MARF1 LOTUS domain; This is the LOTUS domain which is repeated in the C-terminal of of Meiosis regulator and mRNA stability factor 1 (MARF1) protein, an essential regulator of oogenesis required for completion of meiosis and retrotransposon silencing, key to maintain germline integrity. This domain provides RNA-binding properties to this protein, acting as an adapter to recruit targets for the effector domain NYN (pfam01936) at the N-terminal (RNase activity).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034596735  735 LLSAETMSVLQDAPACCLPLFKFTDIYEKKFGHKLNVSDLYKLTDTVAIREQGNGRLVCLLPSSQARQSPLGSSQSHDGS 814
Cdd:pfam19687    1 LLSSETISILQDAPACCLPLFKFTEIYEKKFGHKLIVSDLYKLTDTVAIREQGNGRLVCLLPSSQARQSPLGSSQSHDGS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034596735  815 STNCSPIIFEELEYHEPVCRQHCSNKDFSEHEFDPDSYKIPFVILSLKTFAPQVHSLLQTHEGTVPLLSFPDCYIAEFGD 894
Cdd:pfam19687   81 SANGSPIIFEELEYHEPVCRQHCLNKDFSEHEFDPDSYQIPFVILSLKTFAPQVHSLLQTHEGTVPLLSFPECYAAKFSP 160

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1034596735  895 LEVVQENQGGVPLEHFITCVPGVNIATAQNGIKVVKWIHNKPPPPNTDPWL 945
Cdd:pfam19687  161 LQLGSETMEGVPLEHLITCVPSITIVTAQNGFKVIKWIHNKPPPPNTDPWL 211

The third LOTUS domain on Limkain b1(LKAP); The third LOTUS domain on Limkain b1(LKAP): Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. The protein contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be identified. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034596735  957 LIQFSREVIDLLKSQPSCVIPISHFIPSYHHHFAKQCRVSDYGYSKLIELLEAVPHVLQILGMGSKRLLTLT 1028
Cdd:cd09979      1 LIQFSREVIDLLKSQPSCLLPFSRFIPAYHHHFGKQCRVSDYGYTKLIELLEAVPHVLQILGMGSKRLLTLS 72

The fifth LOTUS domain on Limkain b1(LKAP); The fifth LOTUS domain on Limkain b1(LKAP): Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. The protein contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be identified. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034596735 1117 TKQFSKDVVDLLRHQPHFRMPFNKFIPSYHHHFGRQCKLAYYGFTKLLELFEAIPDTLQVLECGEEKILTL 1187
Cdd:cd09981      1 TKQFSKEVVELLRHQPHFRMPFTKFIPSYHHHFGRQCKLSYYGFTKLLELFEAIPDVVQVLECGEEKYLQL 71

The seventh LOTUS domain on Limkain b1(LKAP); The seventh LOTUS domain on Limkain b1(LKAP): Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. The protein contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be identified. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034596735 1269 LRSLTAQLLVLLMSWEGTTHLSVEELKRHYESTHNTPLNPCEYGFMTLTELLKSLPYLVEVFTNDKMEECVKL 1341
Cdd:cd09983      1 LRSLTAQLLVLLMSWEGASDLSVEELRQHYESVHGTPLNPCEYGFMSLTELLKSLPYLVEVFTNGGGEEYVRL 73

N-terminal LabA-like PIN domain of limkain b1 and similar proteins; Limkain b1 is a human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. Limkain b1 contains multiple copies of LOTUS domains and a conserved RNA recognition motif, this and similar domain architectures are shared by several members of this family, and a function of these architectures in RNA binding or RNA metabolism has been suggested. The function of the N-terminal domain is unknown. This subfamily belongs to LabA-like PIN domain family which includes Synechococcus elongatus PCC 7942 LabA, human ZNF451, uncharacterized Bacillus subtilis YqxD and Escherichia coli YaiI, and the N-terminal domain of a well-conserved group of mainly bacterial proteins with no defined function, which contain a C-terminal LabA_like_C domain. Curiously, a gene labeled NicB from Pseudomonas putida S16, which is described as a putative NADH-dependent hydroxylase involved in the microbial degradation of nicotine also falls into the LabA-like PIN family. The PIN (PilT N terminus) domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its active center, consisting of three highly conserved catalytic residues which coordinate metal ions; in some members, additional metal coordinating residues can be found while some others lack several of these key catalytic residues. The PIN active site is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034596735  352 PIGVFWDIENCSVPSGRSATAVVQRIREKFFK--GHREAEFICVCDISKENKEVIQELNNCQVTVAHINATAKNAADDKL 429
Cdd:cd10910      1 KTGVFWDIENCPVPDGYDARRVGPNIRRALRKlgYSGPVSITAYGDLSKVPKDVLSELSSSGVSLVHVPHGGKKAADKKI 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1034596735  430 RQSLRRFANTHTAPATVVLVSTDV-NFALELSDLRHRhGFHIILVH 474
Cdd:cd10910     81 LVDMLLWALDNPPPANIMLISGDVrDFAYALSRLRSR-GYNVLLAY 125

MARF1 LOTUS domain; This is the LOTUS domain which is repeated in the C-terminal of of Meiosis regulator and mRNA stability factor 1 (MARF1) protein, an essential regulator of oogenesis required for completion of meiosis and retrotransposon silencing, key to maintain germline integrity. This domain provides RNA-binding properties to this protein, acting as an adapter to recruit targets for the effector domain NYN (pfam01936) at the N-terminal (RNase activity).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034596735  735 LLSAETMSVLQDAPACCLPLFKFTDIYEKKFGHKLNVSDLYKLTDTVAIREQGNGRLVCLLPSSQARQSPLGSSQSHDGS 814
Cdd:pfam19687    1 LLSSETISILQDAPACCLPLFKFTEIYEKKFGHKLIVSDLYKLTDTVAIREQGNGRLVCLLPSSQARQSPLGSSQSHDGS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034596735  815 STNCSPIIFEELEYHEPVCRQHCSNKDFSEHEFDPDSYKIPFVILSLKTFAPQVHSLLQTHEGTVPLLSFPDCYIAEFGD 894
Cdd:pfam19687   81 SANGSPIIFEELEYHEPVCRQHCLNKDFSEHEFDPDSYQIPFVILSLKTFAPQVHSLLQTHEGTVPLLSFPECYAAKFSP 160

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1034596735  895 LEVVQENQGGVPLEHFITCVPGVNIATAQNGIKVVKWIHNKPPPPNTDPWL 945
Cdd:pfam19687  161 LQLGSETMEGVPLEHLITCVPSITIVTAQNGFKVIKWIHNKPPPPNTDPWL 211

The second LOTUS domain on Limkain b1(LKAP); The second LOTUS domain on Limkain b1(LKAP): Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. The protein contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be identified. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034596735  861 LKTFAPQVHSLLQTHEGTVPLLSFPDCYIAEFGDLEVVQENQGGVPLEHFITCVPGVNIATAQNGIKVVKW 931
Cdd:cd09978      1 LKTFAPQVHSLLQTHEGTVPLLSFPDCYAAEFSALEVVQEGQGGVPLEHLITCIPGVNIATAQNGIKVIKW 71

RNA recognition motif 2 (RRM2) found in Limkain-b1 (LKAP) and similar proteins; This subfamily corresponds to the RRM2 of LKAP, a novel peroxisomal autoantigen that co-localizes with a subset of cytoplasmic microbodies marked by ABCD3 (ATP-binding cassette subfamily D member 3, known previously as PMP-70) and/or PXF (peroxisomal farnesylated protein, known previously as PEX19). It associates with LIM kinase 2 (LIMK2) and may serve as a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. LKAP contains two RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). However, whether those RRMs are bona fide RNA binding sites remains unclear. Moreover, there is no evidence of LAKP localization in the nucleus. Therefore, if the RRMs are functional, their interaction with RNA species would be restricted to the cytoplasm and peroxisomes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034596735  644 FANGADVQVSNIDYRLSRKELQQLLQEAFARHGKVKSVELSPHTDYQLKAVVQMENLQDAIGAVNSLHRYKIGSKKILVS 723
Cdd:cd12256      1 FSNGVDLQVSNLDYRMSRKELQQMLHNQFKRHGKVKSVELSPQTDGSLKASVRVPSLQDAQYAVSQLHRYKIGSKRIQVS 80

                   ....*....
gi 1034596735  724 LATGAASKS 732
Cdd:cd12256     81 LATGSSNKS 89

The fourth LOTUS domain on Limkain b1(LKAP); The fourth LOTUS domain on Limkain b1(LKAP): Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. The protein contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be identified. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034596735 1033 VKRFTQDLLKLLKSQASKQVIVREFSQAYHWCFSKDWDVTEYGVCELIDIVSEIPDTTICLSQQDNEMVICI 1104
Cdd:cd09980      1 VRRFTQDLLRVLKSQASKQVIVKDFGQAYEWCFGRDWDPVDYGLCDLQDLLSEIPDNTIVIEQQDGDKVISI 72

The sixth LOTUS domain on Limkain b1(LKAP); The sixth LOTUS domain on Limkain b1(LKAP): Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. The protein contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be identified. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034596735 1193 FKALAAQFVKLLRSQKDNCLMMTDLLTEYAKTFGYTFRLQDYDVSSISALTQKLCHVVKVADIESGRQIQL 1263
Cdd:cd09982      1 VKALAAQLVKLLRSQKDSCLMMCDLLTEYSKTFGYTLRLQDYDVSSVPALMQKLCHVVKVVDTESGKQIQL 71

NYN domain; These domains are found in the eukaryotic proteins typified by the Nedd4-binding protein 1 and the bacterial YacP-like proteins (Nedd4-BP1, YacP nucleases; NYN domains). The NYN domain shares a common protein fold with two other previously characterized groups of nucleases, namely the PIN (PilT N-terminal) and FLAP/5' --> 3' exonuclease superfamilies. These proteins share a common set of 4 acidic conserved residues that are predicted to constitute their active site. Based on the conservation of the acidic residues and structural elements Aravind and colleagues suggest that PIN and NYN domains are likely to bind only a single metal ion, unlike the FLAP/5' --> 3' exonuclease superfamily, which binds two metal ions. Based on conserved gene neighborhoods Aravind and colleagues infer that the bacterial members are likely to be components of the processome/degradsome that process tRNAs or ribosomal RNAs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034596735  352 PIGVFWDIENCSVPSGRSATAVVQRIREkffkgHREA-EFICVCDISKEN-KEVIQELNNCQVTVAHINAT-AKNAADDK 428
Cdd:pfam01936    1 RVAVFIDGENCPLPDGVDYRKVLEEIRS-----GGEVvRARAYGNWGDPDlRKFPDALSSTGIPVQHKPLTkGKNAVDVG 75

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034596735  429 LRQSLRRFANTHTaPATVVLVSTDVNFALELSDLRHRHGF-HIILVHKNQASEALLHHANELI 490
Cdd:pfam01936   76 LAVDALELAYDNN-PDTFVLVSGDGDFAPLLERLRERGKRvEVLGAEEPSTSDALINAADRFI 137

OST-HTH/LOTUS domain; A predicted RNA-binding domain found in insect Oskar and vertebrate TDRD5/TDRD7 proteins that nucleate or organize structurally related ribonucleoprotein (RNP) complexes, the polar granule and nuage, is poorly understood. The domain adopts the winged helix-turn- helix fold and bind RNA with a potential specificity for dsRNA.In eukaryotes this domain is often combined in the same polypeptide with protein-protein- or lipid- interaction domains that might play a role in anchoring these proteins to specific cytoskeletal structures. Thus, proteins with this domain might have a key role in the recognition and localization of dsRNA, including miRNAs, rasiRNAs and piRNAs hybridized to their targets. In other cases, this domain is fused to ubiquitin-binding, E3 ligase and ubiquitin-like domains indicating a previously under-appreciated role for ubiquitination in regulating the assembly and stability of nuage-like RNP complexes. Both bacteria and eukaryotes encode a conserved family of proteins that combines this predicted RNA-binding domain with a previously uncharacterized RNase domain belonging to the superfamily that includes the 5'->3' nucleases, PIN and NYN domains.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034596735  963 EVIDLLKSQPSCVIPISHFIPSYHHHFAKQCRVSDYGYSKLIELLEAVPHVLQILGMGSKRLLT 1026
Cdd:pfam12872    1 ELISLLRSDPDGWASLSELGSEYRKLFGEDFDPRNYGFSKLSDLLKAIPDVFEIEKRGGGGLVV 64

OST-HTH/LOTUS domain; A predicted RNA-binding domain found in insect Oskar and vertebrate TDRD5/TDRD7 proteins that nucleate or organize structurally related ribonucleoprotein (RNP) complexes, the polar granule and nuage, is poorly understood. The domain adopts the winged helix-turn- helix fold and bind RNA with a potential specificity for dsRNA.In eukaryotes this domain is often combined in the same polypeptide with protein-protein- or lipid- interaction domains that might play a role in anchoring these proteins to specific cytoskeletal structures. Thus, proteins with this domain might have a key role in the recognition and localization of dsRNA, including miRNAs, rasiRNAs and piRNAs hybridized to their targets. In other cases, this domain is fused to ubiquitin-binding, E3 ligase and ubiquitin-like domains indicating a previously under-appreciated role for ubiquitination in regulating the assembly and stability of nuage-like RNP complexes. Both bacteria and eukaryotes encode a conserved family of proteins that combines this predicted RNA-binding domain with a previously uncharacterized RNase domain belonging to the superfamily that includes the 5'->3' nucleases, PIN and NYN domains.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034596735 1123 DVVDLLRHQPHFRMPFNKFIPSYHHHFGRQCKLAYYGFTKLLELFEAIPDTLQVLECGEEKILT 1186
Cdd:pfam12872    1 ELISLLRSDPDGWASLSELGSEYRKLFGEDFDPRNYGFSKLSDLLKAIPDVFEIEKRGGGGLVV 64

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034596735  652 VSNIDYRLSRKELQQLlqeaFARHGKVKSVELSPHTDYQLK--AVVQMENLQDAIGAVNSLHRYKIGSKKIL 721
Cdd:pfam00076    3 VGNLPPDTTEEDLKDL----FSKFGPIKSIRLVRDETGRSKgfAFVEFEDEEDAEKAIEALNGKELGGRELK 70

MARF1 LOTUS domain; This is the LOTUS domain which is repeated in the C-terminal of of Meiosis regulator and mRNA stability factor 1 (MARF1) protein, an essential regulator of oogenesis required for completion of meiosis and retrotransposon silencing, key to maintain germline integrity. This domain provides RNA-binding properties to this protein, acting as an adapter to recruit targets for the effector domain NYN (pfam01936) at the N-terminal (RNase activity).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034596735  735 LLSAETMSVLQDAPACCLPLFKFTDIYEKKFGHKLNVSDLYKLTDTVAIREQGNGRLVCLLPSSQARQSPLGSSQSHDGS 814
Cdd:pfam19687    1 LLSSETISILQDAPACCLPLFKFTEIYEKKFGHKLIVSDLYKLTDTVAIREQGNGRLVCLLPSSQARQSPLGSSQSHDGS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034596735  815 STNCSPIIFEELEYHEPVCRQHCSNKDFSEHEFDPDSYKIPFVILSLKTFAPQVHSLLQTHEGTVPLLSFPDCYIAEFGD 894
Cdd:pfam19687   81 SANGSPIIFEELEYHEPVCRQHCLNKDFSEHEFDPDSYQIPFVILSLKTFAPQVHSLLQTHEGTVPLLSFPECYAAKFSP 160

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1034596735  895 LEVVQENQGGVPLEHFITCVPGVNIATAQNGIKVVKWIHNKPPPPNTDPWL 945
Cdd:pfam19687  161 LQLGSETMEGVPLEHLITCVPSITIVTAQNGFKVIKWIHNKPPPPNTDPWL 211

The second LOTUS domain on Limkain b1(LKAP); The second LOTUS domain on Limkain b1(LKAP): Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. The protein contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be identified. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034596735  861 LKTFAPQVHSLLQTHEGTVPLLSFPDCYIAEFGDLEVVQENQGGVPLEHFITCVPGVNIATAQNGIKVVKW 931
Cdd:cd09978      1 LKTFAPQVHSLLQTHEGTVPLLSFPDCYAAEFSALEVVQEGQGGVPLEHLITCIPGVNIATAQNGIKVIKW 71

RNA recognition motif 2 (RRM2) found in Limkain-b1 (LKAP) and similar proteins; This subfamily corresponds to the RRM2 of LKAP, a novel peroxisomal autoantigen that co-localizes with a subset of cytoplasmic microbodies marked by ABCD3 (ATP-binding cassette subfamily D member 3, known previously as PMP-70) and/or PXF (peroxisomal farnesylated protein, known previously as PEX19). It associates with LIM kinase 2 (LIMK2) and may serve as a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. LKAP contains two RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). However, whether those RRMs are bona fide RNA binding sites remains unclear. Moreover, there is no evidence of LAKP localization in the nucleus. Therefore, if the RRMs are functional, their interaction with RNA species would be restricted to the cytoplasm and peroxisomes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034596735  644 FANGADVQVSNIDYRLSRKELQQLLQEAFARHGKVKSVELSPHTDYQLKAVVQMENLQDAIGAVNSLHRYKIGSKKILVS 723
Cdd:cd12256      1 FSNGVDLQVSNLDYRMSRKELQQMLHNQFKRHGKVKSVELSPQTDGSLKASVRVPSLQDAQYAVSQLHRYKIGSKRIQVS 80

                   ....*....
gi 1034596735  724 LATGAASKS 732
Cdd:cd12256     81 LATGSSNKS 89

The fourth LOTUS domain on Limkain b1(LKAP); The fourth LOTUS domain on Limkain b1(LKAP): Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. The protein contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be identified. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034596735 1033 VKRFTQDLLKLLKSQASKQVIVREFSQAYHWCFSKDWDVTEYGVCELIDIVSEIPDTTICLSQQDNEMVICI 1104
Cdd:cd09980      1 VRRFTQDLLRVLKSQASKQVIVKDFGQAYEWCFGRDWDPVDYGLCDLQDLLSEIPDNTIVIEQQDGDKVISI 72

The sixth LOTUS domain on Limkain b1(LKAP); The sixth LOTUS domain on Limkain b1(LKAP): Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. The protein contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be identified. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034596735 1193 FKALAAQFVKLLRSQKDNCLMMTDLLTEYAKTFGYTFRLQDYDVSSISALTQKLCHVVKVADIESGRQIQL 1263
Cdd:cd09982      1 VKALAAQLVKLLRSQKDSCLMMCDLLTEYSKTFGYTLRLQDYDVSSVPALMQKLCHVVKVVDTESGKQIQL 71

The first LOTUS domain on Limkain b1(LKAP); The first LOTUS domain on Limkain b1(LKAP): Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. The protein contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be identified. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034596735  733 LSLLSAETMSVLQDAPACCLPLFKFTDIYEKKFGHKLNVSDLYKLTDTVAIREQGNGRLVCL 794
Cdd:cd09977      1 LSLLSSETVSILQDAPACCLPLFKFTEIYEKKFGHKLAVSDLYRLTDTVAIREQGGGRLVCL 62

The fifth LOTUS domain on Limkain b1(LKAP); The fifth LOTUS domain on Limkain b1(LKAP): Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. The protein contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be identified. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034596735  959 QFSREVIDLLKSQPSCVIPISHFIPSYHHHFAKQCRVSDYGYSKLIELLEAVPHVLQILGMGSKRLLTL 1027
Cdd:cd09981      3 QFSKEVVELLRHQPHFRMPFTKFIPSYHHHFGRQCKLSYYGFTKLLELFEAIPDVVQVLECGEEKYLQL 71

NYN domain; These domains are found in the eukaryotic proteins typified by the Nedd4-binding protein 1 and the bacterial YacP-like proteins (Nedd4-BP1, YacP nucleases; NYN domains). The NYN domain shares a common protein fold with two other previously characterized groups of nucleases, namely the PIN (PilT N-terminal) and FLAP/5' --> 3' exonuclease superfamilies. These proteins share a common set of 4 acidic conserved residues that are predicted to constitute their active site. Based on the conservation of the acidic residues and structural elements Aravind and colleagues suggest that PIN and NYN domains are likely to bind only a single metal ion, unlike the FLAP/5' --> 3' exonuclease superfamily, which binds two metal ions. Based on conserved gene neighborhoods Aravind and colleagues infer that the bacterial members are likely to be components of the processome/degradsome that process tRNAs or ribosomal RNAs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034596735  352 PIGVFWDIENCSVPSGRSATAVVQRIREkffkgHREA-EFICVCDISKEN-KEVIQELNNCQVTVAHINAT-AKNAADDK 428
Cdd:pfam01936    1 RVAVFIDGENCPLPDGVDYRKVLEEIRS-----GGEVvRARAYGNWGDPDlRKFPDALSSTGIPVQHKPLTkGKNAVDVG 75

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034596735  429 LRQSLRRFANTHTaPATVVLVSTDVNFALELSDLRHRHGF-HIILVHKNQASEALLHHANELI 490
Cdd:pfam01936   76 LAVDALELAYDNN-PDTFVLVSGDGDFAPLLERLRERGKRvEVLGAEEPSTSDALINAADRFI 137

LOTUS is an uncharacterized small globular domain found in Limkain b1, Oskar and Tudor-containing proteins 5 and 7; LOTUS is an uncharacterized small globular domain found in Limkain b1, Oskar and Tudor-containing proteins 5 and 7. The LOTUS containing proteins are germline-specific and are found in the nuage/polar granules of germ cells. Tudor-containing protein 5 and 7 belong to the evolutionary conserved Tudor domain-containing protein (TDRD) family involved in germ cell development. In mice, TDRD5 and TDRD7 are components of the intermitochondrial cements (IMCs) and the chromatoid bodies (CBs), which are cytoplasmic ribonucleoprotein granules involved in RNA processing for spermatogenesis. Oskar protein is a critical component of the pole plasm in the Drosophila oocyte, which is required for germ cell formation. Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. Limkain b1 contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be characterized. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034596735 1117 TKQFSKDVVDLLRHQPHfRMPFNKFIPSYHHHFGRQCKLAYYGFTKLLELFEAIPDTLQVLECGEEKILTL 1187
Cdd:cd08824      1 LKQLAKQLRSLLQSYPG-GLPLSKLPQLYKKKFGKPLDLSEYGFSKLSDLLEALPGVVIVLSQGGERIVSL 70

LOTUS is an uncharacterized small globular domain found in Limkain b1, Oskar and Tudor-containing proteins 5 and 7; LOTUS is an uncharacterized small globular domain found in Limkain b1, Oskar and Tudor-containing proteins 5 and 7. The LOTUS containing proteins are germline-specific and are found in the nuage/polar granules of germ cells. Tudor-containing protein 5 and 7 belong to the evolutionary conserved Tudor domain-containing protein (TDRD) family involved in germ cell development. In mice, TDRD5 and TDRD7 are components of the intermitochondrial cements (IMCs) and the chromatoid bodies (CBs), which are cytoplasmic ribonucleoprotein granules involved in RNA processing for spermatogenesis. Oskar protein is a critical component of the pole plasm in the Drosophila oocyte, which is required for germ cell formation. Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. Limkain b1 contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be characterized. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034596735 1033 VKRFTQDLLKLLKSQaSKQVIVREFSQAYHWCFSKDWDVTEYGVCELIDIVSEIPDTTICLSQQDNEMVIC 1103
Cdd:cd08824      1 LKQLAKQLRSLLQSY-PGGLPLSKLPQLYKKKFGKPLDLSEYGFSKLSDLLEALPGVVIVLSQGGERIVSL 70

LOTUS is an uncharacterized small globular domain found in Limkain b1, Oskar and Tudor-containing proteins 5 and 7; LOTUS is an uncharacterized small globular domain found in Limkain b1, Oskar and Tudor-containing proteins 5 and 7. The LOTUS containing proteins are germline-specific and are found in the nuage/polar granules of germ cells. Tudor-containing protein 5 and 7 belong to the evolutionary conserved Tudor domain-containing protein (TDRD) family involved in germ cell development. In mice, TDRD5 and TDRD7 are components of the intermitochondrial cements (IMCs) and the chromatoid bodies (CBs), which are cytoplasmic ribonucleoprotein granules involved in RNA processing for spermatogenesis. Oskar protein is a critical component of the pole plasm in the Drosophila oocyte, which is required for germ cell formation. Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. Limkain b1 contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be characterized. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034596735 1269 LRSLTAQLLVLLMSWEGTthLSVEELKRHYESTHNTPLNPCEYGFMTLTELLKSLPYLVEVFTNDkMEECVKL 1341
Cdd:cd08824      1 LKQLAKQLRSLLQSYPGG--LPLSKLPQLYKKKFGKPLDLSEYGFSKLSDLLEALPGVVIVLSQG-GERIVSL 70

LOTUS is an uncharacterized small globular domain found in Limkain b1, Oskar and Tudor-containing proteins 5 and 7; LOTUS is an uncharacterized small globular domain found in Limkain b1, Oskar and Tudor-containing proteins 5 and 7. The LOTUS containing proteins are germline-specific and are found in the nuage/polar granules of germ cells. Tudor-containing protein 5 and 7 belong to the evolutionary conserved Tudor domain-containing protein (TDRD) family involved in germ cell development. In mice, TDRD5 and TDRD7 are components of the intermitochondrial cements (IMCs) and the chromatoid bodies (CBs), which are cytoplasmic ribonucleoprotein granules involved in RNA processing for spermatogenesis. Oskar protein is a critical component of the pole plasm in the Drosophila oocyte, which is required for germ cell formation. Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. Limkain b1 contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be characterized. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034596735  861 LKTFAPQVHSLLQTHEGTVPLLSFPDCYIAEFGDLEVVQEnQGGVPLEHFITCVPGVNIATAQNGIKVVKW 931
Cdd:cd08824      1 LKQLAKQLRSLLQSYPGGLPLSKLPQLYKKKFGKPLDLSE-YGFSKLSDLLEALPGVVIVLSQGGERIVSL 70

OST-HTH/LOTUS domain; A predicted RNA-binding domain found in insect Oskar and vertebrate TDRD5/TDRD7 proteins that nucleate or organize structurally related ribonucleoprotein (RNP) complexes, the polar granule and nuage, is poorly understood. The domain adopts the winged helix-turn- helix fold and bind RNA with a potential specificity for dsRNA.In eukaryotes this domain is often combined in the same polypeptide with protein-protein- or lipid- interaction domains that might play a role in anchoring these proteins to specific cytoskeletal structures. Thus, proteins with this domain might have a key role in the recognition and localization of dsRNA, including miRNAs, rasiRNAs and piRNAs hybridized to their targets. In other cases, this domain is fused to ubiquitin-binding, E3 ligase and ubiquitin-like domains indicating a previously under-appreciated role for ubiquitination in regulating the assembly and stability of nuage-like RNP complexes. Both bacteria and eukaryotes encode a conserved family of proteins that combines this predicted RNA-binding domain with a previously uncharacterized RNase domain belonging to the superfamily that includes the 5'->3' nucleases, PIN and NYN domains.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034596735 1275 QLLVLLMSW-EGTTHLSveELKRHYESTHNTPLNPCEYGFMTLTELLKSLPYLVEVFTNDKMEECV 1339
Cdd:pfam12872    1 ELISLLRSDpDGWASLS--ELGSEYRKLFGEDFDPRNYGFSKLSDLLKAIPDVFEIEKRGGGGLVV 64

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 1034596735  650 VQVSNIDYRLSRKELQQLlqeaFARHGKVKSVELSPHTDYQLK--AVVQMENLQDAIGAVNSLHRYKIGSKKILVS 723
Cdd:cd00590      1 LFVGNLPPDTTEEDLREL----FSKFGEVVSVRIVRDRDGKSKgfAFVEFESPEDAEKALEALNGTELGGRPLKVS 72

LOTUS is an uncharacterized small globular domain found in Limkain b1, Oskar and Tudor-containing proteins 5 and 7; LOTUS is an uncharacterized small globular domain found in Limkain b1, Oskar and Tudor-containing proteins 5 and 7. The LOTUS containing proteins are germline-specific and are found in the nuage/polar granules of germ cells. Tudor-containing protein 5 and 7 belong to the evolutionary conserved Tudor domain-containing protein (TDRD) family involved in germ cell development. In mice, TDRD5 and TDRD7 are components of the intermitochondrial cements (IMCs) and the chromatoid bodies (CBs), which are cytoplasmic ribonucleoprotein granules involved in RNA processing for spermatogenesis. Oskar protein is a critical component of the pole plasm in the Drosophila oocyte, which is required for germ cell formation. Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. Limkain b1 contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be characterized. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034596735  733 LSLLSAETMSVLQDAPaCCLPLFKFTDIYEKKFGHKLNVSD---------LYKLTDTVAIREQGNGRLVCL 794
Cdd:cd08824      1 LKQLAKQLRSLLQSYP-GGLPLSKLPQLYKKKFGKPLDLSEygfsklsdlLEALPGVVIVLSQGGERIVSL 70

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034596735  652 VSNIDYRLSRKELQQLlqeaFARHGKVKSVELSPHTDYQLK--AVVQMENLQDAIGAVNSLHRYKIGSKKIL 721
Cdd:pfam00076    3 VGNLPPDTTEEDLKDL----FSKFGPIKSIRLVRDETGRSKgfAFVEFEDEEDAEKAIEALNGKELGGRELK 70

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        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034596735  650 VQVSNIDYRLSRKELQQLlqeaFARHGKVKSVEL--SPHTDYQLKAVVQMENLQDAIGAVNSLHRYKIGSKKILVSL 724
Cdd:cd12418      3 VRVSNLHPDVTEEDLREL----FGRVGPVKSVKInyDRSGRSTGTAYVVFERPEDAEKAIKQFDGVLLDGQPMKVEL 75

The third LOTUS domain on Limkain b1(LKAP); The third LOTUS domain on Limkain b1(LKAP): Limkain b1 is a novel human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. The protein contains multiple copies of LOTUS domains and a conserved RNA recognition motif. The exact molecular function of LOTUS domain remains to be identified. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034596735 1344 LYLFAKNVRSLLHTYHYQQIFLHEFSMAYTKYVGETLQPKTYGHSSVEELLGAIPQVVWIKGHGHKRIVVL 1414
Cdd:cd09979      1 LIQFSREVIDLLKSQPSCLLPFSRFIPAYHHHFGKQCRVSDYGYTKLIELLEAVPHVLQILGMGSKRLLTL 71

The second LOTUS domain on Tudor-containing protein 5 (TDRD5); The second LOTUS domain on Tudor-containing protein 5 (TDRD5): TDRD5 contains three N-terminal LOTUS domains and a C-terminal Tudor domain. It belongs to the evolutionary conserved Tudor domain-containing protein (TDRD) family involved in germ cell development. In mice TDRD5 is a component of the intermitochondrial cements (IMCs) and the chromatoid bodies (CBs), which are cytoplasmic ribonucleoprotein granules involved in RNA processing for spermatogenesis. The exact molecular function of LOTUS domain on TDRD5 remains to be discovered. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034596735 1122 KDVVDLLRHQPHFRMPFNKfipSYHHHFGRQCKLAYYGFTKLLELFEAIPDTLQVLECGEEKILTL 1187
Cdd:cd09975      6 SELKDLLSHSPVLLSELEK---AYVARFGRSFQYTQYGFFSMLEVLSAASDFIIVKQTRTGSLLLL 68

The first LOTUS domain in Oskar and Tudor-containing proteins 5 and 7; The first LOTUS domain in Oskar and Tudor-containing proteins 5 and 7: The LOTUS containing proteins are germline-specific and are found in the nuage/polar granules of germ cells. Tudor-containing protein 5 and 7 belong to the evolutionary conserved Tudor domain-containing protein (TDRD) family involved in germ cell development. In mice, TDRD5 and TDRD7 are components of the intermitochondrial cements (IMCs) and the chromatoid bodies (CBs), which are cytoplasmic ribonucleoprotein granules involved in RNA processing for spermatogenesis. Oskar protein is a critical component of the pole plasm in the Drosophila oocyte, which is required for germ cell formation.The exact molecular function of LOTUS domain remains to be identified. Its occurrence in proteins associated with RNA metabolism suggests that it might be involved in RNA binding function. The presence of several basic residues and RNA fold recognition motifs support this hypothesis. The RNA binding function might be the first step of regulating mRNA translation or localization.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034596735 1349 KNVRSLLHTyHYQQIFLHEFSMAYTKYVGETLQPKTYGHSSVEELLGAIPQVVWIKGHGHKRIVVLKNDMK 1419
Cdd:cd09972      6 KVLRSLLIS-SKGGLTLSELERDYRELEGEPIPYRKLGYSSLEDFLRSIPDVVTVRSSGGEVLVKAVADEK 75

RNA recognition motif 1 (RRM1) and 2 (RRM2) found in RRM-containing coactivator activator/modulator (CoAA) and similar proteins; This subfamily corresponds to the RRM in CoAA (also known as RBM14 or PSP2) and RNA-binding protein 4 (RBM4). CoAA is a heterogeneous nuclear ribonucleoprotein (hnRNP)-like protein identified as a nuclear receptor coactivator. It mediates transcriptional coactivation and RNA splicing effects in a promoter-preferential manner, and is enhanced by thyroid hormone receptor-binding protein (TRBP). CoAA contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a TRBP-interacting domain. RBM4 is a ubiquitously expressed splicing factor with two isoforms, RBM4A (also known as Lark homolog) and RBM4B (also known as RBM30), which are very similar in structure and sequence. RBM4 may also function as a translational regulator of stress-associated mRNAs as well as play a role in micro-RNA-mediated gene regulation. RBM4 contains two N-terminal RRMs, a CCHC-type zinc finger, and three alanine-rich regions within their C-terminal regions. This family also includes Drosophila RNA-binding protein lark (Dlark), a homolog of human RBM4. It plays an important role in embryonic development and in the circadian regulation of adult eclosion. Dlark shares high sequence similarity with RBM4 at the N-terminal region. However, Dlark has three proline-rich segments instead of three alanine-rich segments within the C-terminal region.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034596735  652 VSNIDYRLSRKELQQLlqeaFARHGKVksVELSPHTDYqlkAVVQMENLQDAIGAVNSLHRYKIGSKKILV 722
Cdd:cd12343      4 VGNLPDAATSEELRAL----FEKYGKV--TECDIVKNY---AFVHMEKEEDAEDAIKALNGYEFMGSRINV 65