Protein: Phosphate-regulating neutral endopeptidase PHEX (EC 3.4.24.-) (Metalloendopeptidase homolog PEX) (Vitamin D-resistant hypophosphatemic rickets protein) (X-linked hypophosphatemia protein) (HYP) (P78562)
Organism: Homo sapiens (Human)
Function: Peptidase that cleaves SIBLING (small integrin-binding ligand, N-linked glycoprotein)-derived ASARM peptides, thus regulating their biological activity. Cleaves ASARM peptides between Ser and Glu or Asp residues. Regulates osteogenic cell differentiation and bone mineralization through the cleavage of the MEPE-derived ASARM peptide. Promotes dentin mineralization and renal phosphate reabsorption by cleaving DMP1- and MEPE-derived ASARM peptides. Inhibits the cleavage of MEPE by CTSB/cathepsin B thus preventing MEPE degradation.
Subcellular location: Cell membrane {ECO:0000269|PubMed:9593714}; Single-pass type II membrane protein {ECO:0000269|PubMed:9593714}.
Sequence: MEAETGSSVETGKKANRGTRIALVVFVGGTLVLGTILFLVSQGLLSLQAKQEYCLKPECIEAAAAILSKVNLSVDPCDNFFRFACDGWISNNPIPEDMPSYGVYPWLRHNVDLKLKELLEKSISRRRDTEAIQKAKILYSSCMNEKAIEKADAKPLLHILRHSPFRWPVLESNIGPEGVWSERKFSLLQTLATFRGQYSNSVFIRLYVSPDDKASNEHILKLDQATLSLAVREDYLDNSTEAKSYRDALYKFMVDTAVLLGANSSRAEHDMKSVLRLEIKIAEIMIPHENRTSEAMYNKMNISELSAMIPQFDWLGYIKKVIDTRLYPHLKDISPSENVVVRVPQYFKDLFRILGSERKKTIANYLVWRMVYSRIPNLSRRFQYRWLEFSRVIQGTTTLLPQWDKCVNFIESALPYVVGKMFVDVYFQEDKKEMMEELVEGVRWAFIDMLEKENEWMDAGTKRKAKEKARAVLAKVGYPEFIMNDTHVNEDLKAIKFSEADYFGNVLQTRKYLAQSDFFWLRKAVPKTEWFTNPTTVNAFYSASTNQIRFPAGELQKPFFWGTEYPRSLSYGAIGVIVGHEFTHGFDNNGRKYDKNGNLDPWWSTESEEKFKEKTKCMINQYSNYYWKKAGLNVKGKRTLGENIADNGGLREAFRAYRKWINDRRQGLEEPLLPGITFTNNQLFFLSYAHVRCNSYRPEAAREQVQIGAHSPPQFRVNGAISNFEEFQKAFNCPPNSTMNRGMDSCRLW
InterPro domains: - IPR000718: Peptidase M13 (family) [36-749]
- IPR018497: Peptidase M13, C-terminal domain (domain) [530-741]
- IPR008753: Peptidase M13, N-terminal domain (domain) [76-479]
- IPR042089: Peptidase M13, domain 2 (homologous_superfamily) [102-525]
- IPR024079: Metallopeptidase, catalytic domain superfamily (homologous_superfamily) [54-749]
Interaction partners: - Fibroblast growth factor 23
- Matrix extracellular phosphoglycoprotein
- Sodium-dependent phosphate transport protein 2C
- Sodium-dependent phosphate transport protein 2A
- Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
- Klotho
- Dentin matrix acidic phosphoprotein 1
- Parathyroid hormone
- Polypeptide N-acetylgalactosaminyltransferase 3
- Spermine synthase
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0072341 (modified amino acid binding), GO:0016787 (hydrolase activity), GO:0008289 (lipid binding), GO:0043167 (ion binding), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0008233 (peptidase activity), GO:0005543 (phospholipid binding), GO:0046983 (protein dimerization activity), GO:0043168 (anion binding), GO:0042802 (identical protein binding), GO:0043169 (cation binding), GO:0001786 (phosphatidylserine binding), GO:0046872 (metal ion binding), GO:0008237 (metallopeptidase activity), GO:1901611 (phosphatidylglycerol binding), GO:0042803 (protein homodimerization activity), GO:0004175 (endopeptidase activity), GO:0008238 (exopeptidase activity), GO:0004222 (metalloendopeptidase activity), GO:0046914 (transition metal ion binding), GO:1901612 (cardiolipin binding), GO:0008270 (zinc ion binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0009628 (response to abiotic stimulus), GO:0048856 (anatomical structure development), GO:0023056 (positive regulation of signaling), GO:0007275 (multicellular organism development), GO:0042221 (response to chemical), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0051240 (positive regulation of multicellular organismal process), GO:0006807 (nitrogen compound metabolic process), GO:0097242 (amyloid-beta clearance), GO:0042445 (hormone metabolic process), GO:0051239 (regulation of multicellular organismal process), GO:0071704 (organic substance metabolic process), GO:0009056 (catabolic process), GO:0003008 (system process), GO:0065008 (regulation of biological quality), GO:0044237 (cellular metabolic process), GO:0048522 (positive regulation of cellular process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0023051 (regulation of signaling), GO:0006950 (response to stress), GO:0044238 (primary metabolic process), GO:0009967 (positive regulation of signal transduction), GO:0001666 (response to hypoxia), GO:1901564 (organonitrogen compound metabolic process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0044248 (cellular catabolic process), GO:0048731 (system development), GO:0070482 (response to oxygen levels), GO:0044057 (regulation of system process), GO:0019538 (protein metabolic process), GO:0048513 (animal organ development), GO:0009966 (regulation of signal transduction), GO:0060255 (regulation of macromolecule metabolic process), GO:0008217 (regulation of blood pressure), GO:0042447 (hormone catabolic process), GO:0043170 (macromolecule metabolic process), GO:0003013 (circulatory system process), GO:0001921 (positive regulation of receptor recycling), GO:0010035 (response to inorganic substance), GO:0010646 (regulation of cell communication), GO:0031325 (positive regulation of cellular metabolic process), GO:0001919 (regulation of receptor recycling), GO:0010647 (positive regulation of cell communication), GO:0031323 (regulation of cellular metabolic process), GO:0043603 (amide metabolic process), GO:1901575 (organic substance catabolic process), GO:0090066 (regulation of anatomical structure size), GO:0010038 (response to metal ion), GO:0003018 (vascular process in circulatory system), GO:1901565 (organonitrogen compound catabolic process), GO:0006518 (peptide metabolic process), GO:0006508 (proteolysis), GO:0008015 (blood circulation), GO:0030163 (protein catabolic process), GO:0051604 (protein maturation), GO:0010613 (positive regulation of cardiac muscle hypertrophy), GO:1903522 (regulation of blood circulation), GO:0035150 (regulation of tube size), GO:0043171 (peptide catabolic process), GO:0003073 (regulation of systemic arterial blood pressure), GO:0036293 (response to decreased oxygen levels), GO:0019229 (regulation of vasoconstriction), GO:0097746 (blood vessel diameter maintenance), GO:0035296 (regulation of tube diameter), GO:0046686 (response to cadmium ion), GO:1901222 (regulation of NIK/NF-kappaB signaling), GO:0010467 (gene expression), GO:0016485 (protein processing), GO:0140448 (signaling receptor ligand precursor processing)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0031090 (organelle membrane), GO:0005794 (Golgi apparatus), GO:0005783 (endoplasmic reticulum), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0098588 (bounding membrane of organelle), GO:0000139 (Golgi membrane)