Full text data of IMPA1
IMPA1
(IMPA)
[Confidence: low (only semi-automatic identification from reviews)]
Inositol monophosphatase 1; IMP 1; IMPase 1; 3.1.3.25 (Inositol-1(or 4)-monophosphatase 1; Lithium-sensitive myo-inositol monophosphatase A1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Inositol monophosphatase 1; IMP 1; IMPase 1; 3.1.3.25 (Inositol-1(or 4)-monophosphatase 1; Lithium-sensitive myo-inositol monophosphatase A1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P29218
ID IMPA1_HUMAN Reviewed; 277 AA.
AC P29218; B2R733; B4DLN3; B7Z6Q4; J3KQT7; Q9UK71;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-DEC-1992, sequence version 1.
DT 22-JAN-2014, entry version 152.
DE RecName: Full=Inositol monophosphatase 1;
DE Short=IMP 1;
DE Short=IMPase 1;
DE EC=3.1.3.25;
DE AltName: Full=Inositol-1(or 4)-monophosphatase 1;
DE AltName: Full=Lithium-sensitive myo-inositol monophosphatase A1;
GN Name=IMPA1; Synonyms=IMPA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Hippocampus;
RX PubMed=1377913;
RA McAllister G., Whiting P., Hammond E.A., Knowles M.R., Atack J.R.,
RA Bailey F.J., Maigetter R., Ragan C.I.;
RT "cDNA cloning of human and rat brain myo-inositol monophosphatase.
RT Expression and characterization of the human recombinant enzyme.";
RL Biochem. J. 284:749-754(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9339367; DOI=10.1006/geno.1997.4862;
RA Sjoeholt G., Molven A., Loevlie R., Wilcox A., Sikela J.M.,
RA Steen V.M.;
RT "Genomic structure and chromosomal localization of a human myo-
RT inositol monophosphatase gene (IMPA).";
RL Genomics 45:113-122(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Parthasarathy R., Parthasarathy L., Vadnal R.E.;
RT "Molecular cloning and expression of human cerebral cortex myo-
RT inositol monophosphatase A1 cDNA.";
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Thymus, and Umbilical cord blood;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Urinary bladder;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20.
RA Parthasarathy L., Parthasarathy R.;
RT "Molecular cloning, genomic organization and promoter analysis of the
RT human brain lithium-sensitive myo-inositol monophosphatase A1
RT isoenzyme.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION,
RP AND MUTAGENESIS OF ASP-93.
RX PubMed=17068342; DOI=10.1074/jbc.M604474200;
RA Ohnishi T., Ohba H., Seo K.-C., Im J., Sato Y., Iwayama Y.,
RA Furuichi T., Chung S.-K., Yoshikawa T.;
RT "Spatial expression patterns and biochemical properties distinguish a
RT second myo-inositol monophosphatase IMPA2 from IMPA1.";
RL J. Biol. Chem. 282:637-646(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH MAGNESIUM IONS.
RX PubMed=1332026; DOI=10.1073/pnas.89.21.10031;
RA Bone R., Springer J.P., Atack J.R.;
RT "Structure of inositol monophosphatase, the putative target of lithium
RT therapy.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:10031-10035(1992).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH SUBSTRATE.
RX PubMed=8068621; DOI=10.1021/bi00198a012;
RA Bone R., Frank L., Springer J.P., Atack J.R.;
RT "Structural studies of metal binding by inositol monophosphatase:
RT evidence for two-metal ion catalysis.";
RL Biochemistry 33:9468-9476(1994).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT GLN-36, AND
RP MUTAGENESIS OF LYS-36.
RX PubMed=8718889; DOI=10.1021/bi9603837;
RA Ganzhorn A.J., Lepage P., Pelton P.D., Strasser F., Vincendon P.,
RA Rondeau J.-M.;
RT "The contribution of lysine-36 to catalysis by human myo-inositol
RT monophosphatase.";
RL Biochemistry 35:10957-10966(1996).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RA Ganzhorn A.J., Rondeau J.-M.;
RT "Structure of an enzyme-substrate complex and the catalytic mechanism
RT of human brain myo-inositol monophosphatase.";
RL Protein Eng. 10:61-70(1997).
CC -!- FUNCTION: Responsible for the provision of inositol required for
CC synthesis of phosphatidylinositol and polyphosphoinositides and
CC has been implicated as the pharmacological target for lithium
CC action in brain. Can use myo-inositol monophosphates, myo-inositol
CC 1,3-diphosphate, myo-inositol 1,4-diphosphate, scyllo-inositol-
CC phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-
CC phosphate, beta-glycerophosphate, and 2'-AMP as substrates.
CC -!- CATALYTIC ACTIVITY: Myo-inositol phosphate + H(2)O = myo-inositol
CC + phosphate.
CC -!- COFACTOR: Magnesium.
CC -!- ENZYME REGULATION: Inhibited by Li(+).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.0-7.5;
CC -!- PATHWAY: Polyol metabolism; myo-inositol biosynthesis; myo-
CC inositol from D-glucose 6-phosphate: step 2/2.
CC -!- SUBUNIT: Homodimer.
CC -!- INTERACTION:
CC Self; NbExp=3; IntAct=EBI-752410, EBI-752410;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P29218-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P29218-2; Sequence=VSP_042521;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=P29218-3; Sequence=VSP_046308;
CC Note=No experimental confirmation available. Ref.4 (BAH13340)
CC sequence is in conflict in position: 17:Q->R;
CC -!- SIMILARITY: Belongs to the inositol monophosphatase family.
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DR EMBL; X66922; CAA47359.1; -; mRNA.
DR EMBL; Y11360; CAA72195.1; -; Genomic_DNA.
DR EMBL; Y11361; CAA72195.1; JOINED; Genomic_DNA.
DR EMBL; Y11362; CAA72195.1; JOINED; Genomic_DNA.
DR EMBL; Y11367; CAA72195.1; JOINED; Genomic_DNA.
DR EMBL; Y11363; CAA72195.1; JOINED; Genomic_DNA.
DR EMBL; Y11364; CAA72195.1; JOINED; Genomic_DNA.
DR EMBL; Y11365; CAA72195.1; JOINED; Genomic_DNA.
DR EMBL; Y11366; CAA72195.1; JOINED; Genomic_DNA.
DR EMBL; AF042729; AAB97468.1; -; mRNA.
DR EMBL; AK297078; BAG59595.1; -; mRNA.
DR EMBL; AK300750; BAH13340.1; -; mRNA.
DR EMBL; AK312823; BAG35680.1; -; mRNA.
DR EMBL; AC090255; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471068; EAW87095.1; -; Genomic_DNA.
DR EMBL; BC008381; AAH08381.1; -; mRNA.
DR EMBL; BC009565; AAH09565.1; -; mRNA.
DR EMBL; AF178754; AAD52997.1; -; Genomic_DNA.
DR PIR; S23130; S23130.
DR RefSeq; NP_001138350.1; NM_001144878.1.
DR RefSeq; NP_001138351.1; NM_001144879.1.
DR RefSeq; NP_005527.1; NM_005536.3.
DR UniGene; Hs.656694; -.
DR PDB; 1AWB; X-ray; 2.50 A; A/B=2-277.
DR PDB; 1IMA; X-ray; 2.30 A; A/B=1-277.
DR PDB; 1IMB; X-ray; 2.20 A; A/B=1-277.
DR PDB; 1IMC; X-ray; 2.60 A; A/B=1-277.
DR PDB; 1IMD; X-ray; 2.60 A; A/B=1-277.
DR PDB; 1IME; X-ray; 2.25 A; A/B=1-277.
DR PDB; 1IMF; X-ray; 2.50 A; A=1-277.
DR PDB; 2HHM; X-ray; 2.10 A; A/B=2-277.
DR PDB; 4AS4; X-ray; 1.70 A; A/B=1-277.
DR PDBsum; 1AWB; -.
DR PDBsum; 1IMA; -.
DR PDBsum; 1IMB; -.
DR PDBsum; 1IMC; -.
DR PDBsum; 1IMD; -.
DR PDBsum; 1IME; -.
DR PDBsum; 1IMF; -.
DR PDBsum; 2HHM; -.
DR PDBsum; 4AS4; -.
DR ProteinModelPortal; P29218; -.
DR SMR; P29218; 3-276.
DR IntAct; P29218; 1.
DR MINT; MINT-1480285; -.
DR STRING; 9606.ENSP00000408526; -.
DR BindingDB; P29218; -.
DR ChEMBL; CHEMBL1786; -.
DR DrugBank; DB01356; Lithium.
DR PhosphoSite; P29218; -.
DR DMDM; 127717; -.
DR REPRODUCTION-2DPAGE; IPI00020906; -.
DR UCD-2DPAGE; P29218; -.
DR PaxDb; P29218; -.
DR PeptideAtlas; P29218; -.
DR PRIDE; P29218; -.
DR DNASU; 3612; -.
DR Ensembl; ENST00000256108; ENSP00000256108; ENSG00000133731.
DR Ensembl; ENST00000311489; ENSP00000311803; ENSG00000133731.
DR Ensembl; ENST00000449740; ENSP00000408526; ENSG00000133731.
DR GeneID; 3612; -.
DR KEGG; hsa:3612; -.
DR UCSC; uc011lfq.1; human.
DR CTD; 3612; -.
DR GeneCards; GC08M082569; -.
DR HGNC; HGNC:6050; IMPA1.
DR HPA; HPA037489; -.
DR MIM; 602064; gene.
DR neXtProt; NX_P29218; -.
DR PharmGKB; PA29860; -.
DR eggNOG; COG0483; -.
DR HOGENOM; HOG000282238; -.
DR HOVERGEN; HBG052123; -.
DR InParanoid; P29218; -.
DR KO; K01092; -.
DR OMA; GMLLITE; -.
DR OrthoDB; EOG7RJPS8; -.
DR PhylomeDB; P29218; -.
DR BioCyc; MetaCyc:HS05783-MONOMER; -.
DR BRENDA; 3.1.3.25; 3474.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P29218; -.
DR UniPathway; UPA00823; UER00788.
DR ChiTaRS; IMPA1; human.
DR EvolutionaryTrace; P29218; -.
DR GeneWiki; IMPA1; -.
DR GenomeRNAi; 3612; -.
DR NextBio; 14127; -.
DR PRO; PR:P29218; -.
DR ArrayExpress; P29218; -.
DR Bgee; P29218; -.
DR CleanEx; HS_IMPA1; -.
DR Genevestigator; P29218; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0008934; F:inositol monophosphate 1-phosphatase activity; IMP:UniProtKB.
DR GO; GO:0052832; F:inositol monophosphate 3-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052833; F:inositol monophosphate 4-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006021; P:inositol biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; IDA:MGI.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IMP:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphorylation; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; IMP:UniProtKB.
DR InterPro; IPR020583; Inositol_monoP_metal-BS.
DR InterPro; IPR020552; Inositol_monoPase_Li-sen.
DR InterPro; IPR000760; Inositol_monophosphatase.
DR InterPro; IPR020550; Inositol_monophosphatase_CS.
DR PANTHER; PTHR20854; PTHR20854; 1.
DR Pfam; PF00459; Inositol_P; 1.
DR PRINTS; PR00377; IMPHPHTASES.
DR PRINTS; PR00378; LIIMPHPHTASE.
DR PROSITE; PS00629; IMP_1; 1.
DR PROSITE; PS00630; IMP_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Hydrolase; Lithium; Magnesium; Metal-binding; Polymorphism;
KW Reference proteome.
FT CHAIN 1 277 Inositol monophosphatase 1.
FT /FTId=PRO_0000142513.
FT REGION 92 95 Substrate binding.
FT REGION 194 196 Substrate binding.
FT METAL 70 70 Magnesium 1.
FT METAL 90 90 Magnesium 1.
FT METAL 90 90 Magnesium 2.
FT METAL 92 92 Magnesium 1; via carbonyl oxygen.
FT METAL 93 93 Magnesium 2.
FT METAL 220 220 Magnesium 2.
FT BINDING 70 70 Substrate.
FT BINDING 213 213 Substrate.
FT BINDING 220 220 Substrate (By similarity).
FT VAR_SEQ 1 1 M -> MGQRPGPVLPAVAVLGQVAKRKVAWLLRWKAVTRTE
FT TAGNSSGVYGFGKMKIFVKYFQKM (in isoform 3).
FT /FTId=VSP_046308.
FT VAR_SEQ 153 277 DITKSLLVTELGSSRTPETVRMVLSNMEKLFCIPVHGIRSV
FT GTAAVNMCLVATGGADAYYEMGIHCWDVAGAGIIVTEAGGV
FT LMDVTGGPFDLMSRRVIAANNRILAERIAKEIQVIPLQRDD
FT ED -> GSGVLEQQLLICALWQLAEQMHIMKWEFTAGMLQE
FT LALLLLKLVAC (in isoform 2).
FT /FTId=VSP_042521.
FT VARIANT 109 109 I -> V (in dbSNP:rs204781).
FT /FTId=VAR_049600.
FT MUTAGEN 36 36 K->Q: 50-fold reduction in activity.
FT MUTAGEN 93 93 D->N: Loss of activity.
FT HELIX 4 26
FT STRAND 34 38
FT STRAND 41 43
FT HELIX 45 61
FT STRAND 66 69
FT HELIX 70 74
FT STRAND 86 93
FT HELIX 95 100
FT STRAND 106 113
FT STRAND 116 124
FT TURN 125 128
FT STRAND 129 134
FT TURN 135 137
FT STRAND 138 141
FT HELIX 154 156
FT STRAND 158 160
FT HELIX 169 183
FT TURN 184 186
FT STRAND 188 192
FT HELIX 196 204
FT STRAND 207 215
FT HELIX 218 230
FT STRAND 234 236
FT STRAND 240 242
FT STRAND 247 255
FT HELIX 256 265
SQ SEQUENCE 277 AA; 30189 MW; 861D5617E1C04627 CRC64;
MADPWQECMD YAVTLARQAG EVVCEAIKNE MNVMLKSSPV DLVTATDQKV EKMLISSIKE
KYPSHSFIGE ESVAAGEKSI LTDNPTWIID PIDGTTNFVH RFPFVAVSIG FAVNKKIEFG
VVYSCVEGKM YTARKGKGAF CNGQKLQVSQ QEDITKSLLV TELGSSRTPE TVRMVLSNME
KLFCIPVHGI RSVGTAAVNM CLVATGGADA YYEMGIHCWD VAGAGIIVTE AGGVLMDVTG
GPFDLMSRRV IAANNRILAE RIAKEIQVIP LQRDDED
//
ID IMPA1_HUMAN Reviewed; 277 AA.
AC P29218; B2R733; B4DLN3; B7Z6Q4; J3KQT7; Q9UK71;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-DEC-1992, sequence version 1.
DT 22-JAN-2014, entry version 152.
DE RecName: Full=Inositol monophosphatase 1;
DE Short=IMP 1;
DE Short=IMPase 1;
DE EC=3.1.3.25;
DE AltName: Full=Inositol-1(or 4)-monophosphatase 1;
DE AltName: Full=Lithium-sensitive myo-inositol monophosphatase A1;
GN Name=IMPA1; Synonyms=IMPA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Hippocampus;
RX PubMed=1377913;
RA McAllister G., Whiting P., Hammond E.A., Knowles M.R., Atack J.R.,
RA Bailey F.J., Maigetter R., Ragan C.I.;
RT "cDNA cloning of human and rat brain myo-inositol monophosphatase.
RT Expression and characterization of the human recombinant enzyme.";
RL Biochem. J. 284:749-754(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9339367; DOI=10.1006/geno.1997.4862;
RA Sjoeholt G., Molven A., Loevlie R., Wilcox A., Sikela J.M.,
RA Steen V.M.;
RT "Genomic structure and chromosomal localization of a human myo-
RT inositol monophosphatase gene (IMPA).";
RL Genomics 45:113-122(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Parthasarathy R., Parthasarathy L., Vadnal R.E.;
RT "Molecular cloning and expression of human cerebral cortex myo-
RT inositol monophosphatase A1 cDNA.";
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Thymus, and Umbilical cord blood;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Urinary bladder;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20.
RA Parthasarathy L., Parthasarathy R.;
RT "Molecular cloning, genomic organization and promoter analysis of the
RT human brain lithium-sensitive myo-inositol monophosphatase A1
RT isoenzyme.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION,
RP AND MUTAGENESIS OF ASP-93.
RX PubMed=17068342; DOI=10.1074/jbc.M604474200;
RA Ohnishi T., Ohba H., Seo K.-C., Im J., Sato Y., Iwayama Y.,
RA Furuichi T., Chung S.-K., Yoshikawa T.;
RT "Spatial expression patterns and biochemical properties distinguish a
RT second myo-inositol monophosphatase IMPA2 from IMPA1.";
RL J. Biol. Chem. 282:637-646(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH MAGNESIUM IONS.
RX PubMed=1332026; DOI=10.1073/pnas.89.21.10031;
RA Bone R., Springer J.P., Atack J.R.;
RT "Structure of inositol monophosphatase, the putative target of lithium
RT therapy.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:10031-10035(1992).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH SUBSTRATE.
RX PubMed=8068621; DOI=10.1021/bi00198a012;
RA Bone R., Frank L., Springer J.P., Atack J.R.;
RT "Structural studies of metal binding by inositol monophosphatase:
RT evidence for two-metal ion catalysis.";
RL Biochemistry 33:9468-9476(1994).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT GLN-36, AND
RP MUTAGENESIS OF LYS-36.
RX PubMed=8718889; DOI=10.1021/bi9603837;
RA Ganzhorn A.J., Lepage P., Pelton P.D., Strasser F., Vincendon P.,
RA Rondeau J.-M.;
RT "The contribution of lysine-36 to catalysis by human myo-inositol
RT monophosphatase.";
RL Biochemistry 35:10957-10966(1996).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RA Ganzhorn A.J., Rondeau J.-M.;
RT "Structure of an enzyme-substrate complex and the catalytic mechanism
RT of human brain myo-inositol monophosphatase.";
RL Protein Eng. 10:61-70(1997).
CC -!- FUNCTION: Responsible for the provision of inositol required for
CC synthesis of phosphatidylinositol and polyphosphoinositides and
CC has been implicated as the pharmacological target for lithium
CC action in brain. Can use myo-inositol monophosphates, myo-inositol
CC 1,3-diphosphate, myo-inositol 1,4-diphosphate, scyllo-inositol-
CC phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-
CC phosphate, beta-glycerophosphate, and 2'-AMP as substrates.
CC -!- CATALYTIC ACTIVITY: Myo-inositol phosphate + H(2)O = myo-inositol
CC + phosphate.
CC -!- COFACTOR: Magnesium.
CC -!- ENZYME REGULATION: Inhibited by Li(+).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.0-7.5;
CC -!- PATHWAY: Polyol metabolism; myo-inositol biosynthesis; myo-
CC inositol from D-glucose 6-phosphate: step 2/2.
CC -!- SUBUNIT: Homodimer.
CC -!- INTERACTION:
CC Self; NbExp=3; IntAct=EBI-752410, EBI-752410;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P29218-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P29218-2; Sequence=VSP_042521;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=P29218-3; Sequence=VSP_046308;
CC Note=No experimental confirmation available. Ref.4 (BAH13340)
CC sequence is in conflict in position: 17:Q->R;
CC -!- SIMILARITY: Belongs to the inositol monophosphatase family.
CC -----------------------------------------------------------------------
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DR EMBL; X66922; CAA47359.1; -; mRNA.
DR EMBL; Y11360; CAA72195.1; -; Genomic_DNA.
DR EMBL; Y11361; CAA72195.1; JOINED; Genomic_DNA.
DR EMBL; Y11362; CAA72195.1; JOINED; Genomic_DNA.
DR EMBL; Y11367; CAA72195.1; JOINED; Genomic_DNA.
DR EMBL; Y11363; CAA72195.1; JOINED; Genomic_DNA.
DR EMBL; Y11364; CAA72195.1; JOINED; Genomic_DNA.
DR EMBL; Y11365; CAA72195.1; JOINED; Genomic_DNA.
DR EMBL; Y11366; CAA72195.1; JOINED; Genomic_DNA.
DR EMBL; AF042729; AAB97468.1; -; mRNA.
DR EMBL; AK297078; BAG59595.1; -; mRNA.
DR EMBL; AK300750; BAH13340.1; -; mRNA.
DR EMBL; AK312823; BAG35680.1; -; mRNA.
DR EMBL; AC090255; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471068; EAW87095.1; -; Genomic_DNA.
DR EMBL; BC008381; AAH08381.1; -; mRNA.
DR EMBL; BC009565; AAH09565.1; -; mRNA.
DR EMBL; AF178754; AAD52997.1; -; Genomic_DNA.
DR PIR; S23130; S23130.
DR RefSeq; NP_001138350.1; NM_001144878.1.
DR RefSeq; NP_001138351.1; NM_001144879.1.
DR RefSeq; NP_005527.1; NM_005536.3.
DR UniGene; Hs.656694; -.
DR PDB; 1AWB; X-ray; 2.50 A; A/B=2-277.
DR PDB; 1IMA; X-ray; 2.30 A; A/B=1-277.
DR PDB; 1IMB; X-ray; 2.20 A; A/B=1-277.
DR PDB; 1IMC; X-ray; 2.60 A; A/B=1-277.
DR PDB; 1IMD; X-ray; 2.60 A; A/B=1-277.
DR PDB; 1IME; X-ray; 2.25 A; A/B=1-277.
DR PDB; 1IMF; X-ray; 2.50 A; A=1-277.
DR PDB; 2HHM; X-ray; 2.10 A; A/B=2-277.
DR PDB; 4AS4; X-ray; 1.70 A; A/B=1-277.
DR PDBsum; 1AWB; -.
DR PDBsum; 1IMA; -.
DR PDBsum; 1IMB; -.
DR PDBsum; 1IMC; -.
DR PDBsum; 1IMD; -.
DR PDBsum; 1IME; -.
DR PDBsum; 1IMF; -.
DR PDBsum; 2HHM; -.
DR PDBsum; 4AS4; -.
DR ProteinModelPortal; P29218; -.
DR SMR; P29218; 3-276.
DR IntAct; P29218; 1.
DR MINT; MINT-1480285; -.
DR STRING; 9606.ENSP00000408526; -.
DR BindingDB; P29218; -.
DR ChEMBL; CHEMBL1786; -.
DR DrugBank; DB01356; Lithium.
DR PhosphoSite; P29218; -.
DR DMDM; 127717; -.
DR REPRODUCTION-2DPAGE; IPI00020906; -.
DR UCD-2DPAGE; P29218; -.
DR PaxDb; P29218; -.
DR PeptideAtlas; P29218; -.
DR PRIDE; P29218; -.
DR DNASU; 3612; -.
DR Ensembl; ENST00000256108; ENSP00000256108; ENSG00000133731.
DR Ensembl; ENST00000311489; ENSP00000311803; ENSG00000133731.
DR Ensembl; ENST00000449740; ENSP00000408526; ENSG00000133731.
DR GeneID; 3612; -.
DR KEGG; hsa:3612; -.
DR UCSC; uc011lfq.1; human.
DR CTD; 3612; -.
DR GeneCards; GC08M082569; -.
DR HGNC; HGNC:6050; IMPA1.
DR HPA; HPA037489; -.
DR MIM; 602064; gene.
DR neXtProt; NX_P29218; -.
DR PharmGKB; PA29860; -.
DR eggNOG; COG0483; -.
DR HOGENOM; HOG000282238; -.
DR HOVERGEN; HBG052123; -.
DR InParanoid; P29218; -.
DR KO; K01092; -.
DR OMA; GMLLITE; -.
DR OrthoDB; EOG7RJPS8; -.
DR PhylomeDB; P29218; -.
DR BioCyc; MetaCyc:HS05783-MONOMER; -.
DR BRENDA; 3.1.3.25; 3474.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P29218; -.
DR UniPathway; UPA00823; UER00788.
DR ChiTaRS; IMPA1; human.
DR EvolutionaryTrace; P29218; -.
DR GeneWiki; IMPA1; -.
DR GenomeRNAi; 3612; -.
DR NextBio; 14127; -.
DR PRO; PR:P29218; -.
DR ArrayExpress; P29218; -.
DR Bgee; P29218; -.
DR CleanEx; HS_IMPA1; -.
DR Genevestigator; P29218; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0008934; F:inositol monophosphate 1-phosphatase activity; IMP:UniProtKB.
DR GO; GO:0052832; F:inositol monophosphate 3-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052833; F:inositol monophosphate 4-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006021; P:inositol biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; IDA:MGI.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IMP:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphorylation; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; IMP:UniProtKB.
DR InterPro; IPR020583; Inositol_monoP_metal-BS.
DR InterPro; IPR020552; Inositol_monoPase_Li-sen.
DR InterPro; IPR000760; Inositol_monophosphatase.
DR InterPro; IPR020550; Inositol_monophosphatase_CS.
DR PANTHER; PTHR20854; PTHR20854; 1.
DR Pfam; PF00459; Inositol_P; 1.
DR PRINTS; PR00377; IMPHPHTASES.
DR PRINTS; PR00378; LIIMPHPHTASE.
DR PROSITE; PS00629; IMP_1; 1.
DR PROSITE; PS00630; IMP_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Hydrolase; Lithium; Magnesium; Metal-binding; Polymorphism;
KW Reference proteome.
FT CHAIN 1 277 Inositol monophosphatase 1.
FT /FTId=PRO_0000142513.
FT REGION 92 95 Substrate binding.
FT REGION 194 196 Substrate binding.
FT METAL 70 70 Magnesium 1.
FT METAL 90 90 Magnesium 1.
FT METAL 90 90 Magnesium 2.
FT METAL 92 92 Magnesium 1; via carbonyl oxygen.
FT METAL 93 93 Magnesium 2.
FT METAL 220 220 Magnesium 2.
FT BINDING 70 70 Substrate.
FT BINDING 213 213 Substrate.
FT BINDING 220 220 Substrate (By similarity).
FT VAR_SEQ 1 1 M -> MGQRPGPVLPAVAVLGQVAKRKVAWLLRWKAVTRTE
FT TAGNSSGVYGFGKMKIFVKYFQKM (in isoform 3).
FT /FTId=VSP_046308.
FT VAR_SEQ 153 277 DITKSLLVTELGSSRTPETVRMVLSNMEKLFCIPVHGIRSV
FT GTAAVNMCLVATGGADAYYEMGIHCWDVAGAGIIVTEAGGV
FT LMDVTGGPFDLMSRRVIAANNRILAERIAKEIQVIPLQRDD
FT ED -> GSGVLEQQLLICALWQLAEQMHIMKWEFTAGMLQE
FT LALLLLKLVAC (in isoform 2).
FT /FTId=VSP_042521.
FT VARIANT 109 109 I -> V (in dbSNP:rs204781).
FT /FTId=VAR_049600.
FT MUTAGEN 36 36 K->Q: 50-fold reduction in activity.
FT MUTAGEN 93 93 D->N: Loss of activity.
FT HELIX 4 26
FT STRAND 34 38
FT STRAND 41 43
FT HELIX 45 61
FT STRAND 66 69
FT HELIX 70 74
FT STRAND 86 93
FT HELIX 95 100
FT STRAND 106 113
FT STRAND 116 124
FT TURN 125 128
FT STRAND 129 134
FT TURN 135 137
FT STRAND 138 141
FT HELIX 154 156
FT STRAND 158 160
FT HELIX 169 183
FT TURN 184 186
FT STRAND 188 192
FT HELIX 196 204
FT STRAND 207 215
FT HELIX 218 230
FT STRAND 234 236
FT STRAND 240 242
FT STRAND 247 255
FT HELIX 256 265
SQ SEQUENCE 277 AA; 30189 MW; 861D5617E1C04627 CRC64;
MADPWQECMD YAVTLARQAG EVVCEAIKNE MNVMLKSSPV DLVTATDQKV EKMLISSIKE
KYPSHSFIGE ESVAAGEKSI LTDNPTWIID PIDGTTNFVH RFPFVAVSIG FAVNKKIEFG
VVYSCVEGKM YTARKGKGAF CNGQKLQVSQ QEDITKSLLV TELGSSRTPE TVRMVLSNME
KLFCIPVHGI RSVGTAAVNM CLVATGGADA YYEMGIHCWD VAGAGIIVTE AGGVLMDVTG
GPFDLMSRRV IAANNRILAE RIAKEIQVIP LQRDDED
//
MIM
602064
*RECORD*
*FIELD* NO
602064
*FIELD* TI
*602064 MYO-INOSITOL MONOPHOSPHATASE 1; IMPA1
*FIELD* TX
CLONING
McAllister et al. (1992) cloned the gene encoding human enzyme IMPase
read more(IMPA1).
GENE STRUCTURE
Sjoholt et al. (1997) determined the genomic structure of the human
IMPA1 gene. They found that it is composed of at least 9 exons and
covers more than 20 kb of sequence on 8q21.13-q21.3. In the 3-prime
untranslated part of the gene, they observed a G-to-A transition and
also 2 short sequences similar to the inositol/cholin-responsive element
consensus. They postulated that 2 additional IMPA-like transcripts
originate from the human genome, 1 from a position close to IMPA1 itself
on chromosome 8 and the other from 18p.
GENE FUNCTION
Manic depressive psychosis (125480) is a serious psychiatric disorder
that in many, but far from all, patients can be treated with lithium.
IMPase has been postulated as a target for the mood-stabilizing effects
of lithium. Variation in the 277-codon coding region of IMPA1 has not
been observed in manic-depressive patients (Steen et al., 1996). Sjoholt
et al. (1997) suggested that polymorphisms or mutations in the noncoding
regions of this gene could influence the lithium response in psychiatric
patients.
In studies on the effect of lithium on Xenopus morphogenesis, Klein and
Melton (1996) concluded that lithium acts through inhibition of glycogen
synthase kinase beta-3 (GSK3B; 605004), and not through inhibition of
IMPase. The authors suggested that their observations could provide
insights into the pathogenesis and treatment of bipolar disorder.
MAPPING
By PCR analysis of both CEPH megabase-insert YAC DNA pools and
human/rodent somatic cell hybrid DNAs, Sjoholt et al. (1997) mapped the
IMPA1 gene to 8q21.13-q21.3.
*FIELD* RF
1. Klein, S. P.; Melton, D. A.: A molecular mechanism for the effect
of lithium on development. Proc. Nat. Acad. Sci. 93: 8455-8459,
1996.
2. McAllister, G.; Whiting, P.; Hammond, E. A.; Knowles, M. R.; Atack,
J. R.; Bailey, F. J.; Maigetter, R.; Ragan, C. I.: cDNA cloning of
human and rat brain myo-inositol monophosphatase: expression and characterization
of the human recombinant enzyme. Biochem. J. 284: 749-754, 1992.
3. Sjoholt, G.; Molven, A.; Lovlie, R.; Wilcox, A.; Sikela, J. M.;
Steen, V. M.: Genomic structure and chromosomal localization of a
human myo-inositol monophosphatase gene (IMPA). Genomics 45: 113-122,
1997.
4. Steen, V. M.; Gulbrandsen, A. K.; Eiken, H. G.; Berle, J. O.:
Lack of genetic variation in the coding region of the myo-inositol
monophosphatase gene in lithium-treated patients with manic depressive
illness. Pharmacogenetics 6: 113-116, 1996.
*FIELD* CN
Dawn Watkins-Chow - updated: 8/23/2002
*FIELD* CD
Victor A. McKusick: 10/17/1997
*FIELD* ED
tkritzer: 02/05/2003
tkritzer: 8/23/2002
dkim: 12/16/1998
dholmes: 11/5/1997
jenny: 10/17/1997
*RECORD*
*FIELD* NO
602064
*FIELD* TI
*602064 MYO-INOSITOL MONOPHOSPHATASE 1; IMPA1
*FIELD* TX
CLONING
McAllister et al. (1992) cloned the gene encoding human enzyme IMPase
read more(IMPA1).
GENE STRUCTURE
Sjoholt et al. (1997) determined the genomic structure of the human
IMPA1 gene. They found that it is composed of at least 9 exons and
covers more than 20 kb of sequence on 8q21.13-q21.3. In the 3-prime
untranslated part of the gene, they observed a G-to-A transition and
also 2 short sequences similar to the inositol/cholin-responsive element
consensus. They postulated that 2 additional IMPA-like transcripts
originate from the human genome, 1 from a position close to IMPA1 itself
on chromosome 8 and the other from 18p.
GENE FUNCTION
Manic depressive psychosis (125480) is a serious psychiatric disorder
that in many, but far from all, patients can be treated with lithium.
IMPase has been postulated as a target for the mood-stabilizing effects
of lithium. Variation in the 277-codon coding region of IMPA1 has not
been observed in manic-depressive patients (Steen et al., 1996). Sjoholt
et al. (1997) suggested that polymorphisms or mutations in the noncoding
regions of this gene could influence the lithium response in psychiatric
patients.
In studies on the effect of lithium on Xenopus morphogenesis, Klein and
Melton (1996) concluded that lithium acts through inhibition of glycogen
synthase kinase beta-3 (GSK3B; 605004), and not through inhibition of
IMPase. The authors suggested that their observations could provide
insights into the pathogenesis and treatment of bipolar disorder.
MAPPING
By PCR analysis of both CEPH megabase-insert YAC DNA pools and
human/rodent somatic cell hybrid DNAs, Sjoholt et al. (1997) mapped the
IMPA1 gene to 8q21.13-q21.3.
*FIELD* RF
1. Klein, S. P.; Melton, D. A.: A molecular mechanism for the effect
of lithium on development. Proc. Nat. Acad. Sci. 93: 8455-8459,
1996.
2. McAllister, G.; Whiting, P.; Hammond, E. A.; Knowles, M. R.; Atack,
J. R.; Bailey, F. J.; Maigetter, R.; Ragan, C. I.: cDNA cloning of
human and rat brain myo-inositol monophosphatase: expression and characterization
of the human recombinant enzyme. Biochem. J. 284: 749-754, 1992.
3. Sjoholt, G.; Molven, A.; Lovlie, R.; Wilcox, A.; Sikela, J. M.;
Steen, V. M.: Genomic structure and chromosomal localization of a
human myo-inositol monophosphatase gene (IMPA). Genomics 45: 113-122,
1997.
4. Steen, V. M.; Gulbrandsen, A. K.; Eiken, H. G.; Berle, J. O.:
Lack of genetic variation in the coding region of the myo-inositol
monophosphatase gene in lithium-treated patients with manic depressive
illness. Pharmacogenetics 6: 113-116, 1996.
*FIELD* CN
Dawn Watkins-Chow - updated: 8/23/2002
*FIELD* CD
Victor A. McKusick: 10/17/1997
*FIELD* ED
tkritzer: 02/05/2003
tkritzer: 8/23/2002
dkim: 12/16/1998
dholmes: 11/5/1997
jenny: 10/17/1997