{PDOC51808}
{PS51808; CHCH}
{BEGIN}
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* Coiled coil-helix-coiled coil-helix (CHCH) domain profile *
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Twin CX(9)C  proteins  constitute a large protein family among all eukaryotes.
They adopt a coiled coil-helix-coiled coil helix (CHCH) fold stabilized by two
disulfide bonds  which  are  formed  by  the four cysteines in the twin CX(9)C
motifs (i.e.  two  pairs of cysteines each spaced by nine residues). The large
majority of  twin  CX(9)C  proteins  contains  a single CHCH domain, while the
others contain  two.  In  those  containing a single CHCH domain, this is most
frequently located in the central part of the sequence, with C-terminal and N-
terminal CHCH domains being less common. In those containing two CHCH domains,
these are  separated by a few amino acids and, taken together, typically cover
a large central part of the sequence. A strong link exists between twin CX(9)C
proteins and  mitochondrial metabolism. Twin CX(9)C proteins are involved in a
limited number  of  tasks,  most  if  not  all  of  which are performed in the
mitochondrial inter-membrane  space  (IMS),  and  which  include being part of
protein complexes,  participating  in cytochrome c oxidase (COX) assembly, and
maintaining mitochondrial   structure.  The  functions  of  most  twin  CX(9)C
proteins vary  around the common theme of playing a scaffolding role which can
tie their observed roles in mitochondrial  structure and function [1,2,3].

The CHCH  domain contains two alpha-helices (alpha1 and alpha2), which form an
antiparallel alpha-hairpin  that is covalently paired by two disulfide bridges
(see <PDB:4YTV>) [4,5].

Some proteins known to contain a CHCH domain are listed below:

 - Cox17,  a  copper  chaperone  acting in cytochrome c oxydase biogenesis. It
   binds a  copper(I)  ion  through  an  additional  CC motif in the N-teminal
   region.
 - Cytochrome  c oxidase subunit 6b-1 and 2 (COX6B-1 and 2), in which the four
   disulfide-bonded cysteines  occur  in a CX9C-CX10C rather than in a perfect
   twin CX(9)C motif.
 - Mia40,  the  central component of a system for protein import into the IMS.
   It promotes  the  oxidative  folding  of  substrate  proteins  by  a thiol-
   disulfide exchange mechanism and thus traps them in the IMS.
 - NADH  dehydrogenase  [ubiquinone] iron-sulfur protein 5 (NDUFS5), accessory
   subunit of  the mitochondrial membrane respiratory chain NADH dehydrogenase
   (Complex I), that is believed not to be involved in catalysis.
 - NADH  dehydrogenase  [ubiquinone]  1  alpha  subcomplex subunit 8 (NDUFA8),
   accessory subunit  of  the  mitochondrial  membrane  respiratory chain NADH
   dehydrogenase (Complex   I),  that  is  believed  not  to  be  involved  in
   catalysis.
 - NADH  dehydrogenase  [ubiquinone]  1  beta  subcomplex  subunit 7 (NDUFB7),
   accessory subunit  of  the  mitochondrial  membrane  respiratory chain NADH
   dehydrogenase (Complex   I),  that  is  believed  not  to  be  involved  in
   catalysis.
 - CX(9)C motif-containing protein 1 to 4 (CMC1 to CMC4).
 - Coiled coil-helix-coiled coil-helix domain-containing protein 1 (CHCHD1),
 - Mdm35, involved in mitochondrial distribution and morphology.

The profile we developed covers the entire CHCH domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: August 2016 / First entry.

[ 1] Westerman B.A., Poutsma A., Steegers E.A.P., Oudejans C.B.M.
     "C2360, a nuclear protein expressed in human proliferative
     cytotrophoblasts, is a  representative member of a novel protein
     family with a conserved coiled coil-helix-coiled coil-helix domain."
     Genomics 83:1094-1104(2004).
     PubMed=15177562; DOI=10.1016/j.ygeno.2003.12.006
[ 2] Cavallaro G.
     "Genome-wide analysis of eukaryotic twin CX9C proteins."
     Mol. Biosyst. 6:2459-2470(2010).
     PubMed=20922212; DOI=10.1039/c0mb00058b
[ 3] Longen S., Bien M., Bihlmaier K., Kloeppel C., Kauff F.,
     Hammermeister M., Westermann B., Herrmann J.M., Riemer J.
     "Systematic analysis of the twin cx(9)c protein family."
     J. Mol. Biol. 393:356-368(2009).
     PubMed=19703468; DOI=10.1016/j.jmb.2009.08.041
[ 4] Banci L., Bertini I., Ciofi-Baffoni S., Jaiswal D., Neri S.,
     Peruzzini R., Winkelmann J.
     "Structural characterization of CHCHD5 and CHCHD7: two atypical human
     twin CX9C proteins."
     J. Struct. Biol. 180:190-200(2012).
     PubMed=22842048; DOI=10.1016/j.jsb.2012.07.007
[ 5] Watanabe Y., Tamura Y., Kawano S., Endo T.
     "Structural and mechanistic insights into phospholipid transfer by
     Ups1-Mdm35 in mitochondria."
     Nat. Commun. 6:7922-7922(2015).
     PubMed=26235513; DOI=10.1038/ncomms8922

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