresponds to the RRM1 in tRNA selenocysteine-associated protein 1 (SECp43), yeast negative growth regulatory protein NGR1 (RBP1), yeast protein NAM8, and similar proteins. SECp43 is an RNA-binding protein associated specifically with eukaryotic selenocysteine tRNA [tRNA(Sec)]. It may play an adaptor role in the mechanism of selenocysteine insertion. SECp43 is located primarily in the nucleus and contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal polar/acidic region. Yeast proteins, NGR1 and NAM8, show high sequence similarity with SECp43. NGR1 is a putative glucose-repressible protein that binds both RNA and single-stranded DNA (ssDNA). It may function in regulating cell growth in early log phase, possibly through its participation in RNA metabolism. NGR1 contains three RRMs, two of which are followed by a glutamine-rich stretch that may be involved in transcriptional activity. In addition, NGR1 has an asparagine-rich region near the C-terminus which also harbors a methionine-rich region. NAM8 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. NAM8 also contains three RRMs.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 995970143  275 LYLGNINPQMNEEMLCQEFGRFGP-LASVKIMwprTDEERARERNCGFVAFMNRRDAERALKNLNGKMIMSFE--MKLGW 351
Cdd:cd12344     2 LWMGDLEPWMDEAYISSCFAKTGEeVVSVKII---RNKQTGKSAGYCFVEFATQEAAEQALEHLNGKPIPNTQqrFRLNW 78

                  ..
gi 995970143  352 GK 353
Cdd:cd12344    79 AS 80

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 995970143  273 TNLYLGNINPQMNEEMLCQEFGRFGPLASVKImwPrTDEERARERNCGFVAFMNRRDAERALKNLNGKMIMSFEMKLGW 351
Cdd:cd12312     1 TSLFVRNVADDTRPDDLRREFGRYGPIVDVYI--P-LDFYTRRPRGFAYIQFEDVRDAEDALYYLDRTRFLGREIEIQF 76

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 995970143  279 NINPQMNEEMLCQEFGRFGPLASVKIMWprtDEERARERNCGFVAFMNRRDAERALKNLNGKMI 342
Cdd:cd12363     8 GLSLYTTERDLREVFSRYGPIEKVQVVY---DQQTGRSRGFGFVYFESVEDAKEAKERLNGQEI 68

RNA recognition motif 1 (RRM1) found in yeast nucleolar protein 3 (Npl3p) and similar proteins; This subfamily corresponds to the RRM1 of Npl3p, also termed mitochondrial targeting suppressor 1 protein, or nuclear polyadenylated RNA-binding protein 1. Npl3p is a major yeast RNA-binding protein that competes with 3'-end processing factors, such as Rna15, for binding to the nascent RNA, protecting the transcript from premature termination and coordinating transcription termination and the packaging of the fully processed transcript for export. It specifically recognizes a class of G/U-rich RNAs. Npl3p is a multi-domain protein containing two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), separated by a short linker and a C-terminal domain rich in glycine, arginine and serine residues.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 995970143  275 LYLGNINPQMNEEMLCQEFGRFGPLASVKIMwprtdeeraRERNCGFVAFMNRRDAERALKNLNGKM 341
Cdd:cd12340     2 LFVRPFPPDTSESAIREIFSPYGPVKEVKML---------SDSNFAFVEFEELEDAIRAKDSVHGRV 59

RNA recognition motif 2 (RRM2) found in Mei2-like proteins and terminal EAR1-like proteins; This subfamily corresponds to the RRM2 of Mei2-like proteins from plant and fungi, terminal EAR1-like proteins from plant, and other eukaryotic homologs. Mei2-like proteins represent an ancient eukaryotic RNA-binding proteins family whose corresponding Mei2-like genes appear to have arisen early in eukaryote evolution, been lost from some lineages such as Saccharomyces cerevisiae and metazoans, and diversified in the plant lineage. The plant Mei2-like genes may function in cell fate specification during development, rather than as stimulators of meiosis. In the fission yeast Schizosaccharomyces pombe, the Mei2 protein is an essential component of the switch from mitotic to meiotic growth. S. pombe Mei2 stimulates meiosis in the nucleus upon binding a specific non-coding RNA. The terminal EAR1-like protein 1 and 2 (TEL1 and TEL2) are mainly found in land plants. They may play a role in the regulation of leaf initiation. All members in this family are putative RNA-binding proteins carrying three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). In addition to the RRMs, the terminal EAR1-like proteins also contain TEL characteristic motifs that allow sequence and putative functional discrimination between them and Mei2-like proteins.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 995970143  275 LYLGNINPQMNEEMLCQEFGRFGPLASVKimwprtdEERARErNCGFVAFMNRRDAERALKNLNGKMIMSFEMKL 349
Cdd:cd12276     4 LLVFNLDAPVSNDELKSLFSKFGEIKEIR-------PTPDKP-SQKFVEFYDVRDAEAALDGLNGRELLGGKLKV 70