URA8_YEAST
ID URA8_YEAST Reviewed; 578 AA.
AC P38627; D6VWS2;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 21-SEP-2011, sequence version 4.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=CTP synthase 2;
DE EC=6.3.4.2;
DE AltName: Full=CTP synthetase 2;
DE AltName: Full=UTP--ammonia ligase 2;
GN Name=URA8; OrderedLocusNames=YJR103W; ORFNames=J1962;
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].
RC STRAIN=ATCC 28383 / FL100 / VTT C-80102;
RX PubMed=8121398; DOI=10.1007/bf00281793;
RA Ozier-Kalogeropoulos O., Adeline M.-T., Yang W.-L., Carman G.M.,
RA Lacroute F.;
RT "Use of synthetic lethal mutants to clone and characterize a novel CTP
RT synthetase gene in Saccharomyces cerevisiae.";
RL Mol. Gen. Genet. 242:431-439(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL EMBO J. 15:2031-2049(1996).
RN [3]
RP GENOME REANNOTATION, AND SEQUENCE REVISION TO 559.
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 BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=7559626; DOI=10.1074/jbc.270.42.24982;
RA Nadkarni A.K., McDonough V.M., Yang W.-L., Stukey J.E.,
RA Ozier-Kalogeropoulos O., Carman G.M.;
RT "Differential biochemical regulation of the URA7- and URA8-encoded CTP
RT synthetases from Saccharomyces cerevisiae.";
RL J. Biol. Chem. 270:24982-24988(1995).
RN [5]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF GLU-161 AND HIS-233.
RX PubMed=9668079; DOI=10.1074/jbc.273.30.18992;
RA Ostrander D.B., O'Brien D.J., Gorman J.A., Carman G.M.;
RT "Effect of CTP synthetase regulation by CTP on phospholipid synthesis in
RT Saccharomyces cerevisiae.";
RL J. Biol. Chem. 273:18992-19001(1998).
RN [6]
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 [7]
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).
CC -!- FUNCTION: Catalyzes the ATP-dependent amination of UTP to CTP with
CC either L-glutamine or ammonia as the source of nitrogen. Plays an
CC important role in the regulation of phospholipid synthesis.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + L-glutamine + UTP = ADP + CTP + 2 H(+) + L-
CC glutamate + phosphate; Xref=Rhea:RHEA:26426, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:37563, ChEBI:CHEBI:43474, ChEBI:CHEBI:46398,
CC ChEBI:CHEBI:58359, ChEBI:CHEBI:456216; EC=6.3.4.2;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Activated by GTP. Subject to allosteric product
CC inhibition by CTP. Inhibited by p-chloromercuriphenylsulfonic acid, N-
CC ethylmaleimide and cyclopentenylcytosine (CPEC).
CC {ECO:0000269|PubMed:7559626, ECO:0000269|PubMed:9668079}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=74 uM for UTP {ECO:0000269|PubMed:7559626};
CC KM=22 uM for ATP {ECO:0000269|PubMed:7559626};
CC KM=0.14 mM for L-glutamine {ECO:0000269|PubMed:7559626};
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:7559626};
CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo pathway;
CC CTP from UDP: step 2/2.
CC -!- SUBUNIT: Homodimer. Oligomerizes to a tetramer in the presence of its
CC substrates UTP and ATP. {ECO:0000269|PubMed:7559626}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}.
CC -!- MISCELLANEOUS: Present with 5370 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the CTP synthase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA89633.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X68196; CAA48277.1; -; Genomic_DNA.
DR EMBL; Z49603; CAA89633.1; ALT_FRAME; Genomic_DNA.
DR EMBL; BK006943; DAA08888.2; -; Genomic_DNA.
DR PIR; S57124; S57124.
DR RefSeq; NP_012637.4; NM_001181761.4.
DR AlphaFoldDB; P38627; -.
DR SMR; P38627; -.
DR BioGRID; 33859; 82.
DR DIP; DIP-3941N; -.
DR IntAct; P38627; 1.
DR MINT; P38627; -.
DR STRING; 4932.YJR103W; -.
DR MEROPS; C26.A36; -.
DR MaxQB; P38627; -.
DR PaxDb; P38627; -.
DR PRIDE; P38627; -.
DR EnsemblFungi; YJR103W_mRNA; YJR103W; YJR103W.
DR GeneID; 853567; -.
DR KEGG; sce:YJR103W; -.
DR SGD; S000003864; URA8.
DR VEuPathDB; FungiDB:YJR103W; -.
DR eggNOG; KOG2387; Eukaryota.
DR GeneTree; ENSGT00910000144179; -.
DR HOGENOM; CLU_011675_5_0_1; -.
DR InParanoid; P38627; -.
DR OMA; FKPGTEW; -.
DR BioCyc; YEAST:YJR103W-MON; -.
DR BRENDA; 6.3.4.2; 984.
DR Reactome; R-SCE-499943; Interconversion of nucleotide di- and triphosphates.
DR UniPathway; UPA00159; UER00277.
DR PRO; PR:P38627; -.
DR Proteomes; UP000002311; Chromosome X.
DR RNAct; P38627; protein.
DR GO; GO:0097268; C:cytoophidium; IDA:SGD.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0000324; C:fungal-type vacuole; HDA:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003883; F:CTP synthase activity; IDA:SGD.
DR GO; GO:0042802; F:identical protein binding; IBA:GO_Central.
DR GO; GO:0044210; P:'de novo' CTP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006241; P:CTP biosynthetic process; IDA:SGD.
DR GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0019856; P:pyrimidine nucleobase biosynthetic process; IBA:GO_Central.
DR CDD; cd03113; CTPS_N; 1.
DR CDD; cd01746; GATase1_CTP_Synthase; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.40.50.880; -; 1.
DR InterPro; IPR029062; Class_I_gatase-like.
DR InterPro; IPR004468; CTP_synthase.
DR InterPro; IPR017456; CTP_synthase_N.
DR InterPro; IPR017926; GATASE.
DR InterPro; IPR033828; GATase1_CTP_Synthase.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11550; PTHR11550; 1.
DR Pfam; PF06418; CTP_synth_N; 1.
DR Pfam; PF00117; GATase; 1.
DR SUPFAM; SSF52317; SSF52317; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00337; PyrG; 1.
DR PROSITE; PS51273; GATASE_TYPE_1; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Glutamine amidotransferase; Ligase;
KW Nucleotide-binding; Pyrimidine biosynthesis; Reference proteome.
FT CHAIN 1..578
FT /note="CTP synthase 2"
FT /id="PRO_0000138284"
FT DOMAIN 305..564
FT /note="Glutamine amidotransferase type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605"
FT ACT_SITE 404
FT /note="For GATase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605"
FT ACT_SITE 537
FT /note="For GATase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605"
FT ACT_SITE 539
FT /note="For GATase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605"
FT MUTAGEN 161
FT /note="E->K: Increases the specific activity 2-fold and
FT decreases sensitivity to CTP product inhibition 5-fold."
FT /evidence="ECO:0000269|PubMed:9668079"
FT MUTAGEN 233
FT /note="H->K: No effect on activity and product inhibition
FT by CTP."
FT /evidence="ECO:0000269|PubMed:9668079"
FT CONFLICT 96..97
FT /note="HV -> QL (in Ref. 1; CAA48277)"
FT /evidence="ECO:0000305"
FT CONFLICT 204
FT /note="S -> L (in Ref. 1; CAA48277)"
FT /evidence="ECO:0000305"
FT CONFLICT 440..446
FT /note="QVVIYMP -> PSSHIHA (in Ref. 1; CAA48277)"
FT /evidence="ECO:0000305"
FT CONFLICT 557..563
FT /note="AASGTLG -> QLRHTC (in Ref. 1; CAA48277)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 578 AA; 64511 MW; 6381F30814CC2D57 CRC64;
MKYVVVSGGV ISGIGKGVLA SSTGMLLKTL GLKVTSIKID PYMNIDAGTM SPLEHGECFV
LDDGGETDLD LGNYERYLGI TLSRDHNITT GKIYSHVISR ERRGDYLGKT VQIVPHLTNA
IQDWIQRVSK IPVDDTGLEP DVCIIELGGT VGDIESAPFV EALRQFQFEV GRENFALIHV
SLVPVIHGEQ KTKPTQAAIK DLRSLGLIPD MIACRCSEEL NRSTIDKIAM FCHVGPEQVV
NVHDVNSTYH VPLLLLKQHM IDYLHSRLKL GEVPLTLEDK ERGSQLLTNW ENMTKNLDDS
DDVVKIALVG KYTNLKDSYL SVTKSLEHAS MKCRRQLEIL WVEASNLEPE TQEVDKNKFH
DSWNKLSSAD GILVPGGFGT RGIEGMILAA KWARESGVPF LGVCLGLQVA AIEFARNVIG
RPNSSSTEFL DETLLAPEDQ VVIYMPEIDK EHMGGTMRLG LRPTIFQPNS EWSNIRKLYG
EVNEVHERHR HRYEINPKIV NDMESRGFIF VGKDETGQRC EIFELKGHPY YVGTQYHPEY
TSKVLEPSRP FWGLVAAASG TLGEVIKDIN LSEGNENE
