# GUF1

Mitochondrial GTP binding elongation factor (Homo Sapiens, GUF1), is a protein which in humans is encoded by the GUF1 gene. The GUF1 protein plays an important role in maintaining proper mitochondrial function, ensuring accuracy when mitochondrial genes are being translated. The gene shows the most expression in the brain, while the least expression is found in the pancreas.

## Function and biochemistry

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. 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
### Locus

GUF1 is located at 4p12 on the positive strand of the chromosome and consists of 17 exons.
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.

### Gene expression

RNA-seq data 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 from various human tissues supported the RNA-seq findings, confirming the reliability of the results.

## Protein

GUF1 encodes three isoforms, 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, and it is widely expressed across all amino acids.
The human GUF1 protein contains 17 motif sites, 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 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 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.

## 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 in many organisms, including vertebrates, and some invertebrates. 20 GUF1 orthologs sorted by taxonomy, sequence data, and classification. The high similarity highlights GUF1's evolutionary importance as it remains conserved in species over time.
Table of Orthologs for Human GUF1 :
| 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

There are four paralogs of GUF1 in humans.
Table of Paralogs for Human GUF1 :
| 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

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

GUF1 interacts with several proteins involved in mitochondrial translation and ribosomal function. 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.