Inosine-5'-monophosphate dehydrogenase 2

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Reviewed, UniProtKB/Swiss-Prot P12268 (IMDH2_HUMAN)

Last modified June 16, 2009. Version 120. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Inosine-5'-monophosphate dehydrogenase 2
      Short name=IMP dehydrogenase 2
    EC=1.1.1.205
Alternative name(s):
    IMPDH-II
    IMPD 2

Gene names

Name:	IMPDH2
Synonyms:	IMPD2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	514 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Rate limiting enzyme in the de novo synthesis of guanine nucleotides and therefore is involved in the regulation of cell growth. It may also have a role in the development of malignancy and the growth progression of some tumors.
Catalytic activity	Inosine 5'-phosphate + NAD⁺ + H₂O = xanthosine 5'-phosphate + NADH.
Cofactor	Potassium.
Pathway	Purine metabolism; XMP biosynthesis via de novo pathway; XMP from IMP: step 1/1.
Subunit structure	Homotetramer.
Tissue specificity	IMP type I is the main species in normal leukocytes and type II predominates over type I in the tumor.
Post-translational modification	The N-terminus is blocked.
Sequence similarities	Belongs to the IMPDH/GMPR family. Contains 2 CBS domains.

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Ontologies

Keywords
Biological process	GMP biosynthesis Purine biosynthesis
Domain	CBS domain Repeat
Ligand	Metal-binding NAD Potassium
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	GMP biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from Experiment. Source: Reactome
Molecular function	IMP dehydrogenase activity Ref.2 Inferred from Experiment. Source: Reactome potassium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct
BCAR3	O75815	1	EBI-353389,EBI-702336
IKBKE	Q14164	1	EBI-353389,EBI-307369
VHL	P40337	1	EBI-353389,EBI-301246

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 514

514

Inosine-5'-monophosphate dehydrogenase 2

PRO_0000093673

Regions

Domain

114 – 173

CBS 1

Domain

179 – 237

CBS 2

Nucleotide binding

253 – 276

NAD

Sites

Active site

331

Thioimidate intermediate Ref.11

Metal binding

326

Potassium; via carbonyl oxygen By similarity

Metal binding

328

Potassium; via carbonyl oxygen By similarity

Binding site

276

Inhibitor

Binding site

333

Inhibitor

Binding site

364

IMP

Binding site

411

IMP

Amino acid modifications

Modified residue

122

Phosphoserine Ref.9

Modified residue

400

Phosphotyrosine Ref.8

Experimental info

Sequence conflict

190 – 191

AG → RS in AAA36112. Ref.1

Secondary structure

514

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P12268-1 [UniParc].

Last modified May 1, 1991. Version 2.
Checksum: 876BEA0EC1DDBEE9
Show »

FASTA

514

55,805

        10         20         30         40         50         60 
MADYLISGGT SYVPDDGLTA QQLFNCGDGL TYNDFLILPG YIDFTADQVD LTSALTKKIT 

        70         80         90        100        110        120 
LKTPLVSSPM DTVTEAGMAI AMALTGGIGF IHHNCTPEFQ ANEVRKVKKY EQGFITDPVV 

       130        140        150        160        170        180 
LSPKDRVRDV FEAKARHGFC GIPITDTGRM GSRLVGIISS RDIDFLKEEE HDCFLEEIMT 

       190        200        210        220        230        240 
KREDLVVAPA GITLKEANEI LQRSKKGKLP IVNEDDELVA IIARTDLKKN RDYPLASKDA 

       250        260        270        280        290        300 
KKQLLCGAAI GTHEDDKYRL DLLAQAGVDV VVLDSSQGNS IFQINMIKYI KDKYPNLQVI 

       310        320        330        340        350        360 
GGNVVTAAQA KNLIDAGVDA LRVGMGSGSI CITQEVLACG RPQATAVYKV SEYARRFGVP 

       370        380        390        400        410        420 
VIADGGIQNV GHIAKALALG ASTVMMGSLL AATTEAPGEY FFSDGIRLKK YRGMGSLDAM 

       430        440        450        460        470        480 
DKHLSSQNRY FSEADKIKVA QGVSGAVQDK GSIHKFVPYL IAGIQHSCQD IGAKSLTQVR 

       490        500        510 
AMMYSGELKF EKRTSSAQVE GGVHSLHSYE KRLF

« Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 2902093] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"Two distinct cDNAs for human IMP dehydrogenase." Natsumeda Y., Ohno S., Kawasaki H., Konno Y., Weber G., Suzuki K. J. Biol. Chem. 265:5292-5295(1990) [PubMed: 1969416] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Spleen.
[3]	"Cloning and sequence of the human type II IMP dehydrogenase gene." Glesne D.A., Huberman E. Biochem. Biophys. Res. Commun. 205:537-544(1994) [PubMed: 7999076] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Blood.
[4]	"Characterization of the human inosine-5'-monophosphate dehydrogenase type II gene." Zimmermann A.G., Spychala J., Mitchell B.S. J. Biol. Chem. 270:6808-6814(1995) [PubMed: 7896827] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: B-cell, Colon and Placenta.
[6]	"Chromosomal localization and structure of the human type II IMP dehydrogenase gene." Glesne D.A., Collart F.R., Varkony T., Drabkin H., Huberman E. Genomics 16:274-277(1993) [PubMed: 8098009] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 461-514.
[7]	"Recombinant human inosine monophosphate dehydrogenase type I and type II proteins. Purification and characterization of inhibitor binding." Hager P.W., Collart F.R., Huberman E., Mitchell B.S. Biochem. Pharmacol. 49:1323-1329(1995) [PubMed: 7763314] [Abstract] Cited for: CHARACTERIZATION.
[8]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-400, MASS SPECTROMETRY.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122, MASS SPECTROMETRY.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]	"Crystal structure of human type II inosine monophosphate dehydrogenase: implications for ligand binding and drug design." Colby T.D., Vanderveen K., Strickler M.D., Markham G.D., Goldstein B.M. Proc. Natl. Acad. Sci. U.S.A. 96:3531-3536(1999) [PubMed: 10097070] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS), ACTIVE SITE.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

J04208 mRNA. Translation: AAA36112.1.
L33842 Genomic DNA. Translation: AAA67054.1.
L39210 Genomic DNA. Translation: AAB70699.1.
BC006124 mRNA. Translation: AAH06124.1.
BC012840 mRNA. Translation: AAH12840.1.
BC015567 mRNA. Translation: AAH15567.1.
L08114 Genomic DNA. Translation: AAA36113.1.

IPI

IPI00291510.

PIR

A31997. I52303.

RefSeq

NP_000875.2.

UniGene

Hs.654400

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B3O	X-ray	2.90	A/B	1-514	[»]
1NF7	X-ray	2.65	A/B	1-514	[»]
1NFB	X-ray	2.90	A/B	1-514	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P12268. 13 interactions.

PTM databases

PhosphoSite

P12268.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00291510.
P12268.

Proteomic databases

PeptideAtlas

P12268.

PRIDE

P12268.

Genome annotation databases

Ensembl

ENSG00000178035. Homo sapiens. [Contig view]

GeneID

3615.

KEGG

hsa:3615.

NMPDR

fig|9606.3.peg.22511.

Organism-specific databases

GeneCards

GC03M049036.

H-InvDB

HIX0018053.

HGNC

HGNC:6053. IMPDH2.

HPA

HPA001400.

MIM

146691. gene.

PharmGKB

PA29863.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P12268.

HOVERGEN

P12268.

OMA

P12268. LGEIMTK.

Enzyme and pathway databases

BRENDA

1.1.1.205. 247.

Reactome

REACT_1698. Nucleotide metabolism.

Gene expression databases

Bgee

P12268.

CleanEx

HS_IMPDH2.

GermOnline

ENSG00000178035. Homo sapiens.

Family and domain databases

InterPro

IPR013785. Aldolase_TIM.
IPR000644. Cysta_beta_synth_core.
IPR005990. IMP_DH.
IPR015875. IMP_DH/GMP_Rdtase_CS.
IPR001093. IMP_DH_GMPRt.
IPR018529. IMP_DH_rel.
[Graphical view]

Gene3D

G3DSA:3.20.20.70. Aldolase_TIM. 1 hit.

Pfam

PF00571. CBS. 1 hit.
PF00478. IMPDH. 1 hit.
[Graphical view]

PIRSF

PIRSF000130. IMPDH. 1 hit.

SMART

SM00116. CBS. 2 hits.
[Graphical view]

TIGRFAMs

TIGR01302. IMP_dehydrog. 1 hit.

PROSITE

PS51371. CBS. 2 hits.
PS00487. IMP_DH_GMP_RED. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

BindingDB

P12268.

DrugBank

DB00688. Mycophenolate mofetil.
DB01024. Mycophenolic acid.
DB00157. NADH.

NextBio

14143.

SOURCE

Search...

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Entry information

Entry name

IMDH2_HUMAN

Accession

Primary (citable) accession number: P12268
Secondary accession number(s): Q6LEF3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	May 1, 1991
Last modified:	June 16, 2009
This is version 120 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

2-D gel databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents