{PDOC50236}
{PS50236; CHCR}
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* Clathrin heavy-chain (CHCR) repeat profile *
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Clathrin is  a  triskelion-shaped  cytoplasmic protein that polymerizes into a
polyhedral lattice  on intracellular membranes to form protein-coated membrane
vesicles. Lattice  formation  induces  the sorting of membrane proteins during
endocytosis and  organelle  biogenesis by interacting with membrane-associated
adaptor molecules.  Clathrin  functions  as  a  trimer,  and these trimers, or
triskelions, are  comprised of three legs joined by a central vertex. Each leg
consists of  one  heavy  chain  and  one light chain. The clathrin heavy-chain
contains a  145-residue  repeat  that  is  present  in seven copies [1,2]. The
clathrin heavy-chain  repeat (CHCR) is also found in nonclathrin proteins such
as Pep3,  Pep5,  Vam6, Vps41, and Vps8 from Saccharomyces cerevisiae and their
orthologs from other eukaryotes [1,3,4,5]. These proteins, like clathrins, are
involved in  vacuolar  maintenance  and  protein  sorting. The CHCR repeats in
these proteins   could   mediate  protein-protein  interactions,  or  possibly
represent clathrin-binding  domains,  or perform clathrin-like functions. CHCR
repeats in  the clathrin heavy chain, Saccharomyces cerevisiae Vamp2 and human
Vamp6 have been implicated in homooligomerization, suggesting that this may be
the primary function of this repeat.

The CHCR  repeat folds into an elongated right-handed superhelix coil of short
alpha-helices (see  <PDB:1B89>)  [1].  Individual  'helix-turn-helix-loop'  or
helix hairpin  units  comprise  the  canonical  repeat  and  stack  along  the
superhelix axis to form a single extended domain. The canonical hairpin repeat
of the  clathrin  superhelix  resembles a tetratrico peptide repeat (TPR) (see
<PDOC50005>), but  is  shorter  and  lacks  the  characteristic spacing of the
hydrophobic residues in TPRs.

The profile we developed covers the entire CHCR repeat.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: April 2013 / First entry.

[ 1] Ybe J.A., Brodsky F.M., Hofmann K., Lin K., Liu S.-H., Chen L.,
     Earnest T.N., Fletterick R.J., Hwang P.K.
     "Clathrin self-assembly is mediated by a tandemly repeated
     superhelix."
     Nature 399:371-375(1999).
     PubMed=10360576; DOI=10.1038/20708
[ 2] Young A.
     "Structural insights into the clathrin coat."
     Semin. Cell Dev. Biol. 18:448-458(2007).
     PubMed=17702618; DOI=10.1016/j.semcdb.2007.07.006
[ 3] Darsow T., Katzmann D.J., Cowles C.R., Emr S.D.
     "Vps41p function in the alkaline phosphatase pathway requires
     homo-oligomerization and interaction with AP-3 through two distinct
     domains."
     Mol. Biol. Cell 12:37-51(2001).
     PubMed=11160821
[ 4] Lin B., White J.T., Utleg A.G., Wang S., Ferguson C., True L.D.,
     Vessella R., Hood L., Nelson P.S.
     "Isolation and characterization of human and mouse WDR19,a novel
     WD-repeat protein exhibiting androgen-regulated expression in prostate
     epithelium."
     Genomics 82:331-342(2003).
     PubMed=12906858
[ 5] Caplan S., Hartnell L.M., Aguilar R.C., Naslavsky N., Bonifacino J.S.
     "Human Vam6p promotes lysosome clustering and fusion in vivo."
     J. Cell Biol. 154:109-122(2001).
     PubMed=11448994

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