CTU1

Summary

CTU1 (cytosolic thiouridylase subunit 1, HGNC:29590) is a protein-coding gene on chromosome 19q13.41, encoding Cytoplasmic tRNA 2-thiolation protein 1 (Q7Z7A3). Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln). It is a selective cancer dependency (DepMap: 28.1% of cell lines).

Predicted to enable tRNA binding activity. Predicted to be involved in tRNA wobble position uridine thiolation. Located in cytosol.

Source: NCBI Gene 90353 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 74 total
• Cancer dependency (DepMap): dependent in 28.1% of screened cell lines
• MANE Select transcript: NM_145232

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29590
Approved symbol	CTU1
Name	cytosolic thiouridylase subunit 1
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	MGC17332, NCS6
Ensembl gene	ENSG00000142544
Ensembl biotype	protein_coding
OMIM	612694
Entrez	90353

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000421832, ENST00000936078, ENST00000951779, ENST00000951780

RefSeq mRNA: 1 — MANE Select: NM_145232 NM_145232

CCDS: CCDS12824

Canonical transcript exons

ENST00000421832 — 3 exons

Exon	Start	End
ENSE00000954833	51104062	51104590
ENSE00001604869	51097606	51099139
ENSE00001768341	51108347	51108409

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 91.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.5331 / max 59.7376, expressed in 1759 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182375	7.5331	1759

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	91.70	silver quality
cerebellar vermis	UBERON:0004720	88.52	gold quality
quadriceps femoris	UBERON:0001377	88.32	gold quality
granulocyte	CL:0000094	77.51	gold quality
lower esophagus mucosa	UBERON:0035834	77.27	gold quality
mucosa of transverse colon	UBERON:0004991	76.08	gold quality
cortical plate	UBERON:0005343	74.55	gold quality
leukocyte	CL:0000738	74.32	gold quality
monocyte	CL:0000576	74.14	gold quality
stromal cell of endometrium	CL:0002255	73.82	gold quality
left ovary	UBERON:0002119	72.95	gold quality
blood	UBERON:0000178	72.16	gold quality
right ovary	UBERON:0002118	71.84	gold quality
ovary	UBERON:0000992	71.76	gold quality
hindlimb stylopod muscle	UBERON:0004252	71.39	gold quality
ventricular zone	UBERON:0003053	71.28	gold quality
ganglionic eminence	UBERON:0004023	71.11	gold quality
esophagus mucosa	UBERON:0002469	70.67	gold quality
myometrium	UBERON:0001296	70.49	gold quality
body of uterus	UBERON:0009853	70.03	gold quality
esophagus	UBERON:0001043	69.87	gold quality
lower esophagus	UBERON:0013473	69.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	69.78	gold quality
right lobe of liver	UBERON:0001114	69.75	gold quality
gastrocnemius	UBERON:0001388	69.58	gold quality
primary visual cortex	UBERON:0002436	69.58	gold quality
left adrenal gland	UBERON:0001234	69.53	gold quality
cortex of kidney	UBERON:0001225	69.43	gold quality
left adrenal gland cortex	UBERON:0035825	69.30	gold quality
muscle layer of sigmoid colon	UBERON:0035805	69.28	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting CTU1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-203B-5P	97.24	68.54	543
HSA-MIR-6718-5P	97.24	68.15	553
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-6823-5P	96.26	65.69	919
HSA-MIR-3943	95.87	64.57	523
HSA-MIR-139-3P	95.24	63.10	316
HSA-MIR-769-5P	94.45	64.56	603
HSA-MIR-1296-5P	93.94	67.71	305
HSA-MIR-6790-3P	88.15	62.55	113

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 28.1% of screened cell lines.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctu1	ENSDARG00000020986
mus_musculus	Ctu1	ENSMUSG00000038888
rattus_norvegicus	Ctu1	ENSRNOG00000018334
drosophila_melanogaster	Ctu1	FBGN0033375
caenorhabditis_elegans		WBGENE00017928

Protein

Protein identifiers

Cytoplasmic tRNA 2-thiolation protein 1 — Q7Z7A3 (reviewed: Q7Z7A3)

Alternative names: ATP-binding domain-containing protein 3, Cancer-associated gene protein, Cytoplasmic tRNA adenylyltransferase 1

All UniProt accessions (1): Q7Z7A3

UniProt curated annotations — full annotation on UniProt →

Function. Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln). Directly binds tRNAs and probably acts by catalyzing adenylation of tRNAs, an intermediate required for 2-thiolation. It is unclear whether it acts as a sulfurtransferase that transfers sulfur from thiocarboxylated URM1 onto the uridine of tRNAs at wobble position.

Subunit / interactions. Component of a complex at least composed of URM1, CTU2/NCS2 and CTU1/ATPBD3. May form a heterodimer with CTU2/NCS2.

Subcellular location. Cytoplasm.

Pathway. tRNA modification; 5-methoxycarbonylmethyl-2-thiouridine-tRNA biosynthesis.

Similarity. Belongs to the TtcA family. CTU1/NCS6/ATPBD3 subfamily.

RefSeq proteins (1): NP_660275* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000541	Ncs6/Tuc1/Ctu1	Family
IPR011063	TilS/TtcA_N	Domain
IPR014729	Rossmann-like_a/b/a_fold	Homologous_superfamily
IPR032442	CTU1_C	Domain
IPR035107	tRNA_thiolation_TtcA_Ctu1	Family
IPR056369	CTU1-like_ATP-bd	Domain

Pfam: PF01171, PF16503

UniProt features (5 total): chain 1, region of interest 1, modified residue 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z7A3-F1	84.51	0.61

Functional residue map

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

Post-translational modifications (1): 200

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6782315	tRNA modification in the nucleus and cytosol

MSigDB gene sets: 99 (showing top): GOBP_TRNA_METABOLIC_PROCESS, GOBP_RNA_MODIFICATION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_TRNA_PROCESSING, REACTOME_METABOLISM_OF_RNA, GOBP_TRNA_MODIFICATION, GOCC_TRANSFERASE_COMPLEX, ER_Q6_02, GOMF_TRNA_BINDING, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, MIKKELSEN_ES_ICP_WITH_H3K4ME3, MIKKELSEN_NPC_ICP_WITH_H3K4ME3, GOBP_TRNA_WOBBLE_BASE_MODIFICATION, BRUINS_UVC_RESPONSE_LATE, GOBP_TRNA_THIO_MODIFICATION

GO Biological Process (5): tRNA wobble uridine modification (GO:0002098), tRNA wobble position uridine thiolation (GO:0002143), protein urmylation (GO:0032447), tRNA thio-modification (GO:0034227), tRNA processing (GO:0008033)

GO Molecular Function (5): tRNA binding (GO:0000049), nucleotidyltransferase activity (GO:0016779), RNA binding (GO:0003723), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (3): cytosolic tRNA wobble base thiouridylase complex (GO:0002144), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
tRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
tRNA wobble base modification	1
tRNA wobble uridine modification	1
tRNA thio-modification	1
protein modification by small protein conjugation	1
tRNA modification	1
RNA processing	1
tRNA metabolic process	1
RNA binding	1
transferase activity, transferring phosphorus-containing groups	1
nucleic acid binding	1
binding	1
catalytic activity	1
intracellular protein-containing complex	1
sulfurtransferase complex	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2662 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTU1	URM1	Q9BTM9	996
CTU1	CTU2	Q2VPK5	991
CTU1	MOCS3	O95396	917
CTU1	ELP3	Q9H9T3	879
CTU1	NFS1	Q9Y697	833
CTU1	MPST	P25325	821
CTU1	MCM5	P33992	719
CTU1	TRMT112	Q9UI30	718
CTU1	ELP4	Q96EB1	716
CTU1	ALKBH8	Q96BT7	703
CTU1	KTI12	Q96EK9	682
CTU1	ELP5	Q8TE02	667
CTU1	TRMU	O75648	647
CTU1	TST	Q16762	627
CTU1	TRMT9B	Q9P272	607

IntAct

90 interactions, top by confidence:

A	B	Type	Score
ACBD6	NMT2	psi-mi:“MI:0914”(association)	0.870
URM1	CTU1	psi-mi:“MI:0915”(physical association)	0.720
URM1	CTU1	psi-mi:“MI:0407”(direct interaction)	0.720
CETN1	SFI1	psi-mi:“MI:0914”(association)	0.640
ZNF414	AHCYL1	psi-mi:“MI:0914”(association)	0.640
VWCE	ZNF316	psi-mi:“MI:0914”(association)	0.530
SCRN1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
VASP	GTPBP1	psi-mi:“MI:0914”(association)	0.530
PLA2G10	CHEK1	psi-mi:“MI:0914”(association)	0.530
FHL5	ZMYM6	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
MAGEA1	MAGEB3	psi-mi:“MI:0914”(association)	0.530
ECHDC2	NDUFS6	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
PBXIP1	KCNN4	psi-mi:“MI:0914”(association)	0.530
CHCHD4	ENSA	psi-mi:“MI:0914”(association)	0.530
DCAF4	CLUH	psi-mi:“MI:0914”(association)	0.530
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530

BioGRID (95): CTU1 (Affinity Capture-MS), CTU1 (Affinity Capture-MS), CTU1 (Affinity Capture-MS), CTU1 (Affinity Capture-MS), CTU1 (Affinity Capture-MS), CTU1 (Affinity Capture-MS), CTU1 (Affinity Capture-MS), CTU1 (Affinity Capture-MS), CTU1 (Affinity Capture-MS), CTU1 (Affinity Capture-MS), CTU1 (Affinity Capture-MS), CTU1 (Affinity Capture-MS), CTU1 (Affinity Capture-MS), CTU1 (Affinity Capture-MS), CTU1 (Affinity Capture-MS)

ESM2 similar proteins: A1AT10, A1TLF2, A5D3W7, A5GBB7, A5USV2, A7H7H6, A7HAB8, A7HC45, A7HD67, A7HDB0, A7HDI5, A7HID3, A7HIY6, A9EPV3, A9ER52, A9FD89, B1I1S7, B4RGP0, B4UCW3, B4UG90, B4UGJ6, B4UGX0, B4UHQ4, B4UKF8, B8J9F5, B8J9N6, B8JDE1, B8JDI0, B8JDK2, B8JE66, C4XS52, O86751, Q1AVW2, Q1CW50, Q1D568, Q1D7T4, Q1ISF4, Q2IG43, Q2IHR2, Q2IIL0

Diamond homologs: A2Q879, A3GGB3, A3PNA9, A4WWJ3, A5DPQ4, A5E3Q3, A6ZTX8, A7TER7, A8JF71, A8M8I3, A8PVM6, A8WR63, B0DK66, B1WBV0, B3LHQ7, B3MI77, B3N7L9, B4GHY8, B4HSL7, B4J5B3, B4KLL0, B4LM02, B4NN33, B4P3W7, B5RV24, B9KNZ4, D4GSH6, O58038, O64862, O76365, O94282, P0CS70, P0CS71, P53088, Q01QT2, Q05AW7, Q0VC66, Q16A99, Q16QI1, Q1GJX4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

306 predictions. Top by Δscore:

Variant	Effect	Δscore
19:51099137:GACC:G	acceptor_loss	1.0000
19:51099139:CCT:C	acceptor_loss	1.0000
19:51099140:C:CC	acceptor_gain	1.0000
19:51099141:T:A	acceptor_loss	1.0000
19:51099143:G:GC	acceptor_gain	1.0000
19:51099135:GTGAC:G	acceptor_gain	0.9900
19:51099136:TGAC:T	acceptor_gain	0.9900
19:51099137:GAC:G	acceptor_gain	0.9900
19:51099138:AC:A	acceptor_gain	0.9900
19:51099139:CC:C	acceptor_gain	0.9900
19:51104056:GCTCA:G	donor_loss	0.9900
19:51104057:CTCAC:C	donor_loss	0.9900
19:51104058:TCA:T	donor_loss	0.9900
19:51104059:CA:C	donor_loss	0.9900
19:51104061:CC:C	donor_loss	0.9900
19:51099143:G:C	acceptor_gain	0.9800
19:51108342:CTCA:C	donor_loss	0.9800
19:51108343:TCA:T	donor_loss	0.9800
19:51108344:CA:C	donor_loss	0.9800
19:51108345:A:AC	donor_gain	0.9800
19:51108345:AC:A	donor_gain	0.9800
19:51108346:C:CC	donor_gain	0.9800
19:51108346:CC:C	donor_gain	0.9800
19:51104100:T:TA	donor_gain	0.9700
19:51104589:TCC:T	acceptor_loss	0.9700
19:51104591:C:CA	acceptor_loss	0.9700
19:51104591:C:CC	acceptor_gain	0.9700
19:51104592:T:G	acceptor_loss	0.9700
19:51108339:ATACT:A	donor_loss	0.9700
19:51108345:ACC:A	donor_gain	0.9700

AlphaMissense

2166 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:51099123:G:C	D175E	0.997
19:51099123:G:T	D175E	0.997
19:51099124:T:A	D175V	0.997
19:51099124:T:G	D175A	0.997
19:51104130:C:T	C147Y	0.997
19:51104384:C:A	K62N	0.997
19:51104384:C:G	K62N	0.997
19:51104127:C:T	G148E	0.996
19:51099099:G:C	N183K	0.995
19:51099099:G:T	N183K	0.995
19:51099124:T:C	D175G	0.995
19:51099125:C:G	D175H	0.995
19:51099137:G:C	H171D	0.995
19:51104310:A:T	V87D	0.995
19:51104381:G:C	D63E	0.995
19:51104381:G:T	D63E	0.995
19:51098753:A:G	C299R	0.994
19:51099132:G:C	N172K	0.994
19:51099132:G:T	N172K	0.994
19:51099139:C:T	G170D	0.994
19:51104116:G:T	R152S	0.994
19:51104382:T:A	D63V	0.994
19:51104382:T:G	D63A	0.994
19:51098752:C:G	C299S	0.993
19:51098753:A:T	C299S	0.993
19:51104379:G:A	S64F	0.993
19:51104383:C:G	D63H	0.993
19:51104391:C:T	G60D	0.993
19:51099114:C:A	E178D	0.992
19:51099114:C:G	E178D	0.992

dbSNP variants (sampled 300 via entrez): RS1000183396 (19:51101128 C>T), RS1000235230 (19:51105106 G>A), RS1000235681 (19:51100885 C>T), RS1000473648 (19:51107328 G>A), RS1000677953 (19:51100177 G>A), RS1000702516 (19:51100792 A>G), RS1001358323 (19:51106659 C>T), RS1001809126 (19:51101518 A>C,G), RS1001829898 (19:51107608 G>A), RS1001984012 (19:51101658 T>A), RS1002078245 (19:51102023 A>C), RS1002147096 (19:51101186 T>G), RS1002902899 (19:51109401 G>A,C), RS1003812223 (19:51104813 T>C), RS1003990850 (19:51104439 G>A,C)

Disease associations

OMIM: gene MIM:612694 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
aristolochic acid I	increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Cisplatin	decreases expression	1
Glucose	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.