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Gene Review

COMMD1  -  copper metabolism (Murr1) domain containing 1

Homo sapiens

Synonyms: C2orf5, COMM domain-containing protein 1, MGC27155, MURR1, Protein Murr1
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Disease relevance of COMMD1


High impact information on COMMD1

  • X-linked inhibitor of apoptosis (XIAP), known primarily for its caspase inhibitory properties, has recently been shown to interact with and regulate the levels of COMMD1, a protein associated with a form of canine copper toxicosis [2].
  • COMMD1-deficient cells demonstrate stabilization of RelA, greater nuclear accumulation of RelA after TNF stimulation, de-repression of several kappaB-responsive genes, and enhanced NF-kappaB-mediated cellular responses [3].
  • We report here that COMMD1 accelerates the ubiquitination and degradation of NF-kappaB subunits through its interaction with a multimeric ubiquitin ligase containing Elongins B and C, Cul2 and SOCS1 (ECS(SOCS1)) [3].
  • XIAP was found to interact with MURR1, a factor recently implicated in copper homeostasis [4].
  • However, cells and tissues derived from Xiap-deficient mice were found to contain reduced copper levels, while suppression of MURR1 resulted in increased intracellular copper in cultured cells [4].

Associations of COMMD1 with chemical compounds


Biological context of COMMD1

  • COMMD proteins inhibit NFkappaB mediated gene expression, and recent mechanistic studies have revealed that COMMD1 controls the ubiquitination of NFkappaB subunits, an event linked to transcriptional termination [6].
  • This review discusses how COMMD1 functions as a regulator of not only copper homeostasis but also sodium transport and the NF-kappaB signaling pathway [7].
  • While screening genes and expressed sequence tags in this region for mutations we found that exon 2 of the MURR1 gene is deleted in both alleles of all affected Bedlington terriers and in single alleles in obligate carriers [8].
  • Recent genetic data have revealed that MURR1, a single copy gene on dog chromosome 10q26, is mutated in this disorder [9].
  • MURR1 is a multifunctional protein that inhibits nuclear factor kappaB (NF-kappaB), a transcription factor with pleiotropic functions affecting innate and adaptive immunity, apoptosis, cell cycle regulation, and oncogenesis [10].

Anatomical context of COMMD1


Regulatory relationships of COMMD1

  • We found that ARF promotes the polyubiquitination of COMMD1 through Lys(63) of ubiquitin but not the polyubiquitination of Lys(48), which does not target COMMD1 for proteasome-dependent proteolysis [12].

Other interactions of COMMD1

  • Studies of the underlying defects in ATP7B and its suspected modifiers ATOX1 and COMMD1 are expected to unravel the disease's genotype-phenotype correlation, and should lead to the design of improved drugs for ameliorating the suffering of patients [13].
  • The three exons of the human MURR1 gene were sequenced after amplification of the genomic DNA by polymerase chain reaction.RESULTS: Our study did not reveal any mutations leading to an amino acid change in the MURR1 sequence of Wilson disease patients [14].

Analytical, diagnostic and therapeutic context of COMMD1

  • METHODS: Polyclonal antibodies raised against full-length recombinant human MURR1 were used for immunoblot analysis and indirect immunofluorescence studies [11].
  • RESULTS: Using Western blot analysis, these antibodies abundantly detected MURR1 as a 23 kDa protein in liver extracts of mice and dogs, but MURR1 was undetectable in the livers of affected Bedlington terriers [11].


  1. Analysis of the human homologue of the canine copper toxicosis gene MURR1 in Wilson disease patients. Stuehler, B., Reichert, J., Stremmel, W., Schaefer, M. J. Mol. Med. (2004) [Pubmed]
  2. XIAP Is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disorders. Mufti, A.R., Burstein, E., Csomos, R.A., Graf, P.C., Wilkinson, J.C., Dick, R.D., Challa, M., Son, J.K., Bratton, S.B., Su, G.L., Brewer, G.J., Jakob, U., Duckett, C.S. Mol. Cell (2006) [Pubmed]
  3. COMMD1 promotes the ubiquitination of NF-kappaB subunits through a cullin-containing ubiquitin ligase. Maine, G.N., Mao, X., Komarck, C.M., Burstein, E. EMBO J. (2007) [Pubmed]
  4. A novel role for XIAP in copper homeostasis through regulation of MURR1. Burstein, E., Ganesh, L., Dick, R.D., van De Sluis, B., Wilkinson, J.C., Klomp, L.W., Wijmenga, C., Brewer, G.J., Nabel, G.J., Duckett, C.S. EMBO J. (2004) [Pubmed]
  5. COMMD1 forms oligomeric complexes targeted to the endocytic membranes via specific interactions with phosphatidylinositol 4,5-bisphosphate. Burkhead, J.L., Morgan, C.T., Shinde, U., Haddock, G., Lutsenko, S. J. Biol. Chem. (2009) [Pubmed]
  6. COMMD proteins and the control of the NFkappaB pathway. Maine, G.N., Burstein, E. Cell Cycle (2007) [Pubmed]
  7. The many faces of the copper metabolism protein MURR1/COMMD1. de Bie, P., van de Sluis, B., Klomp, L., Wijmenga, C. J. Hered. (2005) [Pubmed]
  8. Identification of a new copper metabolism gene by positional cloning in a purebred dog population. van De Sluis, B., Rothuizen, J., Pearson, P.L., van Oost, B.A., Wijmenga, C. Hum. Mol. Genet. (2002) [Pubmed]
  9. The copper toxicosis gene product Murr1 directly interacts with the Wilson disease protein. Tao, T.Y., Liu, F., Klomp, L., Wijmenga, C., Gitlin, J.D. J. Biol. Chem. (2003) [Pubmed]
  10. COMMD proteins, a novel family of structural and functional homologs of MURR1. Burstein, E., Hoberg, J.E., Wilkinson, A.S., Rumble, J.M., Csomos, R.A., Komarck, C.M., Maine, G.N., Wilkinson, J.C., Mayo, M.W., Duckett, C.S. J. Biol. Chem. (2005) [Pubmed]
  11. The ubiquitously expressed MURR1 protein is absent in canine copper toxicosis. Klomp, A.E., van de Sluis, B., Klomp, L.W., Wijmenga, C. J. Hepatol. (2003) [Pubmed]
  12. Tumor suppressor ARF promotes non-classic proteasome-independent polyubiquitination of COMMD1. Huang, Y., Wu, M., Li, H.Y. J. Biol. Chem. (2008) [Pubmed]
  13. Wilson's disease: an update. Das, S.K., Ray, K. Nature clinical practice. Neurology. (2006) [Pubmed]
  14. Copper toxicosis gene MURR1 is not changed in Wilson disease patients with normal blood ceruloplasmin levels. Weiss, K.H., Merle, U., Schaefer, M., Ferenci, P., Fullekrug, J., Stremmel, W. World J. Gastroenterol. (2006) [Pubmed]
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