Activating Compound | Comment | Organism | Structure |
---|---|---|---|
activator of protein kinase C | increases the level of AGT mRNA and increases resistance to N,N'-bis(2-chloroethyl)-N-nitrosourea in HeLa cells | Homo sapiens | |
glucocorticoid | regulates AGT expression | Homo sapiens | |
inhibitor of protein phosphatase | increases the level of AGT mRNA and increases resistance to N,N'-bis(2-chloroethyl)-N-nitrosourea in HeLa cells | Homo sapiens | |
ionizing radiation | induces AGT | Mus musculus | |
P53 | regulates MGMT promoter | Homo sapiens |
Application | Comment | Organism |
---|---|---|
medicine | alkyltransferase activity in tumors protects them from therapeutic agents such as temozolomide and N,N'-bis(2-chloroethyl)-N-nitrosourea, polymorphisms in the AGT gene | Homo sapiens |
medicine | expression of additional AGT in a variety of tissues in transgenic mice protects against carcinogenesis | Mus musculus |
medicine | transgenic rats expressing Ada-C are resistant to mammary tumor induction by N-methyl-N-nitrosourea but not by N-ethyl-N-nitrosourea | Escherichia coli |
Cloned (Comment) | Organism |
---|---|
expression in Escherichia coli | Mus musculus |
expression in Escherichia coli, transgenic overexpression in mouse skin, expression in CHO cells | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
Cys acceptor site is buried in the protein and, in order for reaction with a DNA substrate to take place, a change in conformation of either the substrate or the protein must occur, Glu-172 and Asn-137 play a major structural role in the AGT protein | Escherichia coli |
Protein Variants | Comment | Organism |
---|---|---|
C145A | binds to alkylated DNA in a similar manner to wild type AGT but is unable to carry out the repair transfer, expressed in Escherichia coli, this mutant increases killing and mutagenesis by N-methyl-N'-nitro-N-nitrosoguanidine | Homo sapiens |
C145F | appears to cause a similar change in the AGT structure as alkylation of the active site and provides a model for detailed study of the mechanism of degradation | Homo sapiens |
G160R | is as effective as wild-type in protecting cells from N-methyl-N'-nitro-N-nitrosoguanidine and N,N'-bis(2-chloroethyl)-N-nitrosourea, is strongly resistant to O6-benzylguanine | Homo sapiens |
I143V/K178R | no significant effect on AGT activity, may be an increased risk for lung cancer in individuals with this change | Homo sapiens |
K165R | does not abolish activity on 6-O-methylguanine but greatly reduces the ability to react with O6-benzylguanine | Homo sapiens |
additional information | mutation of Arg-128 to Ala greatly reduces the ability of AGT to repair O6-methylguanine in DNA but has no effect on the alkyl transfer reaction when the free base substrate, O6-benzylguanine is used, stability of AGT is reduced by most mutations at Lys-165 | Homo sapiens |
P140K | stable and extremely resistant to O6-benzylguanine | Homo sapiens |
V139F | has an increased ability to protect against the cytotoxic and mutagenic effects of N-methyl-N'-nitro-N-nitrosoguanidine | Escherichia coli |
Y158H | stable and extremely resistant to O6-benzylguanine | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
formaldehyde | decreases activity at levels up to 3fold higher than the maximally allowed workplace concentration, no decrease at the maximally allowed level | Homo sapiens | |
methyl bromide | - |
Mus musculus | |
methyl bromide | - |
Rattus norvegicus | |
additional information | substances present in the saliva of tobacco and betel nut chewers | Homo sapiens | |
Ni2+ | purified protein is not very sensitive to this metal but the loss of AGT could contribute to the well-known carcinogenicity of nickel | Homo sapiens | |
O6-benzyl-2'-deoxyguanosine | - |
Homo sapiens | |
O6-benzylguanine | binds in the active site pocket, abolishes resistance against therapeutic agents temozolomide and N,N'-bis(2-chloroethyl)-N-nitrosourea | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
nucleus | - |
Homo sapiens | 5634 | - |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
23000 | - |
- |
Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Escherichia coli | - |
- |
- |
Homo sapiens | - |
- |
- |
Mus musculus | - |
- |
- |
Rattus norvegicus | - |
- |
- |
Purification (Comment) | Organism |
---|---|
mutant V139F | Escherichia coli |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
astrocyte | level of AGT is much reduced in mice lacking p53 | Mus musculus | - |
bone marrow | low level | Homo sapiens | - |
breast | AGT expression is increased in breast cancer compared to normal breast | Homo sapiens | - |
colon | - |
Mus musculus | - |
fibroblast | - |
Homo sapiens | - |
glioma cell | - |
Homo sapiens | - |
HeLa cell | - |
Homo sapiens | - |
HeLa-S3 cell | - |
Homo sapiens | - |
liver | - |
Mus musculus | - |
liver | lowered in cirrhotic liver | Homo sapiens | - |
lung | - |
Mus musculus | - |
lung | increased in lung cancers from smokers rather than non-smokers | Homo sapiens | - |
additional information | 3T3 cell line has an amplification of the MGMT gene | Mus musculus | - |
additional information | absent from brain | Homo sapiens | - |
skin | - |
Mus musculus | - |
thymus lymphoma cell line | - |
Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
DNA containing 4-O-methylthymine + [protein-L-cysteine | - |
Escherichia coli | DNA lacking 4-O-methylthymine + [protein]-S-methyl-L-cysteine | - |
? | |
DNA containing 4-O-methylthymine + [protein-L-cysteine | very poor substrate | Homo sapiens | DNA lacking 4-O-methylthymine + [protein]-S-methyl-L-cysteine | - |
? | |
DNA containing 6-O-methylguanine + [protein]-L-cysteine | - |
Escherichia coli | DNA lacking 6-O-methylguanine + [protein]-S-methyl-L-cysteine | - |
? | |
DNA containing 6-O-methylguanine + [protein]-L-cysteine | prefered substrate | Homo sapiens | DNA lacking 6-O-methylguanine + [protein]-S-methyl-L-cysteine | - |
? | |
DNA containing O6-(4-oxo-4-(3-pyridyl)butyl)guanine | - |
Homo sapiens | ? | - |
? | |
additional information | in addition to repairing methyl groups, longer alkyl groups including ethyl-, n-propyl-, n-butyl-, 2-chloroethyl-, 2-hydroxyethyl-, iso-propyl and iso-butyl can be repaired | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
Ada-C | - |
Escherichia coli |
AGT | - |
Mus musculus |
AGT | - |
Escherichia coli |
AGT | - |
Homo sapiens |
AGT | - |
Rattus norvegicus |
carboxyl terminal domain of the inducible Escherichia coli ada alkyltransferase | - |
Escherichia coli |
MGMT | - |
Mus musculus |
MGMT | - |
Homo sapiens |
O6-alkylguanine-DNA alkyl-transferase | - |
Mus musculus |
O6-alkylguanine-DNA alkyl-transferase | - |
Escherichia coli |
O6-alkylguanine-DNA alkyl-transferase | - |
Homo sapiens |
O6-alkylguanine-DNA alkyl-transferase | - |
Rattus norvegicus |