P28328 (PEX2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Peroxisome biogenesis factor 2

Alternative name(s):
35 kDa peroxisomal membrane protein
Peroxin-2
Peroxisomal membrane protein 3
Peroxisome assembly factor 1
Short name=PAF-1
RING finger protein 72

Gene names

Name:	PEX2
Synonyms:	PAF1, PMP3, PMP35, PXMP3, RNF72

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

General annotation (Comments)

Function	Somewhat implicated in the biogenesis of peroxisomes.
Subcellular location	Peroxisome membrane; Multi-pass membrane protein.
Involvement in disease	Peroxisome biogenesis disorder complementation group 5 (PBD-CG5) [MIM:614866]: 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. Peroxisome biogenesis disorder 5A (PBD5A) [MIM:614866]: 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 5B (PBD5B) [MIM:614867]: 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.8
Sequence similarities	Belongs to the pex2/pex10/pex12 family. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Peroxisome biogenesis
Cellular component	Membrane Peroxisome
Disease	Disease mutation Peroxisome biogenesis disorder Zellweger syndrome
Domain	Transmembrane Transmembrane helix Zinc-finger
Ligand	Metal-binding Zinc
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bile acid biosynthetic process Inferred from electronic annotation. Source: Compara cholesterol homeostasis Inferred from electronic annotation. Source: Compara fatty acid beta-oxidation Inferred from mutant phenotype Ref.8PubMed 9765053. Source: UniProtKB negative regulation of epithelial cell proliferation Inferred from mutant phenotype PubMed 18987311. Source: UniProtKB negative regulation of fibroblast proliferation Inferred from mutant phenotype PubMed 18987311. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 18987311. Source: UniProtKB neuron migration Inferred from electronic annotation. Source: Compara protein destabilization Inferred from mutant phenotype PubMed 18987311. Source: UniProtKB protein import into peroxisome matrix Inferred from mutant phenotype Ref.8. Source: UniProtKB regulation of cholesterol biosynthetic process Inferred from electronic annotation. Source: Compara very long-chain fatty acid metabolic process Inferred from mutant phenotype PubMed 9765053. Source: UniProtKB
Cellular_component	Cdc73/Paf1 complex Inferred from direct assay PubMed 18987311. Source: UniProtKB integral to peroxisomal membrane Inferred from mutant phenotype PubMed 12751901. Source: UniProtKB
Molecular_function	zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 305	305	Peroxisome biogenesis factor 2		PRO_0000056369
Regions
	Transmembrane	140 – 159	20	Helical; Potential
	Transmembrane	195 – 213	19	Helical; Potential
	Zinc finger	244 – 284	41	RING-type
Amino acid modifications
	Modified residue	84	1	N6-acetyllysine Ref.7
Natural variations
	Natural variant	55	1	E → K in PBD5B; infantile Refsum disease. Ref.8		VAR_011389
	Natural variant	184	1	C → R. Ref.1 Ref.2 Ref.3 Ref.5 Corresponds to variant rs10087163 [ dbSNP | Ensembl ].		VAR_060784

Sequences

	Sequence		Length	Mass (Da)
	P28328 [UniParc]. Last modified December 15, 2009. Version 2. Checksum: F624F93C613FF2DB	FASTA	305	34,843
	10 20 30 40 50 60 MASRKENAKS ANRVLRISQL DALELNKALE QLVWSQFTQC FHGFKPGLLA RFEPEVKACL 70 80 90 100 110 120 WVFLWRFTIY SKNATVGQSV LNIKYKNDFS PNLRYQPPSK NQKIWYAVCT IGGRWLEERC 130 140 150 160 170 180 YDLFRNHHLA SFGKVKQCVN FVIGLLKLGG LINFLIFLQR GKFATLTERL LGIHSVFCKP 190 200 210 220 230 240 QNICEVGFEY MNRELLWHGF AEFLIFLLPL INVQKLKAKL SSWCIPLTGA PNSDNTLATS 250 260 270 280 290 300 GKECALCGEW PTMPHTIGCE HIFCYFCAKS SFLFDVYFTC PKCGTEVHSL QPLKSGIEMS EVNAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A human gene responsible for Zellweger syndrome that affects peroxisome assembly." Shimozawa N., Tsukamoto T., Suzuki Y., Orii T., Shirayoshi Y., Mori T., Fujiki Y. Science 255:1132-1134(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-184, INVOLVEMENT IN PBD5A. Tissue: Liver.
[2]	"Genomic organization and characterization of human PEX2 encoding a 35-kDa peroxisomal membrane protein." Biermanns M., Gaertner J. Biochem. Biophys. Res. Commun. 273:985-990(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-184.
[3]	Gartner J. Submitted (FEB-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-184. Tissue: Liver.
[4]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] 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], VARIANT ARG-184. Tissue: Kidney and Liver.
[6]	"Ring finger in the peroxisome assembly factor-1." Patarca R., Fletcher M.A. FEBS Lett. 312:1-2(1992) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAIN RING FINGER.
[7]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-84, MASS SPECTROMETRY.
[8]	"Defective PEX gene products correlate with the protein import, biochemical abnormalities, and phenotypic heterogeneity in peroxisome biogenesis disorders." Shimozawa N., Imamura A., Zhang Z., Suzuki Y., Orii T., Tsukamoto T., Osumi T., Fujiki Y., Wanders R.J.A., Besley G., Kondo N. J. Med. Genet. 36:779-781(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PBD5B LYS-55.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	M86852 mRNA. Translation: AAC12785.1. AF133826 Genomic DNA. Translation: AAF97687.1. M85038 mRNA. Translation: AAA60141.1. AC090810 Genomic DNA. No translation available. BC000661 mRNA. No translation available. BC005375 mRNA. Translation: AAH05375.1. BC093043 mRNA. Translation: AAH93043.1.
IPI	IPI00002852.
PIR	A41812.
RefSeq	NP_000309.1. NM_000318.2. NP_001073336.1. NM_001079867.1. NP_001165557.1. NM_001172086.1. NP_001165558.1. NM_001172087.1.
UniGene	Hs.437966.
3D structure databases
ProteinModelPortal	P28328.
SMR	P28328. Positions 239-289.
ModBase	Search...
Protein-protein interaction databases
IntAct	P28328. 7 interactions.
MINT	MINT-1377091.
Protein family/group databases
TCDB	3.A.20.1.1. peroxisomal protein importer (PPI) family.
PTM databases
PhosphoSite	P28328.
Polymorphism databases
DMDM	281185478.
Proteomic databases
PaxDb	P28328.
PRIDE	P28328.
Protocols and materials databases
DNASU	5828.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000357039; ENSP00000349543; ENSG00000164751. ENST00000419564; ENSP00000400984; ENSG00000164751. ENST00000520103; ENSP00000428590; ENSG00000164751. ENST00000522527; ENSP00000428638; ENSG00000164751.
GeneID	5828.
KEGG	hsa:5828.
UCSC	uc003yax.3. human.
Organism-specific databases
CTD	5828.
GeneCards	GC08M077892.
HGNC	HGNC:9717. PEX2.
HPA	HPA011410. HPA027729.
MIM	170993. gene. 614866. phenotype. 614867. phenotype.
neXtProt	NX_P28328.
Orphanet	772. Infantile Refsum disease. 44. Neonatal adrenoleukodystrophy. 912. Zellweger syndrome.
PharmGKB	PA34060.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG245402.
HOGENOM	HOG000294074.
HOVERGEN	HBG000416.
InParanoid	P28328.
KO	K06664.
OMA	QCFHGFK.
OrthoDB	EOG48SGV1.
Gene expression databases
ArrayExpress	P28328.
Bgee	P28328.
CleanEx	HS_PAF1. HS_PXMP3.
Genevestigator	P28328.
GermOnline	ENSG00000164751. Homo sapiens.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR006845. Pex_N. IPR018957. Znf_C3HC4_RING-type. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. IPR017907. Znf_RING_CS. [Graphical view]
Pfam	PF04757. Pex2_Pex12. 1 hit. PF00097. zf-C3HC4. 1 hit. [Graphical view]
SMART	SM00184. RING. 1 hit. [Graphical view]
PROSITE	PS00518. ZF_RING_1. 1 hit. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PEX2. human.
GenomeRNAi	5828.
NextBio	22704.
SOURCE	Search...

Entry information

Entry name

PEX2_HUMAN

Accession

Primary (citable) accession number: P28328
Secondary accession number(s): Q567S6, Q9BW41

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 15, 2009
Last modified:	May 1, 2013
This is version 136 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.