PEX2_HUMAN
ID PEX2_HUMAN Reviewed; 305 AA.
AC P28328; Q567S6; Q9BW41;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2009, sequence version 2.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Peroxisome biogenesis factor 2;
DE AltName: Full=35 kDa peroxisomal membrane protein;
DE AltName: Full=Peroxin-2;
DE AltName: Full=Peroxisomal membrane protein 3;
DE AltName: Full=Peroxisome assembly factor 1;
DE Short=PAF-1;
DE AltName: Full=RING finger protein 72;
GN Name=PEX2; Synonyms=PAF1, PMP3, PMP35, PXMP3, RNF72;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-184, AND INVOLVEMENT IN PBD5A.
RC TISSUE=Liver;
RX PubMed=1546315; DOI=10.1126/science.1546315;
RA Shimozawa N., Tsukamoto T., Suzuki Y., Orii T., Shirayoshi Y., Mori T.,
RA Fujiki Y.;
RT "A human gene responsible for Zellweger syndrome that affects peroxisome
RT assembly.";
RL Science 255:1132-1134(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-184.
RX PubMed=10891359; DOI=10.1006/bbrc.2000.3039;
RA Biermanns M., Gaertner J.;
RT "Genomic organization and characterization of human PEX2 encoding a 35-kDa
RT peroxisomal membrane protein.";
RL Biochem. Biophys. Res. Commun. 273:985-990(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-184.
RC TISSUE=Liver;
RA Gartner J.;
RL Submitted (FEB-1992) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-184.
RC TISSUE=Kidney, and Liver;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP DOMAIN RING FINGER.
RX PubMed=1426230; DOI=10.1016/0014-5793(92)81397-5;
RA Patarca R., Fletcher M.A.;
RT "Ring finger in the peroxisome assembly factor-1.";
RL FEBS Lett. 312:1-2(1992).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-84, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [8]
RP VARIANT PBD5B LYS-55.
RX PubMed=10528859; DOI=10.1136/jmg.36.10.779;
RA Shimozawa N., Imamura A., Zhang Z., Suzuki Y., Orii T., Tsukamoto T.,
RA Osumi T., Fujiki Y., Wanders R.J.A., Besley G., Kondo N.;
RT "Defective PEX gene products correlate with the protein import, biochemical
RT abnormalities, and phenotypic heterogeneity in peroxisome biogenesis
RT disorders.";
RL J. Med. Genet. 36:779-781(1999).
CC -!- FUNCTION: Somewhat implicated in the biogenesis of peroxisomes.
CC -!- INTERACTION:
CC P28328; P40855: PEX19; NbExp=3; IntAct=EBI-713978, EBI-594747;
CC -!- SUBCELLULAR LOCATION: Peroxisome membrane; Multi-pass membrane protein.
CC -!- DISEASE: Peroxisome biogenesis disorder complementation group 5 (PBD-
CC CG5) [MIM:614866]: A peroxisomal disorder arising from a failure of
CC protein import into the peroxisomal membrane or matrix. The peroxisome
CC biogenesis disorders (PBD group) are genetically heterogeneous with at
CC least 14 distinct genetic groups as concluded from complementation
CC studies. Include disorders are: Zellweger syndrome (ZWS), neonatal
CC adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and
CC classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and
CC IRD are distinct from RCDP and constitute a clinical continuum of
CC overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Peroxisome biogenesis disorder 5A (PBD5A) [MIM:614866]: A
CC fatal peroxisome biogenesis disorder belonging to the Zellweger disease
CC spectrum and clinically characterized by severe neurologic dysfunction
CC with profound psychomotor retardation, severe hypotonia and neonatal
CC seizures, craniofacial abnormalities, liver dysfunction, and
CC biochemically by the absence of peroxisomes. Additional features
CC include cardiovascular and skeletal defects, renal cysts, ocular
CC abnormalities, and hearing impairment. Most severely affected
CC individuals with the classic form of the disease (classic Zellweger
CC syndrome) die within the first year of life.
CC {ECO:0000269|PubMed:1546315}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Peroxisome biogenesis disorder 5B (PBD5B) [MIM:614867]: A
CC peroxisome biogenesis disorder that includes neonatal
CC adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two
CC milder manifestations of the Zellweger disease spectrum. The clinical
CC course of patients with the NALD and IRD presentation is variable and
CC may include developmental delay, hypotonia, liver dysfunction,
CC sensorineural hearing loss, retinal dystrophy and vision impairment.
CC Children with the NALD presentation may reach their teens, while
CC patients with the IRD presentation may reach adulthood. The clinical
CC conditions are often slowly progressive in particular with respect to
CC loss of hearing and vision. The biochemical abnormalities include
CC accumulation of phytanic acid, very long chain fatty acids (VLCFA),
CC di- and trihydroxycholestanoic acid and pipecolic acid.
CC {ECO:0000269|PubMed:10528859}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the pex2/pex10/pex12 family. {ECO:0000305}.
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DR EMBL; M86852; AAC12785.1; -; mRNA.
DR EMBL; AF133826; AAF97687.1; -; Genomic_DNA.
DR EMBL; M85038; AAA60141.1; -; mRNA.
DR EMBL; AC090810; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000661; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC005375; AAH05375.1; -; mRNA.
DR EMBL; BC093043; AAH93043.1; -; mRNA.
DR CCDS; CCDS6221.1; -.
DR PIR; A41812; A41812.
DR RefSeq; NP_000309.1; NM_000318.2.
DR RefSeq; NP_001073336.1; NM_001079867.1.
DR RefSeq; NP_001165557.1; NM_001172086.1.
DR RefSeq; NP_001165558.1; NM_001172087.1.
DR AlphaFoldDB; P28328; -.
DR BioGRID; 111786; 14.
DR IntAct; P28328; 11.
DR MINT; P28328; -.
DR STRING; 9606.ENSP00000349543; -.
DR TCDB; 3.A.20.1.1; the peroxisomal protein importer (ppi) family.
DR iPTMnet; P28328; -.
DR PhosphoSitePlus; P28328; -.
DR BioMuta; PEX2; -.
DR DMDM; 281185478; -.
DR EPD; P28328; -.
DR jPOST; P28328; -.
DR MassIVE; P28328; -.
DR MaxQB; P28328; -.
DR PaxDb; P28328; -.
DR PeptideAtlas; P28328; -.
DR PRIDE; P28328; -.
DR ProteomicsDB; 54465; -.
DR Antibodypedia; 2570; 240 antibodies from 33 providers.
DR DNASU; 5828; -.
DR Ensembl; ENST00000357039.9; ENSP00000349543.4; ENSG00000164751.15.
DR Ensembl; ENST00000520103.5; ENSP00000428590.1; ENSG00000164751.15.
DR Ensembl; ENST00000522527.5; ENSP00000428638.1; ENSG00000164751.15.
DR GeneID; 5828; -.
DR KEGG; hsa:5828; -.
DR MANE-Select; ENST00000357039.9; ENSP00000349543.4; NM_000318.3; NP_000309.2.
DR UCSC; uc003yax.4; human.
DR CTD; 5828; -.
DR DisGeNET; 5828; -.
DR GeneCards; PEX2; -.
DR GeneReviews; PEX2; -.
DR HGNC; HGNC:9717; PEX2.
DR HPA; ENSG00000164751; Low tissue specificity.
DR MalaCards; PEX2; -.
DR MIM; 170993; gene.
DR MIM; 614866; phenotype.
DR MIM; 614867; phenotype.
DR neXtProt; NX_P28328; -.
DR OpenTargets; ENSG00000164751; -.
DR Orphanet; 772; Infantile Refsum disease.
DR Orphanet; 44; Neonatal adrenoleukodystrophy.
DR Orphanet; 912; Zellweger syndrome.
DR PharmGKB; PA34060; -.
DR VEuPathDB; HostDB:ENSG00000164751; -.
DR eggNOG; KOG2879; Eukaryota.
DR GeneTree; ENSGT00390000001846; -.
DR HOGENOM; CLU_024591_3_1_1; -.
DR InParanoid; P28328; -.
DR OMA; SCFHGFK; -.
DR OrthoDB; 1494604at2759; -.
DR PhylomeDB; P28328; -.
DR TreeFam; TF105312; -.
DR PathwayCommons; P28328; -.
DR Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR Reactome; R-HSA-9033241; Peroxisomal protein import.
DR Reactome; R-HSA-9603798; Class I peroxisomal membrane protein import.
DR SignaLink; P28328; -.
DR SIGNOR; P28328; -.
DR BioGRID-ORCS; 5828; 35 hits in 1114 CRISPR screens.
DR ChiTaRS; PEX2; human.
DR GeneWiki; PXMP3; -.
DR GenomeRNAi; 5828; -.
DR Pharos; P28328; Tbio.
DR PRO; PR:P28328; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P28328; protein.
DR Bgee; ENSG00000164751; Expressed in seminal vesicle and 201 other tissues.
DR ExpressionAtlas; P28328; baseline and differential.
DR Genevisible; P28328; HS.
DR GO; GO:0016593; C:Cdc73/Paf1 complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005779; C:integral component of peroxisomal membrane; IMP:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005778; C:peroxisomal membrane; HDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IMP:UniProtKB.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0007031; P:peroxisome organization; IMP:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IMP:UniProtKB.
DR GO; GO:0016558; P:protein import into peroxisome matrix; IMP:UniProtKB.
DR GO; GO:0000038; P:very long-chain fatty acid metabolic process; IMP:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR006845; Pex_N.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF04757; Pex2_Pex12; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Disease variant; Membrane; Metal-binding; Peroxisome;
KW Peroxisome biogenesis; Peroxisome biogenesis disorder; Reference proteome;
KW Transmembrane; Transmembrane helix; Zellweger syndrome; Zinc; Zinc-finger.
FT CHAIN 1..305
FT /note="Peroxisome biogenesis factor 2"
FT /id="PRO_0000056369"
FT TRANSMEM 140..159
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 195..213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 244..284
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT MOD_RES 84
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VARIANT 55
FT /note="E -> K (in PBD5B; infantile Refsum disease;
FT dbSNP:rs61752119)"
FT /evidence="ECO:0000269|PubMed:10528859"
FT /id="VAR_011389"
FT VARIANT 184
FT /note="C -> R (in dbSNP:rs10087163)"
FT /evidence="ECO:0000269|PubMed:10891359,
FT ECO:0000269|PubMed:1546315, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.3"
FT /id="VAR_060784"
SQ SEQUENCE 305 AA; 34843 MW; F624F93C613FF2DB CRC64;
MASRKENAKS ANRVLRISQL DALELNKALE QLVWSQFTQC FHGFKPGLLA RFEPEVKACL
WVFLWRFTIY SKNATVGQSV LNIKYKNDFS PNLRYQPPSK NQKIWYAVCT IGGRWLEERC
YDLFRNHHLA SFGKVKQCVN FVIGLLKLGG LINFLIFLQR GKFATLTERL LGIHSVFCKP
QNICEVGFEY MNRELLWHGF AEFLIFLLPL INVQKLKAKL SSWCIPLTGA PNSDNTLATS
GKECALCGEW PTMPHTIGCE HIFCYFCAKS SFLFDVYFTC PKCGTEVHSL QPLKSGIEMS
EVNAL
