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Q13608 (PEX6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length980 AA.
Sequence statusComplete.
Protein existenceEvidence 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.8 Ref.9

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.10

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 processPeroxisome biogenesis
   Cellular componentCytoplasm
Membrane
Peroxisome
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Peroxisome biogenesis disorder
Zellweger syndrome
   DomainRepeat
   LigandATP-binding
Nucleotide-binding
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP catabolic process

Inferred from mutant phenotype PubMed 16854980Ref.1. Source: GOC

peroxisome organization

Inferred from mutant phenotype Ref.2. Source: UniProtKB

protein import into peroxisome matrix, translocation

Inferred from mutant phenotype Ref.1. Source: UniProtKB

protein stabilization

Inferred from mutant phenotype Ref.1. Source: UniProtKB

protein targeting to peroxisome

Inferred from mutant phenotype PubMed 16854980. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay Ref.1. Source: UniProtKB

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_functionATP binding

Inferred from mutant phenotype PubMed 16854980. Source: UniProtKB

ATPase activity

Inferred from mutant phenotype Ref.1. Source: UniProtKB

ATPase activity, coupled

Inferred from mutant phenotype PubMed 16854980. Source: UniProtKB

protein C-terminus binding

Inferred from physical interaction PubMed 16854980. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 16257970PubMed 16854980. Source: UniProtKB

protein complex binding

Inferred from direct assay PubMed 16854980. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PEX1O439332EBI-988581,EBI-988601

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 980980Peroxisome assembly factor 2
PRO_0000084607

Regions

Nucleotide binding470 – 4778ATP Potential
Nucleotide binding744 – 7518ATP Potential

Natural variations

Natural variant791A → P. Ref.10
Corresponds to variant rs61752141 [ dbSNP | Ensembl ].
VAR_058381
Natural variant2741P → L in PBD-CG4. Ref.10
VAR_058382
Natural variant6011R → Q. Ref.10
Corresponds to variant rs34324426 [ dbSNP | Ensembl ].
VAR_058383
Natural variant8091A → V. Ref.10
Corresponds to variant rs35830695 [ dbSNP | Ensembl ].
VAR_048114
Natural variant8121R → Q in PBD4A. Ref.3
VAR_007918
Natural variant8121R → W in PBD4A; atypical. Ref.3
VAR_007919
Natural variant8491N → T in PBD-CG4. Ref.10
VAR_058384
Natural variant8601R → Q in PBD-CG4. Ref.10
VAR_058385
Natural variant8601R → W in PBD-CG4. Ref.10
VAR_058386
Natural variant8821V → I. Ref.10
Corresponds to variant rs2274516 [ dbSNP | Ensembl ].
VAR_048115
Natural variant9241A → S. Ref.10
Corresponds to variant rs34551839 [ dbSNP | Ensembl ].
VAR_058387
Natural variant9391P → Q. Ref.4 Ref.10
Corresponds to variant rs1129187 [ dbSNP | Ensembl ].
VAR_048116

Experimental info

Sequence conflict771S → N in AAC50655. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q13608 [UniParc].

Last modified December 8, 2000. Version 2.
Checksum: 0EC1C2A75CE0038F

FASTA980104,061
        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 

« Hide

References

« Hide '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]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Synovium.
[6]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. expand/collapse author list , 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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.
[8]"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.
[9]"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.
[10]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U56602 Genomic DNA. Translation: AAC50655.1.
D83703 mRNA. Translation: BAA12069.1.
AF108098 expand/collapse EMBL AC list , AF108095, AF108096, AF108097 Genomic DNA. Translation: AAF62564.1.
AB051076 mRNA. Translation: BAB83046.1.
AK314237 mRNA. Translation: BAG36906.1.
CH471081 Genomic DNA. Translation: EAX04125.1.
BC048331 mRNA. Translation: AAH48331.1.
CCDSCCDS4877.1.
PIRS71090.
RefSeqNP_000278.3. NM_000287.3.
UniGeneHs.656425.

3D structure databases

ProteinModelPortalQ13608.
SMRQ13608. Positions 435-971.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111213. 7 interactions.
IntActQ13608. 6 interactions.
MINTMINT-1183928.
STRING9606.ENSP00000303511.

Protein family/group databases

TCDB3.A.20.1.1. the peroxisomal protein importer (ppi) family.

PTM databases

PhosphoSiteQ13608.

Polymorphism databases

DMDM12644408.

Proteomic databases

MaxQBQ13608.
PaxDbQ13608.
PRIDEQ13608.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000304611; ENSP00000303511; ENSG00000124587.
GeneID5190.
KEGGhsa:5190.
UCSCuc003otf.3. human.

Organism-specific databases

CTD5190.
GeneCardsGC06M042978.
GeneReviewsPEX6.
HGNCHGNC:8859. PEX6.
HPAHPA025924.
MIM601498. gene.
614862. phenotype.
614863. phenotype.
neXtProtNX_Q13608.
Orphanet772. Infantile Refsum disease.
44. Neonatal adrenoleukodystrophy.
912. Zellweger syndrome.
PharmGKBPA33201.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0464.
HOGENOMHOG000241031.
HOVERGENHBG002311.
InParanoidQ13608.
KOK13339.
OMAWHDVGGL.
OrthoDBEOG74J979.
PhylomeDBQ13608.
TreeFamTF106428.

Gene expression databases

ArrayExpressQ13608.
BgeeQ13608.
CleanExHS_PEX6.
GenevestigatorQ13608.

Family and domain databases

Gene3D3.40.50.300. 2 hits.
InterProIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF00004. AAA. 2 hits.
[Graphical view]
SMARTSM00382. AAA. 2 hits.
[Graphical view]
SUPFAMSSF52540. SSF52540. 2 hits.
PROSITEPS00674. AAA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPEX6.
GenomeRNAi5190.
NextBio20072.
PROQ13608.
SOURCESearch...

Entry information

Entry namePEX6_HUMAN
AccessionPrimary (citable) accession number: Q13608
Secondary accession number(s): Q5T8W1, Q8WYQ2, Q99476
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: December 8, 2000
Last modified: July 9, 2014
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM