Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q12658 (IMDH_PNECA) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Inosine-5'-monophosphate dehydrogenase

Short name=IMP dehydrogenase
Short name=IMPD
Short name=IMPDH
EC=1.1.1.205
Gene names
Name:GUA1
OrganismPneumocystis carinii
Taxonomic identifier4754 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaTaphrinomycotinaPneumocystidomycetesPneumocystidaceaePneumocystis

Protein attributes

Sequence length529 AA.
Sequence statusComplete.
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. Ref.1 Ref.2

Catalytic activity

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

Cofactor

Potassium By similarity. HAMAP-Rule MF_03156

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. MPA is a potent inhibitor in culture. Ref.1

Pathway

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

Subunit structure

Homotetramer By similarity. HAMAP-Rule MF_03156

Subcellular location

Cytoplasm By similarity HAMAP-Rule MF_03156.

Post-translational modification

The N-terminus is blocked. HAMAP-Rule MF_03156

Sequence similarities

Belongs to the IMPDH/GMPR family.

Contains 2 CBS domains.

Biophysicochemical properties

Kinetic parameters:

KM=21.7 µM for Inosine 5'-phosphate Ref.1

KM=314 µM for NAD+

Ontologies

Keywords
   Biological processGMP biosynthesis
Purine biosynthesis
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   DomainCBS domain
Repeat
   LigandMetal-binding
NAD
Potassium
   Molecular functionOxidoreductase
   Technical termDirect protein sequencing
Gene Ontology (GO)
   Biological_processGMP biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-HAMAP

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionIMP dehydrogenase activity

Inferred from electronic annotation. Source: UniProtKB-HAMAP

adenyl nucleotide binding

Inferred from electronic annotation. Source: InterPro

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-HAMAP

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q12658-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q12658-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 529529Inosine-5'-monophosphate dehydrogenase HAMAP-Rule MF_03156
PRO_0000093679

Regions

Domain124 – 18562CBS 1
Domain187 – 24357CBS 2
Nucleotide binding281 – 2833NAD By similarity
Nucleotide binding331 – 3333NAD By similarity
Region371 – 3733IMP binding By similarity
Region394 – 3952IMP binding By similarity
Region418 – 4225IMP binding By similarity

Sites

Active site3381Thioimidate intermediate By similarity
Metal binding3331Potassium; via carbonyl oxygen By similarity
Metal binding3351Potassium; via carbonyl oxygen By similarity
Metal binding3381Potassium; via carbonyl oxygen By similarity
Metal binding5141Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Metal binding5151Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Binding site3361IMP By similarity
Binding site4551IMP By similarity

Natural variations

Alternative sequence1 – 7575Missing in isoform 2.
VSP_042318

Experimental info

Sequence conflict1871M → I in AAA97462. Ref.1
Sequence conflict2551A → Q in AAA97462. Ref.1
Sequence conflict2971I → N in AAA97462. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 22, 2012. Version 2.
Checksum: 030573A8854ADB5A

FASTA52958,066
        10         20         30         40         50         60 
MGEDSYLCLS EEIKKKLEEY SEKDGYDLDS LICSRRHGGL TYNDIIILPG YIDFEVNSVS 

        70         80         90        100        110        120 
LESHITKKIV LKTPFMSSPM DTVTESDMAI NLALLGGIGV IHHNCTIEEQ TEMVRKVKKF 

       130        140        150        160        170        180 
ENGFITSPIV LSLNHRVRDV RRIKEELGFS GIPITDTGQL NGKLLGIVTS RDIQFHNNDE 

       190        200        210        220        230        240 
SFLSEVMTKD LVTGSEGIRL EEANEILRSC KKGKLPIVDK EGNLTALLSR SDLMKNLHFP 

       250        260        270        280        290        300 
LASKLPDSKQ LICAAAVGTR PDDRIRLKHL VEAGLDIVVL DSSQGNSIYQ INMIKWIKKE 

       310        320        330        340        350        360 
FPNLEVIAGN VVTREQAANL ISAGADALRV GMGSGSICIT QEIMAVGRPQ ATAVYAVSEF 

       370        380        390        400        410        420 
ASKFGVPTIA DGGIENIGHI TKALALGASA VMMGNLLAGT TESPGQYYYR DGQRLKSYRG 

       430        440        450        460        470        480 
MGSIDAMEHL SGKNKGDNAA SSRYFGEADT IRVAQGVSGS VIDKGSLHVY VPYLRTGLQH 

       490        500        510        520 
SLQDIGVQNL TELRKQVKEK NIRFEFRTVA SQLEGNVHGL DSYQKKLWS 

« Hide

Isoform 2 [UniParc].

Checksum: 4B6A5AF9B4451210
Show »

FASTA45449,483

References

[1]"IMP dehydrogenase from Pneumocystis carinii as a potential drug target."
O'Gara M.J., Lee C.H., Weinberg G.A., Nott J.M., Queener S.F.
Antimicrob. Agents Chemother. 41:40-48(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 119-132; 172-186 AND 300-313, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[2]"Differential splicing of Pneumocystis carinii f. sp. carinii inosine 5'-monophosphate dehydrogenase pre-mRNA."
Ye D., Lee C.H., Queener S.F.
Gene 263:151-158(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U42442 mRNA. Translation: AAA97462.1.
AF196975 mRNA. Translation: AAF13230.1.

3D structure databases

ProteinModelPortalQ12658.
SMRQ12658. Positions 39-121, 238-528.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

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]
PANTHERPTHR11911:SF6. PTHR11911:SF6. 1 hit.
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...

Entry information

Entry nameIMDH_PNECA
AccessionPrimary (citable) accession number: Q12658
Secondary accession number(s): Q9UVL0
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 22, 2012
Last modified: June 11, 2014
This is version 84 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways