Molecule Information

General Information of the Molecule (ID: Mol00651)
Name
Serine/arginine-rich splicing factor 2 (SRSF2) ,Homo sapiens
Synonyms
Protein PR264; Splicing component; 35 kDa; Splicing factor SC35; SC-35; Splicing factor; arginine/serine-rich 2; SFRS2
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Molecule Type
Protein
Gene Name
SRSF2
Gene ID
6427
Location
chr17:76734115-76737333[-]
Sequence
MSYGRPPPDVEGMTSLKVDNLTYRTSPDTLRRVFEKYGRVGDVYIPRDRYTKESRGFAFV
RFHDKRDAEDAMDAMDGAVLDGRELRVQMARYGRPPDSHHSRRGPPPRRYGGGGYGRRSR
SPRRRRRSRSRSRSRSRSRSRSRYSRSKSRSRTRSRSRSTSKSRSARRSKSKSSSVSRSR
SRSRSRSRSRSPPPVSKRESKSRSRSKSPPKSPEEEGAVSS
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3D-structure
PDB ID
2KN4
Classification
Rna binding protein
Method
Solution nmr
Resolution
No Resolution Dat Å
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.
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Uniprot ID
SRSF2_HUMAN
Ensembl ID
ENSG00000161547
HGNC ID
HGNC:10783
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Type(s) of Resistant Mechanism of This Molecule
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
3 drug(s) in total
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Cisplatin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Disease Class: Ovarian cancer [ICD-11: 2C73.0] [1]
Resistant Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration O-GlcNAc glycosylation
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A2780/DDP cells Ovarian Homo sapiens (Human) N.A.
SKOV3/DDP cells ovarian Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Immunoprecipitation assay
Experiment for
Drug Resistance		 Cell viability assay; Colony formation assay
Mechanism Description Our findings demonstrate a significant reduction in O-GlcNAc glycosylation of SRSF2 at Ser101 in cisplatin-resistant cells, suggesting that O-GlcNAc modification may regulate cisplatin resistance through alternative splicing of AUF1 to generate p45 or p37 isoforms mediated by SRSF2. The current study demonstrated that phosphorylation of hnRNPA1 at S95 site was significantly increased in cisplatin-resistant ovarian cancer. In addition, phosphorylation at Ser95 regulated recruitment of hnRNPA1 to AUF1 pre-mRNA to compete with SRSR2. Therefore, the phosphorylation of hnRNPA1 mediated by DNA-PK and O-GlcNAc glycosylation of SRSF2 might potentially regulate the alternative splicing of AUF1 and contribute to cisplatin resistance in ovarian cancer.
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Gastric cancer [ICD-11: 2B72.1] [2]
Resistant Disease Gastric cancer [ICD-11: 2B72.1]
 Disease Info 
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
Mitochondrial signaling pathway Inhibition hsa04217
In Vitro Model AGS cells Gastric Homo sapiens (Human) CVCL_0139
MkN-45 cells Gastric Homo sapiens (Human) CVCL_0434
KATO-3 cells Gastric Homo sapiens (Human) CVCL_0371
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay; Flow cytometry assay
Mechanism Description SRSF2, a miR-193a-3p target gene, is downregulated and miR-193a-3p is upregulated, which induces the resistence to cisplatin.
Fluorouracil
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.2] [3]
Sensitive Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Sensitive Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
In Vitro Model BEL-7402 cells Liver Homo sapiens (Human) CVCL_5492
HepG2 cells Liver Homo sapiens (Human) CVCL_0027
Hep3B cells Liver Homo sapiens (Human) CVCL_0326
QGY-7703 cells Liver Homo sapiens (Human) CVCL_6715
SMMC7721 cells Uterus Homo sapiens (Human) CVCL_0534
PLC cells Liver Homo sapiens (Human) CVCL_0485
FOCUS cells Liver Homo sapiens (Human) CVCL_7955
YY-8103 cells Liver Homo sapiens (Human) CVCL_WY40
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 ELISA assay
Experiment for
Drug Resistance		 Flow cytometry assay
Mechanism Description SRSF2 preferentially up-regulates the proapoptotic splicing form of caspase 2 (CASP2L) and sensitizes HCC cells to 5-FU. miR-193a-3p Dictates Resistance of Hepatocellular Carcinoma to 5-Fluorouracil via Repression of SRSF2 Expression.
Paclitaxel
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Bladder cancer [ICD-11: 2C94.0] [4]
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Resistant Drug Paclitaxel
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
DNA damage repair signaling pathway Inhibition hsa03410
Myc/Max signaling pathway Inhibition hsa04218
NF-kappaB signaling pathway Inhibition hsa04064
Notch signaling pathway Activation hsa04330
Oxidative stress signaling pathway Activation hsa00190
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
T24 cells Bladder Homo sapiens (Human) CVCL_0554
BIU87 cells Bladder Homo sapiens (Human) CVCL_6881
H-bc cells Bladder Homo sapiens (Human) CVCL_BT00
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The DNA methylation-regulated miR-193a-3p dictates the multi-chemoresistance of bladder cancer via repression of SRSF2/PLAU/HIC2 expression.
References
Ref 1 Regulation of AUF1 alternative splicing by hnRNPA1 and SRSF2 modulate the sensitivity of ovarian cancer cells to cisplatin. Cell Oncol (Dordr). 2024 Dec;47(6):2349-2366.
Ref 2 Upregulated microRNA-193a-3p is responsible for cisplatin resistance in CD44(+) gastric cancer cells. Cancer Sci. 2019 Feb;110(2):662-673. doi: 10.1111/cas.13894. Epub 2018 Dec 26.
Ref 3 DNA methylation-regulated miR-193a-3p dictates resistance of hepatocellular carcinoma to 5-fluorouracil via repression of SRSF2 expression. J Biol Chem. 2012 Feb 17;287(8):5639-49. doi: 10.1074/jbc.M111.291229. Epub 2011 Nov 23.
Ref 4 The DNA methylation-regulated miR-193a-3p dictates the multi-chemoresistance of bladder cancer via repression of SRSF2/PLAU/HIC2 expression. Cell Death Dis. 2014 Sep 4;5(9):e1402. doi: 10.1038/cddis.2014.367.

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