UniProtKB - Q9NWX6 (THG1_HUMAN)
Protein
Probable tRNA(His) guanylyltransferase
Gene
THG1L
Organism
Homo sapiens (Human)
Status
Functioni
Adds a GMP to the 5'-end of tRNA(His) after transcription and RNase P cleavage. This step is essential for proper recognition of the tRNA and for the fidelity of protein synthesis (Probable). Also functions as a guanyl-nucleotide exchange factor/GEF for the MFN1 and MFN2 mitofusins thereby regulating mitochondrial fusion (PubMed:25008184, PubMed:27307223). By regulating both mitochondrial dynamics and bioenergetic function, it contributes to cell survival following oxidative stress (PubMed:25008184, PubMed:27307223).1 Publication2 Publications
Catalytic activityi
- 5'-end ribonucleotide-tRNAHis + ATP + GTP + H2O = a 5'-phospho-guanosine-ribonucleotide-tRNAHis + AMP + 2 diphosphate + H+1 PublicationEC:2.7.7.791 Publication
Cofactori
Mg2+1 PublicationNote: Binds 2 magnesium ions per subunit.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 58 | Magnesium 1; catalytic1 Publication | 1 | |
Metal bindingi | 58 | Magnesium 2; catalytic1 Publication | 1 | |
Metal bindingi | 59 | Magnesium 1; via carbonyl oxygen; catalytic1 Publication | 1 | |
Metal bindingi | 105 | Magnesium 1; catalytic1 Publication | 1 | |
Metal bindingi | 105 | Magnesium 2; catalytic1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 58 – 63 | GTP1 Publication | 6 | |
Nucleotide bindingi | 104 – 105 | GTP1 Publication | 2 |
GO - Molecular functioni
- ATP binding Source: BHF-UCL
- GTP binding Source: BHF-UCL
- identical protein binding Source: IntAct
- magnesium ion binding Source: BHF-UCL
- nucleotidyltransferase activity Source: Reactome
- tRNA binding Source: BHF-UCL
- tRNA guanylyltransferase activity Source: UniProtKB
GO - Biological processi
- mitochondrial fusion Source: UniProtKB
- protein homotetramerization Source: UniProtKB
- tRNA modification Source: UniProtKB
- tRNA processing Source: UniProtKB
Keywordsi
Molecular function | Nucleotidyltransferase, Transferase |
Biological process | tRNA processing |
Ligand | GTP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.7.79, 2681 |
PathwayCommonsi | Q9NWX6 |
Reactomei | R-HSA-6782315, tRNA modification in the nucleus and cytosol |
Names & Taxonomyi
Protein namesi | Recommended name: Probable tRNA(His) guanylyltransferase (EC:2.7.7.791 Publication)Alternative name(s): Induced in high glucose-11 Publication Short name: IHG-11 Publication Interphase cytoplasmic foci protein 45 tRNA-histidine guanylyltransferase |
Gene namesi | Name:THG1L Synonyms:ICF45 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000113272.13 |
HGNCi | HGNC:26053, THG1L |
MIMi | 618802, gene |
neXtProti | NX_Q9NWX6 |
Subcellular locationi
Mitochondrion
- Mitochondrion outer membrane 1 Publication
Other locations
- Cytoplasm 1 Publication
Cytosol
- cytosol Source: Reactome
Mitochondrion
- mitochondrion Source: LIFEdb
Other locations
- transferase complex Source: BHF-UCL
Keywords - Cellular componenti
Cytoplasm, Membrane, Mitochondrion, Mitochondrion outer membranePathology & Biotechi
Involvement in diseasei
Spinocerebellar ataxia 28 (SCA28)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSpinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA28 is an autosomal dominant cerebellar ataxia (ADCA) with a slow progressive course and no evidence of sensory involvement or cognitive impairment.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_083901 | 55 | V → A in SCA28; decreased mitochondrial fusion. 2 Publications | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 58 | D → A: Reduces activity by 99.5%. 1 Publication | 1 | |
Mutagenesisi | 63 | H → A: Slightly reduced enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 104 | S → A: Slightly reduced enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 105 | D → A: Loss of enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 106 | E → A: Reduces activity by 95%. 1 Publication | 1 | |
Mutagenesisi | 127 | T → A: Abolishes oligomerization. Loss of enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 181 | H → A: Loss of enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 216 | K → A: Reduces activity by 98.5%. 1 Publication | 1 | |
Mutagenesisi | 227 | N → A: Loss of enzyme activity. 1 Publication | 1 |
Keywords - Diseasei
Disease mutation, Neurodegeneration, Spinocerebellar ataxiaOrganism-specific databases
DisGeNETi | 54974 |
MalaCardsi | THG1L |
MIMi | 610246, phenotype |
OpenTargetsi | ENSG00000113272 |
PharmGKBi | PA162405691 |
Miscellaneous databases
Pharosi | Q9NWX6, Tbio |
Polymorphism and mutation databases
BioMutai | THG1L |
DMDMi | 146325755 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000284984 | 1 – 298 | Probable tRNA(His) guanylyltransferaseAdd BLAST | 298 |
Proteomic databases
EPDi | Q9NWX6 |
jPOSTi | Q9NWX6 |
MassIVEi | Q9NWX6 |
MaxQBi | Q9NWX6 |
PaxDbi | Q9NWX6 |
PeptideAtlasi | Q9NWX6 |
PRIDEi | Q9NWX6 |
ProteomicsDBi | 82998 |
PTM databases
iPTMneti | Q9NWX6 |
PhosphoSitePlusi | Q9NWX6 |
Expressioni
Tissue specificityi
Expressed in many tissues.1 Publication
Gene expression databases
Bgeei | ENSG00000113272, Expressed in testis and 197 other tissues |
ExpressionAtlasi | Q9NWX6, baseline and differential |
Genevisiblei | Q9NWX6, HS |
Organism-specific databases
HPAi | ENSG00000113272, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
Hide detailsQ9NWX6
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 120311, 38 interactors |
DIPi | DIP-59479N |
IntActi | Q9NWX6, 15 interactors |
MINTi | Q9NWX6 |
STRINGi | 9606.ENSP00000231198 |
Miscellaneous databases
RNActi | Q9NWX6, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9NWX6 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9NWX6 |
Family & Domainsi
Sequence similaritiesi
Belongs to the tRNA(His) guanylyltransferase family.Curated
Phylogenomic databases
eggNOGi | KOG2721, Eukaryota |
GeneTreei | ENSGT00390000011705 |
HOGENOMi | CLU_044271_0_0_1 |
InParanoidi | Q9NWX6 |
OMAi | TAVMQEF |
OrthoDBi | 1152974at2759 |
PhylomeDBi | Q9NWX6 |
TreeFami | TF325119 |
Family and domain databases
Gene3Di | 3.30.70.3000, 1 hit |
InterProi | View protein in InterPro IPR025845, Thg1_C_dom IPR024956, tRNAHis_GuaTrfase_cat IPR007537, tRNAHis_GuaTrfase_Thg1 IPR038469, tRNAHis_GuaTrfase_Thg1_sf |
PANTHERi | PTHR12729, PTHR12729, 1 hit |
Pfami | View protein in Pfam PF04446, Thg1, 1 hit PF14413, Thg1C, 1 hit |
PIRSFi | PIRSF028980, tRNAHis_guanylyltransferase, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
Q9NWX6-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MWGACKVKVH DSLATISITL RRYLRLGATM AKSKFEYVRD FEADDTCLAH
60 70 80 90 100
CWVVVRLDGR NFHRFAEKHN FAKPNDSRAL QLMTKCAQTV MEELEDIVIA
110 120 130 140 150
YGQSDEYSFV FKRKTNWFKR RASKFMTHVA SQFASSYVFY WRDYFEDQPL
160 170 180 190 200
LYPPGFDGRV VVYPSNQTLK DYLSWRQADC HINNLYNTVF WALIQQSGLT
210 220 230 240 250
PVQAQGRLQG TLAADKNEIL FSEFNINYNN ELPMYRKGTV LIWQKVDEVM
260 270 280 290
TKEIKLPTEM EGKKMAVTRT RTKPVPLHCD IIGDAFWKEH PEILDEDS
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE5RIQ8 | E5RIQ8_HUMAN | Probable tRNA(His) guanylyltransfer... | THG1L | 124 | Annotation score: | ||
H0YC78 | H0YC78_HUMAN | Probable tRNA(His) guanylyltransfer... | THG1L | 34 | Annotation score: |
Sequence cautioni
The sequence AAH01523 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence AAH01852 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 57 | L → Q in BAD96839 (Ref. 5) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_083901 | 55 | V → A in SCA28; decreased mitochondrial fusion. 2 Publications | 1 | |
Natural variantiVAR_031871 | 232 | L → P4 PublicationsCorresponds to variant dbSNP:rs2270812Ensembl. | 1 | |
Natural variantiVAR_083902 | 294 | L → P Found in a patient with a severe multisystemic growth disorder and cerebellar atrophy; unknown pathological significance. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY463216 mRNA Translation: AAS21134.1 AL136669 mRNA Translation: CAB66604.1 AK000553 mRNA Translation: BAA91249.1 AK021663 mRNA Translation: BAB13870.1 CR533503 mRNA Translation: CAG38534.1 AK223119 mRNA Translation: BAD96839.1 CH471062 Genomic DNA Translation: EAW61590.1 CH471062 Genomic DNA Translation: EAW61591.1 BC001523 mRNA Translation: AAH01523.2 Different initiation. BC001852 mRNA Translation: AAH01852.2 Different initiation. BC023521 mRNA Translation: AAH23521.1 |
CCDSi | CCDS4341.1 |
RefSeqi | NP_001304753.1, NM_001317824.1 NP_001304754.1, NM_001317825.1 NP_001304755.1, NM_001317826.1 NP_060342.2, NM_017872.4 |
Genome annotation databases
Ensembli | ENST00000231198; ENSP00000231198; ENSG00000113272 |
GeneIDi | 54974 |
KEGGi | hsa:54974 |
UCSCi | uc003lxd.4, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY463216 mRNA Translation: AAS21134.1 AL136669 mRNA Translation: CAB66604.1 AK000553 mRNA Translation: BAA91249.1 AK021663 mRNA Translation: BAB13870.1 CR533503 mRNA Translation: CAG38534.1 AK223119 mRNA Translation: BAD96839.1 CH471062 Genomic DNA Translation: EAW61590.1 CH471062 Genomic DNA Translation: EAW61591.1 BC001523 mRNA Translation: AAH01523.2 Different initiation. BC001852 mRNA Translation: AAH01852.2 Different initiation. BC023521 mRNA Translation: AAH23521.1 |
CCDSi | CCDS4341.1 |
RefSeqi | NP_001304753.1, NM_001317824.1 NP_001304754.1, NM_001317825.1 NP_001304755.1, NM_001317826.1 NP_060342.2, NM_017872.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3OTB | X-ray | 2.95 | A/B | 30-298 | [»] | |
3OTC | X-ray | 3.01 | A/B | 30-298 | [»] | |
3OTD | X-ray | 2.28 | A/B | 30-298 | [»] | |
3OTE | X-ray | 2.56 | A/B | 30-298 | [»] | |
SMRi | Q9NWX6 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 120311, 38 interactors |
DIPi | DIP-59479N |
IntActi | Q9NWX6, 15 interactors |
MINTi | Q9NWX6 |
STRINGi | 9606.ENSP00000231198 |
PTM databases
iPTMneti | Q9NWX6 |
PhosphoSitePlusi | Q9NWX6 |
Polymorphism and mutation databases
BioMutai | THG1L |
DMDMi | 146325755 |
Proteomic databases
EPDi | Q9NWX6 |
jPOSTi | Q9NWX6 |
MassIVEi | Q9NWX6 |
MaxQBi | Q9NWX6 |
PaxDbi | Q9NWX6 |
PeptideAtlasi | Q9NWX6 |
PRIDEi | Q9NWX6 |
ProteomicsDBi | 82998 |
Protocols and materials databases
Antibodypediai | 28457, 89 antibodies |
DNASUi | 54974 |
Genome annotation databases
Ensembli | ENST00000231198; ENSP00000231198; ENSG00000113272 |
GeneIDi | 54974 |
KEGGi | hsa:54974 |
UCSCi | uc003lxd.4, human |
Organism-specific databases
CTDi | 54974 |
DisGeNETi | 54974 |
EuPathDBi | HostDB:ENSG00000113272.13 |
GeneCardsi | THG1L |
HGNCi | HGNC:26053, THG1L |
HPAi | ENSG00000113272, Low tissue specificity |
MalaCardsi | THG1L |
MIMi | 610246, phenotype 618802, gene |
neXtProti | NX_Q9NWX6 |
OpenTargetsi | ENSG00000113272 |
PharmGKBi | PA162405691 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2721, Eukaryota |
GeneTreei | ENSGT00390000011705 |
HOGENOMi | CLU_044271_0_0_1 |
InParanoidi | Q9NWX6 |
OMAi | TAVMQEF |
OrthoDBi | 1152974at2759 |
PhylomeDBi | Q9NWX6 |
TreeFami | TF325119 |
Enzyme and pathway databases
BRENDAi | 2.7.7.79, 2681 |
PathwayCommonsi | Q9NWX6 |
Reactomei | R-HSA-6782315, tRNA modification in the nucleus and cytosol |
Miscellaneous databases
BioGRID-ORCSi | 54974, 546 hits in 854 CRISPR screens |
ChiTaRSi | THG1L, human |
EvolutionaryTracei | Q9NWX6 |
GeneWikii | THG1L |
GenomeRNAii | 54974 |
Pharosi | Q9NWX6, Tbio |
PROi | PR:Q9NWX6 |
RNActi | Q9NWX6, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000113272, Expressed in testis and 197 other tissues |
ExpressionAtlasi | Q9NWX6, baseline and differential |
Genevisiblei | Q9NWX6, HS |
Family and domain databases
Gene3Di | 3.30.70.3000, 1 hit |
InterProi | View protein in InterPro IPR025845, Thg1_C_dom IPR024956, tRNAHis_GuaTrfase_cat IPR007537, tRNAHis_GuaTrfase_Thg1 IPR038469, tRNAHis_GuaTrfase_Thg1_sf |
PANTHERi | PTHR12729, PTHR12729, 1 hit |
Pfami | View protein in Pfam PF04446, Thg1, 1 hit PF14413, Thg1C, 1 hit |
PIRSFi | PIRSF028980, tRNAHis_guanylyltransferase, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | THG1_HUMAN | |
Accessioni | Q9NWX6Primary (citable) accession number: Q9NWX6 Secondary accession number(s): D3DQJ5 Q9H0S2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 1, 2007 |
Last sequence update: | May 1, 2007 | |
Last modified: | December 2, 2020 | |
This is version 155 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations