P70705 · ATP7A_RAT
- ProteinCopper-transporting ATPase 1
- GeneAtp7a
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1492 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
- ATP + Cu+(in) + H2O = ADP + Cu+(out) + H+ + phosphateThis reaction proceeds in the forward direction.
CHEBI:30616 + Cu+ (in)CHEBI:49552+ CHEBI:15377 = CHEBI:456216 + Cu+ (out)CHEBI:49552+ CHEBI:15378 + CHEBI:43474
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 18 | Cu+ 1 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 19 | Cu+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 22 | Cu+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 182 | Cu+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 185 | Cu+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 288 | Cu+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 291 | Cu+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 388 | Cu+ 4 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 391 | Cu+ 4 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 491 | Cu+ 5 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 494 | Cu+ 5 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 567 | Cu+ 6 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 570 | Cu+ 6 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Active site | 1036 | 4-aspartylphosphate intermediate | ||||
Sequence: D | ||||||
Binding site | 1073 | ATP (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 1293 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 1297 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCopper-transporting ATPase 1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP70705
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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
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).
In response to glutamate translocates to neuron processes with a minor fraction at extrasynaptic sites (PubMed:15634787).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-645 | Cytoplasmic | ||||
Sequence: MEPNMDANSITITVEGMTCISCVRTIEQQIGKVNGVHHIKVSLEEKSATVIYNPKLQTPKTLQEAIDDMGFDALLHNANPLPVLTNTVFLTVTAPLALPWDHIQSTLLKTKGVTGVKISPQQRSAVVTIIPSVVSANQIVELVPDLSLDMGTQEKKSGTSEEHSTPQAGEVLLKMRVEGMTCHSCTSTIEGKVGKLQGVQRIKVSLDNQEATIVYQPHLITAEEIKKQIEAVGFPAFIKKQPKYLKLGAIDVERLKSTPVKSSEGSQQKSPAYPSDSAITFTIDGMHCKSCVSNIESALSTLQYVSSIVVSLENRSAIVKYNASLVTPEILRKAIEAVSPGQYRVSISSEVESPTSSPSSSSLQKMPLNLVSQPLTQEVVININGMTCNSCVQSIEGVISKKPGVKSIHVSLTNSTGTIEYDPLLTSPEPLREAIEDMGFDAVLPADMKEPLVVIAQPSLETPLLPSTTEPENVMTPVQNKCYIQVSGMTCASCVANIERNLRREEGIYSVLVALMAGKAEVRYNPAVIQPRVIAELIRELGFGAVVMENAGEGNGILELVVRGMTCASCVHKIESTLTKHKGIFYCSVALATNKAHIKYDPEIIGPRDIIHTIGNLGFEASLVKKDRSANHLDHKREIKQWRGS | ||||||
Transmembrane | 646-667 | Helical | ||||
Sequence: FLVSLFFCIPVMGLMIYMMVMD | ||||||
Topological domain | 668-706 | Extracellular | ||||
Sequence: HHLATLNHNQNMSNEEMINMHSSMFLERQILPGLSIMNL | ||||||
Transmembrane | 707-726 | Helical | ||||
Sequence: LSLLLCLPVQFCGGWYFYIQ | ||||||
Topological domain | 727-733 | Cytoplasmic | ||||
Sequence: AYKALRH | ||||||
Transmembrane | 734-754 | Helical | ||||
Sequence: KTANMDVLIVLATTIAFAYSL | ||||||
Topological domain | 755-773 | Extracellular | ||||
Sequence: VILLVAMYERAKVNPITFF | ||||||
Transmembrane | 774-794 | Helical | ||||
Sequence: DTPPMLFVFIALGRWLEHIAK | ||||||
Topological domain | 795-927 | Cytoplasmic | ||||
Sequence: GKTSEALAKLISLQATEATIVTLNSENLLLSEEQVDVELVQRGDIIKVVPGGKFPVDGRVIEGHSMVDESLITGEAMPVAKKPGSTVIAGSINQNGSLLIRATHVGADTTLSQIVKLVEEAQTSKAPIQQFAD | ||||||
Transmembrane | 928-951 | Helical | ||||
Sequence: KLSGYFVPFIVLVSIVTLLVWIII | ||||||
Topological domain | 952-981 | Extracellular | ||||
Sequence: GFQNFEIVEAYFPGYNRSISRTETIIRFAF | ||||||
Transmembrane | 982-1003 | Helical | ||||
Sequence: QASITVLCIACPCSLGLATPTA | ||||||
Topological domain | 1004-1348 | Cytoplasmic | ||||
Sequence: VMVGTGVGAQNGILIKGGEPLEMAHKVKVVVFDKTGTITHGTPVVNQVKVLVESNKISRNKILAIVGTAESNSEHPLGAAVTKYCKQELDTETLGTCTDFQVVPGCGISCKVTNIEGLLHKSNLKIEENNIKNASLVQIDAINEQSSPSSSMIIDAHLSNAVNTQQYKVLIGNREWMIRNGLVISNDVDESMIEHERRGRTAVLVTIDDELCGLIAIADTVKPEAELAVHILKSMGLEVVLMTGDNSKTARSIASQVGITKVFAEVLPSHKVAKVKQLQEEGKRVAMVGDGINDSPALAMASVGIAIGTGTDVAIEAADVVLIRNDLLDVVASIDLSRKTVKRIR | ||||||
Transmembrane | 1349-1366 | Helical | ||||
Sequence: INFVFALIYNLIGIPIAA | ||||||
Topological domain | 1367-1377 | Extracellular | ||||
Sequence: GVFLPIGLVLQ | ||||||
Transmembrane | 1378-1397 | Helical | ||||
Sequence: PWMGSAAMAASSVSVVLSSL | ||||||
Topological domain | 1398-1492 | Cytoplasmic | ||||
Sequence: FLKLYRKPTYDNYELRPRSHTGQRSPSEISVHVGIDDTSRNSPRLGLLDRIVNYSRASINSLLSDKRSLNSVVTSEPDKHSLLVGDFREDDDTTL |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, modified residue, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000046313 | 1-1492 | Copper-transporting ATPase 1 | |||
Sequence: MEPNMDANSITITVEGMTCISCVRTIEQQIGKVNGVHHIKVSLEEKSATVIYNPKLQTPKTLQEAIDDMGFDALLHNANPLPVLTNTVFLTVTAPLALPWDHIQSTLLKTKGVTGVKISPQQRSAVVTIIPSVVSANQIVELVPDLSLDMGTQEKKSGTSEEHSTPQAGEVLLKMRVEGMTCHSCTSTIEGKVGKLQGVQRIKVSLDNQEATIVYQPHLITAEEIKKQIEAVGFPAFIKKQPKYLKLGAIDVERLKSTPVKSSEGSQQKSPAYPSDSAITFTIDGMHCKSCVSNIESALSTLQYVSSIVVSLENRSAIVKYNASLVTPEILRKAIEAVSPGQYRVSISSEVESPTSSPSSSSLQKMPLNLVSQPLTQEVVININGMTCNSCVQSIEGVISKKPGVKSIHVSLTNSTGTIEYDPLLTSPEPLREAIEDMGFDAVLPADMKEPLVVIAQPSLETPLLPSTTEPENVMTPVQNKCYIQVSGMTCASCVANIERNLRREEGIYSVLVALMAGKAEVRYNPAVIQPRVIAELIRELGFGAVVMENAGEGNGILELVVRGMTCASCVHKIESTLTKHKGIFYCSVALATNKAHIKYDPEIIGPRDIIHTIGNLGFEASLVKKDRSANHLDHKREIKQWRGSFLVSLFFCIPVMGLMIYMMVMDHHLATLNHNQNMSNEEMINMHSSMFLERQILPGLSIMNLLSLLLCLPVQFCGGWYFYIQAYKALRHKTANMDVLIVLATTIAFAYSLVILLVAMYERAKVNPITFFDTPPMLFVFIALGRWLEHIAKGKTSEALAKLISLQATEATIVTLNSENLLLSEEQVDVELVQRGDIIKVVPGGKFPVDGRVIEGHSMVDESLITGEAMPVAKKPGSTVIAGSINQNGSLLIRATHVGADTTLSQIVKLVEEAQTSKAPIQQFADKLSGYFVPFIVLVSIVTLLVWIIIGFQNFEIVEAYFPGYNRSISRTETIIRFAFQASITVLCIACPCSLGLATPTAVMVGTGVGAQNGILIKGGEPLEMAHKVKVVVFDKTGTITHGTPVVNQVKVLVESNKISRNKILAIVGTAESNSEHPLGAAVTKYCKQELDTETLGTCTDFQVVPGCGISCKVTNIEGLLHKSNLKIEENNIKNASLVQIDAINEQSSPSSSMIIDAHLSNAVNTQQYKVLIGNREWMIRNGLVISNDVDESMIEHERRGRTAVLVTIDDELCGLIAIADTVKPEAELAVHILKSMGLEVVLMTGDNSKTARSIASQVGITKVFAEVLPSHKVAKVKQLQEEGKRVAMVGDGINDSPALAMASVGIAIGTGTDVAIEAADVVLIRNDLLDVVASIDLSRKTVKRIRINFVFALIYNLIGIPIAAGVFLPIGLVLQPWMGSAAMAASSVSVVLSSLFLKLYRKPTYDNYELRPRSHTGQRSPSEISVHVGIDDTSRNSPRLGLLDRIVNYSRASINSLLSDKRSLNSVVTSEPDKHSLLVGDFREDDDTTL | ||||||
Modified residue | 152 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 270 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 327 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 339 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 353 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 357 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 362 | Phosphoserine | ||||
Sequence: S | ||||||
Glycosylation | 678 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 1204 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1422 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1424 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1452 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1455 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1458 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1461 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1465 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1468 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1478 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Structure
Family & Domains
Features
Showing features for domain, motif, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 8-74 | HMA 1 | ||||
Sequence: NSITITVEGMTCISCVRTIEQQIGKVNGVHHIKVSLEEKSATVIYNPKLQTPKTLQEAIDDMGFDAL | ||||||
Domain | 85-151 | HMA 2 | ||||
Sequence: TNTVFLTVTAPLALPWDHIQSTLLKTKGVTGVKISPQQRSAVVTIIPSVVSANQIVELVPDLSLDMG | ||||||
Domain | 171-237 | HMA 3 | ||||
Sequence: VLLKMRVEGMTCHSCTSTIEGKVGKLQGVQRIKVSLDNQEATIVYQPHLITAEEIKKQIEAVGFPAF | ||||||
Domain | 277-343 | HMA 4 | ||||
Sequence: SAITFTIDGMHCKSCVSNIESALSTLQYVSSIVVSLENRSAIVKYNASLVTPEILRKAIEAVSPGQY | ||||||
Domain | 377-443 | HMA 5 | ||||
Sequence: QEVVININGMTCNSCVQSIEGVISKKPGVKSIHVSLTNSTGTIEYDPLLTSPEPLREAIEDMGFDAV | ||||||
Domain | 480-546 | HMA 6 | ||||
Sequence: NKCYIQVSGMTCASCVANIERNLRREEGIYSVLVALMAGKAEVRYNPAVIQPRVIAELIRELGFGAV | ||||||
Domain | 556-622 | HMA 7 | ||||
Sequence: GILELVVRGMTCASCVHKIESTLTKHKGIFYCSVALATNKAHIKYDPEIIGPRDIIHTIGNLGFEAS | ||||||
Motif | 1459-1460 | Endocytosis signal | ||||
Sequence: LL | ||||||
Region | 1478-1492 | PDZD11-binding | ||||
Sequence: SLLVGDFREDDDTTL | ||||||
Motif | 1479-1480 | Endocytosis signal | ||||
Sequence: LL |
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
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IB subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,492
- Mass (Da)162,093
- Last updated1997-02-01 v1
- Checksum34F75152B105AE9F
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8L2UQX4 | A0A8L2UQX4_RAT | Atp7a | 161 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U59245 EMBL· GenBank· DDBJ | AAB06393.1 EMBL· GenBank· DDBJ | mRNA |