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 308153271 207 TTNLYLGNINPQMNEEMLCQEFGRYGPLASVKIMWPRTDEERARERNCGFVAFMTRRDAERALKHLNGKMIMNFEMKLGW 286
Cdd:cd12223    1 TTNLYVGNLPPSVTEEVLLREFGRFGPLASVKIMWPRTEEERRRNRNCGFVAFMSRADAERAMRELNGKDVMGYELKLGW 80

                 ....
gi 308153271 287 GKGV 290
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 308153271 775 TSEEKRAKLREIELKVMKFQDELESGKRPKKSGQSIQEQVELYRDKLLQ 823
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 308153271 207 TTNLYLGNINPQMNEEMLCQEFGRYGPLASVKIMWPRTDEERARERNCGFVAFMTRRDAERALKHLNGKMIMNFEMKLGW 286
Cdd:cd12223    1 TTNLYVGNLPPSVTEEVLLREFGRFGPLASVKIMWPRTEEERRRNRNCGFVAFMSRADAERAMRELNGKDVMGYELKLGW 80

                 ....
gi 308153271 287 GKGV 290
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 308153271 775 TSEEKRAKLREIELKVMKFQDELESGKRPKKSGQSIQEQVELYRDKLLQ 823
Cdd:cd21370    1 IDEERRAKLREIELKVMKYQDELESGKRSRKPGESISEQVEQYRKKLLK 49

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 308153271   209 NLYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprTDEERARERNCGFVAFMTRRDAERALKHLNGKMIMNFEMKL 284
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 308153271  210 LYLGNINPQMNEEMLCQEFGRYGPLASVKIMWPRTDeeraRERNCGFVAFMTRRDAERALKHLNGKMIMNFEMK 283
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRDETG----RSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

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 308153271 474 RDKLEELLRGLTPRKSDIAGGMFFCLTHADAAEEIVECIAESLsiLKTPLPKKIARLYLVSDVLYNSSAKvtNASYYRKF 553
Cdd:cd16981    1 EEALEKKLRSLNNTQQSIQTLSLWCLFHKKHAKQIVKIWLKEL--KKAKPERKLTLLYLANDVLQNSRRK--GAPEFVEA 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 308153271 554 FETKLCQIFSDLNATyktiqghlQSENFKQRVMSCFRAWEEWAVYPDPFLIKLQNI 609
Cdd:cd16981   77 FKKVLPEALALVRSE--------GDESVRKKVLRVLNIWEERNVFGSEFLAELRAI 124

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 308153271  209 NLYLGNINPQMNEEMLCQEFGRYGPLASVKIMWprtdEERARERNCGFVAFMTRRDAERALKHLNGKMI 277
Cdd:TIGR01628 287 NLYVKNLDDTVTDEKLRELFSECGEITSAKVML----DEKGVSRGFGFVCFSNPEEANRAVTEMHGRML 351

glycine-rich RNA-binding protein 4; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 308153271 207 TTNLYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprTDEERARERNCGFVAFMTRRDAERALKHLNGK 275
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 308153271 207 TTNLYLGNINPQMNEEMLCQEFGRYGPLASVKIMWPRTDEERARERNCGFVAFMTRRDAERALKHLNGKMIMNFEMKLGW 286
Cdd:cd12223    1 TTNLYVGNLPPSVTEEVLLREFGRFGPLASVKIMWPRTEEERRRNRNCGFVAFMSRADAERAMRELNGKDVMGYELKLGW 80

                 ....
gi 308153271 287 GKGV 290
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 308153271 775 TSEEKRAKLREIELKVMKFQDELESGKRPKKSGQSIQEQVELYRDKLLQ 823
Cdd:cd21370    1 IDEERRAKLREIELKVMKYQDELESGKRSRKPGESISEQVEQYRKKLLK 49

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 308153271   209 NLYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprTDEERARERNCGFVAFMTRRDAERALKHLNGKMIMNFEMKL 284
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLV---RDKETGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

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 308153271 210 LYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprtDEERARERNCGFVAFMTRRDAERALKHLNGKMIMNFEMKLGW 286
Cdd:cd12614    1 LYVGNLDPRVTEDLLQEIFAVTGPVENCKII----PDKNSKGVNYGFVEYYDRRSAEIAIQTLNGRQIFGQEIKVNW 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 308153271  210 LYLGNINPQMNEEMLCQEFGRYGPLASVKIMWPRTDeeraRERNCGFVAFMTRRDAERALKHLNGKMIMNFEMK 283
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRDETG----RSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

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 308153271 209 NLYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprTDEErARERNCGFVAFMTRRDAERALKHLNGKMI 277
Cdd:cd12381    3 NLYVKNLDDTIDDEKLREEFSPFGTITSAKVM---TDEG-GRSKGFGFVCFSSPEEATKAVTEMNGRII 67

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 308153271 207 TTNLYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprTDEERARERNCGFVAFMTRRDAERALKHLNGKMIM 278
Cdd:COG0724    1 SMKIYVGNLPYSVTEEDLRELFSEYGEVTSVKLI---TDRETGRSRGFGFVEMPDDEEAQAAIEALNGAELM 69

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 308153271 208 TNLYLGNINPQMNEEMLCQEFGRYGPLASVKImwprtdeerARERNCGFVAFMTRRDAERALKHLNGKMIMNFEM-KLGW 286
Cdd:cd12224    2 TTLYVGGLGDKITEKDLRDHFYQFGEIRSITV---------VARQQCAFVQFTTRQAAERAAERTFNKLIIKGRRlKVKW 72

                 ..
gi 308153271 287 GK 288
Cdd:cd12224   73 GR 74

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 308153271 209 NLYLGNINPQMNEEMLCQEFGRYGPLASVKIMWPRTDEERARERNCGFVAFMTRRDAERALKHLNGKMIMN 279
Cdd:cd12355    1 RLWIGNLDPRLTEYHLLKLLSKYGKIKKFDFLFHKTGPLKGQPRGYCFVTFETKEEAEKAIECLNGKLALG 71

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 308153271  475 DKLEELLRGLTPRKSDIAGGMFFCLTHADAAEEIVECIAESLsiLKTPLPKKIARLYLVSDVLYNSSAKvtNASYYRKFF 554
Cdd:pfam04818   1 EALEKKLSSLNNSQESIQTLSKWILFHRKHAKAIVEVWEKYL--KKAKPEKKLHLLYLANDVLQNSRKK--GKSEFADAF 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 308153271  555 ETKLCQIFSDLNATYktiqghlqSENFKQRVMSCFRAWEEWAVYPDPFL 603
Cdd:pfam04818  77 EPVLPEAFASAYKKC--------DEKLKKKLERLLNIWEERNVFSPEVI 117

RNA recognition motif 3 (RRM3) found found in type I polyadenylate-binding proteins; This subfamily corresponds to the RRM3 of type I poly(A)-binding proteins (PABPs), highly conserved proteins that bind to the poly(A) tail present at the 3' ends of most eukaryotic mRNAs. They have been implicated in the regulation of poly(A) tail length during the polyadenylation reaction, translation initiation, mRNA stabilization by influencing the rate of deadenylation and inhibition of mRNA decapping. The family represents type I polyadenylate-binding proteins (PABPs), including polyadenylate-binding protein 1 (PABP-1 or PABPC1), polyadenylate-binding protein 3 (PABP-3 or PABPC3), polyadenylate-binding protein 4 (PABP-4 or APP-1 or iPABP), polyadenylate-binding protein 5 (PABP-5 or PABPC5), polyadenylate-binding protein 1-like (PABP-1-like or PABPC1L), polyadenylate-binding protein 1-like 2 (PABPC1L2 or RBM32), polyadenylate-binding protein 4-like (PABP-4-like or PABPC4L), yeast polyadenylate-binding protein, cytoplasmic and nuclear (PABP or ACBP-67), and similar proteins. PABP-1 is an ubiquitously expressed multifunctional protein that may play a role in 3' end formation of mRNA, translation initiation, mRNA stabilization, protection of poly(A) from nuclease activity, mRNA deadenylation, inhibition of mRNA decapping, and mRNP maturation. Although PABP-1 is thought to be a cytoplasmic protein, it is also found in the nucleus. PABP-1 may be involved in nucleocytoplasmic trafficking and utilization of mRNP particles. PABP-1 contains four copies of RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), a less well conserved linker region, and a proline-rich C-terminal conserved domain (CTD). PABP-3 is a testis-specific poly(A)-binding protein specifically expressed in round spermatids. It is mainly found in mammalian and may play an important role in the testis-specific regulation of mRNA homeostasis. PABP-3 shows significant sequence similarity to PABP-1. However, it binds to poly(A) with a lower affinity than PABP-1. PABP-1 possesses an A-rich sequence in its 5'-UTR and allows binding of PABP and blockage of translation of its own mRNA. In contrast, PABP-3 lacks the A-rich sequence in its 5'-UTR. PABP-4 is an inducible poly(A)-binding protein (iPABP) that is primarily localized to the cytoplasm. It shows significant sequence similarity to PABP-1 as well. The RNA binding properties of PABP-1 and PABP-4 appear to be identical. PABP-5 is encoded by PABPC5 gene within the X-specific subinterval, and expressed in fetal brain and in a range of adult tissues in mammalian, such as ovary and testis. It may play an important role in germ cell development. Moreover, unlike other PABPs, PABP-5 contains only four RRMs, but lacks both the linker region and the CTD. PABP-1-like and PABP-1-like 2 are the orthologs of PABP-1. PABP-4-like is the ortholog of PABP-5. Their cellular functions remain unclear. The family also includes the yeast PABP, a conserved poly(A) binding protein containing poly(A) tails that can be attached to the 3'-ends of mRNAs. The yeast PABP and its homologs may play important roles in the initiation of translation and in mRNA decay. Like vertebrate PABP-1, the yeast PABP contains four RRMs, a linker region, and a proline-rich CTD as well. The first two RRMs are mainly responsible for specific binding to poly(A). The proline-rich region may be involved in protein-protein interactions.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 308153271 208 TNLYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprTDEErARERNCGFVAFMTRRDAERALKHLNGK 275
Cdd:cd12380    2 TNVYVKNFGEDVDDDELKELFEKYGKITSAKVM---KDDS-GKSKGFGFVNFENHEAAQKAVEELNGK 65

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308153271 210 LYLGNINPQMNEEMLCQEFGRYGP-LASVKIMwprTDEERARERNCGFVAFMTRRDAERALKHLNGKMIMNFE--MKLGW 286
Cdd:cd12344    2 LWMGDLEPWMDEAYISSCFAKTGEeVVSVKII---RNKQTGKSAGYCFVEFATQEAAEQALEHLNGKPIPNTQqrFRLNW 78

                 ...
gi 308153271 287 GKG 289
Cdd:cd12344   79 ASF 81

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 308153271 214 NINPQMNEEMLCQEFGRYGPLASVKIMwprTDEERARERNCGFVAFMTRRDAERALKHLNGKMIMNFEMKLGW 286
Cdd:cd12408    6 NLSEDATEEDLRELFRPFGPISRVYLA---KDKETGQSKGFAFVTFETREDAERAIEKLNGFGYDNLILSVEW 75

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 308153271 210 LYLGNINPQMNEEMLCQEFGRYGPLASVKImwPRTDEERA-RERNCGFVAFMTRRDAERALKHLNG 274
Cdd:cd21619    4 IYVGNIDMTINEDALEKIFSRYGQVESVRR--PPIHTDKAdRTTGFGFIKYTDAESAERAMQQADG 67

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 308153271 210 LYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprTDEERARERNCGFVAFMTRRDAERALKHLNGKMIMNFEMKLG 285
Cdd:cd12284    1 LYVGSLHFNITEDMLRGIFEPFGKIEFVQLQ---KDPETGRSKGYGFIQFRDAEDAKKALEQLNGFELAGRPMKVG 73

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 308153271  204 DPTTTNLYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprtDEERARERNCGFVAFMTRRDAERALKHLNGKMI 277
Cdd:TIGR01628 175 LKKFTNLYVKNLDPSVNEDKLRELFAKFGEITSAAVM----KDGSGRSRGFAFVNFEKHEDAAKAVEEMNGKKI 244

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308153271 208 TNLYLGNINPQMNEEMLCQEFGRYGPLASVKImwPrTDEERARERNCGFVAFMTRRDAERALKHLNGKMIMNFEMKLGWG 287
Cdd:cd12312    1 TSLFVRNVADDTRPDDLRREFGRYGPIVDVYI--P-LDFYTRRPRGFAYIQFEDVRDAEDALYYLDRTRFLGREIEIQFA 77

                 ..
gi 308153271 288 KG 289
Cdd:cd12312   78 QG 79

RNA recognition motif 1 (RRM1) and 2 (RRM2) found in CELF/Bruno-like family of RNA binding proteins and plant flowering time control protein FCA; This subfamily corresponds to the RRM1 and RRM2 domains of the CUGBP1 and ETR-3-like factors (CELF) as well as plant flowering time control protein FCA. CELF, also termed BRUNOL (Bruno-like) proteins, is a family of structurally related RNA-binding proteins involved in regulation of pre-mRNA splicing in the nucleus, and control of mRNA translation and deadenylation in the cytoplasm. The family contains six members: CELF-1 (also known as BRUNOL-2, CUG-BP1, NAPOR, EDEN-BP), CELF-2 (also known as BRUNOL-3, ETR-3, CUG-BP2, NAPOR-2), CELF-3 (also known as BRUNOL-1, TNRC4, ETR-1, CAGH4, ER DA4), CELF-4 (BRUNOL-4), CELF-5 (BRUNOL-5) and CELF-6 (BRUNOL-6). They all contain three highly conserved RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C-terminus of the protein. The low sequence conservation of the linker region is highly suggestive of a large variety in the co-factors that associate with the various CELF family members. Based on both, sequence similarity and function, the CELF family can be divided into two subfamilies, the first containing CELFs 1 and 2, and the second containing CELFs 3, 4, 5, and 6. The different CELF proteins may act through different sites on at least some substrates. Furthermore, CELF proteins may interact with each other in varying combinations to influence alternative splicing in different contexts. This subfamily also includes plant flowering time control protein FCA that functions in the posttranscriptional regulation of transcripts involved in the flowering process. FCA contains two RRMs, and a WW protein interaction domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 308153271 210 LYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprTDEERARERNCGFVAFMTRRDAERALKHLNGKMIM 278
Cdd:cd12361    2 LFVGMIPKTASEEDVRPLFEQFGNIEEVQIL---RDKQTGQSKGCAFVTFSTREEALRAIEALHNKKTM 67

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor 3 (SRSF3) and similar proteins; This subfamily corresponds to the RRM of two serine/arginine (SR) proteins, serine/arginine-rich splicing factor 3 (SRSF3) and serine/arginine-rich splicing factor 7 (SRSF7). SRSF3, also termed pre-mRNA-splicing factor SRp20, modulates alternative splicing by interacting with RNA cis-elements in a concentration- and cell differentiation-dependent manner. It is also involved in termination of transcription, alternative RNA polyadenylation, RNA export, and protein translation. SRSF3 is critical for cell proliferation, and tumor induction and maintenance. It can shuttle between the nucleus and cytoplasm. SRSF7, also termed splicing factor 9G8, plays a crucial role in both constitutive splicing and alternative splicing of many pre-mRNAs. Its localization and functions are tightly regulated by phosphorylation. SRSF7 is predominantly present in the nuclear and can shuttle between nucleus and cytoplasm. It cooperates with the export protein, Tap/NXF1, helps mRNA export to the cytoplasm, and enhances the expression of unspliced mRNA. Moreover, SRSF7 inhibits tau E10 inclusion through directly interacting with the proximal downstream intron of E10, a clustering region for frontotemporal dementia with Parkinsonism (FTDP) mutations. Both SRSF3 and SRSF7 contain a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal RS domain rich in serine-arginine dipeptides. The RRM domain is involved in RNA binding, and the RS domain has been implicated in protein shuttling and protein-protein interactions.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 308153271 210 LYLGNINPQMNEEMLCQEFGRYGPLASVKImwprtdeerarERN---CGFVAFMTRRDAERALKHLNGKMIMN 279
Cdd:cd12373    2 VYVGNLGPRVTKRELEDAFEKYGPLRNVWV-----------ARNppgFAFVEFEDPRDAEDAVRALDGRRICG 63

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 308153271 207 TTNLYLGNINPQMNEEMLCQEFGRYGPLASVKIMWPRtdeerarerNCGFVAFMTRRDAERALKHLNGKMIMNFEMKLGW 286
Cdd:cd12227    2 STTLWVGHLSKKVTQEELKNLFEEYGEIQSIDMIPPR---------GCAYVCMKTRQDAHRALQKLKNHKLRGKSIKIAW 72

                 ....*
gi 308153271 287 --GKG 289
Cdd:cd12227   73 apNKG 77

RNA recognition motif 2 (RRM2) found in the Hu proteins family, Drosophila sex-lethal (SXL), and similar proteins; This subfamily corresponds to the RRM2 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 the ubiquitously expressed Hu family member. It has a variety of biological functions mostly related to the regulation of cellular response to DNA damage and other types of stress. Hu proteins perform their cytoplasmic and nuclear molecular functions by coordinately regulating functionally related mRNAs. In the cytoplasm, Hu proteins recognize and bind to AU-rich RNA elements (AREs) in the 3' untranslated regions (UTRs) of certain target mRNAs, such as GAP-43, vascular epithelial growth factor (VEGF), the glucose transporter GLUT1, eotaxin and c-fos, and stabilize those ARE-containing mRNAs. They also bind and regulate the translation of some target mRNAs, such as neurofilament M, GLUT1, and p27. In the nucleus, Hu proteins function as regulators of polyadenylation and alternative splicing. Each Hu protein contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 may cooperate in binding to an ARE. RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions. Also included in this subfamily is 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 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 RRMs that show high preference to bind single-stranded, uridine-rich target RNA transcripts.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 308153271 208 TNLYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprTDEERARERNCGFVAFMTRRDAERALKHLNG 274
Cdd:cd12376    1 ANLYVSGLPKTMTQKELEQLFSQYGRIITSRIL---RDQLTGVSRGVGFIRFDKRIEAEEAIKGLNG 64

RNA recognition motif (RRM) found in U1 small nuclear ribonucleoprotein 70 kDa (U1-70K) and similar proteins; This subfamily corresponds to the RRM of U1-70K, also termed snRNP70, a key component of the U1 snRNP complex, which is one of the key factors facilitating the splicing of pre-mRNA via interaction at the 5' splice site, and is involved in regulation of polyadenylation of some viral and cellular genes, enhancing or inhibiting efficient poly(A) site usage. U1-70K plays an essential role in targeting the U1 snRNP to the 5' splice site through protein-protein interactions with regulatory RNA-binding splicing factors, such as the RS protein ASF/SF2. Moreover, U1-70K protein can specifically bind to stem-loop I of the U1 small nuclear RNA (U1 snRNA) contained in the U1 snRNP complex. It also mediates the binding of U1C, another U1-specific protein, to the U1 snRNP complex. U1-70K contains a conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by an adjacent glycine-rich region at the N-terminal half, and two serine/arginine-rich (SR) domains at the C-terminal half. The RRM is responsible for the binding of stem-loop I of U1 snRNA molecule. Additionally, the most prominent immunodominant region that can be recognized by auto-antibodies from autoimmune patients may be located within the RRM. The SR domains are involved in protein-protein interaction with SR proteins that mediate 5' splice site recognition. For instance, the first SR domain is necessary and sufficient for ASF/SF2 Binding. The family also includes Drosophila U1-70K that is an essential splicing factor required for viability in flies, but its SR domain is dispensable. The yeast U1-70k doesn't contain easily recognizable SR domains and shows low sequence similarity in the RRM region with other U1-70k proteins and therefore not included in this family. The RRM domain is dispensable for yeast U1-70K function.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 308153271 210 LYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprTDEERARERNCGFVAFMTRRDAERALKHLNGKMI 277
Cdd:cd12236    4 LFVARLSYDTTESKLRREFEKYGPIKRVRLV---RDKKTGKSRGYAFIEFEHERDMKAAYKHADGKKI 68

RNA recognition motif 1 (RRM1) found in yeast protein gar2 and similar proteins; This subfamily corresponds to the RRM1 of yeast protein gar2, a novel nucleolar protein required for 18S rRNA and 40S ribosomal subunit accumulation. It shares similar domain architecture with nucleolin from vertebrates and NSR1 from Saccharomyces cerevisiae. The highly phosphorylated N-terminal domain of gar2 is made up of highly acidic regions separated from each other by basic sequences, and contains multiple phosphorylation sites. The central domain of gar2 contains two closely adjacent N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The C-terminal RGG (or GAR) domain of gar2 is rich in glycine, arginine and phenylalanine residues.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 308153271 209 NLYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprTDEERARERNCGFVAFMTRRDAERALKHLNGKMI----MNFEM 282
Cdd:cd12447    1 TLFVGGLSWNVDDPWLKKEFEKYGGVISARVI---TDRGSGRSKGYGYVDFATPEAAQKALAAMSGKEIdgrqINVDF 75

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 308153271 210 LYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprTDEERARERNCGFVAFMTRRDAERALKHLNGKMIMNFEMKLGW 286
Cdd:cd12378    2 LYVGDLHPDVTEAMLYEKFSPAGPVLSIRVC---RDAVTRRSLGYAYVNFQQPADAERALDTLNFDVIKGKPIRIMW 75

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 308153271 208 TNLYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprTDEERARERNCGFVAFMTRRDAERALKHLNGKMIMNFEMKL 284
Cdd:cd21601    1 TALFIGDLDKDVTEEMLRDIFSKYKSLVSVKIC---LDSETKKSLGYGYLNFSDKEDAEKAIEEFNYTPIFGKEVRI 74

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 308153271 208 TNLYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprTDEERARERNCGFVAFMTRRDAERALKHLNG 274
Cdd:cd12651    3 TNLYVTNLPRTITEDELDTIFGAYGNIVQKNLL---RDKLTGRPRGVAFVRYDKREEAQAAISALNG 66

RNA recognition motif (RRM) found in vertebrate RNA binding protein fox-1 homologs and similar proteins; This subfamily corresponds to the RRM of several tissue-specific alternative splicing isoforms of vertebrate RNA binding protein Fox-1 homologs, which show high sequence similarity to the Caenorhabditis elegans feminizing locus on X (Fox-1) gene encoding Fox-1 protein. RNA binding protein Fox-1 homolog 1 (RBFOX1), also termed ataxin-2-binding protein 1 (A2BP1), or Fox-1 homolog A, or hexaribonucleotide-binding protein 1 (HRNBP1), is predominantly expressed in neurons, skeletal muscle and heart. It regulates alternative splicing of tissue-specific exons by binding to UGCAUG elements. Moreover, RBFOX1 binds to the C-terminus of ataxin-2 and forms an ataxin-2/A2BP1 complex involved in RNA processing. RNA binding protein fox-1 homolog 2 (RBFOX2), also termed Fox-1 homolog B, or hexaribonucleotide-binding protein 2 (HRNBP2), or RNA-binding motif protein 9 (RBM9), or repressor of tamoxifen transcriptional activity, is expressed in ovary, whole embryo, and human embryonic cell lines in addition to neurons and muscle. RBFOX2 activates splicing of neuron-specific exons through binding to downstream UGCAUG elements. RBFOX2 also functions as a repressor of tamoxifen activation of the estrogen receptor. RNA binding protein Fox-1 homolog 3 (RBFOX3 or NeuN or HRNBP3), also termed Fox-1 homolog C, is a nuclear RNA-binding protein that regulates alternative splicing of the RBFOX2 pre-mRNA, producing a message encoding a dominant negative form of the RBFOX2 protein. Its message is detected exclusively in post-mitotic regions of embryonic brain. Like RBFOX1, both RBFOX2 and RBFOX3 bind to the hexanucleotide UGCAUG elements and modulate brain and muscle-specific splicing of exon EIIIB of fibronectin, exon N1 of c-src, and calcitonin/CGRP. Members in this family also harbor one RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 308153271 210 LYLGNINPQMNEEMLCQEFGRYGPLASVKIMWprtdEERArERNCGFVAFMTRRDAERALKHLNGKMIM 278
Cdd:cd12407    3 LHVSNIPFRFRDPDLRQMFGQFGTILDVEIIF----NERG-SKGFGFVTFANSADADRAREKLNGTVVE 66

RNA recognition motif (RRM) found in Helicobacter pylori HP0827 protein and similar proteins; This subfamily corresponds to the RRM of H. pylori HP0827, a putative ssDNA-binding protein 12rnp2 precursor, containing one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The ssDNA binding may be important in activation of HP0827.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 308153271 210 LYLGNINPQMNEEMLCQEFGRYGPLASVKIMWprtDEERARERNCGFVAFMTRRDAERALKHLNGKMIM 278
Cdd:cd12399    1 LYVGNLPYSASEEQLKSLFGQFGAVFDVKLPM---DRETKRPRGFGFVELQEEESAEKAIAKLDGTDFM 66

RNA recognition motif 3 (RRM3) found in yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1 and similar proteins; This subfamily corresponds to the RRM3 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. 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 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.

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gi 308153271 208 TNLYLGNINPQMNEEMLCQEFGRYGPLASVKIMwprtdeeraRERNCGFVAFMTRRDAERALKHLNGKMIMNFEMKLGWG 287
Cdd:cd12622    1 TTVYVGNLPPEVTQADLIPLFQNFGVIEEVRVQ---------RDKGFGFVKYDTHEEAALAIQQLNGQPFLGRPIKCSWG 71