UBX2_YEAST
ID UBX2_YEAST Reviewed; 584 AA.
AC Q04228; D6VZG1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=UBX domain-containing protein 2;
DE AltName: Full=Secretion lowering protein 1;
GN Name=UBX2; Synonyms=SEL1; OrderedLocusNames=YML013W; ORFNames=YM9571.05;
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 SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
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, AND INTERACTION WITH CDC48.
RX PubMed=15258615; DOI=10.1038/sj.embor.7400203;
RA Schuberth C., Richly H., Rumpf S., Buchberger A.;
RT "Shp1 and Ubx2 are adaptors of Cdc48 involved in ubiquitin-dependent
RT protein degradation.";
RL EMBO Rep. 5:818-824(2004).
RN [6]
RP FUNCTION, AND INTERACTION WITH CDC48; SSM4 AND HRD1.
RX PubMed=16179953; DOI=10.1038/ncb1298;
RA Neuber O., Jarosch E., Volkwein C., Walter J., Sommer T.;
RT "Ubx2 links the Cdc48 complex to ER-associated protein degradation.";
RL Nat. Cell Biol. 7:993-998(2005).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND IDENTIFICATION IN COMPLEX
RP WITH SSM4; HRD1; NPL4; CDC48 AND UFD1.
RX PubMed=16179952; DOI=10.1038/ncb1299;
RA Schuberth C., Buchberger A.;
RT "Membrane-bound Ubx2 recruits Cdc48 to ubiquitin ligases and their
RT substrates to ensure efficient ER-associated protein degradation.";
RL Nat. Cell Biol. 7:999-1006(2005).
RN [8]
RP FUNCTION, IDENTIFICATION IN THE DOA10 COMPLEX, AND IDENTIFICATION IN THE
RP HRD1 COMPLEX.
RX PubMed=16873066; DOI=10.1016/j.cell.2006.05.043;
RA Carvalho P., Goder V., Rapoport T.A.;
RT "Distinct ubiquitin-ligase complexes define convergent pathways for the
RT degradation of ER proteins.";
RL Cell 126:361-373(2006).
RN [9]
RP ROLE OF HRD1 COMPLEX.
RX PubMed=32327568; DOI=10.1126/science.aaz2449;
RA Wu X., Siggel M., Ovchinnikov S., Mi W., Svetlov V., Nudler E., Liao M.,
RA Hummer G., Rapoport T.A.;
RT "Structural basis of ER-associated protein degradation mediated by the Hrd1
RT ubiquitin ligase complex.";
RL Science 368:0-0(2020).
CC -!- FUNCTION: Integral endoplasmic reticulum membrane protein that
CC coordinates the assembly of the ER-associated protein degradation
CC (ERAD) machinery at the ER membrane. Mediates binding of CDC48 to the
CC E3 ubiquitin ligases SSM4/DOA10 and HRD1, and to ERAD substrates.
CC Component of the DOA10 ubiquitin ligase complex, which is part of the
CC ERAD-C pathway responsible for the rapid degradation of membrane
CC proteins with misfolded cytoplasmic domains. ERAD-C substrates are
CC ubiquitinated through DOA10 in conjunction with the E2 ubiquitin-
CC conjugating enzymes UBC6 and UBC7-CUE1. Also a component of the HRD1
CC ubiquitin ligase complex, which is part of the ERAD-L and ERAD-M
CC pathways responsible for the rapid degradation of soluble lumenal and
CC membrane proteins with misfolded lumenal domains (ERAD-L), or ER-
CC membrane proteins with misfolded transmembrane domains (ERAD-M). ERAD-L
CC substrates are ubiquitinated through HRD1 in conjunction with the E2
CC ubiquitin-conjugating enzymes UBC1 and UBC7-CUE1. Ubiquitinated
CC substrates are then removed to the cytosol via the action of the CDC48-
CC NPL4-UFD1 ATPase complex and targeted to the proteasome.
CC {ECO:0000269|PubMed:15258615, ECO:0000269|PubMed:16179952,
CC ECO:0000269|PubMed:16179953, ECO:0000269|PubMed:16873066}.
CC -!- SUBUNIT: Component of the DOA10 ubiquitin ligase complex which contains
CC E3 ligase SSM4/DOA10 and CDC48-binding protein UBX2/SEL1
CC (PubMed:16873066). Component of the HRD1 ubiquitin ligase complex which
CC contains the E3 ligase HRD1, its cofactors HRD3, USA1 and DER1,
CC substrate recruiting factor YOS9 and UBX2 (PubMed:16873066). In ERAD-L,
CC HRD3 and YOS9 jointly bind misfolded glycoproteins in the endoplasmic
CC reticulum (ER) lumen (PubMed:32327568). Movement of ERAD-L substrates
CC through the ER membrane is facilitated by HRD1 and DER1 which have
CC lateral gates facing each other and which distort the membrane region
CC between the lateral gates, making it much thinner than a normal
CC phospholipid bilayer (PubMed:32327568). Substrates insert into the
CC membrane as a hairpin loop with one strand interacting with DER1 and
CC the other with HRD1 (PubMed:32327568). Both the DOA10 and HRD1
CC ubiquitin ligase complexes interact with the heterotrimeric CDC48-NPL4-
CC UFD1 ATPase complex which is recruited by UBX2 via its interaction with
CC CDC48 and which moves ubiquitinated substrates to the cytosol for
CC targeting to the proteasome (PubMed:15258615, PubMed:16179953,
CC PubMed:16179952, PubMed:16873066). {ECO:0000269|PubMed:15258615,
CC ECO:0000269|PubMed:16179952, ECO:0000269|PubMed:16179953,
CC ECO:0000269|PubMed:16873066, ECO:0000269|PubMed:32327568}.
CC -!- INTERACTION:
CC Q04228; P25694: CDC48; NbExp=15; IntAct=EBI-27730, EBI-4308;
CC Q04228; Q08109: HRD1; NbExp=7; IntAct=EBI-27730, EBI-37613;
CC Q04228; P40318: SSM4; NbExp=5; IntAct=EBI-27730, EBI-18208;
CC Q04228; P53044: UFD1; NbExp=5; IntAct=EBI-27730, EBI-19997;
CC Q04228; Q99220: YOS9; NbExp=3; IntAct=EBI-27730, EBI-34938;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- MISCELLANEOUS: Present with 12600 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
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DR EMBL; Z49810; CAA89939.1; -; Genomic_DNA.
DR EMBL; BK006946; DAA09885.1; -; Genomic_DNA.
DR PIR; S55106; S55106.
DR RefSeq; NP_013699.1; NM_001182371.1.
DR AlphaFoldDB; Q04228; -.
DR BioGRID; 35156; 404.
DR ComplexPortal; CPX-3070; HRD1 ubiquitin ligase complex.
DR ComplexPortal; CPX-3074; Doa10 ubiquitin ligase complex.
DR DIP; DIP-5073N; -.
DR IntAct; Q04228; 16.
DR MINT; Q04228; -.
DR STRING; 4932.YML013W; -.
DR TCDB; 3.A.16.1.6; the endoplasmic reticular retrotranslocon (er-rt) family.
DR iPTMnet; Q04228; -.
DR MaxQB; Q04228; -.
DR PaxDb; Q04228; -.
DR PRIDE; Q04228; -.
DR EnsemblFungi; YML013W_mRNA; YML013W; YML013W.
DR GeneID; 854995; -.
DR KEGG; sce:YML013W; -.
DR SGD; S000004475; UBX2.
DR VEuPathDB; FungiDB:YML013W; -.
DR eggNOG; KOG1363; Eukaryota.
DR HOGENOM; CLU_414514_0_0_1; -.
DR InParanoid; Q04228; -.
DR OMA; QEQDSAY; -.
DR BioCyc; YEAST:G3O-32617-MON; -.
DR Reactome; R-SCE-6798695; Neutrophil degranulation.
DR Reactome; R-SCE-8980692; RHOA GTPase cycle.
DR PRO; PR:Q04228; -.
DR Proteomes; UP000002311; Chromosome XIII.
DR RNAct; Q04228; protein.
DR GO; GO:0000837; C:Doa10p ubiquitin ligase complex; IDA:SGD.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR GO; GO:0000836; C:Hrd1p ubiquitin ligase complex; IPI:ComplexPortal.
DR GO; GO:0000839; C:Hrd1p ubiquitin ligase ERAD-L complex; IDA:SGD.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:SGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:SGD.
DR GO; GO:0005811; C:lipid droplet; IDA:SGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; HDA:SGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:SGD.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:SGD.
DR GO; GO:0043130; F:ubiquitin binding; IBA:GO_Central.
DR GO; GO:0071712; P:ER-associated misfolded protein catabolic process; IC:ComplexPortal.
DR GO; GO:0034389; P:lipid droplet organization; IMP:SGD.
DR GO; GO:0072671; P:mitochondria-associated ubiquitin-dependent protein catabolic process; IMP:SGD.
DR GO; GO:0034982; P:mitochondrial protein processing; IMP:SGD.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:SGD.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:SGD.
DR InterPro; IPR001012; UBX_dom.
DR Pfam; PF00789; UBX; 1.
DR SMART; SM00166; UBX; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Ubl conjugation pathway.
FT CHAIN 1..584
FT /note="UBX domain-containing protein 2"
FT /id="PRO_0000210999"
FT TOPO_DOM 1..80
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 81..101
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 102..151
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 152..172
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 173..584
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 426..570
FT /note="UBX"
SQ SEQUENCE 584 AA; 66761 MW; DA4DDD3D624C17B8 CRC64;
MPVVNHEDSE FHLSHTEEDK LNEFQVITNF PPEDLPDVVR LLRNHGWQLE PALSRYFDGE
WKGEPDQMGE PTQTSTPMAE TLVPPALGPR PLLFTASLPV VRPLPANFRN DFRTIGLNGR
SNTVWSMFES FSYDGNPFLF ILLLIPRIIN RLSATIFTFF CTLLSLHSIS GGGNSGKPKI
SKVPKAPTRE THIPLAEILG DTKDKDAFCE LKSFKPDISF NEALRIAKEE FKFMLLILVG
DTYDTDTDTV DVNSKLLLEK ILLNKKTLQY LRKIDNDLII YLKCVHELEP WLVARQLGVR
NTPEIFLIAN VANKASHSET LPSQRLSILG KLKVNSLNRF LQSLTNVVEK YTPELVVNKT
EMHELRMSRE IKKLQEDAYK KSLEMDRIKA IEKEKSLKHA QDLKLNSTAR QLKWLKACID
EIQPFETTGK QATLQFRTSS GKRFVKKFPS MTTLYQIYQS IGCHIYLAVY SSDPAEWSNA
LQDKIRQLSA DDDMLCFKEG QLETATATTI EELGHIINNE LTSFDLERGK LEFDFELVSP
FPKYTVHPNE HMSVDQVPQL WPNGSLLVEA LDEEDEEDEE NEEQ
