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O14732

- IMPA2_HUMAN

UniProt

O14732 - IMPA2_HUMAN

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Protein

Inositol monophosphatase 2

Gene

IMPA2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

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

Cofactori

Magnesium.1 Publication

Enzyme regulationi

Inhibited by high Li+ and restricted Mg2+ concentrations.2 Publications

Kineticsi

  1. KM=5 mM for myo-inositol 1-monophosphate1 Publication

pH dependencei

Optimum pH is 7.5-8.0.1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi81 – 811Magnesium 1By similarity
Binding sitei81 – 811Substrate1 Publication
Metal bindingi101 – 1011Magnesium 1By similarity
Metal bindingi101 – 1011Magnesium 2By similarity
Metal bindingi103 – 1031Magnesium 1; via carbonyl oxygenBy similarity
Metal bindingi104 – 1041Magnesium 2By similarity
Binding sitei224 – 2241Substrate1 Publication
Metal bindingi231 – 2311Magnesium 2By similarity
Binding sitei231 – 2311SubstrateBy similarity

GO - Molecular functioni

  1. inositol monophosphate 1-phosphatase activity Source: MGI
  2. inositol monophosphate 3-phosphatase activity Source: UniProtKB-EC
  3. inositol monophosphate 4-phosphatase activity Source: UniProtKB-EC
  4. metal ion binding Source: UniProtKB-KW
  5. protein homodimerization activity Source: MGI

GO - Biological processi

  1. inositol biosynthetic process Source: UniProtKB-UniPathway
  2. inositol phosphate dephosphorylation Source: MGI
  3. inositol phosphate metabolic process Source: Reactome
  4. phosphate-containing compound metabolic process Source: ProtInc
  5. phosphatidylinositol phosphorylation Source: InterPro
  6. signal transduction Source: ProtInc
  7. small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Magnesium, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS06822-MONOMER.
BRENDAi3.1.3.25. 3474.
ReactomeiREACT_150352. Synthesis of IP2, IP, and Ins in the cytosol.
UniPathwayiUPA00823; UER00788.

Names & Taxonomyi

Protein namesi
Recommended name:
Inositol monophosphatase 2 (EC:3.1.3.25)
Short name:
IMP 2
Short name:
IMPase 2
Alternative name(s):
Inositol-1(or 4)-monophosphatase 2
Myo-inositol monophosphatase A2
Gene namesi
Name:IMPA2
Synonyms:IMP.18P
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 18

Organism-specific databases

HGNCiHGNC:6051. IMPA2.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. cytosol Source: Reactome
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi104 – 1041D → N: Loss of activity. 1 Publication

Organism-specific databases

PharmGKBiPA29861.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 288288Inositol monophosphatase 2PRO_0000142520Add
BLAST

Proteomic databases

MaxQBiO14732.
PaxDbiO14732.
PRIDEiO14732.

PTM databases

PhosphoSiteiO14732.

Expressioni

Inductioni

Repressed by Li+.

Gene expression databases

BgeeiO14732.
CleanExiHS_IMPA2.
ExpressionAtlasiO14732. baseline and differential.
GenevestigatoriO14732.

Organism-specific databases

HPAiHPA029561.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi109826. 5 interactions.
IntActiO14732. 4 interactions.
MINTiMINT-1413243.
STRINGi9606.ENSP00000269159.

Structurei

Secondary structure

1
288
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi17 – 3822Combined sources
Helixi56 – 7015Combined sources
Beta strandi77 – 848Combined sources
Beta strandi97 – 1048Combined sources
Helixi106 – 1105Combined sources
Beta strandi117 – 1248Combined sources
Beta strandi127 – 1359Combined sources
Turni136 – 1394Combined sources
Beta strandi140 – 1456Combined sources
Turni146 – 1483Combined sources
Beta strandi150 – 1523Combined sources
Helixi165 – 1673Combined sources
Beta strandi169 – 1713Combined sources
Helixi180 – 19516Combined sources
Beta strandi199 – 2035Combined sources
Helixi207 – 2159Combined sources
Beta strandi220 – 2267Combined sources
Helixi229 – 2313Combined sources
Helixi233 – 2419Combined sources
Beta strandi245 – 2473Combined sources
Beta strandi251 – 2533Combined sources
Helixi256 – 2583Combined sources
Beta strandi260 – 2667Combined sources
Helixi267 – 2759Combined sources

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliO14732.
SMRiO14732. Positions 15-281.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14732.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni103 – 1064Substrate binding
Regioni205 – 2073Substrate binding

Sequence similaritiesi

Belongs to the inositol monophosphatase family.Curated

Phylogenomic databases

eggNOGiCOG0483.
GeneTreeiENSGT00390000014699.
HOGENOMiHOG000282238.
HOVERGENiHBG052123.
InParanoidiO14732.
KOiK01092.
OMAiREMAMFI.
OrthoDBiEOG7RJPS8.
PhylomeDBiO14732.
TreeFamiTF313194.

Family and domain databases

InterProiIPR020583. Inositol_monoP_metal-BS.
IPR020552. Inositol_monoPase_Li-sen.
IPR000760. Inositol_monophosphatase.
IPR020550. Inositol_monophosphatase_CS.
[Graphical view]
PANTHERiPTHR20854. PTHR20854. 1 hit.
PfamiPF00459. Inositol_P. 1 hit.
[Graphical view]
PRINTSiPR00377. IMPHPHTASES.
PR00378. LIIMPHPHTASE.
PROSITEiPS00629. IMP_1. 1 hit.
PS00630. IMP_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: O14732-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MKPSGEDQAA LAAGPWEECF QAAVQLALRA GQIIRKALTE EKRVSTKTSA
60 70 80 90 100
ADLVTETDHL VEDLIISELR ERFPSHRFIA EEAAASGAKC VLTHSPTWII
110 120 130 140 150
DPIDGTCNFV HRFPTVAVSI GFAVRQELEF GVIYHCTEER LYTGRRGRGA
160 170 180 190 200
FCNGQRLRVS GETDLSKALV LTEIGPKRDP ATLKLFLSNM ERLLHAKAHG
210 220 230 240 250
VRVIGSSTLA LCHLASGAAD AYYQFGLHCW DLAAATVIIR EAGGIVIDTS
260 270 280
GGPLDLMACR VVAASTREMA MLIAQALQTI NYGRDDEK
Length:288
Mass (Da):31,321
Last modified:January 1, 1998 - v1
Checksum:i30D83FA339AC69B4
GO
Isoform 2 (identifier: O14732-2) [UniParc]FASTAAdd to Basket

Also known as: A2b

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

Show »
Length:261
Mass (Da):28,512
Checksum:iA9D2BC0A05D0DF2F
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti88 – 881A → T.
Corresponds to variant rs16976948 [ dbSNP | Ensembl ].
VAR_049601

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei6 – 3429EDQAA…AGQII → QD in isoform 2. 1 PublicationVSP_013674Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS11855.1. [O14732-1]
RefSeqiNP_055029.1. NM_014214.2. [O14732-1]
UniGeneiHs.743311.

Genome annotation databases

EnsembliENST00000269159; ENSP00000269159; ENSG00000141401. [O14732-1]
GeneIDi3613.
KEGGihsa:3613.
UCSCiuc002kqp.2. human. [O14732-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS11855.1. [O14732-1 ]
RefSeqi NP_055029.1. NM_014214.2. [O14732-1 ]
UniGenei Hs.743311.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
ProteinModelPortali O14732.
SMRi O14732. Positions 15-281.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109826. 5 interactions.
IntActi O14732. 4 interactions.
MINTi MINT-1413243.
STRINGi 9606.ENSP00000269159.

Chemistry

BindingDBi O14732.
ChEMBLi CHEMBL1776.
DrugBanki DB01356. Lithium.

PTM databases

PhosphoSitei O14732.

Proteomic databases

MaxQBi O14732.
PaxDbi O14732.
PRIDEi O14732.

Protocols and materials databases

DNASUi 3613.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000269159 ; ENSP00000269159 ; ENSG00000141401 . [O14732-1 ]
GeneIDi 3613.
KEGGi hsa:3613.
UCSCi uc002kqp.2. human. [O14732-1 ]

Organism-specific databases

CTDi 3613.
GeneCardsi GC18P011981.
HGNCi HGNC:6051. IMPA2.
HPAi HPA029561.
MIMi 605922. gene.
neXtProti NX_O14732.
PharmGKBi PA29861.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0483.
GeneTreei ENSGT00390000014699.
HOGENOMi HOG000282238.
HOVERGENi HBG052123.
InParanoidi O14732.
KOi K01092.
OMAi REMAMFI.
OrthoDBi EOG7RJPS8.
PhylomeDBi O14732.
TreeFami TF313194.

Enzyme and pathway databases

UniPathwayi UPA00823 ; UER00788 .
BioCyci MetaCyc:HS06822-MONOMER.
BRENDAi 3.1.3.25. 3474.
Reactomei REACT_150352. Synthesis of IP2, IP, and Ins in the cytosol.

Miscellaneous databases

ChiTaRSi IMPA2. human.
EvolutionaryTracei O14732.
GeneWikii IMPA2.
GenomeRNAii 3613.
NextBioi 14131.
PROi O14732.
SOURCEi Search...

Gene expression databases

Bgeei O14732.
CleanExi HS_IMPA2.
ExpressionAtlasi O14732. baseline and differential.
Genevestigatori O14732.

Family and domain databases

InterProi IPR020583. Inositol_monoP_metal-BS.
IPR020552. Inositol_monoPase_Li-sen.
IPR000760. Inositol_monophosphatase.
IPR020550. Inositol_monophosphatase_CS.
[Graphical view ]
PANTHERi PTHR20854. PTHR20854. 1 hit.
Pfami PF00459. Inositol_P. 1 hit.
[Graphical view ]
PRINTSi PR00377. IMPHPHTASES.
PR00378. LIIMPHPHTASE.
PROSITEi PS00629. IMP_1. 1 hit.
PS00630. IMP_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.

Entry informationi

Entry nameiIMPA2_HUMAN
AccessioniPrimary (citable) accession number: O14732
Secondary accession number(s): B0YJ29, Q9UJT3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: January 1, 1998
Last modified: October 29, 2014
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3