P90838 · RTCB_CAEEL
- ProteinRNA-splicing ligase RtcB homolog
- Genertcb-1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids505 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalytic subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs (PubMed:25366321).
Required for the ligation of mRNAs and specifically, regulates xbp-1 mRNA splicing during the endoplasmic reticulum stress-induced unfolded protein response (PubMed:25366321, PubMed:25429148).
Has a neuroprotective role in the age-dependent degeneration of dopamine neurons, which is mediated by xbp-1 (PubMed:25429148).
Required for the ligation of mRNAs and specifically, regulates xbp-1 mRNA splicing during the endoplasmic reticulum stress-induced unfolded protein response (PubMed:25366321, PubMed:25429148).
Has a neuroprotective role in the age-dependent degeneration of dopamine neurons, which is mediated by xbp-1 (PubMed:25429148).
Miscellaneous
Ligation probably proceeds through 3 nucleotidyl transfer steps, with 2',3'-cyclic phosphate termini being hydrolyzed to 3'-P termini in a step that precedes 3'-P activation with GMP. In the first nucleotidyl transfer step, RTCB reacts with GTP to form a covalent RTCB-histidine-GMP intermediate with release of PPi; in the second step, the GMP moiety is transferred to the RNA 3'-P; in the third step, the 5'-OH from the opposite RNA strand attacks the activated 3'-P to form a 3',5'-phosphodiester bond and release GMP.
Catalytic activity
- a 3'-end 3'-phospho-ribonucleotide-RNA + a 5'-end dephospho-ribonucleoside-RNA + GTP = a ribonucleotidyl-ribonucleotide-RNA + diphosphate + GMP
Cofactor
Note: Binds 2 manganese ions per subunit.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 119 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 122 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 122 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 226-230 | GMP (UniProtKB | ChEBI) | ||||
Sequence: NHYAE | ||||||
Binding site | 227 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 259 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 353 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 353-354 | GMP (UniProtKB | ChEBI) | ||||
Sequence: HN | ||||||
Binding site | 402-405 | GMP (UniProtKB | ChEBI) | ||||
Sequence: GGSM | ||||||
Binding site | 409 | GMP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Active site | 428 | GMP-histidine intermediate | ||||
Sequence: H | ||||||
Binding site | 428-431 | GMP (UniProtKB | ChEBI) | ||||
Sequence: HGAG | ||||||
Binding site | 504 | GMP (UniProtKB | ChEBI) | ||||
Sequence: K |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | nuclear envelope | |
Cellular Component | nucleus | |
Cellular Component | tRNA-splicing ligase complex | |
Molecular Function | GTP binding | |
Molecular Function | metal ion binding | |
Molecular Function | RNA ligase (ATP) activity | |
Molecular Function | RNA ligase (GTP) activity | |
Biological Process | germ cell development | |
Biological Process | tRNA splicing, via endonucleolytic cleavage and ligation | |
Biological Process | vulval development |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRNA-splicing ligase RtcB homolog
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Nematoda > Chromadorea > Rhabditida > Rhabditina > Rhabditomorpha > Rhabditoidea > Rhabditidae > Peloderinae > Caenorhabditis
Accessions
- Primary accessionP90838
Proteomes
Organism-specific databases
Phenotypes & Variants
Disruption phenotype
Mutants are sterile and few are viable (PubMed:25366321, PubMed:25429148).
Mutants have a slower growth rate, reduced lifespan and have defective vulval development displaying a severe protruding vulva phenotype (PubMed:25366321, PubMed:25429148).
Mutants have disrupted RNA ligase activity which results in the presence of unligated tRNAs and defective tRNA processing (PubMed:25366321).
RNAi-mediated knockdown results in reduced sensitivity to tunicamycin-induced endoplasmic reticulum (ER) stress and significantly reduced levels of spliced xbp-1 mRNA under tunicamycin-induced ER stress and non-stressed conditions (PubMed:25429148).
RNAi-mediated knockdown in dopamine neurons enhances degenerative effects induced by alpha-synuclein and the neurotoxin, 6-OHDA (PubMed:25429148).
Mutants have a slower growth rate, reduced lifespan and have defective vulval development displaying a severe protruding vulva phenotype (PubMed:25366321, PubMed:25429148).
Mutants have disrupted RNA ligase activity which results in the presence of unligated tRNAs and defective tRNA processing (PubMed:25366321).
RNAi-mediated knockdown results in reduced sensitivity to tunicamycin-induced endoplasmic reticulum (ER) stress and significantly reduced levels of spliced xbp-1 mRNA under tunicamycin-induced ER stress and non-stressed conditions (PubMed:25429148).
RNAi-mediated knockdown in dopamine neurons enhances degenerative effects induced by alpha-synuclein and the neurotoxin, 6-OHDA (PubMed:25429148).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 122 | Abolishes ligase activity and is unable to provide a neuroprotective role in degenerating dopamine neurons. | ||||
Sequence: C → A | ||||||
Mutagenesis | 428 | Abolishes ligase activity and does not activate the unfolded protein response pathway in response to endoplasmic reticulum stress induced by tunicamycin. | ||||
Sequence: H → A |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000215112 | 1-505 | RNA-splicing ligase RtcB homolog | |||
Sequence: MPRTFEEECDFIDRLTDTKFRIKKGFVPNMNVEGRFYVNNSLEQLMFDELKFSCDGQGIGGFLPAVRQIANVASLPGIVGHSIGLPDIHSGYGFSIGNIAAFDVGNPESVISPGGVGFDINCGVRLLRTNLFEENVKPLKEQLTQSLFDHIPVGVGSRGAIPMLASDLVECLEMGMDWTLREGYSWAEDKEHCEEYGRMLQADASKVSLRAKKRGLPQLGTLGAGNHYAEVQVVDEIYDKHAASTMGIDEEGQVVVMLHCGSRGLGHQVATDSLVEMEKAMARDGIVVNDKQLACARINSVEGKNYFSGMAAAANFAWVNRSCITFCVRNAFQKTFGMSADDMDMQVIYDVSHNVAKMEEHMVDGRPRQLCVHRKGATRAFPAHHPLIPVDYQLIGQPVLIGGSMGTCSYVLTGTEQGLVETFGTTCHGAGRALSRAKSRRTITWDSVIDDLKKKEISIRIASPKLIMEEAPESYKNVTDVVDTCDAAGISKKAVKLRPIAVIKG |
Proteomic databases
Expression
Gene expression databases
Interaction
Subunit
Catalytic component of the tRNA-splicing ligase complex.
Protein-protein interaction databases
Structure
Sequence
- Sequence statusComplete
- Length505
- Mass (Da)55,230
- Last updated1997-11-01 v2
- ChecksumD528F702E2586909
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Z81505 EMBL· GenBank· DDBJ | CAB04121.2 EMBL· GenBank· DDBJ | Genomic DNA |