ATP7B

Protein identityUniProt · HPA

UniProt accession

P35670

Gene

ATP7B

Ensembl

ENSG00000123191

Chromosome

13

Canonical length

1465 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted membrane proteins, Transporters

Subcellular location

Golgi apparatus

OverviewNCBI Gene

This gene is a member of the P-type cation transport ATPase family and encodes a protein with several membrane-spanning domains, an ATPase consensus sequence, a hinge domain, a phosphorylation site, and at least 2 putative copper-binding sites. This protein is a monomer, and functions as a copper-transporting ATPase which exports copper out of the cells, such as the efflux of hepatic copper into the bile. Alternate transcriptional splice variants, encoding different isoforms with distinct cellular localizations, have been characterized. Mutations in this gene have been associated with Wilson disease which is characterized by copper accumulation. [provided by RefSeq, Dec 2019]

Canonical amino-acid sequenceUniProt

1465 residues, UniProt reviewed canonical sequence.

>P35670|ATP7B
     1  MPEQERQITA REGASRKILS KLSLPTRAWE PAMKKSFAFD NVGYEGGLDG LGPSSQVATS
    61  TVRILGMTCQ SCVKSIEDRI SNLKGIISMK VSLEQGSATV KYVPSVVCLQ QVCHQIGDMG
   121  FEASIAEGKA ASWPSRSLPA QEAVVKLRVE GMTCQSCVSS IEGKVRKLQG VVRVKVSLSN
   181  QEAVITYQPY LIQPEDLRDH VNDMGFEAAI KSKVAPLSLG PIDIERLQST NPKRPLSSAN
   241  QNFNNSETLG HQGSHVVTLQ LRIDGMHCKS CVLNIEENIG QLLGVQSIQV SLENKTAQVK
   301  YDPSCTSPVA LQRAIEALPP GNFKVSLPDG AEGSGTDHRS SSSHSPGSPP RNQVQGTCST
   361  TLIAIAGMTC ASCVHSIEGM ISQLEGVQQI SVSLAEGTAT VLYNPSVISP EELRAAIEDM
   421  GFEASVVSES CSTNPLGNHS AGNSMVQTTD GTPTSVQEVA PHTGRLPANH APDILAKSPQ
   481  STRAVAPQKC FLQIKGMTCA SCVSNIERNL QKEAGVLSVL VALMAGKAEI KYDPEVIQPL
   541  EIAQFIQDLG FEAAVMEDYA GSDGNIELTI TGMTCASCVH NIESKLTRTN GITYASVALA
   601  TSKALVKFDP EIIGPRDIIK IIEEIGFHAS LAQRNPNAHH LDHKMEIKQW KKSFLCSLVF
   661  GIPVMALMIY MLIPSNEPHQ SMVLDHNIIP GLSILNLIFF ILCTFVQLLG GWYFYVQAYK
   721  SLRHRSANMD VLIVLATSIA YVYSLVILVV AVAEKAERSP VTFFDTPPML FVFIALGRWL
   781  EHLAKSKTSE ALAKLMSLQA TEATVVTLGE DNLIIREEQV PMELVQRGDI VKVVPGGKFP
   841  VDGKVLEGNT MADESLITGE AMPVTKKPGS TVIAGSINAH GSVLIKATHV GNDTTLAQIV
   901  KLVEEAQMSK APIQQLADRF SGYFVPFIII MSTLTLVVWI VIGFIDFGVV QRYFPNPNKH
   961  ISQTEVIIRF AFQTSITVLC IACPCSLGLA TPTAVMVGTG VAAQNGILIK GGKPLEMAHK
  1021  IKTVMFDKTG TITHGVPRVM RVLLLGDVAT LPLRKVLAVV GTAEASSEHP LGVAVTKYCK
  1081  EELGTETLGY CTDFQAVPGC GIGCKVSNVE GILAHSERPL SAPASHLNEA GSLPAEKDAV
  1141  PQTFSVLIGN REWLRRNGLT ISSDVSDAMT DHEMKGQTAI LVAIDGVLCG MIAIADAVKQ
  1201  EAALAVHTLQ SMGVDVVLIT GDNRKTARAI ATQVGINKVF AEVLPSHKVA KVQELQNKGK
  1261  KVAMVGDGVN DSPALAQADM GVAIGTGTDV AIEAADVVLI RNDLLDVVAS IHLSKRTVRR
  1321  IRINLVLALI YNLVGIPIAA GVFMPIGIVL QPWMGSAAMA ASSVSVVLSS LQLKCYKKPD
  1381  LERYEAQAHG HMKPLTASQV SVHIGMDDRW RDSPRATPWD QVSYVSQVSL SSLTSDKPSR
  1441  HSAAADDDGD KWSLLLNGRD EEQYI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATP7B 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

Other membrane

Secreted

No

Transmembrane segments

8

Mean surface accessibility (rSASA)

0.36

Highest tissue expression

10 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ATP7B.

Disease | AllUniProt

Conditions ATP7B is implicated in, by any mechanism.

• Wilson disease (WD) MIM:277900

Disease | GeneticClinVar

836 pathogenic / likely-pathogenic of 3,681 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Wilson disease
• Inborn genetic diseases
• ATP7B-related disorder
• Familial cancer of breast
• Hearing loss, autosomal recessive 109

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)

1.19

gnomAD pLI

0

gnomAD missense Z

-0.88

DepMap mean gene effect

0.05

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• copper ion export
• copper ion import
• copper ion transport
• establishment of localization in cell
• intracellular copper ion homeostasis
• intracellular zinc ion homeostasis
• lactation
• monoatomic ion transmembrane transport
• protein maturation
• response to copper ion
• sequestering of calcium ion
• viral translational frameshifting
• xenobiotic detoxification by transmembrane export across the plasma membrane

Molecular functions

• ATP binding
• ATP hydrolysis activity
• copper ion binding
• copper ion transmembrane transporter activity
• P-type divalent copper transporter activity
• P-type monovalent copper transporter activity

Cellular components

• Golgi apparatus
• Golgi membrane
• late endosome
• membrane
• mitochondrion
• plasma membrane
• trans-Golgi network membrane

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
• Copper
• Copper transport
• Cytoplasm
• Endosome
• Golgi apparatus
• Ion transport
• Magnesium
• Membrane
• Metal-binding
• Mitochondrion
• Nucleotide-binding
• Phosphoprotein
• Repeat
• Ribosomal frameshifting
• Translocase
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of ATP7B in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ATOX1
• DCTN4
• COMMD1
• ZBTB16