PHEX_HUMAN
ID PHEX_HUMAN Reviewed; 749 AA.
AC P78562; O00678; Q13646; Q2M325; Q93032; Q99827;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Phosphate-regulating neutral endopeptidase PHEX;
DE EC=3.4.24.- {ECO:0000269|PubMed:18597632, ECO:0000269|PubMed:9593714};
DE AltName: Full=Metalloendopeptidase homolog PEX;
DE AltName: Full=Vitamin D-resistant hypophosphatemic rickets protein;
DE AltName: Full=X-linked hypophosphatemia protein;
DE Short=HYP;
GN Name=PHEX; Synonyms=PEX;
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 [GENOMIC DNA], AND VARIANTS XLHR ARG-85; LEU-534;
RP ARG-579 AND PRO-651.
RX PubMed=9199930; DOI=10.1101/gr.7.6.573;
RA Francis F., Strom T.M., Hennig S., Boeddrich A., Lorenz B., Brandau O.,
RA Mohnike K.L., Cagnoli M., Steffens C., Klages S., Borzym K., Pohl T.,
RA Oudet C.L., Econs M.J., Rowe P.S.N., Reinhardt R., Meitinger T.,
RA Lehrach H.;
RT "Genomic organization of the human PEX gene mutated in X-linked dominant
RT hypophosphatemic rickets.";
RL Genome Res. 7:573-585(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=9077527; DOI=10.1172/jci119276;
RA Beck L., Soumounou Y., Martel J., Krishnamurthy G., Gauthier C.,
RA Goodyer C.G., Tenenhouse H.S.;
RT "Pex/PEX tissue distribution and evidence for a deletion in the 3' region
RT of the Pex gene in X-linked hypophosphatemic mice.";
RL J. Clin. Invest. 99:1200-1209(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Bone;
RX PubMed=9199999; DOI=10.1359/jbmr.1997.12.7.1009;
RA Guo R., Quarles L.D.;
RT "Cloning and sequencing of human PEX from a bone cDNA library: evidence for
RT its developmental stage-specific regulation in osteoblasts.";
RL J. Bone Miner. Res. 12:1009-1017(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=9070861; DOI=10.1006/bbrc.1997.6153;
RA Grieff M., Mumm S., Waeltz P., Mazzarella R., Whyte M.P., Thakker R.V.,
RA Schlessinger D.;
RT "Expression and cloning of the human X-linked hypophosphatemia gene cDNA.";
RL Biochem. Biophys. Res. Commun. 231:635-639(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND TOPOLOGY.
RX PubMed=9593714; DOI=10.1074/jbc.273.22.13729;
RA Lipman M.L., Panda D., Bennett H.P., Henderson J.E., Shane E., Shen Y.,
RA Goltzman D., Karaplis A.C.;
RT "Cloning of human PEX cDNA. Expression, subcellular localization, and
RT endopeptidase activity.";
RL J. Biol. Chem. 273:13729-13737(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS XLHR TYR-85; CYS-166;
RP SER-252; ILE-253 AND VAL-579.
RX PubMed=9106524;
RA Holm I.A., Huang X., Kunkel L.M.;
RT "Mutational analysis of the PEX gene in patients with X-linked
RT hypophosphatemic rickets.";
RL Am. J. Hum. Genet. 60:790-797(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-641.
RX PubMed=7550339; DOI=10.1038/ng1095-130;
RG The HYP consortium;
RA Francis F., Hennig S., Korn B., Reinhardt R., de Jong P., Poustka A.,
RA Lehrach H., Rowe P.S.N., Goulding J.N., Summerfield T., Mountford R.,
RA Read A.P., Popowska E., Pronicka E., Davies K.E., Oriordan J.L.H.,
RA Econs M.J., Nesbitt T., Drezner M.K., Oudet C.L., Pannetier S., Hanauer A.,
RA Strom T.M., Meindl A., Lorenz B., Cagnoli M., Mohnike K.L., Murken J.,
RA Meitinger T.;
RT "A gene (PEX) with homologies to endopeptidases is mutated in patients with
RT X-linked hypophosphatemic rickets.";
RL Nat. Genet. 11:130-136(1995).
RN [10]
RP FUNCTION.
RX PubMed=12220505; DOI=10.1016/s0006-291x(02)02125-3;
RA Guo R., Rowe P.S., Liu S., Simpson L.G., Xiao Z.S., Quarles L.D.;
RT "Inhibition of MEPE cleavage by Phex.";
RL Biochem. Biophys. Res. Commun. 297:38-45(2002).
RN [11]
RP COFACTOR, AND INTERACTION WITH MEPE.
RX PubMed=15664000; DOI=10.1016/j.bone.2004.09.015;
RA Rowe P.S., Garrett I.R., Schwarz P.M., Carnes D.L., Lafer E.M., Mundy G.R.,
RA Gutierrez G.E.;
RT "Surface plasmon resonance (SPR) confirms that MEPE binds to PHEX via the
RT MEPE-ASARM motif: a model for impaired mineralization in X-linked rickets
RT (HYP).";
RL Bone 36:33-46(2005).
RN [12]
RP FUNCTION, AND INTERACTION WITH MEPE.
RX PubMed=18162525; DOI=10.1210/en.2007-1205;
RA Martin A., David V., Laurence J.S., Schwarz P.M., Lafer E.M., Hedge A.M.,
RA Rowe P.S.;
RT "Degradation of MEPE, DMP1, and release of SIBLING ASARM-peptides
RT (minhibins): ASARM-peptide(s) are directly responsible for defective
RT mineralization in HYP.";
RL Endocrinology 149:1757-1772(2008).
RN [13]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18597632; DOI=10.1359/jbmr.080601;
RA Addison W.N., Nakano Y., Loisel T., Crine P., McKee M.D.;
RT "MEPE-ASARM peptides control extracellular matrix mineralization by binding
RT to hydroxyapatite: an inhibition regulated by PHEX cleavage of ASARM.";
RL J. Bone Miner. Res. 23:1638-1649(2008).
RN [14]
RP VARIANTS XLHR SER-77; PRO-138; LEU-534 AND ARG-579.
RX PubMed=9097956; DOI=10.1093/hmg/6.4.539;
RA Rowe P.S.N., Oudet C.L., Francis F., Sinding C., Pannetier S., Econs M.J.,
RA Strom T.M., Meitinger T., Garabedian M., David A., Macher M.-A.,
RA Questiaux E., Popowska E., Pronicka E., Read A.P., Mokrzycki A.,
RA Glorieux F.H., Drezner M.K., Hanauer A., Lehrach H., Goulding J.N.,
RA O'Riordan J.L.H.;
RT "Distribution of mutations in the PEX gene in families with X-linked
RT hypophosphataemic rickets (HYP).";
RL Hum. Mol. Genet. 6:539-549(1997).
RN [15]
RP VARIANT XLHR PRO-555.
RX PubMed=9768646; DOI=10.1210/jcem.83.10.5167;
RA Econs M.J., Friedman N.E., Rowe P.S.N., Speer M.C., Francis F., Strom T.M.,
RA Oudet C.L., Smith J.A., Ninomiya J.T., Lee B.E., Bergen H.;
RT "A PHEX gene mutation is responsible for adult-onset vitamin D-resistant
RT hypophosphatemic osteomalacia: evidence that the disorder is not a distinct
RT entity from X-linked hypophosphatemic rickets.";
RL J. Clin. Endocrinol. Metab. 83:3459-3462(1998).
RN [16]
RP VARIANTS XLHR PHE-317; LEU-534; ARG-579; ARG-621; ASN-680 DEL; THR-720;
RP TYR-731 AND ARG-749.
RX PubMed=9768674; DOI=10.1210/jcem.83.10.5180;
RA Dixon P.H., Christie P.T., Wooding C., Trump D., Grieff M., Holm I.A.,
RA Gertner J.M., Schmidtke J., Shah B., Shaw N., Smith C., Tau C.,
RA Schlessinger D., Whyte M.P., Thakker R.V.;
RT "Mutational analysis of PHEX gene in X-linked hypophosphatemia.";
RL J. Clin. Endocrinol. Metab. 83:3615-3623(1998).
RN [17]
RP VARIANTS XLHR SER-80; PHE-142; GLY-237; CYS-530; ASP-573; SER-733 AND
RP TRP-746.
RX PubMed=10439971; DOI=10.1038/sj.ejhg.5200341;
RA Filisetti D., Ostermann G., von Bredow M., Strom T.M., Filler G.,
RA Ehrich J., Pannetier S., Garnier J.-M., Rowe P.S.N., Francis F.,
RA Julienne A., Hanauer A., Econs M.J., Oudet C.L.;
RT "Non-random distribution of mutations in the PHEX gene, and under-detected
RT missense mutations at non-conserved residues.";
RL Eur. J. Hum. Genet. 7:615-619(1999).
RN [18]
RP VARIANTS XLHR PHE-85; PRO-141; VAL-341 DEL; PRO-567; LYS-680 AND TYR-693.
RX PubMed=10737991;
RX DOI=10.1002/(sici)1098-1004(200004)15:4<383::aid-humu18>3.0.co;2-#;
RA Tyynismaa H., Kaitila I., Naentoe-Salonen K., Ala-Houhala M., Alitalo T.;
RT "Identification of fifteen novel PHEX gene mutations in Finnish patients
RT with hypophosphatemic rickets.";
RL Hum. Mutat. 15:383-384(2000).
RN [19]
RP VARIANTS XLHR ARG-160 AND ASN-444 INS.
RX PubMed=11004247; DOI=10.1203/00006450-200010000-00019;
RA Sato K., Tajima T., Nakae J., Adachi M., Asakura Y., Tachibana K., Suwa S.,
RA Katsumata N., Tanaka T., Hayashi Y., Abe S., Murashita M., Okuhara K.,
RA Shinohara N., Fujieda K.;
RT "Three novel PHEX gene mutations in Japanese patients with X-linked
RT hypophosphatemic rickets.";
RL Pediatr. Res. 48:536-540(2000).
CC -!- FUNCTION: Peptidase that cleaves SIBLING (small integrin-binding
CC ligand, N-linked glycoprotein)-derived ASARM peptides, thus regulating
CC their biological activity (PubMed:9593714, PubMed:15664000,
CC PubMed:18162525, PubMed:18597632). Cleaves ASARM peptides between Ser
CC and Glu or Asp residues (PubMed:18597632). Regulates osteogenic cell
CC differentiation and bone mineralization through the cleavage of the
CC MEPE-derived ASARM peptide (PubMed:18597632). Promotes dentin
CC mineralization and renal phosphate reabsorption by cleaving DMP1- and
CC MEPE-derived ASARM peptides (PubMed:18597632, PubMed:18162525).
CC Inhibits the cleavage of MEPE by CTSB/cathepsin B thus preventing MEPE
CC degradation (PubMed:12220505). {ECO:0000250|UniProtKB:P70669,
CC ECO:0000269|PubMed:12220505, ECO:0000269|PubMed:18162525,
CC ECO:0000269|PubMed:18597632}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:15664000};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:15664000};
CC -!- SUBUNIT: Interacts with MEPE; the interaction is zinc-dependent (via
CC ASARM motif). {ECO:0000269|PubMed:15664000,
CC ECO:0000269|PubMed:18162525}.
CC -!- INTERACTION:
CC P78562; Q9NQ76: MEPE; NbExp=2; IntAct=EBI-2827676, EBI-1753293;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9593714};
CC Single-pass type II membrane protein {ECO:0000269|PubMed:9593714}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in ovary (PubMed:9070861).
CC Expressed at low levels in kidney (PubMed:9070861).
CC {ECO:0000269|PubMed:9070861}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal lung (PubMed:9070861,
CC PubMed:9077527). Expressed in fetal calvaria and to a lesser extent in
CC fetal kidney and skeletal muscles (PubMed:9593714, PubMed:9077527).
CC {ECO:0000269|PubMed:9070861, ECO:0000269|PubMed:9077527,
CC ECO:0000269|PubMed:9593714}.
CC -!- DISEASE: Hypophosphatemic rickets, X-linked dominant (XLHR)
CC [MIM:307800]: A disorder characterized by impaired phosphate uptake in
CC the kidney, which is likely to be caused by abnormal regulation of
CC sodium phosphate cotransport in the proximal tubules. Clinical
CC manifestations include skeletal deformities, growth failure,
CC craniosynostosis, paravertebral calcifications, pseudofractures in
CC lower extremities, and muscular hypotonia with onset in early
CC childhood. X-linked hypophosphatemic rickets is the most common form of
CC hypophosphatemia with an incidence of 1 in 20000.
CC {ECO:0000269|PubMed:10439971, ECO:0000269|PubMed:10737991,
CC ECO:0000269|PubMed:11004247, ECO:0000269|PubMed:9097956,
CC ECO:0000269|PubMed:9106524, ECO:0000269|PubMed:9199930,
CC ECO:0000269|PubMed:9768646, ECO:0000269|PubMed:9768674}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the peptidase M13 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01233, ECO:0000305}.
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DR EMBL; Y08111; CAA69326.1; -; Genomic_DNA.
DR EMBL; Y08112; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08113; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08114; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08115; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08116; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08117; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08118; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08119; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08120; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08121; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08122; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08123; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08124; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08125; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08126; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08127; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08128; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08129; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08130; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08131; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; Y08132; CAA69326.1; JOINED; Genomic_DNA.
DR EMBL; U75645; AAB47749.1; -; mRNA.
DR EMBL; U87284; AAB47562.1; -; mRNA.
DR EMBL; AD000712; AAB51604.1; -; mRNA.
DR EMBL; AH004966; AAB42219.1; -; Genomic_DNA.
DR EMBL; U82970; AAC24487.1; -; mRNA.
DR EMBL; U73024; AAD08630.1; -; Genomic_DNA.
DR EMBL; Y10196; CAA71258.1; -; Genomic_DNA.
DR EMBL; BC105057; AAI05058.1; -; mRNA.
DR EMBL; BC105059; AAI05060.1; -; mRNA.
DR EMBL; U60475; AAC50552.1; -; mRNA.
DR CCDS; CCDS14204.1; -.
DR RefSeq; NP_000435.3; NM_000444.5.
DR RefSeq; NP_001269683.1; NM_001282754.1.
DR AlphaFoldDB; P78562; -.
DR SMR; P78562; -.
DR BioGRID; 111270; 3.
DR IntAct; P78562; 3.
DR STRING; 9606.ENSP00000368682; -.
DR MEROPS; M13.091; -.
DR GlyGen; P78562; 8 sites.
DR iPTMnet; P78562; -.
DR PhosphoSitePlus; P78562; -.
DR BioMuta; PHEX; -.
DR DMDM; 2499917; -.
DR EPD; P78562; -.
DR jPOST; P78562; -.
DR MassIVE; P78562; -.
DR PaxDb; P78562; -.
DR PeptideAtlas; P78562; -.
DR PRIDE; P78562; -.
DR ProteomicsDB; 57655; -.
DR Antibodypedia; 24481; 137 antibodies from 26 providers.
DR DNASU; 5251; -.
DR Ensembl; ENST00000379374.5; ENSP00000368682.4; ENSG00000102174.10.
DR GeneID; 5251; -.
DR KEGG; hsa:5251; -.
DR MANE-Select; ENST00000379374.5; ENSP00000368682.4; NM_000444.6; NP_000435.3.
DR UCSC; uc004dah.5; human.
DR CTD; 5251; -.
DR DisGeNET; 5251; -.
DR GeneCards; PHEX; -.
DR GeneReviews; PHEX; -.
DR HGNC; HGNC:8918; PHEX.
DR HPA; ENSG00000102174; Tissue enhanced (lung).
DR MalaCards; PHEX; -.
DR MIM; 300550; gene.
DR MIM; 307800; phenotype.
DR neXtProt; NX_P78562; -.
DR OpenTargets; ENSG00000102174; -.
DR Orphanet; 89936; X-linked hypophosphatemia.
DR PharmGKB; PA33258; -.
DR VEuPathDB; HostDB:ENSG00000102174; -.
DR eggNOG; KOG3624; Eukaryota.
DR GeneTree; ENSGT00940000157313; -.
DR HOGENOM; CLU_006187_4_1_1; -.
DR InParanoid; P78562; -.
DR OMA; YSSYYWK; -.
DR OrthoDB; 282463at2759; -.
DR PhylomeDB; P78562; -.
DR TreeFam; TF315192; -.
DR BRENDA; 3.4.24.B15; 2681.
DR PathwayCommons; P78562; -.
DR SignaLink; P78562; -.
DR BioGRID-ORCS; 5251; 19 hits in 697 CRISPR screens.
DR ChiTaRS; PHEX; human.
DR GeneWiki; PHEX; -.
DR GenomeRNAi; 5251; -.
DR Pharos; P78562; Tbio.
DR PRO; PR:P78562; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P78562; protein.
DR Bgee; ENSG00000102174; Expressed in secondary oocyte and 91 other tissues.
DR Genevisible; P78562; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
DR GO; GO:0060348; P:bone development; IEA:Ensembl.
DR GO; GO:0030282; P:bone mineralization; IEA:Ensembl.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEA:Ensembl.
DR GO; GO:0071305; P:cellular response to vitamin D; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0042476; P:odontogenesis; IEA:Ensembl.
DR GO; GO:0019637; P:organophosphate metabolic process; IEA:Ensembl.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0060416; P:response to growth hormone; IEA:Ensembl.
DR GO; GO:1990418; P:response to insulin-like growth factor stimulus; IEA:Ensembl.
DR GO; GO:1904383; P:response to sodium phosphate; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR CDD; cd08662; M13; 1.
DR Gene3D; 1.10.1380.10; -; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR000718; Peptidase_M13.
DR InterPro; IPR018497; Peptidase_M13_C.
DR InterPro; IPR042089; Peptidase_M13_dom_2.
DR InterPro; IPR008753; Peptidase_M13_N.
DR PANTHER; PTHR11733; PTHR11733; 1.
DR Pfam; PF01431; Peptidase_M13; 1.
DR Pfam; PF05649; Peptidase_M13_N; 1.
DR PRINTS; PR00786; NEPRILYSIN.
DR PROSITE; PS51885; NEPRILYSIN; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Biomineralization; Cell membrane; Disease variant; Disulfide bond;
KW Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..749
FT /note="Phosphate-regulating neutral endopeptidase PHEX"
FT /id="PRO_0000078228"
FT TOPO_DOM 1..20
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:9593714"
FT TRANSMEM 21..41
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000269|PubMed:9593714"
FT TOPO_DOM 42..641
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:9593714"
FT DOMAIN 53..749
FT /note="Peptidase M13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT ACT_SITE 581
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT ACT_SITE 646
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT BINDING 580
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 584
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 642
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 238
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 263
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 301
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 377
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 484
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 736
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..59
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 77..733
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 85..693
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 142..406
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 617..746
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT VARIANT 77
FT /note="C -> S (in XLHR)"
FT /evidence="ECO:0000269|PubMed:9097956"
FT /id="VAR_006738"
FT VARIANT 80
FT /note="F -> S (in XLHR; sporadic)"
FT /evidence="ECO:0000269|PubMed:10439971"
FT /id="VAR_010616"
FT VARIANT 85
FT /note="C -> F (in XLHR; sporadic)"
FT /evidence="ECO:0000269|PubMed:10737991"
FT /id="VAR_010617"
FT VARIANT 85
FT /note="C -> R (in XLHR; dbSNP:rs1556014287)"
FT /evidence="ECO:0000269|PubMed:9199930"
FT /id="VAR_010618"
FT VARIANT 85
FT /note="C -> Y (in XLHR; dbSNP:rs137853269)"
FT /evidence="ECO:0000269|PubMed:9106524"
FT /id="VAR_006739"
FT VARIANT 138
FT /note="L -> P (in XLHR)"
FT /evidence="ECO:0000269|PubMed:9097956"
FT /id="VAR_006740"
FT VARIANT 141
FT /note="S -> P (in XLHR; sporadic)"
FT /evidence="ECO:0000269|PubMed:10737991"
FT /id="VAR_010619"
FT VARIANT 142
FT /note="C -> F (in XLHR)"
FT /evidence="ECO:0000269|PubMed:10439971"
FT /id="VAR_010620"
FT VARIANT 160
FT /note="L -> R (in XLHR)"
FT /evidence="ECO:0000269|PubMed:11004247"
FT /id="VAR_010621"
FT VARIANT 166
FT /note="R -> C (in XLHR; dbSNP:rs751230094)"
FT /evidence="ECO:0000269|PubMed:9106524"
FT /id="VAR_006741"
FT VARIANT 237
FT /note="D -> G (in XLHR; sporadic)"
FT /evidence="ECO:0000269|PubMed:10439971"
FT /id="VAR_010622"
FT VARIANT 252
FT /note="F -> S (in XLHR; dbSNP:rs267606945)"
FT /evidence="ECO:0000269|PubMed:9106524"
FT /id="VAR_006742"
FT VARIANT 253
FT /note="M -> I (in XLHR; dbSNP:rs267606946)"
FT /evidence="ECO:0000269|PubMed:9106524"
FT /id="VAR_006743"
FT VARIANT 317
FT /note="Y -> F (in XLHR)"
FT /evidence="ECO:0000269|PubMed:9768674"
FT /id="VAR_010623"
FT VARIANT 341
FT /note="Missing (in XLHR; sporadic)"
FT /evidence="ECO:0000269|PubMed:10737991"
FT /id="VAR_010624"
FT VARIANT 444
FT /note="W -> WN (in XLHR)"
FT /evidence="ECO:0000269|PubMed:11004247"
FT /id="VAR_010625"
FT VARIANT 530
FT /note="W -> C (in XLHR; dbSNP:rs1556091855)"
FT /evidence="ECO:0000269|PubMed:10439971"
FT /id="VAR_010626"
FT VARIANT 534
FT /note="P -> L (in XLHR; dbSNP:rs886041363)"
FT /evidence="ECO:0000269|PubMed:9097956,
FT ECO:0000269|PubMed:9199930, ECO:0000269|PubMed:9768674"
FT /id="VAR_006744"
FT VARIANT 555
FT /note="L -> P (in XLHR; dbSNP:rs137853270)"
FT /evidence="ECO:0000269|PubMed:9768646"
FT /id="VAR_010627"
FT VARIANT 567
FT /note="R -> P (in XLHR; sporadic; dbSNP:rs760870713)"
FT /evidence="ECO:0000269|PubMed:10737991"
FT /id="VAR_010628"
FT VARIANT 573
FT /note="A -> D (in XLHR; sporadic; dbSNP:rs1556135308)"
FT /evidence="ECO:0000269|PubMed:10439971"
FT /id="VAR_010629"
FT VARIANT 579
FT /note="G -> R (in XLHR; dbSNP:rs875989883)"
FT /evidence="ECO:0000269|PubMed:9097956,
FT ECO:0000269|PubMed:9199930, ECO:0000269|PubMed:9768674"
FT /id="VAR_006745"
FT VARIANT 579
FT /note="G -> V (in XLHR; dbSNP:rs1057517980)"
FT /evidence="ECO:0000269|PubMed:9106524"
FT /id="VAR_006746"
FT VARIANT 621
FT /note="Q -> R (in XLHR)"
FT /evidence="ECO:0000269|PubMed:9768674"
FT /id="VAR_010630"
FT VARIANT 651
FT /note="R -> P (in XLHR; dbSNP:rs748792378)"
FT /evidence="ECO:0000269|PubMed:9199930"
FT /id="VAR_010631"
FT VARIANT 680
FT /note="N -> K (in XLHR; sporadic; dbSNP:rs1556151526)"
FT /evidence="ECO:0000269|PubMed:10737991"
FT /id="VAR_010633"
FT VARIANT 680
FT /note="Missing (in XLHR)"
FT /evidence="ECO:0000269|PubMed:9768674"
FT /id="VAR_010632"
FT VARIANT 693
FT /note="C -> Y (in XLHR; sporadic; dbSNP:rs1556200989)"
FT /evidence="ECO:0000269|PubMed:10737991"
FT /id="VAR_010634"
FT VARIANT 720
FT /note="A -> T (in XLHR)"
FT /evidence="ECO:0000269|PubMed:9768674"
FT /id="VAR_010635"
FT VARIANT 731
FT /note="F -> Y (in XLHR)"
FT /evidence="ECO:0000269|PubMed:9768674"
FT /id="VAR_010636"
FT VARIANT 733
FT /note="C -> S (in XLHR; sporadic; dbSNP:rs1057517981)"
FT /evidence="ECO:0000269|PubMed:10439971"
FT /id="VAR_010637"
FT VARIANT 746
FT /note="C -> W (in XLHR; sporadic)"
FT /evidence="ECO:0000269|PubMed:10439971"
FT /id="VAR_010638"
FT VARIANT 749
FT /note="W -> R (in XLHR; dbSNP:rs1556206403)"
FT /evidence="ECO:0000269|PubMed:9768674"
FT /id="VAR_010639"
FT CONFLICT 363
FT /note="A -> D (in Ref. 9; AAC50552)"
FT /evidence="ECO:0000305"
FT CONFLICT 403
FT /note="W -> R (in Ref. 9; AAC50552)"
FT /evidence="ECO:0000305"
FT CONFLICT 641
FT /note="G -> A (in Ref. 9; AAC50552)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 749 AA; 86474 MW; 7C4F9F3E2471C6A8 CRC64;
MEAETGSSVE TGKKANRGTR IALVVFVGGT LVLGTILFLV SQGLLSLQAK QEYCLKPECI
EAAAAILSKV NLSVDPCDNF FRFACDGWIS NNPIPEDMPS YGVYPWLRHN VDLKLKELLE
KSISRRRDTE AIQKAKILYS SCMNEKAIEK ADAKPLLHIL RHSPFRWPVL ESNIGPEGVW
SERKFSLLQT LATFRGQYSN SVFIRLYVSP DDKASNEHIL KLDQATLSLA VREDYLDNST
EAKSYRDALY KFMVDTAVLL GANSSRAEHD MKSVLRLEIK IAEIMIPHEN RTSEAMYNKM
NISELSAMIP QFDWLGYIKK VIDTRLYPHL KDISPSENVV VRVPQYFKDL FRILGSERKK
TIANYLVWRM VYSRIPNLSR RFQYRWLEFS RVIQGTTTLL PQWDKCVNFI ESALPYVVGK
MFVDVYFQED KKEMMEELVE GVRWAFIDML EKENEWMDAG TKRKAKEKAR AVLAKVGYPE
FIMNDTHVNE DLKAIKFSEA DYFGNVLQTR KYLAQSDFFW LRKAVPKTEW FTNPTTVNAF
YSASTNQIRF PAGELQKPFF WGTEYPRSLS YGAIGVIVGH EFTHGFDNNG RKYDKNGNLD
PWWSTESEEK FKEKTKCMIN QYSNYYWKKA GLNVKGKRTL GENIADNGGL REAFRAYRKW
INDRRQGLEE PLLPGITFTN NQLFFLSYAH VRCNSYRPEA AREQVQIGAH SPPQFRVNGA
ISNFEEFQKA FNCPPNSTMN RGMDSCRLW
