ID R7WT62_9NOCA Unreviewed; 595 AA. AC R7WT62; DT 24-JUL-2013, integrated into UniProtKB/TrEMBL. DT 24-JUL-2013, sequence version 1. DT 29-MAY-2024, entry version 55. DE RecName: Full=CTP synthase {ECO:0000256|HAMAP-Rule:MF_01227}; DE EC=6.3.4.2 {ECO:0000256|HAMAP-Rule:MF_01227}; DE AltName: Full=Cytidine 5'-triphosphate synthase {ECO:0000256|HAMAP-Rule:MF_01227}; DE AltName: Full=Cytidine triphosphate synthetase {ECO:0000256|HAMAP-Rule:MF_01227}; DE Short=CTP synthetase {ECO:0000256|HAMAP-Rule:MF_01227}; DE Short=CTPS {ECO:0000256|HAMAP-Rule:MF_01227}; DE AltName: Full=UTP--ammonia ligase {ECO:0000256|HAMAP-Rule:MF_01227}; GN Name=pyrG {ECO:0000256|HAMAP-Rule:MF_01227, GN ECO:0000313|EMBL:EOM78470.1}; GN ORFNames=Rrhod_0302 {ECO:0000313|EMBL:EOM78470.1}; OS Rhodococcus rhodnii LMG 5362. OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; Nocardiaceae; OC Rhodococcus. OX NCBI_TaxID=1273125 {ECO:0000313|EMBL:EOM78470.1, ECO:0000313|Proteomes:UP000013525}; RN [1] {ECO:0000313|EMBL:EOM78470.1, ECO:0000313|Proteomes:UP000013525} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=LMG 5362 {ECO:0000313|EMBL:EOM78470.1, RC ECO:0000313|Proteomes:UP000013525}; RX PubMed=23788540; RA Pachebat J.A., van Keulen G., Whitten M.M., Girdwood S., Del Sol R., RA Dyson P.J., Facey P.D.; RT "Draft Genome Sequence of Rhodococcus rhodnii Strain LMG5362, a Symbiont of RT Rhodnius prolixus (Hemiptera, Reduviidae, Triatominae), the Principle RT Vector of Trypanosoma cruzi."; RL Genome Announc. 1:e00329-13(2013). CC -!- FUNCTION: Catalyzes the ATP-dependent amination of UTP to CTP with CC either L-glutamine or ammonia as the source of nitrogen. Regulates CC intracellular CTP levels through interactions with the four CC ribonucleotide triphosphates. {ECO:0000256|HAMAP-Rule:MF_01227}. 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 Evidence={ECO:0000256|ARBA:ARBA00000314, ECO:0000256|HAMAP- CC Rule:MF_01227}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + NH4(+) + UTP = ADP + CTP + 2 H(+) + phosphate; CC Xref=Rhea:RHEA:16597, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:37563, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:46398, ChEBI:CHEBI:456216; Evidence={ECO:0000256|HAMAP- CC Rule:MF_01227}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + L-glutamine = L-glutamate + NH4(+); CC Xref=Rhea:RHEA:15889, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:29985, ChEBI:CHEBI:58359; Evidence={ECO:0000256|HAMAP- CC Rule:MF_01227}; CC -!- ACTIVITY REGULATION: Allosterically activated by GTP, when glutamine is CC the substrate; GTP has no effect on the reaction when ammonia is the CC substrate. The allosteric effector GTP functions by stabilizing the CC protein conformation that binds the tetrahedral intermediate(s) formed CC during glutamine hydrolysis. Inhibited by the product CTP, via CC allosteric rather than competitive inhibition. {ECO:0000256|HAMAP- CC Rule:MF_01227}. CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo pathway; CC CTP from UDP: step 2/2. {ECO:0000256|ARBA:ARBA00005171, CC ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- SUBUNIT: Homotetramer. {ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- MISCELLANEOUS: CTPSs have evolved a hybrid strategy for distinguishing CC between UTP and CTP. The overlapping regions of the product feedback CC inhibitory and substrate sites recognize a common feature in both CC compounds, the triphosphate moiety. To differentiate isosteric CC substrate and product pyrimidine rings, an additional pocket far from CC the expected kinase/ligase catalytic site, specifically recognizes the CC cytosine and ribose portions of the product inhibitor. CC {ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- SIMILARITY: Belongs to the CTP synthase family. CC {ECO:0000256|ARBA:ARBA00007533, ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ CC whole genome shotgun (WGS) entry which is preliminary data. CC {ECO:0000313|EMBL:EOM78470.1}. 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; APMY01000004; EOM78470.1; -; Genomic_DNA. DR RefSeq; WP_010836377.1; NZ_APMY01000004.1. DR AlphaFoldDB; R7WT62; -. DR STRING; 38312.GCA_000720375_09656; -. DR PATRIC; fig|1273125.3.peg.301; -. DR eggNOG; COG0504; Bacteria. DR OrthoDB; 9801107at2; -. DR UniPathway; UPA00159; UER00277. DR Proteomes; UP000013525; Unassembled WGS sequence. DR GO; GO:0097268; C:cytoophidium; IEA:TreeGrafter. DR GO; GO:0005829; C:cytosol; IEA:TreeGrafter. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0003883; F:CTP synthase activity; IEA:UniProtKB-UniRule. DR GO; GO:0004359; F:glutaminase activity; IEA:RHEA. DR GO; GO:0042802; F:identical protein binding; IEA:TreeGrafter. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0044210; P:'de novo' CTP biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-UniRule. DR GO; GO:0019856; P:pyrimidine nucleobase biosynthetic process; IEA:TreeGrafter. DR CDD; cd03113; CTPS_N; 1. DR CDD; cd01746; GATase1_CTP_Synthase; 1. DR Gene3D; 3.40.50.880; -; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR HAMAP; MF_01227; PyrG; 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 NCBIfam; TIGR00337; PyrG; 1. DR PANTHER; PTHR11550; CTP SYNTHASE; 1. DR PANTHER; PTHR11550:SF0; CTP SYNTHASE-RELATED; 1. DR Pfam; PF06418; CTP_synth_N; 1. DR Pfam; PF00117; GATase; 1. DR SUPFAM; SSF52317; Class I glutamine amidotransferase-like; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51273; GATASE_TYPE_1; 1. PE 3: Inferred from homology; KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|HAMAP- KW Rule:MF_01227}; KW Glutamine amidotransferase {ECO:0000256|ARBA:ARBA00022962, KW ECO:0000256|HAMAP-Rule:MF_01227}; KW Ligase {ECO:0000256|ARBA:ARBA00022598, ECO:0000256|HAMAP-Rule:MF_01227}; KW Magnesium {ECO:0000256|HAMAP-Rule:MF_01227}; KW Metal-binding {ECO:0000256|HAMAP-Rule:MF_01227}; KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|HAMAP- KW Rule:MF_01227}; KW Pyrimidine biosynthesis {ECO:0000256|ARBA:ARBA00022975, ECO:0000256|HAMAP- KW Rule:MF_01227}; Reference proteome {ECO:0000313|Proteomes:UP000013525}. FT DOMAIN 13..281 FT /note="CTP synthase N-terminal" FT /evidence="ECO:0000259|Pfam:PF06418" FT DOMAIN 316..546 FT /note="Glutamine amidotransferase" FT /evidence="ECO:0000259|Pfam:PF00117" FT REGION 1..281 FT /note="Amidoligase domain" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT REGION 560..595 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 396 FT /note="Nucleophile" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00605" FT ACT_SITE 396 FT /note="Nucleophile; for glutamine hydrolysis" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT ACT_SITE 527 FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605" FT ACT_SITE 529 FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605" FT BINDING 23 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 23 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 24..29 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 81 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 81 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 155 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 162..164 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 202..207 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 202..207 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 238 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 238 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 256 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 369 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 397..400 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 419 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 480 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" SQ SEQUENCE 595 AA; 64345 MW; F2CCDE88590A76C6 CRC64; MSQSRIHSRT DTKHIFVSGG VASSLGKGLT ASSLGQLLTA RGMRVTMQKL DPYLNVDPGT MNPFQHGEVF VTEDGAETDL DVGHYERFLD RDLSGQANVT TGQVYSTVIA KERRGEYLGD TVQVIPHITD EIKSRILAMG EPDREGIRPD VVITEIGGTV GDIESQPFLE AARQVRHDVG RDNVFFLHVS LVPYLAPSGE LKTKPTQHSV AALRSIGIQP DALILRCDRD VPQSLKSKIA LMCDVDVDGC ISCPDAPSIY DIPKVLHSEG LDAYVVRQLG LPFRDVDWTV WGNLLERVHQ PRETVKIALV GKYVDLPDAY LSVTEALRAG GFGNRAKVEV VWVRSDDVET PAGAAAHLAD VDGILVPGGF GIRGIEGKVG AIRYARARRI PLLGLCLGLQ CVVIEAARSV GLDDANSTEF EPDTTHPVIS TMADQEDVVA GEADLGGTMR LGAYPATLAK GSVVARAYGA EQVSERHRHR YEVNNTYRAR IEKSGLRFSG TSPDGHLVEF VEYAQDEHPF LVATQAHPEL KSRPTRPHPL FAAFVAAALT YKFEERLPVD VHGDDAQSPA PAETDARGDD LAATGAGDVG ETADA //