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P12269

- IMDH2_CRIGR

UniProt

P12269 - IMDH2_CRIGR

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Protein

Inosine-5'-monophosphate dehydrogenase 2

Gene
IMPDH2
Organism
Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Status
Reviewed - 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 By similarity. 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

Potassium.

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 By similarity.UniRule annotation

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei276 – 2761Inhibitor
Metal bindingi326 – 3261Potassium; via carbonyl oxygen By similarity
Metal bindingi328 – 3281Potassium; via carbonyl oxygen By similarity
Binding sitei329 – 3291IMP
Active sitei331 – 3311Thioimidate intermediate
Metal bindingi331 – 3311Potassium; via carbonyl oxygen By similarity
Binding sitei333 – 3331Inhibitor
Binding sitei441 – 4411IMP
Metal bindingi500 – 5001Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Metal bindingi501 – 5011Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Metal bindingi502 – 5021Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi274 – 2763NAD By similarity
Nucleotide bindingi324 – 3263NAD By similarity

GO - Molecular functioni

  1. adenyl nucleotide binding Source: InterPro
  2. IMP dehydrogenase activity Source: UniProtKB-HAMAP
  3. metal ion binding Source: UniProtKB-HAMAP
  4. nucleotide binding Source: UniProtKB

GO - Biological processi

  1. GMP biosynthetic process Source: UniProtKB-HAMAP
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

GMP biosynthesis, Purine biosynthesis

Keywords - Ligandi

Metal-binding, NAD, Potassium

Enzyme and pathway databases

UniPathwayiUPA00601; UER00295.

Names & Taxonomyi

Protein namesi
Recommended name:
Inosine-5'-monophosphate dehydrogenase 2 (EC:1.1.1.205)
Short name:
IMP dehydrogenase 2
Short name:
IMPD 2
Short name:
IMPDH 2
Alternative name(s):
IMPDH-II
Gene namesi
Name:IMPDH2
OrganismiCricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Taxonomic identifieri10029 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeCricetinaeCricetulus
ProteomesiUP000001075: Unassembled WGS sequence

Subcellular locationi

Cytoplasm By similarity. Nucleus By similarity UniRule annotation

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi275 – 2751S → A: No effect. 1 Publication
Mutagenesisi276 – 2761S → A: Increases Ki for MPA 7-fold. 1 Publication
Mutagenesisi329 – 3291S → A: Reduces activity by 87%. 1 Publication
Mutagenesisi331 – 3311C → A: Loss of activity. 1 Publication
Mutagenesisi333 – 3331T → I: Increases Ki for MPA 300-fold. 1 Publication
Mutagenesisi364 – 3641D → A: Loss of activity. 1 Publication
Mutagenesisi368 – 3681Q → A: No effect. 1 Publication
Mutagenesisi441 – 4411Q → A: Reduces activity by over 95% and increases Ki for MPA 25-fold. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 514513Inosine-5'-monophosphate dehydrogenase 2UniRule annotationPRO_0000093672Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei122 – 1221Phosphoserine By similarity
Modified residuei400 – 4001Phosphotyrosine By similarity
Modified residuei416 – 4161Phosphoserine By similarity
Modified residuei511 – 5111N6-acetyllysine By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PRIDEiP12269.

Interactioni

Subunit structurei

Homotetramer.

Structurei

Secondary structure

1
514
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi20 – 234
Helixi32 – 343
Beta strandi35 – 373
Helixi46 – 483
Beta strandi53 – 586
Beta strandi60 – 634
Beta strandi65 – 673
Turni71 – 733
Helixi76 – 8510
Beta strandi88 – 914
Helixi97 – 10812
Beta strandi113 – 1153
Helixi194 – 2007
Beta strandi210 – 2134
Turni214 – 2163
Beta strandi217 – 2226
Helixi224 – 2329
Beta strandi247 – 2504
Helixi255 – 26612
Beta strandi270 – 2734
Helixi281 – 29313
Beta strandi298 – 3047
Helixi307 – 31610
Beta strandi319 – 3235
Helixi333 – 3375
Helixi343 – 35412
Helixi355 – 3573
Beta strandi361 – 3655
Helixi370 – 3789
Beta strandi382 – 3876
Turni388 – 3925
Beta strandi396 – 3983
Beta strandi401 – 4055
Beta strandi407 – 4126
Turni417 – 4193
Beta strandi444 – 4485
Helixi453 – 47018
Helixi476 – 48510
Beta strandi490 – 4923
Helixi495 – 5017

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1JR1X-ray2.60A/B1-514[»]
ProteinModelPortaliP12269.
SMRiP12269. Positions 10-514.

Miscellaneous databases

EvolutionaryTraceiP12269.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini114 – 17360CBS 1Add
BLAST
Domaini179 – 23759CBS 2Add
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.
Contains 2 CBS domains.

Keywords - Domaini

CBS domain, Repeat

Phylogenomic databases

HOVERGENiHBG052122.
KOiK00088.

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.

P12269-1 [UniParc]FASTAAdd to Basket

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MADYLISGGT SYVPDDGLTA QQLFNCGDGL TYNDFLILPG YIDFTADQVD    50
LTSALTKKIT LKTPLVSSPM DTVTEAGMAI AMALTGGIGF IHHNCTPEFQ 100
ANEVRKVKKY EQGFITDPVV LSPKDRVRDV FEAKARHGFC GIPITDTGRM 150
GSRLVGIISS RDIDFLKEEE HDRFLEEIMT KREDLVVAPA GITLKEANEI 200
LQRSKKGKLP IVNENDELVA IIARTDLKKN RDYPLASKDA KKQLLCGAAI 250
GTHEDDKYRL DLLALAGVDV VVLDSSQGNS IFQINMIKYM KEKYPNLQVI 300
GGNVVTAAQA KNLIDAGVDA LRVGMGCGSI CITQEVLACG RPQATAVYKV 350
SEYARRFGVP VIADGGIQNV GHIAKALALG ASTVMMGSLL AATTEAPGEY 400
FFSDGIRLKK YRGMGSLDAM DKHLSSQNRY FSEADKIKVA QGVSGAVQDK 450
GSIHKFVPYL IAGIQHSCQD IGAKSLTQVR AMMYSGELKF EKRTSSAQVE 500
GGVHSLHSYE KRLF 514
Length:514
Mass (Da):55,890
Last modified:October 1, 1989 - v1
Checksum:i5FA0138FA41E8A02
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J04209 mRNA. Translation: AAA36993.1.
JH001800 Genomic DNA. Translation: EGW10487.1.
RefSeqiNP_001233751.1. NM_001246822.1.

Genome annotation databases

GeneIDi100689398.
KEGGicge:100689398.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J04209 mRNA. Translation: AAA36993.1 .
JH001800 Genomic DNA. Translation: EGW10487.1 .
RefSeqi NP_001233751.1. NM_001246822.1.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1JR1 X-ray 2.60 A/B 1-514 [» ]
ProteinModelPortali P12269.
SMRi P12269. Positions 10-514.
ModBasei Search...
MobiDBi Search...

Chemistry

DrugBanki DB01024. Mycophenolic acid.

Proteomic databases

PRIDEi P12269.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 100689398.
KEGGi cge:100689398.

Organism-specific databases

CTDi 3615.

Phylogenomic databases

HOVERGENi HBG052122.
KOi K00088.

Enzyme and pathway databases

UniPathwayi UPA00601 ; UER00295 .

Miscellaneous databases

EvolutionaryTracei P12269.

Family and domain databases

Gene3Di 3.20.20.70. 1 hit.
HAMAPi MF_01964. IMPDH.
InterProi IPR013785. Aldolase_TIM.
IPR000644. CBS_dom.
IPR005990. IMP_DH.
IPR015875. IMP_DH/GMP_Rdtase_CS.
IPR001093. IMP_DH_GMPRt.
[Graphical view ]
Pfami PF00571. CBS. 2 hits.
PF00478. IMPDH. 1 hit.
[Graphical view ]
PIRSFi PIRSF000130. IMPDH. 1 hit.
SMARTi SM00116. CBS. 2 hits.
[Graphical view ]
TIGRFAMsi TIGR01302. IMP_dehydrog. 1 hit.
PROSITEi PS51371. CBS. 2 hits.
PS00487. IMP_DH_GMP_RED. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and sequence analysis of the human and Chinese hamster inosine-5'-monophosphate dehydrogenase cDNAs."
    Collart F.R., Huberman E.
    J. Biol. Chem. 263:15769-15772(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 336-370.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "Structure and mechanism of inosine monophosphate dehydrogenase in complex with the immunosuppressant mycophenolic acid."
    Sintchak M.D., Fleming M.A., Futer O., Raybuck S.A., Chambers S.P., Caron P.R., Murcko M.A., Wilson K.P.
    Cell 85:921-930(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND THE INHIBITOR MYCOPHENOLIC ACID (MPA), MUTAGENESIS OF SER-275; SER-276; SER-329; CYS-331; THR-333; ASP-364; GLN-368 AND GLN-441.

Entry informationi

Entry nameiIMDH2_CRIGR
AccessioniPrimary (citable) accession number: P12269
Secondary accession number(s): G3IB73
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: September 3, 2014
This is version 118 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

3D-structure, Complete proteome, Direct protein sequencing

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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