{PDOC51650}
{PS51650; C2_DOCK}
{PS51651; DOCKER}
{BEGIN}
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* C2 DOCK-type and DOCKER domains profiles *
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Rho guanosine  triphosphatases  (GTPases)  are  critical  regulators  of  cell
motility, polarity,  adhesion,  cytoskeletal organization, proliferation, gene
expression, and  apoptosis.  Conversion  of these biomolecular switches to the
activated GTP-bound  state is controlled by two families of guanine nucleotide
exchanges factors  (GEFs).  DH-PH  proteins  are  a  large  group  of Rho GEFs
comprising a  catalytic  Dbl  homology  (DH)  domain (see <PDOC00605>) with an
adjacent pleckstrin  homology (PH) domain (see <PDOC50003>) within the context
of functionally  diverse  signalling  modules. The evolutionarily distinct and
smaller family  of  DOCK  (dedicator  of cytokinesis) or CDM (CED-5, DOCK1180,
Myoblast city)   proteins  activate  either  Rac  or  Cdc42  to  control  cell
migration, morphogenesis,  and  phagocytosis.  DOCK  proteins  share the DOCK-
type C2  domain  (also  termed the DOCK-homology region (DHR)-1 or CDM-zizimin
homology 1 (CZH1) domain) and the DOCKER domain (also termed the DHR-2 or CZH2
domain) [1,2,3,4,5].

The ~200  residue  DOCK-type  C2  domain  is located toward the N-terminus and
interacts with  phosphatidylinositol  3,4,5-trisphosphate [PtdIns(3,4,5)P3] to
mediate signalling  and  membrane  localization. The central core of the DOCK-
type C2  domain  adopts  an  antiparallel  beta-sandwich with the "type II" C2
domain fold  (a circular permutation of the more common "type I" topology), in
which two  4-stranded  sheets  with  strand  order  6-5-2-3 and 7-8-1-4 create
convex- and concave-exposed faces, respectively (see <PDB:3L4C>) [3].

The DOCKER  domain  is a GEF catalytic domain of ~400 residues situated within
the C-terminus.  The structure of the DOCKER domain differs from that of other
GEF catalytic  domains. It is organized into three lobes of roughly equal size
(lobes A,  B,  and  C),  with the Rho-family binding site and catalytic center
generated entirely  from lobes B and C (see <PDB:2WM9>). Lobe A is formed from
an antiparallel  array  of alpha helices. Through extensive contacts with lobe
B, lobe  A stabilizes the DHR2 domain. Lobe B adopts an unusal architecture of
two antiparallel   beta   sheets  disposed  in  a  loosely  packed  orthogonal
arrangement, whereas lobe C comprises a four-helix bundle [4,5] .

Some DOCK proteins are listed below:

 - Mammalian  Mammalian  dedicator  of  cytokinesis  180  (DOCK180  or DOCK1),
   important for cell migration.
 - Mammalian  DOCK2, important for lymphocyte development, homong, activation,
   adhesion, polarization and migration processes.
 - Mammalian DOCK3 (also known as MOCA), is expressed predominantly in neurons
   and resides in growth cones and membrane ruffles.
 - Mammalian DOCK4, possesses tumor suppressor properties.
 - Mammalian  DOCK9  (zizimin1), plays an important role in dendrite growth in
   hippocampal neurons through activation of Cdc42.
 - Drosophila melanogaster Myoblast city.
 - Caenorhabditis elegans CED-5.

The profiles we developed cover the entire DOCK-type C2 and DOCKER domains.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: January 2020 / Text revised.

[ 1] Meller N., Irani-Tehrani M., Kiosses W.B., Del Pozo M.A.,
     Schwartz M.A.
     "Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho
     proteins."
     Nat. Cell Biol. 4:639-647(2002).
     PubMed=12172552; DOI=10.1038/ncb835
[ 2] Cote J.-F., Vuori K.
     "Identification of an evolutionarily conserved superfamily of
     DOCK180-related proteins with guanine nucleotide exchange activity."
     J. Cell Sci. 115:4901-4913(2002).
     PubMed=12432077
[ 3] Premkumar L., Bobkov A.A., Patel M., Jaroszewski L., Bankston L.A.,
     Stec B., Vuori K., Cote J.-F., Liddington R.C.
     "Structural basis of membrane targeting by the Dock180 family of Rho
     family guanine exchange factors (Rho-GEFs)."
     J. Biol. Chem. 285:13211-13222(2010).
     PubMed=20167601; DOI=10.1074/jbc.M110.102517
[ 4] Yang J., Zhang Z., Roe S.M., Marshall C.J., Barford D.
     "Activation of Rho GTPases by DOCK exchange factors is mediated by a
     nucleotide sensor."
     Science 325:1398-1402(2009).
     PubMed=19745154; DOI=10.1126/science.1174468
[ 5] Kulkarni K., Yang J., Zhang Z., Barford D.
     "Multiple factors confer specific Cdc42 and Rac protein activation by
     dedicator of cytokinesis (DOCK) nucleotide exchange factors."
     J. Biol. Chem. 286:25341-25351(2011).
     PubMed=21613211; DOI=10.1074/jbc.M111.236455

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