ID   RTCA_DROME              Reviewed;         361 AA.
AC   O77264;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   27-MAR-2024, entry version 174.
DE   RecName: Full=RNA 3'-terminal phosphate cyclase {ECO:0000303|PubMed:25961792};
DE            Short=RNA cyclase {ECO:0000303|PubMed:25961792};
DE            Short=RNA-3'-phosphate cyclase {ECO:0000303|PubMed:25961792};
DE            EC=6.5.1.4 {ECO:0000250|UniProtKB:O00442};
GN   Name=Rtca {ECO:0000303|PubMed:25961792,
GN   ECO:0000312|FlyBase:FBgn0025630};
GN   ORFNames=CG4061 {ECO:0000312|FlyBase:FBgn0025630};
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Oregon-R;
RX   PubMed=10731137; DOI=10.1126/science.287.5461.2220;
RA   Benos P.V., Gatt M.K., Ashburner M., Murphy L., Harris D., Barrell B.G.,
RA   Ferraz C., Vidal S., Brun C., Demailles J., Cadieu E., Dreano S., Gloux S.,
RA   Lelaure V., Mottier S., Galibert F., Borkova D., Minana B., Kafatos F.C.,
RA   Louis C., Siden-Kiamos I., Bolshakov S., Papagiannakis G., Spanos L.,
RA   Cox S., Madueno E., de Pablos B., Modolell J., Peter A., Schoettler P.,
RA   Werner M., Mourkioti F., Beinert N., Dowe G., Schaefer U., Jaeckle H.,
RA   Bucheton A., Callister D.M., Campbell L.A., Darlamitsou A., Henderson N.S.,
RA   McMillan P.J., Salles C., Tait E.A., Valenti P., Saunders R.D.C.,
RA   Glover D.M.;
RT   "From sequence to chromosome: the tip of the X chromosome of D.
RT   melanogaster.";
RL   Science 287:2220-2222(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley; TISSUE=Embryo;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=25961792; DOI=10.1038/nn.4019;
RA   Song Y., Sretavan D., Salegio E.A., Berg J., Huang X., Cheng T., Xiong X.,
RA   Meltzer S., Han C., Nguyen T.T., Bresnahan J.C., Beattie M.S., Jan L.Y.,
RA   Jan Y.N.;
RT   "Regulation of axon regeneration by the RNA repair and splicing pathway.";
RL   Nat. Neurosci. 18:817-825(2015).
RN   [6]
RP   FUNCTION.
RX   PubMed=31919191; DOI=10.1101/gad.331330.119;
RA   Vargas E.J.M., Matamoros A.J., Qiu J., Jan C.H., Wang Q., Gorczyca D.,
RA   Han T.W., Weissman J.S., Jan Y.N., Banerjee S., Song Y.;
RT   "The microtubule regulator ringer functions downstream from the RNA
RT   repair/splicing pathway to promote axon regeneration.";
RL   Genes Dev. 34:194-208(2020).
CC   -!- FUNCTION: Catalyzes the conversion of 3'-phosphate to a 2',3'-cyclic
CC       phosphodiester at the end of RNA (By similarity). The mechanism of
CC       action of the enzyme occurs in 3 steps: (A) adenylation of the enzyme
CC       by ATP; (B) transfer of adenylate to an RNA-N3'P to produce RNA-
CC       N3'PP5'A; (C) and attack of the adjacent 2'-hydroxyl on the 3'-
CC       phosphorus in the diester linkage to produce the cyclic end product (By
CC       similarity). Likely functions in some aspects of cellular RNA
CC       processing (By similarity). Function plays an important role in a RNA
CC       repair and splicing pathway which controls axon regeneration in
CC       response to peripheral (PNS) and central nervous system (CNS) injury
CC       (PubMed:25961792, PubMed:31919191). In response to axotomy, negatively
CC       regulates splicing of Xbp1 which in turn activates downstream effectors
CC       which inhibit axon regeneration, including down-regulating the
CC       microtubule regulators ringer and futsch (PubMed:25961792,
CC       PubMed:31919191). {ECO:0000250|UniProtKB:O00442,
CC       ECO:0000269|PubMed:25961792, ECO:0000269|PubMed:31919191}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 3'-end 3'-phospho-ribonucleotide-RNA + ATP = a 3'-end 2',3'-
CC         cyclophospho-ribonucleotide-RNA + AMP + diphosphate;
CC         Xref=Rhea:RHEA:23976, Rhea:RHEA-COMP:10463, Rhea:RHEA-COMP:10464,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:83062,
CC         ChEBI:CHEBI:83064, ChEBI:CHEBI:456215; EC=6.5.1.4;
CC         Evidence={ECO:0000250|UniProtKB:O00442};
CC   -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC       {ECO:0000250|UniProtKB:O00442}. Nucleus {ECO:0000269|PubMed:25961792}.
CC   -!- DEVELOPMENTAL STAGE: In larvae, detected in various types of
CC       multidendritic neurons including class IV and class III dendritic
CC       arborization (da) neurons (at protein level) (PubMed:25961792). In
CC       larvae, expressed in class IV da neurons, and tissues in the peripheral
CC       nervous system (PNS) and the ventral nerve cord (VNC)
CC       (PubMed:25961792). {ECO:0000269|PubMed:25961792}.
CC   -!- DISRUPTION PHENOTYPE: Severed axons of RNAi-mediated knockdown class
CC       III dendritic arborization (da) neurons, display increased
CC       regeneration. {ECO:0000269|PubMed:25961792}.
CC   -!- SIMILARITY: Belongs to the RNA 3'-terminal cyclase family. Type 1
CC       subfamily. {ECO:0000305}.
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DR   EMBL; AE014298; AAF45719.1; -; Genomic_DNA.
DR   EMBL; AL031765; CAA21129.1; -; Genomic_DNA.
DR   EMBL; AY052112; AAK93536.1; -; mRNA.
DR   PIR; T13745; T13745.
DR   RefSeq; NP_001284801.1; NM_001297872.1.
DR   RefSeq; NP_569977.1; NM_130621.3.
DR   AlphaFoldDB; O77264; -.
DR   SMR; O77264; -.
DR   BioGRID; 57719; 6.
DR   DIP; DIP-23093N; -.
DR   STRING; 7227.FBpp0070316; -.
DR   PaxDb; 7227-FBpp0070316; -.
DR   DNASU; 31175; -.
DR   EnsemblMetazoa; FBtr0070330; FBpp0070316; FBgn0025630.
DR   EnsemblMetazoa; FBtr0344156; FBpp0310569; FBgn0025630.
DR   GeneID; 31175; -.
DR   KEGG; dme:Dmel_CG4061; -.
DR   UCSC; CG4061-RA; d. melanogaster.
DR   AGR; FB:FBgn0025630; -.
DR   CTD; 8634; -.
DR   FlyBase; FBgn0025630; Rtca.
DR   VEuPathDB; VectorBase:FBgn0025630; -.
DR   eggNOG; KOG3980; Eukaryota.
DR   HOGENOM; CLU_027882_0_1_1; -.
DR   InParanoid; O77264; -.
DR   OMA; WSPPIDY; -.
DR   OrthoDB; 315241at2759; -.
DR   PhylomeDB; O77264; -.
DR   BioGRID-ORCS; 31175; 0 hits in 1 CRISPR screen.
DR   GenomeRNAi; 31175; -.
DR   PRO; PR:O77264; -.
DR   Proteomes; UP000000803; Chromosome X.
DR   Bgee; FBgn0025630; Expressed in egg chamber and 24 other cell types or tissues.
DR   ExpressionAtlas; O77264; baseline and differential.
DR   GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003963; F:RNA-3'-phosphate cyclase activity; IBA:GO_Central.
DR   GO; GO:0048681; P:negative regulation of axon regeneration; IMP:UniProtKB.
DR   GO; GO:0006396; P:RNA processing; IEA:InterPro.
DR   CDD; cd00874; RNA_Cyclase_Class_II; 1.
DR   Gene3D; 3.65.10.20; RNA 3'-terminal phosphate cyclase domain; 1.
DR   Gene3D; 3.30.360.20; RNA 3'-terminal phosphate cyclase, insert domain; 1.
DR   HAMAP; MF_00200; RTC; 1.
DR   InterPro; IPR013791; RNA3'-term_phos_cycl_insert.
DR   InterPro; IPR023797; RNA3'_phos_cyclase_dom.
DR   InterPro; IPR037136; RNA3'_phos_cyclase_dom_sf.
DR   InterPro; IPR000228; RNA3'_term_phos_cyc.
DR   InterPro; IPR017770; RNA3'_term_phos_cyc_type_1.
DR   InterPro; IPR013792; RNA3'P_cycl/enolpyr_Trfase_a/b.
DR   InterPro; IPR036553; RPTC_insert.
DR   NCBIfam; TIGR03399; RNA_3prim_cycl; 1.
DR   PANTHER; PTHR11096; RNA 3' TERMINAL PHOSPHATE CYCLASE; 1.
DR   PANTHER; PTHR11096:SF0; RNA 3'-TERMINAL PHOSPHATE CYCLASE; 1.
DR   Pfam; PF01137; RTC; 1.
DR   Pfam; PF05189; RTC_insert; 1.
DR   PIRSF; PIRSF005378; RNA3'_term_phos_cycl_euk; 1.
DR   SUPFAM; SSF55205; EPT/RTPC-like; 2.
DR   SUPFAM; SSF52913; RNA 3'-terminal phosphate cyclase, RPTC, insert domain; 1.
DR   Genevisible; O77264; DM.
PE   1: Evidence at protein level;
KW   ATP-binding; Ligase; Nucleotide-binding; Nucleus; Reference proteome.
FT   CHAIN           1..361
FT                   /note="RNA 3'-terminal phosphate cyclase"
FT                   /id="PRO_0000156412"
FT   ACT_SITE        321
FT                   /note="Tele-AMP-histidine intermediate"
FT                   /evidence="ECO:0000250|UniProtKB:P46849"
FT   BINDING         105
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P46849"
FT   BINDING         132
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P46849"
FT   BINDING         295
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P46849"
FT   BINDING         298
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P46849"
FT   BINDING         299
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P46849"
FT   BINDING         321
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P46849"
SQ   SEQUENCE   361 AA;  39503 MW;  CDB65A453BB8CF39 CRC64;
     MDAEKMLEID GSYLEGGGQA LRNALSLSCI LGKPVRVVKI RASRPSPGLS HQHLHGLNLL
     RDITNADVVG NYLLSSTVEF TPRTILDNTY RVETHTAASI TLIYQMALPV LLFAGRPSRL
     IVSGGTNVDF APPVEYMQEV LLPNLKHFGV SFDLKVQRYG FYPRGQGRCQ LDVQPVTKLN
     SGKLVAFGRI KSVSGVAYCA GRLPVNIAID MQQTAQREIH RLWPSQQCSI EPIKHSRQKA
     FHNGAGILMT VNTTSDVVLG ASALGKKRID GHVLGSEASC QLGDYMRKQV CVDDYMQDQL
     IIYMALAVGR STMRTGKLTN HTRTAINVAE QMTGVKFDVA MEPGGQMLVS CKGLGHVNKL
     I
//