and Function Protein Homology Domains
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.
What it does
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).
Kessels, M. M., Cope, M. J. T. V. & Drubin, D. G. (1998) The ADF
homolog (ADF-H) domain: A highly exploited actin-binding module.
||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
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..
||EF hands are calcium-binding
||The Eps15 homology domain (Confalonieri
& Di Fiore, 2001).
Confalonieri, S. & Di Fiore, P. P.
(2001) The Eps15 homology (EH) domain., FEBS letters. in press
||Epsin N-terminal homology. A PIP2
binding domain, like the PH and PX domains.
||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,
& 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.
Wasserman, S. (1998) FH proteins as
cytoskeletal organisers. Trends Cell Biol. 8, 111-115.
||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.
binding domain that binds PI(3)P specifically.
|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.
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.
||A protein module found in Kelch
proteins (amongst others) through which proteins self associate.
|| 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.
||Slp homology domain. Slp is
synaptotagmin-like protein. SHD motif binds melanophilin to Rab27
on melanosomes, melanophilin in turn binds myosin
2. Binds to phosphotyrosine on certain proteins such as various
phosphatidylinositol kinases and phosphatases.
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 .
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.
homology domain 2) (Paunola
et al, 2002).
An approximately 35 amino-acid actin-binding domain found in thymosin,
wave, CAP, WASP,
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.
38-40 residues with two conserved tryptophans. Binds proline rich
motifs such as PPPPY, PPPNY and PPLP.