PHOP1_MOUSE
ID PHOP1_MOUSE Reviewed; 267 AA.
AC Q8R2H9; A2A619;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Phosphoethanolamine/phosphocholine phosphatase;
DE EC=3.1.3.75 {ECO:0000250|UniProtKB:Q8TCT1};
GN Name=Phospho1 {ECO:0000303|PubMed:12464021, ECO:0000312|MGI:MGI:2447348};
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 STRAIN=C57BL/6J;
RX PubMed=12464021; DOI=10.1046/j.1365-2052.2002.00900.x;
RA Houston B., Paton I.R., Burt D.W., Farquharson C.;
RT "Chromosomal localization of the chicken and mammalian orthologues of the
RT orphan phosphatase PHOSPHO1 gene.";
RL Anim. Genet. 33:451-454(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17227223; DOI=10.1359/jbmr.070108;
RA Roberts S., Narisawa S., Harmey D., Millan J.L., Farquharson C.;
RT "Functional involvement of PHOSPHO1 in matrix vesicle-mediated skeletal
RT mineralization.";
RL J. Bone Miner. Res. 22:617-627(2007).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Brown adipose tissue;
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 FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20684022; DOI=10.1002/jbmr.195;
RA Yadav M.C., Simao A.M., Narisawa S., Huesa C., McKee M.D., Farquharson C.,
RA Millan J.L.;
RT "Loss of skeletal mineralization by the simultaneous ablation of PHOSPHO1
RT and alkaline phosphatase function: a unified model of the mechanisms of
RT initiation of skeletal calcification.";
RL J. Bone Miner. Res. 26:286-297(2011).
RN [6]
RP FUNCTION.
RX PubMed=26457330; DOI=10.1016/j.bbrep.2015.09.013;
RA Huesa C., Houston D., Kiffer-Moreira T., Yadav M.M., Millan J.L.,
RA Farquharson C.;
RT "The functional co-operativity of Tissue-nonspecific alkaline phosphatase
RT (TNAP) and PHOSPHO1 during initiation of skeletal mineralization.";
RL Biochem. Biophys. Rep. 4:196-201(2015).
CC -!- FUNCTION: Phosphatase that has a high activity toward
CC phosphoethanolamine (PEA) and phosphocholine (PCho) (By similarity).
CC Involved in the generation of inorganic phosphate for bone
CC mineralization (PubMed:17227223). Acts in a non-redundant manner with
CC PHOSPHO1 in skeletal mineralization: while PHOSPHO1 mediates the
CC initiation of hydroxyapatite crystallization in the matrix vesicles
CC (MVs), ALPL/TNAP catalyzes the spread of hydroxyapatite crystallization
CC in the extracellular matrix (PubMed:26457330, PubMed:20684022).
CC {ECO:0000250|UniProtKB:Q8TCT1, ECO:0000269|PubMed:17227223,
CC ECO:0000269|PubMed:20684022, ECO:0000269|PubMed:26457330}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + phosphoethanolamine = ethanolamine + phosphate;
CC Xref=Rhea:RHEA:16089, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57603, ChEBI:CHEBI:58190; EC=3.1.3.75;
CC Evidence={ECO:0000250|UniProtKB:Q8TCT1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + phosphocholine = choline + phosphate;
CC Xref=Rhea:RHEA:10492, ChEBI:CHEBI:15354, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:295975; EC=3.1.3.75;
CC Evidence={ECO:0000250|UniProtKB:Q8TCT1};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8TCT1};
CC -!- SUBCELLULAR LOCATION: Extracellular vesicle
CC {ECO:0000269|PubMed:17227223}. Note=Localizes to special class of
CC extracellular vesicles, named matrix vesicles (MVs), which are released
CC by osteogenic cells. {ECO:0000269|PubMed:17227223}.
CC -!- TISSUE SPECIFICITY: Has a 120-fold higher level of expression in bone
CC compared with a range of soft tissues. {ECO:0000269|PubMed:17227223}.
CC -!- DISRUPTION PHENOTYPE: Mice display growth plate abnormalities,
CC spontaneous fractures, bowed long bones, osteomalacia and scoliosis in
CC early life (PubMed:20684022). Primary cultures of tibial growth plate
CC chondrocytes and chondrocyte-derived matrix vesicles (MVs) show reduced
CC mineralizing ability, and plasma samples show reduced levels of
CC Alpl/Tnap and elevated plasma diphosphate (inorganic pyrophosphate;
CC PPi) concentrations (PubMed:20684022). Mice lacking both Phospho1 and
CC Alpl/Tnap show a complete absence of skeletal mineralization, leading
CC to perinatal lethality (PubMed:20684022).
CC {ECO:0000269|PubMed:20684022}.
CC -!- SIMILARITY: Belongs to the HAD-like hydrolase superfamily. PHOSPHO
CC family. {ECO:0000305}.
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DR EMBL; AJ457190; CAD29804.1; -; mRNA.
DR EMBL; AL593858; CAM15510.1; -; Genomic_DNA.
DR CCDS; CCDS36288.1; -.
DR RefSeq; NP_694744.1; NM_153104.3.
DR AlphaFoldDB; Q8R2H9; -.
DR SMR; Q8R2H9; -.
DR BioGRID; 231927; 7.
DR IntAct; Q8R2H9; 7.
DR STRING; 10090.ENSMUSP00000057858; -.
DR PhosphoSitePlus; Q8R2H9; -.
DR EPD; Q8R2H9; -.
DR MaxQB; Q8R2H9; -.
DR PaxDb; Q8R2H9; -.
DR PRIDE; Q8R2H9; -.
DR ProteomicsDB; 301815; -.
DR Antibodypedia; 30368; 155 antibodies from 22 providers.
DR DNASU; 237928; -.
DR Ensembl; ENSMUST00000054173; ENSMUSP00000057858; ENSMUSG00000050860.
DR GeneID; 237928; -.
DR KEGG; mmu:237928; -.
DR UCSC; uc007las.2; mouse.
DR CTD; 162466; -.
DR MGI; MGI:2447348; Phospho1.
DR VEuPathDB; HostDB:ENSMUSG00000050860; -.
DR eggNOG; KOG3120; Eukaryota.
DR GeneTree; ENSGT00390000007741; -.
DR HOGENOM; CLU_068983_0_0_1; -.
DR InParanoid; Q8R2H9; -.
DR OMA; RPFHSHE; -.
DR OrthoDB; 1454608at2759; -.
DR PhylomeDB; Q8R2H9; -.
DR TreeFam; TF300112; -.
DR BRENDA; 3.1.3.75; 3474.
DR Reactome; R-MMU-1483191; Synthesis of PC.
DR Reactome; R-MMU-1483213; Synthesis of PE.
DR BioGRID-ORCS; 237928; 4 hits in 71 CRISPR screens.
DR ChiTaRS; Phospho1; mouse.
DR PRO; PR:Q8R2H9; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8R2H9; protein.
DR Bgee; ENSMUSG00000050860; Expressed in hindlimb stylopod muscle and 84 other tissues.
DR ExpressionAtlas; Q8R2H9; baseline and differential.
DR Genevisible; Q8R2H9; MM.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0065010; C:extracellular membrane-bounded organelle; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016791; F:phosphatase activity; IBA:GO_Central.
DR GO; GO:0052731; F:phosphocholine phosphatase activity; ISS:UniProtKB.
DR GO; GO:0052732; F:phosphoethanolamine phosphatase activity; ISS:UniProtKB.
DR GO; GO:0016462; F:pyrophosphatase activity; ISO:MGI.
DR GO; GO:0030282; P:bone mineralization; IMP:UniProtKB.
DR GO; GO:0035630; P:bone mineralization involved in bone maturation; IMP:MGI.
DR GO; GO:0001958; P:endochondral ossification; IMP:MGI.
DR GO; GO:0030500; P:regulation of bone mineralization; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR006384; HAD_hydro_PyrdxlP_Pase-like.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR016965; Pase_PHOSPHO-typ.
DR PANTHER; PTHR20889; PTHR20889; 1.
DR Pfam; PF06888; Put_Phosphatase; 1.
DR PIRSF; PIRSF031051; PyrdxlP_Pase_PHOSPHO2; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR TIGRFAMs; TIGR01489; DKMTPPase-SF; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Magnesium; Metal-binding; Mineral balance; Reference proteome.
FT CHAIN 1..267
FT /note="Phosphoethanolamine/phosphocholine phosphatase"
FT /id="PRO_0000068830"
FT ACT_SITE 32
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8TCT1"
FT ACT_SITE 34
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q96GD0"
FT BINDING 32
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q96GD0"
FT BINDING 34
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q96GD0"
FT BINDING 43
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8TCT1"
FT BINDING 123
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8TCT1"
FT BINDING 203
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q96GD0"
SQ SEQUENCE 267 AA; 29911 MW; 0CEEE66019C0CEA7 CRC64;
MSGCFPAVGL RCLSRDGRMA APGAPRFLLT FDFDETIVDE NSDDSIVRAA PGQQLPESLR
ATYREGYYNE YMQRVFKYLG EQGVRPRDLR AVYETIPLSP GMGDLLQFIA KQGSCFEVIL
ISDANTFGVE SALRAAGHHS LFRRILSNPS GPDARGLLTL RPFHTHSCSR CPANMCKHKV
LSEYLRERAR DGVHFERLFY VGDGANDFCP MGLLAGGDVA FPRRGYPMHR LIQEAQKAEP
SSFRAHVVPW ETAADVRQHL QQVLKMC
