IMPDH2

Protein identityUniProt · HPA

UniProt accession

P12268

Gene

IMPDH2

Ensembl

ENSG00000178035

Chromosome

3

Canonical length

514 aa

Protein class

Enzymes, FDA approved drug targets, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Cytosol,Rods & Rings

Quaternary structure

Homotetramer

OverviewNCBI Gene

This gene encodes the rate-limiting enzyme in the de novo guanine nucleotide biosynthesis. It is thus involved in maintaining cellular guanine deoxy- and ribonucleotide pools needed for DNA and RNA synthesis. The encoded protein catalyzes the NAD-dependent oxidation of inosine-5'-monophosphate into xanthine-5'-monophosphate, which is then converted into guanosine-5'-monophosphate. This gene is up-regulated in some neoplasms, suggesting it may play a role in malignant transformation. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

514 residues, UniProt reviewed canonical sequence.

>P12268|IMPDH2
     1  MADYLISGGT SYVPDDGLTA QQLFNCGDGL TYNDFLILPG YIDFTADQVD LTSALTKKIT
    61  LKTPLVSSPM DTVTEAGMAI AMALTGGIGF IHHNCTPEFQ ANEVRKVKKY EQGFITDPVV
   121  LSPKDRVRDV FEAKARHGFC GIPITDTGRM GSRLVGIISS RDIDFLKEEE HDCFLEEIMT
   181  KREDLVVAPA GITLKEANEI LQRSKKGKLP IVNEDDELVA IIARTDLKKN RDYPLASKDA
   241  KKQLLCGAAI GTHEDDKYRL DLLAQAGVDV VVLDSSQGNS IFQINMIKYI KDKYPNLQVI
   301  GGNVVTAAQA KNLIDAGVDA LRVGMGSGSI CITQEVLACG RPQATAVYKV SEYARRFGVP
   361  VIADGGIQNV GHIAKALALG ASTVMMGSLL AATTEAPGEY FFSDGIRLKK YRGMGSLDAM
   421  DKHLSSQNRY FSEADKIKVA QGVSGAVQDK GSIHKFVPYL IAGIQHSCQD IGAKSLTQVR
   481  AMMYSGELKF EKRTSSAQVE GGVHSLHSYE KRLF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IMPDH2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

297 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IMPDH2.

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 96 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Dystonic disorder

ReferencesPubMed · IEDB

Publications for IMPDH2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.8

gnomAD pLI

0

gnomAD missense Z

2.5

DepMap mean gene effect

-0.6

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• 'de novo' XMP biosynthetic process
• cellular response to interleukin-4
• circadian rhythm
• GMP biosynthetic process
• GTP biosynthetic process
• lymphocyte proliferation

Molecular functions

• DNA binding
• IMP dehydrogenase activity
• metal ion binding
• nucleotide binding
• RNA binding

Cellular components

• cytoplasm
• cytosol
• extracellular exosome
• extracellular region
• ficolin-1-rich granule lumen
• membrane
• nucleus
• peroxisomal membrane
• secretory granule lumen

Protein domainsUniProt · Pfam · InterPro

• CBS domain
• IMP dehydrogenase/GMP reductase
• Inosine-5'-monophosphate dehydrogenase
• Aldolase-type TIM barrel
• IMP dehydrogenase / GMP reductase, conserved site
• IMP dehydrogenase / GMP reductase domain
• CBS domain

KeywordsUniProt

• Acetylation
• CBS domain
• Cytoplasm
• DNA-binding
• GMP biosynthesis
• Isopeptide bond
• Metal-binding
• NAD
• Nucleus
• Oxidoreductase
• Phosphoprotein
• Potassium
• Purine biosynthesis
• Repeat
• RNA-binding
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of IMPDH2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ANKRD9
• CLOCK
• PARP1