PROSITE documentation PDOC50236
Clathrin heavy-chain (CHCR) repeat profile


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 α-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.

Last update:

April 2013 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

CHCR, PS50236; Clathrin heavy-chain (CHCR) repeat profile  (MATRIX)


1AuthorsYbe J.A. Brodsky F.M. Hofmann K. Lin K. Liu S.-H. Chen L. Earnest T.N. Fletterick R.J. Hwang P.K.
TitleClathrin self-assembly is mediated by a tandemly repeated superhelix.
SourceNature 399:371-375(1999).
PubMed ID10360576

2AuthorsYoung A.
TitleStructural insights into the clathrin coat.
SourceSemin. Cell Dev. Biol. 18:448-458(2007).
PubMed ID17702618

3AuthorsDarsow T. Katzmann D.J. Cowles C.R. Emr S.D.
TitleVps41p function in the alkaline phosphatase pathway requires homo-oligomerization and interaction with AP-3 through two distinct domains.
SourceMol. Biol. Cell 12:37-51(2001).
PubMed ID11160821

4AuthorsLin B. White J.T. Utleg A.G. Wang S. Ferguson C. True L.D. Vessella R. Hood L. Nelson P.S.
TitleIsolation and characterization of human and mouse WDR19,a novel WD-repeat protein exhibiting androgen-regulated expression in prostate epithelium.
SourceGenomics 82:331-342(2003).
PubMed ID12906858

5AuthorsCaplan S. Hartnell L.M. Aguilar R.C. Naslavsky N. Bonifacino J.S.
TitleHuman Vam6p promotes lysosome clustering and fusion in vivo.
SourceJ. Cell Biol. 154:109-122(2001).
PubMed ID11448994

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