ATP5F1A

ATP5F1A
Identifiers
Aliases	ATP5F1A, ATP5A, ATP5AL2, ATPM, HEL-S-123m, MC5DN4, MOM2, OMR, ORM, hATP1, COXPD22, ATP synthase, H+ transporting, mitochondrial F1 complex, alpha 1, ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1, cardiac muscle, ATP5A1, ATP synthase F1 subunit alpha
External IDs	OMIM: 164360 MGI: 88115 HomoloGene: 2985 GeneCards: ATP5F1A
Gene location (Human) Chr. Chromosome 18 (human) Band 18q21.1 Start 46,080,248 bp End 46,104,334 bp
Gene location (Mouse) Chr. Chromosome 18 (mouse) Band 18 E3|18 52.38 cM Start 77,861,429 bp End 77,870,569 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right ventricle renal medulla middle temporal gyrus jejunal mucosa tibia parietal pleura kidney tubule palpebral conjunctiva retinal pigment epithelium biceps brachii Top expressed in heart quadriceps femoris muscle kidney renal cortex muscle tissue skeletal muscle tissue proximal tubule cerebellar cortex hippocampus proper neural tube More reference expression data BioGPS n/a
Gene ontology Molecular function nucleotide binding transmembrane transporter activity ATPase activity protein binding MHC class I protein binding ATP binding adenyl ribonucleotide binding RNA binding angiostatin binding proton-transporting ATP synthase activity, rotational mechanism ADP binding Cellular component mitochondrial proton-transporting ATP synthase complex membrane myelin sheath plasma membrane mitochondrial matrix mitochondrion mitochondrial inner membrane proton-transporting ATP synthase complex, catalytic core F(1) COP9 signalosome extracellular exosome extracellular matrix proton-transporting ATP synthase complex mitochondrial proton-transporting ATP synthase complex, catalytic sector F(1) Biological process embryo development lipid metabolism mitochondrial ATP synthesis coupled proton transport ion transport negative regulation of endothelial cell proliferation ATP metabolic process ATP synthesis coupled proton transport ATP biosynthetic process cristae formation positive regulation of blood vessel endothelial cell migration transport response to oxidative stress electron transport chain proton transmembrane transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 498 11946 Ensembl ENSG00000152234 ENSMUSG00000025428 UniProt P25705 Q03265 RefSeq (mRNA) NM_001001935 NM_001001937 NM_001257334 NM_001257335 NM_004046 NM_007505 RefSeq (protein) NP_001001935 NP_001001937 NP_001244263 NP_001244264 NP_004037 NP_031531 Location (UCSC) Chr 18: 46.08 – 46.1 Mb Chr 18: 77.86 – 77.87 Mb PubMed search
Wikidata
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ATP synthase subunit alpha, mitochondrial is an enzyme that in humans is encoded by the ATP5A1 gene.

Structure

The ATP5A1 gene, located on the q arm of chromosome 18 in position 21, is made up of 13 exons and is 20,090 base pairs in length. The ATP5A1 protein weighs 59.7 kDa and is composed of 553 amino acids. The protein is a subunit of the catalytic portion of the F₁F_o ATPase, also known as Complex V, which consists of 14 nuclear and 2 mitochondrial -encoded subunits. As an alpha subunit, ATP5A1 is contained within the catalytic F₁ portion of the complex. The nomenclature of the enzyme has a long history. The F₁ fraction derives its name from the term "Fraction 1" and F_o (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 F_o unit of ATP synthase. The F₁ particle is large and can be seen in the transmission electron microscope by negative staining. These are particles of 9 nm diameter that pepper the inner mitochondrial membrane. They were originally called elementary particles and were thought to contain the entire respiratory apparatus of the mitochondrion, but, through a long series of experiments, Efraim Racker and his colleagues (who first isolated the F₁ particle in 1961) were able to show that this particle is correlated with ATPase activity in uncoupled mitochondria and with the ATPase activity in submitochondrial particles created by exposing mitochondria to ultrasound. This ATPase activity was further associated with the creation of ATP by a long series of experiments in many laboratories.

Function

Mitochondrial membrane ATP synthase (F₁F_o ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F₁ - containing the extramembraneous catalytic core, and F_o - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F₁ is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F₁. Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits. Subunit alpha does not bear the catalytic high-affinity ATP-binding sites.

Clinical significance

Mutations affecting the ATP5A1 gene cause combined oxidative phosphorylation deficiency 22 (COXPD22), a mitochondrial disorder characterized by intrauterine growth retardation, microcephaly, hypotonia, pulmonary hypertension, failure to thrive, encephalopathy, and heart failure. Mutations on the ATP5A1 gene also cause mitochondrial complex V deficiency, nuclear 4 (MC5DN4), a mitochondrial disorder with heterogeneous clinical manifestations including dysmorphic features, psychomotor retardation, hypotonia, growth retardation, cardiomyopathy, enlarged liver, hypoplastic kidneys and elevated lactate levels in urine, plasma and cerebrospinal fluid.

Model organisms

Atp5a1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Abnormal
Body weight	Abnormal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Abnormal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Eye Histopathology	Normal
Citrobacter infection	Normal
All tests and analysis from

Model organisms have been used in the study of ATP5A1 function. A conditional knockout mouse line, called Atp5a1^{tm1a(EUCOMM)Wtsi} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty two tests were carried out on mutant mice and five significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and decreased body weight, lean body mass and hypoproteinemia was observed in female animals.

Further reading

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