ATP7A
ATP7A (ATPase copper transporting alpha, also known as MNK or Copper-transporting ATPase 1) is an ATP-driven copper ion pump that maintains intracellular copper homeostasis. It moves Cu(+) across membranes and shifts its location according to cytosolic copper levels. Browse Assay Genie's current range of ATP7A research reagents below, or read on for the biology behind the target.
ATP7A is an ATP-driven Cu(+) pump. In each catalytic cycle it acquires a Cu(+) ion from a donor protein on the cytoplasmic side of the membrane and delivers it to an acceptor protein on the lumenal side. Transfer is coupled to ATP hydrolysis and to a transient phosphorylation that shifts the pump from an inward-facing to an outward-facing conformation. At low cytosolic copper, the protein sits at the trans-Golgi network, where it supplies Cu(+) to cuproenzymes of the secretory pathway. When cytosolic copper rises, it relocalises to the plasma membrane and exports excess Cu(+). In pigmented cells, it provides the copper cofactor that TYR needs to form an active holoenzyme for melanin biosynthesis in melanosomes.
The ATP7A gene encodes a transmembrane protein that belongs to the P-type cation transport ATPase family (type IB subfamily). Besides the trans-Golgi network, UniProt lists the protein at the cell membrane, melanosome membrane, early endosome membrane, endoplasmic reticulum and cytosol. It is also found in axons, dendrites and the postsynaptic density. In neurons it may play a dual role in function and survival, by regulating copper efflux and synaptic transmission and by supplying Cu(+) to enzymes such as PAM, TYR and SOD3. Alternatively spliced transcript variants have been observed. Mouse and rat both have an Atp7a ortholog.
Mutations in the ATP7A gene are associated with Menkes disease, X-linked distal spinal muscular atrophy and occipital horn syndrome. The earlier gene name, Menkes syndrome, and the alias MNK reflect this history. ATP7A is closely related to ATP7B, another copper-transporting ATPase, and is a useful target for studying copper handling, secretory pathway cuproenzymes and copper-dependent neuronal function.
ATP7A pumps Cu(+) across membranes and exports excess copper, so it is a central protein for studying intracellular copper balance.
The protein moves from the trans-Golgi network to the plasma membrane as cytosolic copper rises, a model for regulated relocalisation.
ATP7A may regulate copper efflux and synaptic transmission and supply Cu(+) to enzymes such as PAM, TYR and SOD3 in neurons.
In melanosomes, ATP7A provides the copper cofactor that TYR needs to form an active holoenzyme for melanin biosynthesis.
ATP7A is an ATP-driven pump for Cu(+) ions. It takes copper from a donor protein on the cytoplasmic side of a membrane and delivers it to an acceptor on the lumenal side. At low copper it supplies secretory pathway cuproenzymes from the trans-Golgi network. At high copper it exports the excess from the plasma membrane.
The alias is MNK, and UniProt names the protein Copper-transporting ATPase 1. Previous HGNC names include Menkes syndrome and ATPase, Cu++ transporting, alpha polypeptide. The gene has alternatively spliced transcript variants. Check the datasheet of any product for its validated reactivity.
Mutations in the ATP7A gene are associated with Menkes disease, X-linked distal spinal muscular atrophy and occipital horn syndrome. Mouse and rat each have an Atp7a ortholog. The human protein belongs to the type IB subfamily of P-type cation transport ATPases.
Other copper-transporting ATPases and members of the wider ATPase family with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q04656; product specifications from Assay Genie datasheets.