UniProtKB - P24547 (IMDH2_MOUSE)
Protein
Inosine-5'-monophosphate dehydrogenase 2
Gene
Impdh2
Organism
Mus musculus (Mouse)
Status
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
- EC:1.1.1.205UniRule annotation
Cofactori
K+UniRule annotation
Activity 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
: XMP biosynthesis via de novo pathway Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes XMP from IMP.UniRule annotationProteins known to be involved in this subpathway in this organism are:
- 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)
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 326 | Potassium; via carbonyl oxygenUniRule annotation | 1 | |
Metal bindingi | 328 | Potassium; via carbonyl oxygenUniRule annotation | 1 | |
Binding sitei | 329 | IMPUniRule annotation | 1 | |
Active sitei | 331 | Thioimidate intermediateUniRule annotation | 1 | |
Metal bindingi | 331 | Potassium; via carbonyl oxygenUniRule annotation | 1 | |
Active sitei | 429 | Proton acceptorUniRule annotation | 1 | |
Binding sitei | 441 | IMPUniRule annotation | 1 | |
Metal bindingi | 500 | Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation | 1 | |
Metal bindingi | 501 | Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation | 1 | |
Metal bindingi | 502 | Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 274 – 276 | NADUniRule annotation | 3 | |
Nucleotide bindingi | 324 – 326 | NADUniRule annotation | 3 |
GO - Molecular functioni
- DNA binding Source: UniProtKB-KW
- identical protein binding Source: MGI
- IMP dehydrogenase activity Source: MGI
- metal ion binding Source: UniProtKB-UniRule
- nucleotide binding Source: UniProtKB
- RNA binding Source: UniProtKB-KW
GO - Biological processi
- cellular response to interleukin-4 Source: MGI
- circadian rhythm Source: UniProtKB
- GMP biosynthetic process Source: UniProtKB-UniRule
- GTP biosynthetic process Source: GO_Central
- lymphocyte proliferation Source: MGI
- purine nucleotide biosynthetic process Source: MGI
- retina development in camera-type eye Source: Ensembl
Keywordsi
Molecular function | DNA-binding, Oxidoreductase, RNA-binding |
Biological process | GMP biosynthesis, Purine biosynthesis |
Ligand | Metal-binding, NAD, Potassium |
Enzyme and pathway databases
BRENDAi | 1.1.1.205, 3474 |
Reactomei | R-MMU-6798695, Neutrophil degranulation R-MMU-73817, Purine ribonucleoside monophosphate biosynthesis |
UniPathwayi | UPA00601;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 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:109367, Impdh2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000093674 | 1 – 514 | Inosine-5'-monophosphate dehydrogenase 2Add BLAST | 514 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 122 | PhosphoserineBy similarity | 1 | |
Modified residuei | 160 | PhosphoserineBy similarity | 1 | |
Cross-linki | 195 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Cross-linki | 208 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 400 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 416 | PhosphoserineCombined sources | 1 | |
Cross-linki | 438 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 511 | N6-acetyllysineBy similarity | 1 |
Post-translational modificationi
Acetylated by CLOCK in a circadian manner.By similarity
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P24547 |
jPOSTi | P24547 |
PaxDbi | P24547 |
PeptideAtlasi | P24547 |
PRIDEi | P24547 |
2D gel databases
REPRODUCTION-2DPAGEi | P24547 |
PTM databases
iPTMneti | P24547 |
PhosphoSitePlusi | P24547 |
SwissPalmi | P24547 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000062867, Expressed in liver and 90 other tissues |
ExpressionAtlasi | P24547, baseline and differential |
Genevisiblei | P24547, MM |
Interactioni
Subunit structurei
Homotetramer.
Interacts with CLOCK; in a circadian manner.
By similarityGO - Molecular functioni
- identical protein binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 204792, 15 interactors |
IntActi | P24547, 4 interactors |
MINTi | P24547 |
STRINGi | 10090.ENSMUSP00000079888 |
Chemistry databases
BindingDBi | P24547 |
Miscellaneous databases
RNActi | P24547, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 114 – 173 | CBS 1UniRule annotationAdd BLAST | 60 | |
Domaini | 179 – 237 | CBS 2UniRule annotationAdd BLAST | 59 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 364 – 366 | IMP bindingUniRule annotation | 3 | |
Regioni | 387 – 388 | IMP bindingUniRule annotation | 2 | |
Regioni | 411 – 415 | IMP bindingUniRule annotation | 5 |
Sequence similaritiesi
Belongs to the IMPDH/GMPR family.UniRule annotation
Keywords - Domaini
CBS domain, RepeatPhylogenomic databases
eggNOGi | KOG2550, Eukaryota |
GeneTreei | ENSGT00940000157726 |
InParanoidi | P24547 |
OMAi | HDYHMTL |
OrthoDBi | 618077at2759 |
PhylomeDBi | P24547 |
TreeFami | TF300378 |
Family and domain databases
CDDi | cd00381, IMPDH, 1 hit |
Gene3Di | 3.20.20.70, 2 hits |
HAMAPi | MF_01964, IMPDH, 1 hit |
InterProi | View protein in InterPro IPR013785, Aldolase_TIM IPR000644, CBS_dom IPR005990, IMP_DH IPR015875, IMP_DH/GMP_Rdtase_CS IPR001093, IMP_DH_GMPRt |
Pfami | View protein in Pfam PF00571, CBS, 2 hits PF00478, IMPDH, 1 hit |
PIRSFi | PIRSF000130, IMPDH, 1 hit |
SMARTi | View protein in SMART SM00116, CBS, 2 hits |
TIGRFAMsi | TIGR01302, IMP_dehydrog, 1 hit |
PROSITEi | View protein in PROSITE PS51371, CBS, 2 hits PS00487, IMP_DH_GMP_RED, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
P24547-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0A6YXS4 | A0A0A6YXS4_MOUSE | Inosine-5'-monophosphate dehydrogen... | Impdh2 | 248 | Annotation score: | ||
A0A0A6YY72 | A0A0A6YY72_MOUSE | Inosine-5'-monophosphate dehydrogen... | Impdh2 | 320 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 458 | P → L AA sequence (PubMed:2572589).Curated | 1 | |
Sequence conflicti | 465 | Q → S AA sequence (PubMed:2572589).Curated | 1 | |
Sequence conflicti | 483 | M → T in AAA39311 (PubMed:1671845).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 333 | T → I in mycophenolic acid resistant cells. | 1 | |
Natural varianti | 351 | S → Y in mycophenolic acid resistant cells. | 1 |
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 |
CCDSi | CCDS40768.1 |
PIRi | JT0565 |
RefSeqi | NP_035960.2, NM_011830.3 |
Genome annotation databases
Ensembli | ENSMUST00000081111; ENSMUSP00000079888; ENSMUSG00000062867 |
GeneIDi | 23918 |
KEGGi | mmu:23918 |
UCSCi | uc009rqg.1, mouse |
Similar proteinsi
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 |
CCDSi | CCDS40768.1 |
PIRi | JT0565 |
RefSeqi | NP_035960.2, NM_011830.3 |
3D structure databases
SMRi | P24547 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 204792, 15 interactors |
IntActi | P24547, 4 interactors |
MINTi | P24547 |
STRINGi | 10090.ENSMUSP00000079888 |
Chemistry databases
BindingDBi | P24547 |
ChEMBLi | CHEMBL3169 |
PTM databases
iPTMneti | P24547 |
PhosphoSitePlusi | P24547 |
SwissPalmi | P24547 |
2D gel databases
REPRODUCTION-2DPAGEi | P24547 |
Proteomic databases
EPDi | P24547 |
jPOSTi | P24547 |
PaxDbi | P24547 |
PeptideAtlasi | P24547 |
PRIDEi | P24547 |
Protocols and materials databases
Antibodypediai | 30367, 361 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000081111; ENSMUSP00000079888; ENSMUSG00000062867 |
GeneIDi | 23918 |
KEGGi | mmu:23918 |
UCSCi | uc009rqg.1, mouse |
Organism-specific databases
CTDi | 3615 |
MGIi | MGI:109367, Impdh2 |
Phylogenomic databases
eggNOGi | KOG2550, Eukaryota |
GeneTreei | ENSGT00940000157726 |
InParanoidi | P24547 |
OMAi | HDYHMTL |
OrthoDBi | 618077at2759 |
PhylomeDBi | P24547 |
TreeFami | TF300378 |
Enzyme and pathway databases
UniPathwayi | UPA00601;UER00295 |
BRENDAi | 1.1.1.205, 3474 |
Reactomei | R-MMU-6798695, Neutrophil degranulation R-MMU-73817, Purine ribonucleoside monophosphate biosynthesis |
Miscellaneous databases
BioGRID-ORCSi | 23918, 7 hits in 18 CRISPR screens |
ChiTaRSi | Impdh2, mouse |
PROi | PR:P24547 |
RNActi | P24547, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000062867, Expressed in liver and 90 other tissues |
ExpressionAtlasi | P24547, baseline and differential |
Genevisiblei | P24547, MM |
Family and domain databases
CDDi | cd00381, IMPDH, 1 hit |
Gene3Di | 3.20.20.70, 2 hits |
HAMAPi | MF_01964, IMPDH, 1 hit |
InterProi | View protein in InterPro IPR013785, Aldolase_TIM IPR000644, CBS_dom IPR005990, IMP_DH IPR015875, IMP_DH/GMP_Rdtase_CS IPR001093, IMP_DH_GMPRt |
Pfami | View protein in Pfam PF00571, CBS, 2 hits PF00478, IMPDH, 1 hit |
PIRSFi | PIRSF000130, IMPDH, 1 hit |
SMARTi | View protein in SMART SM00116, CBS, 2 hits |
TIGRFAMsi | TIGR01302, IMP_dehydrog, 1 hit |
PROSITEi | View protein in PROSITE PS51371, CBS, 2 hits PS00487, IMP_DH_GMP_RED, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | IMDH2_MOUSE | |
Accessioni | P24547Primary (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: | December 2, 2020 | |
This is version 196 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families