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Q4VRV8 (IMDH_TOXGO) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 54. 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
OrganismToxoplasma gondii
Taxonomic identifier5811 [NCBI]
Taxonomic lineageEukaryotaAlveolataApicomplexaConoidasidaCoccidiaEucoccidioridaEimeriorinaSarcocystidaeToxoplasma

Protein attributes

Sequence length551 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

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. Potently inhibited by MPA and adenine dinucleotide analogs such as thiazole-4-carboxamide adenine dinucleotide (TAD). 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 Ref.1.

Sequence similarities

Belongs to the IMPDH/GMPR family.

Contains 2 CBS domains.

Biophysicochemical properties

Kinetic parameters:

KM=144 µM for NAD+ Ref.1

Ontologies

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

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionIMP dehydrogenase activity

Inferred from electronic annotation. Source: UniProtKB-EC

adenyl nucleotide binding

Inferred from electronic annotation. Source: InterPro

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform TgIMPDH (identifier: Q4VRV8-1)

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 TgIMPDH-S (identifier: Q4VRV8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     361-551: ALALGANAVM...LHSFERKLYA → VWRCAEGRRCS
Note: Lacks the active-site flap.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 551551Inosine-5'-monophosphate dehydrogenase HAMAP-Rule MF_03156
PRO_0000415683

Regions

Domain102 – 16362CBS 1
Domain165 – 22157CBS 2
Nucleotide binding258 – 2603NAD By similarity
Nucleotide binding308 – 3103NAD By similarity
Region349 – 3513IMP binding By similarity
Region372 – 3732IMP binding By similarity
Region396 – 4005IMP binding By similarity

Sites

Active site3151Thioimidate intermediate By similarity
Metal binding3101Potassium; via carbonyl oxygen By similarity
Metal binding3121Potassium; via carbonyl oxygen By similarity
Metal binding3151Potassium; via carbonyl oxygen By similarity
Metal binding5361Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Metal binding5371Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Binding site3131IMP By similarity
Binding site4771IMP By similarity

Natural variations

Alternative sequence361 – 551191ALALG…RKLYA → VWRCAEGRRCS in isoform TgIMPDH-S.
VSP_042319

Sequences

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

Last modified July 5, 2005. Version 1.
Checksum: 788A1DAC369E3DE9

FASTA55159,047
        10         20         30         40         50         60 
MADGWDAEKI FNTTVFGFTY DDLILMPGHI DFGVNDVDLS TRITRNLHVR TPIVSSPMDT 

        70         80         90        100        110        120 
VTEHRMAIGC ALMGGMGVIH NNMETARQVA EVQKVKRYEN GFILDPFVLR PSDSVADVYR 

       130        140        150        160        170        180 
IKEKYGYSSV PITDTGMLGG KLLGIVTSRD IDFLTDVHTP LSEVMTSDLV VGHEPVQLAE 

       190        200        210        220        230        240 
ANELLRESKK GKLPIVNDNF ELVALISRND LKKNREFPLA SKDSNKQLLV GAAVSTKPHD 

       250        260        270        280        290        300 
IERAKALQEA GADVLVVDSS QGDSIYQVDL VKRLKAAFPE LQIIGGNVVT ARQAKSLIDA 

       310        320        330        340        350        360 
GVDGLRIGMG SGSICTTQVV CAVGRAQATA VYHVCKYARE HGDVPCIADG GIQNSGHVMK 

       370        380        390        400        410        420 
ALALGANAVM MGSMLAGTEE APGEYYFHNG VRVKTYRGMG SLDAMRAGTR RTASPPARGL 

       430        440        450        460        470        480 
RSPEASPSTA ASSGGASRAS ALSEASPSAK SEASRTSTST GSAARYFAEN QTIRVAQGVS 

       490        500        510        520        530        540 
GCVVDKGTVM QLIPYVIQGV KHGMQDIGAR TLRDLHAQLV GGELRFDVRS GAAQREGDVH 

       550 
DLHSFERKLY A 

« Hide

Isoform TgIMPDH-S [UniParc].

Checksum: 8376164171422C8F
Show »

FASTA37140,366

References

[1]"IMP dehydrogenase from the protozoan parasite Toxoplasma gondii."
Sullivan W.J. Jr., Dixon S.E., Li C., Striepen B., Queener S.F.
Antimicrob. Agents Chemother. 49:2172-2179(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS TGIMPDH AND TGIMPDH-S), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, ENZYME REGULATION.
Strain: RH.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY663109 mRNA. Translation: AAV73841.1.
AY661469 mRNA. Translation: AAV74388.1.

3D structure databases

ProteinModelPortalQ4VRV8.
SMRQ4VRV8. Positions 211-405.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

BRENDA1.1.1.205. 262552.
UniPathwayUPA00601; UER00295.

Family and domain databases

Gene3D3.20.20.70. 2 hits.
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. 2 hits.
[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_TOXGO
AccessionPrimary (citable) accession number: Q4VRV8
Secondary accession number(s): Q4VRV6
Entry history
Integrated into UniProtKB/Swiss-Prot: February 22, 2012
Last sequence update: July 5, 2005
Last modified: February 19, 2014
This is version 54 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways