YJU2

Summary

YJU2 (YJU2 splicing factor homolog, HGNC:25518) is a protein-coding gene on chromosome 19p13.3, encoding Splicing factor YJU2 (Q9BW85). Part of the spliceosome which catalyzes two sequential transesterification reactions, first the excision of the non-coding intron from pre-mRNA and then the ligation of the coding exons to form the mature mRNA. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

Predicted to enable metal ion binding activity. Predicted to be involved in RNA splicing and negative regulation of DNA damage response, signal transduction by p53 class mediator. Part of U2-type catalytic step 1 spliceosome.

Source: NCBI Gene 55702 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 60 total
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_018074

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25518
Approved symbol	YJU2
Name	YJU2 splicing factor homolog
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10374
Ensembl gene	ENSG00000105248
Ensembl biotype	protein_coding
Entrez	55702

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000262962, ENST00000596496, ENST00000872338

RefSeq mRNA: 1 — MANE Select: NM_018074 NM_018074

CCDS: CCDS12124

Canonical transcript exons

ENST00000262962 — 8 exons

Exon	Start	End
ENSE00000664059	4251027	4251171
ENSE00000664060	4254355	4254489
ENSE00000664062	4261994	4262114
ENSE00000664063	4267624	4267774
ENSE00001115426	4268584	4269088
ENSE00001342963	4247080	4247170
ENSE00003578350	4249228	4249328
ENSE00003785724	4258242	4258423

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 88.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.3028 / max 117.1167, expressed in 1811 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173311	19.3028	1811

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	88.93	gold quality
sural nerve	UBERON:0015488	87.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.38	gold quality
apex of heart	UBERON:0002098	86.85	gold quality
gastrocnemius	UBERON:0001388	86.53	gold quality
mucosa of transverse colon	UBERON:0004991	86.45	gold quality
body of stomach	UBERON:0001161	86.36	gold quality
muscle of leg	UBERON:0001383	86.12	gold quality
skin of abdomen	UBERON:0001416	86.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.96	gold quality
calcaneal tendon	UBERON:0003701	85.74	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.59	gold quality
skin of leg	UBERON:0001511	85.55	gold quality
body of pancreas	UBERON:0001150	85.38	gold quality
cerebellar hemisphere	UBERON:0002245	85.25	gold quality
cerebellar cortex	UBERON:0002129	85.21	gold quality
right adrenal gland cortex	UBERON:0035827	85.20	gold quality
right adrenal gland	UBERON:0001233	85.05	gold quality
right lobe of thyroid gland	UBERON:0001119	84.91	gold quality
left uterine tube	UBERON:0001303	84.91	gold quality
right ovary	UBERON:0002118	84.82	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.75	gold quality
esophagus mucosa	UBERON:0002469	84.68	gold quality
cortical plate	UBERON:0005343	84.67	gold quality
left adrenal gland	UBERON:0001234	84.60	gold quality
body of uterus	UBERON:0009853	84.52	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.50	gold quality
left lobe of thyroid gland	UBERON:0001120	84.43	gold quality
left ovary	UBERON:0002119	84.43	gold quality
spinal cord	UBERON:0002240	84.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting YJU2, 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-4533	100.00	69.48	2758
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-4305	97.94	68.63	533
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-6890-3P	97.50	65.71	997
HSA-MIR-328-3P	92.82	64.37	521
HSA-MIR-6089	89.72	61.35	324

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	yju2	ENSDARG00000026185
mus_musculus	Yju2	ENSMUSG00000003208
rattus_norvegicus	Yju2l1	ENSRNOG00000029606
rattus_norvegicus	Yju2	ENSRNOG00000047456
rattus_norvegicus		ENSRNOG00000088743
drosophila_melanogaster	CG8435	FBGN0034084
caenorhabditis_elegans		WBGENE00018149

Paralogs (1): YJU2B (ENSG00000104957)

Protein

Protein identifiers

Splicing factor YJU2 — Q9BW85 (reviewed: Q9BW85)

Alternative names: Coiled-coil domain-containing protein 94

All UniProt accessions (2): Q9BW85, M0R2S3

UniProt curated annotations — full annotation on UniProt →

Function. Part of the spliceosome which catalyzes two sequential transesterification reactions, first the excision of the non-coding intron from pre-mRNA and then the ligation of the coding exons to form the mature mRNA. Plays a role in stabilizing the structure of the spliceosome catalytic core and docking of the branch helix into the active site, producing 5’-exon and lariat intron-3’-intermediates. May protect cells from TP53-dependent apoptosis upon dsDNA break damage through association with PRP19-CD5L complex.

Subunit / interactions. Component of the spliceosome. Present in the activated B complex, the catalytically activated B* complex which catalyzes the branching, the catalytic step 1 C complex catalyzing the exon ligation, and the postcatalytic P complex containing the ligated exons (mRNA) and the excised lariat intron. Identified in the spliceosome C complex; in the complex interacts directly with PRP16.

Subcellular location. Nucleus.

Similarity. Belongs to the CWC16 family. YJU2 subfamily.

RefSeq proteins (1): NP_060544* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007590	Saf4/Yju2	Family
IPR043701	Yju2	Family

Pfam: PF04502

UniProt features (25 total): strand 7, modified residue 5, binding site 4, sequence conflict 2, compositionally biased region 2, helix 2, chain 1, region of interest 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6ZYM	ELECTRON MICROSCOPY	3.4
8I0W	ELECTRON MICROSCOPY	3.4
5YZG	ELECTRON MICROSCOPY	4.1
7A5P	ELECTRON MICROSCOPY	5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BW85-F1	74.49	0.37

Functional residue map

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

Ligand- & substrate-binding residues (4): 43; 46; 80; 83

Post-translational modifications (5): 220, 316, 319, 211, 213

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway

MSigDB gene sets: 183 (showing top): GOBP_REGULATION_OF_DNA_DAMAGE_RESPONSE_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, GOBP_DNA_DAMAGE_RESPONSE, REACTOME_MRNA_SPLICING, GOBP_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, BENPORATH_NOS_TARGETS, GOBP_REGULATION_OF_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, GOBP_SIGNAL_TRANSDUCTION_IN_RESPONSE_TO_DNA_DAMAGE, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS, GOBP_NEGATIVE_REGULATION_OF_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, GOBP_MRNA_CIS_SPLICING_VIA_SPLICEOSOME

GO Biological Process (5): generation of catalytic spliceosome for first transesterification step (GO:0000349), RNA splicing (GO:0008380), negative regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043518), mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397)

GO Molecular Function (2): metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (4): nucleoplasm (GO:0005654), U2-type catalytic step 1 spliceosome (GO:0071006), nucleus (GO:0005634), spliceosomal complex (GO:0005681)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
mRNA Splicing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
spliceosomal conformational changes to generate catalytic conformation	1
protein-RNA complex assembly	1
DNA damage response, signal transduction by p53 class mediator	1
regulation of DNA damage response, signal transduction by p53 class mediator	1
negative regulation of signal transduction by p53 class mediator	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
cation binding	1
binding	1
nuclear lumen	1
cellular anatomical structure	1
U2-type spliceosomal complex	1
U2 snRNP	1
U6 snRNP	1
catalytic step 1 spliceosome	1
intracellular membrane-bounded organelle	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

1076 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
YJU2	CWC25	Q9NXE8	977
YJU2	PRPF18	Q99633	879
YJU2	SLU7	O95391	853
YJU2	DHX38	Q92620	847
YJU2	CWC22	Q9HCG8	836
YJU2	DHX16	O60231	821
YJU2	RBM22	Q9NW64	777
YJU2	RNF113A	O15541	776
YJU2	CWC27	Q6UX04	742
YJU2	DHX8	Q14562	736
YJU2	XAB2	Q9HCS7	736
YJU2	SNRNP200	O75643	712
YJU2	SYF2	O95926	710
YJU2	CDC40	O60508	704
YJU2	DDX23	Q9BUQ8	701

IntAct

101 interactions, top by confidence:

A	B	Type	Score
GOLGA2	YJU2	psi-mi:“MI:0915”(physical association)	0.790
YJU2	GOLGA2	psi-mi:“MI:0915”(physical association)	0.790
YJU2	TFCP2	psi-mi:“MI:0915”(physical association)	0.720
CEP70	YJU2	psi-mi:“MI:0915”(physical association)	0.720
YJU2	CEP70	psi-mi:“MI:0915”(physical association)	0.720
TFCP2	YJU2	psi-mi:“MI:0915”(physical association)	0.720
SETMAR	YJU2	psi-mi:“MI:0915”(physical association)	0.620
OR7C1	YJU2	psi-mi:“MI:0915”(physical association)	0.590
YJU2	TRIM27	psi-mi:“MI:0915”(physical association)	0.560
YJU2	JADE1	psi-mi:“MI:0915”(physical association)	0.560
YJU2	MAD1L1	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	YJU2	psi-mi:“MI:0915”(physical association)	0.560
JADE1	YJU2	psi-mi:“MI:0915”(physical association)	0.560
MAD1L1	YJU2	psi-mi:“MI:0915”(physical association)	0.560
YJU2	GOLGA6A	psi-mi:“MI:0915”(physical association)	0.560
ZNF526	YJU2	psi-mi:“MI:0915”(physical association)	0.560
YJU2	TRIM15	psi-mi:“MI:0915”(physical association)	0.560
CCDC57	YJU2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (134): CCDC94 (Two-hybrid), CCDC94 (Two-hybrid), CCDC94 (Two-hybrid), CCDC94 (Two-hybrid), JADE1 (Two-hybrid), CEP70 (Two-hybrid), CCDC94 (Affinity Capture-MS), CCDC94 (Affinity Capture-MS), PRPF19 (Affinity Capture-MS), XAB2 (Affinity Capture-MS), GPATCH1 (Affinity Capture-MS), TRIM62 (Affinity Capture-MS), CRNKL1 (Affinity Capture-MS), PLRG1 (Affinity Capture-MS), CDC5L (Affinity Capture-MS)

ESM2 similar proteins: A8WHR3, E7EXT2, G5EBY0, O15541, O60141, O74517, O94667, P13994, P28320, P28518, P28519, P34648, P35601, P38326, P53709, P78794, Q09651, Q0JHZ2, Q0VBD2, Q28C44, Q28E45, Q32PZ9, Q56P03, Q5EA37, Q5EAW4, Q5RHY1, Q5RJT2, Q66I85, Q67ER4, Q6C3L4, Q6DBR4, Q6DJK9, Q7K0F0, Q7L590, Q8BP78, Q8IQ05, Q8IY81, Q8N954, Q9BW85, Q9C950

Diamond homologs: A8WHR3, P13994, P28320, Q09651, Q32PZ9, Q54TR4, Q54WR5, Q5EA37, Q66I85, Q6DJK9, Q7K0F0, Q9BW85, Q9D516, Q9D6J3, Q9P7C5, O60141

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

963 predictions. Top by Δscore:

Variant	Effect	Δscore
19:4247169:AC:A	donor_gain	1.0000
19:4247171:G:GG	donor_gain	1.0000
19:4247172:T:G	donor_loss	1.0000
19:4249223:T:TA	acceptor_gain	1.0000
19:4249223:TGCA:T	acceptor_loss	1.0000
19:4249224:GCAG:G	acceptor_loss	1.0000
19:4249225:CAG:C	acceptor_loss	1.0000
19:4249226:A:AG	acceptor_gain	1.0000
19:4249226:A:AT	acceptor_loss	1.0000
19:4249227:G:GA	acceptor_gain	1.0000
19:4249227:GA:G	acceptor_gain	1.0000
19:4249227:GAA:G	acceptor_gain	1.0000
19:4249227:GAAA:G	acceptor_gain	1.0000
19:4249227:GAAAT:G	acceptor_gain	1.0000
19:4249325:TGAGG:T	donor_loss	1.0000
19:4249326:GAG:G	donor_gain	1.0000
19:4249326:GAGGT:G	donor_loss	1.0000
19:4249329:GTGAG:G	donor_loss	1.0000
19:4249330:T:G	donor_loss	1.0000
19:4251022:CGCA:C	acceptor_loss	1.0000
19:4251023:GCA:G	acceptor_loss	1.0000
19:4251024:CAG:C	acceptor_loss	1.0000
19:4251025:A:AG	acceptor_gain	1.0000
19:4251026:G:GG	acceptor_gain	1.0000
19:4251026:GGT:G	acceptor_gain	1.0000
19:4251171:GGTA:G	donor_loss	1.0000
19:4251172:G:GG	donor_gain	1.0000
19:4254350:T:TA	acceptor_gain	1.0000
19:4254351:GCAG:G	acceptor_loss	1.0000
19:4254353:A:AG	acceptor_gain	1.0000

AlphaMissense

2111 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:4247153:G:A	E3K	1.000
19:4247154:A:T	E3V	1.000
19:4247157:G:C	R4P	1.000
19:4247159:A:G	K5E	1.000
19:4247160:A:T	K5I	1.000
19:4247161:A:C	K5N	1.000
19:4247161:A:T	K5N	1.000
19:4249230:A:C	K9N	1.000
19:4249230:A:T	K9N	1.000
19:4249231:T:C	Y10H	1.000
19:4249234:T:G	Y11D	1.000
19:4249246:T:C	F15L	1.000
19:4249247:T:G	F15C	1.000
19:4249248:T:A	F15L	1.000
19:4249248:T:G	F15L	1.000
19:4249303:C:G	R34G	1.000
19:4249307:T:A	L35Q	1.000
19:4249307:T:C	L35P	1.000
19:4249310:T:A	M36K	1.000
19:4249310:T:C	M36T	1.000
19:4249310:T:G	M36R	1.000
19:4249311:G:A	M36I	1.000
19:4249311:G:C	M36I	1.000
19:4249311:G:T	M36I	1.000
19:4249313:C:A	A37D	1.000
19:4249316:C:A	P38H	1.000
19:4249318:T:C	F39L	1.000
19:4249320:C:A	F39L	1.000
19:4249320:C:G	F39L	1.000
19:4249323:C:A	N40K	1.000

dbSNP variants (sampled 300 via entrez): RS1000177947 (19:4264924 C>A), RS1000304578 (19:4259086 T>C), RS1000362208 (19:4257792 A>G), RS1000393285 (19:4257620 C>G,T), RS1000525957 (19:4264012 C>A), RS1000643438 (19:4259980 A>G,T), RS1000901441 (19:4263210 C>G), RS1001109924 (19:4247913 C>G), RS1001157652 (19:4255877 C>A,T), RS1001187159 (19:4251791 A>G,T), RS1001225876 (19:4266569 A>G), RS1001240481 (19:4251961 T>C), RS1001382130 (19:4261384 G>A), RS1001395192 (19:4256479 G>A), RS1001401143 (19:4255641 T>C)

Disease associations

OMIM: gene `` | 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

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	increases abundance, increases expression	2
bisphenol A	increases methylation, decreases methylation, affects cotreatment	1
sodium arsenate	decreases expression	1
arsenite	affects binding, increases reaction	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Cadmium	increases abundance, increases expression	1
Copper	affects binding, decreases expression	1
Disulfiram	decreases expression, affects binding	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Mustard Gas	increases phosphorylation	1
Smoke	decreases expression	1
Thiram	increases expression	1
Valproic Acid	affects expression	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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