PHOP1_HUMAN
ID PHOP1_HUMAN Reviewed; 267 AA.
AC Q8TCT1; E9PAM0; Q17RU6;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Phosphoethanolamine/phosphocholine phosphatase;
DE EC=3.1.3.75 {ECO:0000269|PubMed:15175005};
GN Name=PHOSPHO1 {ECO:0000303|PubMed:12464021, ECO:0000312|HGNC:HGNC:16815};
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).
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 [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RX PubMed=18471996; DOI=10.1016/j.bbrc.2008.04.163;
RA Roberts S.J., Owen H.C., Farquharson C.;
RT "Identification of a novel splice variant of the haloacid dehalogenase:
RT PHOSPHO1.";
RL Biochem. Biophys. Res. Commun. 371:872-876(2008).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-111 (ISOFORM 3).
RC TISSUE=Colon, and Medulla oblongata;
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15175005; DOI=10.1042/bj20040511;
RA Roberts S.J., Stewart A.J., Sadler P.J., Farquharson C.;
RT "Human PHOSPHO1 exhibits high specific phosphoethanolamine and
RT phosphocholine phosphatase activities.";
RL Biochem. J. 382:59-65(2004).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=15050893; DOI=10.1016/j.bone.2003.12.023;
RA Houston B., Stewart A.J., Farquharson C.;
RT "PHOSPHO1 -- a novel phosphatase specifically expressed at sites of
RT mineralisation in bone and cartilage.";
RL Bone 34:629-637(2004).
RN [7]
RP SIMILARITY TO HAD-LIKE HYDROLASE SUPERFAMILY.
RX PubMed=14983068; DOI=10.1093/protein/gzg126;
RA Stewart A.J., Schmid R., Blindauer C.A., Paisey S.J., Farquharson C.;
RT "Comparative modelling of human PHOSPHO1 reveals a new group of
RT phosphatases within the haloacid dehalogenase superfamily.";
RL Protein Eng. 16:889-895(2003).
RN [8]
RP MUTAGENESIS OF ASP-32; ASP-43; ASP-123 AND ASP-203, AND ACTIVE SITE.
RX PubMed=16054448; DOI=10.1016/j.bbapap.2005.06.009;
RA Roberts S.J., Stewart A.J., Schmid R., Blindauer C.A., Bond S.R.,
RA Sadler P.J., Farquharson C.;
RT "Probing the substrate specificities of human PHOSPHO1 and PHOSPHO2.";
RL Biochim. Biophys. Acta 1752:73-82(2005).
CC -!- FUNCTION: Phosphatase that has a high activity toward
CC phosphoethanolamine (PEA) and phosphocholine (PCho) (PubMed:15175005).
CC Involved in the generation of inorganic phosphate for bone
CC mineralization (By similarity). 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 (By similarity).
CC {ECO:0000250|UniProtKB:Q8R2H9, ECO:0000269|PubMed:15175005}.
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:0000269|PubMed:15175005};
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:0000269|PubMed:15175005};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15175005};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3 uM for PEA {ECO:0000269|PubMed:15175005};
CC KM=11.4 uM for PCho {ECO:0000269|PubMed:15175005};
CC pH dependence:
CC Optimum pH is 6.7. {ECO:0000269|PubMed:15175005};
CC -!- INTERACTION:
CC Q8TCT1; Q8NHQ8-2: RASSF8; NbExp=3; IntAct=EBI-14017370, EBI-10976415;
CC -!- SUBCELLULAR LOCATION: Extracellular vesicle
CC {ECO:0000250|UniProtKB:Q8R2H9}. Note=Localizes to special class of
CC extracellular vesicles, named matrix vesicles (MVs), which are released
CC by osteogenic cells. {ECO:0000250|UniProtKB:Q8R2H9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8TCT1-1; Sequence=Displayed;
CC Name=2; Synonyms=PHOSPHO1-3a;
CC IsoId=Q8TCT1-2; Sequence=VSP_040624;
CC Name=3;
CC IsoId=Q8TCT1-3; Sequence=VSP_045709;
CC -!- TISSUE SPECIFICITY: Expressed at sites of mineralization in bone and
CC cartilage. Highly expressed in osteoblast cell line SaOS-2 which
CC produces a mineralized matrix, but not in MG-63 cell line, which do not
CC mineralize. {ECO:0000269|PubMed:15050893}.
CC -!- SIMILARITY: Belongs to the HAD-like hydrolase superfamily. PHOSPHO
CC family. {ECO:0000305}.
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DR EMBL; AJ457189; CAD29803.1; -; mRNA.
DR EMBL; AC004797; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC029931; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC117187; AAI17188.1; -; mRNA.
DR CCDS; CCDS11547.1; -. [Q8TCT1-1]
DR CCDS; CCDS45726.1; -. [Q8TCT1-3]
DR RefSeq; NP_001137276.1; NM_001143804.1. [Q8TCT1-3]
DR RefSeq; NP_848595.1; NM_178500.3. [Q8TCT1-1]
DR AlphaFoldDB; Q8TCT1; -.
DR SMR; Q8TCT1; -.
DR BioGRID; 127819; 59.
DR IntAct; Q8TCT1; 54.
DR STRING; 9606.ENSP00000406909; -.
DR BindingDB; Q8TCT1; -.
DR ChEMBL; CHEMBL6113; -.
DR DrugBank; DB00122; Choline.
DR DrugCentral; Q8TCT1; -.
DR DEPOD; PHOSPHO1; -.
DR iPTMnet; Q8TCT1; -.
DR PhosphoSitePlus; Q8TCT1; -.
DR BioMuta; PHOSPHO1; -.
DR DMDM; 74715842; -.
DR MassIVE; Q8TCT1; -.
DR PaxDb; Q8TCT1; -.
DR PeptideAtlas; Q8TCT1; -.
DR PRIDE; Q8TCT1; -.
DR ProteomicsDB; 19044; -.
DR ProteomicsDB; 74155; -. [Q8TCT1-1]
DR ProteomicsDB; 74156; -. [Q8TCT1-2]
DR Antibodypedia; 30368; 155 antibodies from 22 providers.
DR DNASU; 162466; -.
DR Ensembl; ENST00000310544.9; ENSP00000311925.4; ENSG00000173868.12. [Q8TCT1-1]
DR Ensembl; ENST00000413580.5; ENSP00000406909.1; ENSG00000173868.12. [Q8TCT1-3]
DR Ensembl; ENST00000514112.1; ENSP00000427694.1; ENSG00000173868.12. [Q8TCT1-3]
DR GeneID; 162466; -.
DR KEGG; hsa:162466; -.
DR MANE-Select; ENST00000310544.9; ENSP00000311925.4; NM_178500.4; NP_848595.1.
DR UCSC; uc002ios.2; human. [Q8TCT1-1]
DR CTD; 162466; -.
DR DisGeNET; 162466; -.
DR GeneCards; PHOSPHO1; -.
DR HGNC; HGNC:16815; PHOSPHO1.
DR HPA; ENSG00000173868; Tissue enriched (testis).
DR neXtProt; NX_Q8TCT1; -.
DR OpenTargets; ENSG00000173868; -.
DR PharmGKB; PA33276; -.
DR VEuPathDB; HostDB:ENSG00000173868; -.
DR eggNOG; KOG3120; Eukaryota.
DR GeneTree; ENSGT00390000007741; -.
DR HOGENOM; CLU_068983_0_1_1; -.
DR InParanoid; Q8TCT1; -.
DR OMA; RPFHSHE; -.
DR OrthoDB; 1454608at2759; -.
DR PhylomeDB; Q8TCT1; -.
DR TreeFam; TF300112; -.
DR BioCyc; MetaCyc:HS16266-MON; -.
DR BRENDA; 3.1.3.75; 2681.
DR PathwayCommons; Q8TCT1; -.
DR Reactome; R-HSA-1483191; Synthesis of PC.
DR Reactome; R-HSA-1483213; Synthesis of PE.
DR SignaLink; Q8TCT1; -.
DR BioGRID-ORCS; 162466; 6 hits in 1063 CRISPR screens.
DR GenomeRNAi; 162466; -.
DR Pharos; Q8TCT1; Tchem.
DR PRO; PR:Q8TCT1; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8TCT1; protein.
DR Bgee; ENSG00000173868; Expressed in left testis and 92 other tissues.
DR ExpressionAtlas; Q8TCT1; baseline and differential.
DR Genevisible; Q8TCT1; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031012; C:extracellular matrix; IEA:Ensembl.
DR GO; GO:0065010; C:extracellular membrane-bounded organelle; ISS:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0052732; F:phosphoethanolamine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0016462; F:pyrophosphatase activity; IDA:MGI.
DR GO; GO:0030282; P:bone mineralization; ISS:UniProtKB.
DR GO; GO:0035630; P:bone mineralization involved in bone maturation; IBA:GO_Central.
DR GO; GO:0001958; P:endochondral ossification; IEA:Ensembl.
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 Alternative splicing; Hydrolase; Magnesium; Metal-binding; Mineral balance;
KW Reference proteome.
FT CHAIN 1..267
FT /note="Phosphoethanolamine/phosphocholine phosphatase"
FT /id="PRO_0000068829"
FT ACT_SITE 32
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:16054448"
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:0000305|PubMed:16054448"
FT BINDING 123
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:16054448"
FT BINDING 203
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q96GD0"
FT VAR_SEQ 1..15
FT /note="MSGCFPVSGLRCLSR -> MCQRLWPANQPLPGGLLPRPLSLAPSSSSSCCS
FT PPCSQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:18471996"
FT /id="VSP_040624"
FT VAR_SEQ 1..15
FT /note="MSGCFPVSGLRCLSR -> MCQRLWPWPANQPLPGGLLPRPLSLAPSSSSSC
FT CSPPCSQ (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045709"
FT MUTAGEN 32
FT /note="D->N: Abolishes phosphatase activity."
FT /evidence="ECO:0000269|PubMed:16054448"
FT MUTAGEN 43
FT /note="D->N: Strongly reduces reactivity toward PEA and
FT PCho substrates. Abolishes phosphatase activity; when
FT associated with N-123."
FT /evidence="ECO:0000269|PubMed:16054448"
FT MUTAGEN 123
FT /note="D->N: Strongly reduces reactivity toward PEA and
FT PCho substrates. Abolishes phosphatase activity; when
FT associated with N-43."
FT /evidence="ECO:0000269|PubMed:16054448"
FT MUTAGEN 203
FT /note="D->S: Abolishes phosphatase activity."
FT /evidence="ECO:0000269|PubMed:16054448"
SQ SEQUENCE 267 AA; 29713 MW; 539F65C749D39E81 CRC64;
MSGCFPVSGL RCLSRDGRMA AQGAPRFLLT FDFDETIVDE NSDDSIVRAA PGQRLPESLR
ATYREGFYNE YMQRVFKYLG EQGVRPRDLS AIYEAIPLSP GMSDLLQFVA KQGACFEVIL
ISDANTFGVE SSLRAAGHHS LFRRILSNPS GPDARGLLAL RPFHTHSCAR CPANMCKHKV
LSDYLRERAH DGVHFERLFY VGDGANDFCP MGLLAGGDVA FPRRGYPMHR LIQEAQKAEP
SSFRASVVPW ETAADVRLHL QQVLKSC
