Mitochondrial GTP binding elongation factor (Homo Sapiens, GUF1), is a protein which in humans is encoded by the GUF1gene.[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.
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.
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]
Location of GUF1 on human chromosome 4.
Gene expression
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
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
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
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
Orthologs
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.
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.
The graph above displays the mutation rates of GUF1, Cytochrome C, and the Fibrinogen alpha chain, revealing a positive correlation between divergence time and mutation rates. Notably, GUF1 evolves significantly faster than Cytochrome C and the Fibrinogen alpha chain.
Interacting proteins
The unrooted phylogenetic tree illustrates the evolutionary history of GUF1 orthologs, with circles indicating species group classifications
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
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]
↑ 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. ISSN1877-8755. PMID36905457.
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