Reviewed, UniProtKB/Swiss-Prot P50542 (PEX5_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	639 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 process	Protein transport Transport
Cellular component	Cytoplasm Membrane Peroxisome
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Peroxisome biogenesis disorder Zellweger syndrome
Domain	Repeat TPR repeat
Technical term	3D-structure
Gene Ontology (GO)
Biological process	protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	peroxisomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Ref.5 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PEX12	O00623	2	EBI-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 639

639

Peroxisomal targeting signal 1 receptor

PRO_0000106305

Regions

Repeat

335 – 368

34

TPR 1

Repeat

369 – 402

34

TPR 2

Repeat

403 – 436

34

TPR 3

Repeat

452 – 485

34

TPR 4

Repeat

488 – 521

34

TPR 5

Repeat

522 – 555

34

TPR 6

Repeat

556 – 589

34

TPR 7

Natural variations

Alternative sequence

215 – 251

37

Missing in isoform 2.

VSP_021880

Alternative sequence

283 – 290

8

Missing in isoform 3.

VSP_024106

Natural variant

526

1

N → K in NALD; strongly affects peroxisomal protein import.

VAR_007543

Natural variant

600

1

S → W in IRD; mildly affects peroxisomal protein import.

VAR_031328

Experimental info

Mutagenesis

118

1

W → A: Strongly reduced interaction with PEX14

Mutagenesis

122

1

F → A: Strongly reduced interaction with PEX14

Sequence conflict

425

1

T → I in AAC50103. Ref.1

Secondary structure

1

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639

Helix Strand Turn

Details...

Helix

318 – 321

4

Turn

331 – 334

4

Helix

338 – 347

10

Helix

351 – 363

13

Helix

369 – 381

13

Helix

385 – 398

14

Helix

403 – 415

13

Helix

419 – 431

13

Turn

434 – 436

3

Helix

437 – 439

3

Helix

460 – 481

22

Helix

488 – 500

13

Helix

504 – 517

14

Helix

522 – 534

13

Helix

538 – 551

14

Helix

556 – 569

14

Helix

572 – 587

16

Helix

601 – 614

14

Helix

617 – 619

3

Helix

620 – 624

5

Helix

628 – 634

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 12, 2006. Version 3. Checksum: 9D6951F58AED31AC	FASTA	639	70,865
	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
	Isoform 2 [UniParc]. Checksum: EA4E6FAAF5E11C55		602	66,830
	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 ANSEGTSDAW VDQFTRPVNT SALDMEFERA 250 260 270 280 290 300 KSAIESDVDF WDKLQAELEE MAKRDAEAHP WLSDYDDLTS ATYDKGYQFE EENPLRDHPQ 310 320 330 340 350 360 PFEEGLRRLQ EGDLPNAVLL FEAAVQQDPK HMEAWQYLGT TQAENEQELL AISALRRCLE 370 380 390 400 410 420 LKPDNQTALM ALAVSFTNES LQRQACETLR DWLRYTPAYA HLVTPAEEGA GGAGLGPSKR 430 440 450 460 470 480 ILGSLLSDSL FLEVKELFLA AVRLDPTSID PDVQCGLGVL FNLSGEYDKA VDCFTAALSV 490 500 510 520 530 540 RPNDYLLWNK LGATLANGNQ SEEAVAAYRR ALELQPGYIR SRYNLGISCI NLGAHREAVE 550 560 570 580 590 600 HFLEALNMQR KSRGPRGEGG AMSENIWSTL RLALSMLGQS DAYGAADARD LSTLLTMFGL PQ
	Isoform 3 [UniParc]. Checksum: 9F3B705D888C484B		631	69,872
	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 IELQAELEEM AKRDAEAHPW 310 320 330 340 350 360 LSDYDDLTSA TYDKGYQFEE ENPLRDHPQP FEEGLRRLQE GDLPNAVLLF EAAVQQDPKH 370 380 390 400 410 420 MEAWQYLGTT QAENEQELLA ISALRRCLEL KPDNQTALMA LAVSFTNESL QRQACETLRD 430 440 450 460 470 480 WLRYTPAYAH LVTPAEEGAG GAGLGPSKRI LGSLLSDSLF LEVKELFLAA VRLDPTSIDP 490 500 510 520 530 540 DVQCGLGVLF NLSGEYDKAV DCFTAALSVR PNDYLLWNKL GATLANGNQS EEAVAAYRRA 550 560 570 580 590 600 LELQPGYIRS RYNLGISCIN LGAHREAVEH FLEALNMQRK SRGPRGEGGA MSENIWSTLR 610 620 630 LALSMLGQSD AYGAADARDL STLLTMFGLP Q

References

	« Hide 'large scale' referencesShow '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

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

U19721 mRNA. Translation: AAC50103.1.
Z48054 mRNA. Translation: CAA88131.1.
X84899 mRNA. Translation: CAA59324.1.
BC010621 mRNA. Translation: AAH10621.1.

PIR

A56126.

RefSeq

NP_001124497.1.
NP_001124498.1.

UniGene

Hs.567327

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FCH	X-ray	2.20	A/B	272-639	[»]
2C0L	X-ray	2.30	A	335-639	[»]
2C0M	X-ray	2.50	A/B/C/F	321-639	[»]
2J9Q	X-ray	2.65	A/B	315-639	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P50542.

PTM databases

PhosphoSite

P50542.

Genome annotation databases

Ensembl

ENSG00000139197. Homo sapiens. [Contig view]

GeneID

5830.

KEGG

hsa:5830.

Organism-specific databases

H-InvDB

HIX0010397.

HGNC

HGNC:9719. PEX5.

MIM

202370. phenotype.
214100. phenotype.
266510. phenotype.
600414. gene.

Orphanet

44. Adrenoleukodystrophy, neonatal.
772. Refsum disease, infantile form.
912. Zellweger syndrome.

PharmGKB

PA34063.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

P50542.

Gene expression databases

ArrayExpress

P50542.

CleanEx

HS_PEX5.

GermOnline

ENSG00000139197. Homo sapiens.

Family and domain databases

InterPro

IPR001440. TPR-1.
IPR013026. TPR_region.
[Graphical view]

Pfam

PF00515. TPR_1. 4 hits.
[Graphical view]

SMART

SM00028. TPR. 4 hits.
[Graphical view]

PROSITE

PS50005. TPR. 5 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

LinkHub

P50542.

NextBio

22716.

SOURCE

Search...

Entry information

Entry name

PEX5_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)