The following text describes a protein:
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 (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. 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. In the melanosomes of pigmented cells, provides copper cofactor to TYR to form an active TYR holoenzyme for melanin biosynthesis.
Subcellular Localization:
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. Cell projection, dendrite. Postsynaptic density. Note=Cycles constitutively between the 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. In response to glutamate translocates to neuron processes with a minor fraction at extrasynaptic sites (By similarity).
Domain:
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-1072 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 1478-Leu-Leu-1479 motif mediates endocytosis at the plasma membrane, whereas the di-leucine 1458-Leu-Leu-1459 motif is a sorting signal for retrograde trafficking to TGN via early endosomes.
Sequence:
MEPSVDANSITITVEGMTCISCVRTIEQQIGKVNGVHHIKVSLEEKSATIIYDPKLQTPKTLQEAIDDMGFDALLHNANPLPVLTNTVFLTVTAPLTLPWDHIQSTLLKTKGVTGVKISPQQRSAVVTIIPSVVSASQIVELVPDLSLDMGTQEKKSGACEEHSTPQAGEVMLKMKVEGMTCHSCTSTIEGKVGKLQGVQRIKVSLDNQEATIVFQPHLITAEEIKKQIEAVGFPAFIKKQPKYLKLGAIDVERLKNTPVKSSEGSQQKSPSYPSDSTTMFTIEGMHCKSCVSNIESALSTLQYVSSIVVSLENRSAIVKYNASLVTPEMLRKAIEAISPGQYRVSIASEVESTASSPSSSSLQKMPLNIVSQPLTQEAVININGMTCNSCVQSIEGVISKKPGVKSIHVSLANSTGTIEFDPLLTSPETLREAIEDMGFDAALPDMKEPLVVIAQPSLETPLLPSSNELENVMTSVQNKCYIQVSGMTCASCVANIERNLRREEGIYSVLVALMAGKAEVRYNPAVIQPRVIAEFIRELGFGAMVMENAGEGNGILELVVRGMTCASCVHKIESTLTKHKGIFYCSVALATNKAHIKYDPEIIGPRDIIHTIGSLGFEASLVKKDRSANHLDHKREIKQWRGSFLVSLFFCIPVMGLMVYMMVMDHHLATLHHNQNMSNEEMINMHSAMFLERQILPGLSIMNLLSLLLCLPVQFCGGWYFYIQAYKALKHKTANMDVLIVLATTIAFAYSLVILLVAMFERAKVNPITFFDTPPMLFVFIALGRWLEHIAKGKTSEALAKLISLQATEATIVTLNSENLLLSEEQVDVELVQRGDIIKVVPGGKFPVDGRVIEGHSMVDESLITGEAMPVAKKPGSTVIAGSINQNGSLLIRATHVGADTTLSQIVKLVEEAQTSKAPIQQFADKLSGYFVPFIVLVSIVTLLVWIIIGFQNFEIVETYFPGYNRSISRTETIIRFAFQASITVLCIACPCSLGLATPTAVMVGTGVGAQNGILIKGGEPLEMAHKVKVVVFDKTGTITHGTPVVNQVKVLVESNKISRNKILAIVGTAESNSEHPLGAAVTKYCKKELDTETLGTCTDFQVVPGCGISCKVTNIEGLLHKSNLKIEENNIKNASLVQIDAINEQSSTSSSMIIDAHLSNAVNTQQYKVLIGNREWMIRNGLVISNDVDESMIEHERRGRTAVLVTIDDELCGLIAIADTVKPEAELAVHILKSMGLEVVLMTGDNSKTARSIASQVGITKVFAEVLPSHKVAKVKQLQEEGKRVAMVGDGINDSPALAMANVGIAIGTGTDVAIEAADVVLIRNDLLDVVASIDLSRKTVKRIRINFVFALIYNLVGIPIAAGVFLPIGLVLQPWMGSAAMAASSVSVVLSSLFLKLYRKPTYDNYELHPRSHTGQRSPSEISVHVGIDDTSRNSPRLGLLDRIVNYSRASINSLLSDKRSLNSVVTSEPDKHSLLVGDFREDDDTTL