PHEX

PHEX
Identifiers
Aliases	PHEX, HPDR, HPDR1, HYP, HYP1, LXHR, PEX, XLH, phosphate regulating endopeptidase homolog, X-linked, phosphate regulating endopeptidase homolog X-linked
External IDs	OMIM: 300550 MGI: 107489 HomoloGene: 37310 GeneCards: PHEX
Gene location (Human)
Chr.	X chromosome (human)
End	22,494,713 bp
Gene location (Mouse)
Chr.	X chromosome (mouse)
End	157,415,312 bp
RNA expression pattern
	Top expressed in
	tibia; ; lung; ; right lung; ; upper lobe of left lung; ; organ system; ; endometrium; ; myometrium; ; jejunal mucosa; ; ovary;
	More reference expression data
	n/a
Gene ontology
Molecular function	zinc ion binding; peptidase activity; metalloendopeptidase activity; aminopeptidase activity; hydrolase activity; metallopeptidase activity; metal ion binding;
Cellular component	perinuclear region of cytoplasm; integral component of membrane; plasma membrane; Golgi apparatus; integral component of plasma membrane; endoplasmic reticulum; membrane;
Biological process	organophosphate metabolic process; skeletal system development; cell-cell signaling; bone mineralization; biomineral tissue development; cellular protein modification process; proteolysis; lung development; response to vitamin D; bone development; response to growth hormone; cellular response to vitamin D; cellular response to parathyroid hormone stimulus; response to sodium phosphate; response to insulin-like growth factor stimulus; odontogenesis;
	Sources:Amigo / QuickGO
Orthologs
	5251
	18675
	ENSG00000102174
	ENSMUSG00000057457
	P78562
	P70669
	NM_000444; NM_001282754
	NM_011077
	NP_000435; NP_001269683
	NP_035207
	Wikidata
View/Edit Human	View/Edit Mouse

Phosphate-regulating neutral endopeptidase, X-linked also known as phosphate-regulating gene with homologies to endopeptidases on the X chromosome or metalloendopeptidase homolog PEX is an enzyme that in humans is encoded by the PHEX gene.^[5]^[6] This gene contains 18 exons and is located on the X chromosome.

Function[]

The protein encoded by this gene is a transmembrane endopeptidase that belongs to the type II integral membrane zinc-dependent endopeptidase family. The protein is thought to be involved in bone and dentin mineralization and renal phosphate reabsorption.^[7] The bone and dentin protein osteopontin (OPN) which inhibits mineralization in the skeleton and in teeth is a substrate for PHEX.^[8] In the absence of functional PHEX in the mouse model (Hyp) of X-linked hypophosphatemia (XLH), and in human XLH where PHEX activity is decreased or absent, in addition to renal phosphate wasting, osteopontin and osteopontin fragments accumulate in bone and teeth and may contribute locally to the osteomalacia characteristic of XLH/HYP.^[9]^[10]^[11]^[12]^[13] XLH patients have soft and deformed skeletons and soft teeth that easily become infected.

Clinical significance[]

Mutation of PHEX leads to X-linked hypophosphatemia.^[5]

References[]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000102174 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000057457 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b Francis, F. (October 1995). "A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets (XLH/HYP). The HYP Consortium". Nat. Genet. 11 (2): 130–6. doi:10.1038/ng1095-130. PMID 7550339. S2CID 6424732.
^ Grieff M, Mumm S, Waeltz P, Mazzarella R, Whyte MP, Thakker RV, Schlessinger D (February 1997). "Expression and cloning of the human X-linked hypophosphatemia gene cDNA". Biochem. Biophys. Res. Commun. 231 (3): 635–9. doi:10.1006/bbrc.1997.6153. PMID 9070861.
^ "Entrez Gene: phosphate regulating endopeptidase homolog".
^ Barros, NMT; et al. (2013). "Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia". Journal of Bone and Mineral Research. 28 (3): 688–699. doi:10.1002/jbmr.1766. PMID 22991293.
^ Boukpessi, T; Gaucher, C; Léger, T; Salmon, B; Le Faouder, J; Willig, C; Rowe, PS; Garabédian, M; Meilhac, O; Chaussain, C (August 2010). "Abnormal presence of the matrix extracellular phosphoglycoprotein-derived acidic serine- and aspartate-rich motif peptide in human hypophosphatemic dentin". The American Journal of Pathology. 177 (2): 803–12. doi:10.2353/ajpath.2010.091231. PMC 2913338. PMID 20581062.
^ Boukpessi, T; Hoac, B; Coyac, BR; Leger, T; Garcia, C; Wicart, P; Whyte, MP; Glorieux, FH; Linglart, A; Chaussain, C; McKee, MD (21 November 2016). "Osteopontin and the dento-osseous pathobiology of X-linked hypophosphatemia". Bone. 95: 151–161. doi:10.1016/j.bone.2016.11.019. PMID 27884786.
^ Barros, NM; Hoac, B; Neves, RL; Addison, WN; Assis, DM; Murshed, M; Carmona, AK; McKee, MD (March 2013). "Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia". Journal of Bone and Mineral Research. 28 (3): 688–99. doi:10.1002/jbmr.1766. PMID 22991293.
^ McKee, MD; Hoac, B; Addison, WN; Barros, NM; Millán, JL; Chaussain, C (October 2013). "Extracellular matrix mineralization in periodontal tissues: Noncollagenous matrix proteins, enzymes, and relationship to hypophosphatasia and X-linked hypophosphatemia". Periodontology 2000. 63 (1): 102–22. doi:10.1111/prd.12029. PMC 3766584. PMID 23931057.
^ Salmon, B; Bardet, C; Coyac, BR; Baroukh, B; Naji, J; Rowe, PS; Opsahl Vital, S; Linglart, A; Mckee, MD; Chaussain, C (August 2014). "Abnormal osteopontin and matrix extracellular phosphoglycoprotein localization, and odontoblast differentiation, in X-linked hypophosphatemic teeth". Connective Tissue Research. 55 Suppl 1: 79–82. doi:10.3109/03008207.2014.923864. PMID 25158186. S2CID 19702315.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article on a gene on the human X chromosome and/or its associated protein is a stub. You can help Wikipedia by .

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000102174 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000057457 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid7550339-5] Francis, F. (October 1995). "A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets (XLH/HYP). The HYP Consortium". Nat. Genet. 11 (2): 130–6. doi:10.1038/ng1095-130. PMID 7550339. S2CID 6424732.

[pmid9070861-6] Grieff M, Mumm S, Waeltz P, Mazzarella R, Whyte MP, Thakker RV, Schlessinger D (February 1997). "Expression and cloning of the human X-linked hypophosphatemia gene cDNA". Biochem. Biophys. Res. Commun. 231 (3): 635–9. doi:10.1006/bbrc.1997.6153. PMID 9070861.

[entrez-7] "Entrez Gene: phosphate regulating endopeptidase homolog".

[Barros_2013_688–699-8] Barros, NMT; et al. (2013). "Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia". Journal of Bone and Mineral Research. 28 (3): 688–699. doi:10.1002/jbmr.1766. PMID 22991293.

[9] Boukpessi, T; Gaucher, C; Léger, T; Salmon, B; Le Faouder, J; Willig, C; Rowe, PS; Garabédian, M; Meilhac, O; Chaussain, C (August 2010). "Abnormal presence of the matrix extracellular phosphoglycoprotein-derived acidic serine- and aspartate-rich motif peptide in human hypophosphatemic dentin". The American Journal of Pathology. 177 (2): 803–12. doi:10.2353/ajpath.2010.091231. PMC 2913338. PMID 20581062.

[10] Boukpessi, T; Hoac, B; Coyac, BR; Leger, T; Garcia, C; Wicart, P; Whyte, MP; Glorieux, FH; Linglart, A; Chaussain, C; McKee, MD (21 November 2016). "Osteopontin and the dento-osseous pathobiology of X-linked hypophosphatemia". Bone. 95: 151–161. doi:10.1016/j.bone.2016.11.019. PMID 27884786.

[11] Barros, NM; Hoac, B; Neves, RL; Addison, WN; Assis, DM; Murshed, M; Carmona, AK; McKee, MD (March 2013). "Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia". Journal of Bone and Mineral Research. 28 (3): 688–99. doi:10.1002/jbmr.1766. PMID 22991293.

[12] McKee, MD; Hoac, B; Addison, WN; Barros, NM; Millán, JL; Chaussain, C (October 2013). "Extracellular matrix mineralization in periodontal tissues: Noncollagenous matrix proteins, enzymes, and relationship to hypophosphatasia and X-linked hypophosphatemia". Periodontology 2000. 63 (1): 102–22. doi:10.1111/prd.12029. PMC 3766584. PMID 23931057.

[13] Salmon, B; Bardet, C; Coyac, BR; Baroukh, B; Naji, J; Rowe, PS; Opsahl Vital, S; Linglart, A; Mckee, MD; Chaussain, C (August 2014). "Abnormal osteopontin and matrix extracellular phosphoglycoprotein localization, and odontoblast differentiation, in X-linked hypophosphatemic teeth". Connective Tissue Research. 55 Suppl 1: 79–82. doi:10.3109/03008207.2014.923864. PMID 25158186. S2CID 19702315.

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v t Proteases: metalloendopeptidases (EC 3.4.24)
ADAM proteins	Alpha secretases ADAM9 ADAM10 ADAM17 ADAM19 ADAM2 ADAM7 ADAM8 ADAM11 ADAM12 ADAM15 ADAM18 ADAM22 ADAM23 ADAM28 ADAM33 ADAMTS1 ADAMTS2 ADAMTS3 ADAMTS4 ADAMTS5 ADAMTS8 ADAMTS9 ADAMTS10 ADAMTS12 ADAMTS13
Matrix metalloproteinases	Collagenases MMP1 MMP8 Gelatinases MMP2 MMP9 MMP3 MMP7 MMP10 MMP11 MMP12 MMP13 MMP14 MMP15 MMP16 MMP17 MMP19 MMP20 MMP21 MMP23B MMP24 MMP25 MMP26 MMP27 MMP28
Other	Neprilysin Procollagen peptidase Thermolysin Pregnancy-associated plasma protein A Bone morphogenetic protein 1 Lysostaphin Insulin-degrading enzyme ZMPSTE24

v t Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)