CTPS2

Summary

CTPS2 (CTP synthase 2, HGNC:2520) is a protein-coding gene on chromosome Xp22.2, encoding CTP synthase 2 (Q9NRF8). CTP synthase involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids.

The protein encoded by this gene catalyzes the formation of CTP from UTP with the concomitant deamination of glutamine to glutamate. This protein is the rate-limiting enzyme in the synthesis of cytosine nucleotides, which play an important role in various metabolic processes and provide the precursors necessary for the synthesis of RNA and DNA. Cancer cells that exhibit increased cell proliferation also exhibit an increased activity of this encoded protein. Thus, this protein is an attractive target for selective chemotherapy. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 56474 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 202 total
• GTEx eGene: eQTL in 15 tissues, sQTL in 0 (q < 0.05)
• MANE Select transcript: NM_175859
• Interaction hub: 2,512 STRING partners (top 4% of genes corpus-wide)
• Notable: 202 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2520
Approved symbol	CTPS2
Name	CTP synthase 2
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Aliases	GATD5B
Ensembl gene	ENSG00000047230
Ensembl biotype	protein_coding
OMIM	300380
Entrez	56474

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 42 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000359276

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 1, TSL 5: 1

ENST00000359276, ENST00000380241, ENST00000443824, ENST00000455276, ENST00000483053, ENST00000870414, ENST00000870415, ENST00000870416, ENST00000870417, ENST00000870418, ENST00000870419, ENST00000870420, ENST00000870421, ENST00000870422, ENST00000870423, ENST00000870424, ENST00000870425, ENST00000870426, ENST00000870427, ENST00000870428, ENST00000913871, ENST00000913872, ENST00000913873, ENST00000913874, ENST00000913875, ENST00000913876, ENST00000944979, ENST00000944980, ENST00000944981, ENST00000944982, ENST00000944983, ENST00000944984, ENST00000944985, ENST00000944986, ENST00000944987, ENST00000944988, ENST00000944989, ENST00000997495, ENST00001077646, ENST00001111204, ENST00001111205, ENST00001114822, ENST00001114823, ENST00001133483

RefSeq mRNA: 3 — MANE Select: NM_175859 NM_001144002, NM_019857, NM_175859

CCDS: CCDS14175

Canonical transcript exons

ENST00000359276 — 19 exons

Exon	Start	End
ENSE00001150642	16639147	16639243
ENSE00001150648	16667514	16667557
ENSE00001150654	16667662	16667724
ENSE00001150661	16670580	16670674
ENSE00001150669	16678362	16678450
ENSE00001201944	16609541	16609685
ENSE00001201948	16617150	16617246
ENSE00001201953	16620277	16620332
ENSE00001277888	16590752	16590862
ENSE00001430890	16712335	16712669
ENSE00001612556	16693371	16693487
ENSE00001622171	16691540	16691620
ENSE00001708554	16698923	16699093
ENSE00001710627	16689450	16689601
ENSE00001723130	16698236	16698336
ENSE00001733932	16693141	16693224
ENSE00001778300	16683094	16683226
ENSE00002731939	16702737	16702941
ENSE00003843996	16587999	16589775

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 90.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.9775 / max 137.5056, expressed in 1689 samples.

Highest expression (Bgee): jejunal mucosa, ventricular zone, body of pancreas, endocervix, ovary.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CTPS2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 15 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

15 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Liver	eqtl	2.0e-08	-0.37	X:16771730:T:C
Brain Cortex	eqtl	2.2e-05	-0.69	X:17272039:A:C
Colon Transverse	eqtl	3.8e-05	+0.17	X:16660270:G:C
Brain Hippocampus	eqtl	1.2e-04	-0.73	X:17272039:A:C
Muscle Skeletal	eqtl	1.4e-03	+0.13	X:16663501:T:C
Brain Anterior cingulate cortex BA24	eqtl	1.4e-03	-0.93	X:16903963:G:C
Brain Hypothalamus	eqtl	2.5e-03	-0.66	X:17272039:A:C
Small Intestine Terminal Ileum	eqtl	2.6e-03	+0.24	X:16663645:C:T
Testis	eqtl	4.0e-03	+0.08	X:16841156:T:C
Brain Cerebellum	eqtl	5.2e-03	+0.53	X:16776085:G:A
Nerve Tibial	eqtl	1.1e-02	+0.41	X:16620350:C:T
Skin Not Sun Exposed Suprapubic	eqtl	1.6e-02	+0.10	X:16608907:G:T
Esophagus Mucosa	eqtl	2.0e-02	+0.59	X:16614605:A:G
Artery Tibial	eqtl	2.7e-02	-0.26	X:17667731:G:T
Adipose Subcutaneous	eqtl	4.3e-02	+0.13	X:17354512:C:T

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
198564	6.0931	1602
198565	3.2848	1148
198566	0.3811	208
198567	0.2185	114

Top tissues by expression

showing 100 of 278 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	90.02	gold quality
ventricular zone	UBERON:0003053	89.92	gold quality
body of pancreas	UBERON:0001150	88.60	gold quality
endocervix	UBERON:0000458	87.93	gold quality
right ovary	UBERON:0002118	87.89	gold quality
left ovary	UBERON:0002119	87.85	gold quality
ganglionic eminence	UBERON:0004023	87.69	gold quality
calcaneal tendon	UBERON:0003701	87.46	gold quality
duodenum	UBERON:0002114	86.81	gold quality
adrenal tissue	UBERON:0018303	86.73	gold quality
ovary	UBERON:0000992	86.69	gold quality
right uterine tube	UBERON:0001302	85.92	gold quality
visceral pleura	UBERON:0002401	85.83	gold quality
endometrium	UBERON:0001295	85.63	gold quality
ectocervix	UBERON:0012249	85.61	gold quality
body of uterus	UBERON:0009853	85.30	gold quality
minor salivary gland	UBERON:0001830	85.27	gold quality
right adrenal gland cortex	UBERON:0035827	85.20	gold quality
pancreas	UBERON:0001264	85.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.76	gold quality
body of stomach	UBERON:0001161	84.61	gold quality
rectum	UBERON:0001052	84.55	gold quality
right adrenal gland	UBERON:0001233	84.55	gold quality
embryo	UBERON:0000922	84.46	gold quality
tibial nerve	UBERON:0001323	84.42	gold quality
pleura	UBERON:0000977	84.27	gold quality
parietal pleura	UBERON:0002400	84.19	gold quality
mucosa of stomach	UBERON:0001199	84.18	gold quality
right lobe of liver	UBERON:0001114	84.06	gold quality
skin of abdomen	UBERON:0001416	84.03	gold quality
tibia	UBERON:0000979	84.02	gold quality
small intestine	UBERON:0002108	83.95	gold quality
transverse colon	UBERON:0001157	83.91	gold quality
left adrenal gland cortex	UBERON:0035825	83.90	gold quality
skin of leg	UBERON:0001511	83.85	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.85	gold quality
mucosa of transverse colon	UBERON:0004991	83.77	gold quality
cerebellar hemisphere	UBERON:0002245	83.65	gold quality
left adrenal gland	UBERON:0001234	83.61	gold quality
descending thoracic aorta	UBERON:0002345	83.58	gold quality
cerebellar cortex	UBERON:0002129	83.52	gold quality
stomach	UBERON:0000945	83.46	gold quality
ascending aorta	UBERON:0001496	83.36	gold quality
adrenal cortex	UBERON:0001235	83.33	gold quality
thoracic aorta	UBERON:0001515	83.27	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.25	gold quality
mouth mucosa	UBERON:0003729	83.21	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.20	gold quality
prostate gland	UBERON:0002367	83.18	gold quality
aorta	UBERON:0000947	83.01	gold quality
vagina	UBERON:0000996	82.97	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.93	gold quality
tibial artery	UBERON:0007610	82.92	gold quality
popliteal artery	UBERON:0002250	82.91	gold quality
left lobe of thyroid gland	UBERON:0001120	82.76	gold quality
intestine	UBERON:0000160	82.73	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.69	gold quality
lower esophagus	UBERON:0013473	82.67	gold quality
left uterine tube	UBERON:0001303	82.66	gold quality
adrenal gland	UBERON:0002369	82.66	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.55	gold quality
right lobe of thyroid gland	UBERON:0001119	82.53	gold quality
fundus of stomach	UBERON:0001160	82.41	gold quality
metanephros cortex	UBERON:0010533	82.36	gold quality
right lung	UBERON:0002167	82.35	gold quality
thyroid gland	UBERON:0002046	82.24	gold quality
uterus	UBERON:0000995	82.21	gold quality
colon	UBERON:0001155	82.17	gold quality
cerebellum	UBERON:0002037	82.17	gold quality
female reproductive system	UBERON:0000474	82.12	gold quality
large intestine	UBERON:0000059	82.09	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.08	gold quality
right coronary artery	UBERON:0001625	81.96	gold quality
zone of skin	UBERON:0000014	81.91	gold quality
islet of Langerhans	UBERON:0000006	81.87	gold quality
left coronary artery	UBERON:0001626	81.80	gold quality
cortical plate	UBERON:0005343	81.79	gold quality
saliva-secreting gland	UBERON:0001044	81.78	gold quality
spinal cord	UBERON:0002240	81.71	gold quality
stromal cell of endometrium	CL:0002255	81.32	gold quality
tendon	UBERON:0000043	81.27	gold quality
lower esophagus mucosa	UBERON:0035834	81.18	gold quality
coronary artery	UBERON:0001621	81.04	gold quality
esophagus	UBERON:0001043	81.00	gold quality
omental fat pad	UBERON:0010414	80.99	gold quality
peritoneum	UBERON:0002358	80.98	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.66	gold quality
right atrium auricular region	UBERON:0006631	80.34	gold quality
apex of heart	UBERON:0002098	80.21	gold quality
germinal epithelium of ovary	UBERON:0001304	80.14	gold quality
upper lobe of left lung	UBERON:0008952	79.84	gold quality
adipose tissue	UBERON:0001013	79.74	gold quality
jejunum	UBERON:0002115	79.71	gold quality
esophagus mucosa	UBERON:0002469	79.71	gold quality
gall bladder	UBERON:0002110	79.67	gold quality
corpus callosum	UBERON:0002336	79.47	gold quality
connective tissue	UBERON:0002384	79.44	gold quality
pigmented layer of retina	UBERON:0001782	79.25	gold quality
upper lobe of lung	UBERON:0008948	79.13	gold quality
adenohypophysis	UBERON:0002196	78.96	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.04

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	23.4
Caudate putamen	tissue	16.9
Nucleus accumbens	tissue	13.3
Choroid plexus	tissue	12.1
Ovary	tissue	11.6	high
Duodenum	tissue	11.6	high
Parathyroid gland	tissue	11.4	high
Cerebellum	tissue	9.9	medium
Breast	tissue	9.7	medium
Small intestine	tissue	9.7	high
Locus coeruleus	tissue	9.7
Endometrium 1	tissue	9.6	medium
Hippocampus	tissue	9.4	medium
Retina	tissue	9.1
Cervix	tissue	8.9	medium
Rectum	tissue	8.9	high
Prostate	tissue	8.9	high
Hypothalamus	tissue	8.8
Postcentral gyrus	tissue	8.6
Olfactory bulb	tissue	8.6
Pons	tissue	8.5
Basal ganglia	tissue	8.5	medium
Periaqueductal gray	tissue	8.5
Fallopian tube	tissue	8.5	high
Putamen	tissue	8.3
Ventral forebrain	tissue	8.3
Amygdala	tissue	8.1
Superior colliculi	tissue	8.1
Corpus callosum	tissue	8.1
Hippocampal formation	tissue	8.1
Entorhinal cortex	tissue	8.1
Septum	tissue	8.1
Cerebral cortex	tissue	7.9	high
Substantia nigra	tissue	7.9
Spinal cord	tissue	7.9
Occipital cortex	tissue	7.9
Stomach 1	tissue	7.8	medium
Pancreas	tissue	7.8	medium
Prefrontal cortex	tissue	7.7
Thalamus	tissue	7.7
Temporal cortex	tissue	7.7
Tonsil	tissue	7.6	high
Retrosplenial and cingulate cortex	tissue	7.6
Retrosplenial cortex	tissue	7.6
Colon	tissue	7.5	high
Midbrain	tissue	7.5
Medulla oblongata	tissue	7.5
Insular cortex	tissue	7.5
Somatosensory cortex	tissue	7.2
Liver	tissue	7.0	medium
Smooth muscle	tissue	6.9	medium
Motor cortex	tissue	6.8
Skin 1	tissue	6.7	low
Seminal vesicle	tissue	6.6	medium
Adrenal gland	tissue	6.5	medium
Thyroid gland	tissue	6.4	medium
Gallbladder	tissue	6.4	high
Bone marrow	tissue	6.4	low
Vagina	tissue	6.3	medium
Epididymis	tissue	6.3	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Parieto-temporal junction (white matter) (18.1), Corpus callosum, genu (white matter) (17.4), Cerebellar white matter (16.4), Corpus callosum, splenium (white matter) (16.2), Nucleus raphe obscurus (16.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CTPS2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 88 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-944	99.82	70.85	3042

Functional genomics

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000359276 — one region, missense o/e 0.64.

Literature-anchored findings (GeneRIF, showing 4)

• analysis of the kinetic properties of hCTPS1 and hCTPS2, and determination that Ser(68) is a major site of CTPS2 regulation by phosphorylation (PMID:20739275)
• CTPS2 was identified by genome-wide gene expression analyses as correlated with cellular sensitivity to cisplatin and carboplatin. (PMID:21252287)
• Low CTPS2 expression may be a rationally-based determinant of 5FU resistance. (PMID:21378502)
• Cryo-EM structures reveal that CTPS2 filaments dynamically switch between active and inactive forms in response to changes in substrate and product levels. (PMID:31873303)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ctps2	ENSMUSG00000031360
rattus_norvegicus	Ctps2	ENSRNOG00000004257
drosophila_melanogaster	Ctps	FBGN0266452
caenorhabditis_elegans		WBGENE00012316

Paralogs (1): CTPS1 (ENSG00000171793)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Saccharomyces cerevisiae YJM789	A6ZQ59	99.8%	Diamond
Saccharomyces cerevisiae S288C	P38627	99.8%	Diamond
Cricetulus griseus	P50547	99.5%	Diamond
Xenopus laevis	Q5XHA8	98.5%	Diamond
Bos taurus	Q1RMS2	95.6%	Diamond
Drosophila pseudoobscura pseudoobscura	Q2M197	89.8%	Diamond
Danio rerio	Q6PEI7	87.1%	Diamond
Gallus gallus	Q5F3Z1	86.9%	Diamond
Nakaseomyces glabratus CBS 138	Q6FUD0	84.5%	Diamond
Eremothecium gossypii ATCC 10895	Q751L7	80.3%	Diamond
Schizosaccharomyces pombe 972h-	O42644	68.2%	Diamond
Fusarium graminearum PH-1	O74638	67.2%	Diamond
Neurospora crassa OR74A	Q7RZV2	66.6%	Diamond
Dictyostelium discoideum	Q54V77	60.2%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SQI7	43.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR548AM	ncRNA	100616428
TXLNG	protein-coding	55787
S100G	protein-coding	795
SYAP1	protein-coding	94056

Protein

Protein identifiers

CTP synthase 2 — Q9NRF8 (reviewed: Q9NRF8)

Alternative names: CTP synthetase 2, UTP–ammonia ligase 2

All UniProt accessions (2): Q9NRF8, H0Y5S6

UniProt curated annotations — full annotation on UniProt →

Function. CTP synthase involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids. Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as a source of nitrogen. Constitutes the rate-limiting enzyme in the synthesis of cytosine nucleotides.

Subunit / interactions. Homotetramer. Polymerizes into filaments of stacked tetramers through conserved intertetramer interactions. Filaments dynamically switch between substrate- (active) and product-bound (inactive) conformations with unique architectures.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Activity regulation. Strongly inhibited by CTP.

Pathway. Pyrimidine metabolism; CTP biosynthesis via de novo pathway; CTP from UDP: step 2/2.

Similarity. Belongs to the CTP synthase family.

RefSeq proteins (3): NP_001137474, NP_062831, NP_787055* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004468	CTP_synthase	Family
IPR017456	CTP_synthase_N	Domain
IPR017926	GATASE	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR029062	Class_I_gatase-like	Homologous_superfamily
IPR033828	GATase1_CTP_Synthase	Domain

Pfam: PF00117, PF06418

Enzyme classification (BRENDA)

• EC 6.3.4.2 — CTP synthase (glutamine hydrolysing) (BRENDA: 19 organisms, 51 substrates, 113 inhibitors, 75 Km, 92 kcat entries)

Substrate kinetics (BRENDA)

19 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UTP	0.027–12.4	16
L-GLUTAMINE	0.1–39.4	9
NH3	0.627–2.79	7
NH4+	54–92	6
NH4CL	0.7–4.1	6
NH4OAC	0.94–4.2	6
ATP	0.002–0.54	5
GLUTAMINE	0.196–0.424	4
GLN	0.259–0.497	3
L-GLN	0.027–0.1	3
GLN-OH	0.063–0.165	2
NH2OH	75.3–82.8	2
GTP	0.07	1
2’,3’-DIALDEHYDE ADENOSINE 5’-TRIPHOSPHATE	—	0
2’-DEOXY-GTP	—	0

Catalyzed reactions (Rhea)

• UTP + L-glutamine + ATP + H2O = CTP + L-glutamate + ADP + phosphate + 2 H(+) (RHEA:26426)

UniProt features (118 total): binding site 40, helix 32, strand 28, turn 4, active site 3, modified residue 3, sequence conflict 3, mutagenesis site 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

8 structures by resolution:

PDB	Title	Method	Resolution (Å)
2V4U	Human CTP synthetase 2 - glutaminase domain in complex with 5-OXO-L- NORLEUCINE	X-RAY DIFFRACTION	2.3
2VKT	HUMAN CTP SYNTHETASE 2 - GLUTAMINASE DOMAIN	X-RAY DIFFRACTION	2.5
7MII	Human CTPS2 bound to inhibitor T35	ELECTRON MICROSCOPY	2.7
3IHL	Human CTPS2 crystal structure	X-RAY DIFFRACTION	2.8
7MH1	Human CTPS2 bound to CTP	ELECTRON MICROSCOPY	2.8
7MIH	Human CTPS2 bound to inhibitor R80	ELECTRON MICROSCOPY	2.8
6PK7	cryoEM structure of the product-bound human CTP synthase 2 filament	ELECTRON MICROSCOPY	3.1
6PK4	cryoEM structure of the substrate-bound human CTP synthase 2 filament	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRF8-F1	91.79	0.84

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Ligase, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; mitochondria

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3)

Position	Role
399	for gatase activity
526	for gatase activity
528	for gatase activity

Ligand- & substrate-binding residues (40)

Position	Role
15	ATP
15	CTP
16	ATP
16	CTP
18	CTP
21	ATP
21	CTP
38	UTP
40	UTP
55	UTP
70	ATP
70	Mg(2+)
73	ATP
112	UTP
113	CTP
114	CTP
153	CTP
154	CTP
155	CTP
155	UTP
193	CTP
193	UTP
194	CTP
194	UTP
195	CTP
195	UTP
198	CTP
198	UTP
229	CTP
229	UTP
372	L-glutamine
403	L-glutamine
479	L-glutamine
481	L-glutamine
482	L-glutamine
526	L-glutamine
12	ATP
12	CTP
12	UTP
13	CTP

Post-translational modifications (3)

Type	Positions
Phosphoserine	568, 571, 574

Mutagenesis-validated functional residues (2)

Position	Phenotype
250	promotes inhibition by small compound r80.
355	abolished ability to polymerize into filaments.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-499943	Interconversion of nucleotide di- and triphosphates	—
R-HSA-1430728	Metabolism	—
R-HSA-15869	Metabolism of nucleotides	—

MSigDB gene sets: 151 (showing top): PAL_PRMT5_TARGETS_UP, GOBP_PYRIMIDINE_NUCLEOSIDE_TRIPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOBASE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOBP_NUCLEOBASE_METABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_BIOSYNTHETIC_PROCESS

GO Biological Process (6): pyrimidine nucleotide metabolic process (GO:0006220), CTP biosynthetic process (GO:0006241), pyrimidine nucleobase biosynthetic process (GO:0019856), ‘de novo’ CTP biosynthetic process (GO:0044210), pyrimidine nucleotide biosynthetic process (GO:0006221), small molecule metabolic process (GO:0044281)

GO Molecular Function (7): CTP synthase activity (GO:0003883), ATP binding (GO:0005524), identical protein binding (GO:0042802), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), ligase activity (GO:0016874)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), cytoophidium (GO:0097268)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Metabolism of nucleotides	1
Metabolism	1

GO top-level categories

28 GO namespaces:

Category	Terms
pyrimidine-containing compound biosynthetic process	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cytoplasm	2
nucleotide metabolic process	1
pyrimidine-containing compound metabolic process	1
nucleoside triphosphate biosynthetic process	1
pyrimidine ribonucleoside triphosphate biosynthetic process	1
pyrimidine ribonucleotide biosynthetic process	1
CTP metabolic process	1
pyrimidine nucleobase metabolic process	1
nucleobase biosynthetic process	1
CTP biosynthetic process	1
pyrimidine nucleotide metabolic process	1
nucleotide biosynthetic process	1
metabolic process	1
ligase activity, forming carbon-nitrogen bonds	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
protein binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
supramolecular fiber	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
CTP biosynthetic process	BP	direct assay
cytoophidium	CC	direct assay
cytoplasm	CC	direct assay
mitochondrion	CC	high-throughput
nucleus	CC	direct assay
CTP synthase activity	MF	direct assay
identical protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,512 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTPS2	GMPS	P49915	645
CTPS2	UMPS	P11172	607
CTPS2	IMPDH2	P12268	581
CTPS2	IMPDH1	P20839	575
CTPS2	DHODH	Q02127	536
CTPS2	PFAS	O15067	515
CTPS2	TYMS	P04818	515
CTPS2	TCEANC	Q8N8B7	509
CTPS2	PPAT	Q06203	500
CTPS2	ASNS	P08184	470
CTPS2	UCK1	Q9HA47	453
CTPS2	UCK2	Q9BZX2	452
CTPS2	CMPK1	P30085	452
CTPS2	UCKL1	Q9NWZ5	440
CTPS2	SYAP1	Q96A49	435

IntAct

Human interaction partners of CTPS2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

7 partners by confidence:

Partner	Interaction type	MIscore	Records
CTPS1	physical association	0.850	6
SPG21	physical association	0.670	4
CTBP2	physical association	0.370	1
FGFR1	physical association	0.370	1
MTNR1A	physical association	0.370	1
RPL23A	physical association	0.370	1
RPL37A	physical association	0.370	1

BioGRID (143 interactions; top human partners by supporting records): CTPS1 (Affinity Capture-MS; 7 records), OTUD5 (Affinity Capture-MS; 3 records), SPG21 (Two-hybrid; 2 records), SUGP1 (Affinity Capture-MS; 2 records), TIGD3 (Affinity Capture-MS; 2 records), ACTA1 (Co-fractionation), ACTN1 (Co-fractionation), APLNR (Affinity Capture-MS), APOBEC3C (Affinity Capture-MS), AQP12B (Affinity Capture-MS), ARMC5 (Affinity Capture-MS), ASAH1 (Affinity Capture-MS), ATOH1 (Affinity Capture-MS), BACE2 (Affinity Capture-MS), BCAR1 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
CSNK1A1	down-regulates	CTPS2	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for CTPS2: 202 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

202 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	4
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 2,170):

Position(s)	Effect	Δscore	Sites
X:16589777	acceptor_gain	1.0000
X:16678365	donor_gain	1.0000
X:16683092–16683093	donor_loss	1.0000	5
X:16683227–16683228	acceptor_loss	1.0000	6
X:16693357	donor_gain	1.0000
X:16693494	acceptor_gain	1.0000
X:16699094–16699095	acceptor_loss	1.0000	5
X:16699100	acceptor_gain	1.0000
X:16702735–16702736	donor_loss	1.0000	4
X:16608798	donor_gain	0.9900

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	1.62e-05

Disease associations

OMIM: gene MIM:300380 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST008772_6	Suicide	1e-7

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0007624	suicide

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5291524 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Nucleotide turnover

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 27 [PMID: 36449304]	Inhibition	7.74	pIC50

Binding affinities (BindingDB)

4 measured of 4 human assays (4 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5267968	IC50	13 nM
CHEMBL5283284	IC50	32 nM
CHEMBL5277468	IC50	42 nM
CHEMBL5288393	IC50	383000 nM

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.75	IC50	18	nM	CHEMBL5283284
7.72	IC50	19	nM	CHEMBL5267968
6.62	IC50	242	nM	CHEMBL5277468
6.15	IC50	710	nM	CHEMBL5288393

PubChem BioAssay actives

4 with measured affinity, of 4 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-2-methyl-N-[5-[6-(trifluoromethyl)pyrazin-2-yl]-2-pyridinyl]propanamide	1935766: Inhibition of human CTPS2 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay	ic50	0.0180	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-N-[2-fluoro-4-[6-(trifluoromethyl)pyrazin-2-yl]phenyl]-2-methylpropanamide	1935766: Inhibition of human CTPS2 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay	ic50	0.0190	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-2-methyl-N-(4-pyridin-3-ylphenyl)propanamide	1935766: Inhibition of human CTPS2 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay	ic50	0.2420	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-2-methyl-N-(4-propoxyphenyl)propanamide	1935766: Inhibition of human CTPS2 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay	ic50	0.7100	uM

CTD chemical–gene interactions

55 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	9
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression, affects methylation	5
trichostatin A	affects cotreatment, decreases expression	2
Nickel	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5239171	Binding	Inhibition of human CTPS2 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay	Discovery and Optimization of Potent and Orally Available CTP Synthetase Inhibitors for Use in Treatment of Diseases Driven by Aberrant Immune Cell Proliferation. — *J Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CTPS2 across ~30M SureChEMBL compounds — explore on Sugi Predict.