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O14732 (IMPA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Inositol monophosphatase 2

Short name=IMP 2
Short name=IMPase 2
EC=3.1.3.25
Alternative name(s):
Inositol-1(or 4)-monophosphatase 2
Myo-inositol monophosphatase A2
Gene names
Name:IMPA2
Synonyms:IMP.18P
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length288 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Can use myo-inositol monophosphates, scylloinositol 1,4-diphosphate, glucose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates. Has been implicated as the pharmacological target for lithium Li+ action in brain. Ref.9

Catalytic activity

Myo-inositol phosphate + H2O = myo-inositol + phosphate.

Cofactor

Magnesium. Ref.9

Enzyme regulation

Inhibited by high Li+ and restricted Mg2+ concentrations. Ref.8 Ref.9

Pathway

Polyol metabolism; myo-inositol biosynthesis; myo-inositol from D-glucose 6-phosphate: step 2/2.

Subunit structure

Homodimer. Ref.9 Ref.11

Induction

Repressed by Li+. Ref.8 Ref.9

Sequence similarities

Belongs to the inositol monophosphatase family.

Biophysicochemical properties

Kinetic parameters:

KM=5 mM for myo-inositol 1-monophosphate Ref.9

pH dependence:

Optimum pH is 7.5-8.0.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O14732-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O14732-2)

Also known as: A2b;

The sequence of this isoform differs from the canonical sequence as follows:
     6-34: EDQAALAAGPWEECFQAAVQLALRAGQII → QD

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 288288Inositol monophosphatase 2
PRO_0000142520

Regions

Region103 – 1064Substrate binding
Region205 – 2073Substrate binding

Sites

Metal binding811Magnesium 1 By similarity
Metal binding1011Magnesium 1 By similarity
Metal binding1011Magnesium 2 By similarity
Metal binding1031Magnesium 1; via carbonyl oxygen By similarity
Metal binding1041Magnesium 2 By similarity
Metal binding2311Magnesium 2 By similarity
Binding site811Substrate
Binding site2241Substrate
Binding site2311Substrate By similarity

Natural variations

Alternative sequence6 – 3429EDQAA…AGQII → QD in isoform 2.
VSP_013674
Natural variant881A → T.
Corresponds to variant rs16976948 [ dbSNP | Ensembl ].
VAR_049601

Experimental info

Mutagenesis1041D → N: Loss of activity. Ref.9

Secondary structure

............................................. 288
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 30D83FA339AC69B4

FASTA28831,321
        10         20         30         40         50         60 
MKPSGEDQAA LAAGPWEECF QAAVQLALRA GQIIRKALTE EKRVSTKTSA ADLVTETDHL 

        70         80         90        100        110        120 
VEDLIISELR ERFPSHRFIA EEAAASGAKC VLTHSPTWII DPIDGTCNFV HRFPTVAVSI 

       130        140        150        160        170        180 
GFAVRQELEF GVIYHCTEER LYTGRRGRGA FCNGQRLRVS GETDLSKALV LTEIGPKRDP 

       190        200        210        220        230        240 
ATLKLFLSNM ERLLHAKAHG VRVIGSSTLA LCHLASGAAD AYYQFGLHCW DLAAATVIIR 

       250        260        270        280 
EAGGIVIDTS GGPLDLMACR VVAASTREMA MLIAQALQTI NYGRDDEK 

« Hide

Isoform 2 (A2b) [UniParc].

Checksum: A9D2BC0A05D0DF2F
Show »

FASTA26128,512

References

« Hide 'large scale' references
[1]"A novel human myo-inositol monophosphatase gene, IMP.18p, maps to a susceptibility region for bipolar disorder."
Yoshikawa T., Turner G., Esterling L.E., Sanders A.R., Detera-Wadleigh S.D.
Mol. Psychiatry 2:393-397(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"A human myo-inositol monophosphatase gene (IMPA2) localized in a putative susceptibility region for bipolar disorder on chromosome 18p11.2: genomic structure and polymorphism screening in manic-depressive patients."
Sjoeholt G., Gulbrandsen A.K., Lovlie R., Berle J., Molven A., Steen V.M.
Mol. Psychiatry 5:172-180(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Molecular characterization of a novel form of human brain inositol monophosphatase A2b."
Parthasarathy L., Parthasarathy R.
Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]NHLBI resequencing and genotyping service (RS&G)
Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Skin.
[8]"Lithium modulation of the human inositol monophosphatase 2 (IMPA2) promoter."
Seelan R.S., Parthasarathy L.K., Parthasarathy R.N.
Biochem. Biophys. Res. Commun. 324:1370-1378(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[9]"Spatial expression patterns and biochemical properties distinguish a second myo-inositol monophosphatase IMPA2 from IMPA1."
Ohnishi T., Ohba H., Seo K.-C., Im J., Sato Y., Iwayama Y., Furuichi T., Chung S.-K., Yoshikawa T.
J. Biol. Chem. 282:637-646(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ASP-104, ENZYME REGULATION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, HOMODIMERIZATION.
[10]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Crystal structure of human myo-inositol monophosphatase 2, the product of the putative susceptibility gene for bipolar disorder, schizophrenia, and febrile seizures."
Arai R., Ito K., Ohnishi T., Ohba H., Akasaka R., Bessho Y., Hanawa-Suetsugu K., Yoshikawa T., Shirouzu M., Yokoyama S.
Proteins 67:732-742(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH SUBSTRATE, HOMODIMERIZATION.
[12]"Structure of human inositol monophosphatase 2."
Structural genomics consortium (SGC)
Submitted (FEB-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 16-288.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF014398 mRNA. Translation: AAB70915.1.
AF157102 expand/collapse EMBL AC list , AF157096, AF157097, AF157098, AF157099, AF157100, AF157101 Genomic DNA. Translation: AAD40683.1.
AF200432 mRNA. Translation: AAF07824.1.
BT007061 mRNA. Translation: AAP35710.1.
EF444990 Genomic DNA. Translation: ACA06007.1.
CH471113 Genomic DNA. Translation: EAX01559.1.
BC017176 mRNA. Translation: AAH17176.1.
RefSeqNP_055029.1. NM_014214.2.
UniGeneHs.743311.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CZHX-ray2.70A/B1-288[»]
2CZIX-ray3.00A1-288[»]
2CZKX-ray2.90A1-288[»]
2DDKX-ray2.70A/B1-288[»]
2FVZX-ray2.40A/B/C/D16-288[»]
ProteinModelPortalO14732.
SMRO14732. Positions 15-281.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109826. 2 interactions.
IntActO14732. 4 interactions.
MINTMINT-1413243.
STRING9606.ENSP00000269159.

Chemistry

BindingDBO14732.
ChEMBLCHEMBL1776.
DrugBankDB01356. Lithium.

PTM databases

PhosphoSiteO14732.

Proteomic databases

PaxDbO14732.
PRIDEO14732.

Protocols and materials databases

DNASU3613.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000269159; ENSP00000269159; ENSG00000141401. [O14732-1]
GeneID3613.
KEGGhsa:3613.
UCSCuc002kqp.2. human. [O14732-1]

Organism-specific databases

CTD3613.
GeneCardsGC18P011981.
HGNCHGNC:6051. IMPA2.
HPAHPA029561.
MIM605922. gene.
neXtProtNX_O14732.
PharmGKBPA29861.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0483.
HOGENOMHOG000282238.
HOVERGENHBG052123.
InParanoidO14732.
KOK01092.
OMASNLHPML.
OrthoDBEOG7RJPS8.
PhylomeDBO14732.
TreeFamTF313194.

Enzyme and pathway databases

BioCycMetaCyc:HS06822-MONOMER.
BRENDA3.1.3.25. 3474.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00823; UER00788.

Gene expression databases

ArrayExpressO14732.
BgeeO14732.
CleanExHS_IMPA2.
GenevestigatorO14732.

Family and domain databases

InterProIPR020583. Inositol_monoP_metal-BS.
IPR020552. Inositol_monoPase_Li-sen.
IPR000760. Inositol_monophosphatase.
IPR020550. Inositol_monophosphatase_CS.
[Graphical view]
PANTHERPTHR20854. PTHR20854. 1 hit.
PfamPF00459. Inositol_P. 1 hit.
[Graphical view]
PRINTSPR00377. IMPHPHTASES.
PR00378. LIIMPHPHTASE.
PROSITEPS00629. IMP_1. 1 hit.
PS00630. IMP_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSIMPA2. human.
EvolutionaryTraceO14732.
GeneWikiIMPA2.
GenomeRNAi3613.
NextBio14131.
PROO14732.
SOURCESearch...

Entry information

Entry nameIMPA2_HUMAN
AccessionPrimary (citable) accession number: O14732
Secondary accession number(s): B0YJ29, Q9UJT3
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM