ATP7A_MOUSE
ID ATP7A_MOUSE Reviewed; 1491 AA.
AC Q64430; A2AG69; O35101; P97422; Q64431;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Copper-transporting ATPase 1;
DE EC=7.2.2.8 {ECO:0000250|UniProtKB:Q04656};
DE AltName: Full=Copper pump 1;
DE AltName: Full=Menkes disease-associated protein homolog;
GN Name=Atp7a {ECO:0000303|PubMed:25639447, ECO:0000312|MGI:MGI:99400};
GN Synonyms=Mnk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN MOTTLED PHENOTYPES, AND TISSUE
RP SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=8054976; DOI=10.1038/ng0494-369;
RA Levinson B., Vulpe C., Elder B., Martin C., Verley F., Packman S.,
RA Gitschier J.;
RT "The mottled gene is the mouse homologue of the Menkes disease gene.";
RL Nat. Genet. 6:369-373(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INVOLVEMENT IN MOTTLED PHENOTYPES.
RC STRAIN=BALB/cJ, DL, and ICR X Swiss Webster; TISSUE=Embryo, and Kidney;
RX PubMed=8054977; DOI=10.1038/ng0494-374;
RA Mercer J.F.B., Grimes A., Ambrosini L., Lockhart P., Paynter J.A.,
RA Dierick H., Glover T.W.;
RT "Mutations in the murine homologue of the Menkes gene in dappled and
RT blotchy mice.";
RL Nat. Genet. 6:374-378(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN MOTTLED PHENOTYPES, AND VARIANTS
RP ARG-674 AND PRO-1381.
RC STRAIN=C3H/HeJ; TISSUE=Placenta;
RX PubMed=9385451; DOI=10.1080/15216549700204721;
RA Ohta Y., Shiraishi N., Nishikimi M.;
RT "Occurrence of two missense mutations in Cu-ATPase of the macular mouse, a
RT Menkes disease model.";
RL Biochem. Mol. Biol. Int. 43:913-918(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN MOTTLED PHENOTYPES, AND TISSUE
RP SPECIFICITY.
RC STRAIN=CBA X C3H;
RX PubMed=9215672; DOI=10.1093/hmg/6.7.1037;
RA Grimes A., Hearn C.J., Lockhart P., Newgreen D.F., Mercer J.F.B.;
RT "Molecular basis of the brindled mouse mutant (Mo(br)): a murine model of
RT Menkes disease.";
RL Hum. Mol. Genet. 6:1037-1042(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=12488345; DOI=10.1210/en.2002-220716;
RA Steveson T.C., Ciccotosto G.D., Ma X.M., Mueller G.P., Mains R.E.,
RA Eipper B.A.;
RT "Menkes protein contributes to the function of peptidylglycine alpha-
RT amidating monooxygenase.";
RL Endocrinology 144:188-200(2003).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15634787; DOI=10.1523/jneurosci.3699-04.2005;
RA Schlief M.L., Craig A.M., Gitlin J.D.;
RT "NMDA receptor activation mediates copper homeostasis in hippocampal
RT neurons.";
RL J. Neurosci. 25:239-246(2005).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP SOD3.
RX PubMed=16371425; DOI=10.1096/fj.05-4564fje;
RA Qin Z., Itoh S., Jeney V., Ushio-Fukai M., Fukai T.;
RT "Essential role for the Menkes ATPase in activation of extracellular
RT superoxide dismutase: implication for vascular oxidative stress.";
RL FASEB J. 20:334-336(2006).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP TYRP1.
RX PubMed=18650808; DOI=10.1038/nature07163;
RA Setty S.R., Tenza D., Sviderskaya E.V., Bennett D.C., Raposo G.,
RA Marks M.S.;
RT "Cell-specific ATP7A transport sustains copper-dependent tyrosinase
RT activity in melanosomes.";
RL Nature 454:1142-1146(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-357 AND SER-1457, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-357; SER-362; SER-1464;
RP SER-1467 AND SER-1477, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, Pancreas, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=25639447; DOI=10.1002/path.4511;
RA Hodgkinson V.L., Dale J.M., Garcia M.L., Weisman G.A., Lee J., Gitlin J.D.,
RA Petris M.J.;
RT "X-linked spinal muscular atrophy in mice caused by autonomous loss of
RT ATP7A in the motor neuron.";
RL J. Pathol. 236:241-250(2015).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF
RP 1443-LEU-LEU-1444; 1458-LEU-LEU-1459 AND 1478-LEU-LEU-1479.
RX PubMed=27337370; DOI=10.1039/c6mt00093b;
RA Zhu S., Shanbhag V., Hodgkinson V.L., Petris M.J.;
RT "Multiple di-leucines in the ATP7A copper transporter are required for
RT retrograde trafficking to the trans-Golgi network.";
RL Metallomics 8:993-1001(2016).
CC -!- FUNCTION: ATP-driven copper (Cu(+)) ion pump that plays an important
CC role in intracellular copper ion homeostasis (PubMed:25639447,
CC PubMed:27337370, PubMed:18650808). Within a catalytic cycle, acquires
CC Cu(+) ion from donor protein on the cytoplasmic side of the membrane
CC and delivers it to acceptor protein on the lumenal side. The transfer
CC of Cu(+) ion across the membrane is coupled to ATP hydrolysis and is
CC associated with a transient phosphorylation that shifts the pump
CC conformation from inward-facing to outward-facing state (By
CC similarity). Under physiological conditions, at low cytosolic copper
CC concentration, it is localized at the trans-Golgi network (TGN) where
CC it transfers Cu(+) ions to cuproenzymes of the secretory pathway
CC (PubMed:27337370, PubMed:18650808, PubMed:16371425, PubMed:12488345).
CC Upon elevated cytosolic copper concentrations, it relocalizes to the
CC plasma membrane where it is responsible for the export of excess Cu(+)
CC ions (By similarity). May play a dual role in neuron function and
CC survival by regulating cooper efflux and neuronal transmission at the
CC synapse as well as by supplying Cu(+) ions to enzymes such as PAM, TYR
CC and SOD3 (PubMed:25639447, PubMed:15634787, PubMed:16371425,
CC PubMed:12488345). In the melanosomes of pigmented cells, provides
CC copper cofactor to TYR to form an active TYR holoenzyme for melanin
CC biosynthesis (PubMed:18650808). {ECO:0000250|UniProtKB:Q04656}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + Cu(+)(in) + H2O = ADP + Cu(+)(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:25792, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:49552,
CC ChEBI:CHEBI:456216; EC=7.2.2.8;
CC Evidence={ECO:0000250|UniProtKB:Q04656};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25793;
CC Evidence={ECO:0000250|UniProtKB:Q04656};
CC -!- SUBUNIT: Monomer. Interacts with PDZD11. Interacts with ATOX1 and
CC COMMD1 (By similarity). Interacts with TYRP1 (PubMed:18650808).
CC Directly interacts with SOD3; this interaction is copper-dependent and
CC is required for SOD3 activity (PubMed:16371425).
CC {ECO:0000250|UniProtKB:Q04656, ECO:0000269|PubMed:16371425,
CC ECO:0000269|PubMed:18650808}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000269|PubMed:16371425, ECO:0000269|PubMed:18650808,
CC ECO:0000269|PubMed:27337370}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:27337370}; Multi-pass
CC membrane protein {ECO:0000255}. Melanosome membrane
CC {ECO:0000269|PubMed:18650808}; Multi-pass membrane protein
CC {ECO:0000255}. Early endosome membrane {ECO:0000269|PubMed:27337370};
CC Multi-pass membrane protein {ECO:0000255}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P70705}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P70705}. Postsynaptic density
CC {ECO:0000250|UniProtKB:P70705}. Note=Cycles constitutively between the
CC TGN and the plasma membrane. Predominantly found in the TGN and
CC relocalized to the plasma membrane in response to elevated copper
CC levels (PubMed:27337370). Targeting into melanosomes is regulated by
CC BLOC-1 complex (PubMed:18650808). In response to glutamate translocates
CC to neuron processes with a minor fraction at extrasynaptic sites (By
CC similarity). {ECO:0000250|UniProtKB:P70705,
CC ECO:0000269|PubMed:18650808, ECO:0000269|PubMed:27337370}.
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:25639447, PubMed:8054976,
CC PubMed:12488345). Highly expressed in pituitary endocrine cells
CC (PubMed:12488345). Expressed in melanocytes (at protein level)
CC (PubMed:18650808). Expressed in motor neuron (at protein level)
CC (PubMed:25639447). Expressed in hippocampal neuron (at protein level)
CC (PubMed:15634787). In the kidney, it is detected in the proximal and
CC distal tubules (at protein level) (PubMed:9215672). Expressed in aorta
CC (at protein level) (PubMed:16371425). {ECO:0000269|PubMed:12488345,
CC ECO:0000269|PubMed:15634787, ECO:0000269|PubMed:16371425,
CC ECO:0000269|PubMed:18650808, ECO:0000269|PubMed:25639447,
CC ECO:0000269|PubMed:8054976, ECO:0000269|PubMed:9215672}.
CC -!- DEVELOPMENTAL STAGE: Detected 10 days after birth in pituitary and
CC adrenal endocrine tissues and at a lower level in hypothalamus and
CC atrium (at protein level). {ECO:0000269|PubMed:12488345}.
CC -!- DOMAIN: The ATP binding site comprises residues located in alpha-1 and
CC alpha-2 helices and beta-2 and beta-3 strands, which are involved in
CC van der Waal's interactions, and Glu-1072 which forms an hydrogen bond
CC with the adenine ring. {ECO:0000250|UniProtKB:Q04656}.
CC -!- DOMAIN: The heavy-metal-associated domain (HMA) coordinates a Cu(+) ion
CC via the cysteine residues within the CXXC motif. The transfer of Cu(+)
CC ion from ATOX1 to ATP7A involves the formation of a three-coordinate
CC Cu(+)-bridged heterodimer where the metal is shared between the two
CC metal binding sites of ATOX1 and ATP7A. The Cu(+) ion appears to switch
CC between two coordination modes, forming two links with one protein and
CC one with the other. Cisplatin, a chemotherapeutic drug, can bind the
CC CXXC motif and hinder the release of Cu(+) ion.
CC {ECO:0000250|UniProtKB:Q04656}.
CC -!- DOMAIN: Contains three di-leucine motifs in the C-terminus which are
CC required for recycling from the plasma membrane to the TGN. The di-
CC leucine 1478-Leu-Leu-1479 motif mediates endocytosis at the plasma
CC membrane, whereas the di-leucine 1458-Leu-Leu-1459 motif is a sorting
CC signal for retrograde trafficking to TGN via early endosomes.
CC {ECO:0000269|PubMed:27337370}.
CC -!- DISEASE: Note=Defects in Atp7a are associated with mottled, an X-linked
CC recessive condition characterized by mottled pigmentation of the coat,
CC defects in connective tissue and neonatal or fetal death. It is due to
CC a defect in absorption and transport of copper. The mottled mutants
CC exhibit a diversity of phenotypes. Two of these mutants are called
CC brindled and blotchy and their phenotypes resemble classical Menkes
CC disease (MD) and occipital horn syndrome (OHS) in humans, respectively.
CC Other mutants are called dappled, mosaic, tortoiseshell, pewter, etc.
CC {ECO:0000269|PubMed:8054976, ECO:0000269|PubMed:8054977,
CC ECO:0000269|PubMed:9215672, ECO:0000269|PubMed:9385451}.
CC -!- DISRUPTION PHENOTYPE: Cell-specific silencing in motor neurons is
CC associated with loss of motor neuron cell bodies and progressive
CC denervation of the neuromuscular junctions with aging, consistent with
CC the clinical features of human distal spinal muscular atrophy X-linked
CC disease, 3 (DSMAX3). {ECO:0000269|PubMed:25639447}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IB subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Heavy metal - Issue 79 of
CC February 2007;
CC URL="https://web.expasy.org/spotlight/back_issues/079";
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DR EMBL; U03434; AAA57445.1; -; mRNA.
DR EMBL; U03736; AAB08487.1; -; mRNA.
DR EMBL; AB007134; BAA22369.1; -; mRNA.
DR EMBL; U71091; AAB37301.1; -; mRNA.
DR EMBL; AL672288; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS41097.1; -.
DR PIR; S43793; S43793.
DR RefSeq; NP_033856.3; NM_009726.5.
DR AlphaFoldDB; Q64430; -.
DR SMR; Q64430; -.
DR BioGRID; 198268; 30.
DR CORUM; Q64430; -.
DR IntAct; Q64430; 27.
DR STRING; 10090.ENSMUSP00000058840; -.
DR GlyGen; Q64430; 2 sites.
DR iPTMnet; Q64430; -.
DR PhosphoSitePlus; Q64430; -.
DR SwissPalm; Q64430; -.
DR jPOST; Q64430; -.
DR MaxQB; Q64430; -.
DR PaxDb; Q64430; -.
DR PRIDE; Q64430; -.
DR ProteomicsDB; 277131; -.
DR ABCD; Q64430; 1 sequenced antibody.
DR Antibodypedia; 536; 418 antibodies from 35 providers.
DR DNASU; 11977; -.
DR Ensembl; ENSMUST00000113557; ENSMUSP00000109186; ENSMUSG00000033792.
DR GeneID; 11977; -.
DR KEGG; mmu:11977; -.
DR UCSC; uc012hnn.2; mouse.
DR CTD; 538; -.
DR MGI; MGI:99400; Atp7a.
DR VEuPathDB; HostDB:ENSMUSG00000033792; -.
DR eggNOG; KOG0207; Eukaryota.
DR GeneTree; ENSGT00940000159568; -.
DR HOGENOM; CLU_001771_0_1_1; -.
DR InParanoid; Q64430; -.
DR BRENDA; 7.2.2.8; 3474.
DR BRENDA; 7.2.2.9; 3474.
DR Reactome; R-MMU-6803544; Ion influx/efflux at host-pathogen interface.
DR Reactome; R-MMU-936837; Ion transport by P-type ATPases.
DR BioGRID-ORCS; 11977; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Atp7a; mouse.
DR PRO; PR:Q64430; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q64430; protein.
DR Bgee; ENSMUSG00000033792; Expressed in choroid plexus epithelium and 253 other tissues.
DR ExpressionAtlas; Q64430; baseline and differential.
DR Genevisible; Q64430; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0031526; C:brush border membrane; ISO:MGI.
DR GO; GO:0031252; C:cell leading edge; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0005770; C:late endosome; ISO:MGI.
DR GO; GO:0033162; C:melanosome membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005902; C:microvillus; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
DR GO; GO:0030141; C:secretory granule; ISO:MGI.
DR GO; GO:0005802; C:trans-Golgi network; IDA:MGI.
DR GO; GO:0032588; C:trans-Golgi network membrane; IDA:UniProtKB.
DR GO; GO:0030140; C:trans-Golgi network transport vesicle; ISS:HGNC-UCL.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0051087; F:chaperone binding; ISO:MGI.
DR GO; GO:0005507; F:copper ion binding; ISS:HGNC.
DR GO; GO:0005375; F:copper ion transmembrane transporter activity; IMP:MGI.
DR GO; GO:0032767; F:copper-dependent protein binding; ISS:UniProtKB.
DR GO; GO:1903136; F:cuprous ion binding; ISS:UniProtKB.
DR GO; GO:0043682; F:P-type divalent copper transporter activity; IDA:MGI.
DR GO; GO:0140581; F:P-type monovalent copper transporter activity; ISS:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0016532; F:superoxide dismutase copper chaperone activity; IDA:MGI.
DR GO; GO:0046034; P:ATP metabolic process; IMP:MGI.
DR GO; GO:0001568; P:blood vessel development; IMP:MGI.
DR GO; GO:0001974; P:blood vessel remodeling; IMP:MGI.
DR GO; GO:0051216; P:cartilage development; IMP:MGI.
DR GO; GO:0006584; P:catecholamine metabolic process; IMP:MGI.
DR GO; GO:0006878; P:cellular copper ion homeostasis; IMP:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISO:MGI.
DR GO; GO:0071280; P:cellular response to copper ion; ISO:MGI.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; ISO:MGI.
DR GO; GO:0021954; P:central nervous system neuron development; IMP:MGI.
DR GO; GO:0021702; P:cerebellar Purkinje cell differentiation; IMP:MGI.
DR GO; GO:0030199; P:collagen fibril organization; IMP:MGI.
DR GO; GO:0060003; P:copper ion export; IMP:UniProtKB.
DR GO; GO:0055070; P:copper ion homeostasis; IBA:GO_Central.
DR GO; GO:0015677; P:copper ion import; IMP:MGI.
DR GO; GO:0006825; P:copper ion transport; IDA:MGI.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:MGI.
DR GO; GO:0010273; P:detoxification of copper ion; IMP:MGI.
DR GO; GO:0042417; P:dopamine metabolic process; IMP:MGI.
DR GO; GO:0048251; P:elastic fiber assembly; IMP:MGI.
DR GO; GO:0051542; P:elastin biosynthetic process; IMP:MGI.
DR GO; GO:0042414; P:epinephrine metabolic process; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IMP:MGI.
DR GO; GO:0031069; P:hair follicle morphogenesis; IMP:MGI.
DR GO; GO:0007626; P:locomotory behavior; IMP:MGI.
DR GO; GO:0048286; P:lung alveolus development; IMP:MGI.
DR GO; GO:0007005; P:mitochondrion organization; IMP:MGI.
DR GO; GO:0045914; P:negative regulation of catecholamine metabolic process; IMP:MGI.
DR GO; GO:0034760; P:negative regulation of iron ion transmembrane transport; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI.
DR GO; GO:0070050; P:neuron cellular homeostasis; IMP:MGI.
DR GO; GO:0048812; P:neuron projection morphogenesis; IMP:MGI.
DR GO; GO:0042421; P:norepinephrine biosynthetic process; IMP:MGI.
DR GO; GO:0042415; P:norepinephrine metabolic process; IMP:MGI.
DR GO; GO:0018205; P:peptidyl-lysine modification; IMP:MGI.
DR GO; GO:0043473; P:pigmentation; IMP:MGI.
DR GO; GO:0043085; P:positive regulation of catalytic activity; IMP:MGI.
DR GO; GO:0045793; P:positive regulation of cell size; ISO:MGI.
DR GO; GO:1904960; P:positive regulation of cytochrome-c oxidase activity; IMP:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:MGI.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; ISO:MGI.
DR GO; GO:0048023; P:positive regulation of melanin biosynthetic process; ISS:UniProtKB.
DR GO; GO:1903036; P:positive regulation of response to wounding; ISO:MGI.
DR GO; GO:1901671; P:positive regulation of superoxide dismutase activity; IMP:MGI.
DR GO; GO:0032773; P:positive regulation of tyrosinase activity; ISS:UniProtKB.
DR GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; ISO:MGI.
DR GO; GO:0021860; P:pyramidal neuron development; IMP:MGI.
DR GO; GO:1904959; P:regulation of cytochrome-c oxidase activity; ISO:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0002082; P:regulation of oxidative phosphorylation; IMP:MGI.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IMP:MGI.
DR GO; GO:0019430; P:removal of superoxide radicals; IMP:MGI.
DR GO; GO:0046688; P:response to copper ion; ISO:MGI.
DR GO; GO:0010042; P:response to manganese ion; ISO:MGI.
DR GO; GO:0042428; P:serotonin metabolic process; IMP:MGI.
DR GO; GO:0043588; P:skin development; IMP:MGI.
DR GO; GO:0042093; P:T-helper cell differentiation; IMP:MGI.
DR GO; GO:0006568; P:tryptophan metabolic process; IMP:MGI.
DR GO; GO:0006570; P:tyrosine metabolic process; IMP:MGI.
DR CDD; cd00371; HMA; 6.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR017969; Heavy-metal-associated_CS.
DR InterPro; IPR006122; HMA_Cu_ion-bd.
DR InterPro; IPR006121; HMA_dom.
DR InterPro; IPR036163; HMA_dom_sf.
DR InterPro; IPR027256; P-typ_ATPase_IB.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR Pfam; PF00403; HMA; 6.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SUPFAM; SSF55008; SSF55008; 6.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01525; ATPase-IB_hvy; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 2.
DR TIGRFAMs; TIGR00003; TIGR00003; 6.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
DR PROSITE; PS01047; HMA_1; 6.
DR PROSITE; PS50846; HMA_2; 7.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Cell projection; Copper; Copper transport;
KW Disease variant; Endosome; Glycoprotein; Golgi apparatus; Ion transport;
KW Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Synapse; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1491
FT /note="Copper-transporting ATPase 1"
FT /id="PRO_0000046312"
FT TOPO_DOM 1..644
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 645..666
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 667..705
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 706..725
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 726..732
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 733..753
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 754..772
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 773..793
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 794..926
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 927..950
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 951..980
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 981..1002
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1003..1347
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1348..1365
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1366..1376
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1377..1396
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1397..1491
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 8..74
FT /note="HMA 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 85..151
FT /note="HMA 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 171..237
FT /note="HMA 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 277..343
FT /note="HMA 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 377..443
FT /note="HMA 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 479..545
FT /note="HMA 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 555..621
FT /note="HMA 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT REGION 1477..1491
FT /note="PDZD11-binding"
FT /evidence="ECO:0000250"
FT MOTIF 1458..1459
FT /note="Endocytosis signal"
FT /evidence="ECO:0000269|PubMed:27337370"
FT MOTIF 1478..1479
FT /note="Endocytosis signal"
FT /evidence="ECO:0000269|PubMed:27337370"
FT ACT_SITE 1035
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000305"
FT BINDING 18
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q04656"
FT BINDING 19
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 22
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 182
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 185
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 288
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 291
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 388
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 391
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 490
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 493
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 566
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 569
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 1072
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q04656"
FT BINDING 1292
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 1296
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT MOD_RES 152
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q04656"
FT MOD_RES 270
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04656"
FT MOD_RES 327
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q04656"
FT MOD_RES 339
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04656"
FT MOD_RES 353
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70705"
FT MOD_RES 357
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1203
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P70705"
FT MOD_RES 1421
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04656"
FT MOD_RES 1423
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04656"
FT MOD_RES 1451
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04656"
FT MOD_RES 1454
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04656"
FT MOD_RES 1457
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 1460
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04656"
FT MOD_RES 1464
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1467
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1477
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 677
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 966
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 674
FT /note="H -> R (in MD)"
FT /evidence="ECO:0000269|PubMed:9385451"
FT VARIANT 1381
FT /note="S -> P (in MD)"
FT /evidence="ECO:0000269|PubMed:9385451"
FT MUTAGEN 1443..1444
FT /note="LL->AA: Impaired trafficking from endosome to TGN."
FT /evidence="ECO:0000269|PubMed:27337370"
FT MUTAGEN 1443..1444
FT /note="LL->VV: Has no effect on trafficking from endosome
FT to TGN."
FT /evidence="ECO:0000269|PubMed:27337370"
FT MUTAGEN 1458..1459
FT /note="LL->AA,VV: Impaired trafficking from endosome to
FT TGN."
FT /evidence="ECO:0000269|PubMed:27337370"
FT MUTAGEN 1478..1479
FT /note="LL->AA,VV: Impaired endocytosis associated with
FT retention at the plasma membrane."
FT /evidence="ECO:0000269|PubMed:27337370"
FT CONFLICT 44
FT /note="E -> D (in Ref. 1; AAA57445 and 4; AAB37301)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="I -> V (in Ref. 1; AAA57445 and 4; AAB37301)"
FT /evidence="ECO:0000305"
FT CONFLICT 172
FT /note="M -> R (in Ref. 1; AAA57445 and 4; AAB37301)"
FT /evidence="ECO:0000305"
FT CONFLICT 245..246
FT /note="LK -> PI (in Ref. 2; AAB08487)"
FT /evidence="ECO:0000305"
FT CONFLICT 445
FT /note="P -> PA (in Ref. 2; AAB08487 and 4; AAB37301)"
FT /evidence="ECO:0000305"
FT CONFLICT 470
FT /note="L -> P (in Ref. 2; AAB08487, 3; BAA22369 and 4;
FT AAB37301)"
FT /evidence="ECO:0000305"
FT CONFLICT 515
FT /note="M -> T (in Ref. 1; AAA57445 and 4; AAB37301)"
FT /evidence="ECO:0000305"
FT CONFLICT 717
FT /note="C -> F (in Ref. 2; AAB08487)"
FT /evidence="ECO:0000305"
FT CONFLICT 770
FT /note="T -> A (in Ref. 2; AAB08487)"
FT /evidence="ECO:0000305"
FT CONFLICT 775
FT /note="P -> S (in Ref. 2; AAB08487)"
FT /evidence="ECO:0000305"
FT CONFLICT 885
FT /note="I -> T (in Ref. 2; AAB08487)"
FT /evidence="ECO:0000305"
FT CONFLICT 1169
FT /note="Y -> H (in Ref. 2; AAB08487)"
FT /evidence="ECO:0000305"
FT CONFLICT 1204
FT /note="A -> P (in Ref. 2; AAB08487 and 4; AAB37301)"
FT /evidence="ECO:0000305"
FT CONFLICT 1217
FT /note="I -> M (in Ref. 1; AAA57445)"
FT /evidence="ECO:0000305"
FT CONFLICT 1253
FT /note="R -> Q (in Ref. 1; AAA57445)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1491 AA; 161959 MW; 2FADCC6806994CA5 CRC64;
MEPSVDANSI TITVEGMTCI SCVRTIEQQI GKVNGVHHIK VSLEEKSATI IYDPKLQTPK
TLQEAIDDMG FDALLHNANP LPVLTNTVFL TVTAPLTLPW DHIQSTLLKT KGVTGVKISP
QQRSAVVTII PSVVSASQIV ELVPDLSLDM GTQEKKSGAC EEHSTPQAGE VMLKMKVEGM
TCHSCTSTIE GKVGKLQGVQ RIKVSLDNQE ATIVFQPHLI TAEEIKKQIE AVGFPAFIKK
QPKYLKLGAI DVERLKNTPV KSSEGSQQKS PSYPSDSTTM FTIEGMHCKS CVSNIESALS
TLQYVSSIVV SLENRSAIVK YNASLVTPEM LRKAIEAISP GQYRVSIASE VESTASSPSS
SSLQKMPLNI VSQPLTQEAV ININGMTCNS CVQSIEGVIS KKPGVKSIHV SLANSTGTIE
FDPLLTSPET LREAIEDMGF DAALPDMKEP LVVIAQPSLE TPLLPSSNEL ENVMTSVQNK
CYIQVSGMTC ASCVANIERN LRREEGIYSV LVALMAGKAE VRYNPAVIQP RVIAEFIREL
GFGAMVMENA GEGNGILELV VRGMTCASCV HKIESTLTKH KGIFYCSVAL ATNKAHIKYD
PEIIGPRDII HTIGSLGFEA SLVKKDRSAN HLDHKREIKQ WRGSFLVSLF FCIPVMGLMV
YMMVMDHHLA TLHHNQNMSN EEMINMHSAM FLERQILPGL SIMNLLSLLL CLPVQFCGGW
YFYIQAYKAL KHKTANMDVL IVLATTIAFA YSLVILLVAM FERAKVNPIT FFDTPPMLFV
FIALGRWLEH IAKGKTSEAL AKLISLQATE ATIVTLNSEN LLLSEEQVDV ELVQRGDIIK
VVPGGKFPVD GRVIEGHSMV DESLITGEAM PVAKKPGSTV IAGSINQNGS LLIRATHVGA
DTTLSQIVKL VEEAQTSKAP IQQFADKLSG YFVPFIVLVS IVTLLVWIII GFQNFEIVET
YFPGYNRSIS RTETIIRFAF QASITVLCIA CPCSLGLATP TAVMVGTGVG AQNGILIKGG
EPLEMAHKVK VVVFDKTGTI THGTPVVNQV KVLVESNKIS RNKILAIVGT AESNSEHPLG
AAVTKYCKKE LDTETLGTCT DFQVVPGCGI SCKVTNIEGL LHKSNLKIEE NNIKNASLVQ
IDAINEQSST SSSMIIDAHL SNAVNTQQYK VLIGNREWMI RNGLVISNDV DESMIEHERR
GRTAVLVTID DELCGLIAIA DTVKPEAELA VHILKSMGLE VVLMTGDNSK TARSIASQVG
ITKVFAEVLP SHKVAKVKQL QEEGKRVAMV GDGINDSPAL AMANVGIAIG TGTDVAIEAA
DVVLIRNDLL DVVASIDLSR KTVKRIRINF VFALIYNLVG IPIAAGVFLP IGLVLQPWMG
SAAMAASSVS VVLSSLFLKL YRKPTYDNYE LHPRSHTGQR SPSEISVHVG IDDTSRNSPR
LGLLDRIVNY SRASINSLLS DKRSLNSVVT SEPDKHSLLV GDFREDDDTT L
