Probable tRNA(His) guanylyltransferase (THG1L)
The protein contains 298 amino acids for an estimated molecular weight of 34831 Da.
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). (updated: Feb. 10, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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The reference OMIM entry for this protein is 610246
Spinocerebellar ataxia 28; sca28
A number sign (#) is used with this entry because spinocerebellar ataxia-28 (SCA28) is caused by heterozygous mutation in the AFG3L2 gene (604581). Mutation in the AFG3L2 gene can also cause autosomal recessive spastic ataxia-5 (SPAX5; 614487). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
CLINICAL FEATURES
Cagnoli et al. (2006) reported a 4-generation Italian family in which at least 14 members were affected with juvenile-onset spinocerebellar ataxia inherited in an autosomal dominant pattern. The mean age at onset was 19.5 years (range 12 to 36) with unbalanced standing and gait abnormalities. Other features included limb ataxia, dysarthria, slow and lower limb hyperreflexia. Two patterns of eye movement abnormalities were observed: patients with shorter disease duration had gaze-evoked nystagmus, while those with longer disease duration showed dysmetric saccades, slow saccades, ophthalmoparesis, and ptosis. The disorder was slowly progressive, and there was no evidence of sensory involvement or cognitive impairment. Brain MRI showed cerebellar atrophy. Cagnoli et al. (2010) reported 9 European families, including 8 of French and 1 of Italian origin, with autosomal dominant SCA28 confirmed by genetic analysis. The mean age at onset was 30.7 years (range, 6 to 60 years), and most patients presented with cerebellar ataxia. Other features included dysarthria (68%), ophthalmoplegia (48%) and/or gazed-evoked nystagmus (54%), saccadic pursuit (37%), slow saccades (25%), and ptosis (42%). Six patients had a full pyramidal syndrome, with increased reflexes and Babinski sign, whereas 1 had gait spasticity. Rare individuals had dystonia or parkinsonism. Overall, the disease was slowly progressive and did not result in major functional incapacity.MAPPING
By genomewide linkage analysis of a large Italian family, Cagnoli et al. (2006) identified a candidate disease locus, termed SCA28, on chromosome 18p11.22-q11.2 (maximum 2-point lod score of 4.20 for marker D18S53; maximum multipoint lod score of 4.77 at D18S453). Haplotype analysis defined a 7.9-Mb region between D18S1418 and D18S1104.MOLECULAR GENETICS
In affected members of 5 unrelated families with SCA28, including the family reported by Cagnoli et al. (2006), Di Bella et al. (2010) identified 5 different heterozygous mutations in the AFG3L2 gene (604581.0001-604581.0005). Studies in yeast showed that the mutations affected mitochondrial respiratory and proteolytic functions of the protein by both dominant-negative (E691K; 604581.0001) and loss of function (see, e.g., S674L; 604581.0002) mechanisms. Di Bella et al. (2010) hypothesized that AFG3L2 or specific substrates of AFG3L2 may have an essential function in protecting the cerebellum from neurodegeneration. Cagnoli et al. (2010) identified 6 different missense mutations in exons 15 and 16 of the AFG3L2 gene (see, e.g., 604581.0006-604581.0009) in 9 (2.6%) of 366 Caucasian European probands with autosomal dominant SCA who were negative for the most common triplet expansions in other genes. Pathogenic copy number variations of the AFG3L2 gene were not detected. ... More on the omim web site
Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 610246 was added.
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed