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Reviewed, UniProtKB/Swiss-Prot P50542 (PEX5_HUMAN)

Last modified November 25, 2008. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Peroxisomal targeting signal 1 receptor
      Short name=PTS1 receptor
      Short name=PTS1R
Alternative name(s):
    Peroxisome receptor 1
    Peroxisomal C-terminal targeting signal import receptor
    PTS1-BP
    Peroxin-5
Gene names
Name: PEX5
Synonyms: PXR1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length639 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Binds to the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) and plays an essential role in peroxisomal protein import.

Subunit structure

Interacts with PEX7 and PEX13 By similarity. Interacts with PEX12 and PEX14.

Subcellular location

Cytoplasm. Peroxisome membrane; Peripheral membrane protein. Note= Its distribution appears to be dynamic. It is probably a cycling receptor found mainly in the cytoplasm and as well associated to the peroxisomal membrane through a docking factor (PEX13).

Tissue specificity

Detected in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Involvement in disease

Defects in PEX5 are a cause of neonatal adrenoleukodystrophy (NALD) [MIM:202370]. NALD is a peroxisome biogenesis disorder (PBD) characterized by the accumulation of very long-chain fatty acids, adrenal insufficiency and mental retardation. Inheritance is autosomal recessive.

Defects in PEX5 are a cause of Zellweger syndrome (ZWS) [MIM:214100]. ZWS is a fatal peroxisome biogenesis disorder characterized by dysmorphic facial features, hepatomegaly, ocular abnormalities, renal cysts, hearing impairment, profound psychomotor retardation, severe hypotonia and neonatal seizures. Death occurs within the first year of life.

Defects in PEX5 may be a cause of infantile Refsum disease (IRD) [MIM:266510]. IRD is a mild peroxisome biogenesis disorder (PBD). Clinical features include early onset, mental retardation, minor facial dysmorphism, retinopathy, sensorineural hearing deficit, hepatomegaly, osteoporosis, failure to thrive, and hypocholesterolemia. The biochemical abnormalities include accumulation of phytanic acid, very long chain fatty acids (VLCFA), di- and trihydroxycholestanoic acid and pipecolic acid.

Sequence similarities

Belongs to the peroxisomal targeting signal receptor family.

Contains 7 TPR repeats.

Ontologies

Keywords

   Biological processProtein transport
Transport
   Cellular componentCytoplasm
Membrane
Peroxisome
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Peroxisome biogenesis disorder
Zellweger syndrome
   DomainRepeat
TPR repeat
   Technical term3D-structure

Gene Ontology (GO)

   Biological processprotein transport

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentperoxisomal membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionprotein binding Ref.5

Inferred from physical interaction. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PEX12O006232EBI-597835,EBI-594836

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P50542-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P50542-2)

The sequence of this isoform differs from the canonical sequence as follows:
     215-251: Missing.
Isoform 3 (identifier: P50542-3)

The sequence of this isoform differs from the canonical sequence as follows:
     283-290: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 639639Peroxisomal targeting signal 1 receptor
PRO_0000106305

Regions

Repeat335 – 36834TPR 1
Repeat369 – 40234TPR 2
Repeat403 – 43634TPR 3
Repeat452 – 48534TPR 4
Repeat488 – 52134TPR 5
Repeat522 – 55534TPR 6
Repeat556 – 58934TPR 7

Natural variations

Alternative sequence215 – 25137Missing in isoform 2.
VSP_021880
Alternative sequence283 – 2908Missing in isoform 3.
VSP_024106
Natural variant5261N → K in NALD; strongly affects peroxisomal protein import.
VAR_007543
Natural variant6001S → W in IRD; mildly affects peroxisomal protein import.
VAR_031328

Experimental info

Mutagenesis1181W → A: Strongly reduced interaction with PEX14
Mutagenesis1221F → A: Strongly reduced interaction with PEX14
Sequence conflict4251T → I in AAC50103. Ref.1

Secondary structure

......................................... 639
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 12, 2006. Version 3.
Checksum: 9D6951F58AED31AC

FASTA63970,865
        10         20         30         40         50         60 
MAMRELVEAE CGGANPLMKL AGHFTQDKAL RQEGLRPGPW PPGAPASEAA SKPLGVASED 

        70         80         90        100        110        120 
ELVAEFLQDQ NAPLVSRAPQ TFKMDDLLAE MQQIEQSNFR QAPQRAPGVA DLALSENWAQ 

       130        140        150        160        170        180 
EFLAAGDAVD VTQDYNETDW SQEFISEVTD PLSVSPARWA EEYLEQSEEK LWLGEPEGTA 

       190        200        210        220        230        240 
TDRWYDEYHP EEDLQHTASD FVAKVDDPKL ANSEFLKFVR QIGEGQVSLE SGAGSGRAQA 

       250        260        270        280        290        300 
EQWAAEFIQQ QGTSDAWVDQ FTRPVNTSAL DMEFERAKSA IESDVDFWDK LQAELEEMAK 

       310        320        330        340        350        360 
RDAEAHPWLS DYDDLTSATY DKGYQFEEEN PLRDHPQPFE EGLRRLQEGD LPNAVLLFEA 

       370        380        390        400        410        420 
AVQQDPKHME AWQYLGTTQA ENEQELLAIS ALRRCLELKP DNQTALMALA VSFTNESLQR 

       430        440        450        460        470        480 
QACETLRDWL RYTPAYAHLV TPAEEGAGGA GLGPSKRILG SLLSDSLFLE VKELFLAAVR 

       490        500        510        520        530        540 
LDPTSIDPDV QCGLGVLFNL SGEYDKAVDC FTAALSVRPN DYLLWNKLGA TLANGNQSEE 

       550        560        570        580        590        600 
AVAAYRRALE LQPGYIRSRY NLGISCINLG AHREAVEHFL EALNMQRKSR GPRGEGGAMS 

       610        620        630 
ENIWSTLRLA LSMLGQSDAY GAADARDLST LLTMFGLPQ 

« Hide

Isoform 2 [UniParc].

Checksum: EA4E6FAAF5E11C55
Show »

60266,830
Isoform 3 [UniParc].

Checksum: 9F3B705D888C484B
Show »

63169,872

References

« Hide 'large scale' references
[1]"Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disorders."
Dodt G., Braverman N., Wong C., Moser A., Moser H.W., Watkins P., Valle D., Gould S.J.
Nat. Genet. 9:115-125(1995) [PubMed: 7719337] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INVOLVEMENT IN ZWS, VARIANT NALD LYS-526, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]"Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders."
Wiemer E.A.C., Nuttley W.M., Bertolaet B.L., Li X., Francke U., Wheelock M.J., Anne U.K., Johnson K.R., Subramani S.
J. Cell Biol. 130:51-65(1995) [PubMed: 7790377] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY.
Tissue: Liver.
[3]"Identification and characterization of the putative human peroxisomal C-terminal targeting signal import receptor."
Fransen M., Brees C., Baumgart E., Vanhooren J.C.T., Baes M., Mannaerts G.P., van Veldhoven P.P.
J. Biol. Chem. 270:7731-7736(1995) [PubMed: 7706321] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
Tissue: Liver.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Eye.
[5]"PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor docking in peroxisomal matrix protein import."
Chang C.C., Warren D.S., Sacksteder K.A., Gould S.J.
J. Cell Biol. 147:761-774(1999) [PubMed: 10562279] [Abstract]
Cited for: INTERACTION WITH PEX12.
[6]"The di-aromatic pentapeptide repeats of the human peroxisome import receptor PEX5 are separate high affinity binding sites for the peroxisomal membrane protein PEX14."
Saidowsky J., Dodt G., Kirchberg K., Wegner A., Nastainczyk W., Kunau W.-H., Schliebs W.
J. Biol. Chem. 276:34524-34529(2001) [PubMed: 11438541] [Abstract]
Cited for: INTERACTION WITH PEX14, MUTAGENESIS OF TRP-118 AND PHE-122.
[7]"Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5."
Gatto G.J. Jr., Geisbrecht B.V., Gould S.J., Berg J.M.
Nat. Struct. Biol. 7:1091-1095(2000) [PubMed: 11101887] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 272-639 IN COMPLEX WITH TARGETING PEPTIDE.
[8]"Recognition of a functional peroxisome type 1 target by the dynamic import receptor pex5p."
Stanley W.A., Filipp F.V., Kursula P., Schuller N., Erdmann R., Schliebs W., Sattler M., Wilmanns M.
Mol. Cell 24:653-663(2006) [PubMed: 17157249] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 321-639 IN COMPLEX WITH TARGETING PEPTIDE.
[9]"Functional heterogeneity of C-terminal peroxisome targeting signal 1 in PEX5-defective patients."
Shimozawa N., Zhang Z., Suzuki Y., Imamura A., Tsukamoto T., Osumi T., Fujiki Y., Orii T., Barth P.G., Wanders R.J., Kondo N.
Biochem. Biophys. Res. Commun. 262:504-508(1999) [PubMed: 10462504] [Abstract]
Cited for: VARIANT NALD LYS-526, VARIANT IRD TRP-600, CHARACTERIZATION OF VARIANT NALD LYS-526, CHARACTERIZATION OF VARIANT IRD TRP-600.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

U19721 mRNA. Translation: AAC50103.1.
Z48054 mRNA. Translation: CAA88131.1.
X84899 mRNA. Translation: CAA59324.1.
BC010621 mRNA. Translation: AAH10621.1.
PIRA56126.
RefSeqNP_001124497.1.
NP_001124498.1.
UniGeneHs.567327

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1FCHX-ray2.20A/B272-639[»]
2C0LX-ray2.30A335-639[»]
2C0MX-ray2.50A/B/C/F321-639[»]
2J9QX-ray2.65A/B315-639[»]
ModBaseSearch...

Protein-protein interaction databases

IntActP50542.

PTM databases

PhosphoSiteP50542.

Genome annotation databases

EnsemblENSG00000139197. Homo sapiens. [Contig view]
GeneID5830.
KEGGhsa:5830.

Organism-specific databases

H-InvDBHIX0010397.
HGNCHGNC:9719. PEX5.
MIM202370. phenotype.
214100. phenotype.
266510. phenotype.
600414. gene.
Orphanet44. Adrenoleukodystrophy, neonatal.
772. Refsum disease, infantile form.
912. Zellweger syndrome.
PharmGKBPA34063.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOVERGENP50542.

Gene expression databases

ArrayExpressP50542.
CleanExHS_PEX5.
GermOnlineENSG00000139197. Homo sapiens.

Family and domain databases

InterProIPR001440. TPR-1.
IPR013026. TPR_region.
[Graphical view]
PfamPF00515. TPR_1. 4 hits.
[Graphical view]
SMARTSM00028. TPR. 4 hits.
[Graphical view]
PROSITEPS50005. TPR. 5 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

LinkHubP50542.
NextBio22716.
SOURCESearch...

Entry information

Entry namePEX5_HUMAN
AccessionPrimary (citable) accession number: P50542
Secondary accession number(s): Q15115, Q15266, Q96FN7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: December 12, 2006
Last modified: November 25, 2008
This is version 91 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents