Homo sapiens Protein: ATP7A
Summary
InnateDB Protein IDBP-603725.1
Last Modified 2018-06-05 [Report errors or provide feedback]
Gene Symbol ATP7A
Protein Name ATPase copper transporting alpha
Synonyms DSMAX; MK; MNK; SMAX3;
Species Homo sapiens
Ensembl Protein ENSP00000345728
InnateDB Gene IDBG-116714 (ATP7A)
Protein Structure
UniProt Annotation
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.
Subcellular Localization Golgi apparatus, trans-Golgi network membrane {ECO:0000269PubMed:10484781, ECO:0000269PubMed:9147644, ECO:0000269PubMed:9467005}; Multi-pass membrane protein {ECO:0000255}. Cell membrane {ECO:0000269PubMed:10484781, ECO:0000269PubMed:9147644}; Multi-pass membrane protein {ECO:0000255}. Note=Cycles constitutively between the trans-Golgi network (TGN) and the plasma membrane (PubMed:9147644). Predominantly found in the TGN and relocalized to the plasma membrane in response to elevated copper levels. {ECO:0000269PubMed:9147644}.Isoform 3: Cytoplasm, cytosol {ECO:0000305}.Isoform 5: Endoplasmic reticulum {ECO:0000269PubMed:9467005}.
Disease Associations 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:0000269PubMed:10079817, ECO:0000269PubMed:10319589, ECO:0000269PubMed:10401004, ECO:0000269PubMed:11241493, ECO:0000269PubMed:11350187, ECO:0000269PubMed:15981243, ECO:0000269PubMed:21667063, ECO:0000269PubMed:22992316, ECO:0000269PubMed:7977350, ECO:0000269PubMed:8981948}. Note=The disease is caused by mutations affecting the gene represented in this entry.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:0000269PubMed:11431706, ECO:0000269PubMed:17108763, ECO:0000269PubMed:21667063, ECO:0000269PubMed:9246006}. Note=The disease is caused by mutations affecting the gene represented in this entry.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:0000269PubMed:20170900}. Note=The disease is caused by mutations affecting the gene represented in this entry.
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.
Comments
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 26 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.
Experimentally validated
Total 26 [view]
Protein-Protein 26 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 1 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000166 nucleotide binding
GO:0004008 copper-exporting ATPase activity
GO:0005375 copper ion transmembrane transporter activity
GO:0005507 copper ion binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016532 superoxide dismutase copper chaperone activity
GO:0016787 hydrolase activity
GO:0019829 cation-transporting ATPase activity
GO:0032767 copper-dependent protein binding
GO:0046872 metal ion binding
GO:0048365 Rac GTPase binding
GO:0051087 chaperone binding
GO:1903136 cuprous ion binding
Biological Process
GO:0001568 blood vessel development
GO:0001701 in utero embryonic development
GO:0001889 liver development
GO:0001974 blood vessel remodeling
GO:0002082 regulation of oxidative phosphorylation
GO:0006568 tryptophan metabolic process
GO:0006584 catecholamine metabolic process
GO:0006811 ion transport
GO:0006812 cation transport
GO:0006825 copper ion transport
GO:0006878 cellular copper ion homeostasis
GO:0007005 mitochondrion organization
GO:0007595 lactation
GO:0007626 locomotory behavior
GO:0010041 response to iron(III) ion
GO:0010042 response to manganese ion
GO:0010043 response to zinc ion
GO:0010273 detoxification of copper ion
GO:0010288 response to lead ion
GO:0010468 regulation of gene expression
GO:0010592 positive regulation of lamellipodium assembly
GO:0015677 copper ion import
GO:0015679 plasma membrane copper ion transport
GO:0018205 peptidyl-lysine modification
GO:0019430 removal of superoxide radicals
GO:0019730 antimicrobial humoral response
GO:0021702 cerebellar Purkinje cell differentiation
GO:0021860 pyramidal neuron development
GO:0021954 central nervous system neuron development
GO:0030001 metal ion transport
GO:0030198 extracellular matrix organization
GO:0030199 collagen fibril organization
GO:0031069 hair follicle morphogenesis
GO:0034220 ion transmembrane transport
GO:0034760 negative regulation of iron ion transmembrane transport
GO:0036120 cellular response to platelet-derived growth factor stimulus
GO:0042093 T-helper cell differentiation
GO:0042414 epinephrine metabolic process
GO:0042415 norepinephrine metabolic process
GO:0042417 dopamine metabolic process
GO:0042428 serotonin metabolic process
GO:0043085 positive regulation of catalytic activity
GO:0043086 negative regulation of catalytic activity
GO:0043473 pigmentation
GO:0043588 skin development
GO:0045793 positive regulation of cell size
GO:0046688 response to copper ion
GO:0048251 elastic fiber assembly
GO:0048286 lung alveolus development
GO:0048812 neuron projection morphogenesis
GO:0050679 positive regulation of epithelial cell proliferation
GO:0051216 cartilage development
GO:0051353 positive regulation of oxidoreductase activity
GO:0051542 elastin biosynthetic process
GO:0060003 copper ion export
GO:0071230 cellular response to amino acid stimulus
GO:0071236 cellular response to antibiotic
GO:0071276 cellular response to cadmium ion
GO:0071279 cellular response to cobalt ion
GO:0071280 cellular response to copper ion
GO:0071281 cellular response to iron ion
GO:0071284 cellular response to lead ion
GO:0071456 cellular response to hypoxia
GO:0099132 ATP hydrolysis coupled cation transmembrane transport
GO:1903036 positive regulation of response to wounding
GO:1904754 positive regulation of vascular associated smooth muscle cell migration
GO:1904959 regulation of cytochrome-c oxidase activity
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005770 late endosome
GO:0005783 endoplasmic reticulum
GO:0005794 Golgi apparatus
GO:0005802 trans-Golgi network
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005902 microvillus
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016323 basolateral plasma membrane
GO:0016324 apical plasma membrane
GO:0030140 trans-Golgi network transport vesicle
GO:0030141 secretory granule
GO:0030670 phagocytic vesicle membrane
GO:0031252 cell leading edge
GO:0031526 brush border membrane
GO:0043005 neuron projection
GO:0043025 neuronal cell body
GO:0043204 perikaryon
GO:0045121 membrane raft
GO:0048471 perinuclear region of cytoplasm
Protein Structure and Domains
PDB ID
InterPro IPR001757 P-type ATPase
IPR006121 Heavy metal-associated domain, HMA
IPR006122 Heavy metal-associated domain, copper ion-binding
IPR008250 P-type ATPase, A domain superfamily
IPR017969 Heavy-metal-associated, conserved site
IPR018303 P-type ATPase, phosphorylation site
IPR023214 HAD superfamily
IPR023298 P-type ATPase, transmembrane domain superfamily
IPR023299 P-type ATPase, cytoplasmic domain N
IPR027256 P-type ATPase, subfamily IB
IPR036163 Heavy metal-associated domain superfamily
IPR036412 HAD-like superfamily
PFAM PF00403
PRINTS PR00120
PR00941
PIRSF
SMART
TIGRFAMs
Post-translational Modifications
Modification
Cross-References
SwissProt Q04656
PhosphoSite PhosphoSite-
TrEMBL
UniProt Splice Variant
Entrez Gene 538
UniGene
RefSeq NP_000043
HUGO HGNC:869
OMIM 300011
CCDS CCDS35339
HPRD
IMGT
EMBL
GenPept