Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
0  structures 62  species 0  interactions 121  sequences 5  architectures

Family: YMF19 (PF02326)

Summary: Plant ATP synthase F0

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "MT-ATP8". More...

MT-ATP8 Edit Wikipedia article

ATP8
Identifiers
AliasesATP8, ATPase8, MTMT-ATP synthase F0 subunit 8
External IDsOMIM: 516070 HomoloGene: 124425 GeneCards: ATP8
Gene location (Human)
Mitochondrial DNA (human)
Chr.Mitochondrial DNA (human)[1]
Bandn/aStart8,366 bp[1]
End8,572 bp[1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)Chr M: 0.01 – 0.01 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human
Location of the MT-ATP8 gene in the human mitochondrial genome. MT-ATP8 is one of the two ATP synthase mitochondrial genes (red boxes).
The 46-nucleotide overlap in the reading frames of the human mitochondrial genes MT-ATP8 and MT-ATP6. For each nucleotide triplet (square brackets), the corresponding amino acid is given (one-letter code), either in the +1 frame for MT-ATP8 (in red) or in the +3 frame for MT-ATP6 (in blue).
ATP synthase protein 8 (metazoa)
Identifiers
SymbolATP-synt_8
PfamPF00895
Pfam clanCL0255
InterProIPR001421
Plant ATP synthase F0 subunit 8
Identifiers
SymbolYMF19
PfamPF02326
Pfam clanCL0255
InterProIPR003319
Fungal ATP synthase protein 8 (A6L)
Identifiers
SymbolFun_ATP-synt_8
PfamPF05933
Pfam clanCL0255
InterProIPR009230

MT-ATP8 (or ATP8) is a mitochondrial gene with the full name 'mitochondrially encoded ATP synthase membrane subunit 8' that encodes a subunit of mitochondrial ATP synthase, ATP synthase Fo subunit 8 (or subunit A6L). This subunit belongs to the Fo complex of the large, transmembrane F-type ATP synthase.[3] This enzyme, which is also known as complex V, is responsible for the final step of oxidative phosphorylation in the electron transport chain. Specifically, one segment of ATP synthase allows positively charged ions, called protons, to flow across a specialized membrane inside mitochondria. Another segment of the enzyme uses the energy created by this proton flow to convert a molecule called adenosine diphosphate (ADP) to ATP.[4] Subunit 8 differs in sequence between Metazoa, plants and Fungi.

Structure

The ATP synthase protein 8 of human and other mammals is encoded in the mitochondrial genome by the MT-ATP8 gene. When the complete human mitochondrial genome was first published, the MT-ATP8 gene was described as the unidentified reading frame URF A6L.[3] An unusual feature of the MT-ATP8 gene is its 46-nucleotide overlap with the MT-ATP6 gene. With respect to the reading frame (+1) of MT-ATP8, the MT-ATP6 gene starts on the +3 reading frame.

The MT-ATP8 protein weighs 8 kDa and is composed of 68 amino acids.[5][6] The protein is a subunit of the F1Fo ATPase, also known as Complex V, which consists of 14 nuclear- and 2 mitochondrial-encoded subunits. F-type ATPases consist of two structural domains, F1 containing the extramembraneous catalytic core and Fo containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. As an A subunit, MT-ATP8 is contained within the non-catalytic, transmembrane Fo portion of the complex, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the delta subunit of the catalytic core. Alternatively spliced transcript variants encoding the same isoform have been identified.[7][4]

Function

The MT-ATP8 gene encodes a subunit of mitochondrial ATP synthase, located within the thylakoid membrane and the inner mitochondrial membrane. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation.[7] The Fo region causes rotation of F1, which has a water-soluble component that hydrolyzes ATP and together, the F1Fo creates a pathway for movement of protons across the membrane.[8]

This protein subunit appears to be an integral component of the stator stalk in yeast mitochondrial F-ATPases.[9] The stator stalk is anchored in the membrane, and acts to prevent futile rotation of the ATPase subunits relative to the rotor during coupled ATP synthesis/hydrolysis. This subunit may have an analogous function in Metazoa.

Nomenclature

The nomenclature of the enzyme has a long history. The F1 fraction derives its name from the term "Fraction 1" and Fo (written as a subscript letter "o", not "zero") derives its name from being the binding fraction for oligomycin, a type of naturally-derived antibiotic that is able to inhibit the Fo unit of ATP synthase.[10][11] The Fo region of ATP synthase is a proton pore that is embedded in the mitochondrial membrane. It consists of three main subunits A, B, and C, and (in humans) six additional subunits, d, e, f, g, MT-ATP6 (or F6), and MT-ATP8 (or A6L). 3D structure of E. coli homologue of this subunit was modeled based on electron microscopy data (chain M of PDB: 1c17​). It forms a transmembrane 4-α-bundle.

Clinical Significance

Mutations to MT-ATP8 and other genes affecting oxidative phosphorylation in the mitochondria have been associated with a variety of neurodegenerative and cardiovascular disorders, including mitochondrial complex V deficiency, Leber's hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS), Leigh syndrome, and NARP syndrome. Most of the body's cells contain thousands of mitochondria, each with one or more copies of mitochondrial DNA. The severity of some mitochondrial disorders is associated with the percentage of mitochondria in each cell that has a particular genetic change. People with Leigh syndrome due to a MT-ATP6 gene mutation tend to have a very high percentage of mitochondria with the mutation (from more than 90 percent to 95 percent). The less-severe features of NARP result from a lower percentage of mitochondria with the mutation, typically 70 percent to 90 percent. Because these two conditions result from the same genetic changes and can occur in different members of a single family, researchers believe that they may represent a spectrum of overlapping features instead of two distinct syndromes.[4]

Mitochondrial complex V deficiency presents with heterogeneous clinical manifestations including neuropathy, ataxia, hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy can present with negligible to extreme hypertrophy, minimal to extensive fibrosis and myocyte disarray, absent to severe left ventricular outflow tract obstruction, and distinct septal contours/morphologies with extremely varying clinical course.[12][13]

Mitochondrial complex V deficiency is a shortage (deficiency) or loss of function in complex V of the electron transport chain that can cause a wide variety of signs and symptoms affecting many organs and systems of the body, particularly the nervous system and the heart. The disorder can be life-threatening in infancy or early childhood. Affected individuals may have feeding problems, slow growth, low muscle tone (hypotonia), extreme fatigue (lethargy), and developmental delay. They tend to develop elevated levels of lactic acid in the blood (lactic acidosis), which can cause nausea, vomiting, weakness, and rapid breathing. High levels of ammonia in the blood (hyperammonemia) can also occur in affected individuals, and in some cases result in abnormal brain function (encephalopathy) and damage to other organs.[14] Ataxia, microcephaly, developmental delay and intellectual disability have been observed in patients with a frameshift mutation in MT-ATP6. This causes a C insertion at position 8612 that results in a truncated protein only 36 amino acids long, and two T > C single-nucleotide polymorphisms at positions 8610 and 8614 that result in a homopolymeric cytosine stretch.[15]

Hypertrophic cardiomyopathy, a common feature of mitochondrial complex V deficiency, is characterized by thickening (hypertrophy) of the cardiac muscle that can lead to heart failure.[14] The m.8528T>C mutation occurs in the overlapping region of the MT-ATP6 and MT-ATP8 genes and has been described in multiple patients with infantile cardiomyopathy. This mutation changes the initiation codon in MT-ATP6 to threonine as well as a change from tryptophan to arginine at position 55 of MT-ATP8.[16][13] Individuals with mitochondrial complex V deficiency may also have a characteristic pattern of facial features, including a high forehead, curved eyebrows, outside corners of the eyes that point downward (downslanting palpebral fissures), a prominent bridge of the nose, low-set ears, thin lips, and a small chin (micrognathia).[14]

Infantile hypertrophic cardiomyopathy (CMHI) is also caused by mutations affecting distinct genetic loci, including MT-ATP6 and MT-ATP8. An infantile form of hypertrophic cardiomyopathy, a heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.[12][13]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000228253 - Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ a b Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG (April 1981). "Sequence and organization of the human mitochondrial genome". Nature. 290 (5806): 457–65. doi:10.1038/290457a0. PMID 7219534.
  4. ^ a b c "MT-ATP8". Genetics Home Reference. NCBI.
  5. ^ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (Oct 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  6. ^ "ATP synthase protein 8". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  7. ^ a b "MT-ATP8 mitochondrially encoded ATP synthase 8 [Homo sapiens (human)]". Gene. NCBI.
  8. ^ Velours J, Paumard P, Soubannier V, Spannagel C, Vaillier J, Arselin G, Graves PV (May 2000). "Organisation of the yeast ATP synthase F(0):a study based on cysteine mutants, thiol modification and cross-linking reagents". Biochimica et Biophysica Acta. 1458 (2–3): 443–56. doi:10.1016/S0005-2728(00)00093-1. PMID 10838057.
  9. ^ Stephens AN, Khan MA, Roucou X, Nagley P, Devenish RJ (May 2003). "The molecular neighborhood of subunit 8 of yeast mitochondrial F1F0-ATP synthase probed by cysteine scanning mutagenesis and chemical modification". The Journal of Biological Chemistry. 278 (20): 17867–75. doi:10.1074/jbc.M300967200. PMID 12626501.
  10. ^ Kagawa Y, Racker E (May 1966). "Partial resolution of the enzymes catalyzing oxidative phosphorylation. 8. Properties of a factor conferring oligomycin sensitivity on mitochondrial adenosine triphosphatase". The Journal of Biological Chemistry. 241 (10): 2461–6. PMID 4223640.
  11. ^ Mccarty RE (November 1992). "A PLANT BIOCHEMIST'S VIEW OF H+-ATPases AND ATP SYNTHASES". The Journal of Experimental Biology. 172 (Pt 1): 431–441. PMID 9874753.
  12. ^ a b "MT-ATP8 - ATP synthase protein 8 - Homo sapiens (Human)". www.uniprot.org. UniProt. Retrieved 3 August 2018.  This article incorporates text available under the CC BY 4.0 license.
  13. ^ a b c Ware SM, El-Hassan N, Kahler SG, Zhang Q, Ma YW, Miller E, Wong B, Spicer RL, Craigen WJ, Kozel BA, Grange DK, Wong LJ (May 2009). "Infantile cardiomyopathy caused by a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes". Journal of Medical Genetics. 46 (5): 308–14. doi:10.1136/jmg.2008.063149. PMID 19188198.
  14. ^ a b c "Mitochondrial complex V deficiency". Genetics Home Reference. NCBI. Retrieved 3 August 2018. This article incorporates text from this source, which is in the public domain.
  15. ^ Jackson CB, Hahn D, Schröter B, Richter U, Battersby BJ, Schmitt-Mechelke T, Marttinen P, Nuoffer JM, Schaller A (June 2017). "A novel mitochondrial ATP6 frameshift mutation causing isolated complex V deficiency, ataxia and encephalomyopathy". European Journal of Medical Genetics. 60 (6): 345–351. doi:10.1016/j.ejmg.2017.04.006. hdl:10138/237062. PMID 28412374.
  16. ^ Imai A, Fujita S, Kishita Y, Kohda M, Tokuzawa Y, Hirata T, Mizuno Y, Harashima H, Nakaya A, Sakata Y, Takeda A, Mori M, Murayama K, Ohtake A, Okazaki Y (March 2016). "Rapidly progressive infantile cardiomyopathy with mitochondrial respiratory chain complex V deficiency due to loss of ATPase 6 and 8 protein". International Journal of Cardiology. 207: 203–5. doi:10.1016/j.ijcard.2016.01.026. PMID 26803244.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article incorporates text from the public domain Pfam and InterPro: IPR001421

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Plant ATP synthase F0 Provide feedback

This family corresponds to subunit 8 (YMF19) of the F0 complex of plant and algae mitochondrial F-ATPases ( EC:3.6.1.34).

Literature references

  1. Lang BF, Burger G, O'Kelly CJ, Cedergren R, Golding GB, Lemieux C, Sankoff D, Turmel M, Gray MW; , Nature 1997;387:493-497.: An ancestral mitochondrial DNA resembling a eubacterial genome in miniature PUBMED:9168110 EPMC:9168110

  2. Stahl R, Sun S, L'Homme Y, Ketela T, Brown GG; , Nucleic Acids Res 1994;22:2109-2113.: RNA editing of transcripts of a chimeric mitochondrial gene associated with cytoplasmic male-sterility in Brassica. PUBMED:8029019 EPMC:8029019

  3. Sabar M, Gagliardi D, Balk J, Leaver CJ; , EMBO Rep. 2003;4:381-386.: ORFB is a subunit of F1F(O)-ATP synthase: insight into the basis of cytoplasmic male sterility in sunflower. PUBMED:12671689 EPMC:12671689


Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003319

This entry represents a domain found at the N terminus of subunit 8 (or YMF19) of the F0 complex of mitochondrial F-ATPases from plants and algae [PUBMED:12681508]. This subunit is sometimes found in association and N-terminal to INTERPRO, in higher plants. Subunit 8 differs in sequence between plants, Metazoa (INTERPRO) and fungi (INTERPRO) [PUBMED:12681508, PUBMED:12671689].

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan ATP_synthase (CL0255), which has the following description:

This clan contains subunits of the F0 complex of ATP-synthase. The F0 complex is the non-catalytic unit of ATPase and is involved in proton translocation across membranes.

The clan contains the following 13 members:

ATP-synt_8 ATP-synt_B FliH Fun_ATP-synt_8 HrpE Mt_ATP-synt_B NolV OSCP V-ATPase_G V-ATPase_G_2 vATP-synt_E Yae1_N YMF19

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(23)
Full
(121)
Representative proteomes UniProt
(1589)
NCBI
(5549)
Meta
(957)
RP15
(15)
RP35
(58)
RP55
(99)
RP75
(133)
Jalview View  View  View  View  View  View  View  View  View 
HTML View  View               
PP/heatmap 1 View               

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(23)
Full
(121)
Representative proteomes UniProt
(1589)
NCBI
(5549)
Meta
(957)
RP15
(15)
RP35
(58)
RP55
(99)
RP75
(133)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(23)
Full
(121)
Representative proteomes UniProt
(1589)
NCBI
(5549)
Meta
(957)
RP15
(15)
RP35
(58)
RP55
(99)
RP75
(133)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_984 (release 5.2)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Bashton M , Bateman A
Number in seed: 23
Number in full: 121
Average length of the domain: 83.90 aa
Average identity of full alignment: 49 %
Average coverage of the sequence by the domain: 49.05 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.6 22.6
Trusted cut-off 22.6 22.6
Noise cut-off 22.5 22.5
Model length: 86
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.