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 71891770    642 LLSAETMSVLQDAPACCLPLFKFTDIYEKKFGHKLNVSDLYKLTDTVAIREQGNGRLVCLLPSRQARQSPLGSSQSHDGS 721
Cdd:pfam19687    1 LLSSETISILQDAPACCLPLFKFTEIYEKKFGHKLIVSDLYKLTDTVAIREQGNGRLVCLLPSSQARQSPLGSSQSHDGS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71891770    722 STNCSPIIFEELEYHEPVCRQHCSNKDFSEHEFDPDSYKIPFVILSLKTFAPQVHSLLQTHEGTVPLLSFPDCYIAEFGD 801
Cdd:pfam19687   81 SANGSPIIFEELEYHEPVCRQHCLNKDFSEHEFDPDSYQIPFVILSLKTFAPQVHSLLQTHEGTVPLLSFPECYAAKFSP 160

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 71891770    802 LEVVQENQGGVPLEHFITCVPGVNIATAQNGIKVVKWIHNKPPPPNTDPWL 852
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 71891770  864 LIQFSREVIDLLKSQPSCVIPISHFIPSYHHHFAKQCRVSDYGYSKLIELLEAVPHVLQILGMGSKRLLTLT 935
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 71891770 1024 TKQFSKDVVDLLRHQPHFRMPFNKFIPSYHHHFGRQCKLAYYGFTKLLELFEAIPDTLQVLECGEEKILTL 1094
Cdd:cd09981    1 TKQFSKEVVELLRHQPHFRMPFTKFIPSYHHHFGRQCKLSYYGFTKLLELFEAIPDVVQVLECGEEKYLQL 71

RNA recognition motif 1 (RRM1) found in Limkain-b1 (LKAP) and similar proteins; This subfamily corresponds to the RRM1 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71891770  274 CHTLLYVYNLPANKDGKSVSNRLRRLSDNCGGKVLSITGCSAILRFINQDSAERAQKRMENEDVFGNRIIVSF 346
Cdd:cd12255    1 CHTLLYVYNLPTNRDVKSIRNRLRQLSDNCGGKVLSVSGGSAILRFANQESAERAQKRMEGEDVFGNKISVSF 73

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 71891770 1100 FKALAAQFVKLLRSQKDNCLMMTDLLTEYAKTFGYTFRLQDYDVSSISALTQKLCHVVKVADIESGRQIQL 1170
Cdd:cd09982    1 VKALAAQLVKLLRSQKDSCLMMCDLLTEYSKTFGYTLRLQDYDVSSVPALMQKLCHVVKVVDTESGKQIQL 71

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 71891770    642 LLSAETMSVLQDAPACCLPLFKFTDIYEKKFGHKLNVSDLYKLTDTVAIREQGNGRLVCLLPSRQARQSPLGSSQSHDGS 721
Cdd:pfam19687    1 LLSSETISILQDAPACCLPLFKFTEIYEKKFGHKLIVSDLYKLTDTVAIREQGNGRLVCLLPSSQARQSPLGSSQSHDGS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71891770    722 STNCSPIIFEELEYHEPVCRQHCSNKDFSEHEFDPDSYKIPFVILSLKTFAPQVHSLLQTHEGTVPLLSFPDCYIAEFGD 801
Cdd:pfam19687   81 SANGSPIIFEELEYHEPVCRQHCLNKDFSEHEFDPDSYQIPFVILSLKTFAPQVHSLLQTHEGTVPLLSFPECYAAKFSP 160

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 71891770    802 LEVVQENQGGVPLEHFITCVPGVNIATAQNGIKVVKWIHNKPPPPNTDPWL 852
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 71891770  768 LKTFAPQVHSLLQTHEGTVPLLSFPDCYIAEFGDLEVVQENQGGVPLEHFITCVPGVNIATAQNGIKVVKW 838
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 71891770  551 FANGADVQVSNIDYRLSRKELQQLLQEAFARHGKVKSVELSPHTDYQLKAVVQMENLQDAIGAVNSLHRYKIGSKKILVS 630
Cdd:cd12256    1 FSNGVDLQVSNLDYRMSRKELQQMLHNQFKRHGKVKSVELSPQTDGSLKASVRVPSLQDAQYAVSQLHRYKIGSKRIQVS 80

                 ....*....
gi 71891770  631 LATGAASKS 639
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 71891770  940 VKRFTQDLLKLLKSQASKQVIVREFSQAYHWCFSKDWDVTEYGVCELIDIVSEIPDTTICLSQQDNEMVICI 1011
Cdd:cd09980    1 VRRFTQDLLRVLKSQASKQVIVKDFGQAYEWCFGRDWDPVDYGLCDLQDLLSEIPDNTIVIEQQDGDKVISI 72

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 71891770 1176 LRSLTAQLLVLLMSWEGTTHLSVEELKRHYESTHNTPLNPCEYGFMTLTELLKSLPYLVEVFTNDKMEECVKL 1248
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 71891770  116 PIGVFWDIENCSVPSGRSATAVVQRIREKFFK--GHREAEFICVCDISKENKEVIQELNNCQVTVAHINATAKNAADDKL 193
Cdd:cd10910    1 KTGVFWDIENCPVPDGYDARRVGPNIRRALRKlgYSGPVSITAYGDLSKVPKDVLSELSSSGVSLVHVPHGGKKAADKKI 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 71891770  194 RQSLRRFANTHTAPATVVLVSTDV-NFALELSDLRHRhGFHIILVH 238
Cdd:cd10910   81 LVDMLLWALDNPPPANIMLISGDVrDFAYALSRLRSR-GYNVLLAY 125

MARF1, RNA recognition motif 1; MARF1 (also known as Limkain-b1) is an essential protein for controlling meiosis and retrotransposon surveillance in mouse oocytes, first described as a human autoantigen localized to a subset of ABCD3 and PXF marked peroxisomes. It may function both as an adaptor to recruit specific RNA targets and an effector to catalyze the specific cleavages of target RNAs. MARF1 contains an N-terminal NYN domain, two central RRMs, and C-terminal OST-HTH/LOTUS domains. This domain represents the RNA recognition motif 1 (RRM1) of MARF1.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71891770    276 TLLYVYNLPANKDG---KSVSNRLRRLSDNCGGKVLSITGCSAILRFINQDSAERAQKRMENEDVFGNRIIVSFTPKNRE 352
Cdd:pfam11608    3 NLLFVRNLPVNCDKslqNAVKHRLRRLSDNCGGKVLGISQGTAVLRFGSPEAASRACKRMENEDVYGHRISLSFSLGPRD 82

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 71891770    870 EVIDLLKSQPSCVIPISHFIPSYHHHFAKQCRVSDYGYSKLIELLEAVPHVLQILGMGSKRLLT 933
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 71891770   1030 DVVDLLRHQPHFRMPFNKFIPSYHHHFGRQCKLAYYGFTKLLELFEAIPDTLQVLECGEEKILT 1093
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 71891770    559 VSNIDYRLSRKELQQLlqeaFARHGKVKSVELSPHTDYQLK--AVVQMENLQDAIGAVNSLHRYKIGSKKIL 628
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 71891770    642 LLSAETMSVLQDAPACCLPLFKFTDIYEKKFGHKLNVSDLYKLTDTVAIREQGNGRLVCLLPSRQARQSPLGSSQSHDGS 721
Cdd:pfam19687    1 LLSSETISILQDAPACCLPLFKFTEIYEKKFGHKLIVSDLYKLTDTVAIREQGNGRLVCLLPSSQARQSPLGSSQSHDGS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71891770    722 STNCSPIIFEELEYHEPVCRQHCSNKDFSEHEFDPDSYKIPFVILSLKTFAPQVHSLLQTHEGTVPLLSFPDCYIAEFGD 801
Cdd:pfam19687   81 SANGSPIIFEELEYHEPVCRQHCLNKDFSEHEFDPDSYQIPFVILSLKTFAPQVHSLLQTHEGTVPLLSFPECYAAKFSP 160

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 71891770    802 LEVVQENQGGVPLEHFITCVPGVNIATAQNGIKVVKWIHNKPPPPNTDPWL 852
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 71891770  768 LKTFAPQVHSLLQTHEGTVPLLSFPDCYIAEFGDLEVVQENQGGVPLEHFITCVPGVNIATAQNGIKVVKW 838
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 71891770  551 FANGADVQVSNIDYRLSRKELQQLLQEAFARHGKVKSVELSPHTDYQLKAVVQMENLQDAIGAVNSLHRYKIGSKKILVS 630
Cdd:cd12256    1 FSNGVDLQVSNLDYRMSRKELQQMLHNQFKRHGKVKSVELSPQTDGSLKASVRVPSLQDAQYAVSQLHRYKIGSKRIQVS 80

                 ....*....
gi 71891770  631 LATGAASKS 639
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 71891770  940 VKRFTQDLLKLLKSQASKQVIVREFSQAYHWCFSKDWDVTEYGVCELIDIVSEIPDTTICLSQQDNEMVICI 1011
Cdd:cd09980    1 VRRFTQDLLRVLKSQASKQVIVKDFGQAYEWCFGRDWDPVDYGLCDLQDLLSEIPDNTIVIEQQDGDKVISI 72

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 71891770 1176 LRSLTAQLLVLLMSWEGTTHLSVEELKRHYESTHNTPLNPCEYGFMTLTELLKSLPYLVEVFTNDKMEECVKL 1248
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 71891770  116 PIGVFWDIENCSVPSGRSATAVVQRIREKFFK--GHREAEFICVCDISKENKEVIQELNNCQVTVAHINATAKNAADDKL 193
Cdd:cd10910    1 KTGVFWDIENCPVPDGYDARRVGPNIRRALRKlgYSGPVSITAYGDLSKVPKDVLSELSSSGVSLVHVPHGGKKAADKKI 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 71891770  194 RQSLRRFANTHTAPATVVLVSTDV-NFALELSDLRHRhGFHIILVH 238
Cdd:cd10910   81 LVDMLLWALDNPPPANIMLISGDVrDFAYALSRLRSR-GYNVLLAY 125

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 71891770 1026 QFSKDVVDLLRHQPHFRMPFNKFIPSYHHHFGRQCKLAYYGFTKLLELFEAIPDTLQVLECGEEKILTLT 1095
Cdd:cd09979    3 QFSREVIDLLKSQPSCLLPFSRFIPAYHHHFGKQCRVSDYGYTKLIELLEAVPHVLQILGMGSKRLLTLS 72

PIN domain of Synechococcus elongatus LabA (low-amplitude and bright) and related proteins; The LabA-like PIN domain family includes Synechococcus elongatus PCC 7942 LabA which participates in cyanobacterial circadian timing. It is required for negative feedback regulation of the autokinase/autophosphatase KaiC, a central component of the circadian clock system. In particular, LabA seems necessary for KaiC-dependent repression of gene expression. This family also includes the N-terminal domain of limkain b1, a human autoantigen associated with cytoplasmic vesicles. Other members are the LabA-like PIN domains of 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 this family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71891770  118 GVFWDIENCSVPSGrsatAVVQRIREKFFKGhreAEFICVCDIsKENKEVIQELNNCQVTVAHINATAKNAADDKLRQSL 197
Cdd:cd06167    1 GVLVDADNCSNGFG----ALILRRYAGLFLQ---MGFEKYANI-NAQPLLVPPSNNRGFTVIRVAAKRKDAADVALVRQA 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 71891770  198 RRFANTHTaPATVVLVSTDvnfALELSDLRHR---HGFHIILVHK 239
Cdd:cd06167   73 GRLAYTGA-PDTVVLVSGD---KLDFSDLIEKakeAGLNVIVVGP 113

MARF1, RNA recognition motif 1; MARF1 (also known as Limkain-b1) is an essential protein for controlling meiosis and retrotransposon surveillance in mouse oocytes, first described as a human autoantigen localized to a subset of ABCD3 and PXF marked peroxisomes. It may function both as an adaptor to recruit specific RNA targets and an effector to catalyze the specific cleavages of target RNAs. MARF1 contains an N-terminal NYN domain, two central RRMs, and C-terminal OST-HTH/LOTUS domains. This domain represents the RNA recognition motif 1 (RRM1) of MARF1.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71891770    276 TLLYVYNLPANKDG---KSVSNRLRRLSDNCGGKVLSITGCSAILRFINQDSAERAQKRMENEDVFGNRIIVSFTPKNRE 352
Cdd:pfam11608    3 NLLFVRNLPVNCDKslqNAVKHRLRRLSDNCGGKVLGISQGTAVLRFGSPEAASRACKRMENEDVYGHRISLSFSLGPRD 82

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 71891770 1024 TKQFSKDVVDLLRHQPHfRMPFNKFIPSYHHHFGRQCKLAYYGFTKLLELFEAIPDTLQVLECGEEKILTL 1094
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 71891770  940 VKRFTQDLLKLLKSQaSKQVIVREFSQAYHWCFSKDWDVTEYGVCELIDIVSEIPDTTICLSQQDNEMVIC 1010
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 71891770 1176 LRSLTAQLLVLLMSWEGTthLSVEELKRHYESTHNTPLNPCEYGFMTLTELLKSLPYLVEVFTNDkMEECVKL 1248
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 71891770  768 LKTFAPQVHSLLQTHEGTVPLLSFPDCYIAEFGDLEVVQEnQGGVPLEHFITCVPGVNIATAQNGIKVVKW 838
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 71891770   1182 QLLVLLMSW-EGTTHLSveELKRHYESTHNTPLNPCEYGFMTLTELLKSLPYLVEVFTNDKMEECV 1246
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 71891770  557 VQVSNIDYRLSRKELQQLlqeaFARHGKVKSVELSPHTDYQLK--AVVQMENLQDAIGAVNSLHRYKIGSKKILVS 630
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 71891770  640 LSLLSAETMSVLQDAPaCCLPLFKFTDIYEKKFGHKLNVSD---------LYKLTDTVAIREQGNGRLVCL 701
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 71891770    559 VSNIDYRLSRKELQQLlqeaFARHGKVKSVELSPHTDYQLK--AVVQMENLQDAIGAVNSLHRYKIGSKKIL 628
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 71891770  557 VQVSNIDYRLSRKELQQLlqeaFARHGKVKSVEL--SPHTDYQLKAVVQMENLQDAIGAVNSLHRYKIGSKKILVSL 631
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 71891770 1251 LYLFAKNVRSLLHTYHYQQIFLHEFSMAYTKYVGETLQPKTYGHSSVEELLGAIPQVVWIKGHGHKRIVVL 1321
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 71891770 1029 KDVVDLLRHQPHFRMPFNKfipSYHHHFGRQCKLAYYGFTKLLELFEAIPDTLQVLECGEEKILTL 1094
Cdd:cd09975    6 SELKDLLSHSPVLLSELEK---AYVARFGRSFQYTQYGFFSMLEVLSAASDFIIVKQTRTGSLLLL 68

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71891770  566 LSRKELQQLLQEAFARHGKVKSVELSPHTDYqlkAVVQMENLQDAIGAVNSLHRYKIGSKKILVSLATG 634
Cdd:cd12227   10 LSKKVTQEELKNLFEEYGEIQSIDMIPPRGC---AYVCMKTRQDAHRALQKLKNHKLRGKSIKIAWAPN 75

RNA recognition motif (RRM) found in alkylated DNA repair protein alkB homolog 8 (ALKBH8) and similar proteins; This subfamily corresponds to the RRM of ALKBH8, also termed alpha-ketoglutarate-dependent dioxygenase ABH8, or S-adenosyl-L-methionine-dependent tRNA methyltransferase ABH8, expressed in various types of human cancers. It is essential in urothelial carcinoma cell survival mediated by NOX-1-dependent ROS signals. ALKBH8 has also been identified as a tRNA methyltransferase that catalyzes methylation of tRNA to yield 5-methylcarboxymethyl uridine (mcm5U) at the wobble position of the anticodon loop. Thus, ALKBH8 plays a crucial role in the DNA damage survival pathway through a distinct mechanism involving the regulation of tRNA modification. ALKBH8 localizes to the cytoplasm. It contains the characteristic AlkB domain that is composed of a tRNA methyltransferase motif, a motif homologous to the bacterial AlkB DNA/RNA repair enzyme, and a dioxygenase catalytic core domain encompassing cofactor-binding sites for iron and 2-oxoglutarate. In addition, unlike other AlkB homologs, ALKBH8 contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal S-adenosylmethionine (SAM)-dependent methyltransferase (MT) domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71891770  566 LSRKELQQLlqeaFARHGKVKSVELSPHTDYqlkAVVQMENLQDAIGAVNSLHRYKIGSKKILVSL 631
Cdd:cd12431   15 VSREQLLEV----FEKYGTVEDIVMLPGKPY---SFVSFKSVEEAAKAYNALNGKELELPQQNVPL 73

RNA recognition motif 2 (RRM2) found in RNA-binding protein 28 (RBM28) and similar proteins; This subfamily corresponds to the RRM2 of RBM28 and Nop4p. RBM28 is a specific nucleolar component of the spliceosomal small nuclear ribonucleoproteins (snRNPs), possibly coordinating their transition through the nucleolus. It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), and may play a role in the maturation of both small nuclear and ribosomal RNAs. RBM28 has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an extremely acidic region between RRM2 and RRM3. The family also includes nucleolar protein 4 (Nop4p or Nop77p) encoded by YPL043W from Saccharomyces cerevisiae. It is an essential nucleolar protein involved in processing and maturation of 27S pre-rRNA and biogenesis of 60S ribosomal subunits. Nop4p also contains four RRMs.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 71891770  575 LQEAFARHGKVKSVELSPHTDYQLK--AVVQMENLQDAIGAVNSLHRYKIGSKKILVSLA 632
Cdd:cd12414   16 LKKLFSKFGKVLEVTIPKKPDGKLRgfAFVQFTNVADAAKAIKGMNGKKIKGRPVAVDWA 75