ATP7A

ATPase, Cu++ transporting, alpha polypeptide
PDB rendering based on 1aw0.
Available structures PDB 1AW0, 1KVI, 1KVJ, 1Q8L, 1S6O, 1S6U, 1Y3J, 1Y3K, 1YJR, 1YJT, 1YJU, 1YJV, 2AW0, 2G9O, 2GA7, 2K1R, 2KIJ, 2KMV, 2KMX, 3CJK
Identifiers
Symbols	ATP7A; DSMAX; MK; MNK; SMAX3
External IDs	OMIM: 300011 MGI: 99400 HomoloGene: 35 GeneCards: ATP7A Gene
EC number	3.6.3.4
Gene Ontology Molecular function • nucleotide binding • copper-exporting ATPase activity • copper ion transmembrane transporter activity • copper ion binding • copper ion binding • protein binding • ATP binding • ATP binding • superoxide dismutase copper chaperone activity • hydrolase activity • copper-dependent protein binding • copper-transporting ATPase activity • metal ion binding Cellular component • integral to membrane of membrane fraction • cytoplasm • late endosome • endoplasmic reticulum • endoplasmic reticulum • Golgi apparatus • trans-Golgi network • cytosol • plasma membrane • plasma membrane • membrane • integral to membrane • basolateral plasma membrane • trans-Golgi network transport vesicle • secretory granule • cytoplasmic vesicle • brush border membrane • neuron projection • neuronal cell body • perinuclear region of cytoplasm Biological process • blood vessel development • in utero embryonic development • release of cytochrome c from mitochondria • blood vessel remodeling • regulation of oxidative phosphorylation • ATP catabolic process • tryptophan metabolic process • tyrosine metabolic process • catecholamine metabolic process • ATP biosynthetic process • copper ion transport • copper ion transport • cellular copper ion homeostasis • mitochondrion organization • locomotory behavior • cell death • response to iron(III) ion • response to zinc ion • detoxification of copper ion • regulation of gene expression • copper ion import • peptidyl-lysine modification • removal of superoxide radicals • cerebellar Purkinje cell differentiation • pyramidal neuron development • central nervous system neuron development • metal ion transport • extracellular matrix organization • collagen fibril organization • hair follicle morphogenesis • ion transmembrane transport • hindlimb morphogenesis • T-helper cell differentiation • epinephrine metabolic process • norepinephrine metabolic process • dopamine metabolic process • norepinephrine biosynthetic process • serotonin metabolic process • positive regulation of catalytic activity • pigmentation • neuroprotection • skin development • ATP metabolic process • elastic fiber assembly • lung alveolus development • negative regulation of metalloenzyme activity • positive regulation of metalloenzyme activity • neuron projection morphogenesis • dendrite morphogenesis • cartilage development • positive regulation of oxidoreductase activity • elastin biosynthetic process • transmembrane transport • copper ion export Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	538	11977
Ensembl	ENSG00000165240	ENSMUSG00000033792
UniProt	Q04656	Q64430
RefSeq (mRNA)	NM_000052.5	NM_001109757.1
RefSeq (protein)	NP_000043.3	NP_001103227.1
Location (UCSC)	Chr X: 77.17 – 77.31 Mb	Chr X: 103.22 – 103.32 Mb
PubMed search	[1]	[2]
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Copper-transporting ATPase 1 also known as copper pump 1 or Menkes disease-associated protein is a protein that in humans is encoded by the ATP7A gene.^[1]

Gene

The ATP7A gene is located on the long (q) arm of the X chromosome between positions 13.2 and 13.3, from base pair 76,972,353 to base pair 77,112,036.

Function

ATP7A is important for regulating copper levels in the body. This protein is found in most tissues, but it is absent from the liver. In the small intestine, the ATP7A protein helps control the absorption of copper from food. In other organs and tissues, the ATP7A protein has a dual role and shuttles between two locations within the cell. The protein normally resides in a cell structure called the Golgi apparatus, which modifies and transports newly produced enzymes and other proteins. Here, the ATP7A protein supplies copper to certain enzymes that are critical for the structure and function of bone, skin, hair, blood vessels, and the nervous system. If copper levels in the cell environment are elevated, however, the ATP7A protein moves to the cell membrane and eliminates excess copper from the cell.

Interactions

ATP7A has been shown to interact with ATOX1^[2] and GLRX.^[3]

Clinical significance

Menkes syndrome is caused by mutations in the ATP7A gene. Researchers have identified more than 100 ATP7A mutations that cause Menkes syndrome and occipital horn syndrome, the milder form of Menkes syndrome. Many of these mutations delete part of the gene and are predicted to produce a shortened ATP7A protein that is unable to transport copper. Other mutations insert additional DNA building blocks (base pairs) or use the wrong building blocks, which leads to ATP7A proteins that do not function properly.

The altered proteins that result from ATP7A mutations impair the absorption of copper from food, fail to supply copper to certain enzymes, or get stuck in the cell membrane, unable to shuttle back and forth from the Golgi. As a result of the disrupted activity of the ATP7A protein, copper is poorly distributed to cells in the body. Copper accumulates in some tissues, such as the small intestine and kidneys, while the brain and other tissues have unusually low levels. The decreased supply of copper can reduce the activity of numerous copper-containing enzymes that are necessary for the structure and function of bone, skin, hair, blood vessels, and the nervous system.

References

Further reading

External links

• MeSH ATP7A+protein,+human
• GeneReviews/NCBI/NIH/UW entry on ATP7A-Related Copper Transport Disorders Includes: Menkes Disease, Occipital Horn Syndrome, ATP7A-Related Distal Motor Neuropathy
• OMIM entries on ATP7A-Related Copper Transport Disorders
• GeneCard

v t e PDB gallery 1aw0: FOURTH METAL-BINDING DOMAIN OF THE MENKES COPPER-TRANSPORTING ATPASE, NMR, 20 STRUCTURES   1kvi: Solution Structure of the Reduced Form of the First Heavy Metal Binding Motif of the Menkes Protein   1kvj: Solution Structure of the Cu(I) bound form of the first heavy metal binding motif of the Menkes protein   1q8l: Second Metal Binding Domain of the Menkes ATPase   1s6o: Solution structure and backbone dynamics of the apo-form of the second metal-binding domain of the Menkes protein ATP7A   1s6u: Solution structure and backbone dynamics of the Cu(I) form of the second metal-binding domain of the Menkes protein ATP7A   1y3j: Solution structure of the copper(I) form of the fifth domain of Menkes protein   1y3k: Solution structure of the apo form of the fifth domain of Menkes protein   1yjr: Solution structure of the apo form of the sixth soluble domain A69P mutant of Menkes protein   1yjt: Solution structure of the Cu(I) form of the sixth soluble domain A69P mutant of Menkes protein   1yju: Solution structure of the apo form of the sixth soluble domain of Menkes protein   1yjv: Solution structure of the Cu(I) form of the sixth soluble domain of Menkes protein   2aw0: FOURTH METAL-BINDING DOMAIN OF THE MENKES COPPER-TRANSPORTING ATPASE, NMR, 20 STRUCTURES   2g9o: Solution structure of the apo form of the third metal-binding domain of ATP7A protein (Menkes Disease protein)   2ga7: Solution structure of the copper(I) form of the third metal-binding domain of ATP7A protein (menkes disease protein)