Reviewed, UniProtKB/Swiss-Prot P40855 (PEX19_HUMAN)

Names and origin

Protein names

Recommended 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

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	299 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 process	Peroxisome biogenesis
Cellular component	Cytoplasm Membrane Peroxisome
Coding sequence diversity	Alternative splicing
Disease	Peroxisome biogenesis disorder Zellweger syndrome
PTM	Lipoprotein Phosphoprotein Prenylation
Gene Ontology (GO)
Biological process	protein targeting to peroxisome Ref.8 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	peroxisomal membrane Ref.2 Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Ref.8 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABCD2	Q9UBJ2	1	EBI-594747,EBI-80944
ABCD3	P28288	1	EBI-594747,EBI-80992
PEX12	O00623	1	EBI-594747,EBI-594836
PEX13	Q92968	1	EBI-594747,EBI-594849
PEX14	O75381	1	EBI-594747,EBI-594898
PEX3	P56589	1	EBI-594747,EBI-594885
SLC25A17	O43808	1	EBI-594747,EBI-594912

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 299	299	Peroxisomal biogenesis factor 19		PRO_0000218759
Regions
	Region	1 – 91	91	Necessary for PEX19 function on peroxisome biogenesis
	Region	1 – 56	56	Docking to the peroxisome membrane and binding to PEX3
Amino acid modifications
	Modified residue	35	1	Phosphoserine
	Modified residue	54	1	Phosphoserine
	Modified residue	146	1	Phosphoserine
	Modified residue	147	1	Phosphoserine
	Modified residue	149	1	Phosphoserine
	Modified residue	177	1	Phosphoserine
	Modified residue	184	1	Phosphoserine
	Lipidation	296	1	S-farnesyl cysteine
Natural variations
	Alternative sequence	1 – 59	59	MAAAE…PGDTA → PPLRKAVVSGPKRTGNWRSF W in isoform 5.		VSP_012649
Experimental info
	Mutagenesis	296 – 299	4	Missing: Abolishes binding to PEX10, PEX11B, PEX12 and PEX13. Does not affect binding to PEX3 and PEX16
	Mutagenesis	296	1	C → A: Slightly inhibits PEX19 function on peroxisome biogenesis
	Mutagenesis	296	1	C → S: Abolishes farnesylation. Abolishes PEX19 function on peroxisome biogenesis. Does not affect binding to ABCD1, ABCD2 and ABCD3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (PXF-all) [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 399AF6B79F219100	FASTA	299	32,807
	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
	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		261	29,259
	10 20 30 40 50 60 PPLRKAVVSG PKRTGNWRSF WKDALFASQE KFFQELFDSE LASQATAEFE KAMKELAEEE 70 80 90 100 110 120 PHLVEQFQKL SEAAGRVGSD MTSQQEFTSC LKETLSGLAK NATDLQNSSM SEEELTKAME 130 140 150 160 170 180 GLGMDEGDGE GNILPIMQSI MQNLLSKDVL YPSLKEITEK YPEWLQSHRE SLPPEQFEKY 190 200 210 220 230 240 QEQHSVMCKI CEQFEAETPT DSETTQKARF EMVLDLMQQL QDLGHPPKEL AGEMPPGLNF 250 260 DLDALNLSGP PGASGEQCLI M

References

	« Hide 'large scale' referencesShow '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

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
PIR	I37468.
RefSeq	NP_001124511.1. NP_002848.1.
UniGene	Hs.517232
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:24172N.
IntAct	P40855.
PTM databases
PhosphoSite	P40855.
Genome annotation databases
Ensembl	ENSG00000162735. Homo sapiens. [Contig view]
GeneID	5824.
KEGG	hsa:5824.
Organism-specific databases
H-InvDB	HIX0001216.
HGNC	HGNC:9713. PEX19.
MIM	214100. phenotype. 600279. gene+phenotype. 601539. phenotype.
Orphanet	912. Zellweger syndrome.
PharmGKB	PA34058.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P40855.
HOVERGEN	P40855.
Gene expression databases
ArrayExpress	P40855.
CleanEx	HS_PEX19.
GermOnline	ENSG00000162735. Homo sapiens.
Family and domain databases
InterPro	IPR006708. Pex19. [Graphical view]
PANTHER	PTHR12774. Pex19. 1 hit.
Pfam	PF04614. Pex19. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	22685.
SOURCE	Search...

Entry information

Entry name

PEX19_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)