Protein: Copper-transporting ATPase 1 (EC 7.2.2.8) (Copper pump 1) (Menkes disease-associated protein) (Q04656)
Organism: Homo sapiens (Human)
Function: ATP-driven copper (Cu(+)) ion pump that plays an important role in intracellular copper ion homeostasis. 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. 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. Upon elevated cytosolic copper concentrations, it relocalizes to the plasma membrane where it is responsible for the export of excess Cu(+) ions. 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).
Subcellular location: Golgi apparatus, trans-Golgi network membrane {ECO:0000269|PubMed:10484781, ECO:0000269|PubMed:28389643, ECO:0000269|PubMed:9147644, ECO:0000269|PubMed:9467005}; Multi-pass membrane protein {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:10484781, ECO:0000269|PubMed:28389643, ECO:0000269|PubMed:9147644}; Multi-pass membrane protein {ECO:0000255}. Melanosome membrane {ECO:0000250|UniProtKB:Q64430}; Multi-pass membrane protein {ECO:0000255}. Early endosome membrane {ECO:0000250|UniProtKB:Q64430}; Multi-pass membrane protein {ECO:0000255}. Cell projection, axon {ECO:0000250|UniProtKB:P70705}. Cell projection, dendrite {ECO:0000250|UniProtKB:P70705}. Postsynaptic density {ECO:0000250|UniProtKB:P70705}. Note=Cycles constitutively between the TGN and the plasma membrane (PubMed:9147644). 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 (By similarity). {ECO:0000250|UniProtKB:P70705, ECO:0000250|UniProtKB:Q64430, ECO:0000269|PubMed:9147644}.; SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm, cytosol {ECO:0000305}.; SUBCELLULAR LOCATION: [Isoform 5]: Endoplasmic reticulum {ECO:0000269|PubMed:9467005}.
Interaction partners:
- Copper transport protein ATOX1
- Copper chaperone for superoxide dismutase
- Eukaryotic translation initiation factor 4 gamma 1
- PDZ domain-containing protein 11
- Pro-opiomelanocortin
- Ceruloplasmin
- High affinity copper uptake protein 1
- Protein SLC31A2
- Copper-transporting ATPase 2
- Melanocortin receptor 3
Sequence:
MDPSMGVNSVTISVEGMTCNSCVWTIEQQIGKVNGVHHIKVSLEEKNATIIYDPKLQTPKTLQEAIDDMGFDAVIHNPDPLPVLTDTLFLTVTASLTLPWDHIQSTLLKTKGVTDIKIYPQKRTVAVTIIPSIVNANQIKELVPELSLDTGTLEKKSGACEDHSMAQAGEVVLKMKVEGMTCHSCTSTIEGKIGKLQGVQRIKVSLDNQEATIVYQPHLISVEEMKKQIEAMGFPAFVKKQPKYLKLGAIDVERLKNTPVKSSEGSQQRSPSYTNDSTATFIIDGMHCKSCVSNIESTLSALQYVSSIVVSLENRSAIVKYNASSVTPESLRKAIEAVSPGLYRVSITSEVESTSNSPSSSSLQKIPLNVVSQPLTQETVINIDGMTCNSCVQSIEGVISKKPGVKSIRVSLANSNGTVEYDPLLTSPETLRGAIEDMGFDATLSDTNEPLVVIAQPSSEMPLLTSTNEFYTKGMTPVQDKEEGKNSSKCYIQVTGMTCASCVANIERNLRREEGIYSILVALMAGKAEVRYNPAVIQPPMIAEFIRELGFGATVIENADEGDGVLELVVRGMTCASCVHKIESSLTKHRGILYCSVALATNKAHIKYDPEIIGPRDIIHTIESLGFEASLVKKDRSASHLDHKREIRQWRRSFLVSLFFCIPVMGLMIYMMVMDHHFATLHHNQNMSKEEMINLHSSMFLERQILPGLSVMNLLSFLLCVPVQFFGGWYFYIQAYKALKHKTANMDVLIVLATTIAFAYSLIILLVAMYERAKVNPITFFDTPPMLFVFIALGRWLEHIAKGKTSEALAKLISLQATEATIVTLDSDNILLSEEQVDVELVQRGDIIKVVPGGKFPVDGRVIEGHSMVDESLITGEAMPVAKKPGSTVIAGSINQNGSLLICATHVGADTTLSQIVKLVEEAQTSKAPIQQFADKLSGYFVPFIVFVSIATLLVWIVIGFLNFEIVETYFPGYNRSISRTETIIRFAFQASITVLCIACPCSLGLATPTAVMVGTGVGAQNGILIKGGEPLEMAHKVKVVVFDKTGTITHGTPVVNQVKVLTESNRISHHKILAIVGTAESNSEHPLGTAITKYCKQELDTETLGTCIDFQVVPGCGISCKVTNIEGLLHKNNWNIEDNNIKNASLVQIDASNEQSSTSSSMIIDAQISNALNAQQYKVLIGNREWMIRNGLVINNDVNDFMTEHERKGRTAVLVAVDDELCGLIAIADTVKPEAELAIHILKSMGLEVVLMTGDNSKTARSIASQVGITKVFAEVLPSHKVAKVKQLQEEGKRVAMVGDGINDSPALAMANVGIAIGTGTDVAIEAADVVLIRNDLLDVVASIDLSRKTVKRIRINFVFALIYNLVGIPIAAGVFMPIGLVLQPWMGSAAMAASSVSVVLSSLFLKLYRKPTYESYELPARSQIGQKSPSEISVHVGIDDTSRNSPKLGLLDRIVNYSRASINSLLSDKRSLNSVVTSEPDKHSLLVGDFREDDDTAL