PROSITE documentation PDOC00670

Guanylate kinase-like signature and profile

Description

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.

Last update:

December 2004 / Pattern and text revised.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

GUANYLATE_KINASE_2, PS50052; Guanylate kinase-like domain profile  (MATRIX)
Sequences known to belong to this class detected by the profile: ALL
Other sequence(s) detected in Swiss-Prot: 1.
• Domain architecture view of Swiss-Prot proteins matching PS50052
PS50052
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS50052
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50052
• Scan Swiss-Prot/TrEMBL entries against PS50052
• view ligand binding statistics
Matching PDB structures: 1EX6 1EX7 1GKY 1JXM ... [ALL]
GUANYLATE_KINASE_1, PS00856; Guanylate kinase-like signature  (PATTERN)
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.
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00856
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00856
• Scan Swiss-Prot/TrEMBL entries against PS00856
• view ligand binding statistics
Matching PDB structures: 1EX6 1EX7 1GKY 1JXM ... [ALL]

References

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

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