cutis laxa Several mutations in the ATP7A gene are responsible for a condition called occipital horn syndrome or X-linked cutis laxa, which is considered a mild form of Menkes syndrome. Occipital horn syndrome is characterized by loose and sagging skin, wedge-shaped calcium deposits in a bone at the base of the skull (the occipital bone), coarse hair, and loose joints. Most of the mutations that cause occipital horn syndrome reduce but do not eliminate the production of the ATP7A protein. A shortage of this protein impairs the absorption of copper from food and prevents its normal distribution to cells throughout the body. The decreased supply of copper can reduce the activity of numerous copper-containing enzymes, affecting the structure and function of bone, skin, hair, blood vessels, and the nervous system. The reduced activity of these enzymes underlies the characteristic features of occipital horn syndrome. Menkes syndrome Researchers have identified more than 150 mutations in the ATP7A gene that cause Menkes syndrome. Many of these mutations delete part of the gene and likely result in a shortened ATP7A protein. Other mutations insert additional DNA building blocks (nucleotides) into the gene or change single nucleotides. All of these mutations prevent the production of functional ATP7A protein. As a result, the absorption of copper from food is impaired, and copper is not supplied to certain enzymes. The abnormal protein may get stuck in the cell membrane and become unable to shuttle back and forth from the Golgi apparatus. The disrupted activity of the ATP7A protein causes copper to be 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, affecting the structure and function of bone, skin, hair, blood vessels, and the nervous system. The signs and symptoms of Menkes syndrome are caused by the reduced activity of these copper-containing enzymes.

     The ATP7A gene provides instructions for making a protein that is important for regulating copper levels in the body. Copper is necessary for many cellular functions, but it is toxic when present in excessive amounts. The ATP7A protein is found throughout the body, except in liver cells. In the small intestine, this protein helps control the absorption of copper from food. In other cells, the ATP7A protein has a dual role and shuttles between two cellular locations. The protein normally resides in a cell structure called the Golgi apparatus, which modifies newly produced proteins, including enzymes. In the Golgi apparatus, 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.

The following transcription factors affect gene expression:

• p53

Tissue specificity:

Found in most tissues except liver. Isoform 3 is widely expressed including in liver cell lines. Isoform 1 is expressed in fibroblasts, choriocarcinoma, colon carcinoma and neuroblastoma cell lines. Isoform 2 is expressed in fibroblasts, colon carcinoma and neuroblastoma cell lines.

Molecular Function:

• Atp Binding
• Copper-Dependent Protein Binding
• Copper-Exporting Atpase Activity
• Copper Ion Binding
• Copper Ion Transmembrane Transporter Activity
• Superoxide Dismutase Copper Chaperone Activity

Biological Processes:

• Blood Vessel Development
• Blood Vessel Remodeling
• Cartilage Development
• Catecholamine Metabolic Process
• Cellular Copper Ion Homeostasis
• Central Nervous System Neuron Development
• Cerebellar Purkinje Cell Differentiation
• Collagen Fibril Organization
• Copper Ion Export
• Copper Ion Import
• Copper Ion Transport
• Detoxification Of Copper Ion
• Dopamine Metabolic Process
• Elastic Fiber Assembly
• Elastin Biosynthetic Process
• Epinephrine Metabolic Process
• Extracellular Matrix Organization
• Hair Follicle Morphogenesis
• In Utero Embryonic Development
• Ion Transmembrane Transport
• Lactation
• Locomotory Behavior
• Lung Alveolus Development
• Mitochondrion Organization
• Negative Regulation Of Catalytic Activity
• Neuron Projection Morphogenesis
• Norepinephrine Metabolic Process
• Peptidyl-Lysine Modification
• Pigmentation
• Plasma Membrane Copper Ion Transport
• Positive Regulation Of Catalytic Activity
• Positive Regulation Of Oxidoreductase Activity
• Pyramidal Neuron Development
• Regulation Of Oxidative Phosphorylation
• Removal Of Superoxide Radicals
• Response To Iron(Iii) Ion
• Response To Zinc Ion
• Serotonin Metabolic Process
• Skin Development
• T-Helper Cell Differentiation
• Tryptophan Metabolic Process

Drug Bank:

• Carboplatin
• Cisplatin
• Oxaliplatin