Full text data of PEX19
PEX19
(HK33, PXF)
[Confidence: low (only semi-automatic identification from reviews)]
Peroxisomal biogenesis factor 19 (33 kDa housekeeping protein; Peroxin-19; Peroxisomal farnesylated protein; Flags: Precursor)
Peroxisomal biogenesis factor 19 (33 kDa housekeeping protein; Peroxin-19; Peroxisomal farnesylated protein; Flags: Precursor)
UniProt
P40855
ID PEX19_HUMAN Reviewed; 299 AA.
AC P40855; D3DVE7; Q5QNY4; Q8NI97;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 1.
DT 22-JAN-2014, entry version 141.
DE RecName: Full=Peroxisomal biogenesis factor 19;
DE AltName: Full=33 kDa housekeeping protein;
DE AltName: Full=Peroxin-19;
DE AltName: Full=Peroxisomal farnesylated protein;
DE Flags: Precursor;
GN Name=PEX19; Synonyms=HK33, PXF; ORFNames=OK/SW-cl.22;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Ovary, and Placenta;
RX PubMed=8076834; DOI=10.1016/0378-1119(94)90308-5;
RA Braun A., Kammerer S., Weissenhorn W., Weiss E.H., Cleve H.;
RT "Sequence of a putative human housekeeping gene (HK33) localized on
RT chromosome 1.";
RL Gene 146:291-295(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, ISOPRENYLATION AT CYS-296, AND
RP MUTAGENESIS OF CYS-296.
RC TISSUE=Leukocyte, and Placenta;
RX PubMed=9339377; DOI=10.1006/geno.1997.4914;
RA Kammerer S., Arnold N., Gutensohn W., Mewes H.-W., Kunau W.-H.,
RA Hoefler G., Roscher A.A., Braun A.;
RT "Genomic organization and molecular characterization of a gene
RT encoding HsPXF, a human peroxisomal farnesylated protein.";
RL Genomics 45:200-210(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ISOPRENYLATION AT CYS-296,
RP MUTAGENESIS OF CYS-296, SUBCELLULAR LOCATION, FUNCTION, AND
RP INVOLVEMENT IN PBD12A.
RC TISSUE=Liver;
RX PubMed=10051604; DOI=10.1073/pnas.96.5.2116;
RA Matsuzono Y., Kinoshita N., Tamura S., Shimozawa N., Hamasaki M.,
RA Ghaedi K., Wanders R.J.A., Suzuki Y., Kondo N., Fujiki Y.;
RT "Human PEX19: cDNA cloning by functional complementation, mutation
RT analysis in a patient with Zellweger syndrome, and potential role in
RT peroxisomal membrane assembly.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:2116-2121(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-
RT reactive CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP INTERACTION WITH ABCD1; ABCD2 AND ABCD3, AND MUTAGENESIS OF CYS-296.
RC TISSUE=Brain;
RX PubMed=10777694; DOI=10.1006/bbrc.2000.2572;
RA Gloeckner C.J., Mayerhofer P.U., Landgraf P., Muntau A.C.,
RA Holzinger A., Gerber J.-K., Kammerer S., Adamski J., Roscher A.A.;
RT "Human adrenoleukodystrophy protein and related peroxisomal ABC
RT transporters interact with the peroxisomal assembly protein PEX19p.";
RL Biochem. Biophys. Res. Commun. 271:144-150(2000).
RN [10]
RP FUNCTION, MUTAGENESIS OF CYS-296, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH ABCD1; ABCD2; ABCD3; PEX3; PEX10; PEX11A; PEX11B;
RP PEX12; PEX13; PEX14; PEX16; PXMP2; PXMP4 AND SLC25A17.
RX PubMed=10704444; DOI=10.1083/jcb.148.5.931;
RA Sacksteder K.A., Jones J.M., South S.T., Li X., Liu Y., Gould S.J.;
RT "PEX19 binds multiple peroxisomal membrane proteins, is predominantly
RT cytoplasmic, and is required for peroxisome membrane synthesis.";
RL J. Cell Biol. 148:931-944(2000).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CDKN2A.
RC TISSUE=Testis;
RX PubMed=11259404; DOI=10.1074/jbc.C100011200;
RA Sugihara T., Kaul S.C., Kato J.-Y., Reddel R.R., Nomura H., Wadhwa R.;
RT "Pex19p dampens the p19ARF-p53-p21WAF1 tumor suppressor pathway.";
RL J. Biol. Chem. 276:18649-18652(2001).
RN [12]
RP INTERACTION WITH PEX3; PEX10; PEX11B; PEX12; PEX13 AND PEX16, AND
RP MUTAGENESIS OF 296-CYS--MET-299.
RX PubMed=11390669; DOI=10.1128/MCB.21.13.4413-4424.2001;
RA Fransen M., Wylin T., Brees C., Mannaerts G.P., Van Veldhoven P.P.;
RT "Human pex19p binds peroxisomal integral membrane proteins at regions
RT distinct from their sorting sequences.";
RL Mol. Cell. Biol. 21:4413-4424(2001).
RN [13]
RP FUNCTION, AND INTERACTION WITH ABCD1; ABCD2; ABCD3 AND PEX3.
RX PubMed=11883941; DOI=10.1006/bbrc.2002.6568;
RA Mayerhofer P.U., Kattenfeld T., Roscher A.A., Muntau A.C.;
RT "Two splice variants of human PEX19 exhibit distinct functions in
RT peroxisomal assembly.";
RL Biochem. Biophys. Res. Commun. 291:1180-1186(2002).
RN [14]
RP FUNCTION, INTERACTION WITH PEX3, AND SUBCELLULAR LOCATION.
RX PubMed=15007061; DOI=10.1083/jcb.200311131;
RA Fang Y., Morrell J.C., Jones J.M., Gould S.J.;
RT "PEX3 functions as a PEX19 docking factor in the import of class I
RT peroxisomal membrane proteins.";
RL J. Cell Biol. 164:863-875(2004).
RN [15]
RP FUNCTION, AND INTERACTION WITH PEX11B; PEX16; PXMP2; PXMP4; SLC25A17
RP AND ABCD3.
RX PubMed=14709540; DOI=10.1083/jcb.200304111;
RA Jones J.M., Morrell J.C., Gould S.J.;
RT "PEX19 is a predominantly cytosolic chaperone and import receptor for
RT class 1 peroxisomal membrane proteins.";
RL J. Cell Biol. 164:57-67(2004).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
RP INVOLVEMENT IN PBD-CG14.
RX PubMed=20683989; DOI=10.1002/ajmg.a.33560;
RA Mohamed S., El-Meleagy E., Nasr A., Ebberink M.S., Wanders R.J.,
RA Waterham H.R.;
RT "A mutation in PEX19 causes a severe clinical phenotype in a patient
RT with peroxisomal biogenesis disorder.";
RL Am. J. Med. Genet. A 152:2318-2321(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [20]
RP STRUCTURE BY NMR OF 66-77 IN COMPLEX WITH PEX14.
RX PubMed=19197237; DOI=10.1038/emboj.2009.7;
RA Neufeld C., Filipp F.V., Simon B., Neuhaus A., Schueller N., David C.,
RA Kooshapur H., Madl T., Erdmann R., Schliebs W., Wilmanns M.,
RA Sattler M.;
RT "Structural basis for competitive interactions of Pex14 with the
RT import receptors Pex5 and Pex19.";
RL EMBO J. 28:745-754(2009).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1-44 IN COMPLEX WITH PEX3,
RP AND SUBUNIT.
RX PubMed=21102411; DOI=10.1038/emboj.2010.293;
RA Sato Y., Shibata H., Nakatsu T., Nakano H., Kashiwayama Y.,
RA Imanaka T., Kato H.;
RT "Structural basis for docking of peroxisomal membrane protein carrier
RT Pex19p onto its receptor Pex3p.";
RL EMBO J. 29:4083-4093(2010).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.42 ANGSTROMS) OF 13-33 IN COMPLEX WITH PEX3,
RP SUBUNIT, AND MUTAGENESIS OF PHE-29.
RX PubMed=20554521; DOI=10.1074/jbc.M110.138503;
RA Schmidt F., Treiber N., Zocher G., Bjelic S., Steinmetz M.O.,
RA Kalbacher H., Stehle T., Dodt G.;
RT "Insights into peroxisome function from the structure of PEX3 in
RT complex with a soluble fragment of PEX19.";
RL J. Biol. Chem. 285:25410-25417(2010).
CC -!- FUNCTION: Necessary for early peroxisomal biogenesis. Acts both as
CC a cytosolic chaperone and as an import receptor for peroxisomal
CC membrane proteins (PMPs). Binds and stabilizes newly synthesized
CC PMPs in the cytoplasm by interacting with their hydrophobic
CC membrane-spanning domains, and targets them to the peroxisome
CC membrane by binding to the integral membrane protein PEX3.
CC Excludes CDKN2A from the nucleus and prevents its interaction with
CC MDM2, which results in active degradation of TP53.
CC -!- SUBUNIT: Interacts with a broad range of peroxisomal membrane
CC proteins, including PEX3, PEX10, PEX11A, PEX11B, PEX12, PEX13,
CC PEX14 and PEX16, PXMP2/PMP22, PXMP4/PMP24, SLC25A17/PMP34,
CC ABCD1/ALDP, ABCD2/ALDRP, and ABCD3/PMP70. Also interacts with the
CC tumor suppressor CDKN2A/p19ARF.
CC -!- INTERACTION:
CC P33897:ABCD1; NbExp=3; IntAct=EBI-594747, EBI-81045;
CC P28288:ABCD3; NbExp=4; IntAct=EBI-594747, EBI-80992;
CC O96011:PEX11B; NbExp=11; IntAct=EBI-594747, EBI-594824;
CC O00623:PEX12; NbExp=2; IntAct=EBI-594747, EBI-594836;
CC Q92968:PEX13; NbExp=12; IntAct=EBI-594747, EBI-594849;
CC O75381:PEX14; NbExp=15; IntAct=EBI-594747, EBI-594898;
CC Q9Y5Y5:PEX16; NbExp=6; IntAct=EBI-594747, EBI-981985;
CC P28328:PEX2; NbExp=3; IntAct=EBI-594747, EBI-713978;
CC Q7Z412:PEX26; NbExp=6; IntAct=EBI-594747, EBI-752057;
CC P56589:PEX3; NbExp=20; IntAct=EBI-594747, EBI-594885;
CC Q9NR77:PXMP2; NbExp=2; IntAct=EBI-594747, EBI-1392944;
CC O43808:SLC25A17; NbExp=4; IntAct=EBI-594747, EBI-594912;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Peroxisome membrane; Lipid-
CC anchor; Cytoplasmic side. Note=Mainly cytoplasmic. Some fraction
CC membrane-associated to the outer surface of peroxisomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Experimental confirmation may be lacking for some
CC isoforms;
CC Name=1; Synonyms=PXF-all;
CC IsoId=P40855-1; Sequence=Displayed;
CC Note=The two main transcripts are PXF-all and PXF-delta-2;
CC Name=2; Synonyms=PXF-delta-2, PXF lacking exon 2;
CC IsoId=P40855-2; Sequence=Not described;
CC Note=The two main transcripts are PXF-all and PXF-delta-2;
CC Name=3; Synonyms=PXF-delta-4, PXF lacking exon 4;
CC IsoId=P40855-3; Sequence=Not described;
CC Name=4; Synonyms=PXF-delta-8, PXF lacking part of exon 8;
CC IsoId=P40855-4; Sequence=Not described;
CC Name=5;
CC IsoId=P40855-5; Sequence=VSP_012649;
CC Note=Incomplete sequence;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Isoform 1 is strongly
CC predominant in all tissues except in utero where isoform 2 is the
CC main form.
CC -!- DISEASE: Peroxisome biogenesis disorder complementation group 14
CC (PBD-CG14) [MIM:614886]: A peroxisomal disorder arising from a
CC failure of protein import into the peroxisomal membrane or matrix.
CC The peroxisome biogenesis disorders (PBD group) are genetically
CC heterogeneous with at least 14 distinct genetic groups as
CC concluded from complementation studies. Include disorders are:
CC Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD),
CC infantile Refsum disease (IRD), and classical rhizomelic
CC chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct
CC from RCDP and constitute a clinical continuum of overlapping
CC phenotypes known as the Zellweger spectrum (PBD-ZSS). Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- DISEASE: Peroxisome biogenesis disorder 12A (PBD12A) [MIM:614886]:
CC A fatal peroxisome biogenesis disorder belonging to the Zellweger
CC disease spectrum and clinically characterized by severe neurologic
CC dysfunction with profound psychomotor retardation, severe
CC hypotonia and neonatal seizures, craniofacial abnormalities, liver
CC dysfunction, and biochemically by the absence of peroxisomes.
CC Additional features include cardiovascular and skeletal defects,
CC renal cysts, ocular abnormalities, and hearing impairment. Most
CC severely affected individuals with the classic form of the disease
CC (classic Zellweger syndrome) die within the first year of life.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the peroxin-19 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB93469.1; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PEX19";
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DR EMBL; X75535; CAA53225.1; -; mRNA.
DR EMBL; Y09048; CAA70257.1; -; Genomic_DNA.
DR EMBL; AB018541; BAA76291.1; -; mRNA.
DR EMBL; AB062286; BAB93469.1; ALT_INIT; mRNA.
DR EMBL; BT006879; AAP35525.1; -; mRNA.
DR EMBL; AL513282; CAI12457.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52728.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52729.1; -; Genomic_DNA.
DR EMBL; BC000496; AAH00496.1; -; mRNA.
DR PIR; I37468; I37468.
DR RefSeq; NP_001180573.1; NM_001193644.1.
DR RefSeq; NP_002848.1; NM_002857.3.
DR UniGene; Hs.517232; -.
DR PDB; 2W85; NMR; -; B=66-77.
DR PDB; 2WL8; X-ray; 2.05 A; A/B/C/D=161-283.
DR PDB; 3AJB; X-ray; 2.50 A; B=1-44.
DR PDB; 3MK4; X-ray; 2.42 A; B=14-33.
DR PDBsum; 2W85; -.
DR PDBsum; 2WL8; -.
DR PDBsum; 3AJB; -.
DR PDBsum; 3MK4; -.
DR ProteinModelPortal; P40855; -.
DR SMR; P40855; 171-280.
DR DIP; DIP-24172N; -.
DR IntAct; P40855; 29.
DR MINT; MINT-241394; -.
DR STRING; 9606.ENSP00000357051; -.
DR TCDB; 9.A.17.1.2; the integral membrane peroxisomal protein importer-2 (ppi2) family.
DR PhosphoSite; P40855; -.
DR DMDM; 729723; -.
DR PaxDb; P40855; -.
DR PRIDE; P40855; -.
DR DNASU; 5824; -.
DR Ensembl; ENST00000368072; ENSP00000357051; ENSG00000162735.
DR GeneID; 5824; -.
DR KEGG; hsa:5824; -.
DR UCSC; uc001fvs.2; human.
DR CTD; 5824; -.
DR GeneCards; GC01M160246; -.
DR HGNC; HGNC:9713; PEX19.
DR HPA; HPA044837; -.
DR MIM; 600279; gene.
DR MIM; 614886; phenotype.
DR neXtProt; NX_P40855; -.
DR Orphanet; 772; Infantile Refsum disease.
DR Orphanet; 44; Neonatal adrenoleukodystrophy.
DR Orphanet; 912; Zellweger syndrome.
DR PharmGKB; PA34058; -.
DR eggNOG; NOG133983; -.
DR HOGENOM; HOG000038537; -.
DR HOVERGEN; HBG053573; -.
DR InParanoid; P40855; -.
DR KO; K13337; -.
DR OMA; NKAMEGL; -.
DR OrthoDB; EOG7P5T1P; -.
DR PhylomeDB; P40855; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR EvolutionaryTrace; P40855; -.
DR GeneWiki; PEX19; -.
DR GenomeRNAi; 5824; -.
DR NextBio; 22685; -.
DR PRO; PR:P40855; -.
DR ArrayExpress; P40855; -.
DR Bgee; P40855; -.
DR CleanEx; HS_PEX19; -.
DR Genevestigator; P40855; -.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016021; C:integral to membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IMP:UniProtKB.
DR GO; GO:0005778; C:peroxisomal membrane; IDA:UniProtKB.
DR GO; GO:0043234; C:protein complex; IDA:UniProtKB.
DR GO; GO:0036105; F:peroxisome membrane class-1 targeting sequence binding; IDA:UniProtKB.
DR GO; GO:0061077; P:chaperone-mediated protein folding; IDA:UniProtKB.
DR GO; GO:0072321; P:chaperone-mediated protein transport; IDA:UniProtKB.
DR GO; GO:1900131; P:negative regulation of lipid binding; IDA:UniProtKB.
DR GO; GO:0016559; P:peroxisome fission; IMP:UniProtKB.
DR GO; GO:0016557; P:peroxisome membrane biogenesis; IDA:UniProtKB.
DR GO; GO:0007031; P:peroxisome organization; IMP:UniProtKB.
DR GO; GO:0045046; P:protein import into peroxisome membrane; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR InterPro; IPR006708; Pex19.
DR PANTHER; PTHR12774; PTHR12774; 1.
DR Pfam; PF04614; Pex19; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Lipoprotein; Membrane; Methylation; Peroxisome;
KW Peroxisome biogenesis; Peroxisome biogenesis disorder; Phosphoprotein;
KW Prenylation; Reference proteome; Zellweger syndrome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 296 Peroxisomal biogenesis factor 19.
FT /FTId=PRO_0000218759.
FT PROPEP 297 299 Removed in mature form (Probable).
FT /FTId=PRO_0000393944.
FT REGION 2 91 Necessary for PEX19 function on
FT peroxisome biogenesis.
FT REGION 2 56 Docking to the peroxisome membrane and
FT binding to PEX3.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 35 35 Phosphoserine (By similarity).
FT MOD_RES 296 296 Cysteine methyl ester (Probable).
FT LIPID 296 296 S-farnesyl cysteine.
FT VAR_SEQ 1 59 MAAAEEGCSVGAEADRELEELLESALDDFDKAKPSPAPPST
FT TTAPDASGPQKRSPGDTA -> PPLRKAVVSGPKRTGNWRS
FT FW (in isoform 5).
FT /FTId=VSP_012649.
FT MUTAGEN 29 29 F->A: Abolishes binding to PEX3.
FT MUTAGEN 296 299 Missing: Abolishes binding to PEX10,
FT PEX11B, PEX12 and PEX13. Does not affect
FT binding to PEX3 and PEX16.
FT MUTAGEN 296 296 C->A: Slightly inhibits PEX19 function on
FT peroxisome biogenesis.
FT MUTAGEN 296 296 C->S: Abolishes farnesylation. Abolishes
FT PEX19 function on peroxisome biogenesis.
FT Does not affect binding to ABCD1, ABCD2
FT and ABCD3.
FT HELIX 16 27
FT HELIX 28 31
FT HELIX 67 76
FT HELIX 172 182
FT HELIX 185 196
FT HELIX 199 206
FT HELIX 207 209
FT HELIX 212 234
FT HELIX 241 260
FT HELIX 266 268
SQ SEQUENCE 299 AA; 32807 MW; 399AF6B79F219100 CRC64;
MAAAEEGCSV GAEADRELEE LLESALDDFD KAKPSPAPPS TTTAPDASGP QKRSPGDTAK
DALFASQEKF FQELFDSELA SQATAEFEKA MKELAEEEPH LVEQFQKLSE AAGRVGSDMT
SQQEFTSCLK ETLSGLAKNA TDLQNSSMSE EELTKAMEGL GMDEGDGEGN ILPIMQSIMQ
NLLSKDVLYP SLKEITEKYP EWLQSHRESL PPEQFEKYQE QHSVMCKICE QFEAETPTDS
ETTQKARFEM VLDLMQQLQD LGHPPKELAG EMPPGLNFDL DALNLSGPPG ASGEQCLIM
//
ID PEX19_HUMAN Reviewed; 299 AA.
AC P40855; D3DVE7; Q5QNY4; Q8NI97;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 1.
DT 22-JAN-2014, entry version 141.
DE RecName: Full=Peroxisomal biogenesis factor 19;
DE AltName: Full=33 kDa housekeeping protein;
DE AltName: Full=Peroxin-19;
DE AltName: Full=Peroxisomal farnesylated protein;
DE Flags: Precursor;
GN Name=PEX19; Synonyms=HK33, PXF; ORFNames=OK/SW-cl.22;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Ovary, and Placenta;
RX PubMed=8076834; DOI=10.1016/0378-1119(94)90308-5;
RA Braun A., Kammerer S., Weissenhorn W., Weiss E.H., Cleve H.;
RT "Sequence of a putative human housekeeping gene (HK33) localized on
RT chromosome 1.";
RL Gene 146:291-295(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, ISOPRENYLATION AT CYS-296, AND
RP MUTAGENESIS OF CYS-296.
RC TISSUE=Leukocyte, and Placenta;
RX PubMed=9339377; DOI=10.1006/geno.1997.4914;
RA Kammerer S., Arnold N., Gutensohn W., Mewes H.-W., Kunau W.-H.,
RA Hoefler G., Roscher A.A., Braun A.;
RT "Genomic organization and molecular characterization of a gene
RT encoding HsPXF, a human peroxisomal farnesylated protein.";
RL Genomics 45:200-210(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ISOPRENYLATION AT CYS-296,
RP MUTAGENESIS OF CYS-296, SUBCELLULAR LOCATION, FUNCTION, AND
RP INVOLVEMENT IN PBD12A.
RC TISSUE=Liver;
RX PubMed=10051604; DOI=10.1073/pnas.96.5.2116;
RA Matsuzono Y., Kinoshita N., Tamura S., Shimozawa N., Hamasaki M.,
RA Ghaedi K., Wanders R.J.A., Suzuki Y., Kondo N., Fujiki Y.;
RT "Human PEX19: cDNA cloning by functional complementation, mutation
RT analysis in a patient with Zellweger syndrome, and potential role in
RT peroxisomal membrane assembly.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:2116-2121(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-
RT reactive CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP INTERACTION WITH ABCD1; ABCD2 AND ABCD3, AND MUTAGENESIS OF CYS-296.
RC TISSUE=Brain;
RX PubMed=10777694; DOI=10.1006/bbrc.2000.2572;
RA Gloeckner C.J., Mayerhofer P.U., Landgraf P., Muntau A.C.,
RA Holzinger A., Gerber J.-K., Kammerer S., Adamski J., Roscher A.A.;
RT "Human adrenoleukodystrophy protein and related peroxisomal ABC
RT transporters interact with the peroxisomal assembly protein PEX19p.";
RL Biochem. Biophys. Res. Commun. 271:144-150(2000).
RN [10]
RP FUNCTION, MUTAGENESIS OF CYS-296, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH ABCD1; ABCD2; ABCD3; PEX3; PEX10; PEX11A; PEX11B;
RP PEX12; PEX13; PEX14; PEX16; PXMP2; PXMP4 AND SLC25A17.
RX PubMed=10704444; DOI=10.1083/jcb.148.5.931;
RA Sacksteder K.A., Jones J.M., South S.T., Li X., Liu Y., Gould S.J.;
RT "PEX19 binds multiple peroxisomal membrane proteins, is predominantly
RT cytoplasmic, and is required for peroxisome membrane synthesis.";
RL J. Cell Biol. 148:931-944(2000).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CDKN2A.
RC TISSUE=Testis;
RX PubMed=11259404; DOI=10.1074/jbc.C100011200;
RA Sugihara T., Kaul S.C., Kato J.-Y., Reddel R.R., Nomura H., Wadhwa R.;
RT "Pex19p dampens the p19ARF-p53-p21WAF1 tumor suppressor pathway.";
RL J. Biol. Chem. 276:18649-18652(2001).
RN [12]
RP INTERACTION WITH PEX3; PEX10; PEX11B; PEX12; PEX13 AND PEX16, AND
RP MUTAGENESIS OF 296-CYS--MET-299.
RX PubMed=11390669; DOI=10.1128/MCB.21.13.4413-4424.2001;
RA Fransen M., Wylin T., Brees C., Mannaerts G.P., Van Veldhoven P.P.;
RT "Human pex19p binds peroxisomal integral membrane proteins at regions
RT distinct from their sorting sequences.";
RL Mol. Cell. Biol. 21:4413-4424(2001).
RN [13]
RP FUNCTION, AND INTERACTION WITH ABCD1; ABCD2; ABCD3 AND PEX3.
RX PubMed=11883941; DOI=10.1006/bbrc.2002.6568;
RA Mayerhofer P.U., Kattenfeld T., Roscher A.A., Muntau A.C.;
RT "Two splice variants of human PEX19 exhibit distinct functions in
RT peroxisomal assembly.";
RL Biochem. Biophys. Res. Commun. 291:1180-1186(2002).
RN [14]
RP FUNCTION, INTERACTION WITH PEX3, AND SUBCELLULAR LOCATION.
RX PubMed=15007061; DOI=10.1083/jcb.200311131;
RA Fang Y., Morrell J.C., Jones J.M., Gould S.J.;
RT "PEX3 functions as a PEX19 docking factor in the import of class I
RT peroxisomal membrane proteins.";
RL J. Cell Biol. 164:863-875(2004).
RN [15]
RP FUNCTION, AND INTERACTION WITH PEX11B; PEX16; PXMP2; PXMP4; SLC25A17
RP AND ABCD3.
RX PubMed=14709540; DOI=10.1083/jcb.200304111;
RA Jones J.M., Morrell J.C., Gould S.J.;
RT "PEX19 is a predominantly cytosolic chaperone and import receptor for
RT class 1 peroxisomal membrane proteins.";
RL J. Cell Biol. 164:57-67(2004).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
RP INVOLVEMENT IN PBD-CG14.
RX PubMed=20683989; DOI=10.1002/ajmg.a.33560;
RA Mohamed S., El-Meleagy E., Nasr A., Ebberink M.S., Wanders R.J.,
RA Waterham H.R.;
RT "A mutation in PEX19 causes a severe clinical phenotype in a patient
RT with peroxisomal biogenesis disorder.";
RL Am. J. Med. Genet. A 152:2318-2321(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [20]
RP STRUCTURE BY NMR OF 66-77 IN COMPLEX WITH PEX14.
RX PubMed=19197237; DOI=10.1038/emboj.2009.7;
RA Neufeld C., Filipp F.V., Simon B., Neuhaus A., Schueller N., David C.,
RA Kooshapur H., Madl T., Erdmann R., Schliebs W., Wilmanns M.,
RA Sattler M.;
RT "Structural basis for competitive interactions of Pex14 with the
RT import receptors Pex5 and Pex19.";
RL EMBO J. 28:745-754(2009).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1-44 IN COMPLEX WITH PEX3,
RP AND SUBUNIT.
RX PubMed=21102411; DOI=10.1038/emboj.2010.293;
RA Sato Y., Shibata H., Nakatsu T., Nakano H., Kashiwayama Y.,
RA Imanaka T., Kato H.;
RT "Structural basis for docking of peroxisomal membrane protein carrier
RT Pex19p onto its receptor Pex3p.";
RL EMBO J. 29:4083-4093(2010).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.42 ANGSTROMS) OF 13-33 IN COMPLEX WITH PEX3,
RP SUBUNIT, AND MUTAGENESIS OF PHE-29.
RX PubMed=20554521; DOI=10.1074/jbc.M110.138503;
RA Schmidt F., Treiber N., Zocher G., Bjelic S., Steinmetz M.O.,
RA Kalbacher H., Stehle T., Dodt G.;
RT "Insights into peroxisome function from the structure of PEX3 in
RT complex with a soluble fragment of PEX19.";
RL J. Biol. Chem. 285:25410-25417(2010).
CC -!- FUNCTION: Necessary for early peroxisomal biogenesis. Acts both as
CC a cytosolic chaperone and as an import receptor for peroxisomal
CC membrane proteins (PMPs). Binds and stabilizes newly synthesized
CC PMPs in the cytoplasm by interacting with their hydrophobic
CC membrane-spanning domains, and targets them to the peroxisome
CC membrane by binding to the integral membrane protein PEX3.
CC Excludes CDKN2A from the nucleus and prevents its interaction with
CC MDM2, which results in active degradation of TP53.
CC -!- SUBUNIT: Interacts with a broad range of peroxisomal membrane
CC proteins, including PEX3, PEX10, PEX11A, PEX11B, PEX12, PEX13,
CC PEX14 and PEX16, PXMP2/PMP22, PXMP4/PMP24, SLC25A17/PMP34,
CC ABCD1/ALDP, ABCD2/ALDRP, and ABCD3/PMP70. Also interacts with the
CC tumor suppressor CDKN2A/p19ARF.
CC -!- INTERACTION:
CC P33897:ABCD1; NbExp=3; IntAct=EBI-594747, EBI-81045;
CC P28288:ABCD3; NbExp=4; IntAct=EBI-594747, EBI-80992;
CC O96011:PEX11B; NbExp=11; IntAct=EBI-594747, EBI-594824;
CC O00623:PEX12; NbExp=2; IntAct=EBI-594747, EBI-594836;
CC Q92968:PEX13; NbExp=12; IntAct=EBI-594747, EBI-594849;
CC O75381:PEX14; NbExp=15; IntAct=EBI-594747, EBI-594898;
CC Q9Y5Y5:PEX16; NbExp=6; IntAct=EBI-594747, EBI-981985;
CC P28328:PEX2; NbExp=3; IntAct=EBI-594747, EBI-713978;
CC Q7Z412:PEX26; NbExp=6; IntAct=EBI-594747, EBI-752057;
CC P56589:PEX3; NbExp=20; IntAct=EBI-594747, EBI-594885;
CC Q9NR77:PXMP2; NbExp=2; IntAct=EBI-594747, EBI-1392944;
CC O43808:SLC25A17; NbExp=4; IntAct=EBI-594747, EBI-594912;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Peroxisome membrane; Lipid-
CC anchor; Cytoplasmic side. Note=Mainly cytoplasmic. Some fraction
CC membrane-associated to the outer surface of peroxisomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Experimental confirmation may be lacking for some
CC isoforms;
CC Name=1; Synonyms=PXF-all;
CC IsoId=P40855-1; Sequence=Displayed;
CC Note=The two main transcripts are PXF-all and PXF-delta-2;
CC Name=2; Synonyms=PXF-delta-2, PXF lacking exon 2;
CC IsoId=P40855-2; Sequence=Not described;
CC Note=The two main transcripts are PXF-all and PXF-delta-2;
CC Name=3; Synonyms=PXF-delta-4, PXF lacking exon 4;
CC IsoId=P40855-3; Sequence=Not described;
CC Name=4; Synonyms=PXF-delta-8, PXF lacking part of exon 8;
CC IsoId=P40855-4; Sequence=Not described;
CC Name=5;
CC IsoId=P40855-5; Sequence=VSP_012649;
CC Note=Incomplete sequence;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Isoform 1 is strongly
CC predominant in all tissues except in utero where isoform 2 is the
CC main form.
CC -!- DISEASE: Peroxisome biogenesis disorder complementation group 14
CC (PBD-CG14) [MIM:614886]: A peroxisomal disorder arising from a
CC failure of protein import into the peroxisomal membrane or matrix.
CC The peroxisome biogenesis disorders (PBD group) are genetically
CC heterogeneous with at least 14 distinct genetic groups as
CC concluded from complementation studies. Include disorders are:
CC Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD),
CC infantile Refsum disease (IRD), and classical rhizomelic
CC chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct
CC from RCDP and constitute a clinical continuum of overlapping
CC phenotypes known as the Zellweger spectrum (PBD-ZSS). Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- DISEASE: Peroxisome biogenesis disorder 12A (PBD12A) [MIM:614886]:
CC A fatal peroxisome biogenesis disorder belonging to the Zellweger
CC disease spectrum and clinically characterized by severe neurologic
CC dysfunction with profound psychomotor retardation, severe
CC hypotonia and neonatal seizures, craniofacial abnormalities, liver
CC dysfunction, and biochemically by the absence of peroxisomes.
CC Additional features include cardiovascular and skeletal defects,
CC renal cysts, ocular abnormalities, and hearing impairment. Most
CC severely affected individuals with the classic form of the disease
CC (classic Zellweger syndrome) die within the first year of life.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the peroxin-19 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB93469.1; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PEX19";
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DR EMBL; X75535; CAA53225.1; -; mRNA.
DR EMBL; Y09048; CAA70257.1; -; Genomic_DNA.
DR EMBL; AB018541; BAA76291.1; -; mRNA.
DR EMBL; AB062286; BAB93469.1; ALT_INIT; mRNA.
DR EMBL; BT006879; AAP35525.1; -; mRNA.
DR EMBL; AL513282; CAI12457.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52728.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52729.1; -; Genomic_DNA.
DR EMBL; BC000496; AAH00496.1; -; mRNA.
DR PIR; I37468; I37468.
DR RefSeq; NP_001180573.1; NM_001193644.1.
DR RefSeq; NP_002848.1; NM_002857.3.
DR UniGene; Hs.517232; -.
DR PDB; 2W85; NMR; -; B=66-77.
DR PDB; 2WL8; X-ray; 2.05 A; A/B/C/D=161-283.
DR PDB; 3AJB; X-ray; 2.50 A; B=1-44.
DR PDB; 3MK4; X-ray; 2.42 A; B=14-33.
DR PDBsum; 2W85; -.
DR PDBsum; 2WL8; -.
DR PDBsum; 3AJB; -.
DR PDBsum; 3MK4; -.
DR ProteinModelPortal; P40855; -.
DR SMR; P40855; 171-280.
DR DIP; DIP-24172N; -.
DR IntAct; P40855; 29.
DR MINT; MINT-241394; -.
DR STRING; 9606.ENSP00000357051; -.
DR TCDB; 9.A.17.1.2; the integral membrane peroxisomal protein importer-2 (ppi2) family.
DR PhosphoSite; P40855; -.
DR DMDM; 729723; -.
DR PaxDb; P40855; -.
DR PRIDE; P40855; -.
DR DNASU; 5824; -.
DR Ensembl; ENST00000368072; ENSP00000357051; ENSG00000162735.
DR GeneID; 5824; -.
DR KEGG; hsa:5824; -.
DR UCSC; uc001fvs.2; human.
DR CTD; 5824; -.
DR GeneCards; GC01M160246; -.
DR HGNC; HGNC:9713; PEX19.
DR HPA; HPA044837; -.
DR MIM; 600279; gene.
DR MIM; 614886; phenotype.
DR neXtProt; NX_P40855; -.
DR Orphanet; 772; Infantile Refsum disease.
DR Orphanet; 44; Neonatal adrenoleukodystrophy.
DR Orphanet; 912; Zellweger syndrome.
DR PharmGKB; PA34058; -.
DR eggNOG; NOG133983; -.
DR HOGENOM; HOG000038537; -.
DR HOVERGEN; HBG053573; -.
DR InParanoid; P40855; -.
DR KO; K13337; -.
DR OMA; NKAMEGL; -.
DR OrthoDB; EOG7P5T1P; -.
DR PhylomeDB; P40855; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR EvolutionaryTrace; P40855; -.
DR GeneWiki; PEX19; -.
DR GenomeRNAi; 5824; -.
DR NextBio; 22685; -.
DR PRO; PR:P40855; -.
DR ArrayExpress; P40855; -.
DR Bgee; P40855; -.
DR CleanEx; HS_PEX19; -.
DR Genevestigator; P40855; -.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016021; C:integral to membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IMP:UniProtKB.
DR GO; GO:0005778; C:peroxisomal membrane; IDA:UniProtKB.
DR GO; GO:0043234; C:protein complex; IDA:UniProtKB.
DR GO; GO:0036105; F:peroxisome membrane class-1 targeting sequence binding; IDA:UniProtKB.
DR GO; GO:0061077; P:chaperone-mediated protein folding; IDA:UniProtKB.
DR GO; GO:0072321; P:chaperone-mediated protein transport; IDA:UniProtKB.
DR GO; GO:1900131; P:negative regulation of lipid binding; IDA:UniProtKB.
DR GO; GO:0016559; P:peroxisome fission; IMP:UniProtKB.
DR GO; GO:0016557; P:peroxisome membrane biogenesis; IDA:UniProtKB.
DR GO; GO:0007031; P:peroxisome organization; IMP:UniProtKB.
DR GO; GO:0045046; P:protein import into peroxisome membrane; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR InterPro; IPR006708; Pex19.
DR PANTHER; PTHR12774; PTHR12774; 1.
DR Pfam; PF04614; Pex19; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Lipoprotein; Membrane; Methylation; Peroxisome;
KW Peroxisome biogenesis; Peroxisome biogenesis disorder; Phosphoprotein;
KW Prenylation; Reference proteome; Zellweger syndrome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 296 Peroxisomal biogenesis factor 19.
FT /FTId=PRO_0000218759.
FT PROPEP 297 299 Removed in mature form (Probable).
FT /FTId=PRO_0000393944.
FT REGION 2 91 Necessary for PEX19 function on
FT peroxisome biogenesis.
FT REGION 2 56 Docking to the peroxisome membrane and
FT binding to PEX3.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 35 35 Phosphoserine (By similarity).
FT MOD_RES 296 296 Cysteine methyl ester (Probable).
FT LIPID 296 296 S-farnesyl cysteine.
FT VAR_SEQ 1 59 MAAAEEGCSVGAEADRELEELLESALDDFDKAKPSPAPPST
FT TTAPDASGPQKRSPGDTA -> PPLRKAVVSGPKRTGNWRS
FT FW (in isoform 5).
FT /FTId=VSP_012649.
FT MUTAGEN 29 29 F->A: Abolishes binding to PEX3.
FT MUTAGEN 296 299 Missing: Abolishes binding to PEX10,
FT PEX11B, PEX12 and PEX13. Does not affect
FT binding to PEX3 and PEX16.
FT MUTAGEN 296 296 C->A: Slightly inhibits PEX19 function on
FT peroxisome biogenesis.
FT MUTAGEN 296 296 C->S: Abolishes farnesylation. Abolishes
FT PEX19 function on peroxisome biogenesis.
FT Does not affect binding to ABCD1, ABCD2
FT and ABCD3.
FT HELIX 16 27
FT HELIX 28 31
FT HELIX 67 76
FT HELIX 172 182
FT HELIX 185 196
FT HELIX 199 206
FT HELIX 207 209
FT HELIX 212 234
FT HELIX 241 260
FT HELIX 266 268
SQ SEQUENCE 299 AA; 32807 MW; 399AF6B79F219100 CRC64;
MAAAEEGCSV GAEADRELEE LLESALDDFD KAKPSPAPPS TTTAPDASGP QKRSPGDTAK
DALFASQEKF FQELFDSELA SQATAEFEKA MKELAEEEPH LVEQFQKLSE AAGRVGSDMT
SQQEFTSCLK ETLSGLAKNA TDLQNSSMSE EELTKAMEGL GMDEGDGEGN ILPIMQSIMQ
NLLSKDVLYP SLKEITEKYP EWLQSHRESL PPEQFEKYQE QHSVMCKICE QFEAETPTDS
ETTQKARFEM VLDLMQQLQD LGHPPKELAG EMPPGLNFDL DALNLSGPPG ASGEQCLIM
//
MIM
600279
*RECORD*
*FIELD* NO
600279
*FIELD* TI
*600279 PEROXISOME BIOGENESIS FACTOR 19; PEX19
;;PEROXISOMAL FARNESYLATED PROTEIN; PXF;;
read moreHOUSEKEEPING GENE, 33-KD; HK33;;
HOUSEKEEPING GENE 33;;
PEROXIN 19;;
D1S2223E
*FIELD* TX
DESCRIPTION
The PEX19 gene encodes peroxisomal farnesylated protein, which plays a
role in peroxisomal membrane synthesis (Gotte et al., 1998).
CLONING
James et al. (1994) identified in hamster a farnesylated protein, called
peroxisomal farnesylated protein or PxF, that localized to the outer
surface of peroxisomes. Kammerer et al. (1997) found that the protein
sequence of PxF is 93% identical to that of HK33, a human protein
identified by Braun et al. (1994). Braun et al. (1994) reported that
HK33 is a predicted 299-amino acid protein with a mass of 33 kD by
SDS-PAGE. Northern blot analysis and RT-PCR revealed that HK33 is
expressed ubiquitously as 2.2 to 2.5-kb and 4-kb mRNAs. The fact that
the gene was transcribed in all cells and tissues tested indicated its
status as a housekeeping gene. Braun et al. (1994) demonstrated that at
least 2 different HK33 transcripts result from the use of alternative
polyadenylation sites.
Kammerer et al. (1997) isolated 4 variant HK33, or PEX19, mRNAs produced
by alternative splicing. They found that the proteins encoded by 2 of
the splice variants were farnesylated in vitro. Using immunoelectron
microscopy, Kammerer et al. (1997) showed that PEX19 is localized to the
cytoplasmic surface of peroxisomes in liver cells.
Gotte et al. (1998) identified HK33 as the putative human ortholog of a
S. cerevisiae gene, Pex19p. Pex19p encodes an oleic acid-inducible,
farnesylated protein of 39.7 kD that is essential for peroxisome
biogenesis. They showed that the essential C-terminal region of Pex19p
could be replaced by the corresponding region of HK33. Kammerer et al.
(1997) stated that the peroxisomal localization of PEX19 and its
similarity to Pex19p suggest that PEX19 is involved in the process of
peroxisomal biogenesis or assembly.
By functional complementation of peroxisome deficiency of a mutant
hamster ovary cell line, ZP119, defective in import of both matrix and
membrane proteins, Matsuzono et al. (1999) isolated a human PEX19 cDNA.
A stable transformant of ZP119 with human PEX19 was morphologically and
biochemically restored for peroxisome biogenesis.
GENE STRUCTURE
Kammerer et al. (1997) determined that the PEX19 gene contains 8 exons
and spans approximately 9 kb. The basal promoter is located within the
first 239 bp upstream of the coding region.
MAPPING
By analysis of a somatic cell hybrid panel, Braun et al. (1994) mapped
the PEX19 gene to chromosome 1. Using fluorescence in situ
hybridization, Kammerer et al. (1997) refined the map position to
chromosome 1q22.
MOLECULAR GENETICS
Kinoshita et al. (1998) identified complementation group J (CGJ) from
patients with a peroxisome biogenesis disorder (PBD), such as Zellweger
syndrome (PBD12A; 614886). Two Chinese hamster ovary cell mutants were
also found to belong to this group. In no CGJ mutant cell were
peroxisomal ghosts found.
Matsuzono et al. (1999) found that human PEX19 expression restored
peroxisomal protein import in fibroblasts from a patient with Zellweger
syndrome of CGJ. This patient was found to be homozygous for an
inactivating mutation, a 1-bp insertion (600279.0001). These results
demonstrated that PEX19 is the causative gene for CGJ PBD and suggested
that the C-terminal part of the PEX19 protein, including the CAAX
homology box, is required for its biologic function. Moreover, the PEX19
protein is apparently involved in the initial stage of peroxisome
membrane assembly, before the import of matrix protein.
Mohamed et al. (2010) identified a homozygous frameshift mutation in the
PEX19 gene (600279.0002) in an infant girl, born of consanguineous Saudi
parents, with Zellweger syndrome of complementation group J. She had
neonatal hypotonia, global developmental delay, and multisystem
involvement, resulting in death at age 16 months.
*FIELD* AV
.0001
PEROXISOME BIOGENESIS DISORDER 12A (ZELLWEGER)
PEX19, 1-BP INS, 764A
In a patient with Zellweger syndrome of complementation group J (PBD12A;
614886), Matsuzono et al. (1999) identified homozygosity for a 1-bp
insertion (764insA) in the codon for met255 of the PEX19 gene. The
mutation resulted in a frameshift, inducing a 24-amino acid sequence
entirely distinct from that of normal protein.
.0002
PEROXISOME BIOGENESIS DISORDER 12A (ZELLWEGER)
PEX19, 1-BP DEL, 320A
In an infant girl, born of consanguineous Saudi parents, with Zellweger
syndrome of complementation group J (PBD12A; 614886), Mohamed et al.
(2010) identified a homozygous 1-bp deletion (320delA) in the PEX19
gene, resulting in a frameshift. The patient had neonatal hypotonia,
poor growth, and subtle dysmorphic features, including cranial
asymmetry, triangular face, low hairline, open fontanels, and broad
nasal bridge. Laboratory studies showed elevated liver enzymes,
hyperbilirubinemia, and a very long chain fatty acid (VLCFA) profile
consistent with a PBD. Brain imaging showed cerebral atrophy, cortical
changes, and diffuse demyelination. There was a complete absence of
peroxisomes in patient fibroblasts. The patient had a severe clinical
course, complicated by global developmental delay, refractory seizures,
renal tubular defect, multiple gallstones, and recurrent
hospitalizations. She died of sepsis at age 16 months.
*FIELD* RF
1. Braun, A.; Kammerer, S.; Weissenhorn, W.; Weiss, E. H.; Cleve,
H.: Sequence of a putative human housekeeping gene (HK33) localized
on chromosome 1. Gene 146: 291-295, 1994.
2. Gotte, K.; Girzalsky, W.; Linkert, M.; Baumgart, E.; Kammerer,
S.; Kunau, W.-H.; Erdmann, R.: Pex19p, a farnesylated protein essential
for peroxisome biogenesis. Molec. Cell. Biol. 18: 616-628, 1998.
3. James, G. L.; Goldstein, J. L.; Pathak, R. K.; Anderson, R. G.
W.; Brown, M. S.: PxF, a prenylated protein of peroxisomes J. Biol.
Chem. 269: 14182-14190, 1994.
4. Kammerer, S.; Arnold, N.; Gutensohn, W.; Mewes, H.-W.; Kunau, W.-H.;
Hofler, G.; Roscher, A. A.; Braun, A.: Genomic organization and molecular
characterization of a gene encoding HsPXF, a human peroxisomal farnesylated
protein. Genomics 45: 200-210, 1997.
5. Kinoshita, N.; Ghaedi, K.; Shimozawa, N.; Wanders, R. J. A.; Matsuzono,
Y.; Imanaka, T.; Okumoto, K.; Suzuki, Y.; Kondo, N.; Fujiki, Y.:
Newly identified Chinese hamster ovary cell mutants are defective
in biogenesis of peroxisomal membrane vesicles (peroxisomal ghosts),
representing a novel complementation group in mammals J. Biol. Chem. 273:
24122-24130, 1998.
6. Matsuzono, Y.; Kinoshita, N.; Tamura, S.; Shimozawa, N.; Hamasaki,
M.; Ghaedi, K.; Wanders, R. J. A.; Suzuki, Y.; Kondo, N.; Fujiki,
Y.: Human PEX19: cDNA cloning by functional complementation, mutation
analysis in a patient with Zellweger syndrome, and potential role
in peroxisomal membrane assembly. Proc. Nat. Acad. Sci. 96: 2116-2121,
1999.
7. Mohamed, S.; El-Meleagy, E.; Nasr, A.; Ebberink, M. S.; Wanders,
R. J. A.; Waterham, H. R.: A mutation in PEX19 causes a severe clinical
phenotype in a patient with peroxisomal biogenesis disorder. Am.
J. Med. Genet. 152A: 2318-2321, 2010.
*FIELD* CN
Cassandra L. Kniffin - updated: 6/15/2011
Victor A. McKusick - updated: 4/6/1999
*FIELD* CD
Victor A. McKusick: 1/5/1995
*FIELD* ED
alopez: 10/25/2012
alopez: 10/24/2012
wwang: 7/1/2011
ckniffin: 6/15/2011
tkritzer: 7/20/2004
alopez: 3/17/2004
mgross: 4/7/1999
mgross: 4/6/1999
alopez: 2/5/1999
joanna: 5/7/1997
mark: 5/9/1995
carol: 1/5/1995
*RECORD*
*FIELD* NO
600279
*FIELD* TI
*600279 PEROXISOME BIOGENESIS FACTOR 19; PEX19
;;PEROXISOMAL FARNESYLATED PROTEIN; PXF;;
read moreHOUSEKEEPING GENE, 33-KD; HK33;;
HOUSEKEEPING GENE 33;;
PEROXIN 19;;
D1S2223E
*FIELD* TX
DESCRIPTION
The PEX19 gene encodes peroxisomal farnesylated protein, which plays a
role in peroxisomal membrane synthesis (Gotte et al., 1998).
CLONING
James et al. (1994) identified in hamster a farnesylated protein, called
peroxisomal farnesylated protein or PxF, that localized to the outer
surface of peroxisomes. Kammerer et al. (1997) found that the protein
sequence of PxF is 93% identical to that of HK33, a human protein
identified by Braun et al. (1994). Braun et al. (1994) reported that
HK33 is a predicted 299-amino acid protein with a mass of 33 kD by
SDS-PAGE. Northern blot analysis and RT-PCR revealed that HK33 is
expressed ubiquitously as 2.2 to 2.5-kb and 4-kb mRNAs. The fact that
the gene was transcribed in all cells and tissues tested indicated its
status as a housekeeping gene. Braun et al. (1994) demonstrated that at
least 2 different HK33 transcripts result from the use of alternative
polyadenylation sites.
Kammerer et al. (1997) isolated 4 variant HK33, or PEX19, mRNAs produced
by alternative splicing. They found that the proteins encoded by 2 of
the splice variants were farnesylated in vitro. Using immunoelectron
microscopy, Kammerer et al. (1997) showed that PEX19 is localized to the
cytoplasmic surface of peroxisomes in liver cells.
Gotte et al. (1998) identified HK33 as the putative human ortholog of a
S. cerevisiae gene, Pex19p. Pex19p encodes an oleic acid-inducible,
farnesylated protein of 39.7 kD that is essential for peroxisome
biogenesis. They showed that the essential C-terminal region of Pex19p
could be replaced by the corresponding region of HK33. Kammerer et al.
(1997) stated that the peroxisomal localization of PEX19 and its
similarity to Pex19p suggest that PEX19 is involved in the process of
peroxisomal biogenesis or assembly.
By functional complementation of peroxisome deficiency of a mutant
hamster ovary cell line, ZP119, defective in import of both matrix and
membrane proteins, Matsuzono et al. (1999) isolated a human PEX19 cDNA.
A stable transformant of ZP119 with human PEX19 was morphologically and
biochemically restored for peroxisome biogenesis.
GENE STRUCTURE
Kammerer et al. (1997) determined that the PEX19 gene contains 8 exons
and spans approximately 9 kb. The basal promoter is located within the
first 239 bp upstream of the coding region.
MAPPING
By analysis of a somatic cell hybrid panel, Braun et al. (1994) mapped
the PEX19 gene to chromosome 1. Using fluorescence in situ
hybridization, Kammerer et al. (1997) refined the map position to
chromosome 1q22.
MOLECULAR GENETICS
Kinoshita et al. (1998) identified complementation group J (CGJ) from
patients with a peroxisome biogenesis disorder (PBD), such as Zellweger
syndrome (PBD12A; 614886). Two Chinese hamster ovary cell mutants were
also found to belong to this group. In no CGJ mutant cell were
peroxisomal ghosts found.
Matsuzono et al. (1999) found that human PEX19 expression restored
peroxisomal protein import in fibroblasts from a patient with Zellweger
syndrome of CGJ. This patient was found to be homozygous for an
inactivating mutation, a 1-bp insertion (600279.0001). These results
demonstrated that PEX19 is the causative gene for CGJ PBD and suggested
that the C-terminal part of the PEX19 protein, including the CAAX
homology box, is required for its biologic function. Moreover, the PEX19
protein is apparently involved in the initial stage of peroxisome
membrane assembly, before the import of matrix protein.
Mohamed et al. (2010) identified a homozygous frameshift mutation in the
PEX19 gene (600279.0002) in an infant girl, born of consanguineous Saudi
parents, with Zellweger syndrome of complementation group J. She had
neonatal hypotonia, global developmental delay, and multisystem
involvement, resulting in death at age 16 months.
*FIELD* AV
.0001
PEROXISOME BIOGENESIS DISORDER 12A (ZELLWEGER)
PEX19, 1-BP INS, 764A
In a patient with Zellweger syndrome of complementation group J (PBD12A;
614886), Matsuzono et al. (1999) identified homozygosity for a 1-bp
insertion (764insA) in the codon for met255 of the PEX19 gene. The
mutation resulted in a frameshift, inducing a 24-amino acid sequence
entirely distinct from that of normal protein.
.0002
PEROXISOME BIOGENESIS DISORDER 12A (ZELLWEGER)
PEX19, 1-BP DEL, 320A
In an infant girl, born of consanguineous Saudi parents, with Zellweger
syndrome of complementation group J (PBD12A; 614886), Mohamed et al.
(2010) identified a homozygous 1-bp deletion (320delA) in the PEX19
gene, resulting in a frameshift. The patient had neonatal hypotonia,
poor growth, and subtle dysmorphic features, including cranial
asymmetry, triangular face, low hairline, open fontanels, and broad
nasal bridge. Laboratory studies showed elevated liver enzymes,
hyperbilirubinemia, and a very long chain fatty acid (VLCFA) profile
consistent with a PBD. Brain imaging showed cerebral atrophy, cortical
changes, and diffuse demyelination. There was a complete absence of
peroxisomes in patient fibroblasts. The patient had a severe clinical
course, complicated by global developmental delay, refractory seizures,
renal tubular defect, multiple gallstones, and recurrent
hospitalizations. She died of sepsis at age 16 months.
*FIELD* RF
1. Braun, A.; Kammerer, S.; Weissenhorn, W.; Weiss, E. H.; Cleve,
H.: Sequence of a putative human housekeeping gene (HK33) localized
on chromosome 1. Gene 146: 291-295, 1994.
2. Gotte, K.; Girzalsky, W.; Linkert, M.; Baumgart, E.; Kammerer,
S.; Kunau, W.-H.; Erdmann, R.: Pex19p, a farnesylated protein essential
for peroxisome biogenesis. Molec. Cell. Biol. 18: 616-628, 1998.
3. James, G. L.; Goldstein, J. L.; Pathak, R. K.; Anderson, R. G.
W.; Brown, M. S.: PxF, a prenylated protein of peroxisomes J. Biol.
Chem. 269: 14182-14190, 1994.
4. Kammerer, S.; Arnold, N.; Gutensohn, W.; Mewes, H.-W.; Kunau, W.-H.;
Hofler, G.; Roscher, A. A.; Braun, A.: Genomic organization and molecular
characterization of a gene encoding HsPXF, a human peroxisomal farnesylated
protein. Genomics 45: 200-210, 1997.
5. Kinoshita, N.; Ghaedi, K.; Shimozawa, N.; Wanders, R. J. A.; Matsuzono,
Y.; Imanaka, T.; Okumoto, K.; Suzuki, Y.; Kondo, N.; Fujiki, Y.:
Newly identified Chinese hamster ovary cell mutants are defective
in biogenesis of peroxisomal membrane vesicles (peroxisomal ghosts),
representing a novel complementation group in mammals J. Biol. Chem. 273:
24122-24130, 1998.
6. Matsuzono, Y.; Kinoshita, N.; Tamura, S.; Shimozawa, N.; Hamasaki,
M.; Ghaedi, K.; Wanders, R. J. A.; Suzuki, Y.; Kondo, N.; Fujiki,
Y.: Human PEX19: cDNA cloning by functional complementation, mutation
analysis in a patient with Zellweger syndrome, and potential role
in peroxisomal membrane assembly. Proc. Nat. Acad. Sci. 96: 2116-2121,
1999.
7. Mohamed, S.; El-Meleagy, E.; Nasr, A.; Ebberink, M. S.; Wanders,
R. J. A.; Waterham, H. R.: A mutation in PEX19 causes a severe clinical
phenotype in a patient with peroxisomal biogenesis disorder. Am.
J. Med. Genet. 152A: 2318-2321, 2010.
*FIELD* CN
Cassandra L. Kniffin - updated: 6/15/2011
Victor A. McKusick - updated: 4/6/1999
*FIELD* CD
Victor A. McKusick: 1/5/1995
*FIELD* ED
alopez: 10/25/2012
alopez: 10/24/2012
wwang: 7/1/2011
ckniffin: 6/15/2011
tkritzer: 7/20/2004
alopez: 3/17/2004
mgross: 4/7/1999
mgross: 4/6/1999
alopez: 2/5/1999
joanna: 5/7/1997
mark: 5/9/1995
carol: 1/5/1995
MIM
614886
*RECORD*
*FIELD* NO
614886
*FIELD* TI
#614886 PEROXISOME BIOGENESIS DISORDER 12A (ZELLWEGER); PBD12A
PEROXISOME BIOGENESIS DISORDER, COMPLEMENTATION GROUP 14, INCLUDED;;
read moreCG14, INCLUDED;;
PEROXISOME BIOGENESIS DISORDER, COMPLEMENTATION GROUP J, INCLUDED;;
CGJ, INCLUDED
*FIELD* TX
A number sign (#) is used with this entry because this form of Zellweger
syndrome (PBD12A) is caused by homozygous mutation in the PEX19 gene
(600279) on chromosome 1q22.
DESCRIPTION
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital
anomaly syndrome resulting from disordered peroxisome biogenesis.
Affected children present in the newborn period with profound hypotonia,
seizures, and inability to feed. Characteristic craniofacial anomalies,
eye abnormalities, neuronal migration defects, hepatomegaly, and
chondrodysplasia punctata are present. Children with this condition do
not show any significant development and usually die in the first year
of life (summary by Steinberg et al., 2006).
For a complete phenotypic description and a discussion of genetic
heterogeneity of Zellweger syndrome, see 214100.
Individuals with PBDs of complementation group 14 (CG14, equivalent to
CGJ) have mutations in the PEX19 gene. For information on the history of
PBD complementation groups, see 214100.
CLINICAL FEATURES
Mohamed et al. (2010) studied a patient with Zellweger syndrome, an
infant girl from consanguineous Saudi parents. The patient had neonatal
hypotonia, poor growth, and subtle dysmorphic features, including
cranial asymmetry, triangular face, low hairline, open fontanels, and
broad nasal bridge. Laboratory studies showed elevated liver enzymes,
hyperbilirubinemia, and a very long chain fatty acid (VLCFA) profile
consistent with a PBD. Brain imaging showed cerebral atrophy, cortical
changes, and diffuse demyelination. There was a complete absence of
peroxisomes in patient fibroblasts. The patient had a severe clinical
course, complicated by global developmental delay, refractory seizures,
renal tubular defect, multiple gallstones, and recurrent
hospitalizations. She died of sepsis at age 16 months.
MOLECULAR GENETICS
Kinoshita et al. (1998) identified complementation group J (CGJ) from
patients with Zellweger syndrome. Two Chinese hamster ovary cell mutants
were also found to belong to this group. In no CGJ mutant cell were
peroxisomal ghosts found.
Matsuzono et al. (1999) identified a homozygous 1-bp insertion in the
PEX19 gene (600279.0001) in a patient with Zellweger syndrome of
complementation group J.
Mohamed et al. (2010) identified a homozygous frameshift mutation in the
PEX19 gene (600279.0002) in an infant girl with Zellweger syndrome.
*FIELD* RF
1. Kinoshita, N.; Ghaedi, K.; Shimozawa, N.; Wanders, R. J. A.; Matsuzono,
Y.; Imanaka, T.; Okumoto, K.; Suzuki, Y.; Kondo, N.; Fujiki, Y.:
Newly identified Chinese hamster ovary cell mutants are defective
in biogenesis of peroxisomal membrane vesicles (peroxisomal ghosts),
representing a novel complementation group in mammals J. Biol. Chem. 273:
24122-24130, 1998.
2. Matsuzono, Y.; Kinoshita, N.; Tamura, S.; Shimozawa, N.; Hamasaki,
M.; Ghaedi, K.; Wanders, R. J. A.; Suzuki, Y.; Kondo, N.; Fujiki,
Y.: Human PEX19: cDNA cloning by functional complementation, mutation
analysis in a patient with Zellweger syndrome, and potential role
in peroxisomal membrane assembly. Proc. Nat. Acad. Sci. 96: 2116-2121,
1999.
3. Mohamed, S.; El-Meleagy, E.; Nasr, A.; Ebberink, M. S.; Wanders,
R. J. A.; Waterham, H. R.: A mutation in PEX19 causes a severe clinical
phenotype in a patient with peroxisomal biogenesis disorder. Am.
J. Med. Genet. 152A: 2318-2321, 2010.
4. Steinberg, S. J.; Dodt, G.; Raymond, G. V.; Braverman, N. E.; Moser,
A. B.; Moser, H. W.: Peroxisome biogenesis disorders. Biochim. Biophys.
Acta 1763: 1733-1748, 2006.
*FIELD* CD
Anne M. Stumpf: 10/17/2012
*FIELD* ED
alopez: 10/25/2012
carol: 10/25/2012
alopez: 10/24/2012
*RECORD*
*FIELD* NO
614886
*FIELD* TI
#614886 PEROXISOME BIOGENESIS DISORDER 12A (ZELLWEGER); PBD12A
PEROXISOME BIOGENESIS DISORDER, COMPLEMENTATION GROUP 14, INCLUDED;;
read moreCG14, INCLUDED;;
PEROXISOME BIOGENESIS DISORDER, COMPLEMENTATION GROUP J, INCLUDED;;
CGJ, INCLUDED
*FIELD* TX
A number sign (#) is used with this entry because this form of Zellweger
syndrome (PBD12A) is caused by homozygous mutation in the PEX19 gene
(600279) on chromosome 1q22.
DESCRIPTION
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital
anomaly syndrome resulting from disordered peroxisome biogenesis.
Affected children present in the newborn period with profound hypotonia,
seizures, and inability to feed. Characteristic craniofacial anomalies,
eye abnormalities, neuronal migration defects, hepatomegaly, and
chondrodysplasia punctata are present. Children with this condition do
not show any significant development and usually die in the first year
of life (summary by Steinberg et al., 2006).
For a complete phenotypic description and a discussion of genetic
heterogeneity of Zellweger syndrome, see 214100.
Individuals with PBDs of complementation group 14 (CG14, equivalent to
CGJ) have mutations in the PEX19 gene. For information on the history of
PBD complementation groups, see 214100.
CLINICAL FEATURES
Mohamed et al. (2010) studied a patient with Zellweger syndrome, an
infant girl from consanguineous Saudi parents. The patient had neonatal
hypotonia, poor growth, and subtle dysmorphic features, including
cranial asymmetry, triangular face, low hairline, open fontanels, and
broad nasal bridge. Laboratory studies showed elevated liver enzymes,
hyperbilirubinemia, and a very long chain fatty acid (VLCFA) profile
consistent with a PBD. Brain imaging showed cerebral atrophy, cortical
changes, and diffuse demyelination. There was a complete absence of
peroxisomes in patient fibroblasts. The patient had a severe clinical
course, complicated by global developmental delay, refractory seizures,
renal tubular defect, multiple gallstones, and recurrent
hospitalizations. She died of sepsis at age 16 months.
MOLECULAR GENETICS
Kinoshita et al. (1998) identified complementation group J (CGJ) from
patients with Zellweger syndrome. Two Chinese hamster ovary cell mutants
were also found to belong to this group. In no CGJ mutant cell were
peroxisomal ghosts found.
Matsuzono et al. (1999) identified a homozygous 1-bp insertion in the
PEX19 gene (600279.0001) in a patient with Zellweger syndrome of
complementation group J.
Mohamed et al. (2010) identified a homozygous frameshift mutation in the
PEX19 gene (600279.0002) in an infant girl with Zellweger syndrome.
*FIELD* RF
1. Kinoshita, N.; Ghaedi, K.; Shimozawa, N.; Wanders, R. J. A.; Matsuzono,
Y.; Imanaka, T.; Okumoto, K.; Suzuki, Y.; Kondo, N.; Fujiki, Y.:
Newly identified Chinese hamster ovary cell mutants are defective
in biogenesis of peroxisomal membrane vesicles (peroxisomal ghosts),
representing a novel complementation group in mammals J. Biol. Chem. 273:
24122-24130, 1998.
2. Matsuzono, Y.; Kinoshita, N.; Tamura, S.; Shimozawa, N.; Hamasaki,
M.; Ghaedi, K.; Wanders, R. J. A.; Suzuki, Y.; Kondo, N.; Fujiki,
Y.: Human PEX19: cDNA cloning by functional complementation, mutation
analysis in a patient with Zellweger syndrome, and potential role
in peroxisomal membrane assembly. Proc. Nat. Acad. Sci. 96: 2116-2121,
1999.
3. Mohamed, S.; El-Meleagy, E.; Nasr, A.; Ebberink, M. S.; Wanders,
R. J. A.; Waterham, H. R.: A mutation in PEX19 causes a severe clinical
phenotype in a patient with peroxisomal biogenesis disorder. Am.
J. Med. Genet. 152A: 2318-2321, 2010.
4. Steinberg, S. J.; Dodt, G.; Raymond, G. V.; Braverman, N. E.; Moser,
A. B.; Moser, H. W.: Peroxisome biogenesis disorders. Biochim. Biophys.
Acta 1763: 1733-1748, 2006.
*FIELD* CD
Anne M. Stumpf: 10/17/2012
*FIELD* ED
alopez: 10/25/2012
carol: 10/25/2012
alopez: 10/24/2012