O00623 (PEX12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Peroxisome assembly protein 12

Alternative name(s):
Peroxin-12
Peroxisome assembly factor 3
Short name=PAF-3

Gene names

Name:	PEX12
Synonyms:	PAF3

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	359 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Defects in PEX12 are the cause of peroxisome biogenesis disorder complementation group 3 (PBD-CG3) [MIM:601758]. PBD refers to a group of peroxisomal disorders arising from a failure of protein import into the peroxisomal membrane or matrix. The PBD group is comprised of four disorders: 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. The PBD group is genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Ref.1 Ref.9 Defects in PEX12 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.
Sequence similarities	Belongs to the pex2/pex10/pex12 family. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Cellular component	Membrane Peroxisome
Coding sequence diversity	Polymorphism
Disease	Disease mutation Peroxisome biogenesis disorder Zellweger syndrome
Domain	Transmembrane Transmembrane helix Zinc-finger
Ligand	Metal-binding Zinc
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	protein import into peroxisome matrix Inferred from mutant phenotype Ref.6Ref.1. Source: UniProtKB
Cellular component	integral to peroxisomal membrane Inferred from direct assay Ref.1. Source: UniProtKB
Molecular function	protein C-terminus binding Inferred from physical interaction Ref.6. Source: UniProtKB zinc ion binding Inferred from mutant phenotype Ref.6. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PEX19	P40855	2	EBI-594836,EBI-594747
PEX5	P50542	3	EBI-594836,EBI-597835

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 359	359	Peroxisome assembly protein 12		PRO_0000218610
Regions
	Topological domain	1 – 158	158	Cytoplasmic Potential
	Transmembrane	159 – 179	21	Helical; Potential
	Topological domain	180 – 239	60	Peroxisomal matrix Potential
	Transmembrane	240 – 260	21	Helical; Potential
	Topological domain	261 – 359	99	Cytoplasmic Potential
	Zinc finger	304 – 343	40	RING-type; degenerate
	Compositional bias	280 – 285	6	Poly-Pro
Natural variations
	Natural variant	34	1	R → S in PBD-CG3; Zellweger spectrum. Ref.9		VAR_058389
	Natural variant	178	1	Missing in PBD-CG3; Zellweger spectrum.		VAR_058390
	Natural variant	245	1	L → I. Ref.9 Corresponds to variant rs12941376 [ dbSNP | Ensembl ].		VAR_050495
	Natural variant	320	1	S → F in NALD; attenuates interaction with PEX10 and decreases peroxisomal protein import. Ref.2 Ref.9 Corresponds to variant rs28936697 [ dbSNP | Ensembl ].		VAR_031998
	Natural variant	349	1	Missing in PBD-CG3; Zellweger spectrum.		VAR_058391
Experimental info
	Mutagenesis	304	1	C → W: Abolishes interaction with PEX19; when associated with Q-307. Ref.8
	Mutagenesis	307	1	C → Q: Abolishes interaction with PEX19; when associated with W-304. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	O00623 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 1AF0BE6416422109	FASTA	359	40,797
	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

References

	« Hide 'large scale' referencesShow '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: 9090384] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], INVOLVEMENT IN PBD-CG3. 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: 9632816] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT NALD 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. , 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: 14702039] [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. , 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: 15489334] [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: 10562279] [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: 10704444] [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: 11390669] [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: 19105186] [Abstract] Cited for: VARIANTS PBD-CG3 SER-34; GLN-178 DEL; PHE-320 AND GLN-349 DEL, VARIANT ILE-245.
+	Additional computationally mapped references.

Web resources

GeneReviews

dbPEX, PEX Gene Database

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.
IPI	IPI00012573.
RefSeq	NP_000277.1. NM_000286.2.
UniGene	Hs.591190.
3D structure databases
ProteinModelPortal	O00623.
SMR	O00623. Positions 302-346.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00623. 3 interactions.
MINT	MINT-241654.
STRING	O00623.
Protein family/group databases
TCDB	3.A.20.1.1. peroxisomal protein importer (PPI) family.
Proteomic databases
PRIDE	O00623.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000225873; ENSP00000225873; ENSG00000108733.
GeneID	5193.
KEGG	hsa:5193.
UCSC	uc002hjp.1. human.
Organism-specific databases
CTD	5193.
GeneCards	GC17M033897.
HGNC	HGNC:8854. PEX12.
MIM	214100. phenotype. 601539. phenotype. 601758. gene+phenotype.
neXtProt	NX_O00623.
Orphanet	912. Zellweger syndrome.
PharmGKB	PA33196.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00390000016209.
HOGENOM	HBG390109.
HOVERGEN	HBG053569.
InParanoid	O00623.
OMA	FHYVRSH.
OrthoDB	EOG4BZN37.
PhylomeDB	O00623.
Gene expression databases
ArrayExpress	O00623.
Bgee	O00623.
CleanEx	HS_PEX12.
Genevestigator	O00623.
GermOnline	ENSG00000108733. Homo sapiens.
Family and domain databases
InterPro	IPR017375. Peroxisome_assmbl_p12. IPR006845. Pex_N. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Gene3D	G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.
KO	K13345.
Pfam	PF04757. Pex2_Pex12. 1 hit. [Graphical view]
PIRSF	PIRSF038074. Peroxisome_assembly_p12. 1 hit.
SMART	SM00184. RING. 1 hit. [Graphical view]
PROSITE	PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	20086.
SOURCE	Search...

Entry information

Entry name

PEX12_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 102 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.