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MT000063

UniProt Annotations

Entry Information

Gene Name	ATPase, Cu++ transporting, alpha polypeptide
Protein Entry	ATP7A_HUMAN
UniProt ID	Q04656
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=6; Name=4; IsoId=Q04656-1; Sequence=Displayed; Name=1; IsoId=Q04656-2; Sequence=VSP_000419; Name=2; IsoId=Q04656-3; Sequence=VSP_000420; Name=3; Synonyms=2-16; IsoId=Q04656-4; Sequence=VSP_000424; Note=Lacks 6 transmembrane regions and 5 heavy-metal-associated (HMA) domains.; Name=5; IsoId=Q04656-5; Sequence=VSP_000425; Note=Lacks the transmembrane domains 3 and 4. Expressed at a low level in several tissues of normal individuals and is the only isoform found in patients with OHS.; Name=6; Synonyms=NML45; IsoId=Q04656-6; Sequence=VSP_000421, VSP_000422, VSP_000423; Note=Lacks all transmembrane regions and 5 heavy-metal-associated (HMA) domains, but has a putative nuclear localization signal attached at the N-terminus.;
Catalytic Activity	ATP + H(2)O + Cu(+)(Side 1) = ADP + phosphate + Cu(+)(Side 2).
Disease	Distal spinal muscular atrophy, X-linked, 3 (DSMAX3) [MIM:300489]: A neuromuscular disorder. Distal spinal muscular atrophy, also known as distal hereditary motor neuronopathy, represents a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. {ECO:0000269\|PubMed:20170900}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Menkes disease (MNKD) [MIM:309400]: An X-linked recessive disorder of copper metabolism characterized by generalized copper deficiency. MNKD results in progressive neurodegeneration and connective-tissue disturbances: focal cerebral and cerebellar degeneration, early growth retardation, peculiar hair, hypopigmentation, cutis laxa, vascular complications and death in early childhood. The clinical features result from the dysfunction of several copper-dependent enzymes. A mild form of the disease has been described, in which cerebellar ataxia and moderate developmental delay predominate. {ECO:0000269\|PubMed:10079817, ECO:0000269\|PubMed:10319589, ECO:0000269\|PubMed:10401004, ECO:0000269\|PubMed:11241493, ECO:0000269\|PubMed:11350187, ECO:0000269\|PubMed:15981243, ECO:0000269\|PubMed:22992316, ECO:0000269\|PubMed:7977350, ECO:0000269\|PubMed:8981948}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Occipital horn syndrome (OHS) [MIM:304150]: An X-linked recessive disorder of copper metabolism. Common features are unusual facial appearance, skeletal abnormalities, chronic diarrhea and genitourinary defects. The skeletal abnormalities include occipital horns, short, broad clavicles, deformed radii, ulnae and humeri, narrowing of the rib cage, undercalcified long bones with thin cortical walls and coxa valga. {ECO:0000269\|PubMed:11431706, ECO:0000269\|PubMed:17108763, ECO:0000269\|PubMed:9246006}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Domain	The C-terminal di-leucine, 1487-Leu-Leu-1488, is an endocytic targeting signal which functions in retrieving recycling from the plasma membrane to the TGN. Mutation of the di-leucine signal results in the accumulation of the protein in the plasma membrane.
Function	May supply copper to copper-requiring proteins within the secretory pathway, when localized in the trans-Golgi network. Under conditions of elevated extracellular copper, it relocalized to the plasma membrane where it functions in the efflux of copper from cells.
Interaction	Q5EBL8:PDZD11; NbExp=4; IntAct=EBI-7706409, EBI-1644207;
Similarity	Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IB subfamily. {ECO:0000305}.
Similarity	Contains 6 HMA domains. {ECO:0000255\|PROSITE- ProRule:PRU00280}.
Subcellular Location	Golgi apparatus, trans-Golgi network membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein. Note=Cycles constitutively between the trans- Golgi network (TGN) and the plasma membrane. Predominantly found in the TGN and relocalized to the plasma membrane in response to elevated copper levels.
Subcellular Location	Isoform 3: Cytoplasm, cytosol {ECO:0000305}.
Subcellular Location	Isoform 5: Endoplasmic reticulum.
Subunit	Monomer. Interacts with PDZD11. {ECO:0000269\|PubMed:16051599}.
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.
Web Resource	Name=Protein Spotlight; Note=Heavy metal - Issue 79 of February 2007; URL="http://web.expasy.org/spotlight/back_issues/079";