ID RTCA_HUMAN Reviewed; 366 AA.
AC O00442; Q5VVL5; Q5VVL6; Q96E99;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 27-MAR-2024, entry version 204.
DE RecName: Full=RNA 3'-terminal phosphate cyclase;
DE Short=RNA cyclase;
DE Short=RNA-3'-phosphate cyclase;
DE EC=6.5.1.4 {ECO:0000269|PubMed:9184239};
DE AltName: Full=RNA terminal phosphate cyclase domain-containing protein 1;
DE Short=RTC domain-containing protein 1;
GN Name=RTCA; Synonyms=RPC, RPC1, RTC1, RTCD1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), PARTIAL PROTEIN
RP SEQUENCE, FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Blood;
RX PubMed=9184239; DOI=10.1093/emboj/16.10.2955;
RA Genschik P., Billy E., Swianiewicz M., Filipowicz W.;
RT "The human RNA 3'-terminal phosphate cyclase is a member of a new family of
RT proteins conserved in Eucarya, Bacteria and Archaea.";
RL EMBO J. 16:2955-2967(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP CHARACTERIZATION.
RX PubMed=2199762; DOI=10.1016/0076-6879(90)81147-m;
RA Filipowicz W., Vincente O.;
RT "RNA 3'-terminal phosphate cyclase from HeLa cells.";
RL Methods Enzymol. 181:499-510(1990).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP FUNCTION.
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).
CC -!- FUNCTION: Catalyzes the conversion of 3'-phosphate to a 2',3'-cyclic
CC phosphodiester at the end of RNA (PubMed:9184239). 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
CC (PubMed:9184239). Likely functions in some aspects of cellular RNA
CC processing (PubMed:9184239, PubMed:25961792). Function plays an
CC important role in regulating axon regeneration by inhibiting central
CC nervous system (CNS) axon regeneration following optic nerve injury
CC (PubMed:25961792). {ECO:0000269|PubMed:25961792,
CC ECO:0000269|PubMed:9184239}.
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:0000269|PubMed:9184239};
CC -!- INTERACTION:
CC O00442-2; P32243-2: OTX2; NbExp=3; IntAct=EBI-12886464, EBI-9087860;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:9184239}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O00442-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00442-2; Sequence=VSP_005915;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- SIMILARITY: Belongs to the RNA 3'-terminal cyclase family. Type 1
CC subfamily. {ECO:0000305}.
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DR EMBL; Y11651; CAA72364.1; -; mRNA.
DR EMBL; Y11652; CAA72365.1; -; Genomic_DNA.
DR EMBL; AL445928; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL663111; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471097; EAW72961.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW72962.1; -; Genomic_DNA.
DR EMBL; BC012604; AAH12604.1; -; mRNA.
DR CCDS; CCDS44178.1; -. [O00442-2]
DR CCDS; CCDS768.1; -. [O00442-1]
DR PIR; T48844; T48844.
DR RefSeq; NP_001124313.1; NM_001130841.1. [O00442-2]
DR RefSeq; NP_003720.1; NM_003729.3. [O00442-1]
DR AlphaFoldDB; O00442; -.
DR SMR; O00442; -.
DR BioGRID; 114187; 135.
DR IntAct; O00442; 16.
DR MINT; O00442; -.
DR STRING; 9606.ENSP00000260563; -.
DR GlyGen; O00442; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O00442; -.
DR MetOSite; O00442; -.
DR PhosphoSitePlus; O00442; -.
DR SwissPalm; O00442; -.
DR BioMuta; RTCA; -.
DR EPD; O00442; -.
DR jPOST; O00442; -.
DR MassIVE; O00442; -.
DR MaxQB; O00442; -.
DR PaxDb; 9606-ENSP00000260563; -.
DR PeptideAtlas; O00442; -.
DR ProteomicsDB; 47890; -. [O00442-1]
DR ProteomicsDB; 47891; -. [O00442-2]
DR Pumba; O00442; -.
DR Antibodypedia; 33694; 168 antibodies from 26 providers.
DR DNASU; 8634; -.
DR Ensembl; ENST00000260563.4; ENSP00000260563.4; ENSG00000137996.13. [O00442-2]
DR Ensembl; ENST00000370128.9; ENSP00000359146.4; ENSG00000137996.13. [O00442-1]
DR GeneID; 8634; -.
DR KEGG; hsa:8634; -.
DR MANE-Select; ENST00000370128.9; ENSP00000359146.4; NM_003729.4; NP_003720.1.
DR UCSC; uc001dtc.4; human. [O00442-1]
DR AGR; HGNC:17981; -.
DR CTD; 8634; -.
DR DisGeNET; 8634; -.
DR GeneCards; RTCA; -.
DR HGNC; HGNC:17981; RTCA.
DR HPA; ENSG00000137996; Low tissue specificity.
DR MIM; 611286; gene.
DR neXtProt; NX_O00442; -.
DR OpenTargets; ENSG00000137996; -.
DR PharmGKB; PA34877; -.
DR VEuPathDB; HostDB:ENSG00000137996; -.
DR eggNOG; KOG3980; Eukaryota.
DR GeneTree; ENSGT00530000063404; -.
DR HOGENOM; CLU_027882_0_1_1; -.
DR InParanoid; O00442; -.
DR OMA; WSPPIDY; -.
DR OrthoDB; 315241at2759; -.
DR PhylomeDB; O00442; -.
DR TreeFam; TF300831; -.
DR BRENDA; 6.5.1.4; 2681.
DR PathwayCommons; O00442; -.
DR SignaLink; O00442; -.
DR BioGRID-ORCS; 8634; 6 hits in 1162 CRISPR screens.
DR ChiTaRS; RTCA; human.
DR GenomeRNAi; 8634; -.
DR Pharos; O00442; Tbio.
DR PRO; PR:O00442; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O00442; Protein.
DR Bgee; ENSG00000137996; Expressed in jejunal mucosa and 207 other cell types or tissues.
DR ExpressionAtlas; O00442; baseline and differential.
DR Genevisible; O00442; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0003963; F:RNA-3'-phosphate cyclase activity; IDA:UniProtKB.
DR GO; GO:1905592; P:negative regulation of optical nerve axon regeneration; IEA:Ensembl.
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; IPR020719; RNA3'_term_phos_cycl-like_CS.
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 PROSITE; PS01287; RTC; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Direct protein sequencing; Ligase;
KW Nucleotide-binding; Nucleus; Reference proteome.
FT CHAIN 1..366
FT /note="RNA 3'-terminal phosphate cyclase"
FT /id="PRO_0000156410"
FT ACT_SITE 320
FT /note="Tele-AMP-histidine intermediate"
FT /evidence="ECO:0000250|UniProtKB:P46849"
FT BINDING 104
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P46849"
FT BINDING 131
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P46849"
FT BINDING 294
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P46849"
FT BINDING 297
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 320
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P46849"
FT VAR_SEQ 48
FT /note="L -> LSSGGWKSKIKVLT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_005915"
FT CONFLICT 34
FT /note="L -> S (in Ref. 4; AAH12604)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 366 AA; 39337 MW; D129E680FF08BAD1 CRC64;
MAGPRVEVDG SIMEGGGQIL RVSTALSCLL GLPLRVQKIR AGRSTPGLRP QHLSGLEMIR
DLCDGQLEGA EIGSTEITFT PEKIKGGIHT ADTKTAGSVC LLMQVSMPCV LFAASPSELH
LKGGTNAEMA PQIDYTVMVF KPIVEKFGFI FNCDIKTRGY YPKGGGEVIV RMSPVKQLNP
INLTERGCVT KIYGRAFVAG VLPFKVAKDM AAAAVRCIRK EIRDLYVNIQ PVQEPKDQAF
GNGNGIIIIA ETSTGCLFAG SSLGKRGVNA DKVGIEAAEM LLANLRHGGT VDEYLQDQLI
VFMALANGVS RIKTGPVTLH TQTAIHFAEQ IAKAKFIVKK SEDEEDAAKD TYIIECQGIG
MTNPNL
//
