9.B.158 The Cut Copper Homeostasis (Cut) Family 

CutC is one of the six members of Cut family proteins, involved in prokaryotic copper homeostasis. The human homolog of CutC (hCutC) is an intracellular copper-binding protein with unknown physiological function. The Cut protein family is associated with copper homeostasis and involved in uptake, storage, delivery, and efflux of copper. CutC is a member of the Cut family and is suggested to be involved in efflux trafficking of cuprous ion. Li et al. 2010 reported the biochemical and structural characterization of human CutC (hCutC). hCutC can bind Cu+ with a stoichiometry of 1:1 and an apparent dissociation constant of 15.5+/-2.8 microM. hCutC assumes a typical TIM-barrel fold and forms a tetramer in both crystal structure and solution which is different from the dimeric architecture of the bacterial CutC. Structure analysis and sequence comparison of CutC proteins from different species revealed two strictly conserved Cys residues on the inner surface of the C-terminal end of the TIM-barrel. Mutations of the two Cys residues impair the ability of hCutC to bind Cu+. Their results suggest that hCutC functions as an enzyme with Cu+ as a cofactor rather than a copper transporter.  The potential Cu+-binding site consists of the two Cys residues and other conserved residues in the vicinity.



This family belongs to the .

 

References:

Gupta, S.D., B.T. Lee, J. Camakaris, and H.C. Wu. (1995). Identification of cutC and cutF (nlpE) genes involved in copper tolerance in Escherichia coli. J. Bacteriol. 177: 4207-4215.

Kunjunni, R., S. Sathianathan, M. Behari, P. Chattopadhyay, and V. Subbiah. (2016). Silencing of Human CutC Gene (hCutC) Induces Apoptosis in HepG2 Cells. Biol Trace Elem Res 172: 120-126.

Latorre, M., F. Olivares, A. Reyes-Jara, G. López, and M. González. (2011). CutC is induced late during copper exposure and can modify intracellular copper content in Enterococcus faecalis. Biochem. Biophys. Res. Commun. 406: 633-637.

Li, J., C. Ji, J. Chen, Z. Yang, Y. Wang, X. Fei, M. Zheng, X. Gu, G. Wen, Y. Xie, and Y. Mao. (2005). Identification and characterization of a novel Cut family cDNA that encodes human copper transporter protein CutC. Biochem. Biophys. Res. Commun. 337: 179-183.

Li, Y., J. Du, P. Zhang, and J. Ding. (2010). Crystal structure of human copper homeostasis protein CutC reveals a potential copper-binding site. J Struct Biol 169: 399-405.

Examples:

TC#NameOrganismal TypeExample
9.B.158.1.1

Copper homeostasis protein, CutC of 273 aas and 0 TMSs (Kunjunni et al. 2015). CutC may play  a role in intracellular copper trafficking (Li et al. 2005). Copper induced damage to cells upon hcutC silencing induces apoptosis and provides evidence for the role of hCutC protein in intracellular copper homeostasis (Kunjunni et al. 2016).

CutC of Homo sapiens

 
9.B.158.1.2

Copper homeostasis portein, CutC of 248 aas (Gupta et al. 1995).

CutC of E. coli

 
9.B.158.1.3

CutC of 209 aas.  Responds transcriptionally to copper and participates in the control of intracellular copper homeostasis (Latorre et al. 2011).

CutC of Enterococcus faecalis