GUF1
| GUF1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | GUF1, EF-4, GUF1 homolog, GTPase, EIEE40, EF4, GTP binding elongation factor DEE40 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 617064; MGI: 2140726; HomoloGene: 6505; GeneCards: GUF1; OMA:GUF1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Mitochondrial GTP binding elongation factor (Homo Sapiens, GUF1), is a protein which in humans is encoded by the GUF1 gene.[5] The GUF1 protein plays an important role in maintaining proper mitochondrial function, ensuring accuracy when mitochondrial genes are being translated.[6] The gene shows the most expression in the brain, while the least expression is found in the pancreas.
Function and biochemistry
[edit]GUF1 is a GTPase that hydrolyzes GTP to GDP and plays an important role in maintaining mitochondrial function by ensuring accurate translation of mitochondrial genes.[7] It helps prevent amino acid mis-incorporation under stress by facilitating ribosomal back-translocation during protein synthesis. Additionally, its C-terminal region aids in tRNA interaction, distinguishing it from other GTPases.
The highly conserved C-terminal of GUF1 facilitates tRNA binding, while the N-terminal handles GTP binding and hydrolysis. The G domain supports core GTPase activity.
Gene
[edit]Locus
[edit]GUF1 is located at 4p12 on the positive strand of the chromosome and consists of 17 exons.[8]
GUF1 protein found in the mitochondrial matrix and highly associated with the inner membrane. This protein goes by many names including; EF-4, GUF1 homolog, GTPase, and DEE40. The gene spans 22,000 nucleotides, and the protein it encodes is 669 amino acids long.[5]
Gene expression
[edit]RNA-seq data[5] for GUF1 gene expression across tissue types showed high expression in the brain and cerebellum, with the lowest expression in the pancreas. Other tissues exhibited moderate expression levels. Microarray data[9] from various human tissues supported the RNA-seq findings, confirming the reliability of the results.
Protein
[edit]GUF1 encodes three isoforms,[5] with this article focusing on isoform one. The GUF1 protein has a theoretical pI of 8.75 and a molecular weight of 74.3 kD,[10] and it is widely expressed across all amino acids.[11]
The human GUF1 protein contains 17 motif sites,[12] including 13 phosphorylation sites (e.g., CK2 and PKC-specific), which may regulate its function and signaling pathways. Additionally, there are 3 myristylation and 3 glycosylation sites.
Protein level regulation
[edit]GUF1 is primarily localized to the mitochondria, with 93% of the protein found in this organelle. Deeplocs[13] analysis also shows 22.7% localization to the nucleus and 29.5% to the cytoplasm. This strong mitochondrial localization suggests that GUF1 plays a crucial role in mitochondrial functions. This important role can include things such as protein synthesis and energy production. GUF1 presence in the nucleus and cytoplasm can also indicate involvement in gene regulation.
An analysis via PSORT II[14] illustrates that GUF1 lacks a strong N-terminal signal peptide. This could indicate that this protein is likely not secreted or directed to the secretory pathway. The predicted cleavage site for GUF1 is between positions 44 and 45; this could suggest that the protein might have a segment that is cut off to guide it to the right place in the cell.[15]
Transcript
[edit]GUF1 undergoes alternative splicing and this leads to several transcript variants.
| Isoforms | Session Number | Length | Additional Details |
|---|---|---|---|
| Isoform 1 | NP_068746.2 | 22,000 | fully coding for a functional GUF1 protein |
| Isoform 2 | NP_001332796.1 | 22,000 | exons skipped, results in truncated protein |
| Isoform 3 | NP_001332797.1 | 22,000 | N/A |
Homology
[edit]Orthologs
[edit]GUF1 has orthologs[16] in many organisms, including vertebrates, and some invertebrates. 20 GUF1 orthologs sorted by taxonomy, sequence data, and classification.[16] The high similarity[17] highlights GUF1's evolutionary importance as it remains conserved in species over time.
| TMEM12 | Genes & Species | Common name | taxonomic group | date of divergence (MYA) | accession number | sequence length | sequence identity to human protein | sequence similarity % |
| Mammal | Homo sapiens | Human | Primates | 0 | NP_068746.2 | 669 | 100.0% | 100.0% |
| Macaca mullata | Rhesus monkey | Primates | 28.8 | XP_014993782.1 | 663 | 96.9% | 97.9% | |
| Rattus norvegicus | Norway rat | Rodentia | 87 | NP_001100685.1 | 659 | 86.7% | 93.9% | |
| Canis lupus familiaris | Dog | Carnivora | 94 | XP_038411911.1 | 610 | 94.9% | 89.4% | |
| Bos taurus | Domestic cattle | Artiodactyla | 94 | XP_010804407.1 | 669 | 90.9% | 71.3% | |
| Vombatus ursinus | Common wombat | Diprotodontia | 160 | XP_027691870.1 | 675 | 85.9% | 90.9% | |
| Reptillia/Aves | Elgaria multicarinata webbii | Southern alligator lizard | Squamata | 319 | XP_062991422.1 | 663 | 84.6% | 86.9% |
| Pterocles gutturalis | Yellow-throated sandgrouse | Galliformes | 319 | XP_010085396.1 | 610 | 83.1% | 84.3% | |
| Mesitornis unicolor | Brown Roatelo | Galliformes | 319 | XP_010191475.1 | 610 | 81.6% | 84.0% | |
| Chelonia mydas | Green sea turtle | Testudines | 319 | XP_037753775.1 | 664 | 81.5% | 88.5% | |
| Hirundo rustica | Barn swallow | Passeriformes | 319 | XP_039921140.1 | 658 | 80.4% | 88.5% | |
| Gallus gallus | Chicken | Galliformes | 319 | XP_001232470.2 | 660 | 80.2% | 87.0% | |
| Alligator mississippiensis | American alligator | Crocodilia | 319 | XP_019336662.1 | 738 | 79.0% | 80.8% | |
| Amphibian | Xenopus Tropicalis | Tropical clawed frog | Anura | 352 | XP_002933495.1 | 676 | 80.5% | 83.7% |
| Spea bombifrons | Plains spadefoot toad | Anura | 352 | XP_053314393.1 | 673 | 79.9% | 83.0% | |
| Nanorana parkeri | High himalaya frog | Anura | 352 | XP_018420074.1 | 676 | 79.0% | 84.4% | |
| Lates calcarifer | Barramundi perch | Perciformes | 429 | XP_018525292.1 | 671 | 79.6% | 82.5% | |
| Fish | Danio rerio | Zebrafish | Cypriniformes | 429 | XP_068069393.1 | 680 | 78.1% | 81.7% |
Paralogs
[edit]There are four paralogs of GUF1 in humans.
| TMEM12 | Species | Common name | Accession number | Sequence length | Sequence Identity |
| EEF2 | Homo sapiens | Human | AAH06547.1 | 583 | 40.28% |
| MTIF2 | Homo sapiens | Human | AAH64977.1 | 465 | 28.19% |
| EEF1A1 | Homo sapiens | Human | AAH71619.1 | 441 | 26.86% |
| HBS1L | Homo sapiens | Human | 5LZW_jj | 710 | 25.00% |
Evolutionary history
[edit]GUF1 is a highly conserved protein that first appeared in fish approximately 429 million years ago and remains significant across species due to its conservation among orthologs.
Interacting proteins
[edit]
GUF1 interacts with several proteins involved in mitochondrial translation and ribosomal function.[19] POLR3A is a notable protein, that is involved in RNA transcription. MRPL32, MRPL20, MRPS6, and MRPS9 are the other mitochondrial ribosomal proteins. These proteins are essential for mitochondrial protein synthesis, highlighting GUF1's role in maintaining mitochondrial function. GUF1 also interacts with ribosomal proteins like RPL5, RPL11, RPL23, and RPS11. These interactions further links GUF1 to protein synthesis regulation.
Clinical significance
[edit]A study titled GUF1 Overexpression Improves Pancreatic β Cell Functions in Type 2 Diabetes Mellitus Rats with Roux-en-Y Gastric Bypass Surgery found that GUF1 is upregulated post-surgery, enhancing mitochondrial function, promoting β cell proliferation, and reducing apoptosis, ultimately improving β cell function. Learn more in the suggested reading.[20]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000151806 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029208 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d "GUF1 GTP binding elongation factor GUF1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-13.
- ^ Li, Pengzhou; Dai, Song; Gao, Xiang; Li, Weizheng (2023-08-01). "Guf1 overexpression improves pancreatic β cell functions in type 2 diabetes mellitus rats with Roux-en-Y gastric bypass (RYGB) surgery". Journal of Physiology and Biochemistry. 79 (3): 569–582. doi:10.1007/s13105-023-00952-6. ISSN 1877-8755. PMID 36905457.
- ^ Bauerschmitt, Heike; Funes, Soledad; Herrmann, Johannes M. (2008-06-20). "The membrane-bound GTPase Guf1 promotes mitochondrial protein synthesis under suboptimal conditions". The Journal of Biological Chemistry. 283 (25): 17139–17146. doi:10.1074/jbc.M710037200. ISSN 0021-9258. PMID 18442968.
- ^ Database, GeneCards Human Gene. "GUF1 Gene - GeneCards | GUF1 Protein | GUF1 Antibody". www.genecards.org. Archived from the original on 2022-10-19. Retrieved 2024-12-13.
- ^ "2903547 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-13.
- ^ "Expasy - Error". web.expasy.org. Retrieved 2024-12-13.
- ^ www.ebi.ac.uk https://www.ebi.ac.uk/jdispatcher/seqstats/saps/summary?jobId=saps-I20241128-220646-0628-26096253-p1m&js=pass. Retrieved 2024-12-13.
{{cite web}}: Missing or empty|title=(help) - ^ "Motif Scan". myhits.sib.swiss. Retrieved 2024-12-13.
- ^ "67515AE2002AF0310FF8D5A6 expired". services.healthtech.dtu.dk. Retrieved 2024-12-13.
- ^ "PSORT WWW Server". psort.hgc.jp. Retrieved 2024-12-13.
- ^ "Cleavage site". Biology Articles, Tutorials & Dictionary Online. 2019-10-07. Retrieved 2024-12-13.
- ^ a b "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2024-12-13.
- ^ www.ebi.ac.uk https://www.ebi.ac.uk/jdispatcher/psa/emboss_needle. Retrieved 2024-12-13.
{{cite web}}: Missing or empty|title=(help) - ^ "TimeTree :: The Timescale of Life". timetree.org. Retrieved 2024-12-13.
- ^ "GUF1 protein (human) - STRING interaction network". string-db.org. Retrieved 2024-12-13.
- ^ Li, Pengzhou; Dai, Song; Gao, Xiang; Li, Weizheng (August 2023). "Guf1 overexpression improves pancreatic β cell functions in type 2 diabetes mellitus rats with Roux-en-Y gastric bypass (RYGB) surgery". Journal of Physiology and Biochemistry. 79 (3): 569–582. doi:10.1007/s13105-023-00952-6. ISSN 1877-8755. PMID 36905457.