PROSITE documentation PDOC00670

{PDOC00670}
{PS00856; GUANYLATE_KINASE_1}
{PS50052; GUANYLATE_KINASE_2}
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* Guanylate kinase-like signature and profile *
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Guanylate  kinase   (EC 2.7.4.8)   (GK)  [1]   catalyzes   the   ATP-dependent
phosphorylation of  GMP  into  GDP.  It  is  essential  for  recycling GMP and
indirectly, cGMP.  In prokaryotes (such as Escherichia coli), lower eukaryotes
(such as    yeast)  and  in  vertebrates,  GK  is a highly conserved monomeric
protein of about 200 amino acids. GK has been shown [2,3,4] to be structurally
similar to the following proteins:

 - Protein  A57R  (or  SalG2R)  from various  strains  of Vaccinia virus. This
   protein is  highly similar to GK, but contains a frameshift mutation in the
   N-terminal section and could therefore be inactive in that virus.

The following  proteins are characterized by the presence in their sequence of
one or more copies of the DHR domain, a SH3 domain (see <PDOC50002> as well as
a C-terminal  GK-like  domain,  these  protein are collectively termed  MAGUKs
(membrane-associated guanylate kinase homologs) [5]:

 - Drosophila  lethal(1)discs  large-1  tumor  suppressor protein (gene dlg1).
   This protein  is  associated with septate junctions in developing flies and
   defects in the dlg1 gene cause neoplastic overgrowth of the imaginal disks.
 - Mammalian tight junction protein Zo-1.
 - A  family  of  mammalian  synaptic  proteins that seem to interact with the
   cytoplasmic tail  of NMDA receptor subunits. This familly currently consist
   of SAP90/PSD-95, CHAPSYN-110/PSD-93, SAP97/DLG1 and SAP102.
 - Vertebrate 55 Kd erythrocyte membrane protein (p55). p55 is a palmitoylated,
   membrane-associated protein of unknown function.
 - Caenorhabditis  elegans  protein lin-2, which may play a structural role in
   the induction of the vulva.
 - Rat protein CASK.
 - Human protein DLG2.
 - Human protein DLG3.

There is  an  ATP-binding  site (P-loop) in the N-terminal section of GK. This
region is not conserved in the  GK-like domain of the above proteins which are
therefore unlikely  to  be kinases. However these proteins retain the residues
known, in  GK, to be involved in the binding of GMP. As a signature pattern we
selected a highly conserved region  that  contains two arginine and a tyrosine
which are involved in GMP-binding.

-Consensus pattern: [TS]-[ST]-R-x(2)-[KR]-x(2)-[DE]-x(2)-[GA]-x(2)-Y-x-[FY]-
                    [LIVMKHRT]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for ZO-1.
-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: 1.

-Last update: December 2004 / Pattern and text revised.

[ 1] Stehle T., Schulz G.E.
     "Refined structure of the complex between guanylate kinase and its
     substrate GMP at 2.0 A resolution."
     J. Mol. Biol. 224:1127-1141(1992).
     PubMed=1314905
[ 2] Bryant P.J., Woods D.F.
     "A major palmitoylated membrane protein of human erythrocytes shows
     homology to yeast guanylate kinase and to the product of a Drosophila
     tumor suppressor gene."
     Cell 68:621-622(1992).
     PubMed=1310897
[ 3] Goebl M.G.
     "Is the erythrocyte protein p55 a membrane-bound guanylate kinase?"
     Trends Biochem. Sci. 17:99-99(1992).
     PubMed=1329277
[ 4] Zschocke P.D., Schiltz E., Schulz G.E.
     "Purification and sequence determination of guanylate kinase from pig
     brain."
     Eur. J. Biochem. 213:263-269(1993).
     PubMed=8097461
[ 5] Woods D.F., Bryant P.J.
     "ZO-1, DlgA and PSD-95/SAP90: homologous proteins in tight, septate
     and synaptic cell junctions."
     Mech. Dev. 44:85-89(1993).
     PubMed=8155583

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