UniProt functional annotation for Q9NWX6



	UniProt functional annotation for Q9NWX6

UniProt code: Q9NWX6.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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). {ECO:0000269|PubMed:25008184, ECO:0000269|PubMed:27307223, ECO:0000305|PubMed:21059936}.

Catalytic activity: Reaction=5'-end ribonucleotide-tRNA(His) + ATP + GTP + H2O = a 5'- phospho-guanosine-ribonucleotide-tRNA(His) + AMP + 2 diphosphate + H(+); Xref=Rhea:RHEA:54564, Rhea:RHEA-COMP:14193, Rhea:RHEA- COMP:14917, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:138282, ChEBI:CHEBI:141847, ChEBI:CHEBI:456215; EC=2.7.7.79; Evidence={ECO:0000269|PubMed:21059936};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:21059936}; Note=Binds 2 magnesium ions per subunit. {ECO:0000269|PubMed:21059936};

Subunit: Homotetramer (PubMed:21059936). Interacts with MFN1 and MFN2; functions as a guanyl-nucleotide exchange factor/GEF for MFN2 and also probably MFN1 (PubMed:25008184). {ECO:0000269|PubMed:21059936, ECO:0000269|PubMed:25008184}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:15459185}. Mitochondrion outer membrane {ECO:0000305|PubMed:25008184}.

Tissue specificity: Expressed in many tissues. {ECO:0000269|PubMed:15459185}.

Disease: Spinocerebellar ataxia, autosomal recessive, 28 (SCAR28) [MIM:618800]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR28 patients manifest mild motor developmental delay, gait ataxia, and dysarthria. Some patients show mildly impaired intellectual development. Disease onset is in early childhood. {ECO:0000269|PubMed:27307223, ECO:0000269|PubMed:31168944}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the tRNA(His) guanylyltransferase family. {ECO:0000305}.

Sequence caution: Sequence=AAH01523.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH01852.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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). {ECO:0000269\|PubMed:25008184, ECO:0000269\|PubMed:27307223, ECO:0000305\|PubMed:21059936}.


Catalytic activity:		Reaction=5'-end ribonucleotide-tRNA(His) + ATP + GTP + H2O = a 5'- phospho-guanosine-ribonucleotide-tRNA(His) + AMP + 2 diphosphate + H(+); Xref=Rhea:RHEA:54564, Rhea:RHEA-COMP:14193, Rhea:RHEA- COMP:14917, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:138282, ChEBI:CHEBI:141847, ChEBI:CHEBI:456215; EC=2.7.7.79; Evidence={ECO:0000269\|PubMed:21059936};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:21059936}; Note=Binds 2 magnesium ions per subunit. {ECO:0000269\|PubMed:21059936};
Subunit:		Homotetramer (PubMed:21059936). Interacts with MFN1 and MFN2; functions as a guanyl-nucleotide exchange factor/GEF for MFN2 and also probably MFN1 (PubMed:25008184). {ECO:0000269\|PubMed:21059936, ECO:0000269\|PubMed:25008184}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:15459185}. Mitochondrion outer membrane {ECO:0000305\|PubMed:25008184}.
Tissue specificity:		Expressed in many tissues. {ECO:0000269\|PubMed:15459185}.
Disease:		Spinocerebellar ataxia, autosomal recessive, 28 (SCAR28) [MIM:618800]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR28 patients manifest mild motor developmental delay, gait ataxia, and dysarthria. Some patients show mildly impaired intellectual development. Disease onset is in early childhood. {ECO:0000269\|PubMed:27307223, ECO:0000269\|PubMed:31168944}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the tRNA(His) guanylyltransferase family. {ECO:0000305}.
Sequence caution:		Sequence=AAH01523.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH01852.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};