USA1_YEAST
ID USA1_YEAST Reviewed; 838 AA.
AC Q03714; D6VZE5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=U1 SNP1-associating protein 1;
GN Name=USA1; OrderedLocusNames=YML029W;
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 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 [4]
RP FUNCTION, IDENTIFICATION IN THE HRD1 COMPLEX, AND DISRUPTION PHENOTYPE.
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 [5]
RP TOPOLOGY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 208353 / W303-1A;
RX PubMed=16847258; DOI=10.1073/pnas.0604075103;
RA Kim H., Melen K., Oesterberg M., von Heijne G.;
RT "A global topology map of the Saccharomyces cerevisiae membrane proteome.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376 AND SER-379, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [8]
RP FUNCTION, INTERACTION WITH DER1 AND HRD1, AND DISRUPTION PHENOTYPE.
RX PubMed=20005842; DOI=10.1016/j.molcel.2009.10.015;
RA Horn S.C., Hanna J., Hirsch C., Volkwein C., Schutz A., Heinemann U.,
RA Sommer T., Jarosch E.;
RT "Usa1 functions as a scaffold of the HRD-ubiquitin ligase.";
RL Mol. Cell 36:782-793(2009).
RN [9]
RP FUNCTION, INTERACTION WITH HRD1 AND HRD3, SUBCELLULAR LOCATION, DISRUPTION
RP PHENOTYPE, CHARACTERIZATION OF UBIQUITIN-LIKE DOMAIN, AND CHARACTERIZATION
RP OF FUNCTIONAL REGIONS.
RX PubMed=19898607; DOI=10.1371/journal.pone.0007604;
RA Kim I., Li Y., Muniz P., Rao H.;
RT "Usa1 protein facilitates substrate ubiquitylation through two separate
RT domains.";
RL PLoS ONE 4:E7604-E7604(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-374; SER-376 AND SER-379, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [11]
RP FUNCTION, INTERACTION WITH HRD1, DISRUPTION PHENOTYPE, CHARACTERIZATION OF
RP UBIQUITIN-LIKE DOMAIN, AND CHARACTERIZATION OF FUNCTIONAL REGIONS.
RX PubMed=21074049; DOI=10.1016/j.cell.2010.10.028;
RA Carvalho P., Stanley A.M., Rapoport T.A.;
RT "Retrotranslocation of a misfolded luminal ER protein by the ubiquitin-
RT ligase Hrd1p.";
RL Cell 143:579-591(2010).
RN [12]
RP FUNCTION, DISRUPTION PHENOTYPE, AND CHARACTERIZATION OF UBIQUITIN-LIKE
RP DOMAIN.
RX PubMed=19940128; DOI=10.1074/jbc.m109.067876;
RA Carroll S.M., Hampton R.Y.;
RT "Usa1p is required for optimal function and regulation of the Hrd1p
RT endoplasmic reticulum-associated degradation ubiquitin ligase.";
RL J. Biol. Chem. 285:5146-5156(2010).
RN [13] {ECO:0007744|PDB:6VJZ, ECO:0007744|PDB:6VK0}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.10 ANGSTROMS) OF 500-838 IN COMPLEX
RP WITH DER1; HRD1 AND HRD3, AND INTERACTION WITH DER1.
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: Scaffold protein of the endoplasmic reticulum-associated
CC degradation (ERAD) (also known as endoplasmic reticulum quality
CC control, ERQC) pathway involved in ubiquitin-dependent degradation of
CC misfolded endoplasmic reticulum proteins. 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). Has
CC multiple functions in ERAD including recruitment of DER1 to the HRD1
CC ubiquitin ligase, and regulation of HRD1 activity. Involved in
CC oligomerization of HRD1 and in HRD1 autoubiquitination and degradation.
CC {ECO:0000269|PubMed:16873066, ECO:0000269|PubMed:19898607,
CC ECO:0000269|PubMed:19940128, ECO:0000269|PubMed:20005842,
CC ECO:0000269|PubMed:21074049}.
CC -!- SUBUNIT: Component of the HRD1 ubiquitin ligase complex which contains
CC the E3 ligase HRD1, its cofactors HRD3, USA1 and DER1, substrate
CC recruiting factor YOS9 and CDC48-binding protein UBX2
CC (PubMed:16873066). Within the complex, interacts directly with HRD1
CC (via N-terminus) and DER1 (via C-terminus) and indirectly with HRD3
CC (PubMed:20005842, PubMed:19898607, PubMed:21074049, PubMed:32327568).
CC In ERAD-L, HRD3 and YOS9 jointly bind misfolded glycoproteins in the
CC endoplasmic reticulum (ER) lumen (PubMed:32327568). Movement of ERAD-L
CC substrates through the ER membrane is facilitated by HRD1 and DER1
CC which have lateral gates facing each other and which distort the
CC membrane region between the lateral gates, making it much thinner than
CC a normal phospholipid bilayer (PubMed:32327568). Substrates insert into
CC the membrane as a hairpin loop with one strand interacting with DER1
CC and the other with HRD1 (PubMed:32327568). The HRD1 complex interacts
CC with the heterotrimeric CDC48-NPL4-UFD1 ATPase complex which is
CC recruited by UBX2 via its interaction with CDC48 and which moves
CC ubiquitinated substrates to the cytosol for targeting to the proteasome
CC (PubMed:16873066). {ECO:0000269|PubMed:16873066,
CC ECO:0000269|PubMed:19898607, ECO:0000269|PubMed:20005842,
CC ECO:0000269|PubMed:21074049, ECO:0000269|PubMed:32327568}.
CC -!- INTERACTION:
CC Q03714; P38307: DER1; NbExp=3; IntAct=EBI-27760, EBI-5761;
CC Q03714; Q03714: USA1; NbExp=2; IntAct=EBI-27760, EBI-27760;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:19898607}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:19898607}.
CC -!- DOMAIN: The ubiquitin-like domain is required for HRD1 trans-
CC ubiquitination and degradation. Reported to be involved in ERAD-M but
CC not ERAD-L function (PubMed:20005842). However, a contradictory report
CC states that it is not required for either ERAD-L or ERAD-M function
CC (PubMed:19940128). Reported to be required for HRD1 oligomer formation
CC (PubMed:19940128). However, a contradictory report does not observe any
CC defects in oligomerization following deletion of the domain
CC (PubMed:21074049). {ECO:0000269|PubMed:19940128,
CC ECO:0000269|PubMed:20005842, ECO:0000269|PubMed:21074049}.
CC -!- DISRUPTION PHENOTYPE: Impaired degradation of proteins with misfolded
CC lumenal domains such as CPY*, a mutant, misfolded form of
CC carboxypeptidase Y which is a known ERAD-L substrate. Impaired
CC degradation of proteins with misfolded intramembrane domains. Impaired
CC trans-ubiquitination and degradation of the HRD1 ligase. Degradation of
CC proteins with misfolded cytosolic domains is not affected. Interaction
CC of substrate with HRD1 is reduced; in USA1 and YOS9 double mutants this
CC interaction is completely abolished. {ECO:0000269|PubMed:16873066,
CC ECO:0000269|PubMed:19898607, ECO:0000269|PubMed:19940128,
CC ECO:0000269|PubMed:20005842, ECO:0000269|PubMed:21074049}.
CC -!- MISCELLANEOUS: Present with 1890 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
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DR EMBL; Z46659; CAA86626.1; -; Genomic_DNA.
DR EMBL; BK006946; DAA09869.1; -; Genomic_DNA.
DR PIR; S49750; S49750.
DR RefSeq; NP_013683.1; NM_001182387.1.
DR PDB; 6VJZ; EM; 4.30 A; D=500-838.
DR PDB; 6VK0; EM; 4.10 A; D=500-838.
DR PDBsum; 6VJZ; -.
DR PDBsum; 6VK0; -.
DR AlphaFoldDB; Q03714; -.
DR SMR; Q03714; -.
DR BioGRID; 35140; 138.
DR ComplexPortal; CPX-3070; HRD1 ubiquitin ligase complex.
DR DIP; DIP-6423N; -.
DR IntAct; Q03714; 29.
DR MINT; Q03714; -.
DR STRING; 4932.YML029W; -.
DR CarbonylDB; Q03714; -.
DR iPTMnet; Q03714; -.
DR MaxQB; Q03714; -.
DR PaxDb; Q03714; -.
DR PRIDE; Q03714; -.
DR EnsemblFungi; YML029W_mRNA; YML029W; YML029W.
DR GeneID; 854979; -.
DR KEGG; sce:YML029W; -.
DR SGD; S000004491; USA1.
DR VEuPathDB; FungiDB:YML029W; -.
DR eggNOG; ENOG502QUV9; Eukaryota.
DR HOGENOM; CLU_337435_0_0_1; -.
DR InParanoid; Q03714; -.
DR OMA; VQINQEY; -.
DR BioCyc; YEAST:G3O-32630-MON; -.
DR PRO; PR:Q03714; -.
DR Proteomes; UP000002311; Chromosome XIII.
DR RNAct; Q03714; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IPI: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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0060090; F:molecular adaptor activity; IDA:SGD.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IPI:SGD.
DR GO; GO:1902499; P:positive regulation of protein autoubiquitination; IDA:SGD.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:SGD.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Endoplasmic reticulum; Membrane; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..838
FT /note="U1 SNP1-associating protein 1"
FT /id="PRO_0000114926"
FT TOPO_DOM 1..536
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 537..559
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 560..563
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 564..583
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 584..838
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 259..318
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT REGION 31..240
FT /note="Required for ERAD-L function"
FT REGION 319..418
FT /note="Important for HRD1 oligomer formation"
FT REGION 345..535
FT /note="Interaction with HRD1"
FT REGION 437..490
FT /note="Required for ERAD-L function and HRD1 oligomer
FT formation"
FT REGION 584..838
FT /note="Interaction with DER1"
FT REGION 795..838
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 376
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 379
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
SQ SEQUENCE 838 AA; 96653 MW; 9B93ECA6C5421FD6 CRC64;
MSEYLAQTPC KFTIWSSEID LIRTNLLVNA HPLSTVGRLL QYIHYQIYKQ LRAIYQPEEQ
CTNSEIPHTP LNSINTYFLS YEGRELSATC LLKDITSSSH PDSNHFIRLQ LEKRTSPSGS
AFDLEYDMEG EFNSMNIQFE INTLSSQRIF NSMEPNLPIG TTLARLEKLA LERIKDFEKS
AGNLCGIKED HSVSDLQGFI IKGKQTPMFL NYGSDSDYYK DLNLVDLIGI DFAPAHNSFF
TFLFKMNHEQ NSHIANDEER FVLEFISDAT LSITQMNVKP DTTVKQVKDF ICSVYTHSLN
LRRNDIKLIY KGQLLHENNF AGNSSKISEY IKEPHEVKVH VQINQEYTES GPGFWNEVFN
NPNIFQFMPP DTRSQSPVSF APTQGRSPAA IRGEERGIPY VTESGNDIVP TDELYRKCII
NGDEVVFIPV SELNPQSSYL SVIKGDYGEI KIPISSNDYR INGDNILLSP SAIEQLESAL
NFKIERPRDS TLLHPSGEHV RAADNTSSAN DNNTVENDES AWNRRVVRPL RNSFPLLLVL
IRTFYLIGYN SLVPFFIILE FGSFLPWKYI ILLSLLFIFR TVWNTQEVWN LWRDYLHLNE
IDEVKFSQIK EFINSNSLTL NFYKKCKDTQ SAIDLLMIPN LHEQRLSVYS KYDIEYDTNT
PDVGQLNLLF IKVLSGEIPK DALDELFKEF FELYETTRNM NTLYPQDSLN ELLLMIWKES
QKKDINTLPK YRRWFQTLCS QIAEHNVLDV VLRYIIPDPV NDRVITAVIK NFVLFWVTLL
PYVKEKLDDI VAQRARDREQ PAPSAQQQEN EDEALIIPDE EEPTATGAQP HLYIPDED
