P56589 (PEX3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Peroxisomal biogenesis factor 3

Alternative name(s):
Peroxin-3
Peroxisomal assembly protein PEX3

Gene names

Name:

PEX3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	373 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in peroxisome biosynthesis and integrity. Assembles membrane vesicles before the matrix proteins are translocated. As a docking factor for PEX19, is necessary for the import of peroxisomal membrane proteins in the peroxisomes. Ref.4 Ref.12
Subunit structure	Interacts with PEX19. Ref.10 Ref.11 Ref.15 Ref.16
Subcellular location	Peroxisome membrane; Multi-pass membrane protein Ref.11.
Tissue specificity	Found in all examined tissues.
Involvement in disease	Peroxisome biogenesis disorder complementation group 12 (PBD-CG12) [MIM:614882]: A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS). Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Peroxisome biogenesis disorder 10A (PBD10A) [MIM:614882]: A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and clinically characterized by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.13
Sequence similarities	Belongs to the peroxin-3 family.

Ontologies

Keywords
Biological process	Peroxisome biogenesis
Cellular component	Membrane Peroxisome
Coding sequence diversity	Polymorphism
Disease	Disease mutation Peroxisome biogenesis disorder Zellweger syndrome
Domain	Transmembrane Transmembrane helix
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	peroxisome membrane biogenesis Inferred from electronic annotation. Source: Compara protein import into peroxisome membrane Inferred from mutant phenotype Ref.12. Source: UniProtKB
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara endoplasmic reticulum Inferred from direct assay PubMed 19479899PubMed 21768384. Source: UniProtKB integral to peroxisomal membrane Inferred from direct assay Ref.2Ref.1. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA protein complex Inferred from direct assay PubMed 18174172. Source: UniProtKB protein-lipid complex Inferred from direct assay PubMed 19715730. Source: UniProtKB
Molecular_function	lipid binding Inferred from direct assay PubMed 19715730. Source: UniProtKB protein dimerization activity Inferred from direct assay PubMed 19715730. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PEX19	P40855	4	EBI-594885,EBI-594747

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 373

373

Peroxisomal biogenesis factor 3

PRO_0000208737

Regions

Topological domain

1 – 15

15

Cytoplasmic Potential

Transmembrane

16 – 36

21

Helical; Potential

Topological domain

37 – 116

80

Peroxisomal Potential

Transmembrane

117 – 140

24

Helical; Potential

Topological domain

141 – 373

233

Cytoplasmic Potential

Region

1 – 45

45

Targeting to peroxisomes

Region

120 – 136

17

Interaction with PEX19

Natural variations

Natural variant

82

1

Q → R.
Corresponds to variant rs35220041 [ dbSNP | Ensembl ].

VAR_053572

Natural variant

138

1

G → E in PBD10A. Ref.4

VAR_009304

Experimental info

Mutagenesis

125

1

L → P: Abolishes binding to PEX19 without affecting targeting to peroxisomes; when associated with D-134. Ref.12

Mutagenesis

134

1

N → D: Abolishes binding to PEX19 without affecting targeting to peroxisomes; when associated with P-125. Ref.12

Secondary structure

1

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373

Helix Strand Turn

Details...

Helix

41 – 83

43

Helix

86 – 93

8

Helix

100 – 142

43

Beta strand

147 – 151

5

Helix

158 – 165

8

Helix

166 – 168

3

Helix

169 – 172

4

Helix

174 – 191

18

Beta strand

199 – 201

3

Helix

202 – 217

16

Helix

234 – 237

4

Helix

246 – 248

3

Helix

255 – 271

17

Helix

274 – 296

23

Beta strand

319 – 321

3

Helix

322 – 330

9

Helix

333 – 336

4

Turn

339 – 341

3

Helix

344 – 349

6

Helix

352 – 366

15

Sequences

	Sequence		Length	Mass (Da)
	P56589 [UniParc]. Last modified December 15, 1998. Version 1. Checksum: 3515A1F29656B7CC	FASTA	373	42,140
	10 20 30 40 50 60 MLRSVWNFLK RHKKKCIFLG TVLGGVYILG KYGQKKIREI QEREAAEYIA QARRQYHFES 70 80 90 100 110 120 NQRTCNMTVL SMLPTLREAL MQQLNSESLT ALLKNRPSNK LEIWEDLKII SFTRSTVAVY 130 140 150 160 170 180 STCMLVVLLR VQLNIIGGYI YLDNAAVGKN GTTILAPPDV QQQYLSSIQH LLGDGLTELI 190 200 210 220 230 240 TVIKQAVQKV LGSVSLKHSL SLLDLEQKLK EIRNLVEQHK SSSWINKDGS KPLLCHYMMP 250 260 270 280 290 300 DEETPLAVQA CGLSPRDITT IKLLNETRDM LESPDFSTVL NTCLNRGFSR LLDNMAEFFR 310 320 330 340 350 360 PTEQDLQHGN SMNSLSSVSL PLAKIIPIVN GQIHSVCSET PSHFVQDLLT MEQVKDFAAN 370 VYEAFSTPQQ LEK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of the gene encoding the human peroxisomal assembly protein Pex3p." Kammerer S., Holzinger A., Welsch U., Roscher A.A. FEBS Lett. 429:53-60(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Identification and characterization of the human peroxin PEX3." Soukupova M., Sprenger C., Gorgas K., Kunau W.H., Dodt G. Eur. J. Cell Biol. 78:357-374(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The human PEX3 gene encoding a peroxisomal assembly protein: genomic organization, positional mapping, and mutation analysis in candidate phenotypes." Muntau A.C., Holzinger A., Mayerhofer P.U., Gartner J., Roscher A.A., Kammerer S. Biochem. Biophys. Res. Commun. 268:704-710(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The peroxin pex3p initiates membrane assembly in peroxisome biogenesis." Ghaedi K., Tamura S., Okumoto K., Matsuzono Y., Fujiki Y. Mol. Biol. Cell 11:2085-2102(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CHARACTERIZATION, VARIANT PBD10A GLU-138. Tissue: Liver.
[5]	"Identification of a human transforming gene." Kim J.W. Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin and Uterus.
[10]	"PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis." Sacksteder K.A., Jones J.M., South S.T., Li X., Liu Y., Gould S.J. J. Cell Biol. 148:931-944(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PEX19.
[11]	"Human pex19p binds peroxisomal integral membrane proteins at regions distinct from their sorting sequences." Fransen M., Wylin T., Brees C., Mannaerts G.P., Van Veldhoven P.P. Mol. Cell. Biol. 21:4413-4424(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PEX19, SUBCELLULAR LOCATION.
[12]	"PEX3 functions as a PEX19 docking factor in the import of class I peroxisomal membrane proteins." Fang Y., Morrell J.C., Jones J.M., Gould S.J. J. Cell Biol. 164:863-875(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LEU-125 AND ASN-134.
[13]	"Defective peroxisome membrane synthesis due to mutations in human PEX3 causes Zellweger syndrome, complementation group G." Muntau A.C., Mayerhofer P.U., Paton B.C., Kammerer S., Roscher A.A. Am. J. Hum. Genet. 67:967-975(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PBD-CG12 AND PBD10A.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"Structural basis for docking of peroxisomal membrane protein carrier Pex19p onto its receptor Pex3p." Sato Y., Shibata H., Nakatsu T., Nakano H., Kashiwayama Y., Imanaka T., Kato H. EMBO J. 29:4083-4093(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 49-373 IN COMPLEX WITH PEX19, SUBUNIT.
[16]	"Insights into peroxisome function from the structure of PEX3 in complex with a soluble fragment of PEX19." Schmidt F., Treiber N., Zocher G., Bjelic S., Steinmetz M.O., Kalbacher H., Stehle T., Dodt G. J. Biol. Chem. 285:25410-25417(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.42 ANGSTROMS) OF 41-373 IN COMPLEX WITH PEX19, SUBUNIT.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ001625 mRNA. Translation: CAA04879.1.
AJ131389 mRNA. Translation: CAA10362.1.
AJ009866 , AJ009867, AJ009868, AJ009869, AJ009870, AJ009871, AJ009872, AJ009873, AJ009874 Genomic DNA. Translation: CAA08904.1.
AB035307 mRNA. Translation: BAA97993.1.
AY277600 mRNA. Translation: AAQ18039.1.
CR542062 mRNA. Translation: CAG46859.1.
AL031320 Genomic DNA. Translation: CAB53744.1.
CH471051 Genomic DNA. Translation: EAW47866.1.
BC014551 mRNA. Translation: AAH14551.1.
BC015506 mRNA. Translation: AAH15506.1.

IPI

IPI00010232.

RefSeq

NP_003621.1. NM_003630.2.

UniGene

Hs.592832.
Hs.7277.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3AJB	X-ray	2.50	A	49-373	[»]
3MK4	X-ray	2.42	A	41-373	[»]

ProteinModelPortal

P56589.

ModBase

Search...

Protein-protein interaction databases

IntAct

P56589. 4 interactions.

MINT

MINT-241504.

STRING

9606.ENSP00000356563.

Protein family/group databases

TCDB

9.A.17.1.2. integral membrane peroxisomal protein importer-2 (PPI2) family.

PTM databases

PhosphoSite

P56589.

Polymorphism databases

DMDM

3914303.

Proteomic databases

PaxDb

P56589.

PeptideAtlas

P56589.

PRIDE

P56589.

Protocols and materials databases

DNASU

8504.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000367591; ENSP00000356563; ENSG00000034693.

GeneID

8504.

KEGG

hsa:8504.

UCSC

uc003qjl.3. human.

Organism-specific databases

CTD

8504.

GeneCards

GC06P143772.

HGNC

HGNC:8858. PEX3.

HPA

HPA042830.

MIM

603164. gene.
614882. phenotype.

neXtProt

NX_P56589.

Orphanet

772. Infantile Refsum disease.
44. Neonatal adrenoleukodystrophy.
912. Zellweger syndrome.

PharmGKB

PA33200.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG259038.

HOGENOM

HOG000007212.

HOVERGEN

HBG000467.

InParanoid

P56589.

KO

K13336.

OMA

NIIGGYL.

PhylomeDB

P56589.

Enzyme and pathway databases

Reactome

REACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpress

P56589.

Bgee

P56589.

CleanEx

HS_PEX3.

Genevestigator

P56589.

GermOnline

ENSG00000034693. Homo sapiens.

Family and domain databases

InterPro

IPR006966. Peroxin-3.
[Graphical view]

Pfam

PF04882. Peroxin-3. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P56589.

GenomeRNAi

8504.

NextBio

31825.

SOURCE

Search...

Entry information

Entry name

PEX3_HUMAN

Accession

Primary (citable) accession number: P56589
Secondary accession number(s): Q6FGP5

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	December 15, 1998
Last modified:	May 1, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.