P17812 (PYRG1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
CTP synthase 1
EC=6.3.4.2

Alternative name(s):
CTP synthetase 1
UTP--ammonia ligase 1

Gene names

Name:

CTPS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	591 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen. Ref.6
Catalytic activity	ATP + UTP + NH3 = ADP + phosphate + CTP.
Enzyme regulation	Activated by GTP and inhibited by CTP.
Pathway	Pyrimidine metabolism; CTP biosynthesis via de novo pathway; CTP from UDP: step 2/2.
Sequence similarities	Belongs to the CTP synthase family. Contains 1 glutamine amidotransferase type-1 domain.

Ontologies

Keywords
Biological process	Pyrimidine biosynthesis
Coding sequence diversity	Polymorphism
Domain	Glutamine amidotransferase
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	CTP biosynthetic process Inferred from direct assay Ref.6. Source: UniProtKB glutamine metabolic process Inferred from electronic annotation. Source: UniProtKB-KW nucleobase-containing small molecule interconversion Traceable author statement. Source: Reactome response to drug Traceable author statement. Source: ProtInc
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW CTP synthase activity Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 591

591

CTP synthase 1

PRO_0000138275

Regions

Domain

300 – 554

255

Glutamine amidotransferase type-1

Sites

Active site

399

1

For GATase activity By similarity

Active site

526

1

For GATase activity By similarity

Active site

528

1

For GATase activity By similarity

Amino acid modifications

Modified residue

100

1

N6-acetyllysine Ref.17

Modified residue

562

1

Phosphoserine Ref.9

Modified residue

566

1

Phosphothreonine By similarity

Modified residue

567

1

Phosphotyrosine By similarity

Modified residue

568

1

Phosphoserine Ref.10 Ref.13 Ref.14

Modified residue

571

1

Phosphoserine Ref.8 Ref.10 Ref.12 Ref.13 Ref.14 Ref.16

Modified residue

573

1

Phosphoserine Ref.8 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15

Modified residue

574

1

Phosphoserine Ref.8 Ref.10 Ref.13 Ref.14 Ref.16

Modified residue

575

1

Phosphoserine Ref.5 Ref.7 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16

Modified residue

581

1

Phosphothreonine Ref.13

Modified residue

587

1

Phosphoserine Ref.13

Natural variations

Natural variant

571

1

S → I. Ref.4
Corresponds to variant rs17856308 [ dbSNP | Ensembl ].

VAR_027055

Experimental info

Sequence conflict

305

1

G → A in CAA36386. Ref.1

Sequence conflict

309

1

K → E in CAA36386. Ref.1

Secondary structure

1

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591

Helix Strand Turn

Details...

Beta strand

2 – 8

7

Helix

16 – 28

13

Turn

29 – 31

3

Beta strand

38 – 40

3

Beta strand

87 – 89

3

Helix

90 – 102

13

Turn

113 – 115

3

Helix

116 – 128

13

Beta strand

141 – 147

7

Helix

157 – 164

8

Turn

165 – 169

5

Turn

172 – 174

3

Beta strand

175 – 182

8

Turn

187 – 189

3

Helix

195 – 206

12

Beta strand

212 – 217

6

Helix

226 – 232

7

Turn

233 – 235

3

Helix

250 – 252

3

Helix

253 – 258

6

Turn

259 – 261

3

Helix

262 – 269

8

Sequences

	Sequence		Length	Mass (Da)
	P17812 [UniParc]. Last modified May 15, 2002. Version 2. Checksum: 0B04F9D9390C4152	FASTA	591	66,690
	10 20 30 40 50 60 MKYILVTGGV ISGIGKGIIA SSVGTILKSC GLHVTSIKID PYINIDAGTF SPYEHGEVFV 70 80 90 100 110 120 LDDGGEVDLD LGNYERFLDI RLTKDNNLTT GKIYQYVINK ERKGDYLGKT VQVVPHITDA 130 140 150 160 170 180 IQEWVMRQAL IPVDEDGLEP QVCVIELGGT VGDIESMPFI EAFRQFQFKV KRENFCNIHV 190 200 210 220 230 240 SLVPQPSSTG EQKTKPTQNS VRELRGLGLS PDLVVCRCSN PLDTSVKEKI SMFCHVEPEQ 250 260 270 280 290 300 VICVHDVSSI YRVPLLLEEQ GVVDYFLRRL DLPIERQPRK MLMKWKEMAD RYDRLLETCS 310 320 330 340 350 360 IALVGKYTKF SDSYASVIKA LEHSALAINH KLEIKYIDSA DLEPITSQEE PVRYHEAWQK 370 380 390 400 410 420 LCSAHGVLVP GGFGVRGTEG KIQAIAWARN QKKPFLGVCL GMQLAVVEFS RNVLGWQDAN 430 440 450 460 470 480 STEFDPTTSH PVVVDMPEHN PGQMGGTMRL GKRRTLFQTK NSVMRKLYGD ADYLEERHRH 490 500 510 520 530 540 RFEVNPVWKK CLEEQGLKFV GQDVEGERME IVELEDHPFF VGVQYHPEFL SRPIKPSPPY 550 560 570 580 590 FGLLLASVGR LSHYLQKGCR LSPRDTYSDR SGSSSPDSEI TELKFPSINH D

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of the human CTP synthetase gene by functional complementation with purified human metaphase chromosomes." Yamauchi M., Yamauchi N., Meuth M. EMBO J. 9:2095-2099(1990) [PubMed: 2113467] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-571. Tissue: Eye.
[5]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-575, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"Expression of human CTP synthetase in Saccharomyces cerevisiae reveals phosphorylation by protein kinase A." Han G.-S., Sreenivas A., Choi M.-G., Chang Y.-F., Martin S.S., Baldwin E.P., Carman G.M. J. Biol. Chem. 280:38328-38336(2005) [PubMed: 16179339] [Abstract] Cited for: FUNCTION.
[7]	"Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-575, MASS SPECTROMETRY. Tissue: Colon adenocarcinoma.
[8]	"Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC." Gevaert K., Staes A., Van Damme J., De Groot S., Hugelier K., Demol H., Martens L., Goethals M., Vandekerckhove J. Proteomics 5:3589-3599(2005) [PubMed: 16097034] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-571; SER-573 AND SER-574, MASS SPECTROMETRY. Tissue: Hepatoma.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-562, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-568; SER-571; SER-573; SER-574 AND SER-575, MASS SPECTROMETRY. Tissue: Platelet.
[11]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-575, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-571; SER-573 AND SER-575, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-568; SER-571; SER-573; SER-574; SER-575; THR-581 AND SER-587, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-568; SER-571; SER-573; SER-574 AND SER-575, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[15]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-573, MASS SPECTROMETRY.
[16]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-571; SER-574 AND SER-575, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[17]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-100, MASS SPECTROMETRY.
[18]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]	"Crystal structure of the synthetase domain of human CTP synthetase." Stenmark P., Kursula P., Arrowsmith C., Berglund H., Edwards A., Ehn M., Flodin S., Graslund S., Hammarstrom M., Hallberg B.M., Holmberg Schiavone L., Kotenyova T., Nilsson-ehle P., Ogg D., Persson C., Sagemark J., Schuler H., Sundstrom M. , Thorsell A.G., van den Berg S., Weigelt J., Nordlund P. Submitted (NOV-2005) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-272.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X52142 mRNA. Translation: CAA36386.1.
AL391730 Genomic DNA. Translation: CAH72797.1.
CH471059 Genomic DNA. Translation: EAX07192.1.
CH471059 Genomic DNA. Translation: EAX07193.1.
BC009408 mRNA. Translation: AAH09408.1.

IPI

IPI00290142.

PIR

SYHUTP. S12791.

RefSeq

NP_001896.2. NM_001905.2.

UniGene

Hs.473087.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VO1	X-ray	2.80	A/B	1-273	[»]

ProteinModelPortal

P17812.

SMR

P17812. Positions 1-273, 296-562.

ModBase

Search...

Protein-protein interaction databases

IntAct

P17812. 7 interactions.

MINT

MINT-3008801.

STRING

P17812.

PTM databases

PhosphoSite

P17812.

Polymorphism databases

DMDM

20981706.

Proteomic databases

PeptideAtlas

P17812.

PRIDE

P17812.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000372616; ENSP00000361699; ENSG00000171793.
ENST00000372621; ENSP00000361704; ENSG00000171793.

GeneID

1503.

KEGG

hsa:1503.

UCSC

uc001cgk.2. human.

Organism-specific databases

CTD

1503.

GeneCards

GC01P041479.

H-InvDB

HIX0000479.

HGNC

HGNC:2519. CTPS.

HPA

CAB017111.

MIM

123860. gene.

neXtProt

NX_P17812.

PharmGKB

PA27020.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08333.

GeneTree

ENSGT00390000012473.

HOGENOM

HBG597806.

HOVERGEN

HBG002243.

InParanoid

P17812.

OMA

RVTMQKL.

OrthoDB

EOG4868C4.

PhylomeDB

P17812.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000171793-MONOMER.

BRENDA

6.3.4.2. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P17812.

Bgee

P17812.

CleanEx

HS_CTPS.

Genevestigator

P17812.

GermOnline

ENSG00000171793. Homo sapiens.

Family and domain databases

InterPro

IPR004468. CTP_synthase.
IPR017456. CTP_synthase_N.
IPR017926. GATASE_1.
[Graphical view]

KO

K01937.

PANTHER

PTHR11550. PyrG_synth. 1 hit.

Pfam

PF06418. CTP_synth_N. 1 hit.
PF00117. GATase. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00337. PyrG. 1 hit.

PROSITE

PS51273. GATASE_TYPE_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00130. L-Glutamine.

NextBio

6221.

SOURCE

Search...

Entry information

Entry name

PYRG1_HUMAN

Accession

Primary (citable) accession number: P17812
Secondary accession number(s): D3DPW1, Q5VW67, Q96GK6

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	May 15, 2002
Last modified:	January 25, 2012
This is version 129 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.