ELM Details - LIG_Clathr_ClatBox

LIG_Clathr_ClatBox_2

Functional site class:	Clathrin box
Functional site description:	Clathrin boxes are found on cargo adaptor proteins. They interact with the N-terminal beta-propeller structure of Clathrin heavy chain. Beside the "classical" motif, some variants have been described for various types of adaptor proteins. The same protein can bear several subtypes of Clathrin boxes.
ELM(s):	LIG_Clathr_ClatBox_2, LIG_Clathr_ClatBox_1
LIG_Clathr_ClatBox_2 description:	This variant clathrin box motif (also called the W box) is found in tandem arrangement with a "classical" clathrin box, (LIG_Clathr_ClatBox_1) in a subgroup of cargo adaptor proteins enriched in nerve terminals: the amphiphysins. Both motifs bind the beta propeller structure of Clathrin heavy chain with a similar affinity (PMID 9603201 and 10748223) but at distinct sites and while the classical clathrin box assumes an extended conformation, the W box is compact and helical (PMID 14981508). A synergistic effect of appropriately spaced type 1 and 2 clathrin boxes on clathrin assembly and recruitment has been shown in vitro (PMID 11382783). Amphiphysin 1 is the dominant autoantigen of paraneoplastic stiff-man syndrome.
Pattern:	PWDLW
Present in taxon(s):	Homo sapiens Eukaryota Mus musculus Gallus gallus Rattus norvegicus
Not represented in taxon(s):

See instances for LIG_Clathr_ClatBox_2

Abstract

Clathrin is the main component of the coat that decorates the cytosolic face of carrier vesicles mediating protein and lipid transport in the endocytic and late secretory pathways. In vivo the multimerisation of the clathrin heterohexamer (known as triskelion) and the clathrin-mediated vesicular trafficking are regulated through a complex network of interactions involving clathrin and a number of accessory proteins.
Clathrin boxes are 5-residue-motifs found on cargo adaptor proteins, mostly near their C-terminus or central region. They are found in a large variety of accessory proteins involved in endocytosis and vesicular trafficking (specific adaptors like beta-arrestin and more general adaptor proteins like AP complexes). Unfolded flexible regions or hinges can display multiple copies of the motif, sometime belonging to different subtypes. This organisation is believed to ensure a complex, ajustable network of “weak” cooperative interactions, with the affinity between members defined by the number of motifs they possess. Extended peptides could also promote clathrin assembly by bridging the heavy chains of clathrin molecules engaged in an assembled coat. Clathin box motifs interact with the N-terminus of Clathrin heavy chain, with the so called beta-propeller structure.

Selected references

Drake MT, Traub LM

Interaction of two structurally distinct sequence types with the clathrin terminal domain beta-propeller.

J Biol Chem 2001 Aug 3;276(31) : 28700-9.

PMID: 11382783

Miele AE, Watson PJ, Evans PR, Traub LM, Owen DJ

Two distinct interaction motifs in amphiphysin bind two independent sites on the clathrin terminal domain beta-propeller.

Nat Struct Mol Biol 2004 Mar;11(3) : 242-8.

PMID: 14981508

Ramjaun AR, McPherson PS

Multiple amphiphysin II splice variants display differential clathrin binding: identification of two distinct clathrin-binding sites.

J Neurochem 1998 Jun;70(6) : 2369-76.

PMID: 9603201

Slepnev VI, Ochoa GC, Butler MH, De Camilli P

Tandem arrangement of the clathrin and AP-2 binding domains in amphiphysin 1 and disruption of clathrin coat function by amphiphysin fragments comprising these sites.

J Biol Chem 2000 Jun 9;275(23) : 17583-9.

PMID: 10748223

This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.

Biological Process

  endocytosis

GO:0006897

  receptor mediated endocytosis

GO:0006898

Cellular Component

  cytosol

GO:0005829

  cytoskeleton

GO:0005856

  clathrin-coated endocytic vesicle

GO:0045334

Molecular Function

  clathrin binding

GO:0030276

Instances for LIG_Clathr_ClatBox_2

Sequence	Position	Subsequence (Click for evidence information)	PDB	Gene Name	Protein Description	Organism
AMPH_HUMAN	381-385	MSQTLPWDLWTTSTDL	1UTC	Name=AMPH; Synonyms=AMPH1;	Amphiphysin.	Homo sapiens (Human).
BIN1_HUMAN	416-420	SGQSIPWDLWEPTESP	-	Name=BIN1; Synonyms=AMPHL;	Myc box-dependent-interacting protein 1 (Bridging integrator 1) (Amphiphysin-like protein) (Amphiphysin II) (Box-dependent myc- interacting protein 1).	Homo sapiens (Human).