SRSF2

Summary

SRSF2 (serine and arginine rich splicing factor 2, HGNC:10783) is a protein-coding gene on chromosome 17q25.2, encoding Serine/arginine-rich splicing factor 2 (Q01130). Necessary for the splicing of pre-mRNA. In precision oncology, SRSF2 P95H confers sensitivity to CTX-712 in Myeloid Neoplasm (CIViC Level D); 1 further curated variant–drug associations are listed below. It is a common-essential gene (DepMap: required in 100.0% 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 encoding the same protein and one non-coding transcript variant have been found for this gene. In addition, a pseudogene of this gene has been found on chromosome 11.

Source: NCBI Gene 6427 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 9 total
• Phenotypes (HPO): 67
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• Transcription factor: yes — 12 downstream targets (CollecTRI)
• MANE Select transcript: NM_001195427

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10783
Approved symbol	SRSF2
Name	serine and arginine rich splicing factor 2
Location	17q25.2
Locus type	gene with protein product
Status	Approved
Aliases	SC-35, SC35, PR264, SFRS2A
Ensembl gene	ENSG00000161547
Ensembl biotype	protein_coding
OMIM	600813
Entrez	6427

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000358156, ENST00000359995, ENST00000392485, ENST00000452355, ENST00000508921, ENST00000582449, ENST00000583836, ENST00000585202, ENST00000586778, ENST00000589919, ENST00000592676, ENST00000870175, ENST00000870176, ENST00000870177, ENST00000970524

RefSeq mRNA: 2 — MANE Select: NM_001195427 NM_001195427, NM_003016

CCDS: CCDS11749

Canonical transcript exons

ENST00000359995 — 3 exons

Exon	Start	End
ENSE00001411759	76736154	76736464
ENSE00003902055	76736799	76737331
ENSE00004014464	76734115	76735158

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 312.2169 / max 2917.8955, expressed in 1827 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168290	306.7869	1826
168291	1.7583	842
168284	1.1240	617
168283	0.6046	311
168286	0.5405	154
168285	0.5313	235
168287	0.4367	220
168282	0.4345	173

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.30	gold quality
embryo	UBERON:0000922	99.22	gold quality
tendon of biceps brachii	UBERON:0008188	99.10	gold quality
thymus	UBERON:0002370	99.09	gold quality
ventricular zone	UBERON:0003053	99.06	gold quality
ganglionic eminence	UBERON:0004023	99.01	gold quality
tongue squamous epithelium	UBERON:0006919	98.94	gold quality
granulocyte	CL:0000094	98.93	gold quality
male germ cell	CL:0000015	98.92	gold quality
sperm	CL:0000019	98.89	gold quality
oviduct epithelium	UBERON:0004804	98.89	gold quality
metanephros cortex	UBERON:0010533	98.87	gold quality
lymph node	UBERON:0000029	98.76	gold quality
spleen	UBERON:0002106	98.75	gold quality
vagina	UBERON:0000996	98.74	gold quality
left lobe of thyroid gland	UBERON:0001120	98.73	gold quality
bone marrow	UBERON:0002371	98.73	gold quality
endometrium	UBERON:0001295	98.72	gold quality
endometrium epithelium	UBERON:0004811	98.72	gold quality
trabecular bone tissue	UBERON:0002483	98.71	gold quality
right lobe of thyroid gland	UBERON:0001119	98.68	gold quality
left ovary	UBERON:0002119	98.68	gold quality
ileal mucosa	UBERON:0000331	98.66	gold quality
pharyngeal mucosa	UBERON:0000355	98.66	gold quality
mucosa of urinary bladder	UBERON:0001259	98.66	gold quality
skin of abdomen	UBERON:0001416	98.66	gold quality
esophagus mucosa	UBERON:0002469	98.65	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.65	gold quality
vermiform appendix	UBERON:0001154	98.64	gold quality
thyroid gland	UBERON:0002046	98.64	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	21.63
E-CURD-88	yes	18.44
E-HCAD-5	yes	18.34
E-MTAB-10137	no	1760.03
E-MTAB-7606	no	952.62
E-MTAB-6386	no	797.47
E-HCAD-8	no	46.16
E-HCAD-4	no	31.44
E-CURD-46	no	11.91
E-GEOD-93593	no	6.99
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

12 targets.

Target	Regulation
AURKA
AURKB
COL1A1
HNRNPH1
HNRNPL
MDM2	Activation
RRM2
RSRC2
SRSF1
SRSF2
SRSF7
VIM

Upstream regulators (CollecTRI, top): ARID5A, E2F1, MYB, MYC, NFIC, SRSF1, SRSF2, TBP, ZBTB4

miRNA regulators (miRDB)

191 targeting SRSF2, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• exon identity established through differential antagonism between exonic splicing silencer-bound hnRNP A1 and enhancer-bound SR proteins (PMID:11779509)
• role in c-H-ras alternative splicing regulation (PMID:12665590)
• CRYAB was preferentially localized to nuclear speckles as shown by colocalization with SC35. (PMID:12837281)
• hnRNP A1 binding to the exonic splicing silencer element inhibits splicing of the upstream intron by directly masking the SC35 binding site (PMID:14703516)
• SR proteins 9G8, SC35, ASF/SF2, and SRp40 have effects on the utilization of the A1 to A5 splicing sites of HIV-1 RNA (PMID:15123677)
• hnRNP A1 and ASF/SF2 and SC35 have antagonistic roles in splicing of beta-tropomyosin exon 6B (PMID:15208309)
• alphaB-crystallin has a phosphorylation-dependent role in the ubiquitination of a component of SC35 speckles (PMID:15511225)
• The mutation responsible for aberrant splicing of the E1alpha PDH mRNA increases binding of the SC35 protein in patients with Leigh disease. (PMID:15798212)
• SR proteins ASF/SF2, SC35 and 9G8 can down-regulate the late steps of HIV-1 replication via negative impact on RNA splicing and virion production. (PMID:15907217)
• SC35 domains are hubs that spatially link expression of specific pre-mRNAs to rapid recycling of copious RNA metabolic complexes, thereby facilitating expression of many highly active genes. (PMID:16761280)
• SC35, SRp40, and heterogeneous nuclear ribonucleoprotein A1 interact competitively at the HIV-1 Tat exon 2 splicing site (PMID:16990281)
• This study demonstrates that binding of SC35 to Alu elements on either side of exon 7 in the transcribed pre-mRNA is involved in alternative splicing of amyloid precursor protein exons 7 and 8. (PMID:17353911)
• implicate SC35 as a key player in caffeine-mediated splicing regulation (PMID:18025108)
• Growth hormone deficiency and splicing fidelity: two serine/arginine-rich proteins, ASF/SF2 and SC35, act antagonistically (PMID:18586677)
• E2F1 controls pre-mRNA processing events to induce apoptosis and identify the SC35 Ser-Rich Arg protein as a key direct E2F1-target in this setting. (PMID:18806759)
• Dynamics of SC35 are significantly influenced by the organization of the compartment in which it is localized during the cell cycle. (PMID:19005234)
• Results suggest that pri-miRNA/SC35-containing foci are not major sites of pri-miRNA processing and that pri-miRNA processing is coupled to transcription. (PMID:19177009)
• complex formation between TBX5 and SC35 (PMID:19648116)
• SC35 antagonizes ASF/SF2 and SRp55 by competing for binding to certain sites in exon 5, thereby promoting TF exon 5 exclusion, an event unique to asTF biosynthesis. (PMID:19843576)
• SC35 is pivotal in RA-mediated PKCdelta pre-mRNA alternative splicing (PMID:20547768)
• Most nuclei of TUNEL-positive myocytes in the fibrillating right atria express proliferating cell nuclear antigen, and most nuclei of TUNEL-positive myocytes also express SC-35; none express Ki-67. (PMID:20580447)
• Amyloid-beta peptide alteration of tau exon-10 splicing is causally related to its activation of GSK-3beta which in turn phosphorylates SC35. (PMID:20615469)
• Acetylation and phosphorylation of SRSF2 control cell fate decision in response to cisplatin. (PMID:21157427)
• Data show that SC35 stabilized tau mRNA by binding to the SC35-like element of exon 10. (PMID:21333649)
• The interactions involving the L3 loop, N- and C-termini of the RNA recognition motifs domain of SRSF2 are collectively important for determining selectivity between SRSF2 and RNA. (PMID:22140111)
• SF3B1, U2AF35, SRSF2 and NRAS mutation are unlikely to operate as driver mutations in patients with myelodysplastic syndrome or juvenile myelomonocytic leukemia. (PMID:22238327)
• U2AF1 and SRSF2 mutations are frequent in chronic myelomonocytic leukemia and advanced forms of MDS. U2AF1 and SRSF2 mutations are predictive for shorter survival. (PMID:22323480)
• A negative prognostic impact of SRSF2 mutations in myelodysplastic syndromes. SRSF2 mutations may become useful for clinical risk stratification and treatment decisions in the future. (PMID:22389253)
• SRSF2 mutations contribute to the pathogenesis of LT (leukemic transformation) and may guide novel therapeutic approaches for myeloproliferative neoplasms patients who undergo LT. (PMID:22431577)
• Splicing factor SC35 might take part in the regulation of B7-H3 expression, which could help understand B7-H3 biological function. (PMID:22863587)
• SRSF2 mutations are associated with chronic myelomonocytic leukemia (PMID:22919025)
• SRSF2 mutation is associated with myelodysplastic syndrome. (PMID:22932795)
• In 187 primary myelofibrosis patients, 17% had SRSF2 mutations at P95. They were associated with shorter survival. (PMID:22968464)
• Data show that myelodysplastic chronic myelomonocytic leukemias are characterized by mutations in transcription/epigenetic regulators ASXL1, RUNX1, TET2 and SRSF2. (PMID:23065512)
• data suggest that SF3B1, U2AF1 and SRSF2 mutations occur not only in myeloid lineage tumors but also in lymphoid lineage tumors; data suggest that the splicing gene mutations play important roles in the pathogenesis of hematologic tumors, but rarely in solid tumors (PMID:23280334)
• SRSF2 is the most frequently mutated spliceosome gene in chronic myelomonocytic leukemia, but neither it nor SF3B1 or U2AF35 mutations are prognostically relevant. (PMID:23335386)
• A new function of the splicing factor SRSF2 in the control of E2F1-mediated cell cycle progression in neuroendocrine lung tumors. (PMID:23518498)
• In primary myelofibrosis, SRSF2 mutation appears to be stable and not associated with progression from previous thrombocytosis to cytopenia. (PMID:23660863)
• Protein kinase A interacts with and phosphorylates SC35 and enhances SC35-promoted tau exon 10 inclusion. (PMID:24037441)
• IDH mutations were closely associated with mutations of DNMT3A, ASXL1, and SRSF2, suggesting the interaction of IDH mutations with these gene aberrations may play a role in the development of MDS. (PMID:24115220)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	srsf2a	ENSDARG00000057484
danio_rerio	srsf2b	ENSDARG00000103893
mus_musculus	Srsf2	ENSMUSG00000034120
rattus_norvegicus	Srsf2	ENSRNOG00000000248
drosophila_melanogaster	SC35	FBGN0265298
caenorhabditis_elegans		WBGENE00004701

Paralogs (3): SRSF12 (ENSG00000154548), SRSF10 (ENSG00000188529), SRSF8 (ENSG00000263465)

Protein

Protein identifiers

Serine/arginine-rich splicing factor 2 — Q01130 (reviewed: Q01130)

Alternative names: Protein PR264, Splicing component, 35 kDa, Splicing factor SC35, Splicing factor, arginine/serine-rich 2

All UniProt accessions (3): Q01130, J3KP15, J3QL05

UniProt curated annotations — full annotation on UniProt →

Function. Necessary for the splicing of pre-mRNA. It is required for formation of the earliest ATP-dependent splicing complex and interacts with spliceosomal components bound to both the 5’- and 3’-splice sites during spliceosome assembly. It also is required for ATP-dependent interactions of both U1 and U2 snRNPs with pre-mRNA. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5’- and 3’-splice site binding components, U1 snRNP and U2AF. Binds to purine-rich RNA sequences, either 5’-AGSAGAGTA-3’ (S=C or G) or 5’-GTTCGAGTA-3’. Can bind to beta-globin mRNA and commit it to the splicing pathway. The phosphorylated form (by SRPK2) is required for cellular apoptosis in response to cisplatin treatment.

Subunit / interactions. Interacts with BRDT. In vitro, self-associates and binds SRSF1/SFRS1 (ASF/SF2), SNRNP70 and U2AF1 but not U2AF2. Binds SREK1/SFRS12. Interacts with CCNL1 and CCNL2. Interacts with SCAF11. Interacts with ZRSR2/U2AF1-RS2. Interacts with CCDC55 (via C-terminus).

Subcellular location. Nucleus. Nucleoplasm. Nucleus speckle.

Post-translational modifications. Extensively phosphorylated on serine residues in the RS domain. Phosphorylated by SRPK2 and this causes its redistribution from the nuclear speckle to nucleoplasm and controls cell fate decision in response to cisplatin treatment. KAT5/TIP60 inhibits its phosphorylation by preventing SRPK2 nuclear translocation. Acetylation on Lys-52 by KAT5/TIP60 promotes its proteasomal degradation. This effect is counterbalanced by HDAC6, which positively controls SRSF2 protein level by deacetylating it and preventing its proteasomal degradation.

Induction. Accumulates in a hypoacetylated/phosphorylated form in response to cisplatin treatment.

Similarity. Belongs to the splicing factor SR family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q01130-1	1	yes
Q01130-2	2

RefSeq proteins (2): NP_001182356, NP_003007 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR003954	RRM_euk-type	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR051106	RNA-bind/splicing_reg	Family

Pfam: PF00076

UniProt features (31 total): modified residue 13, strand 7, helix 3, compositionally biased region 2, initiator methionine 1, chain 1, splice variant 1, domain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2KN4	SOLUTION NMR
2LEA	SOLUTION NMR
2LEB	SOLUTION NMR
2LEC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01130-F1	64.07	0.15

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 (13): 26, 52, 189, 191, 204, 206, 208, 212, 220, 2, 2, 22, 25

Function

Pathways and Gene Ontology

Reactome pathways

13 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-72165	mRNA Splicing - Minor 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: 514 (showing top): GGGACCA_MIR133A_MIR133B, E2F_Q4, AGGAAGC_MIR5163P, MODULE_52, E2F_Q4_01, TGCGCANK_UNKNOWN, GCM_MSN, TGCACTT_MIR519C_MIR519B_MIR519A, MODULE_151, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, MORF_SNRP70, MORF_UBE2I, RIZ_ERYTHROID_DIFFERENTIATION_CCNE1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN

GO Biological Process (4): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA processing (GO:0006397), RNA splicing (GO:0008380), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (5): transcription corepressor activity (GO:0003714), RNA binding (GO:0003723), mRNA binding (GO:0003729), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear speck (GO:0016607)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Processing of Capped Intron-Containing Pre-mRNA	3
mRNA Splicing	2
Transport of Mature Transcript to Cytoplasm	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
binding	2
cellular anatomical structure	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
mRNA metabolic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
nucleic acid binding	1
RNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

2810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRSF2	U2AF1	Q01081	997
SRSF2	U2AF2	P26368	973
SRSF2	SNRNP70	P08621	968
SRSF2	SRSF1	Q07955	930
SRSF2	FUS	P35637	899
SRSF2	ASXL1	Q8IXJ9	888
SRSF2	SRPK1	Q96SB4	881
SRSF2	HNRNPH1	P31943	859
SRSF2	RUNX1	Q01196	858
SRSF2	HNRNPH2	P55795	857
SRSF2	SF3B1	O75533	841
SRSF2	TET2	Q6N021	841
SRSF2	HNRNPK	P61978	829
SRSF2	DHX15	O43143	825
SRSF2	CLK1	P49759	815

IntAct

180 interactions, top by confidence:

A	B	Type	Score
SRPK1	SRPK2	psi-mi:“MI:0403”(colocalization)	0.640
SRSF2	CIR1	psi-mi:“MI:0403”(colocalization)	0.540
CIR1	SRSF2	psi-mi:“MI:0915”(physical association)	0.540
SRSF2	CIR1	psi-mi:“MI:0915”(physical association)	0.540
KAT5	SRSF2	psi-mi:“MI:0192”(acetylation reaction)	0.540
SRSF2	KAT5	psi-mi:“MI:0915”(physical association)	0.540
SRSF2	U2AF1	psi-mi:“MI:2364”(proximity)	0.520
U2AF1	SRSF2	psi-mi:“MI:0915”(physical association)	0.520
SRSF2	RANGRF	psi-mi:“MI:0915”(physical association)	0.500
Srek1	SRSF2	psi-mi:“MI:0915”(physical association)	0.480
	SRSF2	psi-mi:“MI:0915”(physical association)	0.460
	SRSF2	psi-mi:“MI:0403”(colocalization)	0.460
ESR1		psi-mi:“MI:0914”(association)	0.460
NCL	SRSF2	psi-mi:“MI:0403”(colocalization)	0.460
NCL	SRSF2	psi-mi:“MI:0915”(physical association)	0.460
CEP164	SRSF2	psi-mi:“MI:0403”(colocalization)	0.450
SRSF2	CDK6	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SRSF2	CSNK2A1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
AIRE	SRSF2	psi-mi:“MI:0915”(physical association)	0.400
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
SRSF2	PA	psi-mi:“MI:0915”(physical association)	0.400
SF3A2	SRSF2	psi-mi:“MI:0915”(physical association)	0.400
HDAC6	SRSF2	psi-mi:“MI:0915”(physical association)	0.400
PAK1	SRSF2	psi-mi:“MI:0915”(physical association)	0.370
SRSF2	SRSF3	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (321): SRSF2 (Affinity Capture-MS), SRSF2 (Two-hybrid), SRSF2 (Two-hybrid), SRSF2 (Two-hybrid), TCF4 (Two-hybrid), CEP72 (Two-hybrid), LZTS2 (Two-hybrid), KRT40 (Two-hybrid), SRSF2 (Affinity Capture-MS), SRSF2 (Affinity Capture-MS), SRSF2 (Biochemical Activity), ACBD3 (Co-fractionation), COPE (Co-fractionation), PSME3 (Co-fractionation), SBNO1 (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: A1C646, A1DGS2, A2R7Z2, A3GGU2, A4QUF0, A4RHN3, A5A6M3, A5DNX9, A5E1Z4, A6SGN8, A6ZZ25, A7EWN6, A7SKE9, A7TFW4, A8NS61, A8WLV5, B0VZS1, B0XS28, B3MSP2, B3MYX2, B3NYY7, B3P935, B4G3E2, B4GUY6, B4I9X1, B4IIC7, B4J4G8, B4JXU2, B4K7S5, B4L710, B4LVR8, B4MA85, B4N1L0, B4NFY1, B4NTY9, B4PP90, B4Q0Y7, B4QS37, C8V330, O35698

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
HDAC6	up-regulates	SRSF2	deacetylation
KAT5	down-regulates	SRSF2	acetylation
SRSF2	“up-regulates quantity by expression”	MDM2	“transcriptional regulation”
DYRK1A	“down-regulates activity”	SRSF2	phosphorylation
SRP54	“up-regulates activity”	SRSF2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 168 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	10	16.1×	9e-08
Transport of Mature Transcript to Cytoplasm	5	15.6×	8e-04
Transport of Mature mRNA derived from an Intron-Containing Transcript	10	12.5×	1e-06
Anchoring of the basal body to the plasma membrane	13	12.1×	1e-08
Processing of Capped Intron-Containing Pre-mRNA	15	10.1×	8e-09
Negative regulation of NOTCH4 signaling	5	9.8×	7e-03
SPOP-mediated proteasomal degradation of PD-L1(CD274)	5	9.4×	8e-03
Loss of Nlp from mitotic centrosomes	7	9.1×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of mRNA processing	5	30.4×	2e-04
spliceosomal complex assembly	5	20.6×	8e-04
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	16.0×	2e-03
intrinsic apoptotic signaling pathway	6	14.7×	7e-04
mRNA export from nucleus	6	12.2×	2e-03
regulation of alternative mRNA splicing, via spliceosome	7	11.7×	7e-04
JNK cascade	6	11.2×	2e-03
mRNA splicing, via spliceosome	17	10.7×	6e-10

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — AML.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

830 predictions. Top by Δscore:

Variant	Effect	Δscore
17:76736180:T:TA	donor_gain	1.0000
17:76735165:T:TC	acceptor_gain	0.9800
17:76736465:C:CC	acceptor_gain	0.9800
17:76735156:CAT:C	acceptor_gain	0.9700
17:76735165:T:C	acceptor_gain	0.9700
17:76735734:C:G	acceptor_gain	0.9700
17:76736319:TGG:T	donor_gain	0.9700
17:76736460:TAGGG:T	acceptor_gain	0.9700
17:76736463:GG:G	acceptor_gain	0.9700
17:76736463:GGCT:G	acceptor_loss	0.9700
17:76736464:GCT:G	acceptor_loss	0.9700
17:76737102:T:TA	donor_gain	0.9700
17:76735159:C:CC	acceptor_gain	0.9600
17:76736462:GGG:G	acceptor_gain	0.9600
17:76736473:G:T	acceptor_gain	0.9600
17:76735157:ATCTA:A	acceptor_loss	0.9500
17:76735158:TCTA:T	acceptor_loss	0.9500
17:76735159:C:CA	acceptor_loss	0.9500
17:76735160:T:G	acceptor_loss	0.9500
17:76736461:AGGG:A	acceptor_gain	0.9500
17:76736793:GTTTA:G	donor_loss	0.9500
17:76736794:TTTAC:T	donor_loss	0.9500
17:76736795:TTA:T	donor_loss	0.9500
17:76736796:TA:T	donor_loss	0.9500
17:76736797:A:C	donor_loss	0.9500
17:76736798:CC:C	donor_loss	0.9500
17:76735700:A:T	acceptor_gain	0.9400
17:76735989:T:TA	donor_gain	0.9400
17:76736216:G:GT	donor_gain	0.9400
17:76736464:GCTGC:G	acceptor_gain	0.9400

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000409899 (17:76736096 C>G,T), RS1000715601 (17:76736918 G>A), RS1000770126 (17:76734278 G>A), RS1000842652 (17:76735588 A>G), RS1001140338 (17:76734686 A>C), RS1001296894 (17:76735125 C>G), RS1002118252 (17:76737983 C>A,G,T), RS1002911686 (17:76734159 A>G), RS1003296233 (17:76737521 TGGAG>T), RS1003754996 (17:76737446 T>A,C,G), RS1004191224 (17:76737345 G>A,C,T), RS1004288611 (17:76737809 T>C), RS1004642046 (17:76736637 G>A,T), RS1004653292 (17:76737254 G>A,C), RS1004725697 (17:76737676 G>A,C)

Disease associations

OMIM: gene MIM:600813 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

67 total (30 of 67 shown, HPO-id order):

HPO	Term
HP:0000939	Osteoporosis
HP:0000980	Pallor
HP:0000989	Pruritus
HP:0001025	Urticaria
HP:0001279	Syncope
HP:0001409	Portal hypertension
HP:0001410	Decreased liver function
HP:0001433	Hepatosplenomegaly
HP:0001541	Ascites
HP:0001649	Tachycardia
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001880	Increased total eosinophil count
HP:0001895	Normochromic anemia
HP:0001897	Normocytic anemia
HP:0001903	Anemia
HP:0001909	Leukemia
HP:0001945	Fever
HP:0001971	Hypersplenism
HP:0001974	Increased total leukocyte count
HP:0002014	Diarrhea
HP:0002018	Nausea
HP:0002024	Malabsorption
HP:0002027	Abdominal pain
HP:0002039	Anorexia
HP:0002086	Abnormality of the respiratory system
HP:0002239	Gastrointestinal hemorrhage

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002071_2	Retinal arteriolar caliber	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004731	eye measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725035 (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

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items; also 1 oncogenic, 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
SRSF2 P95H	CTX-712	Myeloid Neoplasm	Sensitivity/Response	CIViC D	EID11028
SRSF2 P95L	CTX-712	Myeloid Neoplasm	Sensitivity/Response	CIViC D	EID11027

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.03	Kd	9.308	nM	CHEMBL5653589
8.03	ED50	9.308	nM	CHEMBL5653589
6.92	Kd	121	nM	MOLIBRESIB
6.72	IC50	190	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 11 total; 2 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	2149491: Binding affinity to human SRSF2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0093	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	2179082: Binding affinity against SFRS2 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.1210	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	3
sodium arsenite	increases expression, decreases expression	2
Caffeine	affects phosphorylation, increases expression	2
Cisplatin	decreases expression, increases expression, increases activity, increases phosphorylation, decreases reaction (+4 more)	2
Rotenone	decreases expression, increases expression	2
Valproic Acid	affects expression, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
methylethyl ketone	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
kojic acid	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
nickel chloride	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
epigallocatechin gallate	increases expression	1
annonacin	increases reaction, increases splicing, increases expression	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	decreases expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases reaction, increases acetylation, increases degradation	1
perfluorooctane sulfonic acid	decreases expression	1
azoxystrobin	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652533	Binding	Binding affinity to human SRSF2 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

2 cell lines: 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A5MZ	UKAi007-A	Induced pluripotent stem cell	Male
CVCL_A5NA	UKAi007-B	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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