InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ATP7A

Summary

InnateDB Protein

IDBP-77704.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ATP7A

Protein Name

ATPase, Cu++ transporting, alpha polypeptide

Synonyms

DSMAX; MK; MNK; SMAX3;

Species

Homo sapiens

Ensembl Protein

ENSP00000343026

InnateDB Gene

IDBG-77700 (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; 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.Isoform 3: Cytoplasm, cytosol {ECO:0000305}.Isoform 5: Endoplasmic reticulum.

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: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: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 8 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	8 [view]
Protein-Protein	8 [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:0019829	cation-transporting ATPase activity
GO:0032767	copper-dependent protein binding
GO:0046872	metal ion binding

Biological Process

GO:0001568	blood vessel development
GO:0001974	blood vessel remodeling
GO:0002082	regulation of oxidative phosphorylation
GO:0006568	tryptophan metabolic process
GO:0006584	catecholamine metabolic process
GO:0006812	cation transport
GO:0006825	copper ion transport
GO:0006878	cellular copper ion homeostasis
GO:0007005	mitochondrion organization
GO:0007626	locomotory behavior
GO:0010273	detoxification of copper ion
GO:0015677	copper ion import
GO:0018205	peptidyl-lysine modification
GO:0019430	removal of superoxide radicals
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: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:0043473	pigmentation
GO:0043588	skin development
GO:0048251	elastic fiber assembly
GO:0048286	lung alveolus development
GO:0048553	negative regulation of metalloenzyme activity
GO:0048554	positive regulation of metalloenzyme activity
GO:0048812	neuron projection morphogenesis
GO:0051216	cartilage development
GO:0051353	positive regulation of oxidoreductase activity
GO:0051542	elastin biosynthetic process
GO:0055085	transmembrane transport
GO:0060003	copper ion export

Cellular Component

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:0016020	membrane
GO:0016021	integral component of membrane
GO:0016323	basolateral plasma membrane
GO:0030140	trans-Golgi network transport vesicle
GO:0043005	neuron projection
GO:0043025	neuronal cell body
GO:0048471	perinuclear region of cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR001757 Cation-transporting P-type ATPase
IPR001802 Mercuric transport protein periplasmic component/copper chaperone CopZ
IPR006121 Heavy metal-associated domain, HMA
IPR006122 Heavy metal-associated domain, copper ion-binding
IPR008250 P-type ATPase, A domain
IPR023214 HAD-like domain
IPR027256 Cation-transporting P-type ATPase, subfamily IB

PFAM

PF00403
PF00122
PF00702
PF08282
PF13419

PRINTS

PR00119
PR00120
PR00946
PR00941

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q04656