ID MET30_YEAST Reviewed; 640 AA. AC P39014; D6VVN6; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1995, sequence version 1. DT 27-MAR-2024, entry version 211. DE RecName: Full=F-box protein MET30 {ECO:0000305}; DE AltName: Full=E3 ubiquitin ligase complex SCF(Met30) subunit MET30; DE AltName: Full=Methionine-requiring protein 30; GN Name=MET30 {ECO:0000303|PubMed:8524217, ECO:0000312|SGD:S000001308}; GN OrderedLocusNames=YIL046W {ECO:0000312|SGD:S000001308}; 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 [GENOMIC DNA], FUNCTION, AND INTERACTION WITH MET4. RC STRAIN=ATCC 26786 / X2180-1A; RX PubMed=8524217; DOI=10.1128/mcb.15.12.6526; RA Thomas D., Kuras L., Barbey R., Cherest H., Blaiseau P.L., RA Surdin-Kerjan Y.; RT "Met30p, a yeast transcriptional inhibitor that responds to S- RT adenosylmethionine, is an essential protein with WD40 repeats."; RL Mol. Cell. Biol. 15:6526-6534(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169870; RA Churcher C.M., Bowman S., Badcock K., Bankier A.T., Brown D., RA Chillingworth T., Connor R., Devlin K., Gentles S., Hamlin N., Harris D.E., RA Horsnell T., Hunt S., Jagels K., Jones M., Lye G., Moule S., Odell C., RA Pearson D., Rajandream M.A., Rice P., Rowley N., Skelton J., Smith V., RA Walsh S.V., Whitehead S., Barrell B.G.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IX."; RL Nature 387:84-87(1997). RN [3] 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 [4] RP INTERACTION WITH SKP1/CBF3D AND CDC53. RX PubMed=9499404; DOI=10.1101/gad.12.5.692; RA Patton E.E., Willems A.R., Sa D., Kuras L., Thomas D., Craig K.L., RA Tyers M.; RT "Cdc53 is a scaffold protein for multiple Cdc34/Skp1/F-box protein RT complexes that regulate cell division and methionine biosynthesis in RT yeast."; RL Genes Dev. 12:692-705(1998). RN [5] RP FUNCTION, SUBUNIT, AND PATHWAY. RX PubMed=9716410; DOI=10.1101/gad.12.16.2587; RA Kaiser P., Sia R.A.L., Bardes E.S.G., Lew D.J., Reed S.I.; RT "Cdc34 and the F-box protein Met30 are required for degradation of the Cdk- RT inhibitory kinase Swe1."; RL Genes Dev. 12:2587-2597(1998). RN [6] RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND INTERACTION WITH MET4 AND RP SKP1/CBF3D. RX PubMed=10637232; DOI=10.1093/emboj/19.2.282; RA Rouillon A., Barbey R., Patton E.E., Tyers M., Thomas D.; RT "Feedback-regulated degradation of the transcriptional activator Met4 is RT triggered by the SCF(Met30) complex."; RL EMBO J. 19:282-294(2000). RN [7] RP INDUCTION. RX PubMed=11027256; DOI=10.1128/mcb.20.21.7845-7852.2000; RA Smothers D.B., Kozubowski L., Dixon C., Goebl M.G., Mathias N.; RT "The abundance of Met30p limits SCF(Met30p) complex activity and is RT regulated by methionine availability."; RL Mol. Cell. Biol. 20:7845-7852(2000). RN [8] 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 [9] 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 [10] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SKP1/CBF3D, RP HOMOMULTIMERIZATION, AND MUTAGENESIS OF LEU-187 AND GLU-190. RX PubMed=14660673; DOI=10.1074/jbc.m308875200; RA Brunson L.E., Dixon C., Kozubowski L., Mathias N.; RT "The amino-terminal portion of the F-box protein Met30p mediates its RT nuclear import and assimilation into an SCF complex."; RL J. Biol. Chem. 279:6674-6682(2004). RN [11] RP FUNCTION. RX PubMed=15689486; DOI=10.1091/mbc.e04-12-1130; RA Yen J.L., Su N.Y., Kaiser P.; RT "The yeast ubiquitin ligase SCFMet30 regulates heavy metal response."; RL Mol. Biol. Cell 16:1872-1882(2005). RN [12] RP FUNCTION. RX PubMed=15870262; DOI=10.1128/mcb.25.10.3875-3885.2005; RA Su N.Y., Flick K., Kaiser P.; RT "The F-box protein Met30 is required for multiple steps in the budding RT yeast cell cycle."; RL Mol. Cell. Biol. 25:3875-3885(2005). RN [13] RP INTERACTION WITH MET4, AND MUTAGENESIS OF LEU-386; ASN-425; GLN-467 AND RP LEU-530. RX PubMed=15883825; DOI=10.1007/s00438-005-1137-6; RA Brunson L.E., Dixon C., LeFebvre A., Sun L., Mathias N.; RT "Identification of residues in the WD-40 repeat motif of the F-box protein RT Met30p required for interaction with its substrate Met4p."; RL Mol. Genet. Genomics 273:361-370(2005). RN [14] 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 [15] 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-67, AND IDENTIFICATION BY RP 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 [17] RP FUNCTION, AND PATHWAY. RX PubMed=33443148; DOI=10.1073/pnas.2005539118; RA Feng Y., Ariosa A.R., Yang Y., Hu Z., Dengjel J., Klionsky D.J.; RT "Downregulation of autophagy by Met30-mediated Atg9 ubiquitination."; RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021). CC -!- FUNCTION: Substrate-recognition component of the SCF(Met30) complex, an CC E3 ubiquitin ligase complex that mediates the ubiquitination and CC subsequent proteasomal degradation of target proteins (PubMed:9716410, CC PubMed:10637232, PubMed:14660673). Negatively regulates sulfur amino CC acids biosynthesis genes expression (PubMed:8524217, PubMed:15689486, CC PubMed:15870262). Controls cell cycle function (being required for the CC G1/S transition and M-phase but not the S-phase), sulfur metabolism, CC and methionine biosynthesis as part of the SCF(Met30) complex CC (PubMed:8524217, PubMed:15689486, PubMed:15870262). Required for the CC efficient binding of CDC45 and MCM proteins to origins of replication CC (PubMed:8524217, PubMed:15689486, PubMed:15870262). Required for CC efficient expression of G1 cyclins (PubMed:15870262). The SCF(Met30) CC complex catalyzes ubiquitination and degradation of the Cdk-inhibitory CC kinase SWE1 (PubMed:9716410). Involved in the S-adenosylmethionine CC (AdoMet)-mediated inhibition of the transcription function of MET4 CC (PubMed:8524217, PubMed:10637232). The SCF(Met30) complex mediates CC ubiquitination and subsequent degradation of MET4 and the cellular CC response to cadmium (PubMed:10637232). The SCF(Met30) complex acts as CC an inhibitor of autophagy by promoting ubiquitination and degradation CC of ATG9 in normal conditions (PubMed:33443148). CC {ECO:0000269|PubMed:10637232, ECO:0000269|PubMed:14660673, CC ECO:0000269|PubMed:15689486, ECO:0000269|PubMed:15870262, CC ECO:0000269|PubMed:33443148, ECO:0000269|PubMed:8524217, CC ECO:0000269|PubMed:9716410}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:33443148, ECO:0000269|PubMed:9716410}. CC -!- SUBUNIT: Homomultimer (PubMed:14660673). Interacts with CDC53 and CC SKP1/CBF3D to form the E3 ubiquitin ligase complex SCF(Met30) CC (PubMed:14660673, PubMed:9499404, PubMed:9716410, PubMed:33443148). CC Interacts with MET4 (PubMed:10637232, PubMed:15883825, PubMed:8524217). CC {ECO:0000269|PubMed:10637232, ECO:0000269|PubMed:14660673, CC ECO:0000269|PubMed:15883825, ECO:0000269|PubMed:33443148, CC ECO:0000269|PubMed:8524217, ECO:0000269|PubMed:9499404, CC ECO:0000269|PubMed:9716410}. CC -!- INTERACTION: CC P39014; Q12018: CDC53; NbExp=10; IntAct=EBI-11507, EBI-4321; CC P39014; P39014: MET30; NbExp=2; IntAct=EBI-11507, EBI-11507; CC P39014; P32389: MET4; NbExp=7; IntAct=EBI-11507, EBI-10757; CC P39014; P52286: SKP1; NbExp=14; IntAct=EBI-11507, EBI-4090; CC P39014; Q12020: SRL2; NbExp=3; IntAct=EBI-11507, EBI-38714; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14660673}. Nucleus CC {ECO:0000269|PubMed:10637232, ECO:0000269|PubMed:14660673}. CC -!- INDUCTION: Transcriptional activation requires MET4 as well as MET31 CC and MET32. Regulated by intracellular AdoMet levels. L-methionine CC regulates the abundance of MET30. The amount of MET30 regulates the CC activity of the E3 ubiquitin ligase complex SCF(Met30). CC {ECO:0000269|PubMed:10637232, ECO:0000269|PubMed:11027256}. CC -!- MISCELLANEOUS: Present with 217 molecules/cell in log phase SD medium. CC {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the WD repeat MET30/SCONB/SCON-2 family. CC {ECO:0000305}. 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; Z46861; CAA86905.1; -; Genomic_DNA. DR EMBL; L26505; AAA96717.1; -; Genomic_DNA. DR EMBL; BK006942; DAA08502.1; -; Genomic_DNA. DR PIR; S49932; S49932. DR RefSeq; NP_012218.1; NM_001179396.1. DR AlphaFoldDB; P39014; -. DR SMR; P39014; -. DR BioGRID; 34944; 504. DR ComplexPortal; CPX-3249; SCF-MET30 E3 ubiquitin ligase complex. DR DIP; DIP-1439N; -. DR IntAct; P39014; 91. DR MINT; P39014; -. DR STRING; 4932.YIL046W; -. DR iPTMnet; P39014; -. DR MaxQB; P39014; -. DR PaxDb; 4932-YIL046W; -. DR PeptideAtlas; P39014; -. DR EnsemblFungi; YIL046W_mRNA; YIL046W; YIL046W. DR GeneID; 854765; -. DR KEGG; sce:YIL046W; -. DR AGR; SGD:S000001308; -. DR SGD; S000001308; MET30. DR VEuPathDB; FungiDB:YIL046W; -. DR eggNOG; KOG0274; Eukaryota. DR GeneTree; ENSGT00940000174309; -. DR HOGENOM; CLU_000288_103_1_1; -. DR InParanoid; P39014; -. DR OMA; PTHTACY; -. DR OrthoDB; 587035at2759; -. DR BioCyc; YEAST:G3O-31317-MONOMER; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 854765; 9 hits in 10 CRISPR screens. DR PRO; PR:P39014; -. DR Proteomes; UP000002311; Chromosome IX. DR RNAct; P39014; Protein. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0043224; C:nuclear SCF ubiquitin ligase complex; IDA:SGD. DR GO; GO:0005634; C:nucleus; IDA:SGD. DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0043130; F:ubiquitin binding; IDA:SGD. DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IDA:UniProtKB. DR GO; GO:0019344; P:cysteine biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:SGD. DR GO; GO:0009086; P:methionine biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB. DR GO; GO:0007346; P:regulation of mitotic cell cycle; NAS:ComplexPortal. DR GO; GO:0031335; P:regulation of sulfur amino acid metabolic process; NAS:ComplexPortal. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:SGD. DR GO; GO:0046685; P:response to arsenic-containing substance; IDA:SGD. DR GO; GO:0046686; P:response to cadmium ion; IDA:SGD. DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IGI:SGD. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; NAS:ComplexPortal. DR CDD; cd22147; F-box_SpPof1-like; 1. DR CDD; cd00200; WD40; 1. DR Gene3D; 1.20.1280.50; -; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 3. DR InterPro; IPR036047; F-box-like_dom_sf. DR InterPro; IPR001810; F-box_dom. DR InterPro; IPR020472; G-protein_beta_WD-40_rep. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR019775; WD40_repeat_CS. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR PANTHER; PTHR19872; UBIQUITIN LIGASE SPECIFICITY FACTOR/HREP PROTEIN; 1. DR PANTHER; PTHR19872:SF10; UBIQUITIN-BINDING SDF UBIQUITIN LIGASE COMPLEX SUBUNIT; 1. DR Pfam; PF12937; F-box-like; 1. DR Pfam; PF00400; WD40; 6. DR PRINTS; PR00320; GPROTEINBRPT. DR SMART; SM00256; FBOX; 1. DR SMART; SM00320; WD40; 6. DR SUPFAM; SSF81383; F-box domain; 1. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS50181; FBOX; 1. DR PROSITE; PS00678; WD_REPEATS_1; 4. DR PROSITE; PS50082; WD_REPEATS_2; 6. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. PE 1: Evidence at protein level; KW Amino-acid biosynthesis; Cell cycle; Cysteine biosynthesis; Cytoplasm; KW Methionine biosynthesis; Nucleus; Phosphoprotein; Reference proteome; KW Repeat; Transcription; Transcription regulation; Ubl conjugation pathway; KW WD repeat. FT CHAIN 1..640 FT /note="F-box protein MET30" FT /id="PRO_0000051087" FT DOMAIN 181..227 FT /note="F-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080" FT REPEAT 300..328 FT /note="WD 1" FT REPEAT 340..368 FT /note="WD 2" FT REPEAT 380..408 FT /note="WD 3" FT REPEAT 419..449 FT /note="WD 4" FT REPEAT 461..499 FT /note="WD 5" FT REPEAT 509..538 FT /note="WD 6" FT REPEAT 550..578 FT /note="WD 7" FT REPEAT 607..635 FT /note="WD 8" FT REGION 1..299 FT /note="Necessary to mediate nuclear localization" FT REGION 1..84 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 180..277 FT /note="Important for mediating homomultimerization" FT REGION 180..225 FT /note="Interaction with SKP1/CBF3D" FT REGION 277..640 FT /note="Interaction with MET4" FT REGION 481..516 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..22 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 48..84 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 481..504 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 67 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19779198" FT MUTAGEN 187 FT /note="L->D: Strongly reduces nuclear localization; FT inhibits interaction with SKP1/CBF3D." FT /evidence="ECO:0000269|PubMed:14660673" FT MUTAGEN 190 FT /note="E->A: Strongly reduces nuclear localization; FT inhibits interaction with SKP1/CBF3D." FT /evidence="ECO:0000269|PubMed:14660673" FT MUTAGEN 386 FT /note="L->D: Inactivates MET30 and prevents MET4 FT interaction; when associated with A-425 and A-467." FT /evidence="ECO:0000269|PubMed:15883825" FT MUTAGEN 425 FT /note="N->A: Inactivates MET30 and prevents MET4 FT interaction; when associated with D-530 or D-386 and FT A-467." FT /evidence="ECO:0000269|PubMed:15883825" FT MUTAGEN 467 FT /note="Q->A: Inactivates MET30 and prevents MET4 FT interaction; when associated with D-386 and A-425." FT /evidence="ECO:0000269|PubMed:15883825" FT MUTAGEN 530 FT /note="L->D: Inactivates MET30 and prevents MET4 FT interaction; when associated with A-425." FT /evidence="ECO:0000269|PubMed:15883825" FT CONFLICT 61 FT /note="M -> I (in Ref. 1; AAA96717)" FT /evidence="ECO:0000305" SQ SEQUENCE 640 AA; 72835 MW; 5135D4BCA2E1EB97 CRC64; MRRERQRMMS FEDKDKDDLD NSNSNNSSEM TDTAMMPPLK RLLITGSSDD LAQGSSGKKK MTMATRSPSS SPDLATNDSG TRVQPLPEYN FTKFCYRHNP DIQFSPTHTA CYKQDLKRTQ EINANIAKLP LQEQSDIHHI ISKYSNSNDK IRKLILDGIL STSCFPQLSY ISSLVTHMIK IDFISILPQE LSLKILSYLD CQSLCNATRV CRKWQKLADD DRVWYHMCEQ HIDRKCPNCG WGLPLLHMKR ARIQQNSTGS SSNADIQTQT TRPWKVIYRE RFKVESNWRK GHCRIQEFKG HMDGVLTLQF NYRLLFTGSY DSTIGIWDLF TGKLIRRLSG HSDGVKTLYF DDRKLITGSL DKTIRVWNYI TGECISTYRG HSDSVLSVDS YQKVIVSGSA DKTVKVWHVE SRTCYTLRGH TEWVNCVKLH PKSFSCFSCS DDTTIRMWDI RTNSCLKVFR GHVGQVQKII PLTIKDVENL ATDNTSDGSS PQDDPTMTDG ADESDTPSNE QETVLDENIP YPTHLLSCGL DNTIKLWDVK TGKCIRTQFG HVEGVWDIAA DNFRIISGSH DGSIKVWDLQ SGKCMHTFNG RRLQRETQHT QTQSLGDKVA PIACVCIGDS ECFSGDEFGC VKMYKFDLND //