List of human ATPase genes

A list of human ATPase genes is included along with their likely functions and interrelationships. The total quantity of adenosine triphosphate (ATP) in the human body is about 0.1 mole (about 6 x 10 molecules). This ATP is constantly being broken down into adenosine diphosphate (ADP) to provide energy for activity, and then converted back into ATP. At any given time, the total amount of ATP + ADP remains fairly constant. The energy used by our cells requires the hydrolysis of 100 to 150 moles (6 to 9 x 10 molecules) of ATP daily, which is around 50 to 75 kg. Typically, we will use up our body weight of ATP over the course of the day. This means that each ATP molecule is recycled 1000 to 1500 times daily, or about once every minute.
Enzyme reaction
The Nomenclature Committee of the International Union of Biochemistry and Molecular Biology has a classification that is used to assigned an Enzyme Commission number (EC number) to an enzyme. Every EC number is associated with a recommended name for the respective enzyme. EC numbers do not specify enzymes, but enzyme-catalyzed reactions. If different enzymes (for instance from different organisms) catalyze the same reaction, then they receive the same EC number.
Phosphate reaction R00086 describes the ATP synthase (making ATP from ADP in this direction >) <> ATPase process and some of the chemicals involved
# ADP + Orthophosphate (Pi) <=> ATP + H2O : Enzyme ATPase/ATP synthase, aka ATP phosphohydrolase EC 3.6.3.-. EC 3.6.3.- contains the ATPases. Specific reactions with some additional chemicals have a fourth digit to replace the dash (-). These are listed below with their respective reactions.
The enzyme ATPase/ATP synthase reduces the energy barrier. This one phosphate reaction has more human genes (87) and more enzymes (66) to bring it about than any other phosphate reaction.
ATPase
ATPases are a class of enzymes that catalyze the decomposition of ATP into ADP and free phosphate. This dephosphorylation reaction releases energy, which the enzyme (in most cases) harnesses to drive other chemical reactions that would not otherwise occur. All known forms of life widely use this process. Proton-translocating ATPases have fundamental roles in energy conservation, secondary active transport, acidification of intracellular organelles, and cellular pH homeostasis.
There are four classes of ATPases: E, F, P, and V. The F and V classes contain rotary motors.
E-ATPase
E-ATPases are cell-surface enzymes that hydrolyse a range of nucleoside triphosphates (NTP)s, including extracellular ATP.
* Ca transporting (EC 3.6.3.8), where the genes for it are ATP2A1, ATP2A2, ATP2A3, ATP2B1, ATP2B2, ATP2B3, ATP2B4, and ATP2C1.
* Mg transporting: ATP3. Magnesium-ATPase is an ATPase that pumps magnesium. It is found in erythrocytes. There is apparently no human ATP3 gene.
* Cu transporting (EC 3.6.3.4): ATP7A, ATP7B.
* Inorganic ion transporting and metabolism, Class VI, type 11 (EC 3.6.3.1): ATP11A, ATP11B, ATP11C.
* Inorganic ion transporting and metabolism, type 13 (3.6.3.8): ATP13A1, ATP13A2, ATP13A3, ATP13A4, ATP13A5.
F-ATPase
F-ATPase (F1FO-ATPase) can use energy released by ATP hydrolysis to pump protons against their thermodynamic gradient.
* H transporting, mitochondrial (EC 3.6.3.14): ATP5A1, ATP5B, ATP5C1, ATP5C2, ATP5D, ATP5E, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5H, ATP5I, ATP5J, ATP5J2, ATP5L, ATP5L2, ATP5O, and ATP5S.
P-ATPase
P-ATPases are found in the plasma membranes and organelles, and function to transport a variety of different ions across membranes.
* Na /K transporting (EC 3.6.3.9): ATP1A1, ATP1A2, ATP1A3, ATP1A4, ATP1B1, ATP1B2, ATP1B3, and ATP1B4.
* H /K exchanging (EC 3.6.3.10): ATP4A, and ATP4B.
* Amphipaths, such as phosphatidylserine, transporting, Class I, type 8 (EC 3.6.3.1): ATP8A1, ATP8B1, ATP8B2, ATP8B3, and ATP8B4.
* Inorganic ion transporting and metabolism, Class II, type 9 (EC 3.6.3.1): ATP9A and ATP9B.
* Cation transporting, phosphatidylserine and phosphatidylethanolamine transporting, Class V, type 10 (EC 3.6.3.1): ATP10A, ATP10B, and ATP10D.
* H /K transporting, nongastric (EC 3.6.3.10: ATP12A.
V-ATPase
V-ATPases (V1VO-ATPases) are primarily found in vacuoles, catalysing ATP hydrolysis to transport solutes and lower pH in organelles. The vacuolar (V-type) ATPases have a transmembrane proton-conducting sector and an extramembrane catalytic sector.
* H transporting, lysosomal (EC 3.6.3.14): ATP6AP1, ATP6AP2, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, and ATP6V0E.
ATP synthase
An ATP synthase () is a general term for an enzyme that can synthesize adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate by using some form of energy.
There are four classes of ATP synthase: E, F, P, and V. Each is as described above under ATPase, but operating in reverse.
E-ATP synthase
: ADP + Orthophosphate (Pi) + Cu (Out) <=> ATP + H2O + Cu (In) : Enzyme EC 3.6.3.4 copper-exporting ATPase/ATP synthase, aka ATP phosphohydrolase, GeneID: 538 ATP7A ATPase, Cu transporting, alpha polypeptide.
As the synthase EC 3.6.3.4 transports copper out of a cell it converts ADP to ATP. To do so requires Mg as a cofactor. An open question to be resolved is whether ATP7A is translocated to the plasma membrane with the Golgi-derived vesicles, becomes fused with the plasma membrane to transport copper from the cytoplasm to milk, for example, or is involved in loading copper into transport vesicles that merge with the plasma membrane to discharge their content into milk.
ATP7B functions similarly to ATP7A as a monomer that when a synthase exports hepatic copper out of cells into the bile. EC 3.6.3.4 is also ATP7B ATPase, Cu transporting, beta polypeptide, GeneID: 540, also with Mg as a cofactor.
: ADP + Orthophosphate (Pi) + Phospholipid(Out) <=> ATP + H2O + Phospholipid(In) : Enzyme EC 3.6.3.1 phospholipid-translocating ATPase/ATP synthase, aka flippase, GeneID: 23250 ATP11A ATPase, class VI, type 11A. Mg is a cofactor.
The enzyme apparently moves phospholipids from one membrane face to another.
ATP11B enzyme EC 3.6.3.1 functions similarly to ATP11A, for example, in the rabbit leukocyte.
F-ATP synthase
The great majority of ATP is produced by F-ATP synthases (F1FO-ATP synthase) in mitochondrial membranes. F-ATP synthase is an anabolic enzyme that harnesses the energy of a transmembrane electrochemical gradient of protons across the inner membrane generated by oxidative phosphorylation as an energy source for adding an inorganic phosphate group to ADP to form ATP.
When a proton moves down the concentration gradient, it gives the enzyme a spinning motion. The rotor rotates in the membrane plane. This unique spinning motion bonds ADP and Pi together to create ATP.
F-ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, FO, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of five different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative each of the other 3. The general proton channel consists of three main subunits (a, b, c) plus d, e, f, g, h. The ring of rotating proteins consists of ten, eleven or fourteen in number of subunit-c proteins.
The human proton channel appears to have nine subunits (a, b, c, d, e, f, g, F6 and 8).
The mammalian form of this enzyme has been extensively studied using beef heart and rat liver as a source. It is a complex of 16 different subunits with F1: alpha, beta, gamma, delta, epsilon and FO: a, b, c, d, e, f, g, A6L, O subunit, and coupling factor 6 (F6). Associated in the complex under some conditions is an intrinsic inhibitor protein IF1. Human F1FO ATP synthase has been characterized from human heart. The enzyme has the same subunit composition as that from bovine heart. The associated inhibitor protein IF1 is the product of gene EIF1AX.
Human F complex:
Catalytic core (F1 - Fraction 1)
* alpha subunit:
** ATP5A1 and ATPAF2.
* beta subunit:
** ATP5B, ATPAF1, and C16orf7.
* gamma subunit:
** ATP5C1.
* delta subunit:
** ATP5D. The delta complex comprises the peripheral stator that is bound to F0 subunit a, and to the F1 hexamer (3 alpha, 3 beta).
* epsilon subunit:
** ATP5E.
Human proton channel (membrane-spanning component, FO):
* subunit a:
** Subunit 6 ATP6 is the homolog of subunit a. The delta complex interacts with subunit a. Subunit a forms the complex ab2 with the subunit b dimer. Together with F1 components alpha(3), beta(3), and delta form the stator of ATP synthase.
* subunit b:
** ATP5F1 This subunit peripherally connects by multiple contacts with alpha, beta and gamma subunits, and with subunit a.
* subunit c:
** ATP5G1, ATP5G2, ATP5G3 Together with the gamma and epsilon subunits, subunit c forms the centrally located rotor element, which has to be counteracted by a peripheral stator element.
* subunit d:
** ATP5H.
* subunit e:
** ATP5I (ATP5K).
* subunit f:
** ATP5J2 and LOC645225.
* subunit g:
** ATP5L.
* subunit 8 or A6L:
** Fungal ATP synthase FO subunit 8 (A6L) is an EC:3.6.3.14 and may be related to human ATP synthase protein 8 (MT-ATP8). Subunit 8 possesses a single transmembrane domain, which extends across the inner membrane of intact mitochondria. As subunit d is a likely component of the stator stalk and there are cross-links between subunits 8 and d, subunit 8 is a part of the stator stalk.
Connector (links catalytic core with proton channel):
* subunit O (OSCP—the oligomycin sensitivity conferral protein):
** ATP5O ATP5O may be part of the connector linking F1 and FO components and may be involved in transmission of conformational changes or proton conductance.
* subunit F6:
** ATP5J.
* subunit s:
** ATP5S. But others have not found this subunit s (Factor B) to be present in FO.<ref name=Aggeler/>
** ATP5SL.

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