Property Summary

NCBI Gene PubMed Count 60
PubMed Score 131.46
PubTator Score 130.95

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (3)

Expression

  Differential Expression (3)

Disease log2 FC p
osteosarcoma -1.357 2.2e-03
acute myeloid leukemia -1.300 8.7e-03
ovarian cancer 1.800 1.4e-05

Protein-protein Interaction (1)

Gene RIF (49)

PMID Text
26879543 Upon neuronal differentiation, transitions in redox states upregulates expression of ATOX1 and its partner ATP7A, producing higher flux of copper through the secretory pathway.
26866891 Multiple genetic models identified genetic associations with systolic blood pressure and ATOX1.
26784148 results suggest the possibility of a therapy with copper-chelating or ionophore drugs in subtypes of tumors showing specific alterations in ATOX1 expression
26745464 In addition to Atox1, the human cytoplasm also contains Cu chaperones for loading of superoxide dismutase 1 (i.e. CCS) and cytochrome c oxidase in mitochondria (i.e. Cox17). [review]
26745413 C-Terminus of Human Copper Importer Ctr1 Acts as a Binding Site and Transfers Copper to Atox1
26437801 Cu chaperone function of Atox1 mediated through Cu transporter ATP7A is required for VEGF-induced angiogenesis via activation of Cu enzyme lysyl oxidase.
26213915 To identify new interactions partners of Atox1, a yeast two-hybrid screen with a large human placenta library of cDNA fragments using Atox1 as bait, was performed.
25962064 Studied the localization of Atox1 in HeLa cells using fluorescence imaging in combination with in vitro binding experiments to fluorescently labeled DNA duplexes harboring the proposed promotor sequence.
25673218 Human cytoplasmic copper chaperones Atox1 and CCS exchange copper ions in vitro
25111319 Cisplatin is one of the most used anticancer drugs. Its cellular influx and delivery to target DNA may involve the copper chaperone Atox1 protein.
24837030 The data collected here shows that the Atox1 keeps its dimer nature also in the presence of the CTR1 c-terminal domain; however, two geometrical states are assumed by the Atox1.
24824562 The Cu-binding motif in Atox1, as well as in target Cu-binding domains of ATP7A/B, consists of a MX1CXXC motif where X1 = T.
24522867 Human Grx1 can catalyse reduction of Atox1 by glutathione but only in the presence of Cu(I).
24469739 These results indicate that the roles of Atox1 in the regulation of cellular trafficking of platinum drugs are dependent on the coordination configurations.
24445997 Atox1 has a role in copper transport to tumor cell nuclei.
24343031 CTR1 silencing increased the protein levels of copper chaperone ATOX1 and copper chaperone for superoxide dismutase 1 (CCS-1), but decreased copper chaperone for cytochrome c oxidase (COX17).
24036897 Atox1 contains positive residues that mediate membrane association and aid subsequent copper loading.
23778981 the primary coordination site of Atox1 for interaction wtih cisplatin is at the cysteine residues in the Cu(I)-binding sequence Cys(12)GlyGlyCys(15)
23751120 Binding of free cisplatin and reaction with the cisplatin-loaded Atox1 produce the same protein-bound platinum intermediate in the transfer of metal-binding domain (repeat) (MBD)2 from Atox1.
23624903 Knockdown of ATOX1 in non-small cell lung cancer cells was associated with reduction in copper-stimulated cell proliferation. These findings suggest that ATOX1 plays an important role in copper-stimulated proliferation of non-small cell lung cancer cells.
23553875 Based on structural analysis, this work determines that the protein possesses two distinct conformations referred to as "in" and "out" due to the relative positioning of Cys12 (one of Cu(I) binding residues).
23169585 different effects of ATX1 unfolding on Cu(I) affinity
22677543 No major role can be attributed to Atox1 and COMMD in the pathophysiology or clinical variation of Wilson disease.
22648419 GSSG oxidizes copper-coordinating cysteines of Atox1 with formation of an intramolecular disulfide. GSH alone is sufficient to reduce the disulfide, restoring the ability of Atox1 to bind copper; glutaredoxin 1 facilitates this reaction when GSH is low
22574136 thermodynamic parameters of copper (Cu) transfer from the human copper chaperone Atox1 to the fourth metal-binding domain of the Wilson disease protein
21482801 By binding to Atox1 in the cytoplasm, cisPt transport to DNA may be blocked. In agreement with this model, cell line studies demonstrate a correlation between Atox1 expression levels, and cisplatin resistance.
21258123 Unification of the copper(I) binding affinities of the metallo-chaperones Atx1, Atox1, and related proteins: detection probes and affinity standards.
19453293 The interaction between the human copper(I)-chaperone HAH1 (human ATX1 homologue) and a metal-binding domain in one of its partners, namely the P-type copper-transporting ATPase, ATP7A, was characterized.
19146392 Atox1 residues have been conserved to ensure backbone-loop flexibility, electrostatic copper site stabilization, and proper core packing.
18976975 Knockdown of ATX1 antioxidant protein 1 homolog (ATOX1) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells
18685091 Conserved residues modulate copper release in human copper chaperone Atox1.
18558714 Forms a ocomplex with some domains of ATP7B, an interesting property of this class of proteins which have a signaling role in the function of the ATPases.
18416466 No major role can be attributed to Atox1 in the pathophysiology or clinical variation of Wilson disease.
18416466 Observational study of gene-disease association. (HuGE Navigator)
18245776 Atox1 functions as a novel transcription factor that, when activated by copper, undergoes nuclear translocation, DNA binding, and transactivation, thereby contributing to cell proliferation.
17881304 Divergent energetic properties of Atox1 apo- and holo-forms may be linked to conformational changes that facilitate copper transfer to the target.
17616150 The results from the quantum mechanical (QM) and MD simulations suggest that either a two- or three-coordinate exchange reaction is preferred and that it is unlikely that a four-coordinate Cu(I) species plays a role in copper exchange.
17545667 localization of ATP7A between the trans-Golgi network and the plasma membrane may be regulated by the accumulation of the adducts with HAH1, whereas the main role of domains 5 and 6 is to assist copper(I) translocation
16571664 Wilson disease protein is an acceptor of oopper from HAH1 protein.
16172131 a three-domain construct of ATP7A interacts with copper(I) and copper(I)-HAH1
15761197 Atox1 functions not only as a copper chaperone for SOD3 but also as a positive regulator for SOD3 transcription and may have an important role in modulating oxidative stress in the cardiovascular system.
15670166 interaction between the human copper(I) chaperone, HAH1, and one of its two physiological partners, the Menkes disease protein (ATP7A), was investigated in solution using heteronuclear NMR
15476398 Detailed structural and dynamic characterization of the behavior of human HAH1 in solution, in the physiologically relevant reduced apo and copper(I)-bound forms
14709553 handling of copper by Atox1 and copper transfer between Atox1 and WND are under kinetic rather than thermodynamic control
12763797 Regulates the function of ATP7B in Wilson's disease
12686548 X-ray absorption spectroscopy of this copper chaperone reveals a copper center capable of formation with exogenous thiols and phosphines
12679332 A copper-dependent interaction of Atox1 with the metal binding sites of menkes protein was observed
12594858 Gene structure of ATOX1.
12029094 transfers copper to the NH2-terminal domain of the Wilson's disease protein and regulates its catalytic activity

AA Sequence

MPKHEFSVDMTCGGCAEAVSRVLNKLGGVKYDIDLPNKKVCIESEHSMDTLLATLKKTGKTVSYLGLE        1 - 68
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Text Mined References (64)

PMID Year Title
26879543 2016 Neuronal differentiation is associated with a redox-regulated increase of copper flow to the secretory pathway.
26866891 2016 Longitudinal analytical approaches to genetic data.
26784148 2016 ATOX1 gene silencing increases susceptibility to anticancer therapy based on copper ionophores or chelating drugs.
26745464 2016 Extended functional repertoire for human copper chaperones.
26745413 2016 The C-Terminus of Human Copper Importer Ctr1 Acts as a Binding Site and Transfers Copper to Atox1.
26437801 2015 Copper Transport Protein Antioxidant-1 Promotes Inflammatory Neovascularization via Chaperone and Transcription Factor Function.
26213915 2015 Identification of New Potential Interaction Partners for Human Cytoplasmic Copper Chaperone Atox1: Roles in Gene Regulation?
25962064 2015 Human Copper Chaperone Atox1 Translocates to the Nucleus but does not Bind DNA In Vitro.
25673218 2015 Human cytoplasmic copper chaperones Atox1 and CCS exchange copper ions in vitro.
25416956 2014 A proteome-scale map of the human interactome network.
25111319 2014 Structural biology of cisplatin complexes with cellular targets: the adduct with human copper chaperone atox1 in aqueous solution.
24837030 2014 Probing the structural flexibility of the human copper metallochaperone Atox1 dimer and its interaction with the CTR1 c-terminal domain.
24824562 2014 T versus D in the MTCXXC motif of copper transport proteins plays a role in directional metal transport.
24522867 2014 Redox sulfur chemistry of the copper chaperone Atox1 is regulated by the enzyme glutaredoxin 1, the reduction potential of the glutathione couple GSSG/2GSH and the availability of Cu(I).
24469739 2014 Copper binding modulates the platination of human copper chaperone Atox1 by antitumor trans-platinum complexes.
24445997 2014 Roles of Atox1 and p53 in the trafficking of copper-64 to tumor cell nuclei: implications for cancer therapy.
24343031 2014 Changes in copper concentrations affect the protein levels but not the mRNA levels of copper chaperones in human umbilical vein endothelial cells.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24036897 2013 Atox1 contains positive residues that mediate membrane association and aid subsequent copper loading.
23778981 2013 Interaction of cisplatin and analogue Pt(en)Cl2 with the copper metallo-chaperone Atox1.
23751120 2013 Copper chaperone Atox1 interacts with the metal-binding domain of Wilson's disease protein in cisplatin detoxification.
23624903 2013 Knockdown of copper chaperone antioxidant-1 by RNA interference inhibits copper-stimulated proliferation of non-small cell lung carcinoma cells.
23553875 2013 Copper-chaperones with dicoordinated Cu(I)--unique protection mechanism.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23169585 2013 The influence of protein folding on the copper affinities of trafficking and target sites.
22677543 2012 Molecular analysis of Wilson patients: direct sequencing and MLPA analysis in the ATP7B gene and Atox1 and COMMD1 gene analysis.
22648419 2012 Functional partnership of the copper export machinery and glutathione balance in human cells.
22574136 2012 In vitro thermodynamic dissection of human copper transfer from chaperone to target protein.
21667063 2012 The copper-transporting capacity of ATP7A mutants associated with Menkes disease is ameliorated by COMMD1 as a result of improved protein expression.
21482801 2011 Cisplatin binds human copper chaperone Atox1 and promotes unfolding in vitro.
21269460 2011 Initial characterization of the human central proteome.
21258123 2011 Unification of the copper(I) binding affinities of the metallo-chaperones Atx1, Atox1, and related proteins: detection probes and affinity standards.
19608861 2009 Lysine acetylation targets protein complexes and co-regulates major cellular functions.
19453293 2009 Copper(I)-mediated protein-protein interactions result from suboptimal interaction surfaces.
19146392 2009 Differential roles of Met10, Thr11, and Lys60 in structural dynamics of human copper chaperone Atox1.
18685091 2008 Conserved residues modulate copper release in human copper chaperone Atox1.
18558714 2008 Metal binding domains 3 and 4 of the Wilson disease protein: solution structure and interaction with the copper(I) chaperone HAH1.
18416466 2008 Analysis of the human Atox 1 homologue in Wilson patients.
18245776 2008 Novel role of antioxidant-1 (Atox1) as a copper-dependent transcription factor involved in cell proliferation.
17881304 2007 Impact of cofactor on stability of bacterial (CopZ) and human (Atox1) copper chaperones.
17616150 2007 Insights into Cu(I) exchange in HAH1 using quantum mechanical and molecular simulations.
17545667 2007 The different intermolecular interactions of the soluble copper-binding domains of the menkes protein, ATP7A.
16571664 2006 Structure of human Wilson protein domains 5 and 6 and their interplay with domain 4 and the copper chaperone HAH1 in copper uptake.
16172131 2005 A NMR study of the interaction of a three-domain construct of ATP7A with copper(I) and copper(I)-HAH1: the interplay of domains.
15761197 2005 Role of antioxidant-1 in extracellular superoxide dismutase function and expression.
15670166 2005 An NMR study of the interaction between the human copper(I) chaperone and the second and fifth metal-binding domains of the Menkes protein.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15476398 2004 Solution structure of the apo and copper(I)-loaded human metallochaperone HAH1.
15146197 2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation.
14709553 2004 Binding of copper(I) by the Wilson disease protein and its copper chaperone.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12763797 2003 Functional properties of the human copper-transporting ATPase ATP7B (the Wilson's disease protein) and regulation by metallochaperone Atox1.
12686548 2003 X-ray absorption spectroscopy of the copper chaperone HAH1 reveals a linear two-coordinate Cu(I) center capable of adduct formation with exogenous thiols and phosphines.
12679332 2003 Kinetic analysis of the interaction of the copper chaperone Atox1 with the metal binding sites of the Menkes protein.
12594858 2003 Genomic organization of ATOX1, a human copper chaperone.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12420134 2002 Tissue localization of the copper chaperone ATOX1 and its potential role in disease.
12029094 2002 Metallochaperone Atox1 transfers copper to the NH2-terminal domain of the Wilson's disease protein and regulates its catalytic activity.
10982193 2000 Physical mapping of the human ATX1 homologue (HAH1) to the critical region of the 5q- syndrome within 5q32, and immediately adjacent to the SPARC gene.
10966647 2000 Structural basis for copper transfer by the metallochaperone for the Menkes/Wilson disease proteins.
10557326 1999 Interaction of the copper chaperone HAH1 with the Wilson disease protein is essential for copper homeostasis.
10497213 1999 Characterization of the interaction between the Wilson and Menkes disease proteins and the cytoplasmic copper chaperone, HAH1p.
9430722 1998 HAH1 is a copper-binding protein with distinct amino acid residues mediating copper homeostasis and antioxidant defense.
9083055 1997 Identification and functional expression of HAH1, a novel human gene involved in copper homeostasis.