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P12269 (IMDH2_CRIGR) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Inosine-5'-monophosphate dehydrogenase 2

Short name=IMP dehydrogenase 2
Short name=IMPD 2
Short name=IMPDH 2
EC=1.1.1.205
Alternative name(s):
IMPDH-II
Gene names
Name:IMPDH2
OrganismCricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus) [Complete proteome]
Taxonomic identifier10029 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeCricetinaeCricetulus

Protein attributes

Sequence length514 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 By similarity. It may also have a role in the development of malignancy and the growth progression of some tumors. HAMAP-Rule MF_03156

Catalytic activity

Inosine 5'-phosphate + NAD+ + H2O = xanthosine 5'-phosphate + NADH. HAMAP-Rule MF_03156

Cofactor

Potassium.

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 By similarity. HAMAP-Rule MF_03156

Pathway

Purine metabolism; XMP biosynthesis via de novo pathway; XMP from IMP: step 1/1. HAMAP-Rule MF_03156

Subunit structure

Homotetramer.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity HAMAP-Rule MF_03156.

Sequence similarities

Belongs to the IMPDH/GMPR family.

Contains 2 CBS domains.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 514513Inosine-5'-monophosphate dehydrogenase 2 HAMAP-Rule MF_03156
PRO_0000093672

Regions

Domain114 – 17360CBS 1
Domain179 – 23759CBS 2
Nucleotide binding274 – 2763NAD By similarity
Nucleotide binding324 – 3263NAD By similarity
Region364 – 3663IMP binding HAMAP-Rule MF_03156
Region387 – 3882IMP binding HAMAP-Rule MF_03156
Region411 – 4155IMP binding HAMAP-Rule MF_03156

Sites

Active site3311Thioimidate intermediate
Metal binding3261Potassium; via carbonyl oxygen By similarity
Metal binding3281Potassium; via carbonyl oxygen By similarity
Metal binding3311Potassium; via carbonyl oxygen By similarity
Metal binding5001Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Metal binding5011Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Metal binding5021Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Binding site2761Inhibitor
Binding site3291IMP
Binding site3331Inhibitor
Binding site4411IMP

Amino acid modifications

Modified residue1221Phosphoserine By similarity
Modified residue4001Phosphotyrosine By similarity
Modified residue4161Phosphoserine By similarity
Modified residue5111N6-acetyllysine By similarity

Experimental info

Mutagenesis2751S → A: No effect. Ref.3
Mutagenesis2761S → A: Increases Ki for MPA 7-fold. Ref.3
Mutagenesis3291S → A: Reduces activity by 87%. Ref.3
Mutagenesis3311C → A: Loss of activity. Ref.3
Mutagenesis3331T → I: Increases Ki for MPA 300-fold. Ref.3
Mutagenesis3641D → A: Loss of activity. Ref.3
Mutagenesis3681Q → A: No effect. Ref.3
Mutagenesis4411Q → A: Reduces activity by over 95% and increases Ki for MPA 25-fold. Ref.3

Secondary structure

............................................................................ 514
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P12269 [UniParc].

Last modified October 1, 1989. Version 1.
Checksum: 5FA0138FA41E8A02

FASTA51455,890
        10         20         30         40         50         60 
MADYLISGGT SYVPDDGLTA QQLFNCGDGL TYNDFLILPG YIDFTADQVD LTSALTKKIT 

        70         80         90        100        110        120 
LKTPLVSSPM DTVTEAGMAI AMALTGGIGF IHHNCTPEFQ ANEVRKVKKY EQGFITDPVV 

       130        140        150        160        170        180 
LSPKDRVRDV FEAKARHGFC GIPITDTGRM GSRLVGIISS RDIDFLKEEE HDRFLEEIMT 

       190        200        210        220        230        240 
KREDLVVAPA GITLKEANEI LQRSKKGKLP IVNENDELVA IIARTDLKKN RDYPLASKDA 

       250        260        270        280        290        300 
KKQLLCGAAI GTHEDDKYRL DLLALAGVDV VVLDSSQGNS IFQINMIKYM KEKYPNLQVI 

       310        320        330        340        350        360 
GGNVVTAAQA KNLIDAGVDA LRVGMGCGSI CITQEVLACG RPQATAVYKV SEYARRFGVP 

       370        380        390        400        410        420 
VIADGGIQNV GHIAKALALG ASTVMMGSLL AATTEAPGEY FFSDGIRLKK YRGMGSLDAM 

       430        440        450        460        470        480 
DKHLSSQNRY FSEADKIKVA QGVSGAVQDK GSIHKFVPYL IAGIQHSCQD IGAKSLTQVR 

       490        500        510 
AMMYSGELKF EKRTSSAQVE GGVHSLHSYE KRLF 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and sequence analysis of the human and Chinese hamster inosine-5'-monophosphate dehydrogenase cDNAs."
Collart F.R., Huberman E.
J. Biol. Chem. 263:15769-15772(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 336-370.
[2]"The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line."
Xu X., Nagarajan H., Lewis N.E., Pan S., Cai Z., Liu X., Chen W., Xie M., Wang W., Hammond S., Andersen M.R., Neff N., Passarelli B., Koh W., Fan H.C., Wang J., Gui Y., Lee K.H. expand/collapse author list , Betenbaugh M.J., Quake S.R., Famili I., Palsson B.O., Wang J.
Nat. Biotechnol. 29:735-741(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Structure and mechanism of inosine monophosphate dehydrogenase in complex with the immunosuppressant mycophenolic acid."
Sintchak M.D., Fleming M.A., Futer O., Raybuck S.A., Chambers S.P., Caron P.R., Murcko M.A., Wilson K.P.
Cell 85:921-930(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND THE INHIBITOR MYCOPHENOLIC ACID (MPA), MUTAGENESIS OF SER-275; SER-276; SER-329; CYS-331; THR-333; ASP-364; GLN-368 AND GLN-441.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J04209 mRNA. Translation: AAA36993.1.
JH001800 Genomic DNA. Translation: EGW10487.1.
RefSeqNP_001233751.1. NM_001246822.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1JR1X-ray2.60A/B1-514[»]
ProteinModelPortalP12269.
SMRP12269. Positions 10-514.
ModBaseSearch...
MobiDBSearch...

Chemistry

DrugBankDB01024. Mycophenolic acid.

Proteomic databases

PRIDEP12269.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100689398.
KEGGcge:100689398.

Organism-specific databases

CTD32009.

Phylogenomic databases

HOVERGENHBG052122.
KOK00088.

Enzyme and pathway databases

UniPathwayUPA00601; UER00295.

Family and domain databases

Gene3D3.20.20.70. 1 hit.
HAMAPMF_01964. IMPDH.
InterProIPR013785. Aldolase_TIM.
IPR000644. CBS_dom.
IPR005990. IMP_DH.
IPR015875. IMP_DH/GMP_Rdtase_CS.
IPR001093. IMP_DH_GMPRt.
[Graphical view]
PfamPF00571. CBS. 2 hits.
PF00478. IMPDH. 1 hit.
[Graphical view]
PIRSFPIRSF000130. IMPDH. 1 hit.
SMARTSM00116. CBS. 2 hits.
[Graphical view]
TIGRFAMsTIGR01302. IMP_dehydrog. 1 hit.
PROSITEPS51371. CBS. 2 hits.
PS00487. IMP_DH_GMP_RED. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP12269.

Entry information

Entry nameIMDH2_CRIGR
AccessionPrimary (citable) accession number: P12269
Secondary accession number(s): G3IB73
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: June 11, 2014
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways