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Information on EC 3.4.24.B15 - PHEX peptidase and Organism(s) Homo sapiens and UniProt Accession P78562
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3.4.24.B15 PHEX peptidaseSpecify your search results
Word Map
- 3.4.24.B15
- medicine
-
osteomalacia
- phosphoglycoprotein
- osteopontin
-
dentin
- hydroxyapatite
- osteoblast
- camp
-
integrin-binding
-
asarm
-
n-linked
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
phex enzyme, phosphate-regulating neutral endopeptidase, dphex, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PEX
phosphate-regulating gene with homologies to endo-peptidases on the X chromosome
-
phosphate-regulating gene with homologies to endopeptidases on the X chromosome
-
matrix metalloprotease 2 hemopexin domain
-
-
-
-
PHEX
phosphate-regulating gene with homologies to endiopeptidases on the X chromosome
-
-
phosphate-regulating gene with homologies to endopeptidases on the X-chromosome
-
-
PHEX
-
encoded by PHEx i.e. phosphate-regulating gene with homologies to endopeptidase on the X-chromosome
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
proteolytic degradation of proteins
at the N-terminus of aspartate residues, the S1' pocket can accomodate negatively charged side chains of amino acid residues
-
proteolytic degradation of proteins
preference for an acidic residue at position P'1, especially for aspartic acid, glutamic acid gives 5fold lower activity
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CAS REGISTRY NUMBER
COMMENTARY
263550-81-8
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
dentin sialophosphoprotein + H2O
dentin sialoprotein + dentin phosphoprotein + dentin glycoprotein
-
-
-
?
o-aminobenzoyl-GFSDYK-(2,4-dinitrophenyl)-OH + H2O
o-aminobenzoyl-GFS + DYK-(2,4-dinitrophenyl)-OH
-
-
-
?
2-aminobenzoyl-Gly-Phe-Ser-Asp-Tyr-Lys(Dnp)-OH + H2O
2-aminobenzoyl-Gly-Phe-Ser + Asp-Tyr-Lys(Dnp)-OH
-
-
-
-
?
DDSHQ(pS)DESHH(pS)DE(pS)DEL + 2 H2O
DDSHQ(pS) + DESHH(pS) + DE(pS)DEL
-
synthetic peptide derived from human osteopontin ASARM motif sequence, cleavage of DDSHQSDESHHSDESDEL and DD(pS)HQ(pS)DE(pS)HH(pS)DE(pS)DEL is also observed
-
-
?
o-aminobenzoyl-A110WLDSGVQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-A110WL + DSGVQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on residues 107-139 sequence of the enzyme, cleavage site is the Leu-Asp bond
-
?
o-aminobenzoyl-D124HLSDTSTQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-D124HLS + DTSTQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on residues 107-139 sequence of the enzyme, cleavage site is the Ser-Asp bond
-
?
o-aminobenzoyl-G197QRDSQAQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-G197QR + DSQAQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on the MEPE protein sequence
-
?
o-aminobenzoyl-G337SNDIMGQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-G337SN + DIMGQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on the MEPE protein sequence
-
?
o-aminobenzoyl-G386SSDAAEQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-G386SS + DAAEQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on the MEPE protein sequence
-
?
o-aminobenzoyl-GFSDYK-(2,4-dinitrophenyl)-NH2 + H2O
o-aminobenzoyl-GFS + DYK-(2,4-dinitrophenyl)-NH2
-
cleavage site is the Ser-Asp bond
-
?
o-aminobenzoyl-GFSDYK-(2,4-dinitrophenyl)-OH + H2O
o-aminobenzoyl-GFS + DYK-(2,4-dinitrophenyl)-OH
-
best substrate, cleavage site is the Ser-Asp bond
-
?
o-aminobenzoyl-GFSDYQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-GFS + DYQ-N-(2,4-dinitrophenyl)ethylene diamine
-
cleavage site is the Ser-Asp bond
-
?
o-aminobenzoyl-GFSEY-(2,4-dinitrophenyl)K + H2O
o-aminobenzoyl-GFS + EY-(2,4-dinitrophenyl)K
-
low activity, cleavage site is the Ser-Asp bond
-
?
o-aminobenzoyl-IPSDFEGQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-IPS + DFEGQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on the MEPE protein sequence
-
?
o-aminobenzoyl-L134ELDSRQ-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-L134EL + DSRQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on residues 107-139 sequence of the enzyme, cleavage site is the Leu-Asp bond
-
?
o-aminobenzoyl-L94MMDFRGQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-L94MM + DFRGQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on the FGF-23 protein sequence, cleavage site is the Met-Asp bond
-
?
o-aminobenzoyl-N122GYDVYHQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-N122GY + DVYHQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on the FGF-23 protein sequence, cleavage site is the Tyr-Asp bond
-
?
o-aminobenzoyl-N449EMDSFNQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-N449EM + DSFNQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on the MEPE protein sequence
-
?
o-aminobenzoyl-R175RHTQSAEDDSERQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-R175RHTQSAED + DSERQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on the FGF-23 protein sequence, cleavage site is the Asp-Asp bond
-
?
o-aminobenzoyl-R175RHTRSAEDDSERQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-R175RHTRSAED + DSERQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on the FGF-23 protein sequence, cleavage site is the Asp-Asp bond
-
?
o-aminobenzoyl-R441GLDNEIQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-R441GL + DNEIQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on the MEPE protein sequence
-
?
o-aminobenzoyl-R506RDDSSEQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-R506RD + DSSEQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on the MEPE protein sequence
-
?
o-aminobenzoyl-R76SEDAGFQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-R76SE + DAGFQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on the FGF-23 protein sequence, cleavage site is the Glu-Asp bond
-
?
o-aminobenzoyl-S212AEDNSPQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-S212AE + DNSPQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on the FGF-23 protein sequence, cleavage site is the Glu-Asp bond
-
?
o-aminobenzoyl-S513SDSGSQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-S513S + DSGSQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on the MEPE protein sequence
-
?
o-aminobenzoyl-T294HLDTKKQ-N-(2,4-dinitrophenyl)ethylene diamine + H2O
o-aminobenzoyl-T294HL + DTKKQ-N-(2,4-dinitrophenyl)ethylene diamine
-
sequence is based on the MEPE protein sequence
-
?
parathyroid-hormone-related peptide 107-139 + H2O
L-threonyl-L-arginyl-L-seryl-L-alanyl-L-tryptophyl-L-leucyl-L-alpha-aspartyl-L-serylglycyl-L-valyl-L-threonylglycyl-L-serylglycyl-L-leucyl-L-alpha-glutamylglycyl-L-a-aspartyl-L-histidyl-L-leucyl-L-serine + L-alpha-aspartyl-L-threonyl-L-seryl-L-threonyl-L-threonyl-L-seryl-L-leucyl-L-alpha-glutamyl-L-leucyl-L-alpha-aspartyl-L-seryl-L-arginine + L-threonyl-L-arginyl-L-seryl-L-alanyl-L-tryptophyl-L-leucine + L-alpha-aspartyl-L-threonyl-L-seryl-L-threonyl-L-threonyl-L-seryl-L-leucyl-L-alpha-glutamyl-L-leucine + L-alpha-aspartyl-L-seryl-L-arginine
-
-
product determination
?
Z-Ala-Ala-Leu-4-nitroanilide + H2O
Z-Ala-Ala-Leu + 4-nitroaniline
-
chromogenic substrate
-
?
protein + H2O
peptides
-
enzyme is involved in pathology of oncogenic osteomalacia, X-linked hypophosphatemia, and autosomal dominant hypophosphatemic rickets
-
?
protein + H2O
peptides
-
enzyme mutations are responsible for X-chromosome linked hypophosphataemia
-
?
protein + H2O
peptides
-
enzyme mutations are responsible for X-chromosome linked hypophosphataemia by increasing levels of circulating phosphaturic factor
-
?
protein + H2O
peptides
-
participates in postsecretory processing, enzyme is involved in regulation of phosphate levels and in bone metabolism
-
?
protein FGF-23 + H2O
?
-
recombinant wild-type substrate, but not the recombinant mutant FGF-23(R179Q)
-
?
protein FGF-23 + H2O
?
-
i.e. fibroblastic growth factor 23, loss of enzyme activity results in either diminished degradation or increased biosynthesis of FGF-23
-
?
additional information
?
-
major role of PHEX in X-linked dominant hypophosphatemic rickets
-
-
?
additional information
?
-
-
human stanniocalcin STC-1, casein and wild-type as well as mutant FGF-23 proteins are no substrates, recombinant rat parathyroid hormone is no substrate for the wild-type and mutant recombinant enzyme
-
?
additional information
?
-
-
no activity of wild-type and soluble enzyme form with o-aminobenzoyl-RL-N-(2,4-dinitrophenyl)ethylene diamine, no activity with o-aminobenzoyl-GFSEYK-(2,4-dinitrophenyl)-NH2
-
?
additional information
?
-
-
no activity with [Leu]enkephalin, alpha-endorphin, substance P, bradykinin, big-endothelin-1, endothelin-1, alpha-calcitonin, gene-related peptide alpha-CGRP, calcitonin, osteocalcin, parathyroid-hormone-related peptide 1-84, parathyroid-hormone-related peptide 1-34, and osteogenic growth peptide
-
?
additional information
?
-
-
recombinant protein FGF-23, i.e. fibroblastic growth factor 23 seems to be no direct substrate for the enzyme
-
?
additional information
?
-
-
enzyme-deficiency is involved in X-linked hypophosphatemia, XLH, the enzyme inactivates a phosphaturic factor, which may be fibroblast growth factor 23
-
-
?
additional information
?
-
-
glycosaminoglycans interact with PHEX, interfering with its enzyme activity, protein stability and cellular trafficking. This interaction may regulate PHEX function influencing the mineralization process
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
dentin sialophosphoprotein + H2O
dentin sialoprotein + dentin phosphoprotein + dentin glycoprotein
-
-
-
?
protein FGF-23 + H2O
?
-
i.e. fibroblastic growth factor 23, loss of enzyme activity results in either diminished degradation or increased biosynthesis of FGF-23
-
?
protein + H2O
peptides
-
enzyme is involved in pathology of oncogenic osteomalacia, X-linked hypophosphatemia, and autosomal dominant hypophosphatemic rickets
-
?
protein + H2O
peptides
-
enzyme mutations are responsible for X-chromosome linked hypophosphataemia
-
?
protein + H2O
peptides
-
enzyme mutations are responsible for X-chromosome linked hypophosphataemia by increasing levels of circulating phosphaturic factor
-
?
protein + H2O
peptides
-
participates in postsecretory processing, enzyme is involved in regulation of phosphate levels and in bone metabolism
-
?
additional information
?
-
major role of PHEX in X-linked dominant hypophosphatemic rickets
-
-
?
additional information
?
-
-
enzyme-deficiency is involved in X-linked hypophosphatemia, XLH, the enzyme inactivates a phosphaturic factor, which may be fibroblast growth factor 23
-
-
?
additional information
?
-
-
glycosaminoglycans interact with PHEX, interfering with its enzyme activity, protein stability and cellular trafficking. This interaction may regulate PHEX function influencing the mineralization process
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
no inhibition by thiorphan of wild-type and soluble enzyme form
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0015
o-aminobenzoyl-A110WLDSGVQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.0013
o-aminobenzoyl-D124HLSDTSTQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.047
o-aminobenzoyl-G197QRDSQAQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.013
o-aminobenzoyl-G337SNDIMGQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.0024
o-aminobenzoyl-G386SSDAAEQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.053
o-aminobenzoyl-GFSDYK-(2,4-dinitrophenyl)-NH2
-
pseudo-first-order conditions, recombinant soluble enzyme, pH 5.5, 37°C
0.003
o-aminobenzoyl-GFSDYK-(2,4-dinitrophenyl)-OH
-
pseudo-first-order conditions, recombinant soluble enzyme, pH 5.5, 37°C
0.013
o-aminobenzoyl-GFSDYQ-N-(2,4-dinitrophenyl)ethylene diamine
-
pseudo-first-order conditions, recombinant soluble enzyme, pH 5.5, 37°C
0.0009
o-aminobenzoyl-L134ELDSRQ-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.017
o-aminobenzoyl-L94MMDFRGQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.009
o-aminobenzoyl-N122GYDVYHQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.037
o-aminobenzoyl-N449EMDSFNQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.0017
o-aminobenzoyl-R175RHTQSAEDDSERQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.003
o-aminobenzoyl-R175RHTRSAEDDSERQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.007
o-aminobenzoyl-R441GLDNEIQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.005
o-aminobenzoyl-R506RDDSSEQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.004
o-aminobenzoyl-R76SEDAGFQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.022
o-aminobenzoyl-S212AEDNSPQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.032
o-aminobenzoyl-S513SDSGSQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.015
o-aminobenzoyl-T294HLDTKKQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.04
o-aminobenzoyl-A110WLDSGVQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.1
o-aminobenzoyl-D124HLSDTSTQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.2
o-aminobenzoyl-G197QRDSQAQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.01
o-aminobenzoyl-G337SNDIMGQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.3
o-aminobenzoyl-G386SSDAAEQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
1.3
o-aminobenzoyl-GFSDYK-(2,4-dinitrophenyl)-NH2
-
recombinant soluble enzyme, pH 5.5, 37°C
0.5
o-aminobenzoyl-GFSDYK-(2,4-dinitrophenyl)-OH
-
recombinant soluble enzyme, pH 5.5, 37°C
0.6
o-aminobenzoyl-GFSDYQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.05
o-aminobenzoyl-L134ELDSRQ-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.8
o-aminobenzoyl-L94MMDFRGQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.01
o-aminobenzoyl-N122GYDVYHQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.3
o-aminobenzoyl-N449EMDSFNQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.15
o-aminobenzoyl-R175RHTQSAEDDSERQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.2
o-aminobenzoyl-R175RHTRSAEDDSERQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.03
o-aminobenzoyl-R441GLDNEIQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.5
o-aminobenzoyl-R506RDDSSEQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.06
o-aminobenzoyl-R76SEDAGFQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.3
o-aminobenzoyl-S212AEDNSPQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.2
o-aminobenzoyl-S513SDSGSQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
0.02
o-aminobenzoyl-T294HLDTKKQ-N-(2,4-dinitrophenyl)ethylene diamine
-
recombinant soluble enzyme, pH 5.5, 37°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
PHEX and osteopontin are coexpressed in squamous cell carcinoma. Metastatic SCC-22B cells express 2fold more PHEX than primary tumor SCC-22A cells
PHEX and osteopontin are coexpressed in squamous cell carcinoma. Metastatic SCC-22B cells express 2fold more PHEX than primary tumor SCC-22A cells
-
PHEX colocalizes with heparan sulfate at the cell surface of osteoblasts
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
additional information
OHEX is not prominentat the squamous cell carcinoma cell membrane
-
additional information
-
OHEX is not prominentat the squamous cell carcinoma cell membrane
-
additional information
-
enzyme is possibly an ectoenzyme, membrane-spanning region towards the N-terminus
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
in squamous cell carcinoma cells, PHEX is degraded by endogenous cysteine proteases. Inhibition of cysteine proteases rescues membrane PHEX and osteopontin processing
malfunction
physiological function
malfunction
defects in PHEX are responsible for X-linked hypophosphatemic rickets. Loss of enzyme function causes defective mineralization, hypophosphatemia, abnormal vitamin-D metabolism and gross skeletal abnormalities. Loss of enzyme activity leads to increased fibroblast growth factor 23 expression
malfunction
enzyme defects are responsible for X-linked hypophosphatemic rickets
malfunction
-
nonsense mutation in exon 3 of the PHEX gene (Glu96, 286G>T) causing X-linked hypophosphatemia, PHEX gene is located on Xp22.1 and consists of 22 exons encoding a 749-amino-acid protein that is homologous to a family of neutral endopeptidases, including neprilysin, endothelin-converting enzyme-1 and the KELL antigen
malfunction
-
X-linked hypophosphatemia is caused by inactivating mutations in PHEX, a gene encoding for a protease responsible for the degradation and clearance of mineralization-inhibiting ASARM peptides
physiological function
-
nonsense mutation in exon 3 of the PHEX gene (Glu96, 286G>T) causing X-linked hypophosphatemia, PHEX gene is located on Xp22.1 and consists of 22 exons encoding a 749-amino-acid protein that is homologous to a family of neutral endopeptidases, including neprilysin, endothelin-converting enzyme-1 and the KELL antigen
physiological function
-
X-linked hypophosphatemia is caused by inactivating mutations in PHEX, a gene encoding for a protease responsible for the degradation and clearance of mineralization-inhibiting ASARM peptides
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
100000
-
x * 95000, recombinant soluble, deglycosylated mutant, SDS-PAGE, x * 100000, recombinant soluble mutant, SDS-PAGE, x * 105000, native wild-type, SDS-PAGE
105000
-
x * 95000, recombinant soluble, deglycosylated mutant, SDS-PAGE, x * 100000, recombinant soluble mutant, SDS-PAGE, x * 105000, native wild-type, SDS-PAGE
95000
-
x * 95000, recombinant soluble, deglycosylated mutant, SDS-PAGE, x * 100000, recombinant soluble mutant, SDS-PAGE, x * 105000, native wild-type, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 95000, recombinant soluble, deglycosylated mutant, SDS-PAGE, x * 100000, recombinant soluble mutant, SDS-PAGE, x * 105000, native wild-type, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C95X
deletion in exon 2 of the PHEX gene 177delC results in a premature stop codon (C59X), suggesting an inactivating truncation of the PHEX protein
E581V
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site-directed mutagenesis, soluble secreted mutant secPHEXE581V, inactive
additional information
additional information
creation and analysis of splice-site mutations. Among 22 splice-site mutations, exon skipping accounts for 73% (16/22). Non-canonical splice-site mutations can result in splicing errors to the same extent as canonical splice-site mutations such as c.436+3G>C, c.436+4A>C, c.436+6T>C, c.437-3C>G, c.850-3C>G, c.1080-3C>A, c.1482+5G>C, c.1586+6T>C, c.1645+5G>A, c.1645+6T>C, c.1701-16T>A, c.1768+5G>A, and c.1899+5G>A. Non-canonical (c.436+6T>C and c.1586+6T>C) and canonical splice-site mutations (c.1769-1G>C) can generate partial splicing errors (both wild-type and mutant transcripts are detected), resulting in incomplete inactivation of PHEX gene. Mutation c.1645C>T (p.R549*) has no impact on pre-mRNA splicing
additional information
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construction of an active soluble secreted mutant enzyme form secPHEX, enzyme mutations are responsible for X-chromosome linked hypophosphataemia
additional information
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overexpression of human PHEX in enzyme-deficient transgenic mutant Hyp mice does not fully rescue the Hyp mouse phenotype, overview
additional information
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a frameshift mutation (nucleotide 1826-1830delAAAAG, stop after codon 610) in exon 18 is responsible for X-linked hypophosphatemic rickets
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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PHEX is protected by glycosaminoglycans against thermal denaturation. The presence of heparin stabilizes the overall PHEX tertiary structure against denaturation at high temperature
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression as V5-epitope tagged enzyme in an in vitro rabbit reticulocyte lysate system
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functional in vitro expression by a reticulocyte lysate expression system, protein expressed in COS-7 cells is not functional
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gene PHEX, localization on the X chromosome, overexpression under control of the human beta-actin promoter in transgenic mice in all tissue except for pancreas, ovary and brain
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PHEX gene, expression of wild-type and mutants in LLC-PK1 porcine kidney cells
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PHEX gene, i.e. phosphate-regulating gene with homologies to endopeptidase on the X-chromosome, expression as soluble secreted mutant form secPHEX, lacking residues 1-45, in LLC-PK1 porcine kidney cells, deletion mutant enzyme shows catalytic properties similar to the wild-type enzyme
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
PHEX is the key enzyme in the pathogenesis of X-linked hypophosphatemic rickets. Mutational analysis of the PHEX gene reveals three point mutations and two amino acid changes which may be rare polymorphisms, as well as a small deletion, found as a mosaic in the affected patient. Early diagnosis of possibly affected children by molecular genetic analysis is of great importance because it allows early therapeutic intervention before manifestation of skeletal deformities occurs, thereby improving the clinical outcomes
medicine
the present genetic study of a large cohort of hypophosphatemic patients (209 patients representing 118 pedigrees) highlights the major role played by mutations in the PHEX gene as the cause of familial hypophosphatemic rickets. PHEX mutations are found in 79% of all proband
medicine
X-linked hypophosphatemia is a dominant disorder of phosphate homeostasis characterized by growth retardation, rachitic and osteomalacic bone disease, hypophosphatemia, and renal defects in phosphate reabsorption and vitamin D metabolism. The gene responsible for XLH is identified by positional cloning and designated PHEX (formerly PEX) to depict a phosphate regulating gene with homology to endopeptidases on the X chromosome
medicine
a PHEX splice acceptor mutation is found in intron 9 (c.1080-3C>A) in a family with 3 affected individuals with hypophosphatemic rickets. A sporadic case with hypophosphatemic rickets from the Indian subcontinent revealed PHEX mutation (c.1211_1215delACAAAinsTTTACAT, p.Asp404Valfs*5, de novo) located in exon 11. Analysis of all human splice sites adjacent to all 327293 exons across 81814 transcripts among 20345 human genes revealed that cytosine is, with 64.3%, the most frequent nucleobase at the minus 3 splice acceptor position, followed by thymidine with 28.7%, adenine with 6.3%, and guanine with 0.8%
medicine
identification of mutations c.983_987dupCTACC, c.1586+2T>G, c.1206delA, c.436+1G>T, c.1217G>T, and g.22,215,887+-22,395,767del (179880 bp deletion including exon 16+-22 and ZNF645) in patients with hypophosphatemia. Patients with de novo PHEX mutations often have delayed diagnosis and significantly shorter in height than those who have inherited PHEX mutations. Compound heterzygous mutations in SLC34A3 are found in one patient and his asymptomatic sister: c.1335+2T>A and c.1639_1652del14
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Boeckmann, B.; Bairoch, A.; Apweiler, R.; Blatter, M.C.; Estreicher, A.; Gasteiger, E.; Martin M.J.; Michoud, K.; O'Donovan, C.; Phan, I.; Pilbout, S.; Schneider, M.
The SWISS-PROT protein knowledgebase and its supplement TrEMBL
Nucleic Acids Res.
31
365-370
2003
Homo sapiens (P78562), Mus musculus (P70669)
Guo, R.; Liu, S.; Spurney, R.F.; Quarles, L.D.
Analysis of recombinant Phex: an endopeptidase in search of a substrate
Am. J. Physiol.
281
E837-847
2001
Homo sapiens, Mus musculus
Bowe, A.E.; Finnegan, R.; Jan de Beur, S.M.; Cho, J.; Levine, M.A.; Kumar, R.; Schiavi, S.C.
FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate
Biochem. Biophys. Res. Commun.
284
977-981
2001
Homo sapiens
Boileau, G.; Tenenhouse, H.S.; Desgroseillers, L.; Crine, P.
Characterization of PHEX endopeptidase catalytic activity: identification of parathyroid-hormone-related peptide107-139 as a substrate and osteocalcin, PPi and phosphate as inhibitors
Biochem. J.
355
707-713
2001
Homo sapiens
Campos, M.; Couture, C.; Hirata, I.Y.; Juliano, M.A.; Loisel, T.P.; Crine, P.; Juliano, L.; Boileau, G.; Carmona, A.K.
Human recombinant endopeptidase PHEX has a strict S1' specificity for acidic residues and cleaves peptides derived from fibroblast growth factor-23 and matrix extracellular phosphoglycoprotein
Biochem. J.
373
271-279
2003
Homo sapiens
Turner, A.J.; Tanzawa, K.
Mammalian membrane metallopeptidases: NEP, ECE, KELL, and PEX
FASEB J.
11
355-364
1997
Homo sapiens
Liu, S.; Guo, R.; Simpson, L.G.; Xiao, Z.S.; Burnham, C.E.; Quarles, L.D.
Regulation of fibroblastic growth factor 23 expression but not degradation by PHEX
J. Biol. Chem.
278
37419-37426
2003
Homo sapiens
Erben, R.G.; Mayer, D.; Weber, K.; Jonsson, K.; Jueppner, H.; Lanske, B.
Overexpression of human PHEX under the human beta-actin promoter does not fully rescue the Hyp mouse phenotype
J. Bone Miner. Res.
20
1149-1160
2005
Homo sapiens, Mus musculus
Lo, F.S.; Kuo, M.T.; Wang, C.J.; Chang, C.H.; Lee, Z.L.; Van, Y.H.
Two novel PHEX mutations in Taiwanese patients with X-linked hypophosphatemic rickets
Nephron. Physiol.
103
p157-p163
2006
Homo sapiens
Roetzer, K.M.; Varga, F.; Zwettler, E.; Nawrot-Wawrzyniak, K.; Haller, J.; Forster, E.; Klaushofer, K.
Novel PHEX mutation associated with hypophosphatemic rickets
Nephron. Physiol.
106
8-12
2007
Homo sapiens (P78562)
Clausmeyer, S.; Hesse, V.; Clemens, P.C.; Engelbach, M.; Kreuzer, M.; Becker-Rose, P.; Spital, H.; Schulze, E.; Raue, F.
Mutational analysis of the PHEX gene: novel point mutations and detection of large deletions by MLPA in patients with X-linked hypophosphatemic rickets
Calcif. Tissue Int.
85
211-220
2009
Homo sapiens (P78562)
Gaucher, C.; Walrant-Debray, O.; Nguyen, T.M.; Esterle, L.; Garabedian, M.; Jehan, F.
PHEX analysis in 118 pedigrees reveals new genetic clues in hypophosphatemic rickets
Hum. Genet.
125
401-411
2009
Homo sapiens (P78562)
Sabbagh, Y.; Jones, A.O.; Tenenhouse, H.S.
PHEXdb, a locus-specific database for mutations causing X-linked hypophosphatemia
Hum. Mutat.
16
1-6
2000
Homo sapiens (P78562)
Barros, N.M.; Nascimento, F.D.; Oliveira, V.; Juliano, M.A.; Juliano, L.; Loisel, T.; Nader, H.B.; Boileau, G.; Tersariol, I.L.; Carmona, A.K.
The critical interaction of the metallopeptidase PHEX with heparan sulfate proteoglycans
Int. J. Biochem. Cell Biol.
40
2781-2792
2008
Homo sapiens
Guo, R.; Quarles, L.D.
Cloning and sequencing of human PEX from a bone cDNA library: evidence for its developmental stage-specific regulation in osteoblasts
J. Bone Miner. Res.
12
1009-1017
1997
Homo sapiens (P78562), Mus musculus (P70669)
Addison, W.N.; Masica, D.L.; Gray, J.J.; McKee, M.D.
Phosphorylation-dependent inhibition of mineralization by osteopontin ASARM peptides is regulated by PHEX cleavage
J. Bone Miner. Res.
25
695-705
2010
Homo sapiens
Chandran, M.; Chng, C.L.; Zhao, Y.; Bee, Y.M.; Phua, L.Y.; Clarke, B.L.
Novel PHEX Gene Mutation Associated with X Linked Hypophosphatemic Rickets
Nephron. Physiol.
116
17-21
2010
Homo sapiens
Rowe, P.S.
The chicken or the egg: PHEX, FGF23 and SIBLINGs unscrambled
Cell Biochem. Funct.
30
355-375
2012
Homo sapiens (P78562)
Rowe, P.S.
Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway
Crit. Rev. Eukaryot. Gene Expr.
22
61-86
2012
Homo sapiens (P78562)
BinEssa, H.; Zou, M.; Al-Enezi, A.; Alomrani, B.; Al-Faham, M.; Al-Rijjal, R.; Meyer, B.; Shi, Y.
Functional analysis of 22 splice-site mutations in the PHEX, the causative gene in X-linked dominant hypophosphatemic rickets
Bone
125
186-193
2019
Homo sapiens (P78562)
Neves, R.L.; Chiarantin, G.M.D.; Nascimento, F.D.; Pesquero, J.B.; Nader, H.B.; Tersariol, I.L.S.; McKee, M.D.; Carmona, A.K.; Barros, N.M.T.
Expression and inactivation of osteopontin-degrading PHEX enzyme in squamous cell carcinoma
Int. J. Biochem. Cell Biol.
77
155-164
2016
Homo sapiens (P78562), Homo sapiens
Ma, S.; Vega-Warner, V.; Gillies, C.; Sampson, M.; Kher, V.; Sethi, S.; Otto, E.
Whole exome sequencing reveals novel PHEX splice site mutations in patients with hypophosphatemic rickets
PLoS ONE
10
e0130729
2015
Homo sapiens (P78562)
Acar, S.; BinEssa, H.; Demir, K.; Al-Rijjal, R.; Zou, M.; Catli, G.; Anik, A.; Al-Enezi, A.; Oezisik, S.; Al-Faham, M.; Abaci, A.; Duendar, B.; Kattan, W.; Alsagob, M.; Kavukcu, S.; Tamimi, H.; Meyer, B.; Boeber, E.; Shi, Y.
Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia Novel mutations in PHEX and SLC34A3
PLoS ONE
13
e0193388
2018
Homo sapiens (P78562)
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