Names & Taxonomy

Uniprot ID:
P12268
Entry Name:
IMDH2_HUMAN
Status:
reviewed
Protein Names:
Inosine-5'-monophosphate dehydrogenase 2 (IMP dehydrogenase 2) (IMPD 2) (IMPDH 2) (EC 1.1.1.205) (IMPDH-II)
Gene Names:
IMPDH2 IMPD2
Gene Names Primary:
IMPDH2
Organism:
Homo sapiens (Human)

Structure

Length:
514
Sequence:
MADYLISGGTSYVPDDGLTAQQLFNCGDGLTYNDFLILPGYIDFTADQVDLTSALTKKITLKTPLVSSPMDTVTEAGMAIAMALTGGIGFIHHNCTPEFQANEVRKVKKYEQGFITDPVVLSPKDRVRDVFEAKARHGFCGIPITDTGRMGSRLVGIISSRDIDFLKEEEHDCFLEEIMTKREDLVVAPAGITLKEANEILQRSKKGKLPIVNEDDELVAIIARTDLKKNRDYPLASKDAKKQLLCGAAIGTHEDDKYRLDLLAQAGVDVVVLDSSQGNSIFQINMIKYIKDKYPNLQVIGGNVVTAAQAKNLIDAGVDALRVGMGSGSICITQEVLACGRPQATAVYKVSEYARRFGVPVIADGGIQNVGHIAKALALGASTVMMGSLLAATTEAPGEYFFSDGIRLKKYRGMGSLDAMDKHLSSQNRYFSEADKIKVAQGVSGAVQDKGSIHKFVPYLIAGIQHSCQDIGAKSLTQVRAMMYSGELKFEKRTSSAQVEGGVHSLHSYEKRLF
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm

Function

Function:
Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.
Pathway:
Purine metabolism; XMP biosynthesis via de novo pathway; XMP from IMP: step 1/1.
Catalytic Activity:
Inosine 5'-phosphate + NAD(+) + H(2)O = xanthosine 5'-phosphate + NADH.
Cofactor:
COFACTOR: Name=K(+); Xref=ChEBI:CHEBI:29103;
Kinetics:
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=9.3 uM for Inosine 5'-phosphate
Enzyme Regulation:
ENZYME REGULATION: Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH. Subject to product inhibition by XMP and NADH. Also inhibited by ADP.
Active Site:
ACT_SITE 331 331 Thioimidate intermediate.
Cross Reference Drug Bank:
DB01033 DB00688 DB01024
Gene Ontology Go:
cytoplasm
cytosol
extracellular exosome
membrane
nucleus
peroxisomal membrane
DNA binding
IMP dehydrogenase activity
metal ion binding
nucleotide binding
RNA binding
cellular response to interleukin-4
GMP biosynthetic process
lymphocyte proliferation
nucleobase-containing small molecule metabolic process
protein homotetramerization
purine nucleobase metabolic process
purine ribonucleoside monophosphate biosynthetic process
retina development in camera-type eye
small molecule metabolic process
Gene Ontology Biological Process:
cellular response to interleukin-4
GMP biosynthetic process
lymphocyte proliferation
nucleobase-containing small molecule metabolic process
protein homotetramerization
purine nucleobase metabolic process
purine ribonucleoside monophosphate biosynthetic process
retina development in camera-type eye
small molecule metabolic process
Gene Ontology Molecular Function:
DNA binding
IMP dehydrogenase activity
metal ion binding
nucleotide binding
RNA binding
Gene Ontology Cellular Component:
cytoplasm
cytosol
extracellular exosome
membrane
nucleus
peroxisomal membrane
Keywords:
3D-structure
Acetylation
CBS domain
Complete proteome
Cytoplasm
DNA-binding
Direct protein sequencing
GMP biosynthesis
Metal-binding
NAD
Nucleus
Oxidoreductase
Phosphoprotein
Polymorphism
Potassium
Purine biosynthesis
RNA-binding
Reference proteome
Repeat
Interacts With:
Q96GX9; Q9BU20

Publication

PubMed ID:
2902093 1969416 7999076 7896827 15489334 8098009 7903306 7763314 14766016 15592455 17081983 17496727 18669648 19413330 19608861 20068231 21269460 24275569 25944712 10097070