Inositol monophosphatase - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P29218 (IMPA1_HUMAN)

Last modified June 16, 2009. Version 103. History...

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

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Names and origin

Protein names

Recommended name:
    Inositol monophosphatase
    EC=3.1.3.25
Alternative name(s):
    Inositol-1(or 4)-monophosphatase
      Short name=IMPase
      Short name=IMP
    Lithium-sensitive myo-inositol monophosphatase A1

Gene names

Name:	IMPA1
Synonyms:	IMPA

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	277 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	Responsible for the provision of inositol required for synthesis of phosphatidylinositol and polyphosphoinositides and has been implicated as the pharmacological target for lithium action in brain.
Catalytic activity	Myo-inositol phosphate + H₂O = myo-inositol + phosphate.
Cofactor	Magnesium.
Enzyme regulation	Inhibited by Li⁺.
Pathway	Polyol metabolism; myo-inositol biosynthesis; myo-inositol from D-glucose 6-phosphate: step 2/2.
Subunit structure	Homodimer.
Subcellular location	Cytoplasm.
Involvement in disease	The blockade of inositol monophosphatase hydrolysis may underlie the anti-manic and anti-depressant actions of Li⁺.
Sequence similarities	Belongs to the inositol monophosphatase family.

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Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	Lithium Magnesium Metal-binding
Molecular function	Hydrolase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	phosphate metabolic process Ref.1 Inferred from mutant phenotype. Source: UniProtKB phosphatidylinositol biosynthetic process Ref.1 Inferred from mutant phenotype. Source: UniProtKB signal transduction Ref.1 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytoplasm Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	inositol-1(or 4)-monophosphatase activity Ref.1 Inferred from mutant phenotype. Source: UniProtKB lithium ion binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 277

277

Inositol monophosphatase

PRO_0000142513

Sites

Metal binding

Magnesium 1

Metal binding

Magnesium 1

Metal binding

Magnesium 2

Metal binding

Magnesium 1; via carbonyl oxygen

Metal binding

Magnesium 2

Metal binding

220

Magnesium 2

Binding site

Substrate

Binding site

220

Substrate

Natural variations

Natural variant

109

I → V: dbSNP rs204781.

VAR_049600

Experimental info

Mutagenesis

K → Q: 50-fold reduction in activity. Ref.9

Secondary structure

277

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P29218-1 [UniParc].

Last modified December 1, 1992. Version 1.
Checksum: 861D5617E1C04627
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FASTA

277

30,189

        10         20         30         40         50         60 
MADPWQECMD YAVTLARQAG EVVCEAIKNE MNVMLKSSPV DLVTATDQKV EKMLISSIKE 

        70         80         90        100        110        120 
KYPSHSFIGE ESVAAGEKSI LTDNPTWIID PIDGTTNFVH RFPFVAVSIG FAVNKKIEFG 

       130        140        150        160        170        180 
VVYSCVEGKM YTARKGKGAF CNGQKLQVSQ QEDITKSLLV TELGSSRTPE TVRMVLSNME 

       190        200        210        220        230        240 
KLFCIPVHGI RSVGTAAVNM CLVATGGADA YYEMGIHCWD VAGAGIIVTE AGGVLMDVTG 

       250        260        270 
GPFDLMSRRV IAANNRILAE RIAKEIQVIP LQRDDED

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning of human and rat brain myo-inositol monophosphatase. Expression and characterization of the human recombinant enzyme." McAllister G., Whiting P., Hammond E.A., Knowles M.R., Atack J.R., Bailey F.J., Maigetter R., Ragan C.I. Biochem. J. 284:749-754(1992) [PubMed: 1377913] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Hippocampus.
[2]	"Genomic structure and chromosomal localization of a human myo-inositol monophosphatase gene (IMPA)." Sjoeholt G., Molven A., Loevlie R., Wilcox A., Sikela J.M., Steen V.M. Genomics 45:113-122(1997) [PubMed: 9339367] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Molecular cloning and expression of human cerebral cortex myo-inositol monophosphatase A1 cDNA." Parthasarathy R., Parthasarathy L., Vadnal R.E. Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[4]	"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: Urinary bladder.
[5]	"Molecular cloning, genomic organization and promoter analysis of the human brain lithium-sensitive myo-inositol monophosphatase A1 isoenzyme." Parthasarathy L., Parthasarathy R. Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20.
[6]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[7]	"Structure of inositol monophosphatase, the putative target of lithium therapy." Bone R., Springer J.P., Atack J.R. Proc. Natl. Acad. Sci. U.S.A. 89:10031-10035(1992) [PubMed: 1332026] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH MAGNESIUM IONS.
[8]	"Structural studies of metal binding by inositol monophosphatase: evidence for two-metal ion catalysis." Bone R., Frank L., Springer J.P., Atack J.R. Biochemistry 33:9468-9476(1994) [PubMed: 8068621] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH SUBSTRATE.
[9]	"The contribution of lysine-36 to catalysis by human myo-inositol monophosphatase." Ganzhorn A.J., Lepage P., Pelton P.D., Strasser F., Vincendon P., Rondeau J.-M. Biochemistry 35:10957-10966(1996) [PubMed: 8718889] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT GLN-36, MUTAGENESIS OF LYS-36.
[10]	"Structure of an enzyme-substrate complex and the catalytic mechanism of human brain myo-inositol monophosphatase." Ganzhorn A.J., Rondeau J.-M. Protein Eng. 10:61-70(1997) Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
+	Additional computationally mapped references.

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Cross-references

Sequence databases

X66922 mRNA. Translation: CAA47359.1.
Y11360

Y11366 Genomic DNA. Translation: CAA72195.1.
AF042729 mRNA. Translation: AAB97468.1.
BC008381 mRNA. Translation: AAH08381.1.
BC009565 mRNA. Translation: AAH09565.1.
AF178754 Genomic DNA. Translation: AAD52997.1.

IPI

IPI00020906.

PIR

S23130.

RefSeq

NP_005527.1.

UniGene

Hs.695965

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AWB	X-ray	2.50	A/B	2-277	[»]
1IMA	X-ray	2.30	A/B	1-277	[»]
1IMB	X-ray	2.20	A/B	1-277	[»]
1IMC	X-ray	2.60	A/B	1-277	[»]
1IMD	X-ray	2.60	A/B	1-277	[»]
1IME	X-ray	2.25	A/B	1-277	[»]
1IMF	X-ray	2.50	A	1-277	[»]
2HHM	X-ray	2.10	A/B	2-277	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P29218. 1 interaction.

PTM databases

PhosphoSite

P29218.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00020906.

Proteomic databases

PeptideAtlas

P29218.

PRIDE

P29218.

Genome annotation databases

Ensembl

ENSG00000133731. Homo sapiens. [Contig view]

GeneID

3612.

KEGG

hsa:3612.

Organism-specific databases

GeneCards

GC08M082732.

H-InvDB

HIX0007618.

HGNC

HGNC:6050. IMPA1.

MIM

602064. gene.

PharmGKB

PA29860.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P29218.

HOVERGEN

P29218.

OMA

P29218. GFGGPWD.

Enzyme and pathway databases

BRENDA

3.1.3.25. 247.

Gene expression databases

ArrayExpress

P29218.

Bgee

P29218.

CleanEx

HS_IMPA1.

GermOnline

ENSG00000133731. Homo sapiens.

Family and domain databases

InterPro

IPR000760. Inositol_P.
[Graphical view]

PANTHER

PTHR20854. Inositol_P. 1 hit.

Pfam

PF00459. Inositol_P. 1 hit.
[Graphical view]

PRINTS

PR00378. INOSPHPHTASE.

ProDom

PD023420. Inositol_P. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

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

ProtoNet

Search...

Other Resources

DrugBank

DB01356. Lithium.

NextBio

14127.

SOURCE

Search...

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Entry information

Entry name

IMPA1_HUMAN

Accession

Primary (citable) accession number: P29218
Secondary accession number(s): Q9UK71

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 1, 1992
Last modified:	June 16, 2009
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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