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Protein

Inosine-5'-monophosphate dehydrogenase 2

Gene

IMPDH2

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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

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

  1. adenyl nucleotide binding Source: InterPro
  2. DNA binding Source: UniProtKB-KW
  3. IMP dehydrogenase activity Source: UniProtKB-HAMAP
  4. metal ion binding Source: UniProtKB-HAMAP
  5. nucleotide binding Source: UniProtKB
  6. RNA binding Source: UniProtKB-KW

GO - Biological processi

  1. cellular response to interleukin-4 Source: Ensembl
  2. GMP biosynthetic process Source: UniProtKB-HAMAP
  3. lymphocyte proliferation 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

ReactomeiREACT_226478. 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:IMPDH2UniRule annotation
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
ProteomesiUP000009136: Chromosome 22

Subcellular locationi

Cytoplasm UniRule annotation. Nucleus UniRule annotation

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. extracellular vesicular exosome Source: Ensembl
  3. nucleus Source: UniProtKB
  4. peroxisomal membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedUniRule annotation
Chaini2 – 514513Inosine-5'-monophosphate dehydrogenase 2PRO_0000239736Add
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

PaxDbiQ3SWY3.
PRIDEiQ3SWY3.

Interactioni

Subunit structurei

Homotetramer.UniRule annotation

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000025179.

Structurei

3D structure databases

ProteinModelPortaliQ3SWY3.
SMRiQ3SWY3. 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.
GeneTreeiENSGT00530000062923.
HOGENOMiHOG000165752.
HOVERGENiHBG052122.
InParanoidiQ3SWY3.
KOiK00088.
OMAiRVRDVFQ.
OrthoDBiEOG7VTDMM.
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.

Q3SWY3-1 [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 LSPRDRVRDV FEAKARHGFC GIPITDTGRM
160 170 180 190 200
GSHLVGIISS RDIDFLKEEE HDRLLGEIMT KREDLVVAPA GITLKEANEI
210 220 230 240 250
LQRSKKGKLP IVNENDELVA IIARTDLKKN RDYPLASKDA KKQLLCGAAI
260 270 280 290 300
GTHEDDKYRL DLLSQAGVDV VVLDSSQGNS IFQINMIKYI KEKYPSIQVI
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):55,763
Last modified:October 11, 2005 - v1
Checksum:iC41BB20F7FB604BA
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC104602 mRNA. Translation: AAI04603.1.
RefSeqiNP_001029588.1. NM_001034416.1.
UniGeneiBt.2255.

Genome annotation databases

EnsembliENSBTAT00000025179; ENSBTAP00000025179; ENSBTAG00000031837.
GeneIDi511969.
KEGGibta:511969.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC104602 mRNA. Translation: AAI04603.1.
RefSeqiNP_001029588.1. NM_001034416.1.
UniGeneiBt.2255.

3D structure databases

ProteinModelPortaliQ3SWY3.
SMRiQ3SWY3. Positions 10-514.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000025179.

Proteomic databases

PaxDbiQ3SWY3.
PRIDEiQ3SWY3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000025179; ENSBTAP00000025179; ENSBTAG00000031837.
GeneIDi511969.
KEGGibta:511969.

Organism-specific databases

CTDi3615.

Phylogenomic databases

eggNOGiCOG0517.
GeneTreeiENSGT00530000062923.
HOGENOMiHOG000165752.
HOVERGENiHBG052122.
InParanoidiQ3SWY3.
KOiK00088.
OMAiRVRDVFQ.
OrthoDBiEOG7VTDMM.
TreeFamiTF300378.

Enzyme and pathway databases

UniPathwayiUPA00601; UER00295.
ReactomeiREACT_226478. Purine ribonucleoside monophosphate biosynthesis.

Miscellaneous databases

NextBioi20870189.

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

  1. NIH - Mammalian Gene Collection (MGC) project
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Ascending colon.

Entry informationi

Entry nameiIMDH2_BOVIN
AccessioniPrimary (citable) accession number: Q3SWY3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 13, 2006
Last sequence update: October 11, 2005
Last modified: January 7, 2015
This is version 77 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

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.