ID   PEX12_YEAST             Reviewed;         399 AA.
AC   Q04370; D6VZK0; Q6B1L4;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   27-MAR-2024, entry version 175.
DE   RecName: Full=Peroxisome assembly protein 12 {ECO:0000305};
DE   AltName: Full=Peroxin-12 {ECO:0000305};
GN   Name=PEX12 {ECO:0000303|PubMed:11370741, ECO:0000312|SGD:S000004628};
GN   OrderedLocusNames=YMR026C; ORFNames=YM9711.16C;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169872;
RA   Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T.,
RA   Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K.,
RA   Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P.,
RA   Skelton J., Walsh S.V., Whitehead S., Barrell B.G.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.";
RL   Nature 387:90-93(1997).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=17322287; DOI=10.1101/gr.6037607;
RA   Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA   Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA   Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA   Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA   LaBaer J.;
RT   "Approaching a complete repository of sequence-verified protein-encoding
RT   clones for Saccharomyces cerevisiae.";
RL   Genome Res. 17:536-543(2007).
RN   [4]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [5]
RP   FUNCTION.
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   [6]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=11370741; DOI=10.1078/0171-9335-00164;
RA   Albertini M., Girzalsky W., Veenhuis M., Kunau W.H.;
RT   "Pex12p of Saccharomyces cerevisiae is a component of a multi-protein
RT   complex essential for peroxisomal matrix protein import.";
RL   Eur. J. Cell Biol. 80:257-270(2001).
RN   [7]
RP   FUNCTION, AND PATHWAY.
RX   PubMed=19687296; DOI=10.1128/mcb.00388-09;
RA   Platta H.W., El Magraoui F., Baeumer B.E., Schlee D., Girzalsky W.,
RA   Erdmann R.;
RT   "Pex2 and pex12 function as protein-ubiquitin ligases in peroxisomal
RT   protein import.";
RL   Mol. Cell. Biol. 29:5505-5516(2009).
RN   [8]
RP   FUNCTION, PATHWAY, AND IDENTIFICATION IN THE PEX2-PEX10-PEX12
RP   RETROTRANSLOCATION CHANNEL.
RX   PubMed=22471590; DOI=10.1111/j.1742-4658.2012.08591.x;
RA   El Magraoui F., Baeumer B.E., Platta H.W., Baumann J.S., Girzalsky W.,
RA   Erdmann R.;
RT   "The RING-type ubiquitin ligases Pex2p, Pex10p and Pex12p form a
RT   heteromeric complex that displays enhanced activity in an ubiquitin
RT   conjugating enzyme-selective manner.";
RL   FEBS J. 279:2060-2070(2012).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (1.52 ANGSTROMS) OF 330-397 IN COMPLEX WITH ZINC,
RP   FUNCTION, SUBCELLULAR LOCATION, PATHWAY, DOMAIN, IDENTIFICATION IN THE
RP   PEX2-PEX10-PEX12 RETROTRANSLOCATION CHANNEL, AND MUTAGENESIS OF CYS-354.
RX   PubMed=35768507; DOI=10.1038/s41586-022-04903-x;
RA   Feng P., Wu X., Erramilli S.K., Paulo J.A., Knejski P., Gygi S.P.,
RA   Kossiakoff A.A., Rapoport T.A.;
RT   "A peroxisomal ubiquitin ligase complex forms a retrotranslocation
RT   channel.";
RL   Nature 607:374-380(2022).
CC   -!- FUNCTION: Component of a retrotranslocation channel required for
CC       peroxisome organization by mediating export of the PEX5 receptor from
CC       peroxisomes to the cytosol, thereby promoting PEX5 recycling
CC       (PubMed:9090384, PubMed:19687296, PubMed:22471590, PubMed:11370741,
CC       PubMed:35768507). The retrotranslocation channel is composed of PEX2,
CC       PEX10 and PEX12; each subunit contributing transmembrane segments that
CC       coassemble into an open channel that specifically allows the passage of
CC       PEX5 through the peroxisomal membrane (PubMed:35768507). PEX12 also
CC       regulates PEX5 recycling by activating the E3 ubiquitin-protein ligase
CC       activity of PEX10 (PubMed:35768507). When PEX5 recycling is
CC       compromised, PEX12 stimulates PEX10-mediated polyubiquitination of
CC       PEX5, leading to its subsequent degradation (PubMed:35768507).
CC       {ECO:0000269|PubMed:11370741, ECO:0000269|PubMed:19687296,
CC       ECO:0000269|PubMed:22471590, ECO:0000269|PubMed:35768507,
CC       ECO:0000269|PubMed:9090384}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC       {ECO:0000269|PubMed:19687296, ECO:0000269|PubMed:22471590,
CC       ECO:0000269|PubMed:35768507}.
CC   -!- SUBUNIT: Component of the PEX2-PEX10-PEX12 retrotranslocation channel,
CC       composed of PEX2, PEX10 and PEX12. {ECO:0000269|PubMed:22471590,
CC       ECO:0000269|PubMed:35768507}.
CC   -!- INTERACTION:
CC       Q04370; Q05568: PEX10; NbExp=12; IntAct=EBI-2077297, EBI-13194;
CC       Q04370; P80667: PEX13; NbExp=6; IntAct=EBI-2077297, EBI-13206;
CC   -!- SUBCELLULAR LOCATION: Peroxisome membrane {ECO:0000269|PubMed:11370741,
CC       ECO:0000269|PubMed:35768507}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- DOMAIN: The three subunits of the retrotranslocation channel (PEX2,
CC       PEX10 and PEX12) coassemble in the membrane into a channel with an open
CC       10 Angstrom pore (By similarity). The RING-type zinc-fingers that
CC       catalyze PEX5 receptor ubiquitination are positioned above the pore on
CC       the cytosolic side of the complex (By similarity).
CC       {ECO:0000250|UniProtKB:G2Q5N0}.
CC   -!- DOMAIN: The RING-type zinc-finger is degenerated and only coordinates
CC       one zinc ions, preventing E3 ubiquitin-protein ligase activity.
CC       {ECO:0000269|PubMed:35768507}.
CC   -!- MISCELLANEOUS: Present with 907 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the pex2/pex10/pex12 family. {ECO:0000305}.
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DR   EMBL; Z49211; CAA89129.1; -; Genomic_DNA.
DR   EMBL; AY693066; AAT93085.1; -; Genomic_DNA.
DR   EMBL; BK006946; DAA09924.1; -; Genomic_DNA.
DR   PIR; S54028; S54028.
DR   RefSeq; NP_013739.1; NM_001182522.1.
DR   PDB; 7T9X; X-ray; 1.52 A; A/B=330-397.
DR   PDBsum; 7T9X; -.
DR   AlphaFoldDB; Q04370; -.
DR   SMR; Q04370; -.
DR   BioGRID; 35198; 256.
DR   ComplexPortal; CPX-1903; PEX2-PEX10-PEX12 ubiquitin ligase complex.
DR   DIP; DIP-7940N; -.
DR   IntAct; Q04370; 11.
DR   MINT; Q04370; -.
DR   STRING; 4932.YMR026C; -.
DR   TCDB; 3.A.20.1.5; the peroxisomal protein importer (ppi) family.
DR   MaxQB; Q04370; -.
DR   PaxDb; 4932-YMR026C; -.
DR   PeptideAtlas; Q04370; -.
DR   EnsemblFungi; YMR026C_mRNA; YMR026C; YMR026C.
DR   GeneID; 855041; -.
DR   KEGG; sce:YMR026C; -.
DR   AGR; SGD:S000004628; -.
DR   SGD; S000004628; PEX12.
DR   VEuPathDB; FungiDB:YMR026C; -.
DR   eggNOG; KOG0826; Eukaryota.
DR   GeneTree; ENSGT00390000016209; -.
DR   HOGENOM; CLU_031067_0_0_1; -.
DR   InParanoid; Q04370; -.
DR   OMA; VYCWKCI; -.
DR   OrthoDB; 65730at2759; -.
DR   BioCyc; YEAST:G3O-32731-MONOMER; -.
DR   Reactome; R-SCE-9033241; Peroxisomal protein import.
DR   Reactome; R-SCE-9603798; Class I peroxisomal membrane protein import.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 855041; 1 hit in 10 CRISPR screens.
DR   PRO; PR:Q04370; -.
DR   Proteomes; UP000002311; Chromosome XIII.
DR   RNAct; Q04370; Protein.
DR   GO; GO:1990429; C:peroxisomal importomer complex; IDA:SGD.
DR   GO; GO:0005778; C:peroxisomal membrane; IDA:UniProtKB.
DR   GO; GO:0000151; C:ubiquitin ligase complex; IPI:ComplexPortal.
DR   GO; GO:0008320; F:protein transmembrane transporter activity; IDA:UniProtKB.
DR   GO; GO:1990757; F:ubiquitin ligase activator activity; IDA:UniProtKB.
DR   GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:SGD.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProt.
DR   GO; GO:0016558; P:protein import into peroxisome matrix; IMP:SGD.
DR   GO; GO:0016562; P:protein import into peroxisome matrix, receptor recycling; IDA:UniProtKB.
DR   GO; GO:0044721; P:protein import into peroxisome matrix, substrate release; IDA:UniProtKB.
DR   GO; GO:0006513; P:protein monoubiquitination; IBA:GO_Central.
DR   GO; GO:0000209; P:protein polyubiquitination; IDA:UniProt.
DR   GO; GO:0016567; P:protein ubiquitination; IDA:ComplexPortal.
DR   CDD; cd16451; mRING_PEX12; 1.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR   InterPro; IPR017375; PEX12.
DR   InterPro; IPR006845; Pex_N.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   PANTHER; PTHR12888:SF0; PEROXISOME ASSEMBLY PROTEIN 12; 1.
DR   PANTHER; PTHR12888; PEROXISOME ASSEMBLY PROTEIN 12 PEROXIN-12; 1.
DR   Pfam; PF04757; Pex2_Pex12; 1.
DR   PIRSF; PIRSF038074; Peroxisome_assembly_p12; 1.
DR   SUPFAM; SSF57850; RING/U-box; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Membrane; Metal-binding; Peroxisome; Protein transport;
KW   Reference proteome; Transmembrane; Transmembrane helix; Transport;
KW   Ubl conjugation pathway; Zinc; Zinc-finger.
FT   CHAIN           1..399
FT                   /note="Peroxisome assembly protein 12"
FT                   /id="PRO_0000218617"
FT   TOPO_DOM        1..33
FT                   /note="Peroxisomal matrix"
FT                   /evidence="ECO:0000250|UniProtKB:G2Q5N0"
FT   TRANSMEM        34..62
FT                   /note="Helical; Name=TM1"
FT                   /evidence="ECO:0000250|UniProtKB:G2Q5N0"
FT   TOPO_DOM        63..67
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:G2Q5N0"
FT   TRANSMEM        68..92
FT                   /note="Helical; Name=TM2"
FT                   /evidence="ECO:0000250|UniProtKB:G2Q5N0"
FT   TOPO_DOM        93..136
FT                   /note="Peroxisomal matrix"
FT                   /evidence="ECO:0000250|UniProtKB:G2Q5N0"
FT   TRANSMEM        137..168
FT                   /note="Helical; Name=TM3"
FT                   /evidence="ECO:0000250|UniProtKB:G2Q5N0"
FT   TOPO_DOM        169..171
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:G2Q5N0"
FT   TRANSMEM        172..208
FT                   /note="Helical; Name=TM4"
FT                   /evidence="ECO:0000250|UniProtKB:G2Q5N0"
FT   TOPO_DOM        209..277
FT                   /note="Peroxisomal matrix"
FT                   /evidence="ECO:0000250|UniProtKB:G2Q5N0"
FT   TRANSMEM        278..305
FT                   /note="Helical; Name=TM5"
FT                   /evidence="ECO:0000250|UniProtKB:G2Q5N0"
FT   TOPO_DOM        306..399
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:G2Q5N0"
FT   ZN_FING         334..373
FT                   /note="RING-type; degenerate"
FT   REGION          1..24
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         334
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:35768507,
FT                   ECO:0007744|PDB:7T9X"
FT   BINDING         337
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:35768507,
FT                   ECO:0007744|PDB:7T9X"
FT   BINDING         354
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:35768507,
FT                   ECO:0007744|PDB:7T9X"
FT   BINDING         357
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:35768507,
FT                   ECO:0007744|PDB:7T9X"
FT   MUTAGEN         354
FT                   /note="C->S: Abolished zinc-binding and folding, leading to
FT                   impaired protein import into peroxisomes."
FT                   /evidence="ECO:0000269|PubMed:35768507"
FT   CONFLICT        37
FT                   /note="I -> T (in Ref. 3; AAT93085)"
FT                   /evidence="ECO:0000305"
FT   STRAND          330..333
FT                   /evidence="ECO:0007829|PDB:7T9X"
FT   TURN            335..337
FT                   /evidence="ECO:0007829|PDB:7T9X"
FT   STRAND          342..346
FT                   /evidence="ECO:0007829|PDB:7T9X"
FT   STRAND          352..354
FT                   /evidence="ECO:0007829|PDB:7T9X"
FT   HELIX           355..364
FT                   /evidence="ECO:0007829|PDB:7T9X"
FT   TURN            365..367
FT                   /evidence="ECO:0007829|PDB:7T9X"
FT   TURN            370..372
FT                   /evidence="ECO:0007829|PDB:7T9X"
FT   STRAND          379..382
FT                   /evidence="ECO:0007829|PDB:7T9X"
FT   TURN            383..386
FT                   /evidence="ECO:0007829|PDB:7T9X"
FT   STRAND          387..390
FT                   /evidence="ECO:0007829|PDB:7T9X"
SQ   SEQUENCE   399 AA;  45992 MW;  98E6300C2CBFA16A CRC64;
     MSFYSNLPSA GQSSRGSSTS GRNGVGLEPL YPTIFEIMSS QEIDSLLPAS IRYLLANHLV
     ANFPNRYTLR LNKYFFEWFQ AIKGFVEWYH LKTYNSTFID RFYGLQLFSS RDRNLALTQC
     LNPKGQSEWP QGLQLNQQQK SVIFLEKIIL PYITAKLDEI LEKISMNNIF SSDETENKWP
     KRAFLRIYPF IKKLLALSNL LVKLLFLTKR TGSVSLLQYL FKIEYTTVRP LSSELSGLKE
     TKGMDNRLRK TNISSIFALM QGQLSIIPRF LTFMGSQFFP TFIFVLRVYQ WWTTQDMTTK
     LQKRVNDLDE DIPRPPFSSH SDKTEDKEGV SEACPVCEKT VQNPCVLETG YVACYPCAIS
     YLVNNEGHCP VTNKKLLGCT YNKHTNKWEV VTGIRKLLI
//