P12268 (IMDH2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inosine-5'-monophosphate dehydrogenase 2
Short name=IMP dehydrogenase 2
Short name=IMPD 2
Short name=IMPDH 2
EC=1.1.1.205

Alternative name(s):
IMPDH-II

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

Protein attributes

Sequence length	514 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

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. 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.
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.
Subcellular location	Cytoplasm. Nucleus Ref.8.
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.

Ontologies

Keywords
Biological process	GMP biosynthesis Purine biosynthesis
Cellular component	Cytoplasm Nucleus
Domain	CBS domain Repeat
Ligand	DNA-binding Metal-binding NAD Potassium RNA-binding
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	GMP biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW purine base metabolic process Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay Ref.8. Source: UniProtKB
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW IMP dehydrogenase activity Traceable author statement. Source: ProtInc RNA binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW nucleotide binding Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

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

60

CBS 1

Domain

179 – 237

59

CBS 2

Nucleotide binding

253 – 276

24

NAD

Region

329 – 331

3

IMP binding

Region

364 – 366

3

IMP binding

Region

387 – 388

2

IMP binding

Region

411 – 415

5

IMP binding By similarity

Region

441 – 442

2

IMP binding By similarity

Sites

Active site

331

1

Thioimidate intermediate Ref.16

Metal binding

326

1

Potassium; via carbonyl oxygen By similarity

Metal binding

328

1

Potassium; via carbonyl oxygen By similarity

Binding site

68

1

IMP

Binding site

276

1

Inhibitor

Binding site

322

1

IMP

Binding site

333

1

Inhibitor

Amino acid modifications

Modified residue

122

1

Phosphoserine Ref.11 Ref.12

Modified residue

400

1

Phosphotyrosine Ref.9

Modified residue

416

1

Phosphoserine Ref.10 Ref.12 Ref.13

Modified residue

511

1

N6-acetyllysine Ref.14

Experimental info

Sequence conflict

190 – 191

2

AG → RS in AAA36112. Ref.1

Secondary structure

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514

Helix Strand Turn

Details...

Beta strand

17 – 19

3

Helix

20 – 23

4

Beta strand

24 – 27

4

Helix

32 – 34

3

Beta strand

35 – 37

3

Helix

46 – 48

3

Beta strand

53 – 56

4

Beta strand

59 – 63

5

Beta strand

65 – 67

3

Turn

71 – 73

3

Helix

77 – 84

8

Beta strand

89 – 91

3

Helix

97 – 107

11

Beta strand

247 – 250

4

Helix

254 – 265

12

Beta strand

270 – 273

4

Helix

281 – 293

13

Beta strand

297 – 304

8

Helix

307 – 315

9

Beta strand

319 – 323

5

Helix

343 – 354

12

Helix

355 – 357

3

Beta strand

361 – 365

5

Helix

370 – 378

9

Beta strand

382 – 387

6

Turn

388 – 392

5

Beta strand

393 – 397

5

Helix

453 – 470

18

Helix

476 – 485

10

Beta strand

488 – 492

5

Helix

495 – 497

3

Beta strand

507 – 510

4

Sequences

	Sequence		Length	Mass (Da)
	P12268 [UniParc]. Last modified May 1, 1991. Version 2. Checksum: 876BEA0EC1DDBEE9	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

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]	"Inosine 5'-monophosphate dehydrogenase binds nucleic acids in vitro and in vivo." McLean J.E., Hamaguchi N., Belenky P., Mortimer S.E., Stanton M., Hedstrom L. Biochem. J. 379:243-251(2004) [PubMed: 14766016] [Abstract] Cited for: SUBCELLULAR LOCATION, NUCLEIC ACID-BINDING.
[9]	"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.
[10]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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. Tissue: Cervix carcinoma.
[12]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122 AND SER-416, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[13]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[14]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-511, MASS SPECTROMETRY.
[15]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]	"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. NM_000884.2.

UniGene

Hs.654400.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P12268.

SMR

P12268. Positions 10-514.

ModBase

Search...

Protein-protein interaction databases

IntAct

P12268. 6 interactions.

MINT

MINT-2860057.

STRING

P12268.

PTM databases

PhosphoSite

P12268.

Polymorphism databases

DMDM

124419.

2D gel databases

REPRODUCTION-2DPAGE

IPI00291510.
P12268.

UCD-2DPAGE

P12268.

Proteomic databases

PeptideAtlas

P12268.

PRIDE

P12268.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000326739; ENSP00000321584; ENSG00000178035.

GeneID

3615.

KEGG

hsa:3615.

NMPDR

fig|9606.3.peg.22511.

UCSC

uc003cvt.1. human.

Organism-specific databases

CTD

3615.

GeneCards

GC03M049061.

H-InvDB

HIX0018053.

HGNC

HGNC:6053. IMPDH2.

HPA

CAB020717.
HPA001400.

MIM

146691. gene.

neXtProt

NX_P12268.

PharmGKB

PA29863.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG14888.

HOGENOM

HBG298985.

HOVERGEN

HBG052122.

InParanoid

P12268.

OMA

RFLEEIM.

OrthoDB

EOG40VVP8.

PhylomeDB

P12268.

Enzyme and pathway databases

BioCyc

MetaCyc:HS11242-MONOMER.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P12268.

Bgee

P12268.

CleanEx

HS_IMPDH2.

Genevestigator

P12268.

GermOnline

ENSG00000178035. Homo sapiens.

Family and domain databases

InterPro

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

Gene3D

G3DSA:3.20.20.70. Aldolase_TIM. 1 hit.

KO

K00088.

Pfam

PF00571. CBS. 2 hits.
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

BindingDB

P12268.

DrugBank

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

NextBio

14143.

SOURCE

Search...

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:	December 14, 2011
This is version 148 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.