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Protein

Phosphate-regulating neutral endopeptidase

Gene

PHEX

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Probably involved in bone and dentin mineralization and renal phosphate reabsorption.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi580Zinc; catalyticPROSITE-ProRule annotation1
Active sitei581PROSITE-ProRule annotation1
Metal bindingi584Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi642Zinc; catalyticPROSITE-ProRule annotation1
Active sitei646Proton donorPROSITE-ProRule annotation1

GO - Molecular functioni

  • aminopeptidase activity Source: UniProtKB-KW
  • metalloendopeptidase activity Source: ProtInc
  • zinc ion binding Source: ProtInc

GO - Biological processi

  • bone mineralization Source: Ensembl
  • cell-cell signaling Source: ProtInc
  • cellular protein modification process Source: ProtInc
  • organophosphate metabolic process Source: Ensembl
  • proteolysis Source: UniProtKB
  • skeletal system development Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Aminopeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Biomineralization

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000102174-MONOMER.
BRENDAi3.4.24.B15. 2681.

Protein family/group databases

MEROPSiM13.091.

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphate-regulating neutral endopeptidase (EC:3.4.24.-)
Alternative name(s):
Metalloendopeptidase homolog PEX
Vitamin D-resistant hypophosphatemic rickets protein
X-linked hypophosphatemia protein
Short name:
HYP
Gene namesi
Name:PHEX
Synonyms:PEX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:8918. PHEX.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 20CytoplasmicSequence analysisAdd BLAST20
Transmembranei21 – 41Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini42 – 641ExtracellularSequence analysisAdd BLAST600

GO - Cellular componenti

  • endoplasmic reticulum Source: Ensembl
  • Golgi apparatus Source: Ensembl
  • integral component of plasma membrane Source: ProtInc
  • perinuclear region of cytoplasm Source: Ensembl
  • plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Hypophosphatemic rickets, X-linked dominant (XLHR)8 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by impaired phosphate uptake in the kidney, which is likely to be caused by abnormal regulation of sodium phosphate cotransport in the proximal tubules. Clinical manifestations include skeletal deformities, growth failure, craniosynostosis, paravertebral calcifications, pseudofractures in lower extremities, and muscular hypotonia with onset in early childhood. X-linked hypophosphatemic rickets is the most common form of hypophosphatemia with an incidence of 1 in 20000.
See also OMIM:307800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00673877C → S in XLHR. 1 Publication1
Natural variantiVAR_01061680F → S in XLHR; sporadic. 1 Publication1
Natural variantiVAR_01061785C → F in XLHR; sporadic. 1 Publication1
Natural variantiVAR_01061885C → R in XLHR. 1 Publication1
Natural variantiVAR_00673985C → Y in XLHR. 1 PublicationCorresponds to variant rs137853269dbSNPEnsembl.1
Natural variantiVAR_006740138L → P in XLHR. 1 Publication1
Natural variantiVAR_010619141S → P in XLHR; sporadic. 1 Publication1
Natural variantiVAR_010620142C → F in XLHR. 1 Publication1
Natural variantiVAR_010621160L → R in XLHR. 1 Publication1
Natural variantiVAR_006741166R → C in XLHR. 1 PublicationCorresponds to variant rs751230094dbSNPEnsembl.1
Natural variantiVAR_010622237D → G in XLHR; sporadic. 1 Publication1
Natural variantiVAR_006742252F → S in XLHR. 1 PublicationCorresponds to variant rs267606945dbSNPEnsembl.1
Natural variantiVAR_006743253M → I in XLHR. 1 PublicationCorresponds to variant rs267606946dbSNPEnsembl.1
Natural variantiVAR_010623317Y → F in XLHR. 1 Publication1
Natural variantiVAR_010624341Missing in XLHR; sporadic. 1 Publication1
Natural variantiVAR_010625444W → WN in XLHR. 1 Publication1
Natural variantiVAR_010626530W → C in XLHR. 1 Publication1
Natural variantiVAR_006744534P → L in XLHR. 3 Publications1
Natural variantiVAR_010627555L → P in XLHR. 1 PublicationCorresponds to variant rs137853270dbSNPEnsembl.1
Natural variantiVAR_010628567R → P in XLHR; sporadic. 1 Publication1
Natural variantiVAR_010629573A → D in XLHR; sporadic. 1 Publication1
Natural variantiVAR_006745579G → R in XLHR. 3 Publications1
Natural variantiVAR_006746579G → V in XLHR. 1 Publication1
Natural variantiVAR_010630621Q → R in XLHR. 1 Publication1
Natural variantiVAR_010631651R → P in XLHR. 1 Publication1
Natural variantiVAR_010633680N → K in XLHR; sporadic. 1 Publication1
Natural variantiVAR_010632680Missing in XLHR. 1 Publication1
Natural variantiVAR_010634693C → Y in XLHR; sporadic. 1 Publication1
Natural variantiVAR_010635720A → T in XLHR. 1 Publication1
Natural variantiVAR_010636731F → Y in XLHR. 1 Publication1
Natural variantiVAR_010637733C → S in XLHR; sporadic. 1 Publication1
Natural variantiVAR_010638746C → W in XLHR; sporadic. 1 Publication1
Natural variantiVAR_010639749W → R in XLHR. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5251.
MalaCardsiPHEX.
MIMi307800. phenotype.
OpenTargetsiENSG00000102174.
Orphaneti89936. X-linked hypophosphatemia.
PharmGKBiPA33258.

Polymorphism and mutation databases

DMDMi2499917.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000782281 – 749Phosphate-regulating neutral endopeptidaseAdd BLAST749

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi71N-linked (GlcNAc...)Sequence analysis1
Glycosylationi238N-linked (GlcNAc...)Sequence analysis1
Glycosylationi263N-linked (GlcNAc...)Sequence analysis1
Glycosylationi290N-linked (GlcNAc...)Sequence analysis1
Glycosylationi301N-linked (GlcNAc...)Sequence analysis1
Glycosylationi377N-linked (GlcNAc...)Sequence analysis1
Glycosylationi484N-linked (GlcNAc...)Sequence analysis1
Glycosylationi736N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiP78562.
PaxDbiP78562.
PeptideAtlasiP78562.
PRIDEiP78562.

PTM databases

iPTMnetiP78562.
PhosphoSitePlusiP78562.

Expressioni

Tissue specificityi

Lymphocytes and fetal brain; not in adult brain, placenta, skeletal muscle and pancreas; not in adult and fetal heart, lung, liver and kidney.

Gene expression databases

BgeeiENSG00000102174.
CleanExiHS_PHEX.
GenevisibleiP78562. HS.

Organism-specific databases

HPAiHPA029582.

Interactioni

Protein-protein interaction databases

BioGridi111270. 2 interactors.
IntActiP78562. 1 interactor.
STRINGi9606.ENSP00000368682.

Structurei

3D structure databases

ProteinModelPortaliP78562.
SMRiP78562.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase M13 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3624. Eukaryota.
COG3590. LUCA.
GeneTreeiENSGT00760000119162.
HOGENOMiHOG000245574.
HOVERGENiHBG005554.
InParanoidiP78562.
KOiK08636.
OMAiANYLVWR.
OrthoDBiEOG091G025Y.
PhylomeDBiP78562.
TreeFamiTF315192.

Family and domain databases

CDDicd08662. M13. 1 hit.
Gene3Di3.40.390.10. 2 hits.
InterProiIPR024079. MetalloPept_cat_dom.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
[Graphical view]
PANTHERiPTHR11733. PTHR11733. 1 hit.
PfamiPF01431. Peptidase_M13. 1 hit.
PF05649. Peptidase_M13_N. 1 hit.
[Graphical view]
PRINTSiPR00786. NEPRILYSIN.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P78562-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEAETGSSVE TGKKANRGTR IALVVFVGGT LVLGTILFLV SQGLLSLQAK
60 70 80 90 100
QEYCLKPECI EAAAAILSKV NLSVDPCDNF FRFACDGWIS NNPIPEDMPS
110 120 130 140 150
YGVYPWLRHN VDLKLKELLE KSISRRRDTE AIQKAKILYS SCMNEKAIEK
160 170 180 190 200
ADAKPLLHIL RHSPFRWPVL ESNIGPEGVW SERKFSLLQT LATFRGQYSN
210 220 230 240 250
SVFIRLYVSP DDKASNEHIL KLDQATLSLA VREDYLDNST EAKSYRDALY
260 270 280 290 300
KFMVDTAVLL GANSSRAEHD MKSVLRLEIK IAEIMIPHEN RTSEAMYNKM
310 320 330 340 350
NISELSAMIP QFDWLGYIKK VIDTRLYPHL KDISPSENVV VRVPQYFKDL
360 370 380 390 400
FRILGSERKK TIANYLVWRM VYSRIPNLSR RFQYRWLEFS RVIQGTTTLL
410 420 430 440 450
PQWDKCVNFI ESALPYVVGK MFVDVYFQED KKEMMEELVE GVRWAFIDML
460 470 480 490 500
EKENEWMDAG TKRKAKEKAR AVLAKVGYPE FIMNDTHVNE DLKAIKFSEA
510 520 530 540 550
DYFGNVLQTR KYLAQSDFFW LRKAVPKTEW FTNPTTVNAF YSASTNQIRF
560 570 580 590 600
PAGELQKPFF WGTEYPRSLS YGAIGVIVGH EFTHGFDNNG RKYDKNGNLD
610 620 630 640 650
PWWSTESEEK FKEKTKCMIN QYSNYYWKKA GLNVKGKRTL GENIADNGGL
660 670 680 690 700
REAFRAYRKW INDRRQGLEE PLLPGITFTN NQLFFLSYAH VRCNSYRPEA
710 720 730 740
AREQVQIGAH SPPQFRVNGA ISNFEEFQKA FNCPPNSTMN RGMDSCRLW
Length:749
Mass (Da):86,474
Last modified:May 1, 1997 - v1
Checksum:i7C4F9F3E2471C6A8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti363A → D in AAC50552 (PubMed:7550339).Curated1
Sequence conflicti403W → R in AAC50552 (PubMed:7550339).Curated1
Sequence conflicti641G → A in AAC50552 (PubMed:7550339).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00673877C → S in XLHR. 1 Publication1
Natural variantiVAR_01061680F → S in XLHR; sporadic. 1 Publication1
Natural variantiVAR_01061785C → F in XLHR; sporadic. 1 Publication1
Natural variantiVAR_01061885C → R in XLHR. 1 Publication1
Natural variantiVAR_00673985C → Y in XLHR. 1 PublicationCorresponds to variant rs137853269dbSNPEnsembl.1
Natural variantiVAR_006740138L → P in XLHR. 1 Publication1
Natural variantiVAR_010619141S → P in XLHR; sporadic. 1 Publication1
Natural variantiVAR_010620142C → F in XLHR. 1 Publication1
Natural variantiVAR_010621160L → R in XLHR. 1 Publication1
Natural variantiVAR_006741166R → C in XLHR. 1 PublicationCorresponds to variant rs751230094dbSNPEnsembl.1
Natural variantiVAR_010622237D → G in XLHR; sporadic. 1 Publication1
Natural variantiVAR_006742252F → S in XLHR. 1 PublicationCorresponds to variant rs267606945dbSNPEnsembl.1
Natural variantiVAR_006743253M → I in XLHR. 1 PublicationCorresponds to variant rs267606946dbSNPEnsembl.1
Natural variantiVAR_010623317Y → F in XLHR. 1 Publication1
Natural variantiVAR_010624341Missing in XLHR; sporadic. 1 Publication1
Natural variantiVAR_010625444W → WN in XLHR. 1 Publication1
Natural variantiVAR_010626530W → C in XLHR. 1 Publication1
Natural variantiVAR_006744534P → L in XLHR. 3 Publications1
Natural variantiVAR_010627555L → P in XLHR. 1 PublicationCorresponds to variant rs137853270dbSNPEnsembl.1
Natural variantiVAR_010628567R → P in XLHR; sporadic. 1 Publication1
Natural variantiVAR_010629573A → D in XLHR; sporadic. 1 Publication1
Natural variantiVAR_006745579G → R in XLHR. 3 Publications1
Natural variantiVAR_006746579G → V in XLHR. 1 Publication1
Natural variantiVAR_010630621Q → R in XLHR. 1 Publication1
Natural variantiVAR_010631651R → P in XLHR. 1 Publication1
Natural variantiVAR_010633680N → K in XLHR; sporadic. 1 Publication1
Natural variantiVAR_010632680Missing in XLHR. 1 Publication1
Natural variantiVAR_010634693C → Y in XLHR; sporadic. 1 Publication1
Natural variantiVAR_010635720A → T in XLHR. 1 Publication1
Natural variantiVAR_010636731F → Y in XLHR. 1 Publication1
Natural variantiVAR_010637733C → S in XLHR; sporadic. 1 Publication1
Natural variantiVAR_010638746C → W in XLHR; sporadic. 1 Publication1
Natural variantiVAR_010639749W → R in XLHR. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y08111
, Y08112, Y08113, Y08114, Y08115, Y08116, Y08117, Y08118, Y08119, Y08120, Y08121, Y08122, Y08123, Y08124, Y08125, Y08126, Y08127, Y08128, Y08129, Y08130, Y08131, Y08132 Genomic DNA. Translation: CAA69326.1.
U75645 mRNA. Translation: AAB47749.1.
U87284 mRNA. Translation: AAB47562.1.
AD000712 mRNA. Translation: AAB51604.1.
AH004966 Genomic DNA. Translation: AAB42219.1.
U82970 mRNA. Translation: AAC24487.1.
U73024 Genomic DNA. Translation: AAD08630.1.
Y10196 Genomic DNA. Translation: CAA71258.1.
BC105057 mRNA. Translation: AAI05058.1.
BC105059 mRNA. Translation: AAI05060.1.
U60475 mRNA. Translation: AAC50552.1.
CCDSiCCDS14204.1.
RefSeqiNP_000435.3. NM_000444.5.
NP_001269683.1. NM_001282754.1.
UniGeneiHs.495834.

Genome annotation databases

EnsembliENST00000379374; ENSP00000368682; ENSG00000102174.
GeneIDi5251.
KEGGihsa:5251.
UCSCiuc004dah.5. human.

Cross-referencesi

Web resourcesi

PHEXdb

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y08111
, Y08112, Y08113, Y08114, Y08115, Y08116, Y08117, Y08118, Y08119, Y08120, Y08121, Y08122, Y08123, Y08124, Y08125, Y08126, Y08127, Y08128, Y08129, Y08130, Y08131, Y08132 Genomic DNA. Translation: CAA69326.1.
U75645 mRNA. Translation: AAB47749.1.
U87284 mRNA. Translation: AAB47562.1.
AD000712 mRNA. Translation: AAB51604.1.
AH004966 Genomic DNA. Translation: AAB42219.1.
U82970 mRNA. Translation: AAC24487.1.
U73024 Genomic DNA. Translation: AAD08630.1.
Y10196 Genomic DNA. Translation: CAA71258.1.
BC105057 mRNA. Translation: AAI05058.1.
BC105059 mRNA. Translation: AAI05060.1.
U60475 mRNA. Translation: AAC50552.1.
CCDSiCCDS14204.1.
RefSeqiNP_000435.3. NM_000444.5.
NP_001269683.1. NM_001282754.1.
UniGeneiHs.495834.

3D structure databases

ProteinModelPortaliP78562.
SMRiP78562.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111270. 2 interactors.
IntActiP78562. 1 interactor.
STRINGi9606.ENSP00000368682.

Protein family/group databases

MEROPSiM13.091.

PTM databases

iPTMnetiP78562.
PhosphoSitePlusiP78562.

Polymorphism and mutation databases

DMDMi2499917.

Proteomic databases

EPDiP78562.
PaxDbiP78562.
PeptideAtlasiP78562.
PRIDEiP78562.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000379374; ENSP00000368682; ENSG00000102174.
GeneIDi5251.
KEGGihsa:5251.
UCSCiuc004dah.5. human.

Organism-specific databases

CTDi5251.
DisGeNETi5251.
GeneCardsiPHEX.
GeneReviewsiPHEX.
HGNCiHGNC:8918. PHEX.
HPAiHPA029582.
MalaCardsiPHEX.
MIMi300550. gene.
307800. phenotype.
neXtProtiNX_P78562.
OpenTargetsiENSG00000102174.
Orphaneti89936. X-linked hypophosphatemia.
PharmGKBiPA33258.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3624. Eukaryota.
COG3590. LUCA.
GeneTreeiENSGT00760000119162.
HOGENOMiHOG000245574.
HOVERGENiHBG005554.
InParanoidiP78562.
KOiK08636.
OMAiANYLVWR.
OrthoDBiEOG091G025Y.
PhylomeDBiP78562.
TreeFamiTF315192.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000102174-MONOMER.
BRENDAi3.4.24.B15. 2681.

Miscellaneous databases

ChiTaRSiPHEX. human.
GeneWikiiPHEX.
GenomeRNAii5251.
PROiP78562.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102174.
CleanExiHS_PHEX.
GenevisibleiP78562. HS.

Family and domain databases

CDDicd08662. M13. 1 hit.
Gene3Di3.40.390.10. 2 hits.
InterProiIPR024079. MetalloPept_cat_dom.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
[Graphical view]
PANTHERiPTHR11733. PTHR11733. 1 hit.
PfamiPF01431. Peptidase_M13. 1 hit.
PF05649. Peptidase_M13_N. 1 hit.
[Graphical view]
PRINTSiPR00786. NEPRILYSIN.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPHEX_HUMAN
AccessioniPrimary (citable) accession number: P78562
Secondary accession number(s): O00678
, Q13646, Q2M325, Q93032, Q99827
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 1, 1997
Last modified: November 2, 2016
This is version 163 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.