PGP_MOUSE
ID PGP_MOUSE Reviewed; 321 AA.
AC Q8CHP8;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Glycerol-3-phosphate phosphatase {ECO:0000305};
DE Short=G3PP {ECO:0000303|PubMed:26755581};
DE EC=3.1.3.21 {ECO:0000269|PubMed:26755581};
DE AltName: Full=Aspartate-based ubiquitous Mg(2+)-dependent phosphatase {ECO:0000303|PubMed:24338473};
DE Short=AUM {ECO:0000303|PubMed:24338473};
DE EC=3.1.3.48 {ECO:0000269|PubMed:24338473};
DE AltName: Full=Phosphoglycolate phosphatase {ECO:0000303|PubMed:24338473};
DE Short=PGP {ECO:0000303|PubMed:24338473};
GN Name=Pgp {ECO:0000312|MGI:MGI:1914328};
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 [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [2]
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP SPECIFICITY, AND INDUCTION.
RX PubMed=26755581; DOI=10.1073/pnas.1514375113;
RA Mugabo Y., Zhao S., Seifried A., Gezzar S., Al-Mass A., Zhang D.,
RA Lamontagne J., Attane C., Poursharifi P., Iglesias J., Joly E., Peyot M.L.,
RA Gohla A., Madiraju S.R., Prentki M.;
RT "Identification of a mammalian glycerol-3-phosphate phosphatase: Role in
RT metabolism and signaling in pancreatic beta-cells and hepatocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:E430-439(2016).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 44-233 IN COMPLEX WITH MAGNESIUM,
RP CATALYTIC ACTIVITY, COFACTOR, TISSUE SPECIFICITY, MUTAGENESIS OF ASP-34;
RP ARG-41; THR-44; ALA-45; THR-67; SER-71; LYS-72; THR-73 AND LEU-204, ACTIVE
RP SITE, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=24338473; DOI=10.1074/jbc.m113.503359;
RA Seifried A., Knobloch G., Duraphe P.S., Segerer G., Manhard J.,
RA Schindelin H., Schultz J., Gohla A.;
RT "Evolutionary and structural analyses of the mammalian haloacid
RT dehalogenase-type phosphatases AUM and chronophin provide insight into the
RT basis of their different substrate specificities.";
RL J. Biol. Chem. 289:3416-3431(2014).
CC -!- FUNCTION: Glycerol-3-phosphate phosphatase hydrolyzing glycerol-3-
CC phosphate into glycerol. Thereby, regulates the cellular levels of
CC glycerol-3-phosphate a metabolic intermediate of glucose, lipid and
CC energy metabolism (PubMed:26755581). Was also shown to have a 2-
CC phosphoglycolate phosphatase activity and a tyrosine-protein
CC phosphatase activity. However, their physiological relevance is unclear
CC (PubMed:26755581, PubMed:24338473). In vitro, has also a phosphatase
CC activity toward ADP, ATP, GDP and GTP (PubMed:24338473).
CC {ECO:0000269|PubMed:24338473, ECO:0000269|PubMed:26755581}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620; EC=3.1.3.48;
CC Evidence={ECO:0000269|PubMed:24338473};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + sn-glycerol 1-phosphate = glycerol + phosphate;
CC Xref=Rhea:RHEA:46084, ChEBI:CHEBI:15377, ChEBI:CHEBI:17754,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57685; EC=3.1.3.21;
CC Evidence={ECO:0000269|PubMed:26755581};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + sn-glycerol 3-phosphate = glycerol + phosphate;
CC Xref=Rhea:RHEA:66372, ChEBI:CHEBI:15377, ChEBI:CHEBI:17754,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57597; EC=3.1.3.21;
CC Evidence={ECO:0000269|PubMed:26755581};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:24338473};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:24338473};
CC -!- ACTIVITY REGULATION: Inhibited by orthovanadate, beryllium trifluoride,
CC Ca(2+) and EDTA. {ECO:0000269|PubMed:24338473}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.42 mM for ADP {ECO:0000269|PubMed:24338473};
CC KM=1.23 mM for ATP {ECO:0000269|PubMed:24338473};
CC KM=1.48 mM for GDP {ECO:0000269|PubMed:24338473};
CC KM=1.47 mM for GTP {ECO:0000269|PubMed:24338473};
CC KM=1.29 mM for glycerol-3-phosphate {ECO:0000269|PubMed:26755581};
CC Vmax=100 nmol/min/mg enzyme with glycerol-3-phosphate as substrate
CC {ECO:0000269|PubMed:26755581};
CC Note=kcat is 0.1 sec(-1) with glycerol-3-phosphate.
CC {ECO:0000269|PubMed:26755581};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:24338473}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with higher expression in
CC testis, heart, skeletal muscle and islet tissue (at protein level).
CC {ECO:0000269|PubMed:24338473, ECO:0000269|PubMed:26755581}.
CC -!- INDUCTION: Up-regulated in white adipose tissue and down-regulated in
CC brown adipose tissue upon fasting. {ECO:0000269|PubMed:26755581}.
CC -!- SIMILARITY: Belongs to the HAD-like hydrolase superfamily.
CC CbbY/CbbZ/Gph/YieH family. {ECO:0000305}.
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DR EMBL; BC040100; AAH40100.1; -; mRNA.
DR CCDS; CCDS28482.1; -.
DR RefSeq; NP_080230.2; NM_025954.3.
DR PDB; 4BKM; X-ray; 2.65 A; A/B/C/D=114-233.
DR PDBsum; 4BKM; -.
DR AlphaFoldDB; Q8CHP8; -.
DR SMR; Q8CHP8; -.
DR STRING; 10090.ENSMUSP00000052866; -.
DR iPTMnet; Q8CHP8; -.
DR PhosphoSitePlus; Q8CHP8; -.
DR REPRODUCTION-2DPAGE; IPI00380195; -.
DR REPRODUCTION-2DPAGE; Q8CHP8; -.
DR CPTAC; non-CPTAC-3609; -.
DR EPD; Q8CHP8; -.
DR jPOST; Q8CHP8; -.
DR MaxQB; Q8CHP8; -.
DR PaxDb; Q8CHP8; -.
DR PeptideAtlas; Q8CHP8; -.
DR PRIDE; Q8CHP8; -.
DR ProteomicsDB; 288184; -.
DR Antibodypedia; 54763; 150 antibodies from 25 providers.
DR DNASU; 67078; -.
DR Ensembl; ENSMUST00000053024; ENSMUSP00000052866; ENSMUSG00000043445.
DR GeneID; 67078; -.
DR KEGG; mmu:67078; -.
DR UCSC; uc008awe.1; mouse.
DR CTD; 283871; -.
DR MGI; MGI:1914328; Pgp.
DR VEuPathDB; HostDB:ENSMUSG00000043445; -.
DR eggNOG; KOG2882; Eukaryota.
DR GeneTree; ENSGT00940000160577; -.
DR HOGENOM; CLU_043473_0_1_1; -.
DR InParanoid; Q8CHP8; -.
DR OMA; PPMHRET; -.
DR OrthoDB; 982374at2759; -.
DR PhylomeDB; Q8CHP8; -.
DR TreeFam; TF314344; -.
DR BRENDA; 3.1.3.18; 3474.
DR BRENDA; 3.1.3.48; 3474.
DR BRENDA; 3.1.3.74; 3474.
DR BioGRID-ORCS; 67078; 6 hits in 73 CRISPR screens.
DR ChiTaRS; Pgp; mouse.
DR PRO; PR:Q8CHP8; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q8CHP8; protein.
DR Bgee; ENSMUSG00000043445; Expressed in seminiferous tubule of testis and 249 other tissues.
DR Genevisible; Q8CHP8; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0000121; F:glycerol-1-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0043136; F:glycerol-3-phosphatase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0098519; F:nucleotide phosphatase activity, acting on free nucleotides; IDA:UniProtKB.
DR GO; GO:0016791; F:phosphatase activity; IBA:GO_Central.
DR GO; GO:0008967; F:phosphoglycolate phosphatase activity; ISO:MGI.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0016311; P:dephosphorylation; IDA:UniProtKB.
DR GO; GO:0006114; P:glycerol biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006650; P:glycerophospholipid metabolic process; IDA:UniProtKB.
DR GO; GO:0045721; P:negative regulation of gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IDA:UniProtKB.
DR Gene3D; 3.40.50.1000; -; 2.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR006357; HAD-SF_hydro_IIA.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR006349; PGP_euk.
DR Pfam; PF13344; Hydrolase_6; 1.
DR PIRSF; PIRSF000915; PGP-type_phosphatase; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR TIGRFAMs; TIGR01460; HAD-SF-IIA; 1.
DR TIGRFAMs; TIGR01452; PGP_euk; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Carbohydrate metabolism; Hydrolase; Magnesium; Metal-binding;
KW Protein phosphatase; Reference proteome.
FT CHAIN 1..321
FT /note="Glycerol-3-phosphate phosphatase"
FT /id="PRO_0000316889"
FT ACT_SITE 34
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:24338473"
FT ACT_SITE 36
FT /note="Proton donor"
FT /evidence="ECO:0000305"
FT BINDING 34
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P60487"
FT BINDING 36
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P60487"
FT BINDING 260
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P60487"
FT SITE 204
FT /note="Important for substrate specificity"
FT /evidence="ECO:0000305|PubMed:24338473"
FT MUTAGEN 34
FT /note="D->N: Abolishes phosphatase activity."
FT /evidence="ECO:0000269|PubMed:24338473"
FT MUTAGEN 41
FT /note="R->N: Slightly increases phosphatase activity with
FT p-nitrophenylphosphate; when associated with R-44 and I-
FT 45."
FT /evidence="ECO:0000269|PubMed:24338473"
FT MUTAGEN 44
FT /note="T->R: Slightly increases phosphatase activity with
FT p-nitrophenylphosphate; when associated with N-41 and I-
FT 45."
FT /evidence="ECO:0000269|PubMed:24338473"
FT MUTAGEN 45
FT /note="A->I: Slightly increases phosphatase activity with
FT p-nitrophenylphosphate; when associated with N-41 and R-
FT 44."
FT /evidence="ECO:0000269|PubMed:24338473"
FT MUTAGEN 67
FT /note="T->S: Strongly reduces phosphatase activity; when
FT associated with R-71; R-72 and A-73. Abolishes phosphatase
FT activity; when associated with R-72 and A-73."
FT /evidence="ECO:0000269|PubMed:24338473"
FT MUTAGEN 71
FT /note="S->R: Mildly reduces phosphatase activity; when
FT associated with R-72 and A-73. Strongly reduces phosphatase
FT activity; when associated with S-67; R-72 and A-73."
FT /evidence="ECO:0000269|PubMed:24338473"
FT MUTAGEN 72
FT /note="K->R: Mildly reduces phosphatase activity; when
FT associated with R-71 and A-73. Strongly reduces phosphatase
FT activity; when associated with S-67; R-71 and A-73.
FT Abolishes phosphatase activity; when associated with S-67
FT and A-73."
FT /evidence="ECO:0000269|PubMed:24338473"
FT MUTAGEN 73
FT /note="T->A: Abolishes phosphatase activity. Abolishes
FT phosphatase activity; when associated with S-67 and R-72.
FT Strongly reduces phosphatase activity; when associated with
FT S-67; R-71 and R-72. Mildly reduces phosphatase activity;
FT when associated with R-71 and R-72."
FT /evidence="ECO:0000269|PubMed:24338473"
FT MUTAGEN 204
FT /note="L->H: Strongly increases activity with pyridoxal
FT phosphate."
FT /evidence="ECO:0000269|PubMed:24338473"
FT STRAND 120..125
FT /evidence="ECO:0007829|PDB:4BKM"
FT HELIX 127..135
FT /evidence="ECO:0007829|PDB:4BKM"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:4BKM"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:4BKM"
FT HELIX 153..156
FT /evidence="ECO:0007829|PDB:4BKM"
FT STRAND 165..170
FT /evidence="ECO:0007829|PDB:4BKM"
FT HELIX 178..187
FT /evidence="ECO:0007829|PDB:4BKM"
FT STRAND 193..198
FT /evidence="ECO:0007829|PDB:4BKM"
FT STRAND 202..205
FT /evidence="ECO:0007829|PDB:4BKM"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:4BKM"
FT HELIX 215..226
FT /evidence="ECO:0007829|PDB:4BKM"
SQ SEQUENCE 321 AA; 34541 MW; F083ED0432327A83 CRC64;
MAEAEAGGDE ARCVRLSAER AKLLLAEVDT LLFDCDGVLW RGETAVPGAP ETLRALRARG
KRLGFITNNS SKTRTAYAEK LRRLGFGGPV GPEAGLEVFG TAYCSALYLR QRLAGVPDPK
AYVLGSPALA AELEAVGVTS VGVGPDVLHG DGPSDWLAVP LEPDVRAVVV GFDPHFSYMK
LTKAVRYLQQ PDCLLVGTNM DNRLPLENGR FIAGTGCLVR AVEMAAQRQA DIIGKPSRFI
FDCVSQEYGI NPERTVMVGD RLDTDILLGS TCSLKTILTL TGVSSLEDVK SNQESDCMFK
KKMVPDFYVD SIADLLPALQ G
