O14732 (IMPA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	288 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Magnesium Metal-binding
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	inositol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway inositol phosphate dephosphorylation Inferred from direct assay Ref.9. Source: MGI phosphatidylinositol phosphorylation Inferred from electronic annotation. Source: InterPro signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	inositol monophosphate 1-phosphatase activity Inferred from direct assay Ref.9. Source: MGI inositol monophosphate 3-phosphatase activity Inferred from electronic annotation. Source: EC inositol monophosphate 4-phosphatase activity Inferred from electronic annotation. Source: EC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 288

288

Inositol monophosphatase 2

PRO_0000142520

Regions

Region

103 – 106

4

Substrate binding

Region

205 – 207

3

Substrate binding

Sites

Metal binding

81

1

Magnesium 1 By similarity

Metal binding

101

1

Magnesium 1 By similarity

Metal binding

101

1

Magnesium 2 By similarity

Metal binding

103

1

Magnesium 1; via carbonyl oxygen By similarity

Metal binding

104

1

Magnesium 2 By similarity

Metal binding

231

1

Magnesium 2 By similarity

Binding site

81

1

Substrate

Binding site

224

1

Substrate

Binding site

231

1

Substrate By similarity

Natural variations

Alternative sequence

6 – 34

29

EDQAA…AGQII → QD in isoform 2.

VSP_013674

Natural variant

88

1

A → T.
Corresponds to variant rs16976948 [ dbSNP | Ensembl ].

VAR_049601

Experimental info

Mutagenesis

104

1

D → N: Loss of activity. Ref.9

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

288

Helix Strand Turn

Details...

Helix

17 – 38

22

Helix

56 – 70

15

Beta strand

77 – 84

8

Beta strand

97 – 104

8

Helix

106 – 110

5

Beta strand

117 – 124

8

Beta strand

127 – 135

9

Turn

136 – 139

4

Beta strand

140 – 145

6

Turn

146 – 148

3

Beta strand

150 – 152

3

Helix

165 – 167

3

Beta strand

169 – 171

3

Helix

180 – 195

16

Beta strand

199 – 203

5

Helix

207 – 215

9

Beta strand

220 – 226

7

Helix

229 – 231

3

Helix

233 – 241

9

Beta strand

245 – 247

3

Beta strand

251 – 253

3

Helix

256 – 258

3

Beta strand

260 – 266

7

Helix

267 – 275

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 30D83FA339AC69B4	FASTA	288	31,321
	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
	Isoform 2 (A2b) [UniParc]. Checksum: A9D2BC0A05D0DF2F	FASTA	261	28,512
	10 20 30 40 50 60 MKPSGQDRKA LTEEKRVSTK TSAADLVTET DHLVEDLIIS ELRERFPSHR FIAEEAAASG 70 80 90 100 110 120 AKCVLTHSPT WIIDPIDGTC NFVHRFPTVA VSIGFAVRQE LEFGVIYHCT EERLYTGRRG 130 140 150 160 170 180 RGAFCNGQRL RVSGETDLSK ALVLTEIGPK RDPATLKLFL SNMERLLHAK AHGVRVIGSS 190 200 210 220 230 240 TLALCHLASG AADAYYQFGL HCWDLAAATV IIREAGGIVI DTSGGPLDLM ACRVVAASTR 250 260 EMAMLIAQAL QTINYGRDDE K

References

	« Hide 'large scale' referencesShow '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. , 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 , 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.

IPI

IPI00023635.
IPI00555726.

RefSeq

NP_055029.1. NM_014214.2.

UniGene

Hs.743311.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CZH	X-ray	2.70	A/B	1-288	[»]
2CZI	X-ray	3.00	A	1-288	[»]
2CZK	X-ray	2.90	A	1-288	[»]
2DDK	X-ray	2.70	A/B	1-288	[»]
2FVZ	X-ray	2.40	A/B/C/D	16-288	[»]

ProteinModelPortal

O14732.

ModBase

Search...

Protein-protein interaction databases

IntAct

O14732. 3 interactions.

MINT

MINT-1413243.

STRING

9606.ENSP00000269159.

PTM databases

PhosphoSite

O14732.

Proteomic databases

PaxDb

O14732.

PRIDE

O14732.

Protocols and materials databases

DNASU

3613.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000269159; ENSP00000269159; ENSG00000141401.

GeneID

3613.

KEGG

hsa:3613.

UCSC

uc002kqp.2. human.

Organism-specific databases

CTD

3613.

GeneCards

GC18P011971.

HGNC

HGNC:6051. IMPA2.

HPA

HPA029561.

MIM

605922. gene.

neXtProt

NX_O14732.

PharmGKB

PA29861.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0483.

HOGENOM

HOG000282238.

HOVERGEN

HBG052123.

InParanoid

O14732.

KO

K01092.

OMA

INDFVTE.

OrthoDB

EOG42FSJ2.

PhylomeDB

O14732.

Enzyme and pathway databases

BioCyc

MetaCyc:HS06822-MONOMER.

BRENDA

3.1.3.25. 3474.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00823; UER00788.

Gene expression databases

ArrayExpress

O14732.

Bgee

O14732.

CleanEx

HS_IMPA2.

Genevestigator

O14732.

Family and domain databases

InterPro

IPR020583. Inositol_monoP_metal-BS.
IPR020552. Inositol_monoPase_Li-sen.
IPR000760. Inositol_monophosphatase.
IPR020550. Inositol_monophosphatase_CS.
[Graphical view]

PANTHER

PTHR20854. PTHR20854. 1 hit.

Pfam

PF00459. Inositol_P. 1 hit.
[Graphical view]

PRINTS

PR00377. IMPHPHTASES.
PR00378. LIIMPHPHTASE.

PROSITE

PS00629. IMP_1. 1 hit.
PS00630. IMP_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O14732.

ChEMBL

CHEMBL1776.

ChiTaRS

IMPA2. human.

DrugBank

DB01356. Lithium.

EvolutionaryTrace

O14732.

GenomeRNAi

3613.

NextBio

14131.

SOURCE

Search...

Entry information

Entry name

IMPA2_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 118 of the entry and version 1 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.