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Protein

Inosine-5'-monophosphate dehydrogenase 2

Gene

Impdh2

Organism
Mus musculus (Mouse)
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. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.UniRule annotation

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.UniRule annotation

Pathway: XMP biosynthesis via de novo pathway

This protein is involved in step 1 of the subpathway that synthesizes XMP from IMP.UniRule annotation
Proteins known to be involved in this subpathway in this organism are:
  1. Inosine-5'-monophosphate dehydrogenase 1 (Impdh1), Inosine-5'-monophosphate dehydrogenase (Impdh1), Inosine-5'-monophosphate dehydrogenase 2 (Impdh2), Inosine-5'-monophosphate dehydrogenase (Impdh2), Inosine-5'-monophosphate dehydrogenase (Impdh1), Inosine-5'-monophosphate dehydrogenase (Impdh2), Inosine-5'-monophosphate dehydrogenase (Impdh2)
This subpathway is part of the pathway XMP biosynthesis via de novo pathway, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes XMP from IMP, the pathway XMP biosynthesis via de novo pathway and in Purine metabolism.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi326 – 3261Potassium; via carbonyl oxygenUniRule annotation
Metal bindingi328 – 3281Potassium; via carbonyl oxygenUniRule annotation
Binding sitei329 – 3291IMPUniRule annotation
Active sitei331 – 3311Thioimidate intermediateUniRule annotation
Metal bindingi331 – 3311Potassium; via carbonyl oxygenUniRule annotation
Binding sitei441 – 4411IMPUniRule annotation
Metal bindingi500 – 5001Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
Metal bindingi501 – 5011Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
Metal bindingi502 – 5021Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi274 – 2763NADUniRule annotation
Nucleotide bindingi324 – 3263NADUniRule annotation

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • IMP dehydrogenase activity Source: MGI
  • metal ion binding Source: UniProtKB-HAMAP
  • nucleotide binding Source: UniProtKB
  • RNA binding Source: UniProtKB-KW

GO - Biological processi

  • cellular response to interleukin-4 Source: MGI
  • GMP biosynthetic process Source: UniProtKB-HAMAP
  • lymphocyte proliferation Source: MGI
  • protein homotetramerization Source: Ensembl
  • purine nucleotide biosynthetic process Source: MGI
  • retina development in camera-type eye Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

GMP biosynthesis, Purine biosynthesis

Keywords - Ligandi

DNA-binding, Metal-binding, NAD, Potassium, RNA-binding

Enzyme and pathway databases

BRENDAi1.1.1.205. 3474.
ReactomeiREACT_344602. Purine ribonucleoside monophosphate biosynthesis.
UniPathwayiUPA00601; UER00295.

Names & Taxonomyi

Protein namesi
Recommended name:
Inosine-5'-monophosphate dehydrogenase 2UniRule annotation (EC:1.1.1.205UniRule annotation)
Short name:
IMP dehydrogenase 2UniRule annotation
Short name:
IMPD 2UniRule annotation
Short name:
IMPDH 2UniRule annotation
Alternative name(s):
IMPDH-II
Gene namesi
Name:Impdh2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:109367. Impdh2.

Subcellular locationi

  • Cytoplasm UniRule annotation
  • Nucleus UniRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 514513Inosine-5'-monophosphate dehydrogenase 2PRO_0000093674Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei122 – 1221PhosphoserineBy similarity
Modified residuei400 – 4001PhosphotyrosineBy similarity
Modified residuei416 – 4161PhosphoserineBy similarity
Modified residuei511 – 5111N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP24547.
PaxDbiP24547.
PRIDEiP24547.

2D gel databases

REPRODUCTION-2DPAGEP24547.

PTM databases

PhosphoSiteiP24547.

Expressioni

Gene expression databases

BgeeiP24547.
CleanExiMM_IMPDH2.
ExpressionAtlasiP24547. baseline.
GenevisibleiP24547. MM.

Interactioni

Subunit structurei

Homotetramer.

Protein-protein interaction databases

BioGridi204792. 2 interactions.
IntActiP24547. 2 interactions.
MINTiMINT-1869864.
STRINGi10090.ENSMUSP00000079888.

Structurei

3D structure databases

ProteinModelPortaliP24547.
SMRiP24547. Positions 10-514.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini114 – 17360CBS 1UniRule annotationAdd
BLAST
Domaini179 – 23759CBS 2UniRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni364 – 3663IMP bindingUniRule annotation
Regioni387 – 3882IMP bindingUniRule annotation
Regioni411 – 4155IMP bindingUniRule annotation

Sequence similaritiesi

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

Keywords - Domaini

CBS domain, Repeat

Phylogenomic databases

eggNOGiCOG0517.
HOGENOMiHOG000165752.
HOVERGENiHBG052122.
InParanoidiP24547.
KOiK00088.
OMAiRVRDVFQ.
OrthoDBiEOG7VTDMM.
PhylomeDBiP24547.
TreeFamiTF300378.

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]
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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P24547-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADYLISGGT SYVPDDGLTA QQLFNCGDGL TYNDFLILPG YIDFTADQVD
60 70 80 90 100
LTSALTKKIT LKTPLVSSPM DTVTEAGMAI AMALTGGIGF IHHNCTPEFQ
110 120 130 140 150
ANEVRKVKKY EQGFITDPVV LSPKDRVRDV FEAKARHGFC GIPITDTGRM
160 170 180 190 200
GSRLVGIISS RDIDFLKEEE HDRFLEEIMT KREDLVVAPA GVTLKEANEI
210 220 230 240 250
LQRSKKGKLP IVNENDELVA IIARTDLKKN RDYPLASKDA KKQLLCGAAI
260 270 280 290 300
GTHEDDKYRL DLLALAGVDV VVLDSSQGNS IFQINMIKYI KEKYPSLQVI
310 320 330 340 350
GGNVVTAAQA KNLIDAGVDA LRVGMGSGSI CITQEVLACG RPQATAVYKV
360 370 380 390 400
SEYARRFGVP VIADGGIQNV GHIAKALALG ASTVMMGSLL AATTEAPGEY
410 420 430 440 450
FFSDGIRLKK YRGMGSLDAM DKHLSSQNRY FSEADKIKVA QGVSGAVQDK
460 470 480 490 500
GSIHKFVPYL IAGIQHSCQD IGAKSLTQVR AMMYSGELKF EKRTSSAQVE
510
GGVHSLHSYE KRLF
Length:514
Mass (Da):55,815
Last modified:October 3, 2003 - v2
Checksum:i17D25A5C5EBCC439
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti458 – 4581P → L AA sequence (PubMed:2572589).Curated
Sequence conflicti465 – 4651Q → S AA sequence (PubMed:2572589).Curated
Sequence conflicti483 – 4831M → T in AAA39311 (PubMed:1671845).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti333 – 3331T → I in mycophenolic acid resistant cells.
Natural varianti351 – 3511S → Y in mycophenolic acid resistant cells.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M33934 mRNA. Translation: AAA39311.1.
M98333 mRNA. Translation: AAA20181.1.
BC010314 mRNA. Translation: AAH10314.1.
BC052671 mRNA. Translation: AAH52671.1.
CCDSiCCDS40768.1.
PIRiJT0565.
RefSeqiNP_035960.2. NM_011830.3.
UniGeneiMm.6065.

Genome annotation databases

EnsembliENSMUST00000081111; ENSMUSP00000079888; ENSMUSG00000062867.
GeneIDi23918.
KEGGimmu:23918.
UCSCiuc009rqg.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M33934 mRNA. Translation: AAA39311.1.
M98333 mRNA. Translation: AAA20181.1.
BC010314 mRNA. Translation: AAH10314.1.
BC052671 mRNA. Translation: AAH52671.1.
CCDSiCCDS40768.1.
PIRiJT0565.
RefSeqiNP_035960.2. NM_011830.3.
UniGeneiMm.6065.

3D structure databases

ProteinModelPortaliP24547.
SMRiP24547. Positions 10-514.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204792. 2 interactions.
IntActiP24547. 2 interactions.
MINTiMINT-1869864.
STRINGi10090.ENSMUSP00000079888.

Chemistry

BindingDBiP24547.
ChEMBLiCHEMBL3169.

PTM databases

PhosphoSiteiP24547.

2D gel databases

REPRODUCTION-2DPAGEP24547.

Proteomic databases

MaxQBiP24547.
PaxDbiP24547.
PRIDEiP24547.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000081111; ENSMUSP00000079888; ENSMUSG00000062867.
GeneIDi23918.
KEGGimmu:23918.
UCSCiuc009rqg.1. mouse.

Organism-specific databases

CTDi3615.
MGIiMGI:109367. Impdh2.

Phylogenomic databases

eggNOGiCOG0517.
HOGENOMiHOG000165752.
HOVERGENiHBG052122.
InParanoidiP24547.
KOiK00088.
OMAiRVRDVFQ.
OrthoDBiEOG7VTDMM.
PhylomeDBiP24547.
TreeFamiTF300378.

Enzyme and pathway databases

UniPathwayiUPA00601; UER00295.
BRENDAi1.1.1.205. 3474.
ReactomeiREACT_344602. Purine ribonucleoside monophosphate biosynthesis.

Miscellaneous databases

ChiTaRSiImpdh2. mouse.
NextBioi303689.
PROiP24547.
SOURCEiSearch...

Gene expression databases

BgeeiP24547.
CleanExiMM_IMPDH2.
ExpressionAtlasiP24547. baseline.
GenevisibleiP24547. MM.

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]
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

« Hide 'large scale' publications
  1. "Isolation and sequence of a cDNA encoding mouse IMP dehydrogenase."
    Tiedeman A.A., Smith J.M.
    Gene 97:289-293(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Gene amplification and dual point mutations of mouse IMP dehydrogenase associated with cellular resistance to mycophenolic acid."
    Lightfoot T., Snyder F.F.
    Biochim. Biophys. Acta 1217:156-162(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS MYCOPHENOLIC ACID RESISTANT.
    Tissue: Brain.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C3H/He and Czech II.
    Tissue: Mammary gland and Osteoblast.
  4. "Increased activity, amount, and altered kinetic properties of IMP dehydrogenase from mycophenolic acid-resistant neuroblastoma cells."
    Hodges S.D., Fung E., McKay D.J., Renaux B.S., Snyder F.F.
    J. Biol. Chem. 264:18137-18141(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 125-133; 182-194; 289-290; 439-449; 456-466 AND 475-478.
  5. Lubec G., Yang J.W., Zigmond M.
    Submitted (JUL-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 137-149.
    Tissue: Brain.

Entry informationi

Entry nameiIMDH2_MOUSE
AccessioniPrimary (citable) accession number: P24547
Secondary accession number(s): Q61734, Q91Z11
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: October 3, 2003
Last modified: June 24, 2015
This is version 156 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. 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.