SRSF3

Summary

SRSF3 (serine and arginine rich splicing factor 3, HGNC:10785) is a protein-coding gene on chromosome 6p21.31-p21.2, encoding Serine/arginine-rich splicing factor 3 (P84103). Splicing factor, which binds the consensus motif 5’-C[ACU][AU]C[ACU][AC]C-3’ within pre-mRNA and promotes specific exons inclusion during alternative splicing. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Two transcript variants, one protein-coding and the other non-coding, have been found for this gene.

Source: NCBI Gene 6428 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 21 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_003017

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10785
Approved symbol	SRSF3
Name	serine and arginine rich splicing factor 3
Location	6p21.31-p21.2
Locus type	gene with protein product
Status	Approved
Aliases	SRp20
Ensembl gene	ENSG00000112081
Ensembl biotype	protein_coding
OMIM	603364
Entrez	6428

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 14 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000339436, ENST00000373715, ENST00000477442, ENST00000613941, ENST00000614136, ENST00000620242, ENST00000620389, ENST00000620941, ENST00000855355, ENST00000855356, ENST00000930976, ENST00000930977, ENST00000930978, ENST00000930979, ENST00000930980, ENST00000930981, ENST00000930982, ENST00000930983, ENST00000930984, ENST00000930985

RefSeq mRNA: 1 — MANE Select: NM_003017 NM_003017

CCDS: CCDS4823

Canonical transcript exons

ENST00000373715 — 6 exons

Exon	Start	End
ENSE00001027890	36601962	36605600
ENSE00003534391	36601708	36601794
ENSE00003691597	36601152	36601190
ENSE00003719829	36598849	36598983
ENSE00003735440	36596761	36596968
ENSE00003841918	36594362	36594481

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 142.0332 / max 2415.4177, expressed in 1825 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67518	139.5654	1825
67519	0.6707	347
67522	0.6286	380
67520	0.6156	349
67523	0.5529	294

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.57	gold quality
ganglionic eminence	UBERON:0004023	99.53	gold quality
embryo	UBERON:0000922	99.49	gold quality
monocyte	CL:0000576	99.32	gold quality
pericardium	UBERON:0002407	99.31	gold quality
thymus	UBERON:0002370	99.23	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.23	gold quality
endometrium epithelium	UBERON:0004811	99.20	gold quality
vena cava	UBERON:0004087	99.19	gold quality
lymph node	UBERON:0000029	99.18	gold quality
amniotic fluid	UBERON:0000173	99.18	gold quality
epithelium of nasopharynx	UBERON:0001951	99.18	gold quality
calcaneal tendon	UBERON:0003701	99.14	gold quality
cortical plate	UBERON:0005343	99.14	gold quality
pylorus	UBERON:0001166	99.12	gold quality
cardia of stomach	UBERON:0001162	99.11	gold quality
caecum	UBERON:0001153	99.10	gold quality
mononuclear cell	CL:0000842	99.06	gold quality
leukocyte	CL:0000738	99.05	gold quality
ovary	UBERON:0000992	99.05	gold quality
endometrium	UBERON:0001295	99.05	gold quality
penis	UBERON:0000989	99.04	gold quality
vermiform appendix	UBERON:0001154	99.04	gold quality
left ovary	UBERON:0002119	99.04	gold quality
gingival epithelium	UBERON:0001949	99.02	gold quality
cauda epididymis	UBERON:0004360	99.02	gold quality
colonic mucosa	UBERON:0000317	99.01	gold quality
pharyngeal mucosa	UBERON:0000355	99.01	gold quality
olfactory bulb	UBERON:0002264	99.01	gold quality
peritoneum	UBERON:0002358	99.00	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	2314.28
E-HCAD-4	yes	45.73
E-CURD-88	yes	20.90
E-HCAD-13	yes	19.97
E-MTAB-10042	yes	10.82
E-CURD-122	yes	10.70
E-MTAB-10553	yes	7.67
E-MTAB-7008	no	1164.94
E-HCAD-8	no	45.47
E-GEOD-93593	no	9.93
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, BCL6, CTNNB1, TCF4, TCF7L2, TP53

miRNA regulators (miRDB)

170 targeting SRSF3, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-767-5P	99.95	70.85	993

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• insulin induces the proteasome-dependent degradation of SRp20 as well as the subnuclear relocalization of CLIC1 (PMID:15827065)
• These results suggest that the C-terminal domain of RPB1 promotes exon skipping by recruiting SRp20 and that this contributes independently of elongation to the transcriptional control of alternative splicing. (PMID:17028590)
• nucleo-cytoplasmic SR protein, SRp20, functions in internal ribosome entry site (IRES)-mediated translation of a viral RNA. (PMID:17183366)
• abundant SRp20 in cancer cells or undifferentiated keratinocytes is important for the expression of the viral early E6 and E7 by promoting the expression of cellular transcription factor SP1 for transactivation of viral early promoters. (PMID:18945760)
• Study reports the splicing factor SRp20 as a novel target gene of beta-catenin/TCF4 signaling. (PMID:18952824)
• SRp20, SF2/ASF, and CUG-BP1 act antagonistically to regulate IR alternative splicing in vivo and that the relative ratios of SRp20 and SF2/ASF to CUG-BP1 in different cells determine the degree of exon inclusion. (PMID:19047369)
• SRp20 associate with interphase chromatin, and is released from hyperphosphorylated mitotic chromosomes (PMID:19250906)
• ASF/SF2 and SRp20 are two antagonistic splicing factors regulating Rac1b expression in colorectal tumor cells. (PMID:19602482)
• The authors report that siRNA knockdown of SRp20 or 9G8 resulted in about a 10 fold decrease in herpes simplex virus 1 yields and in nuclear accumulation of polyA+ RNA. (PMID:20227104)
• Epstein-Barr Virus SM protein utilizes cellular splicing factor SRp20 to mediate alternative splicing. (PMID:20810723)
• expression of PTB and SRp20 is associated with malignancy of ovarian tumors but not with stage of invasive epithelial ovarian cancer (PMID:20856201)
• Results suggest that increased SRp20 expression in tumor cells is a critical step for tumor initiation, progression, and maintenance. (PMID:21179588)
• Silencing of SFRS3 increased IL-1beta secretion due to elevation of IL-1beta and caspase-1 mRNA in addition to active caspase-1 levels. (PMID:21611201)
• a model in which SRp20 interacts with PCBP2 bound to the viral RNA, and this interaction functions to recruit ribosomes to the viral RNA in a direct or indirect manner, with the participation of additional protein-protein or protein-RNA interactions. (PMID:21779168)
• Relative levels of SRp20, SRp30c, and SRp40 in TM cells control differential expression of the two alternatively spliced isoforms of the GR and thereby regulate GC responsiveness. (PMID:22205602)
• Protein extracts of colon cancer CD133+ cell stem cells were compared to protein extracts of colon cancer cell CD133- stem cells by 2D DIGE. Demonstrated a direct cause-effect relationship between Wnt pathway activation & increased SRp20 expression. (PMID:22623141)
• downregulation of SRSF3 represents an endogenous mechanism for cellular senescence that directly regulates the TP53 alternative splicing to generate p53beta (PMID:22777358)
• This study found that significant changes in serine/arginine protein 20 (Srp20) gene expression in AD cases and confirmed this using a second cohort of control/AD. (PMID:22788679)
• This study does not confirm a role for genetic variants in the SFRS3 and FKBP4 genes in the pathogenesis of corticosteroid-induced ocular hypertension. (PMID:22921020)
• Serine arginine splicing factor 3 is involved in enhanced splicing of glucose-6-phosphate dehydrogenase RNA in response to nutrients and hormones in liver (PMID:23233666)
• results further define the mechanism of SRp20 cellular redistribution during picornavirus infections (PMID:23255796)
• findings disclose an important role of SRSF3 in the regulation of the G1-to-S-phase progression and alternative splicing of HIPK2 in tumor growth (PMID:23503458)
• Digoxin-mediated repression of SRSF3 expression plays a role in the digoxin-mediated inclusion of exon 20 in the IKBKAP transcript generated from the familial dysautonomia mutant allele. (PMID:23711097)
• Work described here examined the punctate pattern of SRp20 localization in the cytoplasm of poliovirus-infected cells, demonstrating the partial co-localization of SRp20 with the stress granule marker protein TIA-1. (PMID:23830997)
• This is the first study that demonstrates that rs1122608 confers protection against ischemic stroke and implicates splicing factor SFSR3 in the disease process (PMID:24190014)
• Stress-inducible truncated SRSF3 may participate in the acceleration of cell growth through facilitating c-Jun-mediated G1 progression under stressful conditions. (PMID:24190040)
• truncated SRSF3 protein may function as a positive regulator of oxidative stress-initiated inflammatory responses in colon cancer cells. (PMID:24284797)
• Data suggest that the oncogenic potential of SRSF3 might be realized, in part, through the translational repression of PDCD4 mRNA. (PMID:24292556)
• Therefore we conclude that SRSF3 promotes exon 9 skipping of caspase-2 pre-mRNA by interacting with exon 8 (PMID:24321384)
• expression either decreased or the protein mislocalized in hepatocellular carcinoma (PMID:25132062)
• Results identified modulation of SRSF3 activity as the molecular mechanism by which ORF57 promotes RNA splicing. (PMID:25234929)
• Depletion of two of the most potent inhibitors of SMP2 exon 7 inclusion, SRSF2 or SRSF3, in cell lines derived from SMA patients, increased SMN2 exon 7 inclusion and SMN protein level. (PMID:25506695)
• we also demonstrated frequent co-overexpression and positive correlation of DARPP-32, SRp20 and CD44E expression levels in human gastric primary tumors. (PMID:26119931)
• This new function of SRSF3 not only explains why overexpression of SRSF3 is required for ovarian cancer cell growth and survival but also offers a new insight into the mechanism of the neoplastic transformation. (PMID:26282282)
• SRSF3 and hnRNP H1 are the first splicing factors identified which regulate the production of these functionally distinct HER2 splice variants and therefore maybe important for the regulation of HER2 signaling. (PMID:26367347)
• PTBP1 and PTBP2 impaired autoregulation of SRSF3 in oral squamous cell carcinoma cancer cells. (PMID:26416554)
• These data indicate that SRSF3 affects a global change of gene expression to maintain cell homeostasis. (PMID:26704980)
• We propose that SRSF3 could act as a coordinator of the expression of PDCD4 protein via two mechanisms on two alternatively spliced mRNA isoforms. (PMID:26773498)
• Results show that YTHDC1 promotes exon inclusion in targeted mRNAs through recruiting pre-mRNA splicing factor SRSF3 while blocking SRSF10 mRNA binding. (PMID:26876937)
• data indicate that the Human Papillomavirus E2 protein links the viral replication cycle to epithelial differentiation via SRSF3, a key cellular regulator of high-risk (HR)-HPV gene expression (PMID:26962216)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	srsf3a	ENSDARG00000025397
danio_rerio	srsf3b	ENSDARG00000059360
mus_musculus	Srsf3	ENSMUSG00000071172
rattus_norvegicus	Srsf3	ENSRNOG00000000520
drosophila_melanogaster	x16	FBGN0028554
drosophila_melanogaster	Rbp1-like	FBGN0030479
drosophila_melanogaster	Rbp1	FBGN0260944

Paralogs (8): SRSF5 (ENSG00000100650), RSRC2 (ENSG00000111011), SRSF9 (ENSG00000111786), SRSF7 (ENSG00000115875), SRSF4 (ENSG00000116350), RSRP1 (ENSG00000117616), SRSF6 (ENSG00000124193), SRSF1 (ENSG00000136450)

Protein

Protein identifiers

Serine/arginine-rich splicing factor 3 — P84103 (reviewed: P84103)

Alternative names: Pre-mRNA-splicing factor SRP20, Splicing factor, arginine/serine-rich 3

All UniProt accessions (3): P84103, A0A087X2D0, B2R6F3

UniProt curated annotations — full annotation on UniProt →

Function. Splicing factor, which binds the consensus motif 5’-C[ACU][AU]C[ACU][AC]C-3’ within pre-mRNA and promotes specific exons inclusion during alternative splicing. Interaction with YTHDC1, a RNA-binding protein that recognizes and binds N6-methyladenosine (m6A)-containing RNAs, promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites within exons. Also functions as an adapter involved in mRNA nuclear export. Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NXF1 pathway); enhances NXF1-NXT1 RNA-binding activity. Involved in nuclear export of m6A-containing mRNAs via interaction with YTHDC1: interaction with YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export.

Subunit / interactions. Interacts with CPSF6. Interacts with RBMY1A1. Interacts with SREK1/SFRS12. Interacts with NXF1. Interacts with YTHDC1, leading to recruitment to RNA elements adjacent to m6A sites. Interacts with SRSP; increases SRSF3 binding to specific exons.

Subcellular location. Nucleus. Nucleus speckle. Cytoplasm.

Post-translational modifications. Phosphorylated by CLK1, CLK2, CLK3 and CLK4. Extensively phosphorylated on serine residues in the RS domain.

Similarity. Belongs to the splicing factor SR family.

Isoforms (2)

UniProt ID	Names	Canonical?
P84103-1	1	yes
P84103-2	2

RefSeq proteins (1): NP_003008* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR050907	SRSF	Family

Pfam: PF00076

UniProt features (27 total): strand 8, modified residue 3, mutagenesis site 3, region of interest 3, compositionally biased region 3, helix 2, repeat 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9ASQ	ELECTRON MICROSCOPY	3
2I2Y	SOLUTION NMR
2I38	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P84103-F1	59.82	0.00

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 (3): 1, 5, 23

Mutagenesis-validated functional residues (3):

Position	Phenotype
86	abolishes interaction with nxf1.
88	abolishes interaction with nxf1.
90	abolishes interaction with nxf1.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72187	mRNA 3’-end processing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-72172	mRNA Splicing
R-HSA-72202	Transport of Mature Transcript to Cytoplasm
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 356 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_RESPONSE_TO_PEPTIDE, AAGTCCA_MIR422B_MIR422A, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, MORF_UBE2I, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MORF_HDAC1, MORF_UBE2N, DITTMER_PTHLH_TARGETS_UP, XU_HGF_SIGNALING_NOT_VIA_AKT1_48HR_DN, GTACAGG_MIR486, PUJANA_CHEK2_PCC_NETWORK, GOBP_NUCLEAR_TRANSPORT, MORF_SKP1A, MUELLER_PLURINET

GO Biological Process (9): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA processing (GO:0006397), mRNA export from nucleus (GO:0006406), RNA splicing (GO:0008380), primary miRNA processing (GO:0031053), regulation of mRNA splicing, via spliceosome (GO:0048024), cellular response to leukemia inhibitory factor (GO:1990830), RNA processing (GO:0006396), mRNA transport (GO:0051028)

GO Molecular Function (8): RNA binding (GO:0003723), mRNA binding (GO:0003729), phospholipase binding (GO:0043274), primary miRNA binding (GO:0070878), protein-RNA sequence-specific adaptor activity (GO:0160134), sequence-specific mRNA binding (GO:1990825), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear speck (GO:0016607), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Processing of Capped Intron-Containing Pre-mRNA	3
Transport of Mature Transcript to Cytoplasm	1
mRNA Splicing	1
Metabolism of RNA	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
gene expression	2
RNA binding	2
binding	2
cellular anatomical structure	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
mRNA metabolic process	1
RNA export from nucleus	1
mRNA transport	1
miRNA processing	1
mRNA splicing, via spliceosome	1
regulation of RNA splicing	1
regulation of mRNA processing	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
RNA biosynthetic process	1
primary metabolic process	1
RNA transport	1
nucleic acid binding	1
enzyme binding	1
protein-RNA adaptor activity	1
mRNA binding	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

314 interactions, top by confidence:

A	B	Type	Score
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
U2AF1	SRSF3	psi-mi:“MI:2364”(proximity)	0.730
U2AF1	SRSF3	psi-mi:“MI:0915”(physical association)	0.730
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SRSF3	CLK3	psi-mi:“MI:0915”(physical association)	0.670
CLK2	SRSF3	psi-mi:“MI:0915”(physical association)	0.670
MRPS30	GTPBP10	psi-mi:“MI:0914”(association)	0.640
HMGB1	SRSF3	psi-mi:“MI:0915”(physical association)	0.610
SRSF3	CIRBP	psi-mi:“MI:0915”(physical association)	0.560
RPL9	SRSF3	psi-mi:“MI:0915”(physical association)	0.560
SRSF3	PRPF31	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	SRSF3	psi-mi:“MI:0915”(physical association)	0.560
RBMX	SRSF3	psi-mi:“MI:0915”(physical association)	0.560
HNRNPK	SRSF3	psi-mi:“MI:0915”(physical association)	0.560
PCBP3	SRSF3	psi-mi:“MI:0915”(physical association)	0.560
SRSF3	SRSF8	psi-mi:“MI:0915”(physical association)	0.560
U2AF2	SRSF3	psi-mi:“MI:0915”(physical association)	0.560
SRSF3	RBM3	psi-mi:“MI:0915”(physical association)	0.560
SRSF3	PCDHB14	psi-mi:“MI:0915”(physical association)	0.560
SRSF3	CNNM3	psi-mi:“MI:0915”(physical association)	0.560
SRSF3	LNX1	psi-mi:“MI:0915”(physical association)	0.560
SRSF3	RNPS1	psi-mi:“MI:0915”(physical association)	0.560
CLK1	SRSF3	psi-mi:“MI:0915”(physical association)	0.560
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
N	NOP56	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
FYTTD1	UBA6	psi-mi:“MI:0914”(association)	0.530

BioGRID (609): SRSF3 (Affinity Capture-MS), SRSF3 (Affinity Capture-MS), SRSF3 (Affinity Capture-MS), SRSF3 (Affinity Capture-MS), SRSF3 (Affinity Capture-MS), SRSF3 (Affinity Capture-MS), SRSF3 (Affinity Capture-MS), COPA (Co-fractionation), COPE (Co-fractionation), DDX47 (Co-fractionation), HEATR1 (Co-fractionation), KHDRBS1 (Co-fractionation), RPL9 (Co-fractionation), SLC3A2 (Co-fractionation), SRSF1 (Co-fractionation)

ESM2 similar proteins: A2RVS6, F4JHI7, O22315, O75494, O81126, O81127, P30352, P84103, P84104, P92964, P92965, P92966, Q01130, Q06A98, Q07955, Q09511, Q0VCY7, Q10021, Q13242, Q13595, Q16629, Q18409, Q23120, Q23121, Q3MHR5, Q3SZR8, Q3T106, Q3YLA6, Q5PPI1, Q5R1W5, Q5R7H2, Q62093, Q69KL9, Q6DII2, Q6K4N0, Q6K9C3, Q6NYA0, Q6PDM2, Q6PDU1, Q6PFR5

Diamond homologs: A0A0D1DZT6, A2RVS6, A5A6M3, D4AE41, F4JHI7, G3V6S8, O22315, O22703, O35326, O75494, O81127, O93235, P19682, P26686, P28644, P30352, P33240, P38159, P60824, P60825, P60826, P78814, P84103, P84104, P84586, P92964, Q01130, Q02427, Q04836, Q06AT9, Q07955, Q08170, Q09167, Q0VCY7, Q10021, Q13242, Q13243, Q13247, Q14011, Q16629

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SRSF3	up-regulates	NXF1	binding
PPM1G	“down-regulates activity”	SRSF3	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 165 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA 3’-end processing	8	15.0×	7e-06
Transport of Mature mRNA derived from an Intron-Containing Transcript	9	13.1×	4e-06
RHOQ GTPase cycle	7	12.1×	1e-04
Mitochondrial translation	9	11.8×	7e-06
Mitochondrial translation initiation	9	10.9×	1e-05
Mitochondrial translation elongation	9	10.9×	1e-05
Mitochondrial ribosome-associated quality control	9	10.5×	1e-05
RNA Polymerase II Transcription Termination	5	10.5×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	8	44.4×	4e-09
regulation of alternative mRNA splicing, via spliceosome	11	19.5×	4e-09
intrinsic apoptotic signaling pathway	6	15.6×	3e-04
mRNA stabilization	5	13.3×	3e-03
mitochondrial translation	9	11.3×	2e-05
regulation of RNA splicing	6	9.5×	3e-03
G1/S transition of mitotic cell cycle	6	8.7×	5e-03
mRNA splicing, via spliceosome	13	8.6×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1013 predictions. Top by Δscore:

Variant	Effect	Δscore
6:36596754:A:AG	acceptor_gain	1.0000
6:36596756:TACA:T	acceptor_loss	1.0000
6:36596757:ACAG:A	acceptor_loss	1.0000
6:36596758:CA:C	acceptor_loss	1.0000
6:36596759:A:AG	acceptor_gain	1.0000
6:36596760:G:GG	acceptor_gain	1.0000
6:36596760:GA:G	acceptor_gain	1.0000
6:36596760:GAA:G	acceptor_gain	1.0000
6:36596760:GAAA:G	acceptor_gain	1.0000
6:36596760:GAAAT:G	acceptor_gain	1.0000
6:36596965:G:GT	donor_gain	1.0000
6:36596965:G:T	donor_gain	1.0000
6:36596966:A:T	donor_gain	1.0000
6:36596966:AAGG:A	donor_loss	1.0000
6:36596967:AGGTG:A	donor_loss	1.0000
6:36596968:GGT:G	donor_loss	1.0000
6:36596969:GT:G	donor_loss	1.0000
6:36596970:T:A	donor_loss	1.0000
6:36598847:A:AG	acceptor_gain	1.0000
6:36598848:G:GG	acceptor_gain	1.0000
6:36598848:GA:G	acceptor_gain	1.0000
6:36598848:GAA:G	acceptor_gain	1.0000
6:36598848:GAAC:G	acceptor_gain	1.0000
6:36598848:GAACA:G	acceptor_gain	1.0000
6:36598980:GCAG:G	donor_loss	1.0000
6:36598981:CAG:C	donor_loss	1.0000
6:36598984:G:GA	donor_loss	1.0000
6:36598985:T:G	donor_loss	1.0000
6:36601147:TTTA:T	acceptor_loss	1.0000
6:36601148:TTA:T	acceptor_loss	1.0000

AlphaMissense

1047 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:36596862:G:A	G34R	1.000
6:36596862:G:C	G34R	1.000
6:36596863:G:A	G34E	1.000
6:36596880:T:A	W40R	1.000
6:36596880:T:C	W40R	1.000
6:36596882:G:C	W40C	1.000
6:36596882:G:T	W40C	1.000
6:36596884:T:A	V41D	1.000
6:36596887:C:A	A42D	1.000
6:36596902:G:A	G47D	1.000
6:36596904:T:C	F48L	1.000
6:36596905:T:C	F48S	1.000
6:36596905:T:G	F48C	1.000
6:36596906:T:A	F48L	1.000
6:36596906:T:G	F48L	1.000
6:36596908:C:A	A49D	1.000
6:36596910:T:C	F50L	1.000
6:36596911:T:C	F50S	1.000
6:36596911:T:G	F50C	1.000
6:36596912:T:A	F50L	1.000
6:36596912:T:G	F50L	1.000
6:36596914:T:A	V51D	1.000
6:36596920:T:C	F53S	1.000
6:36596946:G:C	A62P	1.000
6:36596947:C:A	A62E	1.000
6:36596795:G:C	K11N	0.999
6:36596795:G:T	K11N	0.999
6:36596797:T:A	V12D	0.999
6:36596799:T:G	Y13D	0.999
6:36596803:T:A	V14E	0.999

dbSNP variants (sampled 300 via entrez): RS1000010768 (6:36598198 CAAGGAT>C), RS1000084353 (6:36594256 G>A,T), RS1000150141 (6:36593210 A>C), RS1000868272 (6:36603830 G>A), RS1000879456 (6:36601360 T>C), RS1000995097 (6:36601010 T>C), RS1001735617 (6:36596333 G>A,T), RS1001786877 (6:36594490 C>A), RS1002149699 (6:36598603 C>T), RS1002204483 (6:36600242 C>A,T), RS1002574780 (6:36598972 A>G), RS1002624859 (6:36600666 C>T), RS1002666504 (6:36600437 A>G,T), RS1002755277 (6:36605453 T>G), RS1002877169 (6:36604314 A>G)

Disease associations

OMIM: gene MIM:603364 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST009723_15	Vertical cup-disc ratio (adjusted for vertical disc diameter)	4.000000e-12
GCST009724_5	Vertical cup-disc ratio (multi-trait analysis)	8.000000e-13
GCST011438_6	Glaucoma (primary open-angle)	5.000000e-07
GCST011439_26	Glaucoma (primary open-angle)	3.000000e-08
GCST90002392_754	Mean corpuscular volume	6.000000e-14
GCST90002396_283	Mean reticulocyte volume	4.000000e-15
GCST90002397_128	Mean spheric corpuscular volume	7.000000e-19
GCST90011768_13	Glaucoma (primary open-angle)	8.000000e-08
GCST90011770_4	Glaucoma (primary open-angle)	2.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006939	cup-to-disc ratio measurement
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066169 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.09	Kd	81.28	nM	CHEMBL5653589
7.09	ED50	81.28	nM	CHEMBL5653589
5.97	Kd	1062	nM	CHEMBL3752910
5.97	ED50	1062	nM	CHEMBL3752910
5.36	IC50	4390	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 10 total; 3 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149492: Binding affinity to human SRSF3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0813	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149492: Binding affinity to human SRSF3 incubated for 45 mins by Kinobead based pull down assay	kd	1.0620	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178557: Inhibition of SFRS3 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	4.3900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	4
sodium arsenite	increases expression, affects binding, affects reaction, increases reaction, affects response to substance (+2 more)	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	2
Hydrogen Peroxide	affects expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	increases reaction, affects binding	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
cadmium sulfate	increases expression	1
ethylisopropylamiloride	increases expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
tamibarotene	affects expression	1
yessotoxin	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CD 437	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652534	Binding	Binding affinity to human SRSF3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_KU46	MEF-T7-SRp20	Spontaneously immortalized cell line	Male

Clinical trials (associated diseases)

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