The eighth LOTUS domain on Limkain b1(LKAP); The eighth 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 2092160968 1517 LYLFAKNVRSLLHTYHYQQIFLHEFPTAYCKYTGEVLQPKIYGYNSLEELLGAIPQVVWIKGHGHKRIVVLKNDMK 1592
Cdd:cd09984      1 LYQFAKNVRSLLHTYHYQQIFLHEFSSAYSKYVGETLQPKNYGYNSLEELLGAIPQVVWIKGHGHKRIVVLKNDMK 76

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 2092160968 1130 LIQFSREVIDLLKSQPSCIIPVSKFIPTYHHHFAKQCRVSDYGYSKLMELLEAVPHVLQILGMGSKRLLTLT 1201
Cdd:cd09979      1 LIQFSREVIDLLKSQPSCLLPFSRFIPAYHHHFGKQCRVSDYGYTKLIELLEAVPHVLQILGMGSKRLLTLS 72

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 2092160968  505 CHTLLYVYNLPTNRDSKSVSNRLRRLSDNCGGKVMSISGSSAILRFSNQESAERAHKRMENEDVFGNRIIVSF 577
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 2092160968 1366 VKALAAQLVKLLRSQKDNCLMMTDLLTEYSKTFGYTLRLHDYDVSSVLALMQKLCHVVKAADTESGKQIQL 1436
Cdd:cd09982      1 VKALAAQLVKLLRSQKDSCLMMCDLLTEYSKTFGYTLRLQDYDVSSVPALMQKLCHVVKVVDTESGKQIQL 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 2092160968 1442 LRTLTAQLLVLMMSWDETAFLSVDELKRHYETIHSAPLNPCEYGFMTLSELLKSLPYLVEVFTSDVAEEYVKL 1514
Cdd:cd09983      1 LRSLTAQLLVLLMSWEGASDLSVEELRQHYESVHGTPLNPCEYGFMSLTELLKSLPYLVEVFTNGGGEEYVRL 73

The eighth LOTUS domain on Limkain b1(LKAP); The eighth 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 2092160968 1517 LYLFAKNVRSLLHTYHYQQIFLHEFPTAYCKYTGEVLQPKIYGYNSLEELLGAIPQVVWIKGHGHKRIVVLKNDMK 1592
Cdd:cd09984      1 LYQFAKNVRSLLHTYHYQQIFLHEFSSAYSKYVGETLQPKNYGYNSLEELLGAIPQVVWIKGHGHKRIVVLKNDMK 76

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 2092160968  817 FANGADIQISNIDYRLSRKDLQQILQEIFSRYGKVKSVELSPHTDYQLKAIVQMENLQEAISAVNNLHRYKIGSKRIQVS 896
Cdd:cd12256      1 FSNGVDLQVSNLDYRMSRKELQQMLHNQFKRHGKVKSVELSPQTDGSLKASVRVPSLQDAQYAVSQLHRYKIGSKRIQVS 80

                   ....*....
gi 2092160968  897 LATGAANKS 905
Cdd:cd12256     81 LATGSSNKS 89

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 2092160968 1290 TKQFSKEVVDLLRHQPHFRMPFNKFIPSYHHHFGRQCKLAYYGFTKLLELFEAIPDVLQVLECGEEKILTL 1360
Cdd:cd09981      1 TKQFSKEVVELLRHQPHFRMPFTKFIPSYHHHFGRQCKLSYYGFTKLLELFEAIPDVVQVLECGEEKYLQL 71

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 2092160968 1206 VKRFTQDLLKLLKSQASKQVIVREFLQAYHWCFSKDWDVTEYGVCELADIISEIPDTTICLCQQDNEMIICI 1277
Cdd:cd09980      1 VRRFTQDLLRVLKSQASKQVIVKDFGQAYEWCFGRDWDPVDYGLCDLQDLLSEIPDNTIVIEQQDGDKVISI 72

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 2092160968  347 PIGVFWDIENCSVPTGRSAVAVVQRIREKFFK--GHREAEFICVCDISKENKEVIQELNNCQVTVAHINATAKNAADDKL 424
Cdd:cd10910      1 KTGVFWDIENCPVPDGYDARRVGPNIRRALRKlgYSGPVSITAYGDLSKVPKDVLSELSSSGVSLVHVPHGGKKAADKKI 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 2092160968  425 RQSLRRFADTHTAPATVVLVSTDV-NFALELSDLRHRhGFQIILVH 469
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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2092160968  507 TLLYVYNLPTNRDS---KSVSNRLRRLSDNCGGKVMSISGSSAILRFSNQESAERAHKRMENEDVFGNRIIVSFTP 579
Cdd:pfam11608    3 NLLFVRNLPVNCDKslqNAVKHRLRRLSDNCGGKVLGISQGTAVLRFGSPEAASRACKRMENEDVYGHRISLSFSL 78

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 2092160968 1524 VRSLLHTYHYQQIFLHEFPTAYCKYTGEVLQPKIYGYNSLEELLGAIPQVVWIKGHGHKRIVV 1586
Cdd:pfam12872    2 LISLLRSDPDGWASLSELGSEYRKLFGEDFDPRNYGFSKLSDLLKAIPDVFEIEKRGGGGLVV 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 2092160968 1296 EVVDLLRHQPHFRMPFNKFIPSYHHHFGRQCKLAYYGFTKLLELFEAIPDVLQVLECGEEKILT 1359
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
                   ....*....|....*....|....*....|....*....|.
gi 2092160968 1462 LSVDELKRHYETIHSAPLNPCEYGFMTLSELLKSLPYLVEV 1502
Cdd:pfam12872   14 ASLSELGSEYRKLFGEDFDPRNYGFSKLSDLLKAIPDVFEI 54

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 2092160968  825 ISNIDYRLSRKDLQQIlqeiFSRYGKVKSVELSPHTDYQLK--AIVQMENLQEAISAVNNLHRYKIGSKRI 893
Cdd:pfam00076    3 VGNLPPDTTEEDLKDL----FSKFGPIKSIRLVRDETGRSKgfAFVEFEDEEDAEKAIEALNGKELGGREL 69

RNA recognition motif;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2092160968   509 LYVYNLPTNRDSKSVSNRLRRLsdncgGKVMSI-------SGSS---AILRFSNQESAERAHKRMENEDVFGNRIIV 575
Cdd:smart00360    2 LFVGNLPPDTTEEELRELFSKF-----GKVESVrlvrdkeTGKSkgfAFVEFESEEDAEKALEALNGKELDGRPLKV 73

The eighth LOTUS domain on Limkain b1(LKAP); The eighth 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 2092160968 1517 LYLFAKNVRSLLHTYHYQQIFLHEFPTAYCKYTGEVLQPKIYGYNSLEELLGAIPQVVWIKGHGHKRIVVLKNDMK 1592
Cdd:cd09984      1 LYQFAKNVRSLLHTYHYQQIFLHEFSSAYSKYVGETLQPKNYGYNSLEELLGAIPQVVWIKGHGHKRIVVLKNDMK 76

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 2092160968  817 FANGADIQISNIDYRLSRKDLQQILQEIFSRYGKVKSVELSPHTDYQLKAIVQMENLQEAISAVNNLHRYKIGSKRIQVS 896
Cdd:cd12256      1 FSNGVDLQVSNLDYRMSRKELQQMLHNQFKRHGKVKSVELSPQTDGSLKASVRVPSLQDAQYAVSQLHRYKIGSKRIQVS 80

                   ....*....
gi 2092160968  897 LATGAANKS 905
Cdd:cd12256     81 LATGSSNKS 89

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 2092160968 1290 TKQFSKEVVDLLRHQPHFRMPFNKFIPSYHHHFGRQCKLAYYGFTKLLELFEAIPDVLQVLECGEEKILTL 1360
Cdd:cd09981      1 TKQFSKEVVELLRHQPHFRMPFTKFIPSYHHHFGRQCKLSYYGFTKLLELFEAIPDVVQVLECGEEKYLQL 71

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 2092160968 1206 VKRFTQDLLKLLKSQASKQVIVREFLQAYHWCFSKDWDVTEYGVCELADIISEIPDTTICLCQQDNEMIICI 1277
Cdd:cd09980      1 VRRFTQDLLRVLKSQASKQVIVKDFGQAYEWCFGRDWDPVDYGLCDLQDLLSEIPDNTIVIEQQDGDKVISI 72

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 2092160968  347 PIGVFWDIENCSVPTGRSAVAVVQRIREKFFK--GHREAEFICVCDISKENKEVIQELNNCQVTVAHINATAKNAADDKL 424
Cdd:cd10910      1 KTGVFWDIENCPVPDGYDARRVGPNIRRALRKlgYSGPVSITAYGDLSKVPKDVLSELSSSGVSLVHVPHGGKKAADKKI 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 2092160968  425 RQSLRRFADTHTAPATVVLVSTDV-NFALELSDLRHRhGFQIILVH 469
Cdd:cd10910     81 LVDMLLWALDNPPPANIMLISGDVrDFAYALSRLRSR-GYNVLLAY 125

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 2092160968  906 LSQLSSETMSILQDAPACCLPIFKFTEIYEKKFGHKLIASDLYKLTDTVAIRDQGNGRLVCL 967
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 2092160968 1132 QFSREVIDLLKSQPSCIIPVSKFIPTYHHHFAKQCRVSDYGYSKLMELLEAVPHVLQILGMGSKRLLTL 1200
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 2092160968  347 PIGVFWDIENCSVPTGRSAVAVVQRIREkffkgHREA-EFICVCDISKEN-KEVIQELNNCQVTVAHINAT-AKNAADDK 423
Cdd:pfam01936    1 RVAVFIDGENCPLPDGVDYRKVLEEIRS-----GGEVvRARAYGNWGDPDlRKFPDALSSTGIPVQHKPLTkGKNAVDVG 75

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2092160968  424 LRQSLRRFADTHTaPATVVLVSTDVNFALELSDLRHRHGF-QIILVHKNQASEALLHHAHELI 485
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 2092160968 1130 LIQFSREVIDLLKSQPSCIiPVSKFIPTYHHHFAKQCRVSDYGYSKLMELLEAVPHVLQILGMGSKRLLTL 1200
Cdd:cd08824      1 LKQLAKQLRSLLQSYPGGL-PLSKLPQLYKKKFGKPLDLSEYGFSKLSDLLEALPGVVIVLSQGGERIVSL 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 2092160968 1517 LYLFAKNVRSLLHTYHyQQIFLHEFPTAYCKYTGEVLQPKIYGYNSLEELLGAIPQVVWIKGHGHKRIVVL 1587
Cdd:cd08824      1 LKQLAKQLRSLLQSYP-GGLPLSKLPQLYKKKFGKPLDLSEYGFSKLSDLLEALPGVVIVLSQGGERIVSL 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 2092160968 1366 VKALAAQLVKLLRSQKdNCLMMTDLLTEYSKTFGYTLRLHDYDVSSVLALMQKLCHVVKAADTESGKQIQL 1436
Cdd:cd08824      1 LKQLAKQLRSLLQSYP-GGLPLSKLPQLYKKKFGKPLDLSEYGFSKLSDLLEALPGVVIVLSQGGERIVSL 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 2092160968 1136 EVIDLLKSQPSCIIPVSKFIPTYHHHFAKQCRVSDYGYSKLMELLEAVPHVLQILGMGSKRLLT 1199
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 2092160968 1296 EVVDLLRHQPHFRMPFNKFIPSYHHHFGRQCKLAYYGFTKLLELFEAIPDVLQVLECGEEKILT 1359
Cdd:pfam12872    1 ELISLLRSDPDGWASLSELGSEYRKLFGEDFDPRNYGFSKLSDLLKAIPDVFEIEKRGGGGLVV 64

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2092160968 1442 LRTLTAQLLVLMMSWDETafLSVDELKRHYETIHSAPLNPCEYGFMTLSELLKSLPYLVEVFTSD 1506
Cdd:cd08824      1 LKQLAKQLRSLLQSYPGG--LPLSKLPQLYKKKFGKPLDLSEYGFSKLSDLLEALPGVVIVLSQG 63

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
                   ....*....|....*....|....*....|....*....|.
gi 2092160968 1462 LSVDELKRHYETIHSAPLNPCEYGFMTLSELLKSLPYLVEV 1502
Cdd:pfam12872   14 ASLSELGSEYRKLFGEDFDPRNYGFSKLSDLLKAIPDVFEI 54

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2092160968  820 GADIQISNIDYRLSRKDLQQIlqeiFSRYGKVKSVELSP-HTDYQLK----AIVQMENLQEAISAVNNLHRYKIGSKRIQ 894
Cdd:cd21619      1 SNTIYVGNIDMTINEDALEKI----FSRYGQVESVRRPPiHTDKADRttgfGFIKYTDAESAERAMQQADGILLGRRRLV 76

                   .
gi 2092160968  895 V 895
Cdd:cd21619     77 V 77

The eighth LOTUS domain on Limkain b1(LKAP); The eighth 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 2092160968 1130 LIQFSREVIDLLKSQPSCIIPVSKFIPTYHHHFAKQCRVSDYGYSKLMELLEAVPHVLQILGMGSKRLLTL 1200
Cdd:cd09984      1 LYQFAKNVRSLLHTYHYQQIFLHEFSSAYSKYVGETLQPKNYGYNSLEELLGAIPQVVWIKGHGHKRIVVL 71

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 2092160968  832 LSRKDLQQILQEIFSRYGKVKSVELSPHTDYqlkAIVQMENLQEAISAVNNLHRYKIGSKRIQVSLATG 900
Cdd:cd12227     10 LSKKVTQEELKNLFEEYGEIQSIDMIPPRGC---AYVCMKTRQDAHRALQKLKNHKLRGKSIKIAWAPN 75

RNA recognition motif 3 (RRM3) found in the Hu proteins family; This subfamily corresponds to the RRM3 of the Hu proteins family which represent a group of RNA-binding proteins involved in diverse biological processes. Since the Hu proteins share high homology with the Drosophila embryonic lethal abnormal vision (ELAV) protein, the Hu family is sometimes referred to as the ELAV family. Drosophila ELAV is exclusively expressed in neurons and is required for the correct differentiation and survival of neurons in flies. The neuronal members of the Hu family include Hu-antigen B (HuB or ELAV-2 or Hel-N1), Hu-antigen C (HuC or ELAV-3 or PLE21), and Hu-antigen D (HuD or ELAV-4), which play important roles in neuronal differentiation, plasticity and memory. HuB is also expressed in gonads. Hu-antigen R (HuR or ELAV-1 or HuA) is the ubiquitously expressed Hu family member. It has a variety of biological functions mostly related to the regulation of cellular response to DNA damage and other types of stress. Hu proteins perform their cytoplasmic and nuclear molecular functions by coordinately regulating functionally related mRNAs. In the cytoplasm, Hu proteins recognize and bind to AU-rich RNA elements (AREs) in the 3' untranslated regions (UTRs) of certain target mRNAs, such as GAP-43, vascular epithelial growth factor (VEGF), the glucose transporter GLUT1, eotaxin and c-fos, and stabilize those ARE-containing mRNAs. They also bind and regulate the translation of some target mRNAs, such as neurofilament M, GLUT1, and p27. In the nucleus, Hu proteins function as regulators of polyadenylation and alternative splicing. Each Hu protein contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 may cooperate in binding to an ARE. RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2092160968  830 YRLSRKDLQQILQEIFSRYGKVKSVEL-SPHTDYQLK--AIVQMENLQEAISAVNNLHRYKIGSKRIQVSL 897
Cdd:cd12377      5 YNLAPDADESLLWQLFGPFGAVQNVKIiRDFTTNKCKgyGFVTMTNYDEAAVAIASLNGYRLGGRVLQVSF 75

RNA recognition motif (RRM) found in the scaffold attachment factor (SAFB) family; This subfamily corresponds to the RRM domain of the SAFB family, including scaffold attachment factor B1 (SAFB1), scaffold attachment factor B2 (SAFB2), SAFB-like transcriptional modulator (SLTM), and similar proteins, which are ubiquitously expressed. SAFB1, SAFB2 and SLTM have been implicated in many diverse cellular processes including cell growth and transformation, stress response, and apoptosis. They share high sequence similarities and all contain a scaffold attachment factor-box (SAF-box, also known as SAP domain) DNA-binding motif, an RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a region rich in glutamine and arginine residues. SAFB1 is a nuclear protein with a distribution similar to that of SLTM, but unlike that of SAFB2, which is also found in the cytoplasm. To a large extent, SAFB1 and SLTM might share similar functions, such as the inhibition of an oestrogen reporter gene. The additional cytoplasmic localization of SAFB2 implies that it could play additional roles in the cytoplasmic compartment which are distinct from the nuclear functions shared with SAFB1 and SLTM.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2092160968  841 LQEIFSRYGKVKSVEL--SPHTDYQLK-AIVQMENLQEAISAVNNLHRYKIGSKRIQV 895
Cdd:cd12417     16 LKKIFSKYGKVVSAKVvtSARTPGSRCyGYVTMASVEEADLCIKSLNKTELHGRVITV 73

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 2092160968  825 ISNIDYRLSRKDlqqiLQEIFSRYGKVKSVEL--SPHTDYQLKAIVQMENLQEAISAVNNLHRYKIGSKRIQVSL 897
Cdd:cd12418      5 VSNLHPDVTEED----LRELFGRVGPVKSVKInyDRSGRSTGTAYVVFERPEDAEKAIKQFDGVLLDGQPMKVEL 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2092160968  831 RLSRKDLQQILQEIFSRYGKVksVELSPHTDYqlkAIVQMENLQEAISAVNNLHRYKIGSKRIQV 895
Cdd:cd12343      6 NLPDAATSEELRALFEKYGKV--TECDIVKNY---AFVHMEKEEDAEDAIKALNGYEFMGSRINV 65

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 2092160968 1517 LYLFAKNVRSLLHTYHYQQIFLHEFPTAYCKYTGEVLQPKIYGYNSLEELLGAIPQVVWIKGHGHKRIVVL 1587
Cdd:cd09979      1 LIQFSREVIDLLKSQPSCLLPFSRFIPAYHHHFGKQCRVSDYGYTKLIELLEAVPHVLQILGMGSKRLLTL 71

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2092160968  823 IQISNIDYRLSRKDLQqilqEIFSRYGKVKSVELSPHTDYQLK--AIVQMENLQEAISAVNNLHRYKIGSKRIQVSL 897
Cdd:cd12386      1 IFVANLDYKVGWKKLK----EVFKLAGKVVRADIREDKDGKSRgmGVVQFEHPIEAVQAISMFNGQMLFDRPMRVKM 73