| Structural highlights
Function
[COMD1_HUMAN] Promotes ubiquitination of NF-kappa-B subunit RELA and its subsequent proteasomal degradation. Down-regulates NF-kappa-B activity. Down-regulates SOD1 activity by interfering with its homodimerization. Plays a role in copper ion homeostasis. Can bind one copper ion per monomer. May function to facilitate biliary copper excretion within hepatocytes.[1] [2] [3] [4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
COMMD1 is the prototype of a new protein family that plays a role in several important cellular processes, including NF-kappaB signaling, sodium transport, and copper metabolism. The COMMD proteins interact with one another via a conserved C-terminal domain, whereas distinct functions are predicted to result from a variable N-terminal domain. The COMMD proteins have not been characterized biochemically or structurally. Here, we present the solution structure of the N-terminal domain of COMMD1 (N-COMMD1, residues 1-108). This domain adopts an alpha-helical structure that bears little resemblance to any other helical protein. The compact nature of N-COMMD1 suggests that full-length COMMD proteins are modular, consistent with specific functional properties for each domain. Interactions between N-COMMD1 and partner proteins may occur via complementary electrostatic surfaces. These data provide a new foundation for biochemical characterization of COMMD proteins and for probing COMMD1 protein-protein interactions at the molecular level.
Solution structure of the COMMD1 N-terminal domain.,Sommerhalter M, Zhang Y, Rosenzweig AC J Mol Biol. 2007 Jan 19;365(3):715-21. Epub 2006 Oct 13. PMID:17097678[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Burstein E, Ganesh L, Dick RD, van De Sluis B, Wilkinson JC, Klomp LW, Wijmenga C, Brewer GJ, Nabel GJ, Duckett CS. A novel role for XIAP in copper homeostasis through regulation of MURR1. EMBO J. 2004 Jan 14;23(1):244-54. Epub 2003 Dec 18. PMID:14685266 doi:10.1038/sj.emboj.7600031
- ↑ Burstein E, Hoberg JE, Wilkinson AS, Rumble JM, Csomos RA, Komarck CM, Maine GN, Wilkinson JC, Mayo MW, Duckett CS. COMMD proteins, a novel family of structural and functional homologs of MURR1. J Biol Chem. 2005 Jun 10;280(23):22222-32. Epub 2005 Mar 30. PMID:15799966 doi:http://dx.doi.org/10.1074/jbc.M501928200
- ↑ de Bie P, van de Sluis B, Burstein E, Duran KJ, Berger R, Duckett CS, Wijmenga C, Klomp LW. Characterization of COMMD protein-protein interactions in NF-kappaB signalling. Biochem J. 2006 Aug 15;398(1):63-71. PMID:16573520 doi:http://dx.doi.org/BJ20051664
- ↑ Narindrasorasak S, Kulkarni P, Deschamps P, She YM, Sarkar B. Characterization and copper binding properties of human COMMD1 (MURR1). Biochemistry. 2007 Mar 20;46(11):3116-28. Epub 2007 Feb 20. PMID:17309234 doi:http://dx.doi.org/10.1021/bi0620656
- ↑ Maine GN, Mao X, Komarck CM, Burstein E. COMMD1 promotes the ubiquitination of NF-kappaB subunits through a cullin-containing ubiquitin ligase. EMBO J. 2007 Jan 24;26(2):436-47. Epub 2006 Dec 21. PMID:17183367 doi:http://dx.doi.org/10.1038/sj.emboj.7601489
- ↑ Thoms HC, Loveridge CJ, Simpson J, Clipson A, Reinhardt K, Dunlop MG, Stark LA. Nucleolar targeting of RelA(p65) is regulated by COMMD1-dependent ubiquitination. Cancer Res. 2010 Jan 1;70(1):139-49. doi: 10.1158/0008-5472.CAN-09-1397. PMID:20048074 doi:http://dx.doi.org/10.1158/0008-5472.CAN-09-1397
- ↑ Vonk WI, Wijmenga C, Berger R, van de Sluis B, Klomp LW. Cu,Zn superoxide dismutase maturation and activity are regulated by COMMD1. J Biol Chem. 2010 Sep 10;285(37):28991-9000. doi: 10.1074/jbc.M110.101477. Epub, 2010 Jul 1. PMID:20595380 doi:http://dx.doi.org/10.1074/jbc.M110.101477
- ↑ Sommerhalter M, Zhang Y, Rosenzweig AC. Solution structure of the COMMD1 N-terminal domain. J Mol Biol. 2007 Jan 19;365(3):715-21. Epub 2006 Oct 13. PMID:17097678 doi:10.1016/j.jmb.2006.10.030
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