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O00623 (PEX12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. 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 protein 12
Alternative name(s):
Peroxin-12
Peroxisome assembly factor 3
Short name=PAF-3
Gene names
Name:PEX12
Synonyms:PAF3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length359 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for protein import into peroxisomes. Ref.2

Subunit structure

Interacts with PEX5 and PEX10. Interacts with PEX19 via its cytoplasmic domain. Ref.6 Ref.7 Ref.8

Subcellular location

Peroxisome membrane; Multi-pass membrane protein Ref.2.

Involvement in disease

Peroxisome biogenesis disorder complementation group 3 (PBD-CG3) [MIM:614859]: 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.9

Peroxisome biogenesis disorder 3A (PBD3A) [MIM:614859]: 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

Peroxisome biogenesis disorder 3B (PBD3B) [MIM:266510]: 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.2

Sequence similarities

Belongs to the pex2/pex10/pex12 family.

Contains 1 RING-type zinc finger.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PEX19P408552EBI-594836,EBI-594747
PEX5P505424EBI-594836,EBI-597835

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 359359Peroxisome assembly protein 12
PRO_0000218610

Regions

Topological domain1 – 158158Cytoplasmic Potential
Transmembrane159 – 17921Helical; Potential
Topological domain180 – 23960Peroxisomal matrix Potential
Transmembrane240 – 26021Helical; Potential
Topological domain261 – 35999Cytoplasmic Potential
Zinc finger304 – 34340RING-type; degenerate
Compositional bias280 – 2856Poly-Pro

Natural variations

Natural variant341R → S in PBD-CG3. Ref.9
Corresponds to variant rs147530802 [ dbSNP | Ensembl ].
VAR_058389
Natural variant1781Missing in PBD-CG3. Ref.9
VAR_058390
Natural variant2451L → I. Ref.9
Corresponds to variant rs12941376 [ dbSNP | Ensembl ].
VAR_050495
Natural variant3201S → F in PBD3B; attenuates interaction with PEX10 and decreases peroxisomal protein import. Ref.2 Ref.9
Corresponds to variant rs28936697 [ dbSNP | Ensembl ].
VAR_031998
Natural variant3491Missing in PBD-CG3. Ref.9
VAR_058391

Experimental info

Mutagenesis3041C → W: Abolishes interaction with PEX19; when associated with Q-307. Ref.8
Mutagenesis3071C → Q: Abolishes interaction with PEX19; when associated with W-304. Ref.8

Sequences

Sequence LengthMass (Da)Tools
O00623 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: 1AF0BE6416422109

FASTA35940,797
        10         20         30         40         50         60 
MAEHGAHFTA ASVADDQPSI FEVVAQDSLM TAVRPALQHV VKVLAESNPT HYGFLWRWFD 

        70         80         90        100        110        120 
EIFTLLDLLL QQHYLSRTSA SFSENFYGLK RIVMGDTHKS QRLASAGLPK QQLWKSIMFL 

       130        140        150        160        170        180 
VLLPYLKVKL EKLVSSLREE DEYSIHPPSS RWKRFYRAFL AAYPFVNMAW EGWFLVQQLR 

       190        200        210        220        230        240 
YILGKAQHHS PLLRLAGVQL GRLTVQDIQA LEHKPAKASM MQQPARSVSE KINSALKKAV 

       250        260        270        280        290        300 
GGVALSLSTG LSVGVFFLQF LDWWYSSENQ ETIKSLTALP TPPPPVHLDY NSDSPLLPKM 

       310        320        330        340        350 
KTVCPLCRKT RVNDTVLATS GYVFCYRCVF HYVRSHQACP ITGYPTEVQH LIKLYSPEN 

« Hide

References

« Hide 'large scale' references
[1]"Isolation of the human PEX12 gene, mutated in group 3 of the peroxisome biogenesis disorders."
Chang C.-C., Lee W.-H., Moser H., Valle D., Gould S.J.
Nat. Genet. 15:385-388(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], INVOLVEMENT IN PBD3A.
Tissue: Fetal brain.
[2]"PEX12, the pathogenic gene of group III Zellweger syndrome: cDNA cloning by functional complementation on a CHO cell mutant, patient analysis, and characterization of PEX12p."
Okumoto K., Shimozawa N., Kawai A., Tamura S., Tsukamoto T., Osumi T., Moser H., Wanders R.J.A., Suzuki Y., Kondo N., Fujiki Y.
Mol. Cell. Biol. 18:4324-4336(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PBD3B PHE-320.
[3]"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].
[4]Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: Testis.
[6]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PEX5 AND PEX10.
[7]"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.
[8]"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, MUTAGENESIS OF CYS-304 AND CYS-307.
[9]"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-CG3 SER-34; GLN-178 DEL; PHE-320 AND GLN-349 DEL, VARIANT ILE-245.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U91521 mRNA. Translation: AAC68812.1.
U91522 Genomic DNA. Translation: AAC68813.1.
AB004546 mRNA. Translation: BAA31559.1.
AK312635 mRNA. Translation: BAG35519.1.
CH471147 Genomic DNA. Translation: EAW80143.1.
BC031085 mRNA. Translation: AAH31085.1.
RefSeqNP_000277.1. NM_000286.2.
UniGeneHs.591190.

3D structure databases

ProteinModelPortalO00623.
SMRO00623. Positions 302-346.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111216. 4 interactions.
IntActO00623. 3 interactions.
MINTMINT-241654.
STRING9606.ENSP00000225873.

Protein family/group databases

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

PTM databases

PhosphoSiteO00623.

Proteomic databases

PaxDbO00623.
PRIDEO00623.

Protocols and materials databases

DNASU5193.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000225873; ENSP00000225873; ENSG00000108733.
GeneID5193.
KEGGhsa:5193.
UCSCuc002hjp.3. human.

Organism-specific databases

CTD5193.
GeneCardsGC17M033897.
HGNCHGNC:8854. PEX12.
MIM266510. phenotype.
601758. gene.
614859. phenotype.
neXtProtNX_O00623.
Orphanet772. Infantile Refsum disease.
44. Neonatal adrenoleukodystrophy.
912. Zellweger syndrome.
PharmGKBPA33196.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG328872.
HOGENOMHOG000038427.
HOVERGENHBG053569.
InParanoidO00623.
KOK13345.
OMAFHYVRSH.
OrthoDBEOG73NG3W.
PhylomeDBO00623.
TreeFamTF314511.

Gene expression databases

ArrayExpressO00623.
BgeeO00623.
CleanExHS_PEX12.
GenevestigatorO00623.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR017375. PEX12.
IPR006845. Pex_N.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PANTHERPTHR12888. PTHR12888. 1 hit.
PfamPF04757. Pex2_Pex12. 1 hit.
[Graphical view]
PIRSFPIRSF038074. Peroxisome_assembly_p12. 1 hit.
SMARTSM00184. RING. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPEX12.
GenomeRNAi5193.
NextBio20086.
PROO00623.
SOURCESearch...

Entry information

Entry namePEX12_HUMAN
AccessionPrimary (citable) accession number: O00623
Secondary accession number(s): B2R6M2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 124 of the entry and version 1 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 17

Human chromosome 17: entries, gene names and cross-references to MIM