ATP7A

Protein identityUniProt · HPA

UniProt accession

Q04656

Gene

ATP7A

Ensembl

ENSG00000165240

Chromosome

X

Canonical length

1500 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Subcellular location

Golgi apparatus

OverviewNCBI Gene

This gene encodes a transmembrane protein that functions in copper transport across membranes. This protein is localized to the trans Golgi network, where it is predicted to supply copper to copper-dependent enzymes in the secretory pathway. It relocalizes to the plasma membrane under conditions of elevated extracellular copper, and functions in the efflux of copper from cells. Mutations in this gene are associated with Menkes disease, X-linked distal spinal muscular atrophy, and occipital horn syndrome. Alternatively-spliced transcript variants have been observed. [provided by RefSeq, Aug 2013]

Canonical amino-acid sequenceUniProt

1500 residues, UniProt reviewed canonical sequence.

>Q04656|ATP7A
     1  MDPSMGVNSV TISVEGMTCN SCVWTIEQQI GKVNGVHHIK VSLEEKNATI IYDPKLQTPK
    61  TLQEAIDDMG FDAVIHNPDP LPVLTDTLFL TVTASLTLPW DHIQSTLLKT KGVTDIKIYP
   121  QKRTVAVTII PSIVNANQIK ELVPELSLDT GTLEKKSGAC EDHSMAQAGE VVLKMKVEGM
   181  TCHSCTSTIE GKIGKLQGVQ RIKVSLDNQE ATIVYQPHLI SVEEMKKQIE AMGFPAFVKK
   241  QPKYLKLGAI DVERLKNTPV KSSEGSQQRS PSYTNDSTAT FIIDGMHCKS CVSNIESTLS
   301  ALQYVSSIVV SLENRSAIVK YNASSVTPES LRKAIEAVSP GLYRVSITSE VESTSNSPSS
   361  SSLQKIPLNV VSQPLTQETV INIDGMTCNS CVQSIEGVIS KKPGVKSIRV SLANSNGTVE
   421  YDPLLTSPET LRGAIEDMGF DATLSDTNEP LVVIAQPSSE MPLLTSTNEF YTKGMTPVQD
   481  KEEGKNSSKC YIQVTGMTCA SCVANIERNL RREEGIYSIL VALMAGKAEV RYNPAVIQPP
   541  MIAEFIRELG FGATVIENAD EGDGVLELVV RGMTCASCVH KIESSLTKHR GILYCSVALA
   601  TNKAHIKYDP EIIGPRDIIH TIESLGFEAS LVKKDRSASH LDHKREIRQW RRSFLVSLFF
   661  CIPVMGLMIY MMVMDHHFAT LHHNQNMSKE EMINLHSSMF LERQILPGLS VMNLLSFLLC
   721  VPVQFFGGWY FYIQAYKALK HKTANMDVLI VLATTIAFAY SLIILLVAMY ERAKVNPITF
   781  FDTPPMLFVF IALGRWLEHI AKGKTSEALA KLISLQATEA TIVTLDSDNI LLSEEQVDVE
   841  LVQRGDIIKV VPGGKFPVDG RVIEGHSMVD ESLITGEAMP VAKKPGSTVI AGSINQNGSL
   901  LICATHVGAD TTLSQIVKLV EEAQTSKAPI QQFADKLSGY FVPFIVFVSI ATLLVWIVIG
   961  FLNFEIVETY FPGYNRSISR TETIIRFAFQ ASITVLCIAC PCSLGLATPT AVMVGTGVGA
  1021  QNGILIKGGE PLEMAHKVKV VVFDKTGTIT HGTPVVNQVK VLTESNRISH HKILAIVGTA
  1081  ESNSEHPLGT AITKYCKQEL DTETLGTCID FQVVPGCGIS CKVTNIEGLL HKNNWNIEDN
  1141  NIKNASLVQI DASNEQSSTS SSMIIDAQIS NALNAQQYKV LIGNREWMIR NGLVINNDVN
  1201  DFMTEHERKG RTAVLVAVDD ELCGLIAIAD TVKPEAELAI HILKSMGLEV VLMTGDNSKT
  1261  ARSIASQVGI TKVFAEVLPS HKVAKVKQLQ EEGKRVAMVG DGINDSPALA MANVGIAIGT
  1321  GTDVAIEAAD VVLIRNDLLD VVASIDLSRK TVKRIRINFV FALIYNLVGI PIAAGVFMPI
  1381  GLVLQPWMGS AAMAASSVSV VLSSLFLKLY RKPTYESYEL PARSQIGQKS PSEISVHVGI
  1441  DDTSRNSPKL GLLDRIVNYS RASINSLLSD KRSLNSVVTS EPDKHSLLVG DFREDDDTAL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATP7A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

8

Mean surface accessibility (rSASA)

0.33

Highest tissue expression

12 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ATP7A.

Disease | AllUniProt

Conditions ATP7A is implicated in, by any mechanism.

• Menkes disease (MNK) MIM:309400
• Occipital horn syndrome (OHS) MIM:304150
• Neuronopathy, distal hereditary motor, X-linked (HMNX) MIM:300489

Disease | GeneticClinVar

257 pathogenic / likely-pathogenic of 2,246 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Menkes kinky-hair syndrome
• X-linked distal spinal muscular atrophy type 3
• Cutis laxa, X-linked
• ATP7A-related disorder
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.22

gnomAD pLI

1

gnomAD missense Z

1.53

DepMap mean gene effect

-0.16

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• ATP metabolic process
• blood vessel development
• blood vessel remodeling
• cartilage development
• catecholamine metabolic process
• central nervous system neuron development
• cerebellar Purkinje cell differentiation
• collagen fibril organization
• copper ion export
• copper ion import
• copper ion transport
• dendrite morphogenesis
• detoxification of copper ion
• dopamine metabolic process
• elastic fiber assembly
• epinephrine metabolic process
• establishment of localization in cell
• extracellular matrix organization
• glycoprotein biosynthetic process
• hair follicle morphogenesis
• intracellular copper ion homeostasis
• L-tryptophan metabolic process
• locomotory behavior
• lung alveolus development
• mitochondrion organization
• negative regulation of catecholamine metabolic process
• negative regulation of neuron apoptotic process
• neuron apoptotic process
• neuron cellular homeostasis
• neuron projection morphogenesis
• norepinephrine biosynthetic process
• norepinephrine metabolic process
• pigmentation
• positive regulation of melanin biosynthetic process
• pyramidal neuron development
• regulation of gene expression
• regulation of oxidative phosphorylation
• release of cytochrome c from mitochondria
• removal of superoxide radicals
• serotonin metabolic process
• skin development
• T-helper cell differentiation
• tyrosine metabolic process

Molecular functions

• ATP binding
• ATP hydrolysis activity
• copper ion binding
• copper ion transmembrane transporter activity
• copper-dependent protein binding
• cuprous ion binding
• P-type divalent copper transporter activity
• P-type monovalent copper transporter activity
• superoxide dismutase copper chaperone activity

Cellular components

• axon
• basolateral plasma membrane
• cytosol
• dendrite
• early endosome membrane
• endoplasmic reticulum
• Golgi apparatus
• late endosome
• melanosome membrane
• membrane
• neuron projection
• neuronal cell body
• perinuclear region of cytoplasm
• phagocytic vesicle membrane
• plasma membrane
• postsynaptic density
• trans-Golgi network
• trans-Golgi network membrane
• trans-Golgi network transport vesicle

Protein domainsUniProt · Pfam · InterPro

• P-type ATPase
• Heavy metal-associated domain, HMA
• Heavy metal-associated domain, copper ion-binding
• P-type ATPase, A domain superfamily
• Heavy-metal-associated, conserved site
• P-type ATPase, phosphorylation site
• HAD superfamily
• P-type ATPase, transmembrane domain superfamily
• P-type ATPase, cytoplasmic domain N
• P-type ATPase, subfamily IB
• Heavy metal-associated domain superfamily
• HAD-like superfamily
• P-type ATPase, haloacid dehalogenase domain
• P-type ATPase, A domain
• P-type ATPase actuator domain
• Heavy-metal-associated domain
• haloacid dehalogenase-like hydrolase

KeywordsUniProt

• ATP-binding
• Cell membrane
• Cell projection
• Copper
• Copper transport
• Cytoplasm
• Endoplasmic reticulum
• Endosome
• Glycoprotein
• Golgi apparatus
• Ion transport
• Magnesium
• Membrane
• Metal-binding
• Neurodegeneration
• Neuropathy
• Nucleotide-binding
• Phosphoprotein
• Repeat
• Synapse
• Translocase
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of ATP7A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ATOX1
• COMMD1
• PDZD11
• SOD3
• TYRP1