Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Inosine-5'-monophosphate dehydrogenase 2

Gene

Impdh2

Organism
Rattus norvegicus (Rat)
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 (Impdh1), Inosine-5'-monophosphate dehydrogenase (Impdh2), Inosine-5'-monophosphate dehydrogenase 2 (Impdh2), Inosine-5'-monophosphate dehydrogenase 1 (Impdh1)
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

  • IMP dehydrogenase activity Source: RGD
  • metal ion binding Source: UniProtKB-HAMAP
  • nucleotide binding Source: UniProtKB-HAMAP

GO - Biological processi

  • cellular response to interleukin-4 Source: Ensembl
  • GMP biosynthetic process Source: UniProtKB-HAMAP
  • GTP biosynthetic process Source: GO_Central
  • lymphocyte proliferation Source: Ensembl
  • protein homotetramerization Source: RGD
  • purine nucleotide biosynthetic process Source: RGD
  • retina development in camera-type eye Source: RGD
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-RNO-6798695. Neutrophil degranulation.
R-RNO-73817. 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
Gene namesi
Name:Impdh2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi735092. 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)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00004156742 – 514Inosine-5'-monophosphate dehydrogenase 2Add BLAST513

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei122PhosphoserineBy similarity1
Modified residuei160PhosphoserineBy similarity1
Modified residuei400PhosphotyrosineBy similarity1
Modified residuei416PhosphoserineCombined sources1
Modified residuei511N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiE9PU28.
PeptideAtlasiE9PU28.
PRIDEiE9PU28.

PTM databases

iPTMnetiE9PU28.
PhosphoSitePlusiE9PU28.

Expressioni

Gene expression databases

BgeeiENSRNOG00000031965.
GenevisibleiE9PU28. RN.

Interactioni

Subunit structurei

Homotetramer.UniRule annotation

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000040635.

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

eggNOGiKOG2550. Eukaryota.
COG0516. LUCA.
COG0517. LUCA.
GeneTreeiENSGT00530000062923.
InParanoidiE9PU28.
OMAiIHKFIPY.
OrthoDBiEOG091G0EAV.
PhylomeDBiE9PU28.
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.

E9PU28-1 [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 IVNESDELVA IIARTDLKKN RDYPLASKDT KKQLLCGAAI
260 270 280 290 300
GTHEDDKYRL DLLALAGVDV VVLDSSQGNS IFQINMIKYI KEKYPNLQVI
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
GGVHGLHSYE KRLF
Length:514
Mass (Da):55,815
Last modified:April 5, 2011 - v1
Checksum:i033F6EED4CF64EA6
GO

Sequence databases

UniGeneiRn.8093.

Genome annotation databases

EnsembliENSRNOT00000047717; ENSRNOP00000040635; ENSRNOG00000031965.

Cross-referencesi

Sequence databases

UniGeneiRn.8093.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000040635.

PTM databases

iPTMnetiE9PU28.
PhosphoSitePlusiE9PU28.

Proteomic databases

PaxDbiE9PU28.
PeptideAtlasiE9PU28.
PRIDEiE9PU28.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000047717; ENSRNOP00000040635; ENSRNOG00000031965.

Organism-specific databases

RGDi735092. Impdh2.

Phylogenomic databases

eggNOGiKOG2550. Eukaryota.
COG0516. LUCA.
COG0517. LUCA.
GeneTreeiENSGT00530000062923.
InParanoidiE9PU28.
OMAiIHKFIPY.
OrthoDBiEOG091G0EAV.
PhylomeDBiE9PU28.
TreeFamiTF300378.

Enzyme and pathway databases

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

Miscellaneous databases

PROiE9PU28.

Gene expression databases

BgeeiENSRNOG00000031965.
GenevisibleiE9PU28. RN.

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 nameiIMDH2_RAT
AccessioniPrimary (citable) accession number: E9PU28
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 22, 2012
Last sequence update: April 5, 2011
Last modified: November 30, 2016
This is version 45 of the entry and version 1 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. 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.