P70705 · ATP7A_RAT

  • Protein
    Copper-transporting ATPase 1
  • Gene
    Atp7a
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

ATP-driven copper (Cu+) ion pump that plays an important role in intracellular copper ion homeostasis (By similarity).
Within a catalytic cycle, acquires Cu+ ion from donor protein on the cytoplasmic side of the membrane and delivers it to acceptor protein on the lumenal side. The transfer of Cu+ ion across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to outward-facing state (By similarity).
Under physiological conditions, at low cytosolic copper concentration, it is localized at the trans-Golgi network (TGN) where it transfers Cu+ ions to cuproenzymes of the secretory pathway (By similarity).
Upon elevated cytosolic copper concentrations, it relocalizes to the plasma membrane where it is responsible for the export of excess Cu+ ions (By similarity).
May play a dual role in neuron function and survival by regulating cooper efflux and neuronal transmission at the synapse as well as by supplying Cu+ ions to enzymes such as PAM, TYR and SOD3 (By similarity).
In the melanosomes of pigmented cells, provides copper cofactor to TYR to form an active TYR holoenzyme for melanin biosynthesis (By similarity).

Catalytic activity

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site18Cu+ 1 (UniProtKB | ChEBI)
Binding site19Cu+ 1 (UniProtKB | ChEBI)
Binding site22Cu+ 1 (UniProtKB | ChEBI)
Binding site182Cu+ 2 (UniProtKB | ChEBI)
Binding site185Cu+ 2 (UniProtKB | ChEBI)
Binding site288Cu+ 3 (UniProtKB | ChEBI)
Binding site291Cu+ 3 (UniProtKB | ChEBI)
Binding site388Cu+ 4 (UniProtKB | ChEBI)
Binding site391Cu+ 4 (UniProtKB | ChEBI)
Binding site491Cu+ 5 (UniProtKB | ChEBI)
Binding site494Cu+ 5 (UniProtKB | ChEBI)
Binding site567Cu+ 6 (UniProtKB | ChEBI)
Binding site570Cu+ 6 (UniProtKB | ChEBI)
Active site10364-aspartylphosphate intermediate
Binding site1073ATP (UniProtKB | ChEBI)
Binding site1293Mg2+ (UniProtKB | ChEBI)
Binding site1297Mg2+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentaxon
Cellular Componentbasolateral plasma membrane
Cellular Componentbrush border membrane
Cellular Componentcell leading edge
Cellular Componentcytoplasmic vesicle
Cellular Componentdendrite
Cellular Componentearly endosome membrane
Cellular ComponentGolgi apparatus
Cellular Componentlate endosome
Cellular Componentmelanosome membrane
Cellular Componentmembrane
Cellular Componentmicrovillus
Cellular Componentneuron projection
Cellular Componentneuronal cell body
Cellular Componentperikaryon
Cellular Componentperinuclear region of cytoplasm
Cellular Componentplasma membrane
Cellular Componentpostsynaptic density
Cellular Componentsecretory granule
Cellular Componenttrans-Golgi network
Cellular Componenttrans-Golgi network membrane
Cellular Componenttrans-Golgi network transport vesicle
Molecular FunctionATP binding
Molecular FunctionATP hydrolysis activity
Molecular Functioncopper ion binding
Molecular Functioncopper ion transmembrane transporter activity
Molecular Functioncopper-dependent protein binding
Molecular Functioncuprous ion binding
Molecular FunctionP-type divalent copper transporter activity
Molecular FunctionP-type monovalent copper transporter activity
Molecular Functionprotein-folding chaperone binding
Molecular Functionsmall GTPase binding
Molecular Functionsuperoxide dismutase copper chaperone activity
Biological ProcessATP metabolic process
Biological Processblood vessel development
Biological Processblood vessel remodeling
Biological Processcartilage development
Biological Processcatecholamine metabolic process
Biological Processcellular response to amino acid stimulus
Biological Processcellular response to antibiotic
Biological Processcellular response to cadmium ion
Biological Processcellular response to cobalt ion
Biological Processcellular response to copper ion
Biological Processcellular response to hypoxia
Biological Processcellular response to iron ion
Biological Processcellular response to lead ion
Biological Processcellular response to platelet-derived growth factor stimulus
Biological Processcentral nervous system neuron development
Biological Processcerebellar Purkinje cell differentiation
Biological Processcollagen fibril organization
Biological Processcopper ion export
Biological Processcopper ion homeostasis
Biological Processcopper ion import
Biological Processcopper ion transport
Biological Processdendrite morphogenesis
Biological Processdetoxification of copper ion
Biological Processdopamine metabolic process
Biological Processelastic fiber assembly
Biological Processelastin biosynthetic process
Biological Processepinephrine metabolic process
Biological Processestablishment of localization in cell
Biological Processextracellular matrix organization
Biological Processfemale pregnancy
Biological Processhair follicle morphogenesis
Biological Processhindlimb morphogenesis
Biological Processin utero embryonic development
Biological Processintracellular copper ion homeostasis
Biological Processlactation
Biological Processliver development
Biological Processlocomotory behavior
Biological Processlung alveolus development
Biological Processmitochondrion organization
Biological Processnegative regulation of catecholamine metabolic process
Biological Processnegative regulation of iron ion transmembrane transport
Biological Processnegative regulation of neuron apoptotic process
Biological Processneuron apoptotic process
Biological Processneuron cellular homeostasis
Biological Processneuron projection morphogenesis
Biological Processnorepinephrine biosynthetic process
Biological Processnorepinephrine metabolic process
Biological Processpigmentation
Biological Processpositive regulation of cell size
Biological Processpositive regulation of epithelial cell proliferation
Biological Processpositive regulation of lamellipodium assembly
Biological Processpositive regulation of melanin biosynthetic process
Biological Processpositive regulation of response to wounding
Biological Processpositive regulation of tyrosinase activity
Biological Processpositive regulation of vascular associated smooth muscle cell migration
Biological Processpyramidal neuron development
Biological Processregulation of gene expression
Biological Processregulation of oxidative phosphorylation
Biological Processrelease of cytochrome c from mitochondria
Biological Processremoval of superoxide radicals
Biological Processresponse to copper ion
Biological Processresponse to iron(III) ion
Biological Processresponse to lead ion
Biological Processresponse to manganese ion
Biological Processresponse to zinc ion
Biological Processserotonin metabolic process
Biological Processskin development
Biological ProcessT-helper cell differentiation
Biological Processtryptophan metabolic process
Biological Processtyrosine metabolic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Copper-transporting ATPase 1
  • EC number
  • Alternative names
    • Copper pump 1
    • Menkes disease-associated protein homolog

Gene names

    • Name
      Atp7a
    • Synonyms
      Mnk

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    P70705

Proteomes

Organism-specific databases

Subcellular Location

Golgi apparatus, trans-Golgi network membrane
; Multi-pass membrane protein
Cell membrane
; Multi-pass membrane protein
Melanosome membrane
; Multi-pass membrane protein
Early endosome membrane
; Multi-pass membrane protein
Cell projection, axon
Postsynaptic density
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. Targeting into melanosomes is regulated by BLOC-1 complex (By similarity).
In response to glutamate translocates to neuron processes with a minor fraction at extrasynaptic sites (PubMed:15634787).

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-645Cytoplasmic
Transmembrane646-667Helical
Topological domain668-706Extracellular
Transmembrane707-726Helical
Topological domain727-733Cytoplasmic
Transmembrane734-754Helical
Topological domain755-773Extracellular
Transmembrane774-794Helical
Topological domain795-927Cytoplasmic
Transmembrane928-951Helical
Topological domain952-981Extracellular
Transmembrane982-1003Helical
Topological domain1004-1348Cytoplasmic
Transmembrane1349-1366Helical
Topological domain1367-1377Extracellular
Transmembrane1378-1397Helical
Topological domain1398-1492Cytoplasmic

Keywords

PTM/Processing

Features

Showing features for chain, modified residue, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00000463131-1492Copper-transporting ATPase 1
Modified residue152Phosphothreonine
Modified residue270Phosphoserine
Modified residue327Phosphothreonine
Modified residue339Phosphoserine
Modified residue353Phosphoserine
Modified residue357Phosphoserine
Modified residue362Phosphoserine
Glycosylation678N-linked (GlcNAc...) asparagine
Modified residue1204Phosphothreonine
Modified residue1422Phosphoserine
Modified residue1424Phosphoserine
Modified residue1452Phosphoserine
Modified residue1455Phosphoserine
Modified residue1458Phosphoserine
Modified residue1461Phosphoserine
Modified residue1465Phosphoserine
Modified residue1468Phosphoserine
Modified residue1478Phosphoserine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed in hippocampal neuron (at protein level) (PubMed:15634787).
Expressed in anterior pituitary gland (at protein level) (PubMed:12488345).

Gene expression databases

Interaction

Subunit

Monomer. Interacts with PDZD11. Interacts with ATOX1 and COMMD1 (By similarity).
Interacts with TYRP1 (By similarity).
Directly interacts with SOD3; this interaction is copper-dependent and is required for SOD3 activity (By similarity).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for domain, motif, region.

TypeIDPosition(s)Description
Domain8-74HMA 1
Domain85-151HMA 2
Domain171-237HMA 3
Domain277-343HMA 4
Domain377-443HMA 5
Domain480-546HMA 6
Domain556-622HMA 7
Motif1459-1460Endocytosis signal
Region1478-1492PDZD11-binding
Motif1479-1480Endocytosis signal

Domain

The nucleotide-binding domain consists of a twisted six-stranded antiparallel beta-sheet flanked by two pairs of alpha-helices, forming a hydrophobic pocket that interacts with the adenine ring of ATP. The ATP binding site comprises residues located in alpha-1 and alpha-2 helices and beta-2 and beta-3 strands, which are involved in van der Waal's interactions, and Glu-1073 which forms a hydrogen bond with the adenine ring.
The heavy-metal-associated domain (HMA) coordinates a Cu+ ion via the cysteine residues within the CXXC motif. The transfer of Cu+ ion from ATOX1 to ATP7A involves the formation of a three-coordinate Cu+-bridged heterodimer where the metal is shared between the two metal binding sites of ATOX1 and ATP7A. The Cu+ ion appears to switch between two coordination modes, forming two links with one protein and one with the other. Cisplatin, a chemotherapeutic drug, can bind the CXXC motif and hinder the release of Cu+ ion.
Contains three di-leucine motifs in the C-terminus which are required for recycling from the plasma membrane to the TGN. The di-leucine 1479-Leu-Leu-1480 motif mediates endocytosis at the plasma membrane, whereas the di-leucine 1459-Leu-Leu-1460 motif is a sorting signal for retrograde trafficking to TGN via early endosomes.

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,492
  • Mass (Da)
    162,093
  • Last updated
    1997-02-01 v1
  • Checksum
    34F75152B105AE9F
MEPNMDANSITITVEGMTCISCVRTIEQQIGKVNGVHHIKVSLEEKSATVIYNPKLQTPKTLQEAIDDMGFDALLHNANPLPVLTNTVFLTVTAPLALPWDHIQSTLLKTKGVTGVKISPQQRSAVVTIIPSVVSANQIVELVPDLSLDMGTQEKKSGTSEEHSTPQAGEVLLKMRVEGMTCHSCTSTIEGKVGKLQGVQRIKVSLDNQEATIVYQPHLITAEEIKKQIEAVGFPAFIKKQPKYLKLGAIDVERLKSTPVKSSEGSQQKSPAYPSDSAITFTIDGMHCKSCVSNIESALSTLQYVSSIVVSLENRSAIVKYNASLVTPEILRKAIEAVSPGQYRVSISSEVESPTSSPSSSSLQKMPLNLVSQPLTQEVVININGMTCNSCVQSIEGVISKKPGVKSIHVSLTNSTGTIEYDPLLTSPEPLREAIEDMGFDAVLPADMKEPLVVIAQPSLETPLLPSTTEPENVMTPVQNKCYIQVSGMTCASCVANIERNLRREEGIYSVLVALMAGKAEVRYNPAVIQPRVIAELIRELGFGAVVMENAGEGNGILELVVRGMTCASCVHKIESTLTKHKGIFYCSVALATNKAHIKYDPEIIGPRDIIHTIGNLGFEASLVKKDRSANHLDHKREIKQWRGSFLVSLFFCIPVMGLMIYMMVMDHHLATLNHNQNMSNEEMINMHSSMFLERQILPGLSIMNLLSLLLCLPVQFCGGWYFYIQAYKALRHKTANMDVLIVLATTIAFAYSLVILLVAMYERAKVNPITFFDTPPMLFVFIALGRWLEHIAKGKTSEALAKLISLQATEATIVTLNSENLLLSEEQVDVELVQRGDIIKVVPGGKFPVDGRVIEGHSMVDESLITGEAMPVAKKPGSTVIAGSINQNGSLLIRATHVGADTTLSQIVKLVEEAQTSKAPIQQFADKLSGYFVPFIVLVSIVTLLVWIIIGFQNFEIVEAYFPGYNRSISRTETIIRFAFQASITVLCIACPCSLGLATPTAVMVGTGVGAQNGILIKGGEPLEMAHKVKVVVFDKTGTITHGTPVVNQVKVLVESNKISRNKILAIVGTAESNSEHPLGAAVTKYCKQELDTETLGTCTDFQVVPGCGISCKVTNIEGLLHKSNLKIEENNIKNASLVQIDAINEQSSPSSSMIIDAHLSNAVNTQQYKVLIGNREWMIRNGLVISNDVDESMIEHERRGRTAVLVTIDDELCGLIAIADTVKPEAELAVHILKSMGLEVVLMTGDNSKTARSIASQVGITKVFAEVLPSHKVAKVKQLQEEGKRVAMVGDGINDSPALAMASVGIAIGTGTDVAIEAADVVLIRNDLLDVVASIDLSRKTVKRIRINFVFALIYNLIGIPIAAGVFLPIGLVLQPWMGSAAMAASSVSVVLSSLFLKLYRKPTYDNYELRPRSHTGQRSPSEISVHVGIDDTSRNSPRLGLLDRIVNYSRASINSLLSDKRSLNSVVTSEPDKHSLLVGDFREDDDTTL

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A8L2UQX4A0A8L2UQX4_RATAtp7a161

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U59245
EMBL· GenBank· DDBJ
AAB06393.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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