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Protein

Inosine-5'-monophosphate dehydrogenase

Gene

GUA1

Organism
Pneumocystis carinii
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.UniRule annotation2 Publications

Catalytic activityi

Inosine 5'-phosphate + NAD+ + H2O = xanthosine 5'-phosphate + NADH.UniRule annotation

Cofactori

K(+)UniRule annotation

Enzyme regulationi

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.UniRule annotation1 Publication

Kineticsi

  1. KM=21.7 µM for Inosine 5'-phosphate1 Publication
  2. KM=314 µM for NAD+1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi333 – 3331Potassium; via carbonyl oxygenUniRule annotation
Metal bindingi335 – 3351Potassium; via carbonyl oxygenUniRule annotation
Binding sitei336 – 3361IMPUniRule annotation
Active sitei338 – 3381Thioimidate intermediateUniRule annotation
Metal bindingi338 – 3381Potassium; via carbonyl oxygenUniRule annotation
Binding sitei455 – 4551IMPUniRule annotation
Metal bindingi514 – 5141Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
Metal bindingi515 – 5151Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi281 – 2833NADUniRule annotation
Nucleotide bindingi331 – 3333NADUniRule annotation

GO - Molecular functioni

  1. IMP dehydrogenase activity Source: UniProtKB-HAMAP
  2. metal ion binding Source: UniProtKB-HAMAP
  3. nucleotide binding Source: UniProtKB-HAMAP

GO - Biological processi

  1. GMP biosynthetic process Source: UniProtKB-HAMAP
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

GMP biosynthesis, Purine biosynthesis

Keywords - Ligandi

Metal-binding, NAD, Potassium

Enzyme and pathway databases

BRENDAi1.1.1.205. 4924.
UniPathwayiUPA00601; UER00295.

Names & Taxonomyi

Protein namesi
Recommended name:
Inosine-5'-monophosphate dehydrogenaseUniRule annotation (EC:1.1.1.205UniRule annotation)
Short name:
IMP dehydrogenaseUniRule annotation
Short name:
IMPDUniRule annotation
Short name:
IMPDHUniRule annotation
Gene namesi
Name:GUA1
OrganismiPneumocystis carinii
Taxonomic identifieri4754 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaTaphrinomycotinaPneumocystidomycetesPneumocystidaceaePneumocystis

Subcellular locationi

  1. Cytoplasm UniRule annotation

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 529529Inosine-5'-monophosphate dehydrogenasePRO_0000093679Add
BLAST

Post-translational modificationi

The N-terminus is blocked.

Interactioni

Subunit structurei

Homotetramer.UniRule annotation

Structurei

3D structure databases

ProteinModelPortaliQ12658.
SMRiQ12658. Positions 39-121, 238-528.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini124 – 18562CBS 1UniRule annotationAdd
BLAST
Domaini187 – 24357CBS 2UniRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni371 – 3733IMP bindingUniRule annotation
Regioni394 – 3952IMP bindingUniRule annotation
Regioni418 – 4225IMP bindingUniRule annotation

Sequence similaritiesi

Belongs to the IMPDH/GMPR family.UniRule annotation
Contains 2 CBS domains.UniRule annotation

Keywords - Domaini

CBS domain, Repeat

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
HAMAPiMF_01964. IMPDH.
InterProiIPR013785. Aldolase_TIM.
IPR000644. CBS_dom.
IPR005990. IMP_DH.
IPR015875. IMP_DH/GMP_Rdtase_CS.
IPR001093. IMP_DH_GMPRt.
[Graphical view]
PANTHERiPTHR11911:SF6. PTHR11911:SF6. 1 hit.
PfamiPF00571. CBS. 2 hits.
PF00478. IMPDH. 1 hit.
[Graphical view]
PIRSFiPIRSF000130. IMPDH. 1 hit.
SMARTiSM00116. CBS. 2 hits.
[Graphical view]
TIGRFAMsiTIGR01302. IMP_dehydrog. 1 hit.
PROSITEiPS51371. CBS. 2 hits.
PS00487. IMP_DH_GMP_RED. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q12658-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGEDSYLCLS EEIKKKLEEY SEKDGYDLDS LICSRRHGGL TYNDIIILPG
60 70 80 90 100
YIDFEVNSVS LESHITKKIV LKTPFMSSPM DTVTESDMAI NLALLGGIGV
110 120 130 140 150
IHHNCTIEEQ TEMVRKVKKF ENGFITSPIV LSLNHRVRDV RRIKEELGFS
160 170 180 190 200
GIPITDTGQL NGKLLGIVTS RDIQFHNNDE SFLSEVMTKD LVTGSEGIRL
210 220 230 240 250
EEANEILRSC KKGKLPIVDK EGNLTALLSR SDLMKNLHFP LASKLPDSKQ
260 270 280 290 300
LICAAAVGTR PDDRIRLKHL VEAGLDIVVL DSSQGNSIYQ INMIKWIKKE
310 320 330 340 350
FPNLEVIAGN VVTREQAANL ISAGADALRV GMGSGSICIT QEIMAVGRPQ
360 370 380 390 400
ATAVYAVSEF ASKFGVPTIA DGGIENIGHI TKALALGASA VMMGNLLAGT
410 420 430 440 450
TESPGQYYYR DGQRLKSYRG MGSIDAMEHL SGKNKGDNAA SSRYFGEADT
460 470 480 490 500
IRVAQGVSGS VIDKGSLHVY VPYLRTGLQH SLQDIGVQNL TELRKQVKEK
510 520
NIRFEFRTVA SQLEGNVHGL DSYQKKLWS
Length:529
Mass (Da):58,066
Last modified:February 22, 2012 - v2
Checksum:i030573A8854ADB5A
GO
Isoform 2 (identifier: Q12658-2) [UniParc]FASTAAdd to basket

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

Show »
Length:454
Mass (Da):49,483
Checksum:i4B6A5AF9B4451210
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti187 – 1871M → I in AAA97462 (PubMed:8980752).Curated
Sequence conflicti255 – 2551A → Q in AAA97462 (PubMed:8980752).Curated
Sequence conflicti297 – 2971I → N in AAA97462 (PubMed:8980752).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 7575Missing in isoform 2. 2 PublicationsVSP_042318Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U42442 mRNA. Translation: AAA97462.1.
AF196975 mRNA. Translation: AAF13230.1.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U42442 mRNA. Translation: AAA97462.1.
AF196975 mRNA. Translation: AAF13230.1.

3D structure databases

ProteinModelPortaliQ12658.
SMRiQ12658. Positions 39-121, 238-528.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

UniPathwayiUPA00601; UER00295.
BRENDAi1.1.1.205. 4924.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
HAMAPiMF_01964. IMPDH.
InterProiIPR013785. Aldolase_TIM.
IPR000644. CBS_dom.
IPR005990. IMP_DH.
IPR015875. IMP_DH/GMP_Rdtase_CS.
IPR001093. IMP_DH_GMPRt.
[Graphical view]
PANTHERiPTHR11911:SF6. PTHR11911:SF6. 1 hit.
PfamiPF00571. CBS. 2 hits.
PF00478. IMPDH. 1 hit.
[Graphical view]
PIRSFiPIRSF000130. IMPDH. 1 hit.
SMARTiSM00116. CBS. 2 hits.
[Graphical view]
TIGRFAMsiTIGR01302. IMP_dehydrog. 1 hit.
PROSITEiPS51371. CBS. 2 hits.
PS00487. IMP_DH_GMP_RED. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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.

Entry informationi

Entry nameiIMDH_PNECA
AccessioniPrimary (citable) accession number: Q12658
Secondary accession number(s): Q9UVL0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 22, 2012
Last modified: April 1, 2015
This is version 90 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Direct protein sequencing

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.