ID PEX19_HUMAN Reviewed; 299 AA. AC P40855; Q8NI97; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1995, sequence version 1. DT 25-NOV-2008, entry version 84. DE RecName: Full=Peroxisomal biogenesis factor 19; DE Short=Peroxin-19; DE AltName: Full=Peroxisomal farnesylated protein; DE AltName: Full=33 kDa housekeeping protein; 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 MEDLINE=94357452; 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 MEDLINE=97480732; 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 ZWS. RC TISSUE=Liver; RX MEDLINE=99162567; 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 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 [7] 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 [8] 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 MEDLINE=20171429; 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 [9] 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 [10] RP INTERACTION WITH PEX3; PEX10; PEX11B; PEX12; PEX13 AND PEX16, AND RP MUTAGENESIS OF 296-CYS--MET-299. RX MEDLINE=21286933; PubMed=11390669; RX 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 [11] 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 [12] 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 [13] 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 [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35; SER-54; SER-146; RP SER-147; SER-149; SER-177 AND SER-184, AND MASS SPECTROMETRY. RX PubMed=17287340; DOI=10.1073/pnas.0611217104; RA Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.; RT "Global proteomic profiling of phosphopeptides using electron transfer RT dissociation tandem mass spectrometry."; RL Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-147 AND SER-149, AND RP MASS SPECTROMETRY. 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). 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 Q9UBJ2:ABCD2; NbExp=1; IntAct=EBI-594747, EBI-80944; CC P28288:ABCD3; NbExp=1; IntAct=EBI-594747, EBI-80992; CC O00623:PEX12; NbExp=1; IntAct=EBI-594747, EBI-594836; CC Q92968:PEX13; NbExp=1; IntAct=EBI-594747, EBI-594849; CC O75381:PEX14; NbExp=1; IntAct=EBI-594747, EBI-594898; CC P56589:PEX3; NbExp=1; IntAct=EBI-594747, EBI-594885; CC O43808:SLC25A17; NbExp=1; 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: Defects in PEX19 are the cause of peroxisome biogenesis CC disorder complementation group 14 (PBD-CG14) [MIM:600279]; also CC known as PBD-CGJ. PBD refers to a group of peroxisomal disorders CC arising from a failure of protein import into the peroxisomal CC membrane or matrix. The PBD group is comprised of four disorders: 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. The PBD group is CC genetically heterogeneous with at least 14 distinct genetic groups CC as concluded from complementation studies. CC -!- DISEASE: Defects in PEX19 are a cause of Zellweger syndrome (ZWS) CC [MIM:214100]. ZWS is a fatal peroxisome biogenesis disorder CC characterized by dysmorphic facial features, hepatomegaly, ocular CC abnormalities, renal cysts, hearing impairment, profound CC psychomotor retardation, severe hypotonia and neonatal seizures. CC Death occurs within the first year of life. CC -!- SIMILARITY: Belongs to the peroxin-19 family. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.genetests.org/query?gene=PEX19"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- 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; BC000496; AAH00496.1; -; mRNA. DR PIR; I37468; I37468. DR RefSeq; NP_001124511.1; -. DR RefSeq; NP_002848.1; -. DR UniGene; Hs.517232; -. DR DIP; DIP:24172N; -. DR IntAct; P40855; -. DR PhosphoSite; P40855; -. DR Ensembl; ENSG00000162735; Homo sapiens. DR GeneID; 5824; -. DR KEGG; hsa:5824; -. DR H-InvDB; HIX0001216; -. DR HGNC; HGNC:9713; PEX19. DR MIM; 214100; phenotype. DR MIM; 600279; gene+phenotype. DR MIM; 601539; phenotype. DR Orphanet; 912; Zellweger syndrome. DR PharmGKB; PA34058; -. DR HOGENOM; P40855; -. DR HOVERGEN; P40855; -. DR NextBio; 22685; -. DR ArrayExpress; P40855; -. DR CleanEx; HS_PEX19; -. DR GermOnline; ENSG00000162735; Homo sapiens. DR GO; GO:0005778; C:peroxisomal membrane; IDA:UniProtKB. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0006625; P:protein targeting to peroxisome; IMP:UniProtKB. DR InterPro; IPR006708; Pex19. DR PANTHER; PTHR12774; Pex19; 1. DR Pfam; PF04614; Pex19; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cytoplasm; Lipoprotein; Membrane; Peroxisome; KW Peroxisome biogenesis; Peroxisome biogenesis disorder; Phosphoprotein; KW Prenylation; Zellweger syndrome. FT CHAIN 1 299 Peroxisomal biogenesis factor 19. FT /FTId=PRO_0000218759. FT REGION 1 91 Necessary for PEX19 function on FT peroxisome biogenesis. FT REGION 1 56 Docking to the peroxisome membrane and FT binding to PEX3. FT MOD_RES 35 35 Phosphoserine. FT MOD_RES 54 54 Phosphoserine. FT MOD_RES 146 146 Phosphoserine. FT MOD_RES 147 147 Phosphoserine. FT MOD_RES 149 149 Phosphoserine. FT MOD_RES 177 177 Phosphoserine. FT MOD_RES 184 184 Phosphoserine. 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 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. 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 //