PEX12_HUMAN
ID PEX12_HUMAN Reviewed; 359 AA.
AC O00623; B2R6M2;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Peroxisome assembly protein 12;
DE AltName: Full=Peroxin-12;
DE AltName: Full=Peroxisome assembly factor 3;
DE Short=PAF-3;
GN Name=PEX12; Synonyms=PAF3;
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 [GENOMIC DNA / MRNA], AND INVOLVEMENT IN PBD3A.
RC TISSUE=Fetal brain;
RX PubMed=9090384; DOI=10.1038/ng0497-385;
RA Chang C.-C., Lee W.-H., Moser H., Valle D., Gould S.J.;
RT "Isolation of the human PEX12 gene, mutated in group 3 of the peroxisome
RT biogenesis disorders.";
RL Nat. Genet. 15:385-388(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9632816; DOI=10.1128/mcb.18.7.4324;
RA Okumoto K., Shimozawa N., Kawai A., Tamura S., Tsukamoto T., Osumi T.,
RA Moser H., Wanders R.J.A., Suzuki Y., Kondo N., Fujiki Y.;
RT "PEX12, the pathogenic gene of group III Zellweger syndrome: cDNA cloning
RT by functional complementation on a CHO cell mutant, patient analysis, and
RT characterization of PEX12p.";
RL Mol. Cell. Biol. 18:4324-4336(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 INTERACTION WITH PEX19.
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 [7]
RP INTERACTION WITH PEX19, AND MUTAGENESIS OF CYS-304 AND CYS-307.
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 [8]
RP VARIANT PBD3B PHE-320, CHARACTERIZATION OF VARIANT PBD3B PHE-320, AND
RP INTERACTION WITH PEX5 AND PEX10.
RX PubMed=10562279; DOI=10.1083/jcb.147.4.761;
RA Chang C.C., Warren D.S., Sacksteder K.A., Gould S.J.;
RT "PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor
RT docking in peroxisomal matrix protein import.";
RL J. Cell Biol. 147:761-774(1999).
RN [9]
RP VARIANTS PBD-CG3 SER-34; GLN-178 DEL AND GLN-349 DEL, VARIANT PBD3B
RP PHE-320, AND VARIANT ILE-245.
RX PubMed=19105186; DOI=10.1002/humu.20932;
RA Yik W.Y., Steinberg S.J., Moser A.B., Moser H.W., Hacia J.G.;
RT "Identification of novel mutations and sequence variation in the Zellweger
RT syndrome spectrum of peroxisome biogenesis disorders.";
RL Hum. Mutat. 30:E467-E480(2009).
CC -!- FUNCTION: Required for protein import into peroxisomes.
CC {ECO:0000269|PubMed:9632816}.
CC -!- SUBUNIT: Interacts with PEX5 and PEX10. Interacts with PEX19 via its
CC cytoplasmic domain. {ECO:0000269|PubMed:10562279,
CC ECO:0000269|PubMed:10704444, ECO:0000269|PubMed:11390669}.
CC -!- INTERACTION:
CC O00623; Q9ULC5: ACSL5; NbExp=3; IntAct=EBI-594836, EBI-2876927;
CC O00623; Q15848: ADIPOQ; NbExp=3; IntAct=EBI-594836, EBI-10827839;
CC O00623; Q12982: BNIP2; NbExp=3; IntAct=EBI-594836, EBI-752094;
CC O00623; Q8WVV5: BTN2A2; NbExp=3; IntAct=EBI-594836, EBI-8648738;
CC O00623; Q6UWT4: C5orf46; NbExp=3; IntAct=EBI-594836, EBI-11986083;
CC O00623; P78369: CLDN10; NbExp=3; IntAct=EBI-594836, EBI-13372810;
CC O00623; Q4VAQ0: COL8A2; NbExp=3; IntAct=EBI-594836, EBI-10241815;
CC O00623; Q9BQA9: CYBC1; NbExp=3; IntAct=EBI-594836, EBI-2680384;
CC O00623; Q96LL9: DNAJC30; NbExp=3; IntAct=EBI-594836, EBI-8639143;
CC O00623; Q7Z2K6: ERMP1; NbExp=3; IntAct=EBI-594836, EBI-10976398;
CC O00623; Q7L5A8: FA2H; NbExp=3; IntAct=EBI-594836, EBI-11337888;
CC O00623; Q14318: FKBP8; NbExp=3; IntAct=EBI-594836, EBI-724839;
CC O00623; Q9H0Q3: FXYD6; NbExp=3; IntAct=EBI-594836, EBI-713304;
CC O00623; P29033: GJB2; NbExp=3; IntAct=EBI-594836, EBI-3905204;
CC O00623; Q9Y5U9: IER3IP1; NbExp=3; IntAct=EBI-594836, EBI-725665;
CC O00623; Q9P0N8: MARCHF2; NbExp=3; IntAct=EBI-594836, EBI-10317612;
CC O00623; A0A0C4DFN3: MGLL; NbExp=3; IntAct=EBI-594836, EBI-12866138;
CC O00623; Q16617: NKG7; NbExp=3; IntAct=EBI-594836, EBI-3919611;
CC O00623; Q8IXM6: NRM; NbExp=3; IntAct=EBI-594836, EBI-10262547;
CC O00623; P40855: PEX19; NbExp=2; IntAct=EBI-594836, EBI-594747;
CC O00623; P50542: PEX5; NbExp=4; IntAct=EBI-594836, EBI-597835;
CC O00623; P54315: PNLIPRP1; NbExp=3; IntAct=EBI-594836, EBI-8652812;
CC O00623; P43378: PTPN9; NbExp=3; IntAct=EBI-594836, EBI-742898;
CC O00623; Q8N0V3: RBFA; NbExp=3; IntAct=EBI-594836, EBI-3232108;
CC O00623; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-594836, EBI-8652744;
CC O00623; P60059: SEC61G; NbExp=3; IntAct=EBI-594836, EBI-4402709;
CC O00623; Q9NRQ5: SMCO4; NbExp=3; IntAct=EBI-594836, EBI-8640191;
CC O00623; P10124: SRGN; NbExp=3; IntAct=EBI-594836, EBI-744915;
CC O00623; Q9UNK0: STX8; NbExp=3; IntAct=EBI-594836, EBI-727240;
CC O00623; C9JKN6: THSD7B; NbExp=3; IntAct=EBI-594836, EBI-17192156;
CC O00623; P17152: TMEM11; NbExp=3; IntAct=EBI-594836, EBI-723946;
CC O00623; Q9H0R3: TMEM222; NbExp=3; IntAct=EBI-594836, EBI-347385;
CC O00623; Q9NSU2-1: TREX1; NbExp=3; IntAct=EBI-594836, EBI-16746122;
CC O00623; P49638: TTPA; NbExp=3; IntAct=EBI-594836, EBI-10210710;
CC -!- SUBCELLULAR LOCATION: Peroxisome membrane {ECO:0000269|PubMed:9632816};
CC Multi-pass membrane protein {ECO:0000269|PubMed:9632816}.
CC -!- DISEASE: Peroxisome biogenesis disorder complementation group 3 (PBD-
CC CG3) [MIM:614859]: 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 {ECO:0000269|PubMed:19105186}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Peroxisome biogenesis disorder 3A (PBD3A) [MIM:614859]: 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:9090384}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Peroxisome biogenesis disorder 3B (PBD3B) [MIM:266510]: 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:10562279, ECO:0000269|PubMed:19105186}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the pex2/pex10/pex12 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=dbPEX, PEX Gene Database;
CC URL="https://databases.lovd.nl/shared/genes/PEX12";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U91521; AAC68812.1; -; mRNA.
DR EMBL; U91522; AAC68813.1; -; Genomic_DNA.
DR EMBL; AB004546; BAA31559.1; -; mRNA.
DR EMBL; AK312635; BAG35519.1; -; mRNA.
DR EMBL; CH471147; EAW80143.1; -; Genomic_DNA.
DR EMBL; BC031085; AAH31085.1; -; mRNA.
DR CCDS; CCDS11296.1; -.
DR RefSeq; NP_000277.1; NM_000286.2.
DR AlphaFoldDB; O00623; -.
DR BioGRID; 111216; 42.
DR IntAct; O00623; 35.
DR MINT; O00623; -.
DR STRING; 9606.ENSP00000482609; -.
DR TCDB; 3.A.20.1.1; the peroxisomal protein importer (ppi) family.
DR iPTMnet; O00623; -.
DR PhosphoSitePlus; O00623; -.
DR BioMuta; PEX12; -.
DR EPD; O00623; -.
DR jPOST; O00623; -.
DR MassIVE; O00623; -.
DR MaxQB; O00623; -.
DR PaxDb; O00623; -.
DR PeptideAtlas; O00623; -.
DR PRIDE; O00623; -.
DR ProteomicsDB; 47996; -.
DR Antibodypedia; 27495; 129 antibodies from 26 providers.
DR DNASU; 5193; -.
DR Ensembl; ENST00000225873.9; ENSP00000225873.3; ENSG00000108733.11.
DR GeneID; 5193; -.
DR KEGG; hsa:5193; -.
DR MANE-Select; ENST00000225873.9; ENSP00000225873.3; NM_000286.3; NP_000277.1.
DR UCSC; uc002hjp.4; human.
DR CTD; 5193; -.
DR DisGeNET; 5193; -.
DR GeneCards; PEX12; -.
DR GeneReviews; PEX12; -.
DR HGNC; HGNC:8854; PEX12.
DR HPA; ENSG00000108733; Low tissue specificity.
DR MalaCards; PEX12; -.
DR MIM; 266510; phenotype.
DR MIM; 601758; gene.
DR MIM; 614859; phenotype.
DR neXtProt; NX_O00623; -.
DR OpenTargets; ENSG00000108733; -.
DR Orphanet; 772; Infantile Refsum disease.
DR Orphanet; 44; Neonatal adrenoleukodystrophy.
DR Orphanet; 912; Zellweger syndrome.
DR PharmGKB; PA33196; -.
DR VEuPathDB; HostDB:ENSG00000108733; -.
DR eggNOG; KOG0826; Eukaryota.
DR GeneTree; ENSGT00390000016209; -.
DR InParanoid; O00623; -.
DR OMA; NPAIIET; -.
DR OrthoDB; 1204472at2759; -.
DR PhylomeDB; O00623; -.
DR TreeFam; TF314511; -.
DR PathwayCommons; O00623; -.
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; O00623; -.
DR SIGNOR; O00623; -.
DR BioGRID-ORCS; 5193; 41 hits in 1117 CRISPR screens.
DR ChiTaRS; PEX12; human.
DR GeneWiki; PEX12; -.
DR GenomeRNAi; 5193; -.
DR Pharos; O00623; Tbio.
DR PRO; PR:O00623; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O00623; protein.
DR Bgee; ENSG00000108733; Expressed in secondary oocyte and 184 other tissues.
DR ExpressionAtlas; O00623; baseline and differential.
DR Genevisible; O00623; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005779; C:integral component of peroxisomal membrane; IDA:UniProtKB.
DR GO; GO:1990429; C:peroxisomal importomer complex; IBA:GO_Central.
DR GO; GO:0005778; C:peroxisomal membrane; HDA:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IDA:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IMP:UniProtKB.
DR GO; GO:0007031; P:peroxisome organization; IMP:UniProtKB.
DR GO; GO:0016558; P:protein import into peroxisome matrix; IMP:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; IBA:GO_Central.
DR GO; GO:0006625; P:protein targeting to peroxisome; NAS:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR017375; PEX12.
DR InterPro; IPR006845; Pex_N.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR12888; PTHR12888; 1.
DR Pfam; PF04757; Pex2_Pex12; 1.
DR PIRSF; PIRSF038074; Peroxisome_assembly_p12; 1.
PE 1: Evidence at protein level;
KW Disease variant; Membrane; Metal-binding; Peroxisome;
KW Peroxisome biogenesis disorder; Reference proteome; Transmembrane;
KW Transmembrane helix; Zellweger syndrome; Zinc; Zinc-finger.
FT CHAIN 1..359
FT /note="Peroxisome assembly protein 12"
FT /id="PRO_0000218610"
FT TOPO_DOM 1..158
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 159..179
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 180..239
FT /note="Peroxisomal matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 240..260
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 261..359
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ZN_FING 304..343
FT /note="RING-type; degenerate"
FT VARIANT 34
FT /note="R -> S (in PBD-CG3; benign variant;
FT dbSNP:rs147530802)"
FT /evidence="ECO:0000269|PubMed:19105186"
FT /id="VAR_058389"
FT VARIANT 178
FT /note="Missing (in PBD-CG3)"
FT /evidence="ECO:0000269|PubMed:19105186"
FT /id="VAR_058390"
FT VARIANT 245
FT /note="L -> I (in dbSNP:rs12941376)"
FT /evidence="ECO:0000269|PubMed:19105186"
FT /id="VAR_050495"
FT VARIANT 320
FT /note="S -> F (in PBD3B; attenuates interaction with PEX10
FT and decreases peroxisomal protein import;
FT dbSNP:rs28936697)"
FT /evidence="ECO:0000269|PubMed:10562279,
FT ECO:0000269|PubMed:19105186"
FT /id="VAR_031998"
FT VARIANT 349
FT /note="Missing (in PBD-CG3)"
FT /evidence="ECO:0000269|PubMed:19105186"
FT /id="VAR_058391"
FT MUTAGEN 304
FT /note="C->W: Abolishes interaction with PEX19; when
FT associated with Q-307."
FT /evidence="ECO:0000269|PubMed:11390669"
FT MUTAGEN 307
FT /note="C->Q: Abolishes interaction with PEX19; when
FT associated with W-304."
FT /evidence="ECO:0000269|PubMed:11390669"
SQ SEQUENCE 359 AA; 40797 MW; 1AF0BE6416422109 CRC64;
MAEHGAHFTA ASVADDQPSI FEVVAQDSLM TAVRPALQHV VKVLAESNPT HYGFLWRWFD
EIFTLLDLLL QQHYLSRTSA SFSENFYGLK RIVMGDTHKS QRLASAGLPK QQLWKSIMFL
VLLPYLKVKL EKLVSSLREE DEYSIHPPSS RWKRFYRAFL AAYPFVNMAW EGWFLVQQLR
YILGKAQHHS PLLRLAGVQL GRLTVQDIQA LEHKPAKASM MQQPARSVSE KINSALKKAV
GGVALSLSTG LSVGVFFLQF LDWWYSSENQ ETIKSLTALP TPPPPVHLDY NSDSPLLPKM
KTVCPLCRKT RVNDTVLATS GYVFCYRCVF HYVRSHQACP ITGYPTEVQH LIKLYSPEN
