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Reviewed, UniProtKB/Swiss-Prot P40855 (PEX19_HUMAN)

Last modified November 25, 2008. Version 84. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Peroxisomal biogenesis factor 19
      Short name=Peroxin-19
Alternative name(s):
    Peroxisomal farnesylated protein
    33 kDa housekeeping protein
Gene names
Name: PEX19
Synonyms: HK33, PXF
ORF Names: OK/SW-cl.22
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length299 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Necessary for early peroxisomal biogenesis. Acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Binds and stabilizes newly synthesized PMPs in the cytoplasm by interacting with their hydrophobic membrane-spanning domains, and targets them to the peroxisome membrane by binding to the integral membrane protein PEX3. Excludes CDKN2A from the nucleus and prevents its interaction with MDM2, which results in active degradation of TP53.

Subunit structure

Interacts with a broad range of peroxisomal membrane proteins, including PEX3, PEX10, PEX11A, PEX11B, PEX12, PEX13, PEX14 and PEX16, PXMP2/PMP22, PXMP4/PMP24, SLC25A17/PMP34, ABCD1/ALDP, ABCD2/ALDRP, and ABCD3/PMP70. Also interacts with the tumor suppressor CDKN2A/p19ARF.

Subcellular location

Cytoplasm. Peroxisome membrane; Lipid-anchor; Cytoplasmic side. Note= Mainly cytoplasmic. Some fraction membrane-associated to the outer surface of peroxisomes.

Tissue specificity

Ubiquitously expressed. Isoform 1 is strongly predominant in all tissues except in utero where isoform 2 is the main form.

Involvement in disease

Defects in PEX19 are the cause of peroxisome biogenesis disorder complementation group 14 (PBD-CG14) [MIM:600279]; also known as PBD-CGJ. 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.

Defects in PEX19 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 peroxin-19 family.

Ontologies

Keywords

   Biological processPeroxisome biogenesis
   Cellular componentCytoplasm
Membrane
Peroxisome
   Coding sequence diversityAlternative splicing
   DiseasePeroxisome biogenesis disorder
Zellweger syndrome
   PTMLipoprotein
Phosphoprotein
Prenylation

Gene Ontology (GO)

   Biological processprotein targeting to peroxisome Ref.8

Inferred from mutant phenotype. Source: UniProtKB

   Cellular componentperoxisomal membrane Ref.2

Inferred from direct assay. Source: UniProtKB

   Molecular functionprotein binding Ref.8

Inferred from physical interaction. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Notes: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: P40855-1)

Also known as: PXF-all;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Notes: The two main transcripts are PXF-all and PXF-delta-2.
Isoform 2 (identifier: P40855-2)

Also known as: PXF-delta-2; PXF lacking exon 2;

The sequence of this isoform is not available.
Notes: The two main transcripts are PXF-all and PXF-delta-2.
Isoform 3 (identifier: P40855-3)

Also known as: PXF-delta-4; PXF lacking exon 4;

The sequence of this isoform is not available.
Isoform 4 (identifier: P40855-4)

Also known as: PXF-delta-8; PXF lacking part of exon 8;

The sequence of this isoform is not available.
Isoform 5 (identifier: P40855-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: MAAAEEGCSV...PQKRSPGDTA → PPLRKAVVSGPKRTGNWRSFW
Notes: Incomplete sequence.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 299299Peroxisomal biogenesis factor 19
PRO_0000218759

Regions

Region1 – 9191Necessary for PEX19 function on peroxisome biogenesis
Region1 – 5656Docking to the peroxisome membrane and binding to PEX3

Amino acid modifications

Modified residue351Phosphoserine
Modified residue541Phosphoserine
Modified residue1461Phosphoserine
Modified residue1471Phosphoserine
Modified residue1491Phosphoserine
Modified residue1771Phosphoserine
Modified residue1841Phosphoserine
Lipidation2961S-farnesyl cysteine

Natural variations

Alternative sequence1 – 5959MAAAE…PGDTA → PPLRKAVVSGPKRTGNWRSF W in isoform 5.
VSP_012649

Experimental info

Mutagenesis296 – 2994Missing: Abolishes binding to PEX10, PEX11B, PEX12 and PEX13. Does not affect binding to PEX3 and PEX16
Mutagenesis2961C → A: Slightly inhibits PEX19 function on peroxisome biogenesis
Mutagenesis2961C → S: Abolishes farnesylation. Abolishes PEX19 function on peroxisome biogenesis. Does not affect binding to ABCD1, ABCD2 and ABCD3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PXF-all) [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: 399AF6B79F219100

FASTA29932,807
        10         20         30         40         50         60 
MAAAEEGCSV GAEADRELEE LLESALDDFD KAKPSPAPPS TTTAPDASGP QKRSPGDTAK 

        70         80         90        100        110        120 
DALFASQEKF FQELFDSELA SQATAEFEKA MKELAEEEPH LVEQFQKLSE AAGRVGSDMT 

       130        140        150        160        170        180 
SQQEFTSCLK ETLSGLAKNA TDLQNSSMSE EELTKAMEGL GMDEGDGEGN ILPIMQSIMQ 

       190        200        210        220        230        240 
NLLSKDVLYP SLKEITEKYP EWLQSHRESL PPEQFEKYQE QHSVMCKICE QFEAETPTDS 

       250        260        270        280        290 
ETTQKARFEM VLDLMQQLQD LGHPPKELAG EMPPGLNFDL DALNLSGPPG ASGEQCLIM 

« Hide

Isoform 2 (PXF-delta-2) (PXF lacking exon 2) (Sequence not available).
Isoform 3 (PXF-delta-4) (PXF lacking exon 4) (Sequence not available).
Isoform 4 (PXF-delta-8) (PXF lacking part of exon 8) (Sequence not available).
Isoform 5 [UniParc].

Checksum: 5174D3C039E6A3B6
Show »

26129,259

References

« Hide 'large scale' references
[1]"Sequence of a putative human housekeeping gene (HK33) localized on chromosome 1."
Braun A., Kammerer S., Weissenhorn W., Weiss E.H., Cleve H.
Gene 146:291-295(1994) [PubMed: 8076834] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Ovary and Placenta.
[2]"Genomic organization and molecular characterization of a gene encoding HsPXF, a human peroxisomal farnesylated protein."
Kammerer S., Arnold N., Gutensohn W., Mewes H.-W., Kunau W.-H., Hoefler G., Roscher A.A., Braun A.
Genomics 45:200-210(1997) [PubMed: 9339377] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, ISOPRENYLATION AT CYS-296, MUTAGENESIS OF CYS-296.
Tissue: Leukocyte and Placenta.
[3]"Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly."
Matsuzono Y., Kinoshita N., Tamura S., Shimozawa N., Hamasaki M., Ghaedi K., Wanders R.J.A., Suzuki Y., Kondo N., Fujiki Y.
Proc. Natl. Acad. Sci. U.S.A. 96:2116-2121(1999) [PubMed: 10051604] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ISOPRENYLATION AT CYS-296, MUTAGENESIS OF CYS-296, SUBCELLULAR LOCATION, FUNCTION, INVOLVEMENT IN ZWS.
Tissue: Liver.
[4]"Identification of immuno-peptidmics that are recognized by tumor-reactive CTL generated from TIL of colon cancer patients."
Shichijo S., Itoh K.
Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
Tissue: Colon adenocarcinoma.
[5]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]"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: Lung.
[7]"Human adrenoleukodystrophy protein and related peroxisomal ABC transporters interact with the peroxisomal assembly protein PEX19p."
Gloeckner C.J., Mayerhofer P.U., Landgraf P., Muntau A.C., Holzinger A., Gerber J.-K., Kammerer S., Adamski J., Roscher A.A.
Biochem. Biophys. Res. Commun. 271:144-150(2000) [PubMed: 10777694] [Abstract]
Cited for: INTERACTION WITH ABCD1; ABCD2 AND ABCD3, MUTAGENESIS OF CYS-296.
Tissue: Brain.
[8]"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: FUNCTION, MUTAGENESIS OF CYS-296, SUBCELLULAR LOCATION, INTERACTION WITH ABCD1; ABCD2; ABCD3; PEX3; PEX10; PEX11A; PEX11B; PEX12; PEX13; PEX14; PEX16; PXMP2; PXMP4 AND SLC25A17.
[9]"Pex19p dampens the p19ARF-p53-p21WAF1 tumor suppressor pathway."
Sugihara T., Kaul S.C., Kato J.-Y., Reddel R.R., Nomura H., Wadhwa R.
J. Biol. Chem. 276:18649-18652(2001) [PubMed: 11259404] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CDKN2A.
Tissue: Testis.
[10]"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 PEX3; PEX10; PEX11B; PEX12; PEX13 AND PEX16, MUTAGENESIS OF 296-CYS--MET-299.
[11]"Two splice variants of human PEX19 exhibit distinct functions in peroxisomal assembly."
Mayerhofer P.U., Kattenfeld T., Roscher A.A., Muntau A.C.
Biochem. Biophys. Res. Commun. 291:1180-1186(2002) [PubMed: 11883941] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ABCD1; ABCD2; ABCD3 AND PEX3.
[12]"PEX3 functions as a PEX19 docking factor in the import of class I peroxisomal membrane proteins."
Fang Y., Morrell J.C., Jones J.M., Gould S.J.
J. Cell Biol. 164:863-875(2004) [PubMed: 15007061] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PEX3, SUBCELLULAR LOCATION.
[13]"PEX19 is a predominantly cytosolic chaperone and import receptor for class 1 peroxisomal membrane proteins."
Jones J.M., Morrell J.C., Gould S.J.
J. Cell Biol. 164:57-67(2004) [PubMed: 14709540] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PEX11B; PEX16; PXMP2; PXMP4; SLC25A17 AND ABCD3.
[14]"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry."
Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.
Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35; SER-54; SER-146; SER-147; SER-149; SER-177 AND SER-184, MASS SPECTROMETRY.
[15]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-147 AND SER-149, MASS SPECTROMETRY.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

X75535 mRNA. Translation: CAA53225.1.
Y09048 Genomic DNA. Translation: CAA70257.1.
AB018541 mRNA. Translation: BAA76291.1.
AB062286 mRNA. Translation: BAB93469.1. Different initiation.
BT006879 mRNA. Translation: AAP35525.1.
BC000496 mRNA. Translation: AAH00496.1.
PIRI37468.
RefSeqNP_001124511.1.
NP_002848.1.
UniGeneHs.517232

3D structure databases

ModBaseSearch...

Protein-protein interaction databases

DIPDIP:24172N.
IntActP40855.

PTM databases

PhosphoSiteP40855.

Genome annotation databases

EnsemblENSG00000162735. Homo sapiens. [Contig view]
GeneID5824.
KEGGhsa:5824.

Organism-specific databases

H-InvDBHIX0001216.
HGNCHGNC:9713. PEX19.
MIM214100. phenotype.
600279. gene+phenotype.
601539. phenotype.
Orphanet912. Zellweger syndrome.
PharmGKBPA34058.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMP40855.
HOVERGENP40855.

Gene expression databases

ArrayExpressP40855.
CleanExHS_PEX19.
GermOnlineENSG00000162735. Homo sapiens.

Family and domain databases

InterProIPR006708. Pex19.
[Graphical view]
PANTHERPTHR12774. Pex19. 1 hit.
PfamPF04614. Pex19. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio22685.
SOURCESearch...

Entry information

Entry namePEX19_HUMAN
AccessionPrimary (citable) accession number: P40855
Secondary accession number(s): Q8NI97
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: November 25, 2008
This is version 84 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents