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Protein

Inosine-5'-monophosphate dehydrogenase 1

Gene

Impdh1

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

Pathwayi: 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)DescriptionActionsGraphical viewLength
Metal bindingi326Potassium; via carbonyl oxygenUniRule annotation1
Metal bindingi328Potassium; via carbonyl oxygenUniRule annotation1
Binding sitei329IMPUniRule annotation1
Active sitei331Thioimidate intermediateUniRule annotation1
Metal bindingi331Potassium; via carbonyl oxygenUniRule annotation1
Active sitei429Proton acceptorUniRule annotation1
Binding sitei441IMPUniRule annotation1
Metal bindingi500Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation1
Metal bindingi501Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation1
Metal bindingi502Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi274 – 276NADUniRule annotation3
Nucleotide bindingi324 – 326NADUniRule annotation3

GO - Molecular functioni

GO - Biological processi

  • GMP biosynthetic process Source: UniProtKB-HAMAP
  • GTP biosynthetic process Source: GO_Central
  • lymphocyte proliferation Source: MGI
  • purine nucleotide biosynthetic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

GMP biosynthesis, Purine biosynthesis

Keywords - Ligandi

Metal-binding, NAD, Potassium

Enzyme and pathway databases

ReactomeiR-MMU-6798695. Neutrophil degranulation.
R-MMU-73817. Purine ribonucleoside monophosphate biosynthesis.
UniPathwayiUPA00601; UER00295.

Names & Taxonomyi

Protein namesi
Recommended name:
Inosine-5'-monophosphate dehydrogenase 1UniRule annotation (EC:1.1.1.205UniRule annotation)
Short name:
IMP dehydrogenase 1UniRule annotation
Short name:
IMPD 1UniRule annotation
Short name:
IMPDH 1UniRule annotation
Alternative name(s):
IMPDH-I
Gene namesi
Name:Impdh1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:96567. Impdh1.

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)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000936712 – 514Inosine-5'-monophosphate dehydrogenase 1Add BLAST513

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei160PhosphoserineBy similarity1
Modified residuei341Omega-N-methylarginineCombined sources1
Modified residuei355Omega-N-methylarginineCombined sources1

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiP50096.
MaxQBiP50096.
PaxDbiP50096.
PRIDEiP50096.

PTM databases

iPTMnetiP50096.
PhosphoSitePlusiP50096.

Expressioni

Gene expression databases

BgeeiENSMUSG00000003500.
CleanExiMM_IMPDH1.
ExpressionAtlasiP50096. baseline and differential.
GenevisibleiP50096. MM.

Interactioni

Subunit structurei

Homotetramer.

Protein-protein interaction databases

BioGridi204791. 2 interactors.
IntActiP50096. 1 interactor.
MINTiMINT-4098666.
STRINGi10090.ENSMUSP00000077289.

Structurei

3D structure databases

ProteinModelPortaliP50096.
SMRiP50096.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini114 – 173CBS 1UniRule annotationAdd BLAST60
Domaini179 – 237CBS 2UniRule annotationAdd BLAST59

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni364 – 366IMP bindingUniRule annotation3
Regioni387 – 388IMP bindingUniRule annotation2
Regioni411 – 415IMP bindingUniRule annotation5

Sequence similaritiesi

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

Keywords - Domaini

CBS domain, Repeat

Phylogenomic databases

eggNOGiENOG410ISZP. Eukaryota.
COG0517. LUCA.
GeneTreeiENSGT00530000062923.
HOGENOMiHOG000165752.
HOVERGENiHBG052122.
InParanoidiP50096.
KOiK00088.
TreeFamiTF300378.

Family and domain databases

CDDicd00381. IMPDH. 1 hit.
Gene3Di3.20.20.70. 1 hit.
HAMAPiMF_01964. IMPDH. 1 hit.
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.

P50096-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADYLISGGT GYVPEDGLTA QQLFANADGL TYNDFLILPG FIDFIADEVD
60 70 80 90 100
LTSALTRKIT LKTPLISSPM DTVTEADMAI AMALMGGIGF IHHNCTPEFQ
110 120 130 140 150
ANEVRKVKKF EQGFITDPVV LSPSHTVGDV LEAKIQHGFS GIPITATGTM
160 170 180 190 200
GSKLVGIVTS RDIDFLAEKD HTTLLSEVMT PRVELVVAPA GVTLKEANEI
210 220 230 240 250
LQRSKKGKLP IVNDQDELVA IIARTDLKKN RDYPLASKDS HKQLLCGAAV
260 270 280 290 300
GTREDDKYRL DLLTQAGADV IVLDSSQGNS VYQIAMVHYI KQKYPHLQVI
310 320 330 340 350
GGNVVTAAQA KNLIDAGVDG LRVGMGCGSI CITQEVMACG RPQGTAVYKV
360 370 380 390 400
AEYARRFGVP VIADGGIQTV GHVVKALALG ASTVMMGSLL AATTEAPGEY
410 420 430 440 450
FFSDGVRLKK YRGMGSLDAM EKSSSSQKRY FSEGDKVKIA QGVSGSIQDK
460 470 480 490 500
GSIQKFVPYL IAGIQHGCQD IGAQSLSVLR SMMYSGELKF EKRTMSAQIE
510
GGVHGLHSYE KRLY
Length:514
Mass (Da):55,279
Last modified:July 27, 2011 - v2
Checksum:i69E2DD40F03701F2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti21 – 22QQ → HE in AAA18285 (PubMed:7690562).Curated2
Sequence conflicti273L → H in AAA18285 (PubMed:7690562).Curated1
Sequence conflicti414M → I in AAA18285 (PubMed:7690562).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U00978 mRNA. Translation: AAA18285.1.
AK171139 mRNA. Translation: BAE42272.1.
CH466533 Genomic DNA. Translation: EDL13790.1.
BC053416 mRNA. Translation: AAH53416.1.
CCDSiCCDS39449.1.
RefSeqiNP_001289862.1. NM_001302933.1.
NP_001289863.1. NM_001302934.1.
NP_035959.2. NM_011829.3.
UniGeneiMm.260707.
Mm.488550.

Genome annotation databases

EnsembliENSMUST00000078155; ENSMUSP00000077289; ENSMUSG00000003500.
ENSMUST00000159124; ENSMUSP00000124931; ENSMUSG00000003500.
ENSMUST00000162099; ENSMUSP00000124541; ENSMUSG00000003500.
GeneIDi23917.
KEGGimmu:23917.
UCSCiuc009bda.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U00978 mRNA. Translation: AAA18285.1.
AK171139 mRNA. Translation: BAE42272.1.
CH466533 Genomic DNA. Translation: EDL13790.1.
BC053416 mRNA. Translation: AAH53416.1.
CCDSiCCDS39449.1.
RefSeqiNP_001289862.1. NM_001302933.1.
NP_001289863.1. NM_001302934.1.
NP_035959.2. NM_011829.3.
UniGeneiMm.260707.
Mm.488550.

3D structure databases

ProteinModelPortaliP50096.
SMRiP50096.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204791. 2 interactors.
IntActiP50096. 1 interactor.
MINTiMINT-4098666.
STRINGi10090.ENSMUSP00000077289.

PTM databases

iPTMnetiP50096.
PhosphoSitePlusiP50096.

Proteomic databases

EPDiP50096.
MaxQBiP50096.
PaxDbiP50096.
PRIDEiP50096.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000078155; ENSMUSP00000077289; ENSMUSG00000003500.
ENSMUST00000159124; ENSMUSP00000124931; ENSMUSG00000003500.
ENSMUST00000162099; ENSMUSP00000124541; ENSMUSG00000003500.
GeneIDi23917.
KEGGimmu:23917.
UCSCiuc009bda.2. mouse.

Organism-specific databases

CTDi3614.
MGIiMGI:96567. Impdh1.

Phylogenomic databases

eggNOGiENOG410ISZP. Eukaryota.
COG0517. LUCA.
GeneTreeiENSGT00530000062923.
HOGENOMiHOG000165752.
HOVERGENiHBG052122.
InParanoidiP50096.
KOiK00088.
TreeFamiTF300378.

Enzyme and pathway databases

UniPathwayiUPA00601; UER00295.
ReactomeiR-MMU-6798695. Neutrophil degranulation.
R-MMU-73817. Purine ribonucleoside monophosphate biosynthesis.

Miscellaneous databases

ChiTaRSiImpdh1. mouse.
PROiP50096.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000003500.
CleanExiMM_IMPDH1.
ExpressionAtlasiP50096. baseline and differential.
GenevisibleiP50096. MM.

Family and domain databases

CDDicd00381. IMPDH. 1 hit.
Gene3Di3.20.20.70. 1 hit.
HAMAPiMF_01964. IMPDH. 1 hit.
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...

Entry informationi

Entry nameiIMDH1_MOUSE
AccessioniPrimary (citable) accession number: P50096
Secondary accession number(s): Q7TSG7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 143 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, 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

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 one 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.