cwf21 domain found in Arabidopsis thaliana protein RRC1 and similar proteins; RRC1, also called reduced red-light responses in cry1cry2 background 1, is a SR-like splicing factor required for phytochrome B (phyB) signal transduction and involved in phyB-dependent alternative splicing. This subfamily also includes protein RRC1-like, which may also function as a SR-like splicing factor. SR family splicing factors are characterized by the presence of a domain rich in arginine and serine dipeptides, called the RS domain. This model represents the cwf21 domain of RRC1 and similar proteins. The cwf21 domain is involved in mRNA splicing; it binds directly to the spliceosomal protein Prp8.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 22326718 798 IDVEQRQKLRHIEIALIEYRESLEEQGMKNSEEIERKVAIHRKRLEADG 846
Cdd:cd21371   1 ADEERRQKLRQVEVAVMEYRESLEEQGMKNKEEIERKVAEHRKRLEADA 49

Surp module; This domain is also known as the SWAP domain. SWAP stands for Suppressor-of-White-APricot. It has been suggested that these domains may be RNA binding.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 22326718   335 QIIDTMALNVLDGGCAFEQAIMERGRGNPLFNFLFELGSKEHTYYVWRLYSF 386
Cdd:pfam01805   1 DIIKKTAQFVARNGPEFEALLMEREERNPQFDFLFDPDDPLHAYYRWKLEEY 52

cwf21 domain found in Arabidopsis thaliana protein RRC1 and similar proteins; RRC1, also called reduced red-light responses in cry1cry2 background 1, is a SR-like splicing factor required for phytochrome B (phyB) signal transduction and involved in phyB-dependent alternative splicing. This subfamily also includes protein RRC1-like, which may also function as a SR-like splicing factor. SR family splicing factors are characterized by the presence of a domain rich in arginine and serine dipeptides, called the RS domain. This model represents the cwf21 domain of RRC1 and similar proteins. The cwf21 domain is involved in mRNA splicing; it binds directly to the spliceosomal protein Prp8.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 22326718 798 IDVEQRQKLRHIEIALIEYRESLEEQGMKNSEEIERKVAIHRKRLEADG 846
Cdd:cd21371   1 ADEERRQKLRQVEVAVMEYRESLEEQGMKNKEEIERKVAEHRKRLEADA 49

Surp module; This domain is also known as the SWAP domain. SWAP stands for Suppressor-of-White-APricot. It has been suggested that these domains may be RNA binding.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 22326718   335 QIIDTMALNVLDGGCAFEQAIMERGRGNPLFNFLFELGSKEHTYYVWRLYSF 386
Cdd:pfam01805   1 DIIKKTAQFVARNGPEFEALLMEREERNPQFDFLFDPDDPLHAYYRWKLEEY 52

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 22326718   450 DEFEDMLRALTLERSQIREAMGFALDNAEAAGEVVEVLTEslTLKETSIPTKVARLMLVSDIIHNSsaRVKNASAYRTKF 529
Cdd:pfam04818   1 EALEKKLSSLNNSQESIQTLSKWILFHRKHAKAIVEVWEK--YLKKAKPEKKLHLLYLANDVLQNS--RKKGKSEFADAF 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 22326718   530 EATLPDImesFNDLYHSVHgritaEALRERVLKVLQVWADWFLFSDAYI 578
Cdd:pfam04818  77 EPVLPEA---FASAYKKCD-----EKLKKKLERLLNIWEERNVFSPEVI 117

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 22326718 449 RDEFEDMLRALTLERSQIREAMGFALDNAEAAGEVVEVLTEslTLKETSIPTKVARLMLVSDIIHNSsaRVKNASAYRTK 528
Cdd:cd16981   1 EEALEKKLRSLNNTQQSIQTLSLWCLFHKKHAKQIVKIWLK--ELKKAKPERKLTLLYLANDVLQNS--RRKGAPEFVEA 76

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 22326718 529 FEATLPDIMESFNdlyhsvhgRITAEALRERVLKVLQVWADWFLFSDAYINGLRA 583
Cdd:cd16981  77 FKKVLPEALALVR--------SEGDESVRKKVLRVLNIWEERNVFGSEFLAELRA 123

cwf21 domain; The cwf21 family is involved in mRNA splicing. It has been isolated as a subcomplex of the splicosome in Schizosaccharomyces pombe. The function of the cwf21 domain is to bind directly to the spliceosomal protein Prp8. Mutations in the cwf21 domain prevent Prp8 from binding. The structure of this domain has recently been solved which shows this domain to be composed of two alpha helices.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 22326718   804 QKLRHIEIALIEYRESLEEQGMkNSEEIERKVAIHRKRLEAD 845
Cdd:pfam08312   4 ERKREIEVKVLELRDELEEQGL-SEEEIEEKVDELRKKLLAE 44

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22326718 186 TTNLYVVNLSSKVDENFLLRTFGRFGPIASVKIMwprTEEEKRRERHCGFVAFMNRADGEAAKEKMQG 253
Cdd:COG0724   1 SMKIYVGNLPYSVTEEDLRELFSEYGEVTSVKLI---TDRETGRSRGFGFVEMPDDEEAQAAIEALNG 65

cwf21 domain found in Arabidopsis thaliana protein RRC1 and similar proteins; RRC1, also called reduced red-light responses in cry1cry2 background 1, is a SR-like splicing factor required for phytochrome B (phyB) signal transduction and involved in phyB-dependent alternative splicing. This subfamily also includes protein RRC1-like, which may also function as a SR-like splicing factor. SR family splicing factors are characterized by the presence of a domain rich in arginine and serine dipeptides, called the RS domain. This model represents the cwf21 domain of RRC1 and similar proteins. The cwf21 domain is involved in mRNA splicing; it binds directly to the spliceosomal protein Prp8.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 22326718 798 IDVEQRQKLRHIEIALIEYRESLEEQGMKNSEEIERKVAIHRKRLEADG 846
Cdd:cd21371   1 ADEERRQKLRQVEVAVMEYRESLEEQGMKNKEEIERKVAEHRKRLEADA 49

Surp module; This domain is also known as the SWAP domain. SWAP stands for Suppressor-of-White-APricot. It has been suggested that these domains may be RNA binding.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 22326718   335 QIIDTMALNVLDGGCAFEQAIMERGRGNPLFNFLFELGSKEHTYYVWRLYSF 386
Cdd:pfam01805   1 DIIKKTAQFVARNGPEFEALLMEREERNPQFDFLFDPDDPLHAYYRWKLEEY 52

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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22326718 187 TNLYVVNLSSKVDENFLLRTFGRFGPIASVKImwPRTEeekrrerHCGFVAFMNRADGEAAKEKMQGIIVYEYELKIGWG 266
Cdd:cd12346   2 TTVFVGGLDPNVTEEDLRVLFGPFGEIVYVKI--PPGK-------GCGFVQFVNRASAEAAIQKLQGTPIGGSRIRLSWG 72

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 22326718 189 LYVVNLSSKVDENFLLRTFGRFGPIASVKIMWPRTEEEKRrerhCGFVAFMNRADGEAAKEKMQGIIVYEYELKI 263
Cdd:cd00590   1 LFVGNLPPDTTEEDLRELFSKFGEVVSVRIVRDRDGKSKG----FAFVEFESPEDAEKALEALNGTELGGRPLKV 71

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22326718    188 NLYVVNLSSKVDENFLLRTFGRFGPIASVKIMWPRTEEEKRRerhCGFVAFMNRADGEAAKEKMQGIIVYEYELKI 263
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRDKETGKSKG---FAFVEFESEEDAEKALEALNGKELDGRPLKV 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 22326718   189 LYVVNLSSKVDENFLLRTFGRFGPIASVKIMwprtEEEKRRERHCGFVAFMNRADGEAAKEKMQGIIVYEYELK 262
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLV----RDETGRSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22326718 183 DPQTTN--LYVVNLSSKVDENFLLRTFGRFGPIASVKIMWPRTEEEKRRerhcGFVAFMNRADGEAAKEKMQGIIVYEYE 260
Cdd:cd12555   2 DDQRANrtLFLGNLDITVTENDLRRAFDRFGVITEVDIKRPGRGQTSTY----GFLKFENLDMAHRAKLAMSGKVIGRNP 77

                ....*....
gi 22326718 261 LKIGWGKVV 269
Cdd:cd12555  78 IKIGYGKAT 86

RNA recognition motif 2 (RRM2) found in the Spen (split end) protein family; This subfamily corresponds to the RRM2 domain in the Spen (split end) protein family which includes RNA binding motif protein 15 (RBM15), putative RNA binding motif protein 15B (RBM15B), and similar proteins found in Metazoa. RBM15, also termed one-twenty two protein 1 (OTT1), conserved in eukaryotes, is 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 possess mRNA export activity and can facilitate the access of DEAD-box protein DBP5 to mRNA at the nuclear pore complex (NPC). RNA-binding protein 15B (RBM15B), also termed one twenty-two 3 (OTT3), is a paralog of RBM15 and therefore has post-transcriptional regulatory activity. It is a nuclear protein sharing with RBM15 the association with the splicing factor compartment and the nuclear envelope as well as the binding to mRNA export factors NXF1 and Aly/REF. Members in this family belong to the Spen (split end) protein family, which share a domain architecture comprising of 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22326718 186 TTNLYVVNLSSKVDENFLLRTFGRFGPIASVKIMWPRTEEEKRRerhcGFVAFMNRADGEAAKEKMQGIIVYEYELKIGW 265
Cdd:cd12309   2 TRTLFVGNLEITITEEELRRAFERYGVVEDVDIKRPPRGQGNAY----AFVKFLNLDMAHRAKVAMSGQYIGRNQIKIGY 77

                ..
gi 22326718 266 GK 267
Cdd:cd12309  78 GK 79

cwf21 domain found in fungal complexed with CEF1 protein 21 (CWC21) and similar proteins; This subfamily includes 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. Both CWC21 and CWF21 are pre-mRNA-splicing factors that may function at or prior to the first catalytic step of splicing at the catalytic center of the spliceosome, together with ISY1. SRRM2 is required for pre-mRNA splicing as a component of the spliceosome. SRRM3 may play a role in regulating breast cancer cell invasiveness. It may be involved in RYBP-mediated breast cancer progression. Members of this family contain a cwf21 domain at the N-terminus. The cwf21 domain is involved in mRNA splicing; it binds directly to the spliceosomal protein Prp8.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 22326718 799 DVEQRQKLRHIEIALIEYRESLEEQGMkNSEEIERKVAIHRKRLEAD 845
Cdd:cd21372   3 EILEHERKRQIELKCLELRDELEDEGL-SEEEIEEKVDELREKLLKE 48

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 22326718 188 NLYVVNLSSKVDENFLLRTFGRFGPIASVKIMWPRTEEEKRRErhcGFVAFMNRADGEAAKEKMQGIIVYEYELKIGW 265
Cdd:cd12619   3 NIFVGDLSPEVTDAALFNAFSDFPSCSDARVMWDQKTGRSRGY---GFVSFRSQQDAQNAINSMNGKWLGSRPIRCNW 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22326718   183 DPQTTNLYVVNLSSKVDENFLLRTFGRFGPIASVKIMwprtEEEKRRERHCGFVAFMNRADGEAAKEKMQGI 254
Cdd:TIGR01628 175 LKKFTNLYVKNLDPSVNEDKLRELFAKFGEITSAAVM----KDGSGRSRGFAFVNFEKHEDAAKAVEEMNGK 242

RNA recognition motif 1 (RRM1) found in yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1 and similar proteins; This subgroup corresponds to the RRM1 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 22326718 189 LYVVNLSSKVDENFLLRTFGRFGPIASVKIMwprtEEEKRRERHCGFVAFMNRADGEAAKEKMQGIIVYEYELKIGW 265
Cdd:cd12614   1 LYVGNLDPRVTEDLLQEIFAVTGPVENCKII----PDKNSKGVNYGFVEYYDRRSAEIAIQTLNGRQIFGQEIKVNW 73

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22326718 188 NLYVVNLSSKVDENFLLRTFGRFGPIASVKIMwprtEEEKRRERHCGFVAFMNRADGEAAKEKMQGIIV 256
Cdd:cd12381   3 NLYVKNLDDTIDDEKLREEFSPFGTITSAKVM----TDEGGRSKGFGFVCFSSPEEATKAVTEMNGRII 67

RNA recognition motif (RRM) found in SR-related and CTD-associated factor 4 (SCAF4), SR-related and CTD-associated factor 8 (SCAF8) and similar proteins; This subfamily corresponds to the RRM in a new class of SCAFs (SR-like CTD-associated factors), including SCAF4, SCAF8 and similar proteins. The biological role of SCAF4 remains unclear, but it shows high sequence similarity to SCAF8 (also termed CDC5L complex-associated protein 7, or RNA-binding motif protein 16, or CTD-binding SR-like protein RA8). SCAF8 is a nuclear matrix protein that interacts specifically with a highly serine-phosphorylated form of the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II (pol II). The pol II CTD plays a role in coupling transcription and pre-mRNA processing. In addition, SCAF8 co-localizes primarily with transcription sites that are enriched in nuclear matrix fraction, which is known to contain proteins involved in pre-mRNA processing. Thus, SCAF8 may play a direct role in coupling with both, transcription and pre-mRNA processing, processes. SCAF8 and SCAF4 both contain a conserved N-terminal CTD-interacting domain (CID), an atypical RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNPs (ribonucleoprotein domain), and serine/arginine-rich motifs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22326718 186 TTNLYVVNLSSKVDENFLLRTFGRFGPIASVKIMWPRTeeekrrerhCGFVAFMNRADGEAAKEKMQGIIVYEYELKIGW 265
Cdd:cd12227   2 STTLWVGHLSKKVTQEELKNLFEEYGEIQSIDMIPPRG---------CAYVCMKTRQDAHRALQKLKNHKLRGKSIKIAW 72

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22326718 188 NLYVVNLSSKVDENFLLRTFGRFGPIASVKIMWPRTEEEKRRERHCGFVAFMNRADGEAAKEKMQGIIVYEYELKIGW 265
Cdd:cd12355   1 RLWIGNLDPRLTEYHLLKLLSKYGKIKKFDFLFHKTGPLKGQPRGYCFVTFETKEEAEKAIECLNGKLALGKKLVVRW 78

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22326718 186 TTNLYVVNLSSKVDENFLLRTFGRFGPIASVKIMwprTEEEKRRERHCGFVAFMNRADGEAAKEKMQG 253
Cdd:COG0724   1 SMKIYVGNLPYSVTEEDLRELFSEYGEVTSVKLI---TDRETGRSRGFGFVEMPDDEEAQAAIEALNG 65

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 22326718 187 TNLYVVNLSSKVDENFLLRTFGRFGPIASVKIMwprteeekrRERHCGFVAFMNRADGEAAKEKMQGIIVYEYELKIGWG 266
Cdd:cd12354   1 TTVYVGNITKGLTEALLQQTFSPFGQILEVRVF---------PDKGYAFIRFDSHEAATHAIVSVNGTIINGQAVKCSWG 71

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 22326718   134 KREQEIRERRNQDRENSRDHNsdntsssrfdelpdyfdpsgrlgslddgdpQTTNLYVVNLSSKVDENFLLRTFGRFGPI 213
Cdd:TIGR01628 263 EREAELRRKFEELQQERKMKA------------------------------QGVNLYVKNLDDTVTDEKLRELFSECGEI 312

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 22326718   214 ASVKIMwprtEEEKRRERHCGFVAFMNRADGEAAKEKMQGIIV 256
Cdd:TIGR01628 313 TSAKVM----LDEKGVSRGFGFVCFSNPEEANRAVTEMHGRML 351

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 22326718 798 IDVEQRQKLRHIEIALIEYRESLEEQG--MKNSEEIERKVAIHRKRL 842
Cdd:cd21370   1 IDEERRAKLREIELKVMKYQDELESGKrsRKPGESISEQVEQYRKKL 47

RNA recognition motif 2 (RRM2) found in Drosophila sex-lethal (SXL) and similar proteins; This subfamily corresponds to the RRM2 of the sex-lethal protein (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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22326718 187 TNLYVVNLSSKVDENFLLRTFGRFGPIASVKIMwprTEEEKRRERHCGFVAFMNRADGEAAKEKMQGII 255
Cdd:cd12651   3 TNLYVTNLPRTITEDELDTIFGAYGNIVQKNLL---RDKLTGRPRGVAFVRYDKREEAQAAISALNGTI 68

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 22326718   171 DPSGRLGSlddgdpqTTNLYVVNLSSKVDENFLLRTFGRFGPIASVKIMwprtEEEKRRERHCGFVAFMNRADGEAAKEK 250
Cdd:TIGR01628  80 DPSLRRSG-------VGNIFVKNLDKSVDNKALFDTFSKFGNILSCKVA----TDENGKSRGYGFVHFEKEESAKAAIQK 148

                          90
                  ....*....|....
gi 22326718   251 MQGIIVYEYELKIG 264
Cdd:TIGR01628 149 VNGMLLNDKEVYVG 162

RNA recognition motif 2 (RRM2) found found in type I polyadenylate-binding proteins; This subfamily corresponds to the RRM2 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 mammalian, such as ovary and testis. It may play an important role in germ cell development. 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22326718 188 NLYVVNLSSKVDENFLLRTFGRFGPIASVKIMwprtEEEKRRERHCGFVAFMNRADGEAAKEKMQGIIVYeyelkigwGK 267
Cdd:cd12379   4 NIFIKNLDKSIDNKALYDTFSAFGNILSCKVA----TDENGGSKGYGFVHFETEEAAERAIEKVNGMLLN--------GK 71

                ...
gi 22326718 268 VVF 270
Cdd:cd12379  72 KVF 74

cwf21 domain found in serine/arginine repetitive matrix proteins, SRRM2, SRRM3 and similar proteins; This subfamily includes SRRM2 and SRRM3, both of which contain a cwf21 domain at the N-terminus. SRRM2, also called 300 kDa nuclear matrix antigen, serine/arginine-rich splicing factor-related nuclear matrix protein of 300 kDa, SR-related nuclear matrix protein of 300 kDa, Ser/Arg-related nuclear matrix protein of 300 kDa, splicing coactivator subunit SRm300, or Tax-responsive enhancer element-binding protein 803 (TaxREB803), is required for pre-mRNA splicing as component of the spliceosome. SRRM3 may play a role in regulating breast cancer cell invasiveness. It may be involved in RYBP-mediated breast cancer progression. The cwf21 domain is involved in mRNA splicing; it binds directly to the spliceosomal protein Prp8.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 22326718 807 RHIEIALIEYRESLEEQGMkNSEEIERKVAIHRKRL 842
Cdd:cd21373  12 RKIEVKCLELEDLLEEQGY-TEEEIQAKVDEYRALL 46

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 22326718 183 DPqtTNLYVVNLSSKVDEN--FLLRTFGRFGPIASVKI-MWPRTEEEKRRerhcGFVAFMNRADGEAAKEKMQGIIVYEY 259
Cdd:cd21622   2 DP--CNLFVKNLDDTVITNkeDLEQLFSPFGQIVSSYLaTYPGTGISKGF----GFVAFSKPEDAAKAKETLNGVMVGRK 75

                ....*.
gi 22326718 260 ELKIGW 265
Cdd:cd21622  76 RIFVSY 81

RNA recognition motif 2 (RRM2) found in Nicotiana sylvestris chloroplastic 33 kDa ribonucleoprotein (NsCP33) and similar proteins; The family includes NsCP33, Arabidopsis thaliana chloroplastic 31 kDa ribonucleoprotein (CP31A) and mitochondrial glycine-rich RNA-binding protein 2 (AtGR-RBP2). NsCP33 may be involved in splicing and/or processing of chloroplast RNA's. AtCP31A, also called RNA-binding protein 1/2/3 (AtRBP33), or RNA-binding protein CP31A, or RNA-binding protein RNP-T, or RNA-binding protein cp31, is required for specific RNA editing events in chloroplasts and stabilizes specific chloroplast mRNAs, as well as for normal chloroplast development under cold stress conditions by stabilizing transcripts of numerous mRNAs under these conditions. CP31A may modulate telomere replication through RNA binding domains. AtGR-RBP2, also called AtRBG2, or glycine-rich protein 2 (AtGRP2), or mitochondrial RNA-binding protein 1a (At-mRBP1a), plays a role in RNA transcription or processing during stress. It binds RNAs and DNAs sequence with a preference to single-stranded nucleic acids. AtGR-RBP2 displays strong affinity to poly(U) sequence. It exerts cold and freezing tolerance, probably by exhibiting an RNA chaperone activity during the cold and freezing adaptation process. Some members in this family contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the second RRM motif.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22326718 188 NLYVVNLSSKVDENFLLRTFGRFGPIASVKIMwprTEEEKRRERHCGFVAFMNRADGEAAKEKMQG 253
Cdd:cd21608   1 KLYVGNLSWDTTEDDLRDLFSEFGEVESAKVI---TDRETGRSRGFGFVTFSTAEAAEAAIDALNG 63

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 22326718 189 LYVVNLSSKVDENFLLRTFGRFGPIASVKImwPRTEEEKRRErhCGFVAFMNRADGEAAKEKMQG 253
Cdd:cd12414   2 LIVRNLPFKCTEDDLKKLFSKFGKVLEVTI--PKKPDGKLRG--FAFVQFTNVADAAKAIKGMNG 62

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22326718 188 NLYVVNLSSKVDENFLLRTFGRFGPIASVKIMWPRTEEEKRRErhcGFVAFMNRADGEAAKEKMQGIIVYEYELKI 263
Cdd:cd12375   1 NLIVNYLPQSMTQEELRSLFGAIGPIESCKLVRDKITGQSLGY---GFVNYRDPNDARKAINTLNGLDLENKRLKV 73

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.