| IED ID | IndEnz0016000029 |
| Enzyme Type ID | tyrosinase000029 |
| Protein Name |
Copper-transporting ATPase 1 EC 7.2.2.8 Copper pump 1 Menkes disease-associated protein homolog |
| Gene Name | Atp7a Mnk |
| Organism | Rattus norvegicus (Rat) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MEPNMDANSITITVEGMTCISCVRTIEQQIGKVNGVHHIKVSLEEKSATVIYNPKLQTPKTLQEAIDDMGFDALLHNANPLPVLTNTVFLTVTAPLALPWDHIQSTLLKTKGVTGVKISPQQRSAVVTIIPSVVSANQIVELVPDLSLDMGTQEKKSGTSEEHSTPQAGEVLLKMRVEGMTCHSCTSTIEGKVGKLQGVQRIKVSLDNQEATIVYQPHLITAEEIKKQIEAVGFPAFIKKQPKYLKLGAIDVERLKSTPVKSSEGSQQKSPAYPSDSAITFTIDGMHCKSCVSNIESALSTLQYVSSIVVSLENRSAIVKYNASLVTPEILRKAIEAVSPGQYRVSISSEVESPTSSPSSSSLQKMPLNLVSQPLTQEVVININGMTCNSCVQSIEGVISKKPGVKSIHVSLTNSTGTIEYDPLLTSPEPLREAIEDMGFDAVLPADMKEPLVVIAQPSLETPLLPSTTEPENVMTPVQNKCYIQVSGMTCASCVANIERNLRREEGIYSVLVALMAGKAEVRYNPAVIQPRVIAELIRELGFGAVVMENAGEGNGILELVVRGMTCASCVHKIESTLTKHKGIFYCSVALATNKAHIKYDPEIIGPRDIIHTIGNLGFEASLVKKDRSANHLDHKREIKQWRGSFLVSLFFCIPVMGLMIYMMVMDHHLATLNHNQNMSNEEMINMHSSMFLERQILPGLSIMNLLSLLLCLPVQFCGGWYFYIQAYKALRHKTANMDVLIVLATTIAFAYSLVILLVAMYERAKVNPITFFDTPPMLFVFIALGRWLEHIAKGKTSEALAKLISLQATEATIVTLNSENLLLSEEQVDVELVQRGDIIKVVPGGKFPVDGRVIEGHSMVDESLITGEAMPVAKKPGSTVIAGSINQNGSLLIRATHVGADTTLSQIVKLVEEAQTSKAPIQQFADKLSGYFVPFIVLVSIVTLLVWIIIGFQNFEIVEAYFPGYNRSISRTETIIRFAFQASITVLCIACPCSLGLATPTAVMVGTGVGAQNGILIKGGEPLEMAHKVKVVVFDKTGTITHGTPVVNQVKVLVESNKISRNKILAIVGTAESNSEHPLGAAVTKYCKQELDTETLGTCTDFQVVPGCGISCKVTNIEGLLHKSNLKIEENNIKNASLVQIDAINEQSSPSSSMIIDAHLSNAVNTQQYKVLIGNREWMIRNGLVISNDVDESMIEHERRGRTAVLVTIDDELCGLIAIADTVKPEAELAVHILKSMGLEVVLMTGDNSKTARSIASQVGITKVFAEVLPSHKVAKVKQLQEEGKRVAMVGDGINDSPALAMASVGIAIGTGTDVAIEAADVVLIRNDLLDVVASIDLSRKTVKRIRINFVFALIYNLIGIPIAAGVFLPIGLVLQPWMGSAAMAASSVSVVLSSLFLKLYRKPTYDNYELRPRSHTGQRSPSEISVHVGIDDTSRNSPRLGLLDRIVNYSRASINSLLSDKRSLNSVVTSEPDKHSLLVGDFREDDDTTL |
| Enzyme Length | 1492 |
| Uniprot Accession Number | P70705 |
| Absorption | |
| Active Site | ACT_SITE 1036; /note=4-aspartylphosphate intermediate; /evidence=ECO:0000250 |
| Activity Regulation | |
| Binding Site | BINDING 1073; /note=ATP; /evidence=ECO:0000250|UniProtKB:Q04656 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + Cu(+)(in) + H2O = ADP + Cu(+)(out) + H(+) + phosphate; Xref=Rhea:RHEA:25792, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:49552, ChEBI:CHEBI:456216; EC=7.2.2.8; Evidence={ECO:0000250|UniProtKB:Q04656};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25793; Evidence={ECO:0000250|UniProtKB:Q04656}; |
| DNA Binding | |
| EC Number | 7.2.2.8 |
| Enzyme 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). {ECO:0000250|UniProtKB:Q04656, ECO:0000250|UniProtKB:Q64430}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Binding site (1); Chain (1); Domain (7); Glycosylation (1); Metal binding (15); Modified residue (17); Motif (2); Region (1); Topological domain (9); Transmembrane (8) |
| Keywords | ATP-binding;Cell junction;Cell membrane;Cell projection;Copper;Copper transport;Endosome;Glycoprotein;Golgi apparatus;Ion transport;Magnesium;Membrane;Metal-binding;Nucleotide-binding;Phosphoprotein;Reference proteome;Repeat;Synapse;Translocase;Transmembrane;Transmembrane helix;Transport |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane {ECO:0000250|UniProtKB:Q04656, ECO:0000250|UniProtKB:Q64430}; Multi-pass membrane protein {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:Q04656, ECO:0000250|UniProtKB:Q64430}; 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:0000269|PubMed:15634787}. Cell projection, dendrite {ECO:0000269|PubMed:15634787}. Cell junction, synapse, postsynaptic density {ECO:0000269|PubMed:15634787}. 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). {ECO:0000250|UniProtKB:Q04656, ECO:0000250|UniProtKB:Q64430, ECO:0000269|PubMed:15634787}. |
| Modified Residue | MOD_RES 152; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:Q04656; MOD_RES 270; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q04656; MOD_RES 327; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:Q04656; MOD_RES 339; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q04656; MOD_RES 353; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 357; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q04656; MOD_RES 362; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q64430; MOD_RES 1204; /note=Phosphothreonine; /evidence=ECO:0007744|PubMed:16641100; MOD_RES 1422; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q04656; MOD_RES 1424; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q04656; MOD_RES 1452; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q04656; MOD_RES 1455; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q04656; MOD_RES 1458; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q04656; MOD_RES 1461; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q04656; MOD_RES 1465; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 1468; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q64430; MOD_RES 1478; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q64430 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10864443; 12840169; 15591161; 15637178; 16081413; 16185750; 16629162; 16741141; 17158254; 17584760; 19679821; 20027333; 20671235; 20836889; 21346155; 22442359; 23174565; 23349186; 23814049; 24174620; 24316150; 24614235; 24927960; 25156967; 25319798; 25349135; 25579025; 26170456; 26722473; 27331785; 28089327; |
| Motif | MOTIF 1459..1460; /note=Endocytosis signal; /evidence=ECO:0000250|UniProtKB:Q64430; MOTIF 1479..1480; /note=Endocytosis signal; /evidence=ECO:0000250|UniProtKB:Q64430 |
| Gene Encoded By | |
| Mass | 162,093 |
| Kinetics | |
| Metal Binding | METAL 18; /note=Cu(+) 1; /evidence=ECO:0000250|UniProtKB:Q04656; METAL 19; /note=Cu(+) 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00280; METAL 22; /note=Cu(+) 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00280; METAL 182; /note=Cu(+) 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00280; METAL 185; /note=Cu(+) 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00280; METAL 288; /note=Cu(+) 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00280; METAL 291; /note=Cu(+) 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00280; METAL 388; /note=Cu(+) 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00280; METAL 391; /note=Cu(+) 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00280; METAL 491; /note=Cu(+) 5; /evidence=ECO:0000255|PROSITE-ProRule:PRU00280; METAL 494; /note=Cu(+) 5; /evidence=ECO:0000255|PROSITE-ProRule:PRU00280; METAL 567; /note=Cu(+) 6; /evidence=ECO:0000255|PROSITE-ProRule:PRU00280; METAL 570; /note=Cu(+) 6; /evidence=ECO:0000255|PROSITE-ProRule:PRU00280; METAL 1293; /note=Magnesium; METAL 1297; /note=Magnesium |
| Rhea ID | RHEA:25792; RHEA:25793 |
| Cross Reference Brenda | 7.2.2.8;7.2.2.9; |