IMPA1_HUMAN
ID IMPA1_HUMAN Reviewed; 277 AA.
AC P29218; B2R733; B4DLN3; B7Z6Q4; J3KQT7; Q9UK71;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Inositol monophosphatase 1;
DE Short=IMP 1;
DE Short=IMPase 1;
DE EC=3.1.3.25 {ECO:0000269|PubMed:1377913, ECO:0000269|PubMed:17068342, ECO:0000269|PubMed:8068620, ECO:0000269|PubMed:8718889, ECO:0000269|PubMed:9462881};
DE AltName: Full=D-galactose 1-phosphate phosphatase {ECO:0000303|PubMed:9462881};
DE EC=3.1.3.94 {ECO:0000269|PubMed:9462881};
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CATALYTIC ACTIVITY.
RC TISSUE=Hippocampus;
RX PubMed=1377913; DOI=10.1042/bj2840749;
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., Steen V.M.;
RT "Genomic structure and chromosomal localization of a human myo-inositol
RT 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-inositol
RT 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., 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., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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 human
RT brain lithium-sensitive myo-inositol monophosphatase A1 isoenzyme.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=9462881; DOI=10.1016/s0006-8993(97)01042-1;
RA Parthasarathy R., Parthasarathy L., Vadnal R.;
RT "Brain inositol monophosphatase identified as a galactose 1-phosphatase.";
RL Brain Res. 778:99-106(1997).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, 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., Furuichi T.,
RA 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 [11]
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 [12]
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 [13]
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., Buerckstuemmer T.,
RA 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-168, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP INVOLVEMENT IN MRT59.
RX PubMed=26416544; DOI=10.1038/mp.2015.150;
RA Figueiredo T., Melo U.S., Pessoa A.L., Nobrega P.R., Kitajima J.P.,
RA Rusch H., Vaz F., Lucato L.T., Zatz M., Kok F., Santos S.;
RT "A homozygous loss-of-function mutation in inositol monophosphatase 1
RT (IMPA1) causes severe intellectual disability.";
RL Mol. Psychiatry 21:1125-1129(2016).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH GADOLINIUM IONS,
RP METAL-BINDING SITE, AND SUBUNIT.
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 [17]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH MYO-INOSITOL
RP 1-PHOSPHATE AND GADOLINIUM ION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, METAL-BINDING SITE, AND MUTAGENESIS OF SER-165 AND
RP GLU-213.
RX PubMed=8068620; DOI=10.1021/bi00198a011;
RA Bone R., Frank L., Springer J.P., Pollack S.J., Osborne S.A., Atack J.R.,
RA Knowles M.R., McAllister G., Ragan C.I., Broughton H.B.;
RT "Structural analysis of inositol monophosphatase complexes with
RT substrates.";
RL Biochemistry 33:9460-9467(1994).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE ANALOG
RP AND MANGANESE, AND COFACTOR.
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: evidence
RT for two-metal ion catalysis.";
RL Biochemistry 33:9468-9476(1994).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT GLN-36, MUTAGENESIS OF
RP LYS-36, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, AND ACTIVITY REGULATION.
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 [20]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH 1D-MYO-INOSITOL
RP 1-PHOSPHATE AND CALCIUM, AND METAL-BINDING SITE.
RA Ganzhorn A.J., Rondeau J.-M.;
RT "Structure of an enzyme-substrate complex and the catalytic mechanism of
RT human brain myo-inositol monophosphatase.";
RL Protein Eng. 10:61-70(1997).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH MAGNESIUM, COFACTOR,
RP AND SUBUNIT.
RX PubMed=23027737; DOI=10.1107/s1744309112035191;
RA Singh N., Halliday A.C., Knight M., Lack N.A., Lowe E., Churchill G.C.;
RT "Cloning, expression, purification, crystallization and X-ray analysis of
RT inositol monophosphatase from Mus musculus and Homo sapiens.";
RL Acta Crystallogr. F 68:1149-1152(2012).
CC -!- FUNCTION: Responsible for the provision of inositol required for
CC synthesis of phosphatidylinositol and polyphosphoinositides and has
CC been implicated as the pharmacological target for lithium action in
CC brain. Has broad substrate specificity and can use myo-inositol
CC monophosphates, myo-inositol 1,3-diphosphate, myo-inositol 1,4-
CC diphosphate, scyllo-inositol-phosphate, D-galactose 1-phosphate,
CC glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-
CC glycerophosphate, and 2'-AMP as substrates.
CC {ECO:0000269|PubMed:17068342, ECO:0000269|PubMed:8718889,
CC ECO:0000269|PubMed:9462881}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a myo-inositol phosphate + H2O = myo-inositol + phosphate;
CC Xref=Rhea:RHEA:24056, ChEBI:CHEBI:15377, ChEBI:CHEBI:17268,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:84139; EC=3.1.3.25;
CC Evidence={ECO:0000269|PubMed:1377913, ECO:0000269|PubMed:8068620,
CC ECO:0000269|PubMed:8718889, ECO:0000269|PubMed:9462881};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=alpha-D-galactose 1-phosphate + H2O = D-galactose + phosphate;
CC Xref=Rhea:RHEA:29315, ChEBI:CHEBI:4139, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58336; EC=3.1.3.94;
CC Evidence={ECO:0000269|PubMed:9462881};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:17068342, ECO:0000269|PubMed:8718889,
CC ECO:0000269|PubMed:9462881, ECO:0000303|PubMed:23027737,
CC ECO:0000303|PubMed:8068621};
CC -!- ACTIVITY REGULATION: Activity with myo-inositol monophosphate and D-
CC galactose 1-phosphate is inhibited by Li(+), Ca(2+) and Mn(2+), but
CC also by Mg(2+) at concentrations above 3 mM.
CC {ECO:0000269|PubMed:17068342, ECO:0000269|PubMed:8718889,
CC ECO:0000269|PubMed:9462881}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=42 uM for D-myo-inositol 1-phosphate {ECO:0000269|PubMed:8068620};
CC KM=62 uM for L-myo-inositol 1-phosphate {ECO:0000269|PubMed:8068620};
CC pH dependence:
CC Optimum pH is 7.0-7.5. {ECO:0000269|PubMed:17068342};
CC -!- PATHWAY: Polyol metabolism; myo-inositol biosynthesis; myo-inositol
CC from D-glucose 6-phosphate: step 2/2.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:1332026,
CC ECO:0000269|PubMed:23027737, ECO:0000269|PubMed:8068620,
CC ECO:0000269|PubMed:8068621, ECO:0000269|PubMed:9462881}.
CC -!- INTERACTION:
CC P29218; P29218: IMPA1; NbExp=4; IntAct=EBI-752410, EBI-752410;
CC P29218; O14732: IMPA2; NbExp=3; IntAct=EBI-752410, EBI-725233;
CC P29218-3; P54253: ATXN1; NbExp=3; IntAct=EBI-12330251, EBI-930964;
CC P29218-3; G5E9A7: DMWD; NbExp=3; IntAct=EBI-12330251, EBI-10976677;
CC P29218-3; P42858: HTT; NbExp=6; IntAct=EBI-12330251, EBI-466029;
CC P29218-3; P29218-3: IMPA1; NbExp=3; IntAct=EBI-12330251, EBI-12330251;
CC P29218-3; O14732: IMPA2; NbExp=3; IntAct=EBI-12330251, EBI-725233;
CC P29218-3; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-12330251, EBI-5235340;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17068342}.
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 Name=3;
CC IsoId=P29218-3; Sequence=VSP_046308;
CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 59
CC (MRT59) [MIM:617323]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period.
CC {ECO:0000269|PubMed:26416544}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the inositol monophosphatase superfamily.
CC {ECO:0000305}.
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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 CCDS; CCDS47883.1; -. [P29218-3]
DR CCDS; CCDS47884.1; -. [P29218-2]
DR CCDS; CCDS6231.1; -. [P29218-1]
DR PIR; S23130; S23130.
DR RefSeq; NP_001138350.1; NM_001144878.1. [P29218-3]
DR RefSeq; NP_001138351.1; NM_001144879.1. [P29218-2]
DR RefSeq; NP_005527.1; NM_005536.3. [P29218-1]
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 PDB; 6GIU; X-ray; 1.39 A; A/B=1-277.
DR PDB; 6GJ0; X-ray; 1.73 A; A/B=1-277.
DR PDB; 6ZK0; X-ray; 1.47 A; AAA/BBB=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 PDBsum; 6GIU; -.
DR PDBsum; 6GJ0; -.
DR PDBsum; 6ZK0; -.
DR AlphaFoldDB; P29218; -.
DR SMR; P29218; -.
DR BioGRID; 109825; 36.
DR IntAct; P29218; 7.
DR MINT; P29218; -.
DR STRING; 9606.ENSP00000408526; -.
DR ChEMBL; CHEMBL1786; -.
DR DrugBank; DB03542; L-Myo-Inositol-1-Phosphate.
DR DrugBank; DB14509; Lithium carbonate.
DR DrugBank; DB01356; Lithium cation.
DR DrugBank; DB14507; Lithium citrate.
DR DrugBank; DB14508; Lithium succinate.
DR DrugCentral; P29218; -.
DR GuidetoPHARMACOLOGY; 1463; -.
DR DEPOD; IMPA1; -.
DR GlyGen; P29218; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P29218; -.
DR PhosphoSitePlus; P29218; -.
DR SwissPalm; P29218; -.
DR BioMuta; IMPA1; -.
DR DMDM; 127717; -.
DR REPRODUCTION-2DPAGE; IPI00020906; -.
DR UCD-2DPAGE; P29218; -.
DR EPD; P29218; -.
DR jPOST; P29218; -.
DR MassIVE; P29218; -.
DR MaxQB; P29218; -.
DR PaxDb; P29218; -.
DR PeptideAtlas; P29218; -.
DR PRIDE; P29218; -.
DR ProteomicsDB; 54529; -. [P29218-1]
DR ProteomicsDB; 54530; -. [P29218-2]
DR Antibodypedia; 25334; 156 antibodies from 27 providers.
DR DNASU; 3612; -.
DR Ensembl; ENST00000256108.10; ENSP00000256108.5; ENSG00000133731.10. [P29218-1]
DR Ensembl; ENST00000311489.8; ENSP00000311803.4; ENSG00000133731.10. [P29218-2]
DR Ensembl; ENST00000449740.6; ENSP00000408526.2; ENSG00000133731.10. [P29218-3]
DR GeneID; 3612; -.
DR KEGG; hsa:3612; -.
DR MANE-Select; ENST00000256108.10; ENSP00000256108.5; NM_005536.4; NP_005527.1.
DR UCSC; uc003ych.3; human. [P29218-1]
DR CTD; 3612; -.
DR DisGeNET; 3612; -.
DR GeneCards; IMPA1; -.
DR HGNC; HGNC:6050; IMPA1.
DR HPA; ENSG00000133731; Low tissue specificity.
DR MalaCards; IMPA1; -.
DR MIM; 602064; gene.
DR MIM; 617323; phenotype.
DR neXtProt; NX_P29218; -.
DR OpenTargets; ENSG00000133731; -.
DR PharmGKB; PA29860; -.
DR VEuPathDB; HostDB:ENSG00000133731; -.
DR eggNOG; KOG2951; Eukaryota.
DR GeneTree; ENSGT00940000154634; -.
DR HOGENOM; CLU_044118_1_0_1; -.
DR InParanoid; P29218; -.
DR OMA; RVDGYWE; -.
DR PhylomeDB; P29218; -.
DR TreeFam; TF313194; -.
DR BioCyc; MetaCyc:HS05783-MON; -.
DR BRENDA; 3.1.3.25; 2681.
DR PathwayCommons; P29218; -.
DR Reactome; R-HSA-1855183; Synthesis of IP2, IP, and Ins in the cytosol.
DR SABIO-RK; P29218; -.
DR SignaLink; P29218; -.
DR UniPathway; UPA00823; UER00788.
DR BioGRID-ORCS; 3612; 16 hits in 1083 CRISPR screens.
DR ChiTaRS; IMPA1; human.
DR EvolutionaryTrace; P29218; -.
DR GeneWiki; IMPA1; -.
DR GenomeRNAi; 3612; -.
DR Pharos; P29218; Tclin.
DR PRO; PR:P29218; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P29218; protein.
DR Bgee; ENSG00000133731; Expressed in secondary oocyte and 207 other tissues.
DR ExpressionAtlas; P29218; baseline and differential.
DR Genevisible; P29218; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008934; F:inositol monophosphate 1-phosphatase activity; IDA:MGI.
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:0052834; F:inositol monophosphate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0031403; F:lithium ion binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:MGI.
DR GO; GO:0006021; P:inositol biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006020; P:inositol metabolic process; IBA:GO_Central.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; IDA:UniProtKB.
DR GO; GO:0006796; P:phosphate-containing compound metabolic process; IMP:UniProtKB.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IMP:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; IMP:UniProtKB.
DR CDD; cd01639; IMPase; 1.
DR InterPro; IPR033942; IMPase.
DR InterPro; IPR020583; Inositol_monoP_metal-BS.
DR InterPro; IPR020552; Inositol_monoPase_Li-sen.
DR InterPro; IPR000760; Inositol_monophosphatase-like.
DR InterPro; IPR020550; Inositol_monophosphatase_CS.
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; Cytoplasm; Hydrolase;
KW Intellectual disability; Lithium; Magnesium; Metal-binding; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..277
FT /note="Inositol monophosphatase 1"
FT /id="PRO_0000142513"
FT BINDING 70
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:23027737,
FT ECO:0000269|PubMed:8068621, ECO:0000303|PubMed:1332026,
FT ECO:0000303|PubMed:8068620"
FT BINDING 70
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:8068620,
FT ECO:0000303|PubMed:8068621"
FT BINDING 90
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:23027737,
FT ECO:0000269|PubMed:8068621, ECO:0000303|PubMed:1332026,
FT ECO:0000303|PubMed:8068620"
FT BINDING 90
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23027737,
FT ECO:0000269|PubMed:8068621"
FT BINDING 92..95
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:8068620,
FT ECO:0000303|PubMed:8068621"
FT BINDING 92
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:23027737,
FT ECO:0000269|PubMed:8068621, ECO:0000303|PubMed:1332026,
FT ECO:0000303|PubMed:8068620"
FT BINDING 93
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23027737,
FT ECO:0000269|PubMed:8068621"
FT BINDING 194..196
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:8068620"
FT BINDING 213
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:8068620,
FT ECO:0000303|PubMed:8068621"
FT BINDING 220
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23027737,
FT ECO:0000269|PubMed:8068621"
FT BINDING 220
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:8068620"
FT MOD_RES 168
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1
FT /note="M -> MGQRPGPVLPAVAVLGQVAKRKVAWLLRWKAVTRTETAGNSSGVYGF
FT GKMKIFVKYFQKM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046308"
FT VAR_SEQ 153..277
FT /note="DITKSLLVTELGSSRTPETVRMVLSNMEKLFCIPVHGIRSVGTAAVNMCLVA
FT TGGADAYYEMGIHCWDVAGAGIIVTEAGGVLMDVTGGPFDLMSRRVIAANNRILAERIA
FT KEIQVIPLQRDDED -> GSGVLEQQLLICALWQLAEQMHIMKWEFTAGMLQELALLLL
FT KLVAC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042521"
FT VARIANT 109
FT /note="I -> V (in dbSNP:rs204781)"
FT /id="VAR_049600"
FT MUTAGEN 36
FT /note="K->Q: 50-fold reduction in activity."
FT /evidence="ECO:0000269|PubMed:8718889"
FT MUTAGEN 93
FT /note="D->N: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17068342"
FT MUTAGEN 165
FT /note="S->A,I: Reduced enzyme activity with myo-inositol 1-
FT phosphate."
FT /evidence="ECO:0000269|PubMed:8068620"
FT MUTAGEN 213
FT /note="E->Q: Strongly reduced affinity for myo-inositol 1-
FT phosphate and strongly reduced enzyme activity with myo-
FT inositol 1-phosphate."
FT /evidence="ECO:0000269|PubMed:8068620"
FT HELIX 6..27
FT /evidence="ECO:0007829|PDB:6GIU"
FT STRAND 34..38
FT /evidence="ECO:0007829|PDB:6GIU"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:6GIU"
FT HELIX 45..61
FT /evidence="ECO:0007829|PDB:6GIU"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:6GIU"
FT HELIX 70..74
FT /evidence="ECO:0007829|PDB:6GIU"
FT STRAND 86..93
FT /evidence="ECO:0007829|PDB:6GIU"
FT HELIX 95..100
FT /evidence="ECO:0007829|PDB:6GIU"
FT STRAND 106..113
FT /evidence="ECO:0007829|PDB:6GIU"
FT STRAND 116..124
FT /evidence="ECO:0007829|PDB:6GIU"
FT TURN 125..128
FT /evidence="ECO:0007829|PDB:6GIU"
FT STRAND 129..134
FT /evidence="ECO:0007829|PDB:6GIU"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:6GIU"
FT STRAND 138..141
FT /evidence="ECO:0007829|PDB:6GIU"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:6GIU"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:6GIU"
FT HELIX 169..183
FT /evidence="ECO:0007829|PDB:6GIU"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:6GIU"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:6GIU"
FT HELIX 196..204
FT /evidence="ECO:0007829|PDB:6GIU"
FT STRAND 207..215
FT /evidence="ECO:0007829|PDB:6GIU"
FT HELIX 218..221
FT /evidence="ECO:0007829|PDB:6GIU"
FT HELIX 224..230
FT /evidence="ECO:0007829|PDB:6GIU"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:6GIU"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:6GIU"
FT STRAND 247..255
FT /evidence="ECO:0007829|PDB:6GIU"
FT HELIX 256..263
FT /evidence="ECO:0007829|PDB:6GIU"
FT CONFLICT P29218-3:17
FT /note="Q -> R (in Ref. 4; BAH13340)"
FT /evidence="ECO:0000305"
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
