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
Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
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

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 (Impdh), Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2), Inosine-5'-monophosphate dehydrogenase (Impdh)
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
Binding sitei276Inhibitor1
Metal bindingi326Potassium; via carbonyl oxygenUniRule annotation1
Metal bindingi328Potassium; via carbonyl oxygenUniRule annotation1
Binding sitei329IMP1
Active sitei331Thioimidate intermediate1
Metal bindingi331Potassium; via carbonyl oxygenUniRule annotation1
Binding sitei333Inhibitor1
Active sitei429Proton acceptorUniRule annotation1
Binding sitei441IMP1
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

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 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
OrganismiCricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Taxonomic identifieri10029 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeCricetinaeCricetulus
Proteomesi
  • UP000001075 Componenti: Unassembled WGS sequence

Subcellular locationi

  • Cytoplasm UniRule annotation
  • Nucleus UniRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi275S → A: No effect. 1 Publication1
Mutagenesisi276S → A: Increases Ki for MPA 7-fold. 1 Publication1
Mutagenesisi329S → A: Reduces activity by 87%. 1 Publication1
Mutagenesisi331C → A: Loss of activity. 1 Publication1
Mutagenesisi333T → I: Increases Ki for MPA 300-fold. 1 Publication1
Mutagenesisi364D → A: Loss of activity. 1 Publication1
Mutagenesisi368Q → A: No effect. 1 Publication1
Mutagenesisi441Q → A: Reduces activity by over 95% and increases Ki for MPA 25-fold. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000936722 – 514Inosine-5'-monophosphate dehydrogenase 2Add BLAST513

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei122PhosphoserineBy similarity1
Modified residuei160PhosphoserineBy similarity1
Modified residuei400PhosphotyrosineBy similarity1
Modified residuei416PhosphoserineBy similarity1
Modified residuei511N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PRIDEiP12269.

Interactioni

Subunit structurei

Homotetramer.UniRule annotation1 Publication

Structurei

Secondary structure

1514
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi20 – 23Combined sources4
Helixi32 – 34Combined sources3
Beta strandi35 – 37Combined sources3
Helixi46 – 48Combined sources3
Beta strandi53 – 58Combined sources6
Beta strandi60 – 63Combined sources4
Beta strandi65 – 67Combined sources3
Turni71 – 73Combined sources3
Helixi76 – 85Combined sources10
Beta strandi88 – 91Combined sources4
Helixi97 – 108Combined sources12
Beta strandi113 – 115Combined sources3
Helixi194 – 200Combined sources7
Beta strandi210 – 213Combined sources4
Turni214 – 216Combined sources3
Beta strandi217 – 222Combined sources6
Helixi224 – 232Combined sources9
Beta strandi247 – 250Combined sources4
Helixi255 – 266Combined sources12
Beta strandi270 – 273Combined sources4
Helixi281 – 293Combined sources13
Beta strandi298 – 304Combined sources7
Helixi307 – 316Combined sources10
Beta strandi319 – 323Combined sources5
Helixi333 – 337Combined sources5
Helixi343 – 354Combined sources12
Helixi355 – 357Combined sources3
Beta strandi361 – 365Combined sources5
Helixi370 – 378Combined sources9
Beta strandi382 – 387Combined sources6
Turni388 – 392Combined sources5
Beta strandi396 – 398Combined sources3
Beta strandi401 – 405Combined sources5
Beta strandi407 – 412Combined sources6
Turni417 – 419Combined sources3
Beta strandi444 – 448Combined sources5
Helixi453 – 470Combined sources18
Helixi476 – 485Combined sources10
Beta strandi490 – 492Combined sources3
Helixi495 – 501Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JR1X-ray2.60A/B1-514[»]
ProteinModelPortaliP12269.
SMRiP12269.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP12269.

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 binding3
Regioni387 – 388IMP binding2
Regioni411 – 415IMP binding5

Sequence similaritiesi

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

Keywords - Domaini

CBS domain, Repeat

Phylogenomic databases

HOVERGENiHBG052122.
InParanoidiP12269.
KOiK00088.

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.

P12269-1 [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 GITLKEANEI
210 220 230 240 250
LQRSKKGKLP IVNENDELVA IIARTDLKKN RDYPLASKDA KKQLLCGAAI
260 270 280 290 300
GTHEDDKYRL DLLALAGVDV VVLDSSQGNS IFQINMIKYM KEKYPNLQVI
310 320 330 340 350
GGNVVTAAQA KNLIDAGVDA LRVGMGCGSI 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):55,890
Last modified:October 1, 1989 - v1
Checksum:i5FA0138FA41E8A02
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
J04209 mRNA. Translation: AAA36993.1.
JH001800 Genomic DNA. Translation: EGW10487.1.
RefSeqiNP_001233751.1. NM_001246822.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JR1X-ray2.60A/B1-514[»]
ProteinModelPortaliP12269.
SMRiP12269.
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PRIDEiP12269.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100689398.
KEGGicge:100689398.

Organism-specific databases

CTDi3615.

Phylogenomic databases

HOVERGENiHBG052122.
InParanoidiP12269.
KOiK00088.

Enzyme and pathway databases

UniPathwayiUPA00601; UER00295.

Miscellaneous databases

EvolutionaryTraceiP12269.
PROiP12269.

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_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: November 2, 2016
This is version 133 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, Reference proteome

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

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.