UBA4_YEAST
ID UBA4_YEAST Reviewed; 440 AA.
AC P38820; D3DL61;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Adenylyltransferase and sulfurtransferase UBA4 {ECO:0000255|HAMAP-Rule:MF_03049};
DE AltName: Full=Needs CLA4 to survive protein 3;
DE AltName: Full=Ubiquitin-like protein activator 4 {ECO:0000255|HAMAP-Rule:MF_03049};
DE Includes:
DE RecName: Full=Adenylyltransferase UBA4 {ECO:0000255|HAMAP-Rule:MF_03049};
DE EC=2.7.7.- {ECO:0000255|HAMAP-Rule:MF_03049};
DE Includes:
DE RecName: Full=Sulfurtransferase UBA4 {ECO:0000255|HAMAP-Rule:MF_03049};
DE EC=2.8.1.- {ECO:0000255|HAMAP-Rule:MF_03049};
GN Name=UBA4 {ECO:0000255|HAMAP-Rule:MF_03049}; Synonyms=NCS3;
GN OrderedLocusNames=YHR111W;
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=8091229; DOI=10.1126/science.8091229;
RA Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z.,
RA Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., Kucaba T.,
RA Hillier L.W., Jier M., Johnston L., Langston Y., Latreille P., Louis E.J.,
RA Macri C., Mardis E., Menezes S., Mouser L., Nhan M., Rifkin L., Riles L.,
RA St Peter H., Trevaskis E., Vaughan K., Vignati D., Wilcox L., Wohldman P.,
RA Waterston R., Wilson R., Vaudin M.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome
RT VIII.";
RL Science 265:2077-2082(1994).
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 FUNCTION, INTERACTION WITH URM1, AND MUTAGENESIS OF CYS-225.
RX PubMed=10713047; DOI=10.1074/jbc.275.11.7462;
RA Furukawa K., Mizushima N., Noda T., Ohsumi Y.;
RT "A protein conjugation system in yeast with homology to biosynthetic enzyme
RT reaction of prokaryotes.";
RL J. Biol. Chem. 275:7462-7465(2000).
RN [4]
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 [5]
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 [6]
RP FUNCTION IN 2-THIOLATION OF TRNA, AND MUTAGENESIS OF CYS-225 AND CYS-397.
RX PubMed=18491921; DOI=10.1021/bi800477u;
RA Schmitz J., Chowdhury M.M., Haenzelmann P., Nimtz M., Lee E.Y.,
RA Schindelin H., Leimkuehler S.;
RT "The sulfurtransferase activity of Uba4 presents a link between ubiquitin-
RT like protein conjugation and activation of sulfur carrier proteins.";
RL Biochemistry 47:6479-6489(2008).
RN [7]
RP FUNCTION IN 2-THIOLATION OF TRNA.
RX PubMed=18664566; DOI=10.1074/jbc.m804043200;
RA Nakai Y., Nakai M., Hayashi H.;
RT "Thio-modification of yeast cytosolic tRNA requires a ubiquitin-related
RT system that resembles bacterial sulfur transfer systems.";
RL J. Biol. Chem. 283:27469-27476(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-326, AND IDENTIFICATION BY
RP 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 [9]
RP FUNCTION IN 2-THIOLATION OF TRNA.
RX PubMed=18755837; DOI=10.1261/rna.1184108;
RA Huang B., Lu J., Bystroem A.S.;
RT "A genome-wide screen identifies genes required for formation of the wobble
RT nucleoside 5-methoxycarbonylmethyl-2-thiouridine in Saccharomyces
RT cerevisiae.";
RL RNA 14:2183-2194(2008).
RN [10]
RP FUNCTION IN 2-THIOLATION OF TRNA, INTERACTION WITH NCS2; NCS6 AND URM1, AND
RP MUTAGENESIS OF CYS-225 AND CYS-397.
RX PubMed=19145231; DOI=10.1038/nature07643;
RA Leidel S., Pedrioli P.G.A., Bucher T., Brost R., Costanzo M., Schmidt A.,
RA Aebersold R., Boone C., Hofmann K., Peter M.;
RT "Ubiquitin-related modifier Urm1 acts as a sulphur carrier in thiolation of
RT eukaryotic transfer RNA.";
RL Nature 458:228-233(2009).
RN [11]
RP FUNCTION IN 2-THIOLATION OF TRNA, INTERACTION WITH URM1, AND MUTAGENESIS OF
RP CYS-225 AND CYS-397.
RX PubMed=19151091; DOI=10.1093/nar/gkn1023;
RA Noma A., Sakaguchi Y., Suzuki T.;
RT "Mechanistic characterization of the sulfur-relay system for eukaryotic 2-
RT thiouridine biogenesis at tRNA wobble positions.";
RL Nucleic Acids Res. 37:1335-1352(2009).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA
CC wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln). Acts
CC by mediating the C-terminal thiocarboxylation of sulfur carrier URM1.
CC Its N-terminus first activates URM1 as acyl-adenylates (-COAMP), then
CC the persulfide sulfur on the catalytic cysteine is transferred to URM1
CC to form thiocarboxylation (-COSH) of its C-terminus. The reaction
CC probably involves hydrogen sulfide that is generated from the
CC persulfide intermediate and that acts as nucleophile towards URM1.
CC Subsequently, a transient disulfide bond is formed. Does not use
CC thiosulfate as sulfur donor; NFS1 probably acting as a sulfur donor for
CC thiocarboxylation reactions. Prior mcm(5) tRNA modification by the
CC elongator complex is required for 2-thiolation. May also be involved in
CC protein urmylation. {ECO:0000269|PubMed:10713047,
CC ECO:0000269|PubMed:18491921, ECO:0000269|PubMed:18664566,
CC ECO:0000269|PubMed:18755837, ECO:0000269|PubMed:19145231,
CC ECO:0000269|PubMed:19151091}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03049};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_03049};
CC -!- PATHWAY: tRNA modification; 5-methoxycarbonylmethyl-2-thiouridine-tRNA
CC biosynthesis. {ECO:0000255|HAMAP-Rule:MF_03049}.
CC -!- INTERACTION:
CC P38820; P38820: UBA4; NbExp=3; IntAct=EBI-24676, EBI-24676;
CC P38820; P40554: URM1; NbExp=7; IntAct=EBI-24676, EBI-24940;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03049,
CC ECO:0000269|PubMed:14562095}.
CC -!- MISCELLANEOUS: Present with 2620 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the HesA/MoeB/ThiF
CC family. UBA4 subfamily. {ECO:0000255|HAMAP-Rule:MF_03049}.
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DR EMBL; U00059; AAB68852.1; -; Genomic_DNA.
DR EMBL; BK006934; DAA06805.1; -; Genomic_DNA.
DR PIR; S48953; S48953.
DR RefSeq; NP_011979.1; NM_001179241.1.
DR AlphaFoldDB; P38820; -.
DR SMR; P38820; -.
DR BioGRID; 36544; 334.
DR DIP; DIP-1883N; -.
DR IntAct; P38820; 13.
DR MINT; P38820; -.
DR STRING; 4932.YHR111W; -.
DR iPTMnet; P38820; -.
DR MaxQB; P38820; -.
DR PaxDb; P38820; -.
DR PRIDE; P38820; -.
DR EnsemblFungi; YHR111W_mRNA; YHR111W; YHR111W.
DR GeneID; 856511; -.
DR KEGG; sce:YHR111W; -.
DR SGD; S000001153; UBA4.
DR VEuPathDB; FungiDB:YHR111W; -.
DR eggNOG; KOG2017; Eukaryota.
DR GeneTree; ENSGT00940000160847; -.
DR HOGENOM; CLU_013325_1_2_1; -.
DR InParanoid; P38820; -.
DR OMA; GTIGAMQ; -.
DR BioCyc; YEAST:G3O-31153-MON; -.
DR BRENDA; 2.7.7.B4; 984.
DR BRENDA; 2.8.1.B2; 984.
DR Reactome; R-SCE-947581; Molybdenum cofactor biosynthesis.
DR UniPathway; UPA00988; -.
DR PRO; PR:P38820; -.
DR Proteomes; UP000002311; Chromosome VIII.
DR RNAct; P38820; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005829; C:cytosol; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016779; F:nucleotidyltransferase activity; IDA:UniProtKB.
DR GO; GO:0070733; F:protein adenylyltransferase activity; IMP:SGD.
DR GO; GO:0016783; F:sulfurtransferase activity; IDA:UniProtKB.
DR GO; GO:0004792; F:thiosulfate sulfurtransferase activity; IDA:SGD.
DR GO; GO:0042292; F:URM1 activating enzyme activity; IDA:SGD.
DR GO; GO:0007114; P:cell budding; IGI:SGD.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:SGD.
DR GO; GO:0001403; P:invasive growth in response to glucose limitation; IMP:SGD.
DR GO; GO:0032447; P:protein urmylation; IDA:SGD.
DR GO; GO:2000220; P:regulation of pseudohyphal growth; IMP:SGD.
DR GO; GO:0034227; P:tRNA thio-modification; IMP:UniProtKB.
DR GO; GO:0002143; P:tRNA wobble position uridine thiolation; IMP:SGD.
DR GO; GO:0002098; P:tRNA wobble uridine modification; IMP:UniProtKB.
DR Gene3D; 3.40.250.10; -; 1.
DR HAMAP; MF_03049; MOCS3_Uba4; 1.
DR InterPro; IPR028885; MOCS3/Uba4.
DR InterPro; IPR001763; Rhodanese-like_dom.
DR InterPro; IPR036873; Rhodanese-like_dom_sf.
DR InterPro; IPR045886; ThiF/MoeB/HesA.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR InterPro; IPR035985; Ubiquitin-activating_enz.
DR PANTHER; PTHR10953; PTHR10953; 1.
DR Pfam; PF00581; Rhodanese; 1.
DR Pfam; PF00899; ThiF; 1.
DR SMART; SM00450; RHOD; 1.
DR SUPFAM; SSF69572; SSF69572; 1.
DR PROSITE; PS50206; RHODANESE_3; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Cytoplasm; Metal-binding; Multifunctional enzyme;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase;
KW tRNA processing; Ubl conjugation pathway; Zinc.
FT CHAIN 1..440
FT /note="Adenylyltransferase and sulfurtransferase UBA4"
FT /id="PRO_0000120587"
FT DOMAIN 339..438
FT /note="Rhodanese"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT ACT_SITE 225
FT /note="Glycyl thioester intermediate; for
FT adenylyltransferase activity"
FT ACT_SITE 397
FT /note="Cysteine persulfide intermediate; for
FT sulfurtransferase activity"
FT BINDING 77
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 98
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 105..109
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 122
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 166..167
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 208
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 211
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 286
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 289
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MUTAGEN 225
FT /note="C->A,S: Abolishes adenylyltransferase activity but
FT not sulfurtransferase activity."
FT /evidence="ECO:0000269|PubMed:10713047,
FT ECO:0000269|PubMed:18491921, ECO:0000269|PubMed:19145231,
FT ECO:0000269|PubMed:19151091"
FT MUTAGEN 397
FT /note="C->A,S: Abolishes sulfurtransferase activity but not
FT adenylyltransferase activity."
FT /evidence="ECO:0000269|PubMed:18491921,
FT ECO:0000269|PubMed:19145231, ECO:0000269|PubMed:19151091"
SQ SEQUENCE 440 AA; 49361 MW; CF686FCA74D29F30 CRC64;
MNDYHLEDTT SELEALRLEN AQLREQLAKR EDSSRDYPLS LEEYQRYGRQ MIVEETGGVA
GQVKLKNTKV LVVGAGGLGC PALPYLAGAG VGQIGIVDND VVETSNLHRQ VLHDSSRVGM
LKCESARQYI TKLNPHINVV TYPVRLNSSN AFDIFKGYNY ILDCTDSPLT RYLVSDVAVN
LGITVVSASG LGTEGQLTIL NFNNIGPCYR CFYPTPPPPN AVTSCQEGGV IGPCIGLVGT
MMAVETLKLI LGIYTNENFS PFLMLYSGFP QQSLRTFKMR GRQEKCLCCG KNRTITKEAI
EKGEINYELF CGARNYNVCE PDERISVDAF QRIYKDDEFL AKHIFLDVRP SHHYEISHFP
EAVNIPIKNL RDMNGDLKKL QEKLPSVEKD SNIVILCRYG NDSQLATRLL KDKFGFSNVR
DVRGGYFKYI DDIDQTIPKY
