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P38697 (IMDH2_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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
Gene names
Name:IMD2
Synonyms:PUR5
Ordered Locus Names:YHR216W
OrganismSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]
Taxonomic identifier559292 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces

Protein attributes

Sequence length523 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. In contrast to the other IMPDH alleles IMD3 and IMD4, the enzymatic activity of IMD2 seems to be intrinsically drug resistant. Ref.5 Ref.6 Ref.7

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 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. Seems to be able to form heterotetramers composed from more than 1 of the 3 IMPDH gene products (IMD2-4). Ref.6

Subcellular location

Cytoplasm Ref.3.

Induction

Induced by MPA resulting in resistance to the drug. Repressed by nutrient limitation. Ref.5

Miscellaneous

Present with 7870 molecules/cell in log phase SD medium.

Sequence similarities

Belongs to the IMPDH/GMPR family.

Contains 2 CBS domains.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 523523Inosine-5'-monophosphate dehydrogenase 2 HAMAP-Rule MF_03156
PRO_0000093682

Regions

Domain121 – 18363CBS 1
Domain184 – 24057CBS 2
Nucleotide binding278 – 2803NAD By similarity
Nucleotide binding328 – 3303NAD By similarity
Region368 – 3703IMP binding By similarity
Region391 – 3922IMP binding By similarity
Region415 – 4195IMP binding By similarity

Sites

Active site3351Thioimidate intermediate By similarity
Metal binding3301Potassium; via carbonyl oxygen By similarity
Metal binding3321Potassium; via carbonyl oxygen By similarity
Metal binding3351Potassium; via carbonyl oxygen By similarity
Metal binding5081Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Metal binding5091Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Metal binding5101Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Binding site3331IMP By similarity
Binding site4491IMP By similarity

Experimental info

Mutagenesis2531S → A: Reduces drug-resistance to MPA. Ref.7
Mutagenesis3351C → A: Inactivates the proteins ability to provide drug-resistance in vivo. Ref.6

Sequences

Sequence LengthMass (Da)Tools
P38697 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: 7CA3EC11238906B9

FASTA52356,530
        10         20         30         40         50         60 
MAAIRDYKTA LDFTKSLPRP DGLSVQELMD SKIRGGLTYN DFLILPGLVD FASSEVSLQT 

        70         80         90        100        110        120 
KLTRNITLNI PLVSSPMDTV TESEMATFMA LLGGIGFIHH NCTPEDQADM VRRVKNYENG 

       130        140        150        160        170        180 
FINNPIVISP TTTVGEAKSM KEKYGFAGFP VTTDGKRNAK LVGVITSRDI QFVEDNSLLV 

       190        200        210        220        230        240 
QDVMTKNPVT GAQGITLSEG NEILKKIKKG RLLVVDEKGN LVSMLSRTDL MKNQNYPLAS 

       250        260        270        280        290        300 
KSANTKQLLC GASIGTMDAD KERLRLLVKA GLDVVILDSS QGNSIFELNM LKWVKESFPG 

       310        320        330        340        350        360 
LEVIAGNVVT REQAANLIAA GADGLRIGMG TGSICITQEV MACGRPQGTA VYNVCEFANQ 

       370        380        390        400        410        420 
FGVPCMADGG VQNIGHITKA LALGSSTVMM GGMLAGTTES PGEYFYQDGK RLKAYRGMGS 

       430        440        450        460        470        480 
IDAMQKTGTK GNASTSRYFS ESDSVLVAQG VSGAVVDKGS IKKFIPYLYN GLQHSCQDIG 

       490        500        510        520 
CRSLTLLKNN VQRGKVRFEF RTASAQLEGG VHNLHSYEKR LHN 

« Hide

References

« Hide 'large scale' references
[1]"Complete nucleotide sequence of Saccharomyces cerevisiae chromosome VIII."
Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z., Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., Kucaba T., Hillier L.W., Jier M., Johnston L., Langston Y., Latreille P. expand/collapse author list , Louis E.J., Macri C., Mardis E., Menezes S., Mouser L., Nhan M., Rifkin L., Riles L., St Peter H., Trevaskis E., Vaughan K., Vignati D., Wilcox L., Wohldman P., Waterston R., Wilson R., Vaudin M.
Science 265:2077-2082(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 204508 / S288c.
[2]Saccharomyces Genome Database
Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases
Cited for: GENOME REANNOTATION.
Strain: ATCC 204508 / S288c.
[3]"Global analysis of protein localization in budding yeast."
Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K.
Nature 425:686-691(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[4]"Global analysis of protein expression in yeast."
Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S.
Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[5]"Functional distinctions between IMP dehydrogenase genes in providing mycophenolate resistance and guanine prototrophy to yeast."
Hyle J.W., Shaw R.J., Reines D.
J. Biol. Chem. 278:28470-28478(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[6]"Detection of the mycophenolate-inhibited form of IMP dehydrogenase in vivo."
McPhillips C.C., Hyle J.W., Reines D.
Proc. Natl. Acad. Sci. U.S.A. 101:12171-12176(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF CYS-335, SUBUNIT.
[7]"Dissection of the molecular basis of mycophenolate resistance in Saccharomyces cerevisiae."
Jenks M.H., Reines D.
Yeast 22:1181-1190(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF SER-253.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U00029 Genomic DNA. Translation: AAB69728.1.
BK006934 Genomic DNA. Translation: DAA06915.1.
PIRS48997.
RefSeqNP_012088.3. NM_001179347.3.

3D structure databases

ProteinModelPortalP38697.
SMRP38697. Positions 10-521.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid36651. 61 interactions.
DIPDIP-2840N.
IntActP38697. 37 interactions.
MINTMINT-521280.
STRING4932.YHR216W.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblFungiYHR216W; YHR216W; YHR216W.
GeneID856626.
KEGGsce:YHR216W.

Organism-specific databases

CYGDYHR216w.
SGDS000001259. IMD2.

Phylogenomic databases

GeneTreeENSGT00530000062923.
HOGENOMHOG000165752.
KOK00088.
OrthoDBEOG793BHK.

Enzyme and pathway databases

BioCycYEAST:YHR216W-MONOMER.
SABIO-RKP38697.
UniPathwayUPA00601; UER00295.

Gene expression databases

GenevestigatorP38697.

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...

Other

NextBio982568.

Entry information

Entry nameIMDH2_YEAST
AccessionPrimary (citable) accession number: P38697
Secondary accession number(s): D3DLH1
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: February 19, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

Yeast chromosome VIII

Yeast (Saccharomyces cerevisiae) chromosome VIII: entries and gene names

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways