Q13608 (PEX6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Peroxisome assembly factor 2
Short name=PAF-2

Alternative name(s):
Peroxin-6
Peroxisomal biogenesis factor 6
Peroxisomal-type ATPase 1

Gene names

Name:	PEX6
Synonyms:	PXAAA1

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	980 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in peroxisome biosynthesis. Required for stability of the PTS1 receptor. Anchored by PEX26 to peroxisome membranes, possibly to form heteromeric AAA ATPase complexes required for the import of proteins into peroxisomes.
Subunit structure	Interacts directly with PEX26 and PEX1. Mediates the indirect interaction between PEX1 and PEX26. Interacts with ZFAND6. Ref.6 Ref.7
Subcellular location	Cytoplasm. Peroxisome membrane. Note: Associated with peroxisomal membranes.
Involvement in disease	Peroxisome biogenesis disorder complementation group 4 (PBD-CG4) [MIM:614862]: 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.8 Peroxisome biogenesis disorder 4A (PBD4A) [MIM:614862]: 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.1 Ref.3 Peroxisome biogenesis disorder 4B (PBD4B) [MIM:614863]: A peroxisome biogenesis disorder that includes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two milder manifestations of the Zellweger disease spectrum. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy and vision impairment. Children with the NALD presentation may reach their teens, while patients with the IRD presentation may reach adulthood. The clinical conditions are often slowly progressive in particular with respect to loss of hearing and vision. The biochemical abnormalities include accumulation of phytanic acid, very long chain fatty acids (VLCFA), di- and trihydroxycholestanoic acid and pipecolic acid. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4
Sequence similarities	Belongs to the AAA ATPase family.

Ontologies

Keywords
Biological process	Peroxisome biogenesis
Cellular component	Cytoplasm Membrane Peroxisome
Coding sequence diversity	Polymorphism
Disease	Disease mutation Peroxisome biogenesis disorder Zellweger syndrome
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein import into peroxisome matrix, translocation Inferred from mutant phenotype Ref.1. Source: UniProtKB protein stabilization Inferred from mutant phenotype Ref.1. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay PubMed 16854980. Source: UniProtKB peroxisomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell peroxisome Inferred from direct assay PubMed 11439091PubMed 16854980. Source: UniProtKB
Molecular_function	ATP binding Inferred from mutant phenotype PubMed 16854980. Source: UniProtKB ATPase activity, coupled Inferred from mutant phenotype PubMed 16854980. Source: UniProtKB protein complex binding Inferred from direct assay PubMed 16854980. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PEX1	O43933	2	EBI-988581,EBI-988601

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 980	980	Peroxisome assembly factor 2		PRO_0000084607
Regions
	Nucleotide binding	470 – 477	8	ATP Potential
	Nucleotide binding	744 – 751	8	ATP Potential
Natural variations
	Natural variant	79	1	A → P. Ref.8		VAR_058381
	Natural variant	274	1	P → L in PBD-CG4. Ref.8		VAR_058382
	Natural variant	601	1	R → Q. Ref.8 Corresponds to variant rs34324426 [ dbSNP | Ensembl ].		VAR_058383
	Natural variant	809	1	A → V. Ref.8 Corresponds to variant rs35830695 [ dbSNP | Ensembl ].		VAR_048114
	Natural variant	812	1	R → Q in PBD4A. Ref.3		VAR_007918
	Natural variant	812	1	R → W in PBD4A; atypical. Ref.3		VAR_007919
	Natural variant	849	1	N → T in PBD-CG4. Ref.8		VAR_058384
	Natural variant	860	1	R → Q in PBD-CG4. Ref.8		VAR_058385
	Natural variant	860	1	R → W in PBD-CG4. Ref.8		VAR_058386
	Natural variant	882	1	V → I. Ref.8 Corresponds to variant rs2274516 [ dbSNP | Ensembl ].		VAR_048115
	Natural variant	924	1	A → S. Ref.8 Corresponds to variant rs34551839 [ dbSNP | Ensembl ].		VAR_058387
	Natural variant	939	1	P → Q. Ref.4 Ref.8 Corresponds to variant rs1129187 [ dbSNP | Ensembl ].		VAR_048116
Experimental info
	Sequence conflict	77	1	S → N in AAC50655. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q13608 [UniParc]. Last modified December 8, 2000. Version 2. Checksum: 0EC1C2A75CE0038F	FASTA	980	104,061
	10 20 30 40 50 60 MALAVLRVLE PFPTETPPLA VLLPPGGPWP AAELGLVLAL RPAGESPAGP ALLVAALEGP 70 80 90 100 110 120 DAGTEEQGPG PPQLLVSRAL LRLLALGSGA WVRARAVRRP PALGWALLGT SLGPGLGPRV 130 140 150 160 170 180 GPLLVRRGET LPVPGPRVLE TRPALQGLLG PGTRLAVTEL RGRARLCPES GDSSRPPPPP 190 200 210 220 230 240 VVSSFAVSGT VRRLQGVLGG TGDSLGVSRS CLRGLGLFQG EWVWVAQARE SSNTSQPHLA 250 260 270 280 290 300 RVQVLEPRWD LSDRLGPGSG PLGEPLADGL ALVPATLAFN LGCDPLEMGE LRIQRYLEGS 310 320 330 340 350 360 IAPEDKGSCS LLPGPPFARE LHIEIVSSPH YSTNGNYDGV LYRHFQIPRV VQEGDVLCVP 370 380 390 400 410 420 TIGQVEILEG SPEKLPRWRE MFFKVKKTVG EAPDGPASAY LADTTHTSLY MVGSTLSPVP 430 440 450 460 470 480 WLPSEESTLW SSLSPPGLEA LVSELCAVLK PRLQPGGALL TGTSSVLLRG PPGCGKTTVV 490 500 510 520 530 540 AAACSHLGLH LLKVPCSSLC AESSGAVETK LQAIFSRARR CRPAVLLLTA VDLLGRDRDG 550 560 570 580 590 600 LGEDARVMAV LRHLLLNEDP LNSCPPLMVV ATTSRAQDLP ADVQTAFPHE LEVPALSEGQ 610 620 630 640 650 660 RLSILRALTA HLPLGQEVNL AQLARRCAGF VVGDLYALLT HSSRAACTRI KNSGLAGGLT 670 680 690 700 710 720 EEDEGELCAA GFPLLAEDFG QALEQLQTAH SQAVGAPKIP SVSWHDVGGL QEVKKEILET 730 740 750 760 770 780 IQLPLEHPEL LSLGLRRSGL LLHGPPGTGK TLLAKAVATE CSLTFLSVKG PELINMYVGQ 790 800 810 820 830 840 SEENVREVFA RARAAAPCII FFDELDSLAP SRGRSGDSGG VMDRVVSQLL AELDGLHSTQ 850 860 870 880 890 900 DVFVIGATNR PDLLDPALLR PGRFDKLVFV GANEDRASQL RVLSAITRKF KLEPSVSLVN 910 920 930 940 950 960 VLDCCPPQLT GADLYSLCSD AMTAALKRRV HDLEEGLEPG SSALMLTMED LLQAAARLQP 970 980 SVSEQELLRY KRIQRKFAAC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The peroxisome biogenesis disorder group 4 gene, PXAAA1, encodes a cytoplasmic ATPase required for stability of the PTS1 receptor." Yahraus T., Braverman N., Dodt G., Kalish J.E., Morrell J.C., Moser H.W., Valle D., Gould S.J. EMBO J. 15:2914-2923(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], INVOLVEMENT IN PBD4A.
[2]	"Human peroxisome assembly factor-2 (PAF-2): a gene responsible for group C peroxisome biogenesis disorder in humans." Fukuda S., Shimozawa N., Suzuki Y., Zhang Z., Tomatsu S., Tsukamoto T., Hashiguchi N., Osumi T., Masuno M., Imaizumi K., Kuroki Y., Fujiki Y., Orii T., Kondo N. Am. J. Hum. Genet. 59:1210-1220(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Genomic structure and identification of 11 novel mutations of the PEX6 'peroxisome assembly factor-2' gene in patients with peroxisome biogenesis disorders." Zhang Z., Suzuki Y., Shimozawa N., Fukuda S., Imamura A., Tsukamoto T., Osumi T., Fujiki Y., Orii T., Wanders R.J.A., Barth P.G., Moser H.W., Paton B.C., Besley G.T., Kondo N. Hum. Mutat. 13:487-496(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PBD4A GLN-812 AND TRP-812.
[4]	"The peroxin Pex6p gene is impaired in peroxisomal biogenesis disorders of complementation group 6." Matsumoto N., Tamura S., Moser A., Moser H.W., Braverman N., Suzuki Y., Shimozawa N., Kondo N., Fujiki Y. J. Hum. Genet. 46:273-277(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-939, INVOLVEMENT IN PBD4B.
[5]	"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: Colon.
[6]	"The pathogenic peroxin Pex26p recruits the Pex1p-Pex6p AAA ATPase complexes to peroxisomes." Matsumoto N., Tamura S., Fujiki Y. Nat. Cell Biol. 5:454-460(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PEX26 AND PEX1.
[7]	"AWP1/ZFAND6 functions in Pex5 export by interacting with cys-monoubiquitinated Pex5 and Pex6 AAA ATPase." Miyata N., Okumoto K., Mukai S., Noguchi M., Fujiki Y. Traffic 13:168-183(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZFAND6.
[8]	"Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders." Yik W.Y., Steinberg S.J., Moser A.B., Moser H.W., Hacia J.G. Hum. Mutat. 30:E467-E480(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PBD-CG4 LEU-274; THR-849; GLN-860 AND TRP-860, VARIANTS PRO-79; GLN-601; VAL-809; ILE-882; SER-924 AND GLN-939.
+	Additional computationally mapped references.

Web resources

GeneReviews

dbPEX, PEX Gene Database

Cross-references

Sequence databases
EMBL GenBank DDBJ	U56602 Genomic DNA. Translation: AAC50655.1. D83703 mRNA. Translation: BAA12069.1. AF108098 , AF108095, AF108096, AF108097 Genomic DNA. Translation: AAF62564.1. AB051076 mRNA. Translation: BAB83046.1. BC048331 mRNA. Translation: AAH48331.1.
IPI	IPI00299182.
PIR	S71090.
RefSeq	NP_000278.3. NM_000287.3.
UniGene	Hs.656425.
3D structure databases
ProteinModelPortal	Q13608.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13608. 5 interactions.
MINT	MINT-1183928.
STRING	9606.ENSP00000303511.
Protein family/group databases
TCDB	3.A.20.1.1. peroxisomal protein importer (PPI) family.
PTM databases
PhosphoSite	Q13608.
Polymorphism databases
DMDM	12644408.
Proteomic databases
PaxDb	Q13608.
PRIDE	Q13608.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000304611; ENSP00000303511; ENSG00000124587.
GeneID	5190.
KEGG	hsa:5190.
UCSC	uc003otf.3. human.
Organism-specific databases
CTD	5190.
GeneCards	GC06M042978.
HGNC	HGNC:8859. PEX6.
HPA	HPA025924.
MIM	601498. gene. 614862. phenotype. 614863. phenotype.
neXtProt	NX_Q13608.
Orphanet	772. Infantile Refsum disease. 44. Neonatal adrenoleukodystrophy. 912. Zellweger syndrome.
PharmGKB	PA33201.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0464.
HOGENOM	HOG000241031.
HOVERGEN	HBG002311.
InParanoid	Q13608.
KO	K13339.
OMA	SWHDVGG.
OrthoDB	EOG47WNNP.
PhylomeDB	Q13608.
Gene expression databases
ArrayExpress	Q13608.
Bgee	Q13608.
CleanEx	HS_PEX6.
Genevestigator	Q13608.
GermOnline	ENSG00000124587. Homo sapiens.
Family and domain databases
InterPro	IPR003593. AAA+_ATPase. IPR003959. ATPase_AAA_core. IPR003960. ATPase_AAA_CS. [Graphical view]
Pfam	PF00004. AAA. 2 hits. [Graphical view]
SMART	SM00382. AAA. 2 hits. [Graphical view]
PROSITE	PS00674. AAA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	5190.
NextBio	20072.
SOURCE	Search...

Entry information

Entry name

PEX6_HUMAN

Accession

Primary (citable) accession number: Q13608
Secondary accession number(s): Q8WYQ2, Q99476

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	December 8, 2000
Last modified:	May 1, 2013
This is version 121 of the entry and version 2 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.