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Information on EC 2.7.4.8 - guanylate kinase and Organism(s) Homo sapiens and UniProt Accession O14936

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EC Tree
IUBMB Comments
dGMP can also act as acceptor, and dATP can act as donor.
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Select one or more organisms in this record:
This record set is specific for:
Homo sapiens
UNIPROT: O14936
Word Map
  • 2.7.4.8
  • synapses
  • nmda
  • cell-cell
  • hippocampal
  • synapse-associated
  • excitatory
  • domain-containing
  • magi-1
  • n-methyl-d-aspartate
  • zonula
  • spine
  • multiprotein
  • adherens
  • kinase-like
  • carma1
  • glutamatergic
  • palmitoylated
  • dgmp
  • crumbs
  • occludens-1
  • septate
  • discs-large
  • pdz-binding
  • synaptogenesis
  • ampars
  • neurexins
  • junction-associated
  • mucosa-associated
  • kinase-associated
  • shank
  • tcr-induced
  • nephrin
  • neuroligins
  • card-containing
  • medicine
  • drug development
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The taxonomic range for the selected organisms is: Homo sapiens
Reaction Schemes
+
=
+
Synonyms
5'-GMP kinase, apo-EcGMPK, ATP: GMP phosphotransferase, ATP:GMP phosphotransferase, BmGK, CASK polypeptide, Cavbeta1b, Cavbeta2a, deoxyguanylate kinase, DLG1/SAP97, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5'-GMP kinase
-
-
-
-
ATP:GMP phosphotransferase
CASK polypeptide
265980
cf. EC 2.7.11.1, the protein contains a guanylate kinase domain
deoxyguanylate kinase
-
-
-
-
DLG1/SAP97
247
-
GMP kinase
-
-
-
-
GMPK
296777
-
guanosine monophosphate kinase
-
-
-
-
guanylate kinase
247
-
kinase, guanylate (phosphorylating)
-
-
-
-
membrane associated guanylate kinase
247
-
membrane associated guanylate kinase protein
247
-
membrane-associated guanylate kinase
247
-
post-synaptic density-95 membrane associated guanylate kinase
247
-
PSD-95 MAGUK
247
-
PSD-95alpha
247
-
PSD-95beta
247
-
additional information
247
the enzyme belongs to the post-synaptic density-95 membrane associated guanylate kinase, MAGUK, family of scaffolding proteins,
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:(d)GMP phosphotransferase
dGMP can also act as acceptor, and dATP can act as donor.
CAS REGISTRY NUMBER
COMMENTARY hide
9026-59-9
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
aciclovir (ACV-MP)
?
show the reaction diagram
-
-
-
-
?
ATP + (R)-3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutylphosphonic acid
(R)-ganciclovir phosphonate monophosphate
show the reaction diagram
-
i.e. R-ganciclovir phosphonate, (S) enantiomer 100fold less efficient, used for racemic resolution
-
?
ATP + 6-thioguanosine 5'-monophosphate
ADP + 8-thioguanosine 5'-diphosphate
show the reaction diagram
-
-
-
-
?
ATP + 8-azaguanosine 5'-monophosphate
ADP + 8-azaguanosine 5'-diphosphate
show the reaction diagram
-
-
-
-
?
ATP + dGMP
ADP + dGDP
show the reaction diagram
-
-
-
-
r
ATP + ganciclovir
ADP + ganciclovir phosphate
show the reaction diagram
-
-
-
-
?
ATP + ganciclovir monophosphate
?
show the reaction diagram
-
-
-
-
?
ATP + GDP
ADP + GMP
show the reaction diagram
-
-
?
ATP + GDP
ADP + GTP
show the reaction diagram
-
-
?
ATP + GDP
ADP + guanosine 5'-tetraphosphate
show the reaction diagram
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
ATP + IMP
ADP + IDP
show the reaction diagram
-
very poor substrate
-
-
?
dATP + dGMP
dADP + dGDP
show the reaction diagram
-
-
-
-
?
dATP + GMP
dADP + GDP
show the reaction diagram
-
-
-
-
?
dGMP + ATP
dGDP + ADP
show the reaction diagram
-
-
-
-
?
GMP + ATP
GDP + ADP
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
aciclovir (ACV-MP)
?
show the reaction diagram
-
-
-
-
?
ATP + ganciclovir
ADP + ganciclovir phosphate
show the reaction diagram
-
-
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
Q16774
-
-
-
?
dGMP + ATP
dGDP + ADP
show the reaction diagram
-
-
-
-
?
GMP + ATP
GDP + ADP
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
no activator
K+
-
activation
Mn2+
-
requirement
NH4+
-
activation
additional information
-
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5,5'-dithiobis(2-nitrobenzoate)
-
-
9-(1,3-dihydroxy-2-propylmethyl)guanine 5'-monophosphate
-
-
9-(2-hydroxyethoxymethyl)guanine 5'-monophosphate
-
-
N-ethylmaleimide
-
-
p-chloromercuribenzoic acid
-
1,4-dithiothreitol reverses
p-hydroxymercuribenzoate
-
-
P1 -(5'-adenosyl)-P5 -(5'-guanosyl)pentaphosphate
a non-hydrolysable bi-substrate analogue
additional information
-
no inhibition by 2-mercaptoethanol, 1,4-dithiothreitol; no inhibition by guanosine, AMP, CMP, UMP, XMP, 6-thioinosine 5'-phosphate
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.052
(R)-ganciclovir phosphonate
-
pH 7.5, 37C
2.1
6-thioguanosine 5'-monophosphate
-
pH 7.5, 30C
0.091
8-azaguanosine 5'-monophosphate
-
pH 7.5, 30C
0.19
ATP
-
pH 7.5, 30C
0.03 - 0.074
dGMP
0.047
ganciclovir monophosphate
-
pH 7.5, 37C
0.015 - 0.27
GMP
additional information
additional information
-
kinetic parameters of several substrates for 4 isoenzymes
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.043 - 0.067
9-(1,3-dihydroxy-2-propylmethyl)guanine 5'-monophosphate
0.45 - 0.84
9-(2-hydroxyethoxymethyl)guanine 5'-monophosphate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.9
-
4 isoelectric variants, agarose gel electrophoresis and isoelectric focusing
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
CASK polypeptide, cf. EC 2.7.11.1
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
CSKP_HUMAN
926
0
105123
Swiss-Prot
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
21700
-
deduced from the amino acid composition
22000
22010
deduced from the amino acid composition and detected by mass spectrometry, adducts with sulfate and not phosphate are detected in mass spectrometry
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
PSD-MAGUK's major phosphorylation sites, regulation by phosphorylation through Ser/Thr protein kinases and also Tyr-dependent kinases, overview
CRYSTALLIZATION/commentary
ORGANISM
UNIPROT
LITERATURE
purified the GK domain fragment of human DLG1, hanging drop vapor diffusion method, mixing of 6.5 mg/ml protein in 20 mM Tris-HCl buffer, pH 8.0, 150 mM NaCl and 2 mM dithiothreitol, with reservoir solution containing 0.2 M sodium thiocyanate and 22% PEG 3350, 20C, X-ray diffraction structure determination and analysis at 2.2 A resolution, molecular replacement and selenomethionine single-wavelength anomalous dispersion, using the PSD-95 GK domain, PDB ID 1JXO, as a search model
SAP97 SH3-guanylate kinase/p-LGN18 complex, hanging drop vapor diffusion method, using 0.2M ammonium nitrate, 20% (w/v) polyethylene glycol 3350
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C3S/C5S
-
PSD-95aC3S/C5S mutant
S35N/V168F
-
the mutations significantly suppress enzyme catalytic activity
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50
-
10 min, inactivation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
bovine serum albumin stabilizes during purification
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
0C, below, in 70% saturated ammonium sulfate, several years
-
PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
4 isoenzymes purified by a method that includes GMP agarose chromatography and isoelectric focusing
-
method
-
method that includes DEAE-cellulose, Sephadex-75 chromatography and isoelectric focusing
-
Ni2+-NTA agarose affinity column chromatography and gel filtration
-
recombinant His-tagged GK domain fragment of human DLG1 from Escherichia coli by anion exchange chromatography and gel filtration. The tag is cleaved by TEV protease
recombinant N-terminally His6-tagged and SUMO-tagged enzyme from Escherichia coli strain BL21-(DE3)-pLysS by nickel affinity chromatography and gel filtration
CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells
-
recombinant expression of His-tagged GK domain fragment of human DLG1 in Escherichia coli
recombinant expression of the N-terminally His6-tagged and SUMO-tagged enzyme in Escherichia coli strain BL21-(DE3)-pLysS
transient expression in HEK293 cells, with N-methyl-D-aspartate receptor, wild-type and mutant, cell surface co-expression
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
there is an approximately 40% drop in guanylate kinase mRNA expression in cell lines resistant to 9-[2-(phosphonomethoxyethyl)guanine] and 9-[2-(phosphonomethoxyethyl)diaminopurine]
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Agarwal, K.C.; Miech, R.P.; Parks, R.E.
Guanylate kinases from human erythrocytes, hog brain, and rat liver
Methods Enzymol.
51
483-490
1978
Homo sapiens, Rattus norvegicus, Sus scrofa
Manually annotated by BRENDA team
Boehme, R.E.
Phosphorylation of the antiviral precursor 9-(1,3-dihydroxy-2-propoxymethyl)guanine monophosphate by guanylate kinase isozymes
J. Biol. Chem.
259
12346-12349
1984
Homo sapiens
Manually annotated by BRENDA team
Brady, W.A.; Kokoris, M.S.; Fitzgibbon, M.; Black, M.E.
Cloning, characterization, and modeling of mouse and human guanylate kinases
J. Biol. Chem.
271
16734-16740
1996
Homo sapiens, Mus musculus, Mus musculus (Q64520)
Manually annotated by BRENDA team
Prinz, H.; Lavie, A.; Scheidig, A.J.; Spangenberg, O.; Konrad, M.
Binding of nucleotides to guanylate kinase, p21(ras), and nucleoside-diphosphate kinase studied by nano-electrospray mass spectrometry
J. Biol. Chem.
274
35337-35342
1999
Homo sapiens (Q16774)
Manually annotated by BRENDA team
Miller, W.H.; Beauchamp, L.M.; Meade, E.; Reardon, J.E.; Biron, K.K.; Smith, A.A.; Goss, C.A.; Miller, R.L.
Phosphorylation of ganciclovir phosphonate by cellular GMP kinase determines the stereoselectivity of anti-human cytomegalovirus activity
Nucleosides Nucleotides Nucleic Acids
19
341-356
2000
Homo sapiens, Sus scrofa
Manually annotated by BRENDA team
Willmon, C.L.; Krabbenhoft, E.; Black, M.E.
A guanylate kinase/HSV-1 thymidine kinase fusion protein enhances prodrug-mediated cell killing
Gene Ther.
13
1309-1312
2006
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Gardoni, F.; Marcello, E.; Di Luca, M.
Postsynaptic density-membrane associated guanylate kinase proteins (PSD-MAGUKs) and their role in CNS disorders
Neuroscience
158
324-333
2008
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Mertlikova-Kaiserova, H.; Rumlova, M.; Tloustova, E.; Prochazkova, E.; Holy, A.; Votruba, I.
Point mutations in human guanylate kinase account for acquired resistance to anticancer nucleotide analogue PMEG
Biochem. Pharmacol.
82
131-138
2011
Homo sapiens
Manually annotated by BRENDA team
Zhu, J.; Shang, Y.; Xia, C.; Wang, W.; Wen, W.; Zhang, M.
Guanylate kinase domains of the MAGUK family scaffold proteins as specific phospho-protein-binding modules
EMBO J.
30
4986-4997
2011
Homo sapiens, Rattus norvegicus (Q62696)
Manually annotated by BRENDA team
Dembowski, J.A.; An, P.; Scoulos-Hanson, M.; Yeo, G.; Han, J.; Fu, X.D.; Grabowski, P.J.
Alternative splicing of a novel inducible exon diversifies the CASK guanylate kinase domain
J. Nucleic Acids
2012
816237
2012
Homo sapiens (O14936)
Manually annotated by BRENDA team
Mori, S.; Tezuka, Y.; Arakawa, A.; Handa, N.; Shirouzu, M.; Akiyama, T.; Yokoyama, S.
Crystal structure of the guanylate kinase domain from discs large homolog 1 (DLG1/SAP97)
Biochem. Biophys. Res. Commun.
435
334-338
2013
Homo sapiens, Homo sapiens (Q12959)
Manually annotated by BRENDA team
Jain, R.; Khan, N.; Menzel, A.; Rajkovic, I.; Konrad, M.; Techert, S.
Insights into open/closed conformations of the catalytically active human guanylate kinase as investigated by small-angle X-ray scattering
Eur. Biophys. J.
45
81-89
2016
Homo sapiens, Homo sapiens (Q16774)
Manually annotated by BRENDA team
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