RTCB_CAEEL
ID RTCB_CAEEL Reviewed; 505 AA.
AC P90838;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=RNA-splicing ligase RtcB homolog {ECO:0000255|HAMAP-Rule:MF_03144};
DE EC=6.5.1.8 {ECO:0000255|HAMAP-Rule:MF_03144, ECO:0000269|PubMed:25366321, ECO:0000269|PubMed:25429148};
DE AltName: Full=3'-phosphate/5'-hydroxy nucleic acid ligase {ECO:0000255|HAMAP-Rule:MF_03144};
GN Name=rtcb-1 {ECO:0000312|WormBase:F16A11.2a};
GN ORFNames=F16A11.2 {ECO:0000312|WormBase:F16A11.2a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP HIS-428.
RX PubMed=25366321; DOI=10.15252/embr.201439531;
RA Kosmaczewski S.G., Edwards T.J., Han S.M., Eckwahl M.J., Meyer B.I.,
RA Peach S., Hesselberth J.R., Wolin S.L., Hammarlund M.;
RT "The RtcB RNA ligase is an essential component of the metazoan unfolded
RT protein response.";
RL EMBO Rep. 15:1278-1285(2014).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF CYS-122.
RX PubMed=25429148; DOI=10.1523/jneurosci.1945-14.2014;
RA Ray A., Zhang S., Rentas C., Caldwell K.A., Caldwell G.A.;
RT "RTCB-1 mediates neuroprotection via XBP-1 mRNA splicing in the unfolded
RT protein response pathway.";
RL J. Neurosci. 34:16076-16085(2014).
CC -!- FUNCTION: Catalytic subunit of the tRNA-splicing ligase complex that
CC acts by directly joining spliced tRNA halves to mature-sized tRNAs
CC (PubMed:25366321). Required for the ligation of mRNAs and specifically,
CC regulates xbp-1 mRNA splicing during the endoplasmic reticulum stress-
CC induced unfolded protein response (PubMed:25366321, PubMed:25429148).
CC Has a neuroprotective role in the age-dependent degeneration of
CC dopamine neurons, which is mediated by xbp-1 (PubMed:25429148).
CC {ECO:0000269|PubMed:25366321, ECO:0000269|PubMed:25429148}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3'-end 3'-phospho-ribonucleotide-RNA + a 5'-end dephospho-
CC ribonucleoside-RNA + GTP = a ribonucleotidyl-ribonucleotide-RNA +
CC diphosphate + GMP; Xref=Rhea:RHEA:68076, Rhea:RHEA-COMP:10463,
CC Rhea:RHEA-COMP:13936, Rhea:RHEA-COMP:17355, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:37565, ChEBI:CHEBI:58115, ChEBI:CHEBI:83062,
CC ChEBI:CHEBI:138284, ChEBI:CHEBI:173118; EC=6.5.1.8;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03144,
CC ECO:0000269|PubMed:25366321, ECO:0000269|PubMed:25429148};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3'-end 2',3'-cyclophospho-ribonucleotide-RNA + a 5'-end
CC dephospho-ribonucleoside-RNA + GTP + H2O = a ribonucleotidyl-
CC ribonucleotide-RNA + diphosphate + GMP + H(+); Xref=Rhea:RHEA:68080,
CC Rhea:RHEA-COMP:10464, Rhea:RHEA-COMP:13936, Rhea:RHEA-COMP:17355,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:37565, ChEBI:CHEBI:58115, ChEBI:CHEBI:83064,
CC ChEBI:CHEBI:138284, ChEBI:CHEBI:173118; EC=6.5.1.8;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03144,
CC ECO:0000269|PubMed:25366321, ECO:0000269|PubMed:25429148};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03144};
CC Note=Binds 2 manganese ions per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_03144};
CC -!- SUBUNIT: Catalytic component of the tRNA-splicing ligase complex.
CC {ECO:0000255|HAMAP-Rule:MF_03144}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25366321}. Cytoplasm
CC {ECO:0000269|PubMed:25366321}.
CC -!- DISRUPTION PHENOTYPE: Mutants are sterile and few are viable
CC (PubMed:25366321, PubMed:25429148). Mutants have a slower growth rate,
CC reduced lifespan and have defective vulval development displaying a
CC severe protruding vulva phenotype (PubMed:25366321, PubMed:25429148).
CC Mutants have disrupted RNA ligase activity which results in the
CC presence of unligated tRNAs and defective tRNA processing
CC (PubMed:25366321). RNAi-mediated knockdown results in reduced
CC sensitivity to tunicamycin-induced endoplasmic reticulum (ER) stress
CC and significantly reduced levels of spliced xbp-1 mRNA under
CC tunicamycin-induced ER stress and non-stressed conditions
CC (PubMed:25429148). RNAi-mediated knockdown in dopamine neurons enhances
CC degenerative effects induced by alpha-synuclein and the neurotoxin, 6-
CC OHDA (PubMed:25429148). {ECO:0000269|PubMed:25366321,
CC ECO:0000269|PubMed:25429148}.
CC -!- MISCELLANEOUS: Ligation probably proceeds through 3 nucleotidyl
CC transfer steps, with 2',3'-cyclic phosphate termini being hydrolyzed to
CC 3'-P termini in a step that precedes 3'-P activation with GMP. In the
CC first nucleotidyl transfer step, RTCB reacts with GTP to form a
CC covalent RTCB-histidine-GMP intermediate with release of PPi; in the
CC second step, the GMP moiety is transferred to the RNA 3'-P; in the
CC third step, the 5'-OH from the opposite RNA strand attacks the
CC activated 3'-P to form a 3',5'-phosphodiester bond and release GMP.
CC {ECO:0000250|UniProtKB:Q9Y3I0, ECO:0000255|HAMAP-Rule:MF_03144}.
CC -!- SIMILARITY: Belongs to the RtcB family. {ECO:0000255|HAMAP-
CC Rule:MF_03144}.
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DR EMBL; Z81505; CAB04121.2; -; Genomic_DNA.
DR PIR; T21006; T21006.
DR RefSeq; NP_492498.1; NM_060097.4.
DR AlphaFoldDB; P90838; -.
DR SMR; P90838; -.
DR STRING; 6239.F16A11.2; -.
DR EPD; P90838; -.
DR PaxDb; P90838; -.
DR PeptideAtlas; P90838; -.
DR EnsemblMetazoa; F16A11.2a.1; F16A11.2a.1; WBGene00008877.
DR GeneID; 184556; -.
DR KEGG; cel:CELE_F16A11.2; -.
DR UCSC; F16A11.2; c. elegans.
DR CTD; 184556; -.
DR WormBase; F16A11.2a; CE23663; WBGene00008877; rtcb-1.
DR eggNOG; KOG3833; Eukaryota.
DR GeneTree; ENSGT00940000155911; -.
DR HOGENOM; CLU_022279_0_0_1; -.
DR InParanoid; P90838; -.
DR OMA; QTRGVEC; -.
DR OrthoDB; 394775at2759; -.
DR PhylomeDB; P90838; -.
DR BRENDA; 6.5.1.8; 1045.
DR PRO; PR:P90838; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00008877; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:WormBase.
DR GO; GO:0005635; C:nuclear envelope; ISS:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0072669; C:tRNA-splicing ligase complex; ISS:WormBase.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003972; F:RNA ligase (ATP) activity; IMP:WormBase.
DR GO; GO:0007281; P:germ cell development; IMP:WormBase.
DR GO; GO:0000971; P:tRNA exon ligation utilizing 2',3' cyclic phosphate of 5'-exon as source of linkage phosphate; IMP:WormBase.
DR GO; GO:0040025; P:vulval development; IMP:WormBase.
DR Gene3D; 3.90.1860.10; -; 1.
DR HAMAP; MF_03144; RtcB_euk; 1.
DR InterPro; IPR001233; RtcB.
DR InterPro; IPR036025; RtcB-like_sf.
DR InterPro; IPR027513; RtcB_euk.
DR PANTHER; PTHR11118; PTHR11118; 1.
DR Pfam; PF01139; RtcB; 1.
DR SUPFAM; SSF103365; SSF103365; 1.
DR PROSITE; PS01288; UPF0027; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; GTP-binding; Ligase; Manganese; Metal-binding;
KW Nucleotide-binding; Nucleus; Reference proteome; tRNA processing.
FT CHAIN 1..505
FT /note="RNA-splicing ligase RtcB homolog"
FT /id="PRO_0000215112"
FT ACT_SITE 428
FT /note="GMP-histidine intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03144"
FT BINDING 119
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03144"
FT BINDING 122
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03144"
FT BINDING 122
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03144"
FT BINDING 226..230
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03144"
FT BINDING 227
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03144"
FT BINDING 259
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03144"
FT BINDING 353..354
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03144"
FT BINDING 353
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03144"
FT BINDING 402..405
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03144"
FT BINDING 409
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03144"
FT BINDING 428..431
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03144"
FT BINDING 504
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03144"
FT MUTAGEN 122
FT /note="C->A: Abolishes ligase activity and is unable to
FT provide a neuroprotective role in degenerating dopamine
FT neurons."
FT /evidence="ECO:0000269|PubMed:25429148"
FT MUTAGEN 428
FT /note="H->A: Abolishes ligase activity and does not
FT activate the unfolded protein response pathway in response
FT to endoplasmic reticulum stress induced by tunicamycin."
FT /evidence="ECO:0000269|PubMed:25366321"
SQ SEQUENCE 505 AA; 55230 MW; D528F702E2586909 CRC64;
MPRTFEEECD FIDRLTDTKF RIKKGFVPNM NVEGRFYVNN SLEQLMFDEL KFSCDGQGIG
GFLPAVRQIA NVASLPGIVG HSIGLPDIHS GYGFSIGNIA AFDVGNPESV ISPGGVGFDI
NCGVRLLRTN LFEENVKPLK EQLTQSLFDH IPVGVGSRGA IPMLASDLVE CLEMGMDWTL
REGYSWAEDK EHCEEYGRML QADASKVSLR AKKRGLPQLG TLGAGNHYAE VQVVDEIYDK
HAASTMGIDE EGQVVVMLHC GSRGLGHQVA TDSLVEMEKA MARDGIVVND KQLACARINS
VEGKNYFSGM AAAANFAWVN RSCITFCVRN AFQKTFGMSA DDMDMQVIYD VSHNVAKMEE
HMVDGRPRQL CVHRKGATRA FPAHHPLIPV DYQLIGQPVL IGGSMGTCSY VLTGTEQGLV
ETFGTTCHGA GRALSRAKSR RTITWDSVID DLKKKEISIR IASPKLIMEE APESYKNVTD
VVDTCDAAGI SKKAVKLRPI AVIKG
