Full text data of CTPS1
CTPS1
(CTPS)
[Confidence: low (only semi-automatic identification from reviews)]
CTP synthase 1; 6.3.4.2 (CTP synthetase 1; UTP--ammonia ligase 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
CTP synthase 1; 6.3.4.2 (CTP synthetase 1; UTP--ammonia ligase 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P17812
ID PYRG1_HUMAN Reviewed; 591 AA.
AC P17812; D3DPW1; Q5VW67; Q96GK6;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-MAY-2002, sequence version 2.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=CTP synthase 1;
DE EC=6.3.4.2;
DE AltName: Full=CTP synthetase 1;
DE AltName: Full=UTP--ammonia ligase 1;
GN Name=CTPS1; Synonyms=CTPS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=2113467;
RA Yamauchi M., Yamauchi N., Meuth M.;
RT "Molecular cloning of the human CTP synthetase gene by functional
RT complementation with purified human metaphase chromosomes.";
RL EMBO J. 9:2095-2099(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-571.
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION.
RX PubMed=16179339; DOI=10.1074/jbc.M509622200;
RA Han G.-S., Sreenivas A., Choi M.-G., Chang Y.-F., Martin S.S.,
RA Baldwin E.P., Carman G.M.;
RT "Expression of human CTP synthetase in Saccharomyces cerevisiae
RT reveals phosphorylation by protein kinase A.";
RL J. Biol. Chem. 280:38328-38336(2005).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Prostate cancer;
RX PubMed=17487921; DOI=10.1002/elps.200600782;
RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.;
RT "Toward a global characterization of the phosphoproteome in prostate
RT cancer cells: identification of phosphoproteins in the LNCaP cell
RT line.";
RL Electrophoresis 28:2027-2034(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-568; SER-571; SER-573;
RP SER-574; SER-575 AND SER-587, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-571; SER-574 AND
RP SER-575, AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-100, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-574 AND SER-575, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-562; SER-573 AND
RP SER-575, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-272.
RA Stenmark P., Kursula P., Arrowsmith C., Berglund H., Edwards A.,
RA Ehn M., Flodin S., Graslund S., Hammarstrom M., Hallberg B.M.,
RA Holmberg Schiavone L., Kotenyova T., Nilsson-ehle P., Ogg D.,
RA Persson C., Sagemark J., Schuler H., Sundstrom M., Thorsell A.G.,
RA van den Berg S., Weigelt J., Nordlund P.;
RT "Crystal structure of the synthetase domain of human CTP synthetase.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: Catalyzes the ATP-dependent amination of UTP to CTP with
CC either L-glutamine or ammonia as the source of nitrogen.
CC -!- CATALYTIC ACTIVITY: ATP + UTP + L-glutamine = ADP + phosphate +
CC CTP + L-glutamate.
CC -!- ENZYME REGULATION: Activated by GTP and inhibited by CTP.
CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo
CC pathway; CTP from UDP: step 2/2.
CC -!- SIMILARITY: Belongs to the CTP synthase family.
CC -!- SIMILARITY: Contains 1 glutamine amidotransferase type-1 domain.
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DR EMBL; X52142; CAA36386.1; -; mRNA.
DR EMBL; AL391730; CAH72797.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07192.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07193.1; -; Genomic_DNA.
DR EMBL; BC009408; AAH09408.1; -; mRNA.
DR PIR; S12791; SYHUTP.
DR RefSeq; NP_001896.2; NM_001905.2.
DR RefSeq; XP_005270593.1; XM_005270536.1.
DR UniGene; Hs.473087; -.
DR PDB; 2VO1; X-ray; 2.80 A; A/B=1-273.
DR PDBsum; 2VO1; -.
DR ProteinModelPortal; P17812; -.
DR SMR; P17812; 1-273, 296-562.
DR IntAct; P17812; 10.
DR MINT; MINT-3008801; -.
DR STRING; 9606.ENSP00000361699; -.
DR DrugBank; DB00130; L-Glutamine.
DR PhosphoSite; P17812; -.
DR DMDM; 20981706; -.
DR PaxDb; P17812; -.
DR PeptideAtlas; P17812; -.
DR PRIDE; P17812; -.
DR Ensembl; ENST00000372616; ENSP00000361699; ENSG00000171793.
DR Ensembl; ENST00000372621; ENSP00000361704; ENSG00000171793.
DR GeneID; 1503; -.
DR KEGG; hsa:1503; -.
DR UCSC; uc001cgk.4; human.
DR CTD; 1503; -.
DR GeneCards; GC01P041445; -.
DR H-InvDB; HIX0000479; -.
DR HGNC; HGNC:2519; CTPS1.
DR HPA; CAB017111; -.
DR MIM; 123860; gene.
DR neXtProt; NX_P17812; -.
DR PharmGKB; PA27020; -.
DR eggNOG; COG0504; -.
DR HOGENOM; HOG000077514; -.
DR HOVERGEN; HBG002243; -.
DR InParanoid; P17812; -.
DR KO; K01937; -.
DR OMA; IIEMPEH; -.
DR OrthoDB; EOG7M3HZZ; -.
DR PhylomeDB; P17812; -.
DR BioCyc; MetaCyc:HS10382-MONOMER; -.
DR BRENDA; 6.3.4.2; 2681.
DR Reactome; REACT_111217; Metabolism.
DR UniPathway; UPA00159; UER00277.
DR EvolutionaryTrace; P17812; -.
DR GeneWiki; CTP_synthase_1; -.
DR GenomeRNAi; 1503; -.
DR NextBio; 6221; -.
DR PRO; PR:P17812; -.
DR ArrayExpress; P17812; -.
DR Bgee; P17812; -.
DR CleanEx; HS_CTPS; -.
DR Genevestigator; P17812; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003883; F:CTP synthase activity; IDA:UniProtKB.
DR GO; GO:0044210; P:'de novo' CTP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006241; P:CTP biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
DR GO; GO:0042493; P:response to drug; TAS:ProtInc.
DR InterPro; IPR004468; CTP_synthase.
DR InterPro; IPR017456; CTP_synthase_N.
DR InterPro; IPR017926; GATASE.
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; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00337; PyrG; 1.
DR PROSITE; PS51273; GATASE_TYPE_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Complete proteome;
KW Glutamine amidotransferase; Ligase; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Pyrimidine biosynthesis;
KW Reference proteome.
FT CHAIN 1 591 CTP synthase 1.
FT /FTId=PRO_0000138275.
FT DOMAIN 300 554 Glutamine amidotransferase type-1.
FT ACT_SITE 399 399 For GATase activity (By similarity).
FT ACT_SITE 526 526 For GATase activity (By similarity).
FT ACT_SITE 528 528 For GATase activity (By similarity).
FT MOD_RES 100 100 N6-acetyllysine.
FT MOD_RES 562 562 Phosphoserine.
FT MOD_RES 568 568 Phosphoserine.
FT MOD_RES 571 571 Phosphoserine.
FT MOD_RES 573 573 Phosphoserine.
FT MOD_RES 574 574 Phosphoserine.
FT MOD_RES 575 575 Phosphoserine.
FT MOD_RES 587 587 Phosphoserine.
FT VARIANT 571 571 S -> I (in dbSNP:rs17856308).
FT /FTId=VAR_027055.
FT CONFLICT 305 305 G -> A (in Ref. 1; CAA36386).
FT CONFLICT 309 309 K -> E (in Ref. 1; CAA36386).
FT STRAND 2 8
FT STRAND 10 15
FT HELIX 16 29
FT STRAND 34 40
FT STRAND 87 89
FT HELIX 90 102
FT TURN 103 108
FT HELIX 113 130
FT STRAND 134 136
FT STRAND 141 147
FT HELIX 154 156
FT HELIX 157 169
FT HELIX 172 174
FT STRAND 175 182
FT HELIX 195 207
FT STRAND 212 217
FT HELIX 224 233
FT HELIX 238 240
FT STRAND 241 244
FT HELIX 250 252
FT HELIX 253 259
FT HELIX 262 270
SQ SEQUENCE 591 AA; 66690 MW; 0B04F9D9390C4152 CRC64;
MKYILVTGGV ISGIGKGIIA SSVGTILKSC GLHVTSIKID PYINIDAGTF SPYEHGEVFV
LDDGGEVDLD LGNYERFLDI RLTKDNNLTT GKIYQYVINK ERKGDYLGKT VQVVPHITDA
IQEWVMRQAL IPVDEDGLEP QVCVIELGGT VGDIESMPFI EAFRQFQFKV KRENFCNIHV
SLVPQPSSTG EQKTKPTQNS VRELRGLGLS PDLVVCRCSN PLDTSVKEKI SMFCHVEPEQ
VICVHDVSSI YRVPLLLEEQ GVVDYFLRRL DLPIERQPRK MLMKWKEMAD RYDRLLETCS
IALVGKYTKF SDSYASVIKA LEHSALAINH KLEIKYIDSA DLEPITSQEE PVRYHEAWQK
LCSAHGVLVP GGFGVRGTEG KIQAIAWARN QKKPFLGVCL GMQLAVVEFS RNVLGWQDAN
STEFDPTTSH PVVVDMPEHN PGQMGGTMRL GKRRTLFQTK NSVMRKLYGD ADYLEERHRH
RFEVNPVWKK CLEEQGLKFV GQDVEGERME IVELEDHPFF VGVQYHPEFL SRPIKPSPPY
FGLLLASVGR LSHYLQKGCR LSPRDTYSDR SGSSSPDSEI TELKFPSINH D
//
ID PYRG1_HUMAN Reviewed; 591 AA.
AC P17812; D3DPW1; Q5VW67; Q96GK6;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-MAY-2002, sequence version 2.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=CTP synthase 1;
DE EC=6.3.4.2;
DE AltName: Full=CTP synthetase 1;
DE AltName: Full=UTP--ammonia ligase 1;
GN Name=CTPS1; Synonyms=CTPS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=2113467;
RA Yamauchi M., Yamauchi N., Meuth M.;
RT "Molecular cloning of the human CTP synthetase gene by functional
RT complementation with purified human metaphase chromosomes.";
RL EMBO J. 9:2095-2099(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-571.
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION.
RX PubMed=16179339; DOI=10.1074/jbc.M509622200;
RA Han G.-S., Sreenivas A., Choi M.-G., Chang Y.-F., Martin S.S.,
RA Baldwin E.P., Carman G.M.;
RT "Expression of human CTP synthetase in Saccharomyces cerevisiae
RT reveals phosphorylation by protein kinase A.";
RL J. Biol. Chem. 280:38328-38336(2005).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Prostate cancer;
RX PubMed=17487921; DOI=10.1002/elps.200600782;
RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.;
RT "Toward a global characterization of the phosphoproteome in prostate
RT cancer cells: identification of phosphoproteins in the LNCaP cell
RT line.";
RL Electrophoresis 28:2027-2034(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-568; SER-571; SER-573;
RP SER-574; SER-575 AND SER-587, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-571; SER-574 AND
RP SER-575, AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-100, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-574 AND SER-575, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-562; SER-573 AND
RP SER-575, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-272.
RA Stenmark P., Kursula P., Arrowsmith C., Berglund H., Edwards A.,
RA Ehn M., Flodin S., Graslund S., Hammarstrom M., Hallberg B.M.,
RA Holmberg Schiavone L., Kotenyova T., Nilsson-ehle P., Ogg D.,
RA Persson C., Sagemark J., Schuler H., Sundstrom M., Thorsell A.G.,
RA van den Berg S., Weigelt J., Nordlund P.;
RT "Crystal structure of the synthetase domain of human CTP synthetase.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: Catalyzes the ATP-dependent amination of UTP to CTP with
CC either L-glutamine or ammonia as the source of nitrogen.
CC -!- CATALYTIC ACTIVITY: ATP + UTP + L-glutamine = ADP + phosphate +
CC CTP + L-glutamate.
CC -!- ENZYME REGULATION: Activated by GTP and inhibited by CTP.
CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo
CC pathway; CTP from UDP: step 2/2.
CC -!- SIMILARITY: Belongs to the CTP synthase family.
CC -!- SIMILARITY: Contains 1 glutamine amidotransferase type-1 domain.
CC -----------------------------------------------------------------------
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DR EMBL; X52142; CAA36386.1; -; mRNA.
DR EMBL; AL391730; CAH72797.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07192.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07193.1; -; Genomic_DNA.
DR EMBL; BC009408; AAH09408.1; -; mRNA.
DR PIR; S12791; SYHUTP.
DR RefSeq; NP_001896.2; NM_001905.2.
DR RefSeq; XP_005270593.1; XM_005270536.1.
DR UniGene; Hs.473087; -.
DR PDB; 2VO1; X-ray; 2.80 A; A/B=1-273.
DR PDBsum; 2VO1; -.
DR ProteinModelPortal; P17812; -.
DR SMR; P17812; 1-273, 296-562.
DR IntAct; P17812; 10.
DR MINT; MINT-3008801; -.
DR STRING; 9606.ENSP00000361699; -.
DR DrugBank; DB00130; L-Glutamine.
DR PhosphoSite; P17812; -.
DR DMDM; 20981706; -.
DR PaxDb; P17812; -.
DR PeptideAtlas; P17812; -.
DR PRIDE; P17812; -.
DR Ensembl; ENST00000372616; ENSP00000361699; ENSG00000171793.
DR Ensembl; ENST00000372621; ENSP00000361704; ENSG00000171793.
DR GeneID; 1503; -.
DR KEGG; hsa:1503; -.
DR UCSC; uc001cgk.4; human.
DR CTD; 1503; -.
DR GeneCards; GC01P041445; -.
DR H-InvDB; HIX0000479; -.
DR HGNC; HGNC:2519; CTPS1.
DR HPA; CAB017111; -.
DR MIM; 123860; gene.
DR neXtProt; NX_P17812; -.
DR PharmGKB; PA27020; -.
DR eggNOG; COG0504; -.
DR HOGENOM; HOG000077514; -.
DR HOVERGEN; HBG002243; -.
DR InParanoid; P17812; -.
DR KO; K01937; -.
DR OMA; IIEMPEH; -.
DR OrthoDB; EOG7M3HZZ; -.
DR PhylomeDB; P17812; -.
DR BioCyc; MetaCyc:HS10382-MONOMER; -.
DR BRENDA; 6.3.4.2; 2681.
DR Reactome; REACT_111217; Metabolism.
DR UniPathway; UPA00159; UER00277.
DR EvolutionaryTrace; P17812; -.
DR GeneWiki; CTP_synthase_1; -.
DR GenomeRNAi; 1503; -.
DR NextBio; 6221; -.
DR PRO; PR:P17812; -.
DR ArrayExpress; P17812; -.
DR Bgee; P17812; -.
DR CleanEx; HS_CTPS; -.
DR Genevestigator; P17812; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003883; F:CTP synthase activity; IDA:UniProtKB.
DR GO; GO:0044210; P:'de novo' CTP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006241; P:CTP biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
DR GO; GO:0042493; P:response to drug; TAS:ProtInc.
DR InterPro; IPR004468; CTP_synthase.
DR InterPro; IPR017456; CTP_synthase_N.
DR InterPro; IPR017926; GATASE.
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; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00337; PyrG; 1.
DR PROSITE; PS51273; GATASE_TYPE_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Complete proteome;
KW Glutamine amidotransferase; Ligase; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Pyrimidine biosynthesis;
KW Reference proteome.
FT CHAIN 1 591 CTP synthase 1.
FT /FTId=PRO_0000138275.
FT DOMAIN 300 554 Glutamine amidotransferase type-1.
FT ACT_SITE 399 399 For GATase activity (By similarity).
FT ACT_SITE 526 526 For GATase activity (By similarity).
FT ACT_SITE 528 528 For GATase activity (By similarity).
FT MOD_RES 100 100 N6-acetyllysine.
FT MOD_RES 562 562 Phosphoserine.
FT MOD_RES 568 568 Phosphoserine.
FT MOD_RES 571 571 Phosphoserine.
FT MOD_RES 573 573 Phosphoserine.
FT MOD_RES 574 574 Phosphoserine.
FT MOD_RES 575 575 Phosphoserine.
FT MOD_RES 587 587 Phosphoserine.
FT VARIANT 571 571 S -> I (in dbSNP:rs17856308).
FT /FTId=VAR_027055.
FT CONFLICT 305 305 G -> A (in Ref. 1; CAA36386).
FT CONFLICT 309 309 K -> E (in Ref. 1; CAA36386).
FT STRAND 2 8
FT STRAND 10 15
FT HELIX 16 29
FT STRAND 34 40
FT STRAND 87 89
FT HELIX 90 102
FT TURN 103 108
FT HELIX 113 130
FT STRAND 134 136
FT STRAND 141 147
FT HELIX 154 156
FT HELIX 157 169
FT HELIX 172 174
FT STRAND 175 182
FT HELIX 195 207
FT STRAND 212 217
FT HELIX 224 233
FT HELIX 238 240
FT STRAND 241 244
FT HELIX 250 252
FT HELIX 253 259
FT HELIX 262 270
SQ SEQUENCE 591 AA; 66690 MW; 0B04F9D9390C4152 CRC64;
MKYILVTGGV ISGIGKGIIA SSVGTILKSC GLHVTSIKID PYINIDAGTF SPYEHGEVFV
LDDGGEVDLD LGNYERFLDI RLTKDNNLTT GKIYQYVINK ERKGDYLGKT VQVVPHITDA
IQEWVMRQAL IPVDEDGLEP QVCVIELGGT VGDIESMPFI EAFRQFQFKV KRENFCNIHV
SLVPQPSSTG EQKTKPTQNS VRELRGLGLS PDLVVCRCSN PLDTSVKEKI SMFCHVEPEQ
VICVHDVSSI YRVPLLLEEQ GVVDYFLRRL DLPIERQPRK MLMKWKEMAD RYDRLLETCS
IALVGKYTKF SDSYASVIKA LEHSALAINH KLEIKYIDSA DLEPITSQEE PVRYHEAWQK
LCSAHGVLVP GGFGVRGTEG KIQAIAWARN QKKPFLGVCL GMQLAVVEFS RNVLGWQDAN
STEFDPTTSH PVVVDMPEHN PGQMGGTMRL GKRRTLFQTK NSVMRKLYGD ADYLEERHRH
RFEVNPVWKK CLEEQGLKFV GQDVEGERME IVELEDHPFF VGVQYHPEFL SRPIKPSPPY
FGLLLASVGR LSHYLQKGCR LSPRDTYSDR SGSSSPDSEI TELKFPSINH D
//
MIM
123860
*RECORD*
*FIELD* NO
123860
*FIELD* TI
*123860 CYTIDINE 5-PRIME TRIPHOSPHATE SYNTHETASE; CTPS
;;CTP SYNTHETASE;;
CTP SYNTHASE
read more*FIELD* TX
DESCRIPTION
The catalytic conversion of UTP to CTP is accomplished by the enzyme
cytidine-5-prime-triphosphate synthetase (UTP:L-glutamine amido ligase;
EC 6.3.4.2). The enzyme, encoded by the CTPS gene, is important in the
biosynthesis of phospholipids and nucleic acids, and plays a key role in
cell growth, development, and tumorigenesis (summary by Thomas et al.,
1989).
CLONING
Thomas et al. (1989) isolated a cDNA clone of the CTP synthetase gene
from a rat liver cDNA library. It is a key regulatory enzyme in
pyrimidine biosynthesis. These authors isolated both cDNA and genomic
gene sequences from the rat and Chinese hamster.
Yamauchi et al. (1990) cloned the CTPS gene and showed that the open
reading frame encodes 591 amino acids that have a striking degree of
similarity to the structural gene in E. coli.
GENE STRUCTURE
Yamauchi et al. (1991) determined that the CTPS genomic sequence is
distributed in 19 exons covering about 35 kb.
MAPPING
Yamauchi et al. (1991) assigned the structural CTPS gene to chromosome
1p by study of a panel of human/rodent somatic cell hybrids and the CTPS
cDNA. By a method of mapping that combines fluorescence in situ
hybridization with replicated prometaphase R-bands (Takahashi et al.,
1990), Takahashi et al. (1991) mapped the CTPS gene to 1p34.3-p34.1. By
high-resolution banding analysis, they further narrowed the assignment
to 1p34.1; see Yamauchi et al. (1991).
MOLECULAR GENETICS
Mutations eliminating the feedback regulation of CTPS result in
multidrug resistance and mutator phenotype in Chinese hamster ovary
(CHO) cells. The region to which the CTPS gene has been mapped is the
location of breakpoints involved in several tumor types. Yamauchi et al.
(1993) found that inactivating mutations clustered in a highly conserved
region of the gene make it feasible to assess the role of such mutations
in the development of drug resistance encountered in the treatment of
malignant disease and not readily explained by altered expression of the
multidrug resistance genes (e.g., 171050).
Whelan et al. (1993) found that dominantly acting mutations that
eliminate the allosteric regulation of CTP synthetase confer a form of
multidrug resistance and a mutator phenotype on cultured Chinese hamster
ovary cells. Mutations responsible for this phenotype were identified in
23 independent strains selected for resistance to arabinosyl cytosine
and 5-fluorouracil. All these mutations were due to base substitutions
at 7 sites within a highly conserved region of the CTPS gene.
*FIELD* SA
Takahashi et al. (1991)
*FIELD* RF
1. Takahashi, E.; Hori, T.; O'Connell, P.; Leppert, M.; White, R.
: R-banding and nonisotopic in situ hybridization: precise localization
of the human type II collagen gene (COL2A1). Hum. Genet. 86: 14-16,
1990.
2. Takahashi, E.; Yamauchi, M.; Tsuji, H.; Hitomi, A.; Meuth, M.;
Hori, T.: Chromosome mapping of the human cytidine-5-prime-triphosphate
synthetase (CTPS) gene to band 1p34.1-p34.3 by fluorescence in situ
hybridization. Hum. Genet. 88: 119-121, 1991.
3. Takahashi, E.-I.; Yamauchi, M.; Ayusawa, D.; Kaneda, S.; Seno,
T.; Meuth, M.; Hori, T.-A.: Chromosome mappings of the human cytidine-5-prime-triphosphate
synthetase (CTPS) gene and the human ubiquitin-activating enzyme UBE1
gene by fluorescence in situ hybridization. (Abstract) Cytogenet.
Cell Genet. 58: 1864 only, 1991.
4. Thomas, P. E.; Sen, S.; Lamb, B. J.; Chu, E. H. Y.: Cloning and
expression of mammalian CTP synthetase genes. (Abstract) Am. J. Hum.
Genet. 45 (suppl.): A11 only, 1989.
5. Whelan, J.; Phear, G.; Yamauchi, M.; Meuth, M.: Clustered base
substitutions in CTP synthetase conferring drug resistance in Chinese
hamster ovary cells. Nature Genet. 3: 317-322, 1993.
6. Yamauchi, M.; Takahashi, E.; Whelan, J.; Phear, G.; Meuth, M.:
Mapping and functional analysis of the cytidine triphosphate synthetase
(CTPS) gene. (Abstract) Human Genome Mapping Workshop 93 1 only,
1993.
7. Yamauchi, M.; Yamauchi, N.; Meuth, M.: Molecular cloning of the
human CTP synthetase gene by functional complementation with purified
human metaphase chromosomes. EMBO J. 9: 2095-2099, 1990.
8. Yamauchi, M.; Yamauchi, N.; Phear, G.; Spurr, N. K.; Martinsson,
T.; Weith, A.; Meuth, M.: Genomic organization and chromosomal localization
of the human CTP synthetase gene (CTPS). Genomics 11: 1088-1096,
1991.
*FIELD* CD
Victor A. McKusick: 11/16/1989
*FIELD* ED
alopez: 03/02/2012
alopez: 7/19/2010
carol: 7/8/1998
carol: 2/17/1994
carol: 12/2/1993
carol: 1/14/1993
supermim: 3/16/1992
carol: 2/21/1992
carol: 1/3/1992
*RECORD*
*FIELD* NO
123860
*FIELD* TI
*123860 CYTIDINE 5-PRIME TRIPHOSPHATE SYNTHETASE; CTPS
;;CTP SYNTHETASE;;
CTP SYNTHASE
read more*FIELD* TX
DESCRIPTION
The catalytic conversion of UTP to CTP is accomplished by the enzyme
cytidine-5-prime-triphosphate synthetase (UTP:L-glutamine amido ligase;
EC 6.3.4.2). The enzyme, encoded by the CTPS gene, is important in the
biosynthesis of phospholipids and nucleic acids, and plays a key role in
cell growth, development, and tumorigenesis (summary by Thomas et al.,
1989).
CLONING
Thomas et al. (1989) isolated a cDNA clone of the CTP synthetase gene
from a rat liver cDNA library. It is a key regulatory enzyme in
pyrimidine biosynthesis. These authors isolated both cDNA and genomic
gene sequences from the rat and Chinese hamster.
Yamauchi et al. (1990) cloned the CTPS gene and showed that the open
reading frame encodes 591 amino acids that have a striking degree of
similarity to the structural gene in E. coli.
GENE STRUCTURE
Yamauchi et al. (1991) determined that the CTPS genomic sequence is
distributed in 19 exons covering about 35 kb.
MAPPING
Yamauchi et al. (1991) assigned the structural CTPS gene to chromosome
1p by study of a panel of human/rodent somatic cell hybrids and the CTPS
cDNA. By a method of mapping that combines fluorescence in situ
hybridization with replicated prometaphase R-bands (Takahashi et al.,
1990), Takahashi et al. (1991) mapped the CTPS gene to 1p34.3-p34.1. By
high-resolution banding analysis, they further narrowed the assignment
to 1p34.1; see Yamauchi et al. (1991).
MOLECULAR GENETICS
Mutations eliminating the feedback regulation of CTPS result in
multidrug resistance and mutator phenotype in Chinese hamster ovary
(CHO) cells. The region to which the CTPS gene has been mapped is the
location of breakpoints involved in several tumor types. Yamauchi et al.
(1993) found that inactivating mutations clustered in a highly conserved
region of the gene make it feasible to assess the role of such mutations
in the development of drug resistance encountered in the treatment of
malignant disease and not readily explained by altered expression of the
multidrug resistance genes (e.g., 171050).
Whelan et al. (1993) found that dominantly acting mutations that
eliminate the allosteric regulation of CTP synthetase confer a form of
multidrug resistance and a mutator phenotype on cultured Chinese hamster
ovary cells. Mutations responsible for this phenotype were identified in
23 independent strains selected for resistance to arabinosyl cytosine
and 5-fluorouracil. All these mutations were due to base substitutions
at 7 sites within a highly conserved region of the CTPS gene.
*FIELD* SA
Takahashi et al. (1991)
*FIELD* RF
1. Takahashi, E.; Hori, T.; O'Connell, P.; Leppert, M.; White, R.
: R-banding and nonisotopic in situ hybridization: precise localization
of the human type II collagen gene (COL2A1). Hum. Genet. 86: 14-16,
1990.
2. Takahashi, E.; Yamauchi, M.; Tsuji, H.; Hitomi, A.; Meuth, M.;
Hori, T.: Chromosome mapping of the human cytidine-5-prime-triphosphate
synthetase (CTPS) gene to band 1p34.1-p34.3 by fluorescence in situ
hybridization. Hum. Genet. 88: 119-121, 1991.
3. Takahashi, E.-I.; Yamauchi, M.; Ayusawa, D.; Kaneda, S.; Seno,
T.; Meuth, M.; Hori, T.-A.: Chromosome mappings of the human cytidine-5-prime-triphosphate
synthetase (CTPS) gene and the human ubiquitin-activating enzyme UBE1
gene by fluorescence in situ hybridization. (Abstract) Cytogenet.
Cell Genet. 58: 1864 only, 1991.
4. Thomas, P. E.; Sen, S.; Lamb, B. J.; Chu, E. H. Y.: Cloning and
expression of mammalian CTP synthetase genes. (Abstract) Am. J. Hum.
Genet. 45 (suppl.): A11 only, 1989.
5. Whelan, J.; Phear, G.; Yamauchi, M.; Meuth, M.: Clustered base
substitutions in CTP synthetase conferring drug resistance in Chinese
hamster ovary cells. Nature Genet. 3: 317-322, 1993.
6. Yamauchi, M.; Takahashi, E.; Whelan, J.; Phear, G.; Meuth, M.:
Mapping and functional analysis of the cytidine triphosphate synthetase
(CTPS) gene. (Abstract) Human Genome Mapping Workshop 93 1 only,
1993.
7. Yamauchi, M.; Yamauchi, N.; Meuth, M.: Molecular cloning of the
human CTP synthetase gene by functional complementation with purified
human metaphase chromosomes. EMBO J. 9: 2095-2099, 1990.
8. Yamauchi, M.; Yamauchi, N.; Phear, G.; Spurr, N. K.; Martinsson,
T.; Weith, A.; Meuth, M.: Genomic organization and chromosomal localization
of the human CTP synthetase gene (CTPS). Genomics 11: 1088-1096,
1991.
*FIELD* CD
Victor A. McKusick: 11/16/1989
*FIELD* ED
alopez: 03/02/2012
alopez: 7/19/2010
carol: 7/8/1998
carol: 2/17/1994
carol: 12/2/1993
carol: 1/14/1993
supermim: 3/16/1992
carol: 2/21/1992
carol: 1/3/1992