# GUF1

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{{#invoke:Infobox_gene|getTemplateData|QID=Q18045424}}

'''Mitochondrial GTP binding elongation factor (''Homo Sapiens'', GUF1)''', is a [protein](/source/protein) which in humans is encoded by the ''GUF1'' [gene](/source/gene).<ref name=":0">{{Cite web |title=GUF1 GTP binding elongation factor GUF1 [Homo sapiens (human)] - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene/60558 |access-date=2024-12-13 |website=www.ncbi.nlm.nih.gov}}</ref> The GUF1 protein plays an important role in maintaining proper [mitochondrial](/source/mitochondrial) function, ensuring accuracy when mitochondrial genes are being translated.<ref>{{Cite journal |last1=Li |first1=Pengzhou |last2=Dai |first2=Song |last3=Gao |first3=Xiang |last4=Li |first4=Weizheng |date=2023-08-01 |title=Guf1 overexpression improves pancreatic β cell functions in type 2 diabetes mellitus rats with Roux-en-Y gastric bypass (RYGB) surgery |url=https://link.springer.com/article/10.1007/s13105-023-00952-6 |journal=Journal of Physiology and Biochemistry |language=en |volume=79 |issue=3 |pages=569–582 |doi=10.1007/s13105-023-00952-6 |pmid=36905457 |issn=1877-8755|url-access=subscription }}</ref> The gene shows the most expression in the brain, while the least expression is found in the [pancreas](/source/pancreas).

== Function and biochemistry ==
GUF1 is a [GTPase](/source/GTPase) that [hydrolyzes](/source/Hydrolysis) GTP to GDP and plays an important role in maintaining mitochondrial function by ensuring accurate translation of mitochondrial genes.<ref>{{Cite journal |last1=Bauerschmitt |first1=Heike |last2=Funes |first2=Soledad |last3=Herrmann |first3=Johannes M. |date=2008-06-20 |title=The membrane-bound GTPase Guf1 promotes mitochondrial protein synthesis under suboptimal conditions |journal=The Journal of Biological Chemistry |volume=283 |issue=25 |pages=17139–17146 |doi=10.1074/jbc.M710037200 |doi-access=free |issn=0021-9258 |pmid=18442968}}</ref> It helps prevent [amino acid](/source/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](/source/hydrolysis). The G domain supports core GTPase activity.

== Gene ==

=== Locus ===
GUF1 is [located](/source/Locus_(genetics)) at 4p12 on the positive strand of the [chromosome](/source/chromosome) and consists of 17 [exon](/source/exon)s.<ref>{{Cite web |last=Database |first=GeneCards Human Gene |title=GUF1 Gene - GeneCards {{!}} GUF1 Protein {{!}} GUF1 Antibody |url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=GUF1 |archive-url=https://web.archive.org/web/20221019160230/https://www.genecards.org/cgi-bin/carddisp.pl?gene=GUF1 |archive-date=2022-10-19 |access-date=2024-12-13 |website=www.genecards.org |language=en |url-status=live }}</ref>

''GUF1'' protein found in the mitochondrial matrix and highly associated with the inner [membrane](/source/membrane). This protein goes by many names including; [EF-4](/source/EF-4), GUF1 homolog, [GTPase](/source/GTPase), and DEE40. The gene spans 22,000 [nucleotide](/source/nucleotide)s, and the protein it encodes is 669 amino acids long.<ref name=":0" />
left|thumb|450x450px|Location of GUF1 on human chromosome 4.

=== Gene expression ===
RNA-seq data<ref name=":0" /> for GUF1 gene expression across tissue types showed high expression in the [brain](/source/brain) and [cerebellum](/source/cerebellum), with the lowest expression in the pancreas. Other tissues exhibited moderate expression levels. Microarray data<ref>{{Cite web |title=2903547 - GEO Profiles - NCBI |url=https://www.ncbi.nlm.nih.gov/geoprofiles?term=(GUF1)%20AND%20GDS424 |access-date=2024-12-13 |website=www.ncbi.nlm.nih.gov}}</ref> from various human tissues supported the RNA-seq findings, confirming the reliability of the results.

== Protein ==
GUF1 encodes three isoforms,<ref name=":0" /> 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,<ref>{{Cite web |title=Expasy - Error |url=https://web.expasy.org/cgi-bin/compute_pi/pi_tool.cgi |access-date=2024-12-13 |website=web.expasy.org}}</ref> and it is widely expressed across all amino acids.<ref>{{Cite web |title=Job Dispatcher homepage &#124; EMBL-EBI |url=https://www.ebi.ac.uk/jdispatcher/seqstats/saps/summary?jobId=saps-I20241128-220646-0628-26096253-p1m&js=pass |access-date=2024-12-13 |website=www.ebi.ac.uk}}</ref>

The human GUF1 protein contains 17 [motif](/source/Motif_(software)) sites,<ref>{{Cite web |title=Motif Scan |url=https://myhits.sib.swiss/cgi-bin/motif_scan |access-date=2024-12-13 |website=myhits.sib.swiss |language=en |archive-date=2021-06-02 |archive-url=https://web.archive.org/web/20210602212349/https://myhits.sib.swiss/cgi-bin/motif_scan |url-status=dead }}</ref> including 13 [phosphorylation](/source/phosphorylation) sites (e.g., [CK2](/source/Potassium_carbonate) and [PKC](/source/PKC_alpha)-specific), which may regulate its function and signaling pathways. Additionally, there are 3 [myristylation](/source/Myristoylation) and 3 [glycosylation](/source/glycosylation) sites.

=== Protein level regulation ===
GUF1 is primarily localized to the mitochondria, with 93% of the protein found in this organelle. Deeplocs<ref>{{Cite web |title=67515AE2002AF0310FF8D5A6 expired |url=https://services.healthtech.dtu.dk/cgi-bin/webface2.cgi?jobid=67515AE2002AF0310FF8D5A6&wait=20 |access-date=2024-12-13 |website=services.healthtech.dtu.dk}}</ref> analysis also shows 22.7% localization to the [nucleus](/source/Cell_nucleus) and 29.5% to the [cytoplasm](/source/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](/source/protein_synthesis) and energy production. GUF1 presence in the nucleus and [cytoplasm](/source/cytoplasm) can also indicate involvement in [gene regulation](/source/Regulation_of_gene_expression).

An analysis via PSORT II<ref>{{Cite web |title=PSORT WWW Server |url=https://psort.hgc.jp/ |access-date=2024-12-13 |website=psort.hgc.jp}}</ref> illustrates that GUF1 lacks a strong [N-terminal](/source/N-terminus) 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.<ref>{{Cite web |date=2019-10-07 |title=Cleavage site |url=https://www.biologyonline.com/dictionary/cleavage-site#:~:text=Cleavage%20site-,Definition,the%20phosphodiester%20bond%20between%20them. |access-date=2024-12-13 |website=Biology Articles, Tutorials & Dictionary Online |language=en-US}}</ref>

== Transcript ==
GUF1 undergoes alternative splicing and this leads to several transcript variants. 
{| class="wikitable"
|+
!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<ref name="blast.ncbi.nlm.nih.gov">{{Cite web |title=Protein BLAST: search protein databases using a protein query |url=https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastp&PAGE_TYPE=BlastSearch&LINK_LOC=blasthome |access-date=2024-12-13 |website=blast.ncbi.nlm.nih.gov}}</ref> in many organisms, including [vertebrate](/source/vertebrate)s, and some [invertebrate](/source/invertebrate)s. 20 GUF1 orthologs sorted by [taxonomy](/source/taxonomy), [sequence data](/source/Sequence_dating), and classification.<ref name="blast.ncbi.nlm.nih.gov"/> The high similarity<ref>{{Cite web |title=Job Dispatcher homepage &#124; EMBL-EBI |url=https://www.ebi.ac.uk/jdispatcher/psa/emboss_needle |access-date=2024-12-13 |website=www.ebi.ac.uk}}</ref> highlights GUF1's evolutionary importance as it remains conserved in species over time.
{| class="wikitable sortable mw-collapsible"
|+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](/source/Human)''
|Human
|Primates
|'''0'''
|NP_068746.2
|669
|'''100.0%'''
|100.0%
|-
|
|''[Macaca mullata](/source/Rhesus_macaque)''
|Rhesus monkey
|Primates
|'''28.8'''
|XP_014993782.1
|663
|'''96.9%'''
|97.9%
|-
|
|''[Rattus norvegicus](/source/Brown_rat)''
|Norway rat
|Rodentia
|'''87'''
|NP_001100685.1
|659
|'''86.7%'''
|93.9%
|-
|
|''[Canis lupus familiaris](/source/Dog)''
|Dog
|Carnivora
|'''94'''
|XP_038411911.1
|610
|'''94.9%'''
|89.4%
|-
|
|''[Bos taurus](/source/Cattle)''
|Domestic cattle
|Artiodactyla
|'''94'''
|XP_010804407.1
|669
|'''90.9%'''
|71.3%
|-
|
|''[Vombatus ursinus](/source/Common_wombat)''
|Common wombat
|Diprotodontia
|'''160'''
|XP_027691870.1
|675
|'''85.9%'''
|90.9%
|-
|Reptillia/Aves
|''[Elgaria multicarinata webbii](/source/Elgaria_multicarinata_webbii)''
|Southern alligator lizard
|Squamata
|'''319'''
|XP_062991422.1
|663
|'''84.6%'''
|86.9%
|-
|
|''[Pterocles gutturalis](/source/Pterocles_gutturalis)''
|Yellow-throated sandgrouse
|Galliformes
|'''319'''
|XP_010085396.1
|610
|'''83.1%'''
|84.3%
|-
|
|''[Mesitornis unicolor](/source/Mesitornis_unicolor)''
|Brown Roatelo
|Galliformes
|'''319'''
|XP_010191475.1
|610
|'''81.6%'''
|84.0%
|-
|
|''[Chelonia mydas](/source/Chelonia_mydas)''
|Green sea turtle
|Testudines
|'''319'''
|XP_037753775.1
|664
|'''81.5%'''
|88.5%
|-
|
|''[Hirundo rustica](/source/Hirundo_rustica)''
|Barn swallow
|Passeriformes
|'''319'''
|XP_039921140.1
|658
|'''80.4%'''
|88.5%
|-
|
|''[Gallus gallus](/source/Gallus_gallus)''
|Chicken
|Galliformes
|'''319'''
|XP_001232470.2
|660
|'''80.2%'''
|87.0%
|-
|
|''[Alligator mississippiensis](/source/Alligator_mississippiensis)''
|American alligator
|Crocodilia
|'''319'''
|XP_019336662.1
|738
|'''79.0%'''
|80.8%
|-
|Amphibian
|''[Xenopus Tropicalis](/source/Western_clawed_frog)''
|Tropical clawed frog
|Anura
|'''352'''
|XP_002933495.1
|676
|'''80.5%'''
|83.7%
|-
|
|''[Spea bombifrons](/source/Plains_spadefoot_toad)''
|Plains spadefoot toad
|Anura
|'''352'''
|XP_053314393.1
|673
|'''79.9%'''
|83.0%
|-
|
|''[Nanorana parkeri](/source/Nanorana_parkeri)''
|High himalaya frog
|Anura
|'''352'''
|XP_018420074.1
|676
|'''79.0%'''
|84.4%
|-
|
|''[Lates calcarifer](/source/Barramundi)''
|Barramundi perch
|Perciformes
|'''429'''
|XP_018525292.1
|671
|'''79.6%'''
|82.5%
|-
|Fish
|''[Danio rerio](/source/Zebrafish)''
|Zebrafish
|Cypriniformes
|'''429'''
|XP_068069393.1
|680
|'''78.1%'''
|81.7%
|}

=== Paralogs ===
There are four [paralogs](/source/Sequence_homology) of GUF1 in humans.
{| class="wikitable sortable mw-collapsible"
|+Table of Paralogs for Human GUF1
|TMEM12
|Species
|Common name
|Accession number
|Sequence length
|Sequence Identity
|-
|EEF2
|[''Homo sapiens''](/source/Human)
|Human
|AAH06547.1
|583
|40.28%
|-
|MTIF2
|[''Homo sapiens''](/source/Human)
|Human
|AAH64977.1
|465
|28.19%
|-
|EEF1A1
|[''Homo sapiens''](/source/Human)
|Human
|AAH71619.1
|441
|26.86%
|-
|HBS1L
|[''Homo sapiens''](/source/Human)
|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.[[File:GUF1 Date of Divergence.png|thumb|The graph above displays the [mutation](/source/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.|363x363px|left]]

== Interacting proteins ==
[[File:GUF1 Phylogenetic tree.png|thumb|The unrooted [phylogenetic tree](/source/phylogenetic_tree)<ref>{{Cite web |title=TimeTree :: The Timescale of Life |url=https://timetree.org/ |access-date=2024-12-13 |website=timetree.org |language=en}}</ref> illustrates the evolutionary history of GUF1 orthologs, with circles indicating species group classifications|365x365px]]
GUF1 interacts with several proteins involved in mitochondrial translation and [ribosomal](/source/Ribosome) function.<ref>{{Cite web |title=GUF1 protein (human) - STRING interaction network |url=https://string-db.org/cgi/network?taskId=bWMdIPNmIBGJ&sessionId=bFvQCB3MCpna |access-date=2024-12-13 |website=string-db.org}}</ref> POLR3A is a notable protein, that is involved in RNA [transcription](/source/Transcription_(biology)). [MRPL32](/source/Mitochondrial_ribosomal_protein_L32), [MRPL20](/source/Mitochondrial_ribosomal_protein_L20), [MRPS6](/source/MRPS6), and [MRPS9](/source/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](/source/60S_ribosomal_protein_L5), [RPL11](/source/60S_ribosomal_protein_L11), [RPL23](/source/60S_ribosomal_protein_L23), and [RPS11](/source/40S_ribosomal_protein_S11). 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](/source/Diabetes) Mellitus Rats with Roux-en-Y [Gastric Bypass Surgery](/source/Gastric_bypass_surgery)'' found that GUF1 is upregulated post-surgery, enhancing mitochondrial function, promoting β [cell proliferation](/source/cell_proliferation), and reducing [apoptosis](/source/apoptosis), ultimately improving β cell function. Learn more in the suggested reading.<ref>{{Cite journal |last1=Li |first1=Pengzhou |last2=Dai |first2=Song |last3=Gao |first3=Xiang |last4=Li |first4=Weizheng |date=August 2023 |title=Guf1 overexpression improves pancreatic β cell functions in type 2 diabetes mellitus rats with Roux-en-Y gastric bypass (RYGB) surgery |journal=Journal of Physiology and Biochemistry |volume=79 |issue=3 |pages=569–582 |doi=10.1007/s13105-023-00952-6 |issn=1877-8755 |pmid=36905457}}</ref>

== References ==
{{Reflist}}

---
Adapted from the Wikipedia article [GUF1](https://en.wikipedia.org/wiki/GUF1) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/GUF1?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.