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   25-JAN-2012, entry version 102.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND INVOLVEMENT IN PBD-CG3.
RC   TISSUE=Fetal brain;
RX   MEDLINE=97245716; 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
RT   peroxisome biogenesis disorders.";
RL   Nat. Genet. 15:385-388(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND
RP   CHARACTERIZATION OF VARIANT NALD PHE-320.
RX   MEDLINE=98298276; PubMed=9632816;
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
RT   cloning by functional complementation on a CHO cell mutant, patient
RT   analysis, and 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
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   [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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
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   [7]
RP   INTERACTION WITH PEX19.
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   [8]
RP   INTERACTION WITH PEX19, AND MUTAGENESIS OF CYS-304 AND CYS-307.
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   [9]
RP   VARIANTS PBD-CG3 SER-34; GLN-178 DEL; PHE-320 AND GLN-349 DEL, AND
RP   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
RT   Zellweger syndrome spectrum of peroxisome biogenesis disorders.";
RL   Hum. Mutat. 30:E467-E480(2009).
CC   -!- FUNCTION: Required for protein import into peroxisomes.
CC   -!- SUBUNIT: Interacts with PEX5 and PEX10. Interacts with PEX19 via
CC       its cytoplasmic domain.
CC   -!- INTERACTION:
CC       P40855:PEX19; NbExp=2; IntAct=EBI-594836, EBI-594747;
CC       P50542:PEX5; NbExp=3; IntAct=EBI-594836, EBI-597835;
CC   -!- SUBCELLULAR LOCATION: Peroxisome membrane; Multi-pass membrane
CC       protein.
CC   -!- DISEASE: Defects in PEX12 are the cause of peroxisome biogenesis
CC       disorder complementation group 3 (PBD-CG3) [MIM:601758]. PBD
CC       refers to a group of peroxisomal disorders arising from a failure
CC       of protein import into the peroxisomal membrane or matrix. The PBD
CC       group is comprised of four disorders: Zellweger syndrome (ZWS),
CC       neonatal adrenoleukodystrophy (NALD), infantile Refsum disease
CC       (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP).
CC       ZWS, NALD and IRD are distinct from RCDP and constitute a clinical
CC       continuum of overlapping phenotypes known as the Zellweger
CC       spectrum. The PBD group is genetically heterogeneous with at least
CC       14 distinct genetic groups as concluded from complementation
CC       studies.
CC   -!- DISEASE: Defects in PEX12 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 pex2/pex10/pex12 family.
CC   -!- SIMILARITY: Contains 1 RING-type zinc finger.
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PEX12";
CC   -!- WEB RESOURCE: Name=dbPEX, PEX Gene Database;
CC       URL="http://www.dbpex.org/home.php?select_db=PEX12";
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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   IPI; IPI00012573; -.
DR   RefSeq; NP_000277.1; NM_000286.2.
DR   UniGene; Hs.591190; -.
DR   ProteinModelPortal; O00623; -.
DR   SMR; O00623; 302-346.
DR   IntAct; O00623; 3.
DR   MINT; MINT-241654; -.
DR   STRING; O00623; -.
DR   TCDB; 3.A.20.1.1; peroxisomal protein importer (PPI) family.
DR   PRIDE; O00623; -.
DR   Ensembl; ENST00000225873; ENSP00000225873; ENSG00000108733.
DR   GeneID; 5193; -.
DR   KEGG; hsa:5193; -.
DR   UCSC; uc002hjp.1; human.
DR   CTD; 5193; -.
DR   GeneCards; GC17M033897; -.
DR   HGNC; HGNC:8854; PEX12.
DR   MIM; 214100; phenotype.
DR   MIM; 601539; phenotype.
DR   MIM; 601758; gene+phenotype.
DR   neXtProt; NX_O00623; -.
DR   Orphanet; 912; Zellweger syndrome.
DR   PharmGKB; PA33196; -.
DR   GeneTree; ENSGT00390000016209; -.
DR   HOGENOM; HBG390109; -.
DR   HOVERGEN; HBG053569; -.
DR   InParanoid; O00623; -.
DR   OMA; FHYVRSH; -.
DR   OrthoDB; EOG4BZN37; -.
DR   PhylomeDB; O00623; -.
DR   NextBio; 20086; -.
DR   ArrayExpress; O00623; -.
DR   Bgee; O00623; -.
DR   CleanEx; HS_PEX12; -.
DR   Genevestigator; O00623; -.
DR   GermOnline; ENSG00000108733; Homo sapiens.
DR   GO; GO:0005779; C:integral to peroxisomal membrane; IDA:UniProtKB.
DR   GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IMP:UniProtKB.
DR   GO; GO:0016558; P:protein import into peroxisome matrix; IMP:UniProtKB.
DR   InterPro; IPR017375; Peroxisome_assmbl_p12.
DR   InterPro; IPR006845; Pex_N.
DR   InterPro; IPR001841; Znf_RING.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   Gene3D; G3DSA:3.30.40.10; Znf_RING/FYVE/PHD; 1.
DR   KO; K13345; -.
DR   Pfam; PF04757; Pex2_Pex12; 1.
DR   PIRSF; PIRSF038074; Peroxisome_assembly_p12; 1.
DR   SMART; SM00184; RING; 1.
DR   PROSITE; PS00518; ZF_RING_1; FALSE_NEG.
DR   PROSITE; PS50089; ZF_RING_2; FALSE_NEG.
PE   1: Evidence at protein level;
KW   Complete proteome; Disease mutation; Membrane; Metal-binding;
KW   Peroxisome; Peroxisome biogenesis disorder; Polymorphism;
KW   Reference proteome; Transmembrane; Transmembrane helix;
KW   Zellweger syndrome; Zinc; Zinc-finger.
FT   CHAIN         1    359       Peroxisome assembly protein 12.
FT                                /FTId=PRO_0000218610.
FT   TOPO_DOM      1    158       Cytoplasmic (Potential).
FT   TRANSMEM    159    179       Helical; (Potential).
FT   TOPO_DOM    180    239       Peroxisomal matrix (Potential).
FT   TRANSMEM    240    260       Helical; (Potential).
FT   TOPO_DOM    261    359       Cytoplasmic (Potential).
FT   ZN_FING     304    343       RING-type; degenerate.
FT   COMPBIAS    280    285       Poly-Pro.
FT   VARIANT      34     34       R -> S (in PBD-CG3; Zellweger spectrum).
FT                                /FTId=VAR_058389.
FT   VARIANT     178    178       Missing (in PBD-CG3; Zellweger spectrum).
FT                                /FTId=VAR_058390.
FT   VARIANT     245    245       L -> I (in dbSNP:rs12941376).
FT                                /FTId=VAR_050495.
FT   VARIANT     320    320       S -> F (in NALD; attenuates interaction
FT                                with PEX10 and decreases peroxisomal
FT                                protein import; dbSNP:rs28936697).
FT                                /FTId=VAR_031998.
FT   VARIANT     349    349       Missing (in PBD-CG3; Zellweger spectrum).
FT                                /FTId=VAR_058391.
FT   MUTAGEN     304    304       C->W: Abolishes interaction with PEX19;
FT                                when associated with Q-307.
FT   MUTAGEN     307    307       C->Q: Abolishes interaction with PEX19;
FT                                when associated with W-304.
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
//