Reviewed, UniProtKB/Swiss-Prot P29218 (IMPA1_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	277 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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. Can use myo-inositol monophosphates, myo-inositol-1,3-diphosphate, myo-inositol-1,4-diphosphate, scyllo-inositol-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates. Ref.9
Catalytic activity	Myo-inositol phosphate + H2O = myo-inositol + phosphate.
Cofactor	Magnesium. Ref.9
Enzyme regulation	Inhibited by Li+. Ref.9
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.
Biophysicochemical properties	pH dependence: Optimum pH is 7.0-7.5.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	Lithium Magnesium Metal-binding
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome
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	identical protein binding Inferred from physical interaction. Source: IntAct 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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-752410,EBI-752410

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 277

277

Inositol monophosphatase

PRO_0000142513

Regions

Region

92 – 95

4

Substrate binding

Region

194 – 196

3

Substrate binding

Sites

Metal binding

70

1

Magnesium 1

Metal binding

90

1

Magnesium 1

Metal binding

90

1

Magnesium 2

Metal binding

92

1

Magnesium 1; via carbonyl oxygen

Metal binding

93

1

Magnesium 2

Metal binding

220

1

Magnesium 2

Binding site

70

1

Substrate

Binding site

213

1

Substrate

Binding site

220

1

Substrate By similarity

Natural variations

Natural variant

109

1

I → V: dbSNP rs204781.

VAR_049600

Experimental info

Mutagenesis

36

1

K → Q: 50-fold reduction in activity. Ref.12

Mutagenesis

93

1

D → N: Loss of activity. Ref.9

Secondary structure

1

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277

Helix Strand Turn

Details...

Helix

6 – 26

21

Beta strand

33 – 38

6

Beta strand

42 – 44

3

Helix

45 – 61

17

Beta strand

66 – 69

4

Helix

70 – 74

5

Beta strand

86 – 93

8

Helix

95 – 100

6

Beta strand

106 – 113

8

Beta strand

116 – 124

9

Turn

125 – 128

4

Beta strand

129 – 134

6

Turn

135 – 137

3

Beta strand

138 – 141

4

Helix

154 – 156

3

Beta strand

158 – 160

3

Helix

169 – 183

15

Turn

184 – 186

3

Beta strand

188 – 192

5

Helix

196 – 204

9

Beta strand

207 – 215

9

Helix

218 – 221

4

Helix

224 – 230

7

Beta strand

234 – 236

3

Beta strand

247 – 255

9

Helix

256 – 265

10

Sequences

	Sequence		Length	Mass (Da)
	P29218-1 [UniParc]. Last modified December 1, 1992. Version 1. Checksum: 861D5617E1C04627	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

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]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thymus.
[5]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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.
[7]	"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.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[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: 17068342] [Abstract] Cited for: FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, MUTAGENESIS OF ASP-93.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X66922 mRNA. Translation: CAA47359.1.
Y11360 , Y11361, Y11362, Y11367, Y11363, Y11364, Y11365, Y11366 Genomic DNA. Translation: CAA72195.1.
AF042729 mRNA. Translation: AAB97468.1.
AK312823 mRNA. Translation: BAG35680.1.
CH471068 Genomic DNA. Translation: EAW87095.1.
BC008381 mRNA. Translation: AAH08381.1.
BC009565 mRNA. Translation: AAH09565.1.
AF178754 Genomic DNA. Translation: AAD52997.1.

IPI

IPI00020906.

PIR

S23130.

RefSeq

NP_001138350.1.
NP_001138351.1.
NP_005527.1.

UniGene

Hs.695965

3D structure databases

PDBPDBe

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.

STRING

P29218.

PTM databases

PhosphoSite

P29218.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00020906.

Proteomic databases

PeptideAtlas

P29218.

PRIDE

P29218.

Genome annotation databases

Ensembl

ENST00000256108; ENSP00000256108; ENSG00000133731; Homo sapiens. [Genome view]
ENST00000311489; ENSP00000311803; ENSG00000133731; Homo sapiens. [Genome view]
ENST00000449740; ENSP00000408526; ENSG00000133731; Homo sapiens. [Genome view]

GeneID

3612.

KEGG

hsa:3612.

UCSC

uc003ych.1. human.

Organism-specific databases

CTD

3612.

GeneCards

GC08M082732.

H-InvDB

HIX0007618.

HGNC

HGNC:6050. IMPA1.

MIM

602064. gene.

PharmGKB

PA29860.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P29218.

HOVERGEN

P29218.

OMA

GFGGPWD.

Enzyme and pathway databases

BRENDA

3.1.3.25. 247.

Gene expression databases

ArrayExpress

P29218.

Bgee

P29218.

CleanEx

HS_IMPA1.

Genevestigator

P29218.

GermOnline

ENSG00000133731. Homo sapiens.

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. Inositol_P. 1 hit.

Pfam

PF00459. Inositol_P. 1 hit.
[Graphical view]

PRINTS

PR00377. IMPHPHTASES.
PR00378. LIIMPHPHTASE.

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...

Entry information

Entry name

IMPA1_HUMAN

Accession

Primary (citable) accession number: P29218
Secondary accession number(s): B2R733, Q9UK71

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 1, 1992
Last modified:	November 3, 2009
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.