IMPA1_MOUSE
ID IMPA1_MOUSE Reviewed; 277 AA.
AC O55023;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Inositol monophosphatase 1;
DE Short=IMP 1;
DE Short=IMPase 1;
DE EC=3.1.3.25 {ECO:0000250|UniProtKB:P29218};
DE AltName: Full=D-galactose 1-phosphate phosphatase {ECO:0000250|UniProtKB:P29218};
DE EC=3.1.3.94 {ECO:0000250|UniProtKB:P29218};
DE AltName: Full=Inositol-1(or 4)-monophosphatase 1;
DE AltName: Full=Lithium-sensitive myo-inositol monophosphatase A1;
GN Name=Impa1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Parthasarathy L., Parthasarathy R., Vadnal R.E.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP INDUCTION.
RX PubMed=12877981; DOI=10.1016/s0169-328x(03)00120-7;
RA Shamir A., Shaltiel G., Greenberg M.L., Belmaker R.H., Agam G.;
RT "The effect of lithium on expression of genes for inositol biosynthetic
RT enzymes in mouse hippocampus; a comparison with the yeast model.";
RL Brain Res. Mol. Brain Res. 115:104-110(2003).
RN [3]
RP TISSUE SPECIFICITY.
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.43 ANGSTROMS) IN COMPLEX WITH MAGNESIUM AND
RP PHOSPHATE, SUBUNIT, AND COFACTOR.
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:0000250|UniProtKB:P29218}.
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:0000250|UniProtKB:P29218};
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:0000250|UniProtKB:P29218};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000303|PubMed:23027737};
CC -!- ACTIVITY REGULATION: Inhibited by Li(+), Ca(2+) and Mn(2+), but also by
CC Mg(2+) at concentrations above 3 mM. {ECO:0000250|UniProtKB:P29218}.
CC -!- PATHWAY: Polyol metabolism; myo-inositol biosynthesis; myo-inositol
CC from D-glucose 6-phosphate: step 2/2.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:23027737}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P29218}.
CC -!- TISSUE SPECIFICITY: Mostly expressed in brain, small intestine, testis,
CC kidney, and spleen (at protein level). {ECO:0000269|PubMed:17068342}.
CC -!- INDUCTION: By lithium Li(+) in hippocamp.
CC {ECO:0000269|PubMed:12877981}.
CC -!- SIMILARITY: Belongs to the inositol monophosphatase superfamily.
CC {ECO:0000305}.
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DR EMBL; AF042730; AAB97469.1; -; mRNA.
DR CCDS; CCDS17240.1; -.
DR PDB; 4AS5; X-ray; 2.43 A; A/B/C/D=1-277.
DR PDBsum; 4AS5; -.
DR AlphaFoldDB; O55023; -.
DR SMR; O55023; -.
DR IntAct; O55023; 2.
DR STRING; 10090.ENSMUSP00000068174; -.
DR iPTMnet; O55023; -.
DR PhosphoSitePlus; O55023; -.
DR SwissPalm; O55023; -.
DR EPD; O55023; -.
DR jPOST; O55023; -.
DR MaxQB; O55023; -.
DR PaxDb; O55023; -.
DR PeptideAtlas; O55023; -.
DR PRIDE; O55023; -.
DR ProteomicsDB; 269480; -.
DR MGI; MGI:1933158; Impa1.
DR eggNOG; KOG2951; Eukaryota.
DR InParanoid; O55023; -.
DR PhylomeDB; O55023; -.
DR BRENDA; 3.1.3.25; 3474.
DR Reactome; R-MMU-1855183; Synthesis of IP2, IP, and Ins in the cytosol.
DR UniPathway; UPA00823; UER00788.
DR ChiTaRS; Impa1; mouse.
DR PRO; PR:O55023; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O55023; protein.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008934; F:inositol monophosphate 1-phosphatase activity; ISO: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; ISS:UniProtKB.
DR GO; GO:0031403; F:lithium ion binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO: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; ISS:UniProtKB.
DR GO; GO:0006796; P:phosphate-containing compound metabolic process; ISO:MGI.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; ISO:MGI.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
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; Cytoplasm; Hydrolase; Lithium; Magnesium; Metal-binding;
KW Reference proteome.
FT CHAIN 1..277
FT /note="Inositol monophosphatase 1"
FT /id="PRO_0000142514"
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 BINDING 70
FT /ligand="substrate"
FT /evidence="ECO:0000305"
FT BINDING 90..95
FT /ligand="substrate"
FT /evidence="ECO:0000305"
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 BINDING 90
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23027737"
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 BINDING 93
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23027737"
FT BINDING 194..196
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P29218"
FT BINDING 213
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P29218"
FT BINDING 220
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23027737"
FT BINDING 220
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P29218"
FT HELIX 4..26
FT /evidence="ECO:0007829|PDB:4AS5"
FT STRAND 34..38
FT /evidence="ECO:0007829|PDB:4AS5"
FT HELIX 45..61
FT /evidence="ECO:0007829|PDB:4AS5"
FT STRAND 65..69
FT /evidence="ECO:0007829|PDB:4AS5"
FT HELIX 70..74
FT /evidence="ECO:0007829|PDB:4AS5"
FT STRAND 86..93
FT /evidence="ECO:0007829|PDB:4AS5"
FT HELIX 95..100
FT /evidence="ECO:0007829|PDB:4AS5"
FT STRAND 106..113
FT /evidence="ECO:0007829|PDB:4AS5"
FT STRAND 116..124
FT /evidence="ECO:0007829|PDB:4AS5"
FT TURN 125..128
FT /evidence="ECO:0007829|PDB:4AS5"
FT STRAND 129..134
FT /evidence="ECO:0007829|PDB:4AS5"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:4AS5"
FT STRAND 138..141
FT /evidence="ECO:0007829|PDB:4AS5"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:4AS5"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:4AS5"
FT HELIX 169..183
FT /evidence="ECO:0007829|PDB:4AS5"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:4AS5"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:4AS5"
FT HELIX 196..204
FT /evidence="ECO:0007829|PDB:4AS5"
FT STRAND 207..215
FT /evidence="ECO:0007829|PDB:4AS5"
FT HELIX 218..230
FT /evidence="ECO:0007829|PDB:4AS5"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:4AS5"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:4AS5"
FT STRAND 247..254
FT /evidence="ECO:0007829|PDB:4AS5"
FT HELIX 256..265
FT /evidence="ECO:0007829|PDB:4AS5"
SQ SEQUENCE 277 AA; 30436 MW; EDBDB7BD24748E9D CRC64;
MADPWQECMD YAVILARQAG EMIREALKNE MDVMIKSSPA DLVTVTDQKV EKMLMSSIKE
KYPCHSFIGE ESVAAGEKTV FTESPTWFID PIDGTTNFVH RFPFVAVSIG FLVNKEMEFG
IVYSCVEDKM YTGRKGKGAF CNGQKLQVSQ QEDITKSLLV TELGSSRKPE TLRIVLSNME
KLCSIPIHGI RSVGTAAVNM CLVATGGADA YYEMGIHCWD MAGAGIIVTE AGGVLMDVTG
GPFDLMSRRI IAANSITLAK RIAKEIEIIP LQRDDES
