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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224028248  60 SLTVRNLPQYVSNELLEEAFSVFGQVERAVVIVDDRGRPSGKGIVEFSGKPAARKALDRCSEGSFLLTTFPRPVTVEPMD 139
Cdd:cd12591    1 ALTVKNLPQFVSNELLEEAFSVFGQVERAVVIVDDRGRPTGKGIVEFSGKPAARKALDRCSDGAFLLTAFPRPVTVEPMD 80

RNA recognition motif 2 (RRM2) found in vertebrate 54 kDa nuclear RNA- and DNA-binding protein (p54nrb); This subgroup corresponds to the RRM2 of p54nrb, also termed non-POU domain-containing octamer-binding protein (NonO), or 55 kDa nuclear protein (NMT55), or DNA-binding p52/p100 complex 52 kDa subunit. p54nrb is a multifunctional protein involved in numerous nuclear processes including transcriptional regulation, splicing, DNA unwinding, nuclear retention of hyperedited double-stranded RNA, viral RNA processing, control of cell proliferation, and circadian rhythm maintenance. It is ubiquitously expressed and highly conserved in vertebrates. It binds both, single- and double-stranded RNA and DNA, and also possesses inherent carbonic anhydrase activity. p54nrb forms a heterodimer with paraspeckle component 1 (PSPC1 or PSP1), localizing to paraspeckles in an RNA-dependent manner. It also forms a heterodimer with polypyrimidine tract-binding protein-associated-splicing factor (PSF). p54nrb contains two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), at the N-terminus.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224028248  60 SLTVRNLPQYVSNELLEEAFSVFGQVERAVVIVDDRGRPSGKGIVEFSGKPAARKALDRCSEGSFLLTTFPRPVTVEPMD 139
Cdd:cd12591    1 ALTVKNLPQFVSNELLEEAFSVFGQVERAVVIVDDRGRPTGKGIVEFSGKPAARKALDRCSDGAFLLTAFPRPVTVEPMD 80

RNA recognition motif 1 (RRM1) found in vertebrate 54 kDa nuclear RNA- and DNA-binding protein (p54nrb); This subgroup corresponds to the RRM1 of p54nrb, also termed non-POU domain-containing octamer-binding protein (NonO), or 55 kDa nuclear protein (NMT55), or DNA-binding p52/p100 complex 52 kDa subunit. p54nrb is a multifunctional protein involved in numerous nuclear processes including transcriptional regulation, splicing, DNA unwinding, nuclear retention of hyperedited double-stranded RNA, viral RNA processing, control of cell proliferation, and circadian rhythm maintenance. It is ubiquitously expressed and highly conserved in vertebrates. p54nrb binds both, single- and double-stranded RNA and DNA, and also possesses inherent carbonic anhydrase activity. It forms a heterodimer with paraspeckle component 1 (PSPC1 or PSP1), localizing to paraspeckles in an RNA-dependent manneras well as with polypyrimidine tract-binding protein-associated-splicing factor (PSF). p54nrb contains two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), at the N-terminus.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 224028248   1 MRKLFEKYGKAGEVFIHKDKGFGFIRLETRTLAEIAKVELDNMPLRGKQLRVRF 54
Cdd:cd12588   18 MRKLFEKYGKAGEVFIHKDKGFGFIRLETRTLAEIAKVELDNMPLRGKQLRVRF 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 224028248   18 KDKGFGFIRLETRTLAEIAKVELDNMPLRGKQLRV-RFACHS----------ASLTVRNLPQYVSNELLEEAFSVFGQVE 86
Cdd:TIGR01628 127 KSRGYGFVHFEKEESAKAAIQKVNGMLLNDKEVYVgRFIKKHereaaplkkfTNLYVKNLDPSVNEDKLRELFAKFGEIT 206

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 224028248   87 RAVVIVDDRGRPSGKGIVEFSGKPAARKALDRCSEGSFLLTTFPRPVTVEPMDQLDDEEGLPEKLVIKNQQFHKEREQ 164
Cdd:TIGR01628 207 SAAVMKDGSGRSRGFAFVNFEKHEDAAKAVEEMNGKKIGLAKEGKKLYVGRAQKRAEREAELRRKFEELQQERKMKAQ 284

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 224028248  58 SASLTVRNLPQYVSNELLEEAFSVFGQVERAVVIVD-DRGRPSGKGIVEFSGKPAARKALD 117
Cdd:COG0724    1 SMKIYVGNLPYSVTEEDLRELFSEYGEVTSVKLITDrETGRSRGFGFVEMPDDEEAQAAIE 61

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 224028248   2 RKLFEKYGKAGEVFIHKD------KGFGFIRLETRTLAEIAKVELDNMPLRGKQLRVRFA 55
Cdd:COG0724   19 RELFSEYGEVTSVKLITDretgrsRGFGFVEMPDDEEAQAAIEALNGAELMGRTLKVNEA 78

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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 224028248    1 MRKLFEKYGKAGEVFIHKD-----KGFGFIRLETRTLAEIAKVELDNMPLRGKQLR 51
Cdd:pfam00076  15 LKDLFSKFGPIKSIRLVRDetgrsKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

NOPS domain, including C-terminal coiled-coil region, in 54 kDa nuclear RNA- and DNA-binding protein (p54nrb) and similar proteins; The family contains a DBHS domain (for Drosophila behavior, human splicing), which comprises two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a charged protein-protein interaction NOPS (NONA and PSP1) domain. This model corresponds to the NOPS domain, with a long helical C-terminal extension, found in p54nrb, also termed non-POU domain-containing octamer-binding protein (NONO), or 55 kDa nuclear protein (NMT55), or DNA-binding p52/p100 complex 52 kDa subunit. It is a multi-functional protein involved in numerous nuclear processes including transcriptional regulation, splicing, DNA unwinding, nuclear retention of hyperedited double-stranded RNA, viral RNA processing, control of cell proliferation, and circadian rhythm maintenance. p54nrb is ubiquitously expressed and highly conserved in vertebrates. It binds both single- and double-stranded RNA and DNA, and also possesses inherent carbonic anhydrase activity. p54nrb forms a heterodimer with paraspeckle component 1 (PSPC1 or PSP1), localizing to paraspeckles in an RNA-dependent manner. It also forms a heterodimer with polypyrimidine tract-binding protein-associated-splicing factor (PSF). The NOPS domain specifically binds to the second RNA recognition motif (RRM2) domain of the partner DBHS protein via a substantial interaction surface. Its highly conserved C-terminal residues are critical for functional DBHS dimerization while the highly conserved C-terminal helical extension, forming a right-handed antiparallel heterodimeric coiled-coil, is essential for paraspeckle localization to subnuclear bodies.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224028248 130 PRPVTVEPMDQLDDEEGLPEKLVIKNQQFHKEREQPPRFAQPGSFEYEYAMRWKALIEMEKQQQDQVDRNIKEAREKLEM 209
Cdd:cd12947    1 PRPVTVEPMDQLDDEEGLPEKLVIKNQQYHKEREQPPRFAQPGSFEYEYAMRWKALIEMEKQQQEQVDRNIKEAREKLEM 80

                         90
                 ....*....|....
gi 224028248 210 EMEAARHEHQVMLM 223
Cdd:cd12947   81 EMEAARHEHQVMLM 94

RNA recognition motif 2 (RRM2) found in vertebrate 54 kDa nuclear RNA- and DNA-binding protein (p54nrb); This subgroup corresponds to the RRM2 of p54nrb, also termed non-POU domain-containing octamer-binding protein (NonO), or 55 kDa nuclear protein (NMT55), or DNA-binding p52/p100 complex 52 kDa subunit. p54nrb is a multifunctional protein involved in numerous nuclear processes including transcriptional regulation, splicing, DNA unwinding, nuclear retention of hyperedited double-stranded RNA, viral RNA processing, control of cell proliferation, and circadian rhythm maintenance. It is ubiquitously expressed and highly conserved in vertebrates. It binds both, single- and double-stranded RNA and DNA, and also possesses inherent carbonic anhydrase activity. p54nrb forms a heterodimer with paraspeckle component 1 (PSPC1 or PSP1), localizing to paraspeckles in an RNA-dependent manner. It also forms a heterodimer with polypyrimidine tract-binding protein-associated-splicing factor (PSF). p54nrb contains two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), at the N-terminus.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224028248  60 SLTVRNLPQYVSNELLEEAFSVFGQVERAVVIVDDRGRPSGKGIVEFSGKPAARKALDRCSEGSFLLTTFPRPVTVEPMD 139
Cdd:cd12591    1 ALTVKNLPQFVSNELLEEAFSVFGQVERAVVIVDDRGRPTGKGIVEFSGKPAARKALDRCSDGAFLLTAFPRPVTVEPMD 80

NOPS domain, including C-terminal helical extension region, in the p54nrb/PSF/PSP1 family; All members in this family contain a DBHS domain (for Drosophila behavior, human splicing), which comprises two conserved RNA recognition motifs (RRM1 and RRM2), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a charged protein-protein interaction NOPS (NONA and PSP1) domain with a long helical C-terminal extension. The NOPS domain specifically binds to RRM2 domain of the partner DBHS protein via a substantial interaction surface. Its highly conserved C-terminal residues are critical for functional DBHS dimerization while the highly conserved C-terminal helical extension, forming a right-handed antiparallel heterodimeric coiled-coil, is essential for localization of these proteins to subnuclear bodies. PSF has an additional large N-terminal domain that differentiates it from other family members. The p54nrb/PSF/PSP1 family includes 54 kDa nuclear RNA- and DNA-binding protein (p54nrb), polypyrimidine tract-binding protein (PTB)-associated-splicing factor (PSF) and paraspeckle protein 1 (PSP1), which are ubiquitously expressed and are well conserved in vertebrates. p54nrb, also termed NONO or NMT55, is a multi-functional protein involved in numerous nuclear processes including transcriptional regulation, splicing, DNA unwinding, nuclear retention of hyperedited double-stranded RNA, viral RNA processing, control of cell proliferation, and circadian rhythm maintenance. PSF, also termed POMp100, is also a multi-functional protein that binds RNA, single-stranded DNA (ssDNA), double-stranded DNA (dsDNA) and many factors, and mediates diverse activities in the cell. PSP1, also termed PSPC1, is a novel nucleolar factor that accumulates within a new nucleoplasmic compartment, termed paraspeckles, and diffusely distributes in the nucleoplasm. The cellular function of PSP1 remains unknown currently. The family also includes some p54nrb/PSF/PSP1 homologs from invertebrate species. For instance, the Drosophila melanogaster gene no-ontransient A (nonA) encoding puff-specific protein Bj6 (also termed NONA) and Chironomus tentans hrp65 gene encoding protein Hrp65. D. melanogaster NONA is involved in eye development and behavior and may play a role in circadian rhythm maintenance, similar to vertebrate p54nrb. C. tentans Hrp65 is a component of nuclear fibers associated with ribonucleoprotein particles in transit from the gene to the nuclear pore.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224028248 130 PRPVTVEPMDQLDDEEGLPEKLVIKNQQFHKEREQPPRFAQPGSFEYEYAMRWKALIEMEKQQQDQVDRNIKEAREKLEM 209
Cdd:cd12931    1 PRPVVVEPLEQRDEEDGLPERNVKKNAGYQKEREVGPRFAPPGSFEYEFGQRWKALYELEKQQREQLEKELKEAREKLEA 80

                         90
                 ....*....|
gi 224028248 210 EMEAARHEHQ 219
Cdd:cd12931   81 EMEAARYEHQ 90

RNA recognition motif 2 (RRM2) found in vertebrate polypyrimidine tract-binding protein (PTB)-associated-splicing factor (PSF); This subgroup corresponds to the RRM2 of PSF, also termed proline- and glutamine-rich splicing factor, or 100 kDa DNA-pairing protein (POMp100), or 100 kDa subunit of DNA-binding p52/p100 complex, a multifunctional protein that mediates diverse activities in the cell. It is ubiquitously expressed and highly conserved in vertebrates. PSF binds not only RNA but also both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) and facilitates the renaturation of complementary ssDNAs. It promotes the formation of D-loops in superhelical duplex DNA, and is involved in cell proliferation. PSF can also interact with multiple factors. It is an RNA-binding component of spliceosomes and binds to insulin-like growth factor response element (IGFRE). Moreover, PSF functions as a transcriptional repressor interacting with Sin3A and mediating silencing through the recruitment of histone deacetylases (HDACs) to the DNA binding domain (DBD) of nuclear hormone receptors. PSF is an essential pre-mRNA splicing factor and is dissociated from PTB and binds to U1-70K and serine-arginine (SR) proteins during apoptosis. PSF forms a heterodimer with the nuclear protein p54nrb, also known as non-POU domain-containing octamer-binding protein (NonO). The PSF/p54nrb complex displays a variety of functions, such as DNA recombination and RNA synthesis, processing, and transport. PSF contains two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), which are responsible for interactions with RNA and for the localization of the protein in speckles. It also contains an N-terminal region rich in proline, glycine, and glutamine residues, which may play a role in interactions recruiting other molecules.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224028248  60 SLTVRNLPQYVSNELLEEAFSVFGQVERAVVIVDDRGRPSGKGIVEFSGKPAARKALDRCSEGSFLLTTFPRPVTVEPMD 139
Cdd:cd12590    1 ALSVRNLSPYVSNELLEEAFSQFGPIERAVVIVDDRGRSTGKGIVEFASKPAARKAFERCSEGVFLLTTTPRPVIVEPLE 80

NOPS domain, including C-terminal coiled-coil region, in p54nrb/PSF/PSP1 homologs from invertebrate species; The family contains a DBHS domain (for Drosophila behavior, human splicing), which comprises two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a charged protein-protein interaction NOPS (NONA and PSP1) domain. This model corresponds to the NOPS domain, with a long helical C-terminal extension , found in Drosophila melanogaster gene no-ontransient A (nonA) encoding puff-specific protein Bj6 (also termed NONA), Chironomus tentans hrp65 gene encoding protein Hrp65 and similar proteins. D. melanogaster NONA is involved in eye development and behavior, and may play a role in circadian rhythm maintenance, similar to vertebrate p54nrb. C. tentans hrp65 is a component of nuclear fibers associated with ribonucleoprotein particles in transit from the gene to the nuclear pore. The NOPS domain specifically binds to the second RNA recognition motif (RRM2) domain of the partner DBHS protein via a substantial interaction surface. Its highly conserved C-terminal residues are critical for functional DBHS dimerization while the highly conserved C-terminal helical extension, forming a right-handed antiparallel heterodimeric coiled-coil, is essential for localization of these proteins to subnuclear bodies.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224028248 130 PRPVTVEPMDQLDDEEGLPEK-LVIKNQQFHKEREQPPRFAQPGSFEYEYAMRWKALIEMEKQQQDQVDRNIKEAREKLE 208
Cdd:cd12945    1 LRPCVVEPMEEIDDEDGLPEKsLNKKNPEFNKERSIGPRFAEPNSFEHEYGTRWKQLHELYKQKEEALKRELKMEEEKLE 80

                         90
                 ....*....|....*....
gi 224028248 209 MEMEAARHEHQVMLMRQDL 227
Cdd:cd12945   81 AQMEYARYEHETELLREQL 99

RNA recognition motif 1 (RRM1) found in vertebrate 54 kDa nuclear RNA- and DNA-binding protein (p54nrb); This subgroup corresponds to the RRM1 of p54nrb, also termed non-POU domain-containing octamer-binding protein (NonO), or 55 kDa nuclear protein (NMT55), or DNA-binding p52/p100 complex 52 kDa subunit. p54nrb is a multifunctional protein involved in numerous nuclear processes including transcriptional regulation, splicing, DNA unwinding, nuclear retention of hyperedited double-stranded RNA, viral RNA processing, control of cell proliferation, and circadian rhythm maintenance. It is ubiquitously expressed and highly conserved in vertebrates. p54nrb binds both, single- and double-stranded RNA and DNA, and also possesses inherent carbonic anhydrase activity. It forms a heterodimer with paraspeckle component 1 (PSPC1 or PSP1), localizing to paraspeckles in an RNA-dependent manneras well as with polypyrimidine tract-binding protein-associated-splicing factor (PSF). p54nrb contains two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), at the N-terminus.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 224028248   1 MRKLFEKYGKAGEVFIHKDKGFGFIRLETRTLAEIAKVELDNMPLRGKQLRVRF 54
Cdd:cd12588   18 MRKLFEKYGKAGEVFIHKDKGFGFIRLETRTLAEIAKVELDNMPLRGKQLRVRF 71

RNA recognition motif 1 (RRM1) found in vertebrate polypyrimidine tract-binding protein (PTB)-associated-splicing factor (PSF); This subgroup corresponds to the RRM1 of PSF, also termed proline- and glutamine-rich splicing factor, or 100 kDa DNA-pairing protein (POMp100), or 100 kDa subunit of DNA-binding p52/p100 complex, a multifunctional protein that mediates diverse activities in the cell. It is ubiquitously expressed and highly conserved in vertebrates. PSF binds not only RNA but also both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) and facilitates the renaturation of complementary ssDNAs. Besides, it promotes the formation of D-loops in superhelical duplex DNA, and is involved in cell proliferation. PSF can also interact with multiple factors. It is an RNA-binding component of spliceosomes and binds to insulin-like growth factor response element (IGFRE). PSF functions as a transcriptional repressor interacting with Sin3A and mediating silencing through the recruitment of histone deacetylases (HDACs) to the DNA binding domain (DBD) of nuclear hormone receptors. Additionally, PSF is an essential pre-mRNA splicing factor and is dissociated from PTB and binds to U1-70K and serine-arginine (SR) proteins during apoptosis. PSF forms a heterodimer with the nuclear protein p54nrb, also known as non-POU domain-containing octamer-binding protein (NonO). The PSF/p54nrb complex displays a variety of functions, such as DNA recombination and RNA synthesis, processing, and transport. PSF contains two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), which are responsible for interactions with RNA and for the localization of the protein in speckles. It also contains an N-terminal region rich in proline, glycine, and glutamine residues, which may play a role in interactions recruiting other molecules.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 224028248   2 RKLFEKYGKAGEVFIHKDKGFGFIRLETRTLAEIAKVELDNMPLRGKQLRVRF 54
Cdd:cd12587   19 KRLFAKYGEPGEVFINKGKGFGFIKLESRALAEIAKAELDDTPMRGRQLRVRF 71

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 224028248   61 LTVRNLPQYVSNELLEEAFSVFGQVERAVVIVDDRGRPSGKGIVEFSGKPAARKALDRC 119
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRDETGRSKGFAFVEFEDEEDAEKAIEAL 59

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 224028248   18 KDKGFGFIRLETRTLAEIAKVELDNMPLRGKQLRV-RFACHS----------ASLTVRNLPQYVSNELLEEAFSVFGQVE 86
Cdd:TIGR01628 127 KSRGYGFVHFEKEESAKAAIQKVNGMLLNDKEVYVgRFIKKHereaaplkkfTNLYVKNLDPSVNEDKLRELFAKFGEIT 206

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 224028248   87 RAVVIVDDRGRPSGKGIVEFSGKPAARKALDRCSEGSFLLTTFPRPVTVEPMDQLDDEEGLPEKLVIKNQQFHKEREQ 164
Cdd:TIGR01628 207 SAAVMKDGSGRSRGFAFVNFEKHEDAAKAVEEMNGKKIGLAKEGKKLYVGRAQKRAEREAELRRKFEELQQERKMKAQ 284

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 224028248  58 SASLTVRNLPQYVSNELLEEAFSVFGQVERAVVIVD-DRGRPSGKGIVEFSGKPAARKALD 117
Cdd:COG0724    1 SMKIYVGNLPYSVTEEDLRELFSEYGEVTSVKLITDrETGRSRGFGFVEMPDDEEAQAAIE 61

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor SRSF2, SRSF8 and similar proteins; This subfamily corresponds to the RRM of SRSF2 and SRSF8. SRSF2, also termed protein PR264, or splicing component, 35 kDa (splicing factor SC35 or SC-35), is a prototypical SR protein that plays important roles in the alternative splicing of pre-mRNA. It is also involved in transcription elongation by directly or indirectly mediating the recruitment of elongation factors to the C-terminal domain of polymerase II. SRSF2 is exclusively localized in the nucleus and is restricted to nuclear processes. It contains 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. The RRM is responsible for the specific recognition of 5'-SSNG-3' (S=C/G) RNA. In the regulation of alternative splicing events, it specifically binds to cis-regulatory elements on the pre-mRNA. The RS domain modulates SRSF2 activity through phosphorylation, directly contacts RNA, and promotes protein-protein interactions with the spliceosome. SRSF8, also termed SRP46 or SFRS2B, is a novel mammalian SR splicing factor encoded by a PR264/SC35 functional retropseudogene. SRSF8 is localized in the nucleus and does not display the same activity as PR264/SC35. It functions as an essential splicing factor in complementing a HeLa cell S100 extract deficient in SR proteins. Like SRSF2, SRSF8 contains a single N-terminal RRM and a C-terminal RS domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 224028248   1 MRKLFEKYGKAGEVFIHKDK------GFGFIRLETRTLAEIAKVELDNMPLRGKQLRV 52
Cdd:cd12311   15 LRRVFEKYGEVGDVYIPRDRytresrGFAFVRFYDKRDAEDAIDAMDGAELDGRELRV 72

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 224028248  61 LTVRNLPQYVSNELLEEAFSVFGQVERAVVIVDDR-GRPSGKGIVEFSGKPAARKALD 117
Cdd:cd21608    2 LYVGNLSWDTTEDDLRDLFSEFGEVESAKVITDREtGRSRGFGFVTFSTAEAAEAAID 59

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 224028248   2 RKLFEKYGKAGEVFIHKD------KGFGFIRLETRTLAEIAKVELDNMPLRGKQLRVRFA 55
Cdd:COG0724   19 RELFSEYGEVTSVKLITDretgrsRGFGFVEMPDDEEAQAAIEALNGAELMGRTLKVNEA 78

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 224028248  61 LTVRNLPQYVSNELLEEAFSVFGQVERAVVIVDDRGRPSGKGIVEFSGKPAARKALDRCSEGSFLlttfPRPVTV 135
Cdd:cd12414    2 LIVRNLPFKCTEDDLKKLFSKFGKVLEVTIPKKPDGKLRGFAFVQFTNVADAAKAIKGMNGKKIK----GRPVAV 72

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
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 224028248  61 LTVRNLPQYVSNELLEEAFSVFGQVERAVVIVDDRGRPSGKGIVEFSGKPAARKAL 116
Cdd:cd12381    4 LYVKNLDDTIDDEKLREEFSPFGTITSAKVMTDEGGRSKGFGFVCFSSPEEATKAV 59

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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 224028248   1 MRKLFEKYGKAGEVFIHKDKGFGFIRLETRTLAEIAKVELDNMPLRGKQLR 51
Cdd:cd12354   17 LQQTFSPFGQILEVRVFPDKGYAFIRFDSHEAATHAIVSVNGTIINGQAVK 67

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 224028248    3 KLFEKYGKAGEVF---------IHKDKGFGFIRLETRTLAEIAKVELDNMPLRGKQLRVRFACHSASLT--------VRN 65
Cdd:TIGR01628  16 KLYDLFKPFGPVLsvrvcrdsvTRRSLGYGYVNFQNPADAERALETMNFKRLGGKPIRIMWSQRDPSLRrsgvgnifVKN 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224028248   66 LPQYVSNELLEEAFSVFGQVERAVVIVDDRGRPSGKGIVEFSGKPAARKALDRCSegSFLLTTfpRPVTVEPMDQLDDEE 145
Cdd:TIGR01628  96 LDKSVDNKALFDTFSKFGNILSCKVATDENGKSRGYGFVHFEKEESAKAAIQKVN--GMLLND--KEVYVGRFIKKHERE 171

                         170
                  ....*....|....
gi 224028248  146 GLPEK----LVIKN 155
Cdd:TIGR01628 172 AAPLKkftnLYVKN 185

RNA recognition motif (RRM) found in THO complex subunit 4 (THOC4) and similar proteins; This subgroup corresponds to the RRM of THOC4, also termed transcriptional coactivator Aly/REF, or ally of AML-1 and LEF-1, or bZIP-enhancing factor BEF, an mRNA transporter protein with a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). It is involved in RNA transportation from the nucleus. THOC4 was initially identified as a transcription coactivator of LEF-1 and AML-1 for the TCRalpha enhancer function. In addition, THOC4 specifically binds to rhesus (RH) promoter in erythroid. It might be a novel transcription cofactor for erythroid-specific genes.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 224028248  61 LTVRNLPQYVSNELLEEAFSVFGQVERAVVIVDDRGRPSGKGIVEFSGKPAARKALDR 118
Cdd:cd12680    3 LLVSNLDFGVSDADIKELFAEFGTLKKAAVHYDRSGRSLGTAEVVFERRADALKAMKQ 60

RNA recognition motif 3 (RRM3) found in heterogeneous nuclear ribonucleoprotein R (hnRNP R) and similar proteins; This subfamily corresponds to the RRM3 in hnRNP R, hnRNP Q, and APOBEC-1 complementation factor (ACF). hnRNP R is a ubiquitously expressed nuclear RNA-binding protein that specifically bind mRNAs with a preference for poly(U) stretches and has been implicated in mRNA processing and mRNA transport, and also acts as a regulator to modify binding to ribosomes and RNA translation. hnRNP Q is also a ubiquitously expressed nuclear RNA-binding protein. It has been identified as a component of the spliceosome complex, as well as a component of the apobec-1 editosome, and has been implicated in the regulation of specific mRNA transport. ACF is an RNA-binding subunit of a core complex that interacts with apoB mRNA to facilitate C to U RNA editing. It may also act as an apoB mRNA recognition factor and chaperone and play a key role in cell growth and differentiation. This family also includes two functionally unknown RNA-binding proteins, RBM46 and RBM47. All members contain three conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 224028248  60 SLTVRNLPQYVSNELLEEAFSVFGQVERAVVIVDdrgrpsgKGIVEFSGKPAARKALDR----CSEGSFLLTTFPRP 132
Cdd:cd12251    3 VLYVRNLMLSTTEEKLRELFSEYGKVERVKKIKD-------YAFVHFEERDDAVKAMEEmngkELEGSEIEVSLAKP 72

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 224028248    1 MRKLFEKYGKAGEVFIHKD-----KGFGFIRLETRTLAEIAKVELDNMPLRGKQLR 51
Cdd:pfam00076  15 LKDLFSKFGPIKSIRLVRDetgrsKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 224028248   1 MRKLFEKYGKAGEVFIHKD------KGFGFIRLETRTLAEIAKVELDNMPLRGKQLRVRFA 55
Cdd:cd12399   15 LKSLFGQFGAVFDVKLPMDretkrpRGFGFVELQEEESAEKAIAKLDGTDFMGRTIRVNEA 75

ELAV/HuD family splicing factor; This model describes the ELAV/HuD subfamily of splicing factors found in metazoa. HuD stands for the human paraneoplastic encephalomyelitis antigen D of which there are 4 variants in human. ELAV stnds for the Drosophila Embryonic lethal abnormal visual protein. ELAV-like splicing factors are also known in human as HuB (ELAV-like protein 2), HuC (ELAV-like protein 3, Paraneoplastic cerebellar degeneration-associated antigen) and HuR (ELAV-like protein 1). These genes are most closely related to the sex-lethal subfamily of splicing factors found in Dipteran insects (TIGR01659). These proteins contain 3 RNA-recognition motifs (rrm: pfam00076).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224028248    1 MRKLFEKYGKAGEVFIHKDK------GFGFIRLETRTLAEIAKVELDNMPLRGKQLRVRFACHS------ASLTVRNLPQ 68
Cdd:TIGR01661  20 IRSLFTSIGEIESCKLVRDKvtgqslGYGFVNYVRPEDAEKAVNSLNGLRLQNKTIKVSYARPSsdsikgANLYVSGLPK 99

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 224028248   69 YVSNELLEEAFSVFGQVERAVVIVDD-RGRPSGKGIVEFSGKPAARKAL 116
Cdd:TIGR01661 100 TMTQHELESIFSPFGQIITSRILSDNvTGLSKGVGFIRFDKRDEADRAI 148

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein M (hnRNP M) and similar proteins; This subfamily corresponds to the RRM2 of heterogeneous nuclear ribonucleoprotein M (hnRNP M), myelin expression factor 2 (MEF-2 or MyEF-2 or MST156) and similar proteins. hnRNP M is pre-mRNA binding protein that may play an important role in the pre-mRNA processing. It also preferentially binds to poly(G) and poly(U) RNA homopolymers. hnRNP M is able to interact with early spliceosomes, further influencing splicing patterns of specific pre-mRNAs. It functions as the receptor of carcinoembryonic antigen (CEA) that contains the penta-peptide sequence PELPK signaling motif. In addition, hnRNP M and another splicing factor Nova-1 work together as dopamine D2 receptor (D2R) pre-mRNA-binding proteins. They regulate alternative splicing of D2R pre-mRNA in an antagonistic manner. hnRNP M contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an unusual hexapeptide-repeat region rich in methionine and arginine residues (MR repeat motif). MEF-2 is a sequence-specific single-stranded DNA (ssDNA) binding protein that binds specifically to ssDNA derived from the proximal (MB1) element of the myelin basic protein (MBP) promoter and represses transcription of the MBP gene. MEF-2 shows high sequence homology with hnRNP M. It also contains three RRMs, which may be responsible for its ssDNA binding activity.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 224028248  63 VRNLPQYVSNELLEEAFSVFGQVERAVVIVDDRGRPSGKGIVEFSGKPAARKALDRCSeGSFLlttFPRPVTVEpMD 139
Cdd:cd12386    3 VANLDYKVGWKKLKEVFKLAGKVVRADIREDKDGKSRGMGVVQFEHPIEAVQAISMFN-GQML---FDRPMRVK-MD 74

RNA recognition motif (RRM) found in heterogeneous nuclear ribonucleoprotein (hnRNP) H protein family, epithelial splicing regulatory proteins (ESRPs), Drosophila RNA-binding protein Fusilli, RNA-binding protein 12 (RBM12) and similar proteins; The family includes RRM domains in the hnRNP H protein family, G-rich sequence factor 1 (GRSF-1), ESRPs (also termed RBM35), Drosophila Fusilli, RBM12 (also termed SWAN), RBM12B, RBM19 (also termed RBD-1) and similar proteins. The hnRNP H protein family includes hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H'), hnRNP F and hnRNP H3 (also termed hnRNP 2H9), which represent a group of nuclear RNA binding proteins that are involved in pre-mRNA processing. GRSF-1 is a cytoplasmic poly(A)+ mRNA binding protein which interacts with RNA in a G-rich element-dependent manner. It may function in RNA packaging, stabilization of RNA secondary structure, or other macromolecular interactions. ESRP1 (also termed RBM35A) and ESRP2 (also termed RBM35B) are epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of fibroblast growth factor receptor 2 (FGFR2), ENAH (also termed hMena), CD44 and CTNND1 (also termed p120-Catenin) transcripts. Fusilli shows high sequence homology to ESRPs. It can regulate endogenous FGFR2 splicing and functions as a splicing factor. The biological roles of both, RBM12 and RBM12B, remain unclear. RBM19 is a nucleolar protein conserved in eukaryotes. It is involved in ribosome biogenesis by processing rRNA. In addition, it is essential for preimplantation development. Members in this family contain 2~6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 224028248  63 VRNLPQYVSNELLEEAFSVFGQVERAVVIV-DDRGRPSGKGIVEFSGKPAARKALDR 118
Cdd:cd12254    4 LRGLPFSATEEDIRDFFSGLDIPPDGIHIVyDDDGRPTGEAYVEFASEEDAQRALRR 60

RNA recognition motif (RRM) found in the Aly/REF family; This subfamily corresponds to the RRM of Aly/REF family which includes THO complex subunit 4 (THOC4, also termed Aly/REF), S6K1 Aly/REF-like target (SKAR, also termed PDIP3 or PDIP46) and similar proteins. THOC4 is an mRNA transporter protein with a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). It is involved in RNA transportation from the nucleus, and was initially identified as a transcription coactivator of LEF-1 and AML-1 for the TCRalpha enhancer function. In addition, THOC4 specifically binds to rhesus (RH) promoter in erythroid, and might be a novel transcription cofactor for erythroid-specific genes. SKAR shows high sequence homology with THOC4 and possesses one RRM as well. SKAR is widely expressed and localizes to the nucleus. It may be a critical player in the function of S6K1 in cell and organism growth control by binding the activated, hyperphosphorylated form of S6K1 but not S6K2. Furthermore, SKAR functions as a protein partner of the p50 subunit of DNA polymerase delta. In addition, SKAR may have particular importance in pancreatic beta cell size determination and insulin secretion.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 224028248  61 LTVRNLPQYVSNELLEEAFSVFGQVERAVVIVDDRGRPSGKGIVEFSGKPAARKALD 117
Cdd:cd12418    3 VRVSNLHPDVTEEDLRELFGRVGPVKSVKINYDRSGRSTGTAYVVFERPEDAEKAIK 59

RNA recognition motif 2 (RRM2) found in yeast nuclear polyadenylated RNA-binding protein 4 (Hrp1p or Nab4p) and similar proteins; This subfamily corresponds to the RRM1 of Hrp1p and similar proteins. Hrp1p or Nab4p, also termed cleavage factor IB (CFIB), is a sequence-specific trans-acting factor that is essential for mRNA 3'-end formation in yeast Saccharomyces cerevisiae. It can be UV cross-linked to RNA and specifically recognizes the (UA)6 RNA element required for both, the cleavage and poly(A) addition steps. Moreover, Hrp1p can shuttle between the nucleus and the cytoplasm, and play an additional role in the export of mRNAs to the cytoplasm. Hrp1p also interacts with Rna15p and Rna14p, two components of CF1A. In addition, Hrp1p functions as a factor directly involved in modulating the activity of the nonsense-mediated mRNA decay (NMD) pathway; it binds specifically to a downstream sequence element (DSE)-containing RNA and interacts with Upf1p, a component of the surveillance complex, further triggering the NMD pathway. Hrp1p contains two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an arginine-glycine-rich region harboring repeats of the sequence RGGF/Y.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 224028248  63 VRNLPQYVSNELLEEAFSVFGQVERAVVIVD-DRGRPSGKGIVEFSGKPAARKAL 116
Cdd:cd12330    4 VGGLAPDVTEEEFKEYFEQFGTVVDAVVMLDhDTGRSRGFGFVTFDSESAVEKVL 58

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 224028248  61 LTVRNLPQYVSNELLEEAFSVFGQVErAVVIVDDR--GRPSGKGIVEFSGKPAARKALDRCSEGSF 124
Cdd:cd12399    1 LYVGNLPYSASEEQLKSLFGQFGAVF-DVKLPMDRetKRPRGFGFVELQEEESAEKAIAKLDGTDF 65

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 224028248  75 LEEAFSVFGQVERAVVIVD-DRGRPSGKGIVEFSGKPAARKAL 116
Cdd:cd12449   17 LEEVFSKYGQISEVVVVKDrETQRSRGFGFVTFENPDDAKDAM 59

RNA recognition motif 2 (RRM2) found found in vertebrate ribonucleoprotein PTB-binding 1 (raver-1); This subgroup corresponds to the RRM2 of raver-1, a ubiquitously expressed heterogeneous nuclear ribonucleoprotein (hnRNP) that serves as a co-repressor of the nucleoplasmic splicing repressor polypyrimidine tract-binding protein (PTB)-directed splicing of select mRNAs. It shuttles between the cytoplasm and the nucleus and can accumulate in the perinucleolar compartment, a dynamic nuclear substructure that harbors PTB. Raver-1 also modulates focal adhesion assembly by binding to the cytoskeletal proteins, including alpha-actinin, vinculin, and metavinculin (an alternatively spliced isoform of vinculin) at adhesion complexes, particularly in differentiated muscle tissue. Raver-1 contains three N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two putative nuclear localization signals (NLS) at the N- and C-termini, a central leucine-rich region, and a C-terminal region harboring two PTB-binding [SG][IL]LGxxP motifs. Raver1 binds to PTB through the PTB-binding motifs at its C-terminal half, and binds to other partners, such as RNA having the sequence UCAUGCAGUCUG, through its N-terminal RRMs. Interestingly, the 12-nucleotide RNA having the sequence UCAUGCAGUCUG with micromolar affinity is found in vinculin mRNA. Additional research indicates that the RRM1 of raver-1 directs its interaction with the tail domain of activated vinculin. Then the raver1/vinculin tail (Vt) complex binds to vinculin mRNA, which is permissive for vinculin binding to F-actin.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 224028248  61 LTVRNLPQYVSNELLEEAFSVFGQVERAVVIVDDR-GRPSGKGIVEFSGKPAARKA 115
Cdd:cd12665    2 LCIANLPPSYTQQQFEELVRPFGNLERCFLVYSETtGHSKGYGFVEYMKKDSAARA 57

RNA recognition motif (RRM) found in AZoospermia (DAZ) autosomal homologs, DAZL (DAZ-like) and BOULE; This subfamily corresponds to the RRM domain of two Deleted in AZoospermia (DAZ) autosomal homologs, DAZL (DAZ-like) and BOULE. BOULE is the founder member of the family and DAZL arose from BOULE in an ancestor of vertebrates. The DAZ gene subsequently originated from a duplication transposition of the DAZL gene. Invertebrates contain a single DAZ homolog, BOULE, while vertebrates, other than catarrhine primates, possess both BOULE and DAZL genes. The catarrhine primates possess BOULE, DAZL, and DAZ genes. The family members encode closely related RNA-binding proteins that are required for fertility in numerous organisms. These proteins contain an RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a varying number of copies of a DAZ motif, believed to mediate protein-protein interactions. DAZL and BOULE contain a single copy of the DAZ motif, while DAZ proteins can contain 8-24 copies of this repeat. Although their specific biochemical functions remain to be investigated, DAZL proteins may interact with poly(A)-binding proteins (PABPs), and act as translational activators of specific mRNAs during gametogenesis.

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gi 224028248   1 MRKLFEKYGKAGEVFIHKD-----KGFGFIRLETRTLAEIAKVELDNMPLRGKQLRVRFA 55
Cdd:cd12412   19 LREFFSKFGKVKDVKIIKDragvsKGYGFVTFETQEDAEKIQKWGANLVFKGKKLNVGPA 78

RNA recognition motif 2 (RRM2) found in splicing factor 3B subunit 4 (SF3B4) and similar proteins; This subfamily corresponds to the RRM2 of SF3B4, also termed pre-mRNA-splicing factor SF3b 49 kDa (SF3b50), or spliceosome-associated protein 49 (SAP 49). SF3B4 is a component of the multiprotein complex splicing factor 3b (SF3B), an integral part of the U2 small nuclear ribonucleoprotein (snRNP) and the U11/U12 di-snRNP. SF3B is essential for the accurate excision of introns from pre-messenger RNA, and is involved in the recognition of the pre-mRNA's branch site within the major and minor spliceosomes. SF3B4 functions to tether U2 snRNP with pre-mRNA at the branch site during spliceosome assembly. It is an evolutionarily highly conserved protein with orthologs across diverse species. SF3B4 contains two closely adjacent N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). It binds directly to pre-mRNA and also interacts directly and highly specifically with another SF3B subunit called SAP 145.

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gi 224028248  59 ASLTVRNLPQYVSNELLEEAFSVFGQVERAVVIV--DDRGRPSGKGIVEFSGKPAARKALDrCSEGSFLLTtfpRPVTVE 136
Cdd:cd12335    2 ANLFIGNLDPEVDEKLLYDTFSAFGVILQTPKIMrdPDTGNSKGFGFVSFDSFEASDAAIE-AMNGQYLCN---RPITVS 77

RNA recognition motif 3 (RRM3) found in RNA-binding protein 19 (RBM19) and RNA recognition motif 2 found in multiple RNA-binding domain-containing protein 1 (MRD1); This subfamily corresponds to the RRM3 of RBM19 and RRM2 of MRD1. RBM19, also termed RNA-binding domain-1 (RBD-1), is a nucleolar protein conserved in eukaryotes involved in ribosome biogenesis by processing rRNA and is essential for preimplantation development. It has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). MRD1 is encoded by a novel yeast gene MRD1 (multiple RNA-binding domain). It is well conserved in yeast and its homologs exist in all eukaryotes. MRD1 is present in the nucleolus and the nucleoplasm. It interacts with the 35 S precursor rRNA (pre-rRNA) and U3 small nucleolar RNAs (snoRNAs). It is essential for the initial processing at the A0-A2 cleavage sites in the 35 S pre-rRNA. MRD1 contains 5 conserved RRMs, which may play an important structural role in organizing specific rRNA processing events.