Q9NRF8 (PYRG2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
CTP synthase 2
EC=6.3.4.2

Alternative name(s):
CTP synthetase 2
UTP--ammonia ligase 2

Gene names

Name:

CTPS2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	586 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. Constitutes the rate-limiting enzyme in the synthesis of cytosine nucleotides. Ref.1 Ref.6
Catalytic activity	ATP + UTP + NH3 = ADP + phosphate + 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
Domain	Glutamine amidotransferase
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	'de novo' CTP biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway glutamine metabolic process Inferred from electronic annotation. Source: UniProtKB-KW nucleobase-containing small molecule interconversion Traceable author statement. Source: Reactome pyrimidine nucleotide metabolic process Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW CTP synthase activity Inferred from experiment. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 586

586

CTP synthase 2

PRO_0000247033

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

568

1

Phosphoserine Ref.8 Ref.9 Ref.11

Modified residue

571

1

Phosphoserine Ref.7 Ref.8 Ref.9 Ref.11

Modified residue

574

1

Phosphoserine Ref.8 Ref.9

Experimental info

Sequence conflict

220

1

T → S in BAB14814. Ref.2

Sequence conflict

233

1

F → L in BAB14607. Ref.2

Sequence conflict

304

1

V → A in BAB14607. Ref.2

Secondary structure

1

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586

Helix Strand Turn

Details...

Beta strand

2 – 8

7

Beta strand

10 – 15

6

Helix

16 – 28

13

Turn

29 – 31

3

Beta strand

34 – 40

7

Beta strand

87 – 89

3

Helix

90 – 102

13

Turn

103 – 108

6

Helix

113 – 129

17

Beta strand

141 – 147

7

Helix

154 – 156

3

Helix

157 – 169

13

Helix

172 – 174

3

Beta strand

175 – 182

8

Turn

187 – 189

3

Helix

195 – 206

12

Beta strand

212 – 220

9

Helix

224 – 233

10

Helix

238 – 240

3

Beta strand

241 – 245

5

Helix

252 – 259

8

Helix

262 – 270

9

Beta strand

297 – 306

10

Helix

312 – 314

3

Helix

315 – 327

13

Beta strand

330 – 338

9

Helix

339 – 342

4

Helix

344 – 349

6

Helix

351 – 363

13

Beta strand

365 – 369

5

Helix

378 – 390

13

Beta strand

395 – 398

4

Helix

400 – 413

14

Beta strand

419 – 422

4

Beta strand

429 – 435

7

Beta strand

449 – 458

10

Helix

463 – 467

5

Beta strand

472 – 480

9

Beta strand

482 – 484

3

Helix

486 – 488

3

Helix

490 – 492

3

Beta strand

495 – 503

9

Beta strand

508 – 518

11

Beta strand

520 – 526

7

Helix

527 – 530

4

Helix

538 – 548

11

Helix

551 – 556

6

Sequences

	Sequence		Length	Mass (Da)
	Q9NRF8 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: AC1CF2E67D89741B	FASTA	586	65,678
	10 20 30 40 50 60 MKYILVTGGV ISGIGKGIIA SSIGTILKSC GLRVTAIKID PYINIDAGTF SPYEHGEVFV 70 80 90 100 110 120 LNDGGEVDLD LGNYERFLDI NLYKDNNITT GKIYQHVINK ERRGDYLGKT VQVVPHITDA 130 140 150 160 170 180 VQEWVMNQAK VPVDGNKEEP QICVIELGGT IGDIEGMPFV EAFRQFQFKA KRENFCNIHV 190 200 210 220 230 240 SLVPQLSATG EQKTKPTQNS VRALRGLGLS PDLIVCRSST PIEMAVKEKI SMFCHVNPEQ 250 260 270 280 290 300 VICIHDVSST YRVPVLLEEQ SIVKYFKERL HLPIGDSASN LLFKWRNMAD RYERLQKICS 310 320 330 340 350 360 IALVGKYTKL RDCYASVFKA LEHSALAINH KLNLMYIDSI DLEKITETED PVKFHEAWQK 370 380 390 400 410 420 LCKADGILVP GGFGIRGTLG KLQAISWART KKIPFLGVCL GMQLAVIEFA RNCLNLKDAD 430 440 450 460 470 480 STEFRPNAPV PLVIDMPEHN PGNLGGTMRL GIRRTVFKTE NSILRKLYGD VPFIEERHRH 490 500 510 520 530 540 RFEVNPNLIK QFEQNDLSFV GQDVDGDRME IIELANHPYF VGVQFHPEFS SRPMKPSPPY 550 560 570 580 LGLLLAATGN LNAYLQQGCK LSSSDRYSDA SDDSFSEPRI AELEIS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a cDNA encoding an isoform of human CTP synthetase." van Kuilenburg A.B.P., Meinsma R., Vreken P., Waterham H.R., van Gennip A.H. Biochim. Biophys. Acta 1492:548-552(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta and Retinoblastoma.
[3]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung and Testis.
[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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-571, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-568; SER-571 AND SER-574, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-568; SER-571 AND SER-574, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-568 AND SER-571, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF226667 mRNA. Translation: AAF91241.1.
AK023549 mRNA. Translation: BAB14607.1.
AK024070 mRNA. Translation: BAB14814.1.
AK125332 mRNA. Translation: BAG54184.1.
AK125348 mRNA. Translation: BAG54188.1.
AL445467, AC073909 Genomic DNA. Translation: CAI40086.1.
CH471074 Genomic DNA. Translation: EAW98912.1.
BC006256 mRNA. Translation: AAH06256.2.
BC034986 mRNA. Translation: AAH34986.1.

IPI

IPI00645702.

RefSeq

NP_001137474.1. NM_001144002.1.
NP_062831.3. NM_019857.3.
NP_787055.1. NM_175859.1.

UniGene

Hs.227049.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2V4U	X-ray	2.30	A	297-562	[»]
2VKT	X-ray	2.50	A	297-562	[»]
3IHL	X-ray	2.80	A/B	1-275	[»]

ProteinModelPortal

Q9NRF8.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NRF8. 6 interactions.

MINT

MINT-1443035.

STRING

9606.ENSP00000352222.

PTM databases

PhosphoSite

Q9NRF8.

Polymorphism databases

DMDM

74752919.

Proteomic databases

PaxDb

Q9NRF8.

PRIDE

Q9NRF8.

Protocols and materials databases

DNASU

56474.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000359276; ENSP00000352222; ENSG00000047230.
ENST00000380241; ENSP00000369590; ENSG00000047230.
ENST00000443824; ENSP00000401264; ENSG00000047230.

GeneID

56474.

KEGG

hsa:56474.

UCSC

uc004cxk.3. human.

Organism-specific databases

CTD

56474.

GeneCards

GC0XM016606.

HGNC

HGNC:2520. CTPS2.

HPA

HPA017437.

MIM

300380. gene.

neXtProt

NX_Q9NRF8.

PharmGKB

PA27021.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0504.

HOGENOM

HOG000077514.

HOVERGEN

HBG002243.

InParanoid

Q9NRF8.

KO

K01937.

OMA

FEVNPNL.

OrthoDB

EOG4868C4.

Enzyme and pathway databases

BioCyc

MetaCyc:HS00585-MONOMER.

BRENDA

6.3.4.2. 2681.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00159; UER00277.

Gene expression databases

ArrayExpress

Q9NRF8.

Bgee

Q9NRF8.

CleanEx

HS_CTPS2.

Genevestigator

Q9NRF8.

GermOnline

ENSG00000047230. Homo sapiens.

Family and domain databases

InterPro

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

PANTHER

PTHR11550. PTHR11550. 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

EvolutionaryTrace

Q9NRF8.

GenomeRNAi

56474.

NextBio

62001.

SOURCE

Search...

Entry information

Entry name

PYRG2_HUMAN

Accession

Primary (citable) accession number: Q9NRF8
Secondary accession number(s): B3KWM2 , Q9BRI0, Q9H809, Q9H8K9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 25, 2006
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 103 of the entry and version 1 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.