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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958769537  772 SILLVSELPEDGFTEEDIRKAFQPFGKISDVLLVPCRNEAYLEMEFKKAVTSIMKYIETMPLVIKGKSVKVCVPGK 847
Cdd:cd12716      1 CVVLISNLPEKGYTVEEISNLAKPFGGVNDILILSSHKKAYLEMNFKEAVDSMVKYYETFPVLVGGKRLKISMAEK 76

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958769537  836 KGKSVKVCVPGKKKPQNK----EMKKKPLDLKKSASALKKETDASKVIENVTSASSAKSGQIKSSTVKVNKSAGKSAGSV 911
Cdd:PTZ00121  1297 KAEEKKKADEAKKKAEEAkkadEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKKEEA 1376

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958769537  912 KSVVTVAAKGKASIKTAKSGKKSLE--AKKSGNIKNKDYNKpvtvSANSEVKASREDKatgKTAVETTSGALEATENEPV 989
Cdd:PTZ00121  1377 KKKADAAKKKAEEKKKADEAKKKAEedKKKADELKKAAAAK----KKADEAKKKAEEK---KKADEAKKKAEEAKKADEA 1449

                   ....*.
gi 1958769537  990 SKEMEE 995
Cdd:PTZ00121  1450 KKKAEE 1455

RNA recognition motif 1 (RRM1) and 2 (RRM2) found in vertebrate nuclear protein 220 (NP220); This subgroup corresponds to RRM1 and RRM2 of NP220, also termed zinc finger protein 638 (ZN638), or cutaneous T-cell lymphoma-associated antigen se33-1, or zinc finger matrin-like protein, a large nucleoplasmic DNA-binding protein that binds to cytidine-rich sequences, such as CCCCC (G/C), in double-stranded DNA (dsDNA). NP220 contains multiple domains, including MH1, MH2, and MH3, domains homologous to the acidic nuclear protein matrin 3; RS, an arginine/serine-rich domain commonly found in pre-mRNA splicing factors; PstI-HindIII, a domain essential for DNA binding; acidic repeat, a domain with nine repeats of the sequence LVTVDEVIEEEDL; and a Cys2-His2 zinc finger-like motif that is also present in matrin 3. It may be involved in packaging, transferring, or processing transcripts. This subgroup corresponds to the domain of MH2 that contains two tandem RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958769537  772 SILLVSELPEDGFTEEDIRKAFQPFGKISDVLLVPCRNEAYLEMEFKKAVTSIMKYIETMPLVIKGKSVKVCVPGK 847
Cdd:cd12716      1 CVVLISNLPEKGYTVEEISNLAKPFGGVNDILILSSHKKAYLEMNFKEAVDSMVKYYETFPVLVGGKRLKISMAEK 76

RNA recognition motif;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958769537   774 LLVSELPEDgFTEEDIRKAFQPFGKISDVLLVP------CRNEAYLEMEFKKAVTSIMKYIETMplVIKGKSVKV 842
Cdd:smart00360    2 LFVGNLPPD-TTEEELRELFSKFGKVESVRLVRdketgkSKGFAFVEFESEEDAEKALEALNGK--ELDGRPLKV 73

hnRNP-L/PTB/hephaestus splicing factor family; Included in this family of heterogeneous ribonucleoproteins are PTB (polypyrimidine tract binding protein) and hnRNP-L. These proteins contain four RNA recognition motifs (rrm: pfam00067).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958769537  998 VVFISNLPNKgySTE-EIYNLAKPFGALKDILVLSSHKKAYIEI-NKKSADSMVKFYTCFPICMDGNQLSIS-------- 1067
Cdd:TIGR01649    4 VVHVRNLPQD--VVEaDLVEALIPFGPVSYVMMLPGKRQALVEFeDEESAKACVNFATSVPIYIRGQPAFFNystsqeik 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958769537 1068 -MAPEDVDLKDEEALFTTLIQESDPEANIDEIYNRFvhldnlpedglqcvlcvgHQFGKVDRYVFMSNRNKV--ILQLES 1144
Cdd:TIGR01649   82 rDGNSDFDSAGPNKVLRVIVENPMYPITLDVLYQIF------------------NPYGKVLRIVTFTKNNVFqaLVEFES 143

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958769537 1145 PESALSMYNFLkqNPQNIgdHVLSCTLS---PKMDS-EVQKKNDPELGKESPDLKNSPvDESEVQTAADS 1210
Cdd:TIGR01649  144 VNSAQHAKAAL--NGADI--YNGCCTLKieyAKPTRlNVKYNDDDSRDYTNPDLPGRR-DPGLDQTHRQR 208

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
                   ....*....|....*....|....*....|....*....|....*...
gi 1958769537  774 LLVSELPEDgFTEEDIRKAFQPFGKISDVLLVP-----CRNEAYLEME 816
Cdd:pfam00076    1 LFVGNLPPD-TTEEDLKDLFSKFGPIKSIRLVRdetgrSKGFAFVEFE 47

RNA recognition motif 1 (RRM1) and 2 (RRM2) found in vertebrate nuclear protein 220 (NP220); This subgroup corresponds to RRM1 and RRM2 of NP220, also termed zinc finger protein 638 (ZN638), or cutaneous T-cell lymphoma-associated antigen se33-1, or zinc finger matrin-like protein, a large nucleoplasmic DNA-binding protein that binds to cytidine-rich sequences, such as CCCCC (G/C), in double-stranded DNA (dsDNA). NP220 contains multiple domains, including MH1, MH2, and MH3, domains homologous to the acidic nuclear protein matrin 3; RS, an arginine/serine-rich domain commonly found in pre-mRNA splicing factors; PstI-HindIII, a domain essential for DNA binding; acidic repeat, a domain with nine repeats of the sequence LVTVDEVIEEEDL; and a Cys2-His2 zinc finger-like motif that is also present in matrin 3. It may be involved in packaging, transferring, or processing transcripts. This subgroup corresponds to the domain of MH2 that contains two tandem RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958769537  772 SILLVSELPEDGFTEEDIRKAFQPFGKISDVLLVPCRNEAYLEMEFKKAVTSIMKYIETMPLVIKGKSVKVCVPGK 847
Cdd:cd12716      1 CVVLISNLPEKGYTVEEISNLAKPFGGVNDILILSSHKKAYLEMNFKEAVDSMVKYYETFPVLVGGKRLKISMAEK 76

RNA recognition motif 2 (RRM2) found in vertebrate matrin-3; This subgroup corresponds to the RRM2 of Matrin 3 (MATR3 or P130), a highly conserved inner nuclear matrix protein with a bipartite nuclear localization signal (NLS), two zinc finger domains predicted to bind DNA, and two RNA recognition motifs (RRM), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), that are known to interact with RNA. MATR3 has been implicated in various biological processes. It is involved in RNA processing by interacting with other nuclear proteins to anchor hyperedited RNAs to the nuclear matrix. It plays a role in mRNA stabilization through maintaining the stability of certain mRNA species. Besides, it modulates the activity of proximal promoters by binding to highly repetitive sequences of matrix/scaffold attachment region (MAR/SAR). The phosphorylation of MATR3 is assumed to cause neuronal death. It is phosphorylated by the protein kinase ATM, which activates the cellular response to double strand breaks in the DNA. Its phosphorylation by protein kinase A (PKA) is responsible for the activation of the N-methyl-d-aspartic acid (NMDA) receptor. Furthermore, MATR3 has been identified as both a Ca2+-dependent CaM-binding protein and a downstream substrate of caspases. Additional research indicates that matrin 3 also binds Rev/Rev responsive element (RRE)-containing viral RNA and functions as a cofactor that mediates the post-transcriptional regulation of HIV-1.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958769537  773 ILLVSELPEDGFTEEDIRKAFQPFGKISDVLLVPCRNEAYLEMEFKKAVTSIMKYIETMPLVIKGKSVKVCVPGKKK 849
Cdd:cd12715      2 VIHLSNLPHSGYSDAAVLKLAEPYGKVKNYILMRMKNQAFLEMESREDAMAMVDHCKKKPLWFQGRCVKVDLSQKYK 78

RNA recognition motif (RRM) found in polypyrimidine tract-binding protein 1 (PTB or hnRNP I), heterogeneous nuclear ribonucleoprotein L (hnRNP-L), and similar proteins; This subfamily corresponds to the RRM1 of the majority of family members that include polypyrimidine tract-binding protein 1 (PTB or hnRNP I), polypyrimidine tract-binding protein 2 (PTBP2 or nPTB), regulator of differentiation 1 (Rod1), heterogeneous nuclear ribonucleoprotein L (hnRNP-L), heterogeneous nuclear ribonucleoprotein L-like (hnRNP-LL), polypyrimidine tract-binding protein homolog 3 (PTBPH3), polypyrimidine tract-binding protein homolog 1 and 2 (PTBPH1 and PTBPH2), and similar proteins. PTB is an important negative regulator of alternative splicing in mammalian cells and also functions at several other aspects of mRNA metabolism, including mRNA localization, stabilization, polyadenylation, and translation. PTBP2 is highly homologous to PTB and is perhaps specific to the vertebrates. Unlike PTB, PTBP2 is enriched in the brain and in some neural cell lines. It binds more stably to the downstream control sequence (DCS) RNA than PTB does but is a weaker repressor of splicing in vitro. PTBP2 also greatly enhances the binding of two other proteins, heterogeneous nuclear ribonucleoprotein (hnRNP) H and KH-type splicing-regulatory protein (KSRP), to the DCS RNA. The binding properties of PTBP2 and its reduced inhibitory activity on splicing imply roles in controlling the assembly of other splicing-regulatory proteins. Rod1 is a mammalian polypyrimidine tract binding protein (PTB) homolog of a regulator of differentiation in the fission yeast Schizosaccharomyces pombe, where the nrd1 gene encodes an RNA binding protein negatively regulates the onset of differentiation. ROD1 is predominantly expressed in hematopoietic cells or organs. It might play a role controlling differentiation in mammals. hnRNP-L is a higher eukaryotic specific subunit of human KMT3a (also known as HYPB or hSet2) complex required for histone H3 Lys-36 trimethylation activity. It plays both, nuclear and cytoplasmic, roles in mRNA export of intronless genes, IRES-mediated translation, mRNA stability, and splicing. hnRNP-LL protein plays a critical and unique role in the signal-induced regulation of CD45 and acts as a global regulator of alternative splicing in activated T cells. The family also includes polypyrimidine tract binding protein homolog 3 (PTBPH3) found in plant. Although its biological roles remain unclear, PTBPH3 shows significant sequence similarity to other family members, all of which contain four RNA recognition motifs (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain). Although their biological roles remain unclear, both PTBPH1 and PTBPH2 show significant sequence similarity to PTB. However, in contrast to PTB, they have three RRMs. In addition, this family also includes RNA-binding motif protein 20 (RBM20) that is an alternative splicing regulator associated with dilated cardiomyopathy (DCM) and contains only one RRM.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958769537  779 LPEDGfTEEDIRKAFQPFGKISDVLLVPCRNEAYLEMEFKKAVTSIMKYIETMPLVIKGKSVKV 842
Cdd:cd12421      7 LPPDA-TEADLVALGLPFGKVTNVLLLKGKNQALVEMEDVESASSMVNYYTTVPPLIRGRPVYV 69

RNA recognition motif 2 (RRM2) found in vertebrate matrin-3; This subgroup corresponds to the RRM2 of Matrin 3 (MATR3 or P130), a highly conserved inner nuclear matrix protein with a bipartite nuclear localization signal (NLS), two zinc finger domains predicted to bind DNA, and two RNA recognition motifs (RRM), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), that are known to interact with RNA. MATR3 has been implicated in various biological processes. It is involved in RNA processing by interacting with other nuclear proteins to anchor hyperedited RNAs to the nuclear matrix. It plays a role in mRNA stabilization through maintaining the stability of certain mRNA species. Besides, it modulates the activity of proximal promoters by binding to highly repetitive sequences of matrix/scaffold attachment region (MAR/SAR). The phosphorylation of MATR3 is assumed to cause neuronal death. It is phosphorylated by the protein kinase ATM, which activates the cellular response to double strand breaks in the DNA. Its phosphorylation by protein kinase A (PKA) is responsible for the activation of the N-methyl-d-aspartic acid (NMDA) receptor. Furthermore, MATR3 has been identified as both a Ca2+-dependent CaM-binding protein and a downstream substrate of caspases. Additional research indicates that matrin 3 also binds Rev/Rev responsive element (RRE)-containing viral RNA and functions as a cofactor that mediates the post-transcriptional regulation of HIV-1.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958769537  998 VVFISNLPNKGYSTEEIYNLAKPFGALKDILVLSSHKKAYIEI-NKKSADSMVKFYTCFPICMDGNQLSISMA 1069
Cdd:cd12715      2 VIHLSNLPHSGYSDAAVLKLAEPYGKVKNYILMRMKNQAFLEMeSREDAMAMVDHCKKKPLWFQGRCVKVDLS 74

RNA recognition motif;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958769537   774 LLVSELPEDgFTEEDIRKAFQPFGKISDVLLVP------CRNEAYLEMEFKKAVTSIMKYIETMplVIKGKSVKV 842
Cdd:smart00360    2 LFVGNLPPD-TTEEELRELFSKFGKVESVRLVRdketgkSKGFAFVEFESEEDAEKALEALNGK--ELDGRPLKV 73

RNA recognition motif (RRM) found in vertebrate RNA-binding protein 20 (RBM20); This subfamily corresponds to the RRM of RBM20, an alternative splicing regulator associated with dilated cardiomyopathy (DCM). It contains only one copy of RNA-recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958769537  997 SVVFISNLPNKGYSTEEIYNLAKPFGALKDILVLSSHKKAYIEIN-KKSADSMVKFYTCFPICMDGNQLSISMA 1069
Cdd:cd12685      1 RVVHICNLPEGSCTENDVINLGLPFGKVTNYILMRSTNQAFLEMAyTEAAQAMVQYYQEKPAMINEEKLLIRMS 74

RNA recognition motif (RRM) found in polypyrimidine tract-binding protein 1 (PTB or hnRNP I), heterogeneous nuclear ribonucleoprotein L (hnRNP-L), and similar proteins; This subfamily corresponds to the RRM1 of the majority of family members that include polypyrimidine tract-binding protein 1 (PTB or hnRNP I), polypyrimidine tract-binding protein 2 (PTBP2 or nPTB), regulator of differentiation 1 (Rod1), heterogeneous nuclear ribonucleoprotein L (hnRNP-L), heterogeneous nuclear ribonucleoprotein L-like (hnRNP-LL), polypyrimidine tract-binding protein homolog 3 (PTBPH3), polypyrimidine tract-binding protein homolog 1 and 2 (PTBPH1 and PTBPH2), and similar proteins. PTB is an important negative regulator of alternative splicing in mammalian cells and also functions at several other aspects of mRNA metabolism, including mRNA localization, stabilization, polyadenylation, and translation. PTBP2 is highly homologous to PTB and is perhaps specific to the vertebrates. Unlike PTB, PTBP2 is enriched in the brain and in some neural cell lines. It binds more stably to the downstream control sequence (DCS) RNA than PTB does but is a weaker repressor of splicing in vitro. PTBP2 also greatly enhances the binding of two other proteins, heterogeneous nuclear ribonucleoprotein (hnRNP) H and KH-type splicing-regulatory protein (KSRP), to the DCS RNA. The binding properties of PTBP2 and its reduced inhibitory activity on splicing imply roles in controlling the assembly of other splicing-regulatory proteins. Rod1 is a mammalian polypyrimidine tract binding protein (PTB) homolog of a regulator of differentiation in the fission yeast Schizosaccharomyces pombe, where the nrd1 gene encodes an RNA binding protein negatively regulates the onset of differentiation. ROD1 is predominantly expressed in hematopoietic cells or organs. It might play a role controlling differentiation in mammals. hnRNP-L is a higher eukaryotic specific subunit of human KMT3a (also known as HYPB or hSet2) complex required for histone H3 Lys-36 trimethylation activity. It plays both, nuclear and cytoplasmic, roles in mRNA export of intronless genes, IRES-mediated translation, mRNA stability, and splicing. hnRNP-LL protein plays a critical and unique role in the signal-induced regulation of CD45 and acts as a global regulator of alternative splicing in activated T cells. The family also includes polypyrimidine tract binding protein homolog 3 (PTBPH3) found in plant. Although its biological roles remain unclear, PTBPH3 shows significant sequence similarity to other family members, all of which contain four RNA recognition motifs (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain). Although their biological roles remain unclear, both PTBPH1 and PTBPH2 show significant sequence similarity to PTB. However, in contrast to PTB, they have three RRMs. In addition, this family also includes RNA-binding motif protein 20 (RBM20) that is an alternative splicing regulator associated with dilated cardiomyopathy (DCM) and contains only one RRM.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958769537  998 VVFISNLPNKgySTE-EIYNLAKPFGALKDILVLSSHKKAYIEI-NKKSADSMVKFYTCFPICMDGNQL 1064
Cdd:cd12421      1 VVHIRNLPPD--ATEaDLVALGLPFGKVTNVLLLKGKNQALVEMeDVESASSMVNYYTTVPPLIRGRPV 67

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958769537  774 LLVSELPEDgFTEEDIRKAFQPFGKISDVLLVP-----CRNEAYLEMEFKKAVTSIMKYIETMplVIKGKSVKV 842
Cdd:cd00590      1 LFVGNLPPD-TTEEDLRELFSKFGEVVSVRIVRdrdgkSKGFAFVEFESPEDAEKALEALNGT--ELGGRPLKV 71

RNA recognition motif 1 (RRM1) found in vertebrate polypyrimidine tract-binding protein 1 (PTB); This subgroup corresponds to the RRM1 of PTB, also known as 58 kDa RNA-binding protein PPTB-1 or heterogeneous nuclear ribonucleoprotein I (hnRNP I), an important negative regulator of alternative splicing in mammalian cells. PTB also functions at several other aspects of mRNA metabolism, including mRNA localization, stabilization, polyadenylation, and translation. PTB contains four RNA recognition motifs (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain). RRM1 and RRM2 are independent from each other and separated by flexible linkers. By contrast, there is an unusual and conserved interdomain interaction between RRM3 and RRM4. It is widely held that only RRMs 3 and 4 are involved in RNA binding and RRM2 mediates PTB homodimer formation. However, new evidence shows that the RRMs 1 and 2 also contribute substantially to RNA binding. Moreover, PTB may not always dimerize to repress splicing. It is a monomer in solution.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958769537  998 VVFISNLPNKgYSTEEIYNLAKPFGALKDILVLSSHKKAYIEIN-KKSADSMVKFYT 1053
Cdd:cd12777      2 VIHVRKLPND-VTEAEVISLGLPFGKVTNLLMLKGKNQAFIEMNtEEAANTMVNYYT 57

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958769537  847 KKKPQNKEMKKKPLDLKKSASALKKETDASKVIENVTSASSAKsgqiksstvKVNKSAGKSAGSVKSVVTVAAKGKASIK 926
Cdd:PTZ00121  1375 EAKKKADAAKKKAEEKKKADEAKKKAEEDKKKADELKKAAAAK---------KKADEAKKKAEEKKKADEAKKKAEEAKK 1445

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958769537  927 TAKSGKKSLEAKKSGNIKNKDYNKPVTVSANSEVKASREDKATGKTAVETTSGALEATENEPVSKEMEEM 996
Cdd:PTZ00121  1446 ADEAKKKAEEAKKAEEAKKKAEEAKKADEAKKKAEEAKKADEAKKKAEEAKKKADEAKKAAEAKKKADEA 1515

RNA recognition motif 1 (RRM1) found in vertebrate regulator of differentiation 1 (Rod1); This subgroup corresponds to the RRM1 of ROD1 coding protein Rod1, a mammalian polypyrimidine tract binding protein (PTB) homolog of a regulator of differentiation in the fission yeast Schizosaccharomyces pombe, where the nrd1 gene encodes an RNA binding protein that negatively regulates the onset of differentiation. ROD1 is predominantly expressed in hematopoietic cells or organs. It might play a role controlling differentiation in mammals. Rod1 contains four repeats of RNA recognition motifs (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain) and does have RNA binding activities.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958769537  769 SSNSILLVSELPEDgFTEEDIRKAFQPFGKISDVLLVPCRNEAYLEMEFKKAVTSIMKYIETMPLVIKGKSVKV 842
Cdd:cd12779      3 SPSRVLHIRKIPND-VTEAEVISLGLPFGKVTNLLMLKGKNQAFLEMASEEAAVTMVNYYTTVTPHLRNQPVYI 75

hnRNP-L/PTB/hephaestus splicing factor family; Included in this family of heterogeneous ribonucleoproteins are PTB (polypyrimidine tract binding protein) and hnRNP-L. These proteins contain four RNA recognition motifs (rrm: pfam00067).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958769537  998 VVFISNLPNKgySTE-EIYNLAKPFGALKDILVLSSHKKAYIEI-NKKSADSMVKFYTCFPICMDGNQLSIS-------- 1067
Cdd:TIGR01649    4 VVHVRNLPQD--VVEaDLVEALIPFGPVSYVMMLPGKRQALVEFeDEESAKACVNFATSVPIYIRGQPAFFNystsqeik 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958769537 1068 -MAPEDVDLKDEEALFTTLIQESDPEANIDEIYNRFvhldnlpedglqcvlcvgHQFGKVDRYVFMSNRNKV--ILQLES 1144
Cdd:TIGR01649   82 rDGNSDFDSAGPNKVLRVIVENPMYPITLDVLYQIF------------------NPYGKVLRIVTFTKNNVFqaLVEFES 143

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958769537 1145 PESALSMYNFLkqNPQNIgdHVLSCTLS---PKMDS-EVQKKNDPELGKESPDLKNSPvDESEVQTAADS 1210
Cdd:TIGR01649  144 VNSAQHAKAAL--NGADI--YNGCCTLKieyAKPTRlNVKYNDDDSRDYTNPDLPGRR-DPGLDQTHRQR 208

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        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958769537  772 SILLVSELPEDgFTEEDIRKAFQPFGKISDVLLVPCRNEAYLEMEfKKAVTSIMKyIETMPLVIKGKSVKV 842
Cdd:cd12588      2 SRLFVGNLPPD-ITEEEMRKLFEKYGKAGEVFIHKDKGFGFIRLE-TRTLAEIAK-VELDNMPLRGKQLRV 69

hnRNP-L/PTB/hephaestus splicing factor family; Included in this family of heterogeneous ribonucleoproteins are PTB (polypyrimidine tract binding protein) and hnRNP-L. These proteins contain four RNA recognition motifs (rrm: pfam00067).

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958769537  776 VSELPEDgFTEEDIRKAFQPFGKISDVLLVPCRNEAYLEMEFKKAVTSIMKYIETMPLVIKGKSV 840
Cdd:TIGR01649    7 VRNLPQD-VVEADLVEALIPFGPVSYVMMLPGKRQALVEFEDEESAKACVNFATSVPIYIRGQPA 70

RNA recognition motif 1 (RRM1) found in vertebrate matrin-3; This subgroup corresponds to the RRM1 of Matrin 3 (MATR3 or P130), a highly conserved inner nuclear matrix protein with a bipartite nuclear localization signal (NLS), two zinc finger domains predicted to bind DNA, and two RNA recognition motifs (RRM), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), that are known to interact with RNA. MATR3 has been implicated in various biological processes. It is involved in RNA processing by interacting with other nuclear proteins to anchor hyperedited RNAs to the nuclear matrix. It plays a role in mRNA stabilization through maintaining the stability of certain mRNA species. Besides, it modulates the activity of proximal promoters by binding to highly repetitive sequences of matrix/scaffold attachment region (MAR/SAR). The phosphorylation of MATR3 is assumed to cause neuronal death. It is phosphorylated by the protein kinase ATM, which activates the cellular response to double strand breaks in the DNA. Its phosphorylation by protein kinase A (PKA) is responsible for the activation of the N-methyl-d-aspartic acid (NMDA) receptor. Furthermore, MATR3 has been identified as both a Ca2+-dependent CaM-binding protein and a downstream substrate of caspases. Additional research indicates that matrin 3 also binds Rev/Rev responsive element (RRE)-containing viral RNA and functions as a cofactor that mediates the post-transcriptional regulation of HIV-1.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1958769537  794 QPFGKISDVLLVPCRNEAYLEMEFKKAVTSIMKYIETMPLVIKGKSVKV 842
Cdd:cd12714     23 EPFGIITNHLILNKINEAFIEMATTEEAQAAVDYYMTTPALVFGKPVRV 71

RNA recognition motif 1 (RRM1) found in polypyrimidine tract-binding protein 1 (PTB or hnRNP I) and similar proteins; This subfamily corresponds to the RRM1 of polypyrimidine tract-binding protein 1 (PTB or hnRNP I), polypyrimidine tract-binding protein 2 (PTBP2 or nPTB), regulator of differentiation 1 (Rod1), and similar proteins found in Metazoa. PTB is an important negative regulator of alternative splicing in mammalian cells and functions at several aspects of mRNA metabolism, including mRNA localization, stabilization, polyadenylation, and translation. PTBP2 is highly homologous to PTB and is perhaps specific to the vertebrates. Unlike PTB, PTBP2 is enriched in the brain and in some neural cell lines. It binds more stably to the downstream control sequence (DCS) RNA than PTB does but is a weaker repressor of splicing in vitro. PTBP2 also greatly enhances the binding of two other proteins, heterogeneous nuclear ribonucleoprotein (hnRNP) H and KH-type splicing-regulatory protein (KSRP), to the DCS RNA. The binding properties of PTBP2 and its reduced inhibitory activity on splicing imply roles in controlling the assembly of other splicing-regulatory proteins. PTBP2 also contains four RRMs. ROD1 coding protein Rod1 is a mammalian PTB homolog of a regulator of differentiation in the fission yeast Schizosaccharomyces pombe, where the nrd1 gene encodes an RNA binding protein and negatively regulates the onset of differentiation. ROD1 is predominantly expressed in hematopoietic cells or organs. It may play a role controlling differentiation in mammals. All members in this family contain four RNA recognition motifs (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958769537  998 VVFISNLPnkGYSTE-EIYNLAKPFGALKDILVLSSHKKAYIEIN-KKSADSMVKFYT 1053
Cdd:cd12688      2 VLHIRKLP--CDVTEaEVISLGLPFGKVTNLLMLKGKNQAFLEMAtEEAAVTMVNYYT 57

DNA topoisomerase 2-like protein; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958769537  810 EAYLEMEFKKAVTSIMKyIETMPLVIKGKSVKVcvpGKKKPQNKEMKKKPLDLKKSASALKK------ETDASKVIENVT 883
Cdd:PTZ00108  1138 EEALEEQEEVEEKEIAK-EQRLKSKTKGKASKL---RKPKLKKKEKKKKKSSADKSKKASVVgnskrvDSDEKRKLDDKP 1213

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958769537  884 SASSAKSGQIKSSTVKVNKSAGKSAGSVKSVVTVAAKGKASIKTAKSGKKSLEakKSGNIKNKD-YNKPVTVSANSEVKA 962
Cdd:PTZ00108  1214 DNKKSNSSGSDQEDDEEQKTKPKKSSVKRLKSKKNNSSKSSEDNDEFSSDDLS--KEGKPKNAPkRVSAVQYSPPPPSKR 1291

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958769537  963 SREDKATGKTAVETTSGA----LEATENEPVSKEMEEmsvvfISNLPNKGYSTEEIYNLAKPFGALK 1025
Cdd:PTZ00108  1292 PDGESNGGSKPSSPTKKKvkkrLEGSLAALKKKKKSE-----KKTARKKKSKTRVKQASASQSSRLL 1353

RNA recognition motif 1 (RRM1) found in the p54nrb/PSF/PSP1 family; This subfamily corresponds to the RRM1 of the p54nrb/PSF/PSP1 family, including 54 kDa nuclear RNA- and DNA-binding protein (p54nrb or NonO or NMT55), polypyrimidine tract-binding protein (PTB)-associated-splicing factor (PSF or POMp100), paraspeckle protein 1 (PSP1 or PSPC1), which are ubiquitously expressed and are conserved in vertebrates. p54nrb 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 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 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. This subfamily also includes some p54nrb/PSF/PSP1 homologs from invertebrate species, such as 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. All family members contain 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 module. PSF has an additional large N-terminal domain that differentiates it from other family members.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1958769537  774 LLVSELPEDgFTEEDIRKAFQPFGKISDVLLVPCRNEAYLEME 816
Cdd:cd12332      4 LFVGNLPND-ITEEEFKELFQKYGEVSEVFLNKGKGFGFIRLD 45

RNA recognition motif 2 (RRM2) found in squamous cell carcinoma antigen recognized by T-cells 3 (SART3) and similar proteins; This subfamily corresponds to the RRM2 of SART3, also termed Tat-interacting protein of 110 kDa (Tip110), is an RNA-binding protein expressed in the nucleus of the majority of proliferating cells, including normal cells and malignant cells, but not in normal tissues except for the testes and fetal liver. It is involved in the regulation of mRNA splicing probably via its complex formation with RNA-binding protein with a serine-rich domain (RNPS1), a pre-mRNA-splicing factor. SART3 has also been identified as a nuclear Tat-interacting protein that regulates Tat transactivation activity through direct interaction and functions as an important cellular factor for HIV-1 gene expression and viral replication. In addition, SART3 is required for U6 snRNP targeting to Cajal bodies. It binds specifically and directly to the U6 snRNA, interacts transiently with the U6 and U4/U6 snRNPs, and promotes the reassembly of U4/U6 snRNPs after splicing in vitro. SART3 contains an N-terminal half-a-tetratricopeptide repeat (HAT)-rich domain, a nuclearlocalization signal (NLS) domain, and two C-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958769537  774 LLVSELPEDGfTEEDIRKAFQPFGKISDVLLVPCRNE-----AYLEMEFK-KAVTSIMKYIETMplvIKGKSVKV 842
Cdd:cd12392      5 LFVKGLPFSC-TKEELEELFKQHGTVKDVRLVTYRNGkpkglAYVEYENEaDASQAVLKTDGTE---IKDHTISV 75

RNA recognition motif 1 (RRM1) found in polypyrimidine tract-binding protein 1 (PTB or hnRNP I) and similar proteins; This subfamily corresponds to the RRM1 of polypyrimidine tract-binding protein 1 (PTB or hnRNP I), polypyrimidine tract-binding protein 2 (PTBP2 or nPTB), regulator of differentiation 1 (Rod1), and similar proteins found in Metazoa. PTB is an important negative regulator of alternative splicing in mammalian cells and functions at several aspects of mRNA metabolism, including mRNA localization, stabilization, polyadenylation, and translation. PTBP2 is highly homologous to PTB and is perhaps specific to the vertebrates. Unlike PTB, PTBP2 is enriched in the brain and in some neural cell lines. It binds more stably to the downstream control sequence (DCS) RNA than PTB does but is a weaker repressor of splicing in vitro. PTBP2 also greatly enhances the binding of two other proteins, heterogeneous nuclear ribonucleoprotein (hnRNP) H and KH-type splicing-regulatory protein (KSRP), to the DCS RNA. The binding properties of PTBP2 and its reduced inhibitory activity on splicing imply roles in controlling the assembly of other splicing-regulatory proteins. PTBP2 also contains four RRMs. ROD1 coding protein Rod1 is a mammalian PTB homolog of a regulator of differentiation in the fission yeast Schizosaccharomyces pombe, where the nrd1 gene encodes an RNA binding protein and negatively regulates the onset of differentiation. ROD1 is predominantly expressed in hematopoietic cells or organs. It may play a role controlling differentiation in mammals. All members in this family contain four RNA recognition motifs (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1958769537 1101 RFVHLDNLPEDGLQC-VLCVGHQFGKVDRYVFMSNRNKVILQLESPESALSMYNF 1154
Cdd:cd12688      1 RVLHIRKLPCDVTEAeVISLGLPFGKVTNLLMLKGKNQAFLEMATEEAAVTMVNY 55

RNA recognition motif 1 (RRM1) found in vertebrate regulator of differentiation 1 (Rod1); This subgroup corresponds to the RRM1 of ROD1 coding protein Rod1, a mammalian polypyrimidine tract binding protein (PTB) homolog of a regulator of differentiation in the fission yeast Schizosaccharomyces pombe, where the nrd1 gene encodes an RNA binding protein that negatively regulates the onset of differentiation. ROD1 is predominantly expressed in hematopoietic cells or organs. It might play a role controlling differentiation in mammals. Rod1 contains four repeats of RNA recognition motifs (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain) and does have RNA binding activities.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958769537  998 VVFISNLPNKgYSTEEIYNLAKPFGALKDILVLSSHKKAYIEI-NKKSADSMVKFYTCFP 1056
Cdd:cd12779      7 VLHIRKIPND-VTEAEVISLGLPFGKVTNLLMLKGKNQAFLEMaSEEAAVTMVNYYTTVT 65

adenylate kinase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958769537  861 DLKKSASALKKETDASKVIENVTSASSAKSGQIKSSTVKVNKSAGKSAGSVKSVVTVAAKgKASIKTAKSGKKSleAKKS 940
Cdd:PRK13808   198 NAKKAAKTPAAKSGAKKASAKAKSAAKKVSKKKAAKTAVSAKKAAKTAAKAAKKAKKTAK-KALKKAAKAVKKA--AKKA 274

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1958769537  941 GniknKDYNKPVTVSANSEVKASREDKATGKTAVETTSGALEATENEPVSK 991
Cdd:PRK13808   275 A----KAAAKAAKGAAKATKGKAKAKKKAGKKAAAGSKAKATAKAPKRGAK 321

adenylate kinase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958769537  846 GKKKPQNKEMKKKPLDLKKSASALKKETDASKVIENVTSASSAKSGQIKSSTVKVNKSAGKSAG--SVKSVVTVAAKG-K 922
Cdd:PRK13808   197 ANAKKAAKTPAAKSGAKKASAKAKSAAKKVSKKKAAKTAVSAKKAAKTAAKAAKKAKKTAKKALkkAAKAVKKAAKKAaK 276

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1958769537  923 ASIKTAKSGKKSLEAKKSGNIKNKDYNKPVTvSANSEVKASREdKATGKTAVETT 977
Cdd:PRK13808   277 AAAKAAKGAAKATKGKAKAKKKAGKKAAAGS-KAKATAKAPKR-GAKGKKAKKVT 329