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Structure and Function Protein Homology Domains

The SMART web site in Heidelberg is very useful tool for searching the databases for proteins containing protein domains.  Searches can be made by searching by sequence or the name of the domain.

Domain           What it does
ADFH Actin Depolymerizing Factor Homology domain.  (See ADF/cofilin).  ADF/Cofilins are 14-21 kDa proteins which share a fold, but no recognisable homology to the gelsolin repeat (Lappalainen et al, 1998).

Lappalainen, P., Kessels, M. M., Cope, M. J. T. V. & Drubin, D. G. (1998) The ADF homolog (ADF-H) domain: A highly exploited actin-binding module.
Mol.Biol.Cell. 9, 1951-1959.

BH1
BH3
CH Calponin Homology domain. A domain found in a variety of actin-binding proteins in the a-actinin family.  Although named after calponin, its self an actin binding protein, calponin binds actin through a region other than the CH domain. (See Gimona et al, 2001)

Gimona, M., Djinovic-Carugo, K., Kranewitter, W. J. & Winder, S. J. (2001) Functional plasticity of CH domains. FEBS letters. in press

C2 Generally bind lipids, but C2A domains of some proteins (e.g. JFC1) bind phosphoinositides phosphorylated at the 3'  position (Catz et al, 2002).  Other C2 containing proteins include synaptotagmins.

Catz, S. D., Johnson, J. L. & Baboir, B. M. (2002) The C2A domain of JFC1 binds to 3'--phosphorylated phosphoinositides and directs plasma membrane association in living cells. PNAS. 99, 11652-11657..

DH
EF EF hands are calcium-binding motifs 
EH The Eps15 homology domain (Confalonieri & Di Fiore, 2001).

Confalonieri, S. & Di Fiore, P. P. (2001) The Eps15 homology (EH) domain., FEBS letters. in press

ENTH Epsin N-terminal homology. A PIP2 binding domain, like the PH and PX domains.
EVH1 (WH1) Enabled/VASP homology domain. Binds polyproline petides with the consensus FPPPP.

Renfranz, P. J. & Beckerle, M. C. (2002) Doing (F/L)PPPPs: EVH1 domains and their proline-rich partners in cell polarity and migration., Curr.Op.Cell Biol. 14, 88-103.

FH Formin Homology (Frazier & Field, 1997; Wasserman, 1998).  A motif first recognised in the profilin-binding protein Diaphanous (mDia).

Frazier, J. A. & Field, C. M. (1997) Actin cytoskeleton: Are FH proteins local organizers? Curr.Biol. 7, R414-R417.

Wasserman, S. (1998) FH proteins as cytoskeletal organisers. Trends Cell Biol. 8, 111-115.

FHA Forked Head Associated protein. Binds phospho-threonine residues in proteins analogous to the way in which SH2 binds phospho-tyrosines.

Durocher, D. & Jackson, S.P. (2001) The FHA domain. FEBS letters. in press.

FYVE A polyphosphatidylinositol  binding domain that binds PI(3)P specifically.
PDZ

(DHR, GLGF)

Consist of approximately 90 residue repeats found in a number of proteins associated with membranous proteins such as receptors,  signal transduction proteins and channels. They function as protein -protein recognition modules and are involved in clustering of protein assemblages.  The name PDZ is derived from its appearance in ZO-1 a zonula occludens protein. (see Bezprozvanny & Maximov, 2001).

 Bezprozvanny, I. & Maximov, A. (2001) Classification of PDZ domains, FEBS letters. in press

PH Pleckstrin Homology.  (See Peckstrin)  A c100 residue domain that binds to polyphosphatidylinositol (See PIP2-binding Actin Binding Proteins).  Some PH domains also bind F-actin (Yao et al, 1999).

Blomberg, N., Baraldi, E., Nilges, M. & Saraste, M. (1999) The PH superfold: a structural scaffold for multiple functions., TIBS. 24, 441-445.

Lemmon, M. A. & Ferguson, K. M. (2000) Signal-dependent membrane targeting by pleckstrin homology (PH) domains., Biochem. J. 350, 1-18.

Yao, L., Janmey, P., Frigeri, L. G., Han, W., Fujita, J., Kawakami, Y., Apgar, J. R. & Kawakami, T. (1999) Pleckstrin homology domains interact with filamentous actin., J.Biol.Chem. 274, 19752-19761.

POZ (BTB) A protein module found in Kelch proteins (amongst others) through which proteins self associate.
PX  The Phox homology domain. A phosphatidylinositol binding domain (Xu et al, 2001), first identified in the NADPH oxidase subunits, p47phox and p40phox in neutrophils.  The PX domain has been identified in a wide variety of proteins.

Ellson, C. D., Andrews, S., Stephens, L. R. & Hawkins, P. T. (2002) The PX domain: a new phosphinositide-binding module., J.Cell Sci. 115, 1099-1105.

Xu, Y., Seet, L.-F., Hanson, B. & Hong, W. (2001) The Phox homology (PX) domain, a new player in phosphoinositide signalling., Biochem. J. 360, 513-530.

SHD Slp homology domain. Slp is synaptotagmin-like protein.  SHD motif binds melanophilin to Rab27 on melanosomes, melanophilin in turn binds myosin Va.
SH2 Src Homolgy 2.  Binds to phosphotyrosine on certain proteins such as various phosphatidylinositol kinases and phosphatases.
SH3 Two subclasses I and II both bind proline rich sequences. Class I binds R-X-P-L-P-X-P.  Class II bind P-P-L-P-X-R .
WD (WD-40) The motif starts with GH, then a core of about 36-46 residues and ends with the eponymous WD. The 7 WD repeats of the b-subunit of the heterotrimeric G-proteins forms a b-propeller each of whose blades, a single WD motif is a four stranded b-sheet.  No common function has been established for the WD repeat.  A variety of proteins are recognised by WD repeat containing proteins.

Suzuki, K., Nishihata, J., Arai, Y., Honma, N., Yamamoto, K., Irimura, T. & Toyoshima, S. (1995) Molecular cloning of a novel actin-binding protein, p57, with a WD repeat and a leucine zipper motif, FEBS Lett. 364, 283-288.

Steimle, P. A., Naismith, T., Licate, L. & Egelhoff, T. T. (2001) WD repeat domains target Dictyostelium myosin heavy chain kinases by binding to myosin filaments., J.Biol.Chem. 276, 6853-6860.

WH2 (WASP homology domain 2) (Paunola et al, 2002). An approximately 35 amino-acid actin-binding domain found in thymosin, ciboulot, verprolin, wave, CAP, WASP, actobindin.  Thymosins and actobindin share homology with the villin head piece but this is apparently excluded from this group.

Paunola, E., Mattila, P. K. & Lappalainen, P. (2002) WH2 domain: a small, versatile adapter for actin monomers. FEBS letters. 513, 92-97.

WW Composed of 38-40 residues with two conserved tryptophans.  Binds proline rich motifs such as PPPPY, PPPNY and PPLP.
 
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