Molecule Information

General Information of the Molecule (ID: Mol01834)

• Name: Splicing factor 3B subunit 1 (SF3B1) ,Homo sapiens
• Synonyms: Splicing factor 3B subunit 1; (Pre-mRNA-splicing factor SF3b 155 kDa subunit; SF3b155; Spliceosome-associated protein 155; SAP 155
• Molecule Type: Protein
• Gene Name: SF3B1
• Gene ID: 23451
• Location: chr2:197,388,515-197,435,079[-]
• Sequence:
  MAKIAKTHEDIEAQIREIQGKKAALDEAQGVGLDSTGYYDQEIYGGSDSRFAGYVTSIAA
  TELEDDDDDYSSSTSLLGQKKPGYHAPVALLNDIPQSTEQYDPFAEHRPPKIADREDEYK
  KHRRTMIISPERLDPFADGGKTPDPKMNARTYMDVMREQHLTKEEREIRQQLAEKAKAGE
  LKVVNGAAASQPPSKRKRRWDQTADQTPGATPKKLSSWDQAETPGHTPSLRWDETPGRAK
  GSETPGATPGSKIWDPTPSHTPAGAATPGRGDTPGHATPGHGGATSSARKNRWDETPKTE
  RDTPGHGSGWAETPRTDRGGDSIGETPTPGASKRKSRWDETPASQMGGSTPVLTPGKTPI
  GTPAMNMATPTPGHIMSMTPEQLQAWRWEREIDERNRPLSDEELDAMFPEGYKVLPPPAG
  YVPIRTPARKLTATPTPLGGMTGFHMQTEDRTMKSVNDQPSGNLPFLKPDDIQYFDKLLV
  DVDESTLSPEEQKERKIMKLLLKIKNGTPPMRKAALRQITDKAREFGAGPLFNQILPLLM
  SPTLEDQERHLLVKVIDRILYKLDDLVRPYVHKILVVIEPLLIDEDYYARVEGREIISNL
  AKAAGLATMISTMRPDIDNMDEYVRNTTARAFAVVASALGIPSLLPFLKAVCKSKKSWQA
  RHTGIKIVQQIAILMGCAILPHLRSLVEIIEHGLVDEQQKVRTISALAIAALAEAATPYG
  IESFDSVLKPLWKGIRQHRGKGLAAFLKAIGYLIPLMDAEYANYYTREVMLILIREFQSP
  DEEMKKIVLKVVKQCCGTDGVEANYIKTEILPPFFKHFWQHRMALDRRNYRQLVDTTVEL
  ANKVGAAEIISRIVDDLKDEAEQYRKMVMETIEKIMGNLGAADIDHKLEEQLIDGILYAF
  QEQTTEDSVMLNGFGTVVNALGKRVKPYLPQICGTVLWRLNNKSAKVRQQAADLISRTAV
  VMKTCQEEKLMGHLGVVLYEYLGEEYPEVLGSILGALKAIVNVIGMHKMTPPIKDLLPRL
  TPILKNRHEKVQENCIDLVGRIADRGAEYVSAREWMRICFELLELLKAHKKAIRRATVNT
  FGYIAKAIGPHDVLATLLNNLKVQERQNRVCTTVAIAIVAETCSPFTVLPALMNEYRVPE
  LNVQNGVLKSLSFLFEYIGEMGKDYIYAVTPLLEDALMDRDLVHRQTASAVVQHMSLGVY
  GFGCEDSLNHLLNYVWPNVFETSPHVIQAVMGALEGLRVAIGPCRMLQYCLQGLFHPARK
  VRDVYWKIYNSIYIGSQDALIAHYPRIYNDDKNTYIRYELDYIL
• Function: Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex. SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA. Together with other U2 snRNP complex components may also play a role in the selective processing of microRNAs (miRNAs) from the long primary miRNA transcript, pri-miR-17-92. May also be involved in the assembly of the 'E' complex. Belongs also to the minor U12-dependent spliceosome, which is involved in the splicing of rare class of nuclear pre-mRNA intron.
• Uniprot ID: SF3B1_HUMAN
• Ensembl ID: ENSG00000115524
• HGNC ID: HGNC:10768

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Preclinical Drug(s) 3 drug(s) in total

E7107

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Hematologic Cancer [1]

• Sensitive Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Sensitive Drug: E7107
• Molecule Alteration: Missense mutation; p.K700E (c.2098A>G)
• Experimental Note: Identified from the Human Clinical Data

Spliceosome inhibitors

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Spliceosome inhibitors
• Molecule Alteration: Missense mutation; p.K700E (c.2098A>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: Capan-1 cells; Pancreas; Homo sapiens (Human); CVCL_0237
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: HEC1A cells; Uterus; Homo sapiens (Human); CVCL_0293
• In Vitro Model: Panc 0504 cells; Pancreas; Homo sapiens (Human); CVCL_1637
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: HEC59 cells; Endometrium; Homo sapiens (Human); CVCL_2930
• In Vitro Model: ESS-1 cells; Endometrium; Homo sapiens (Human); CVCL_1205
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Spliceosome inhibitors
• Molecule Alteration: Missense mutation; p.K666N (c.1998G>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: Capan-1 cells; Pancreas; Homo sapiens (Human); CVCL_0237
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: HEC1A cells; Uterus; Homo sapiens (Human); CVCL_0293
• In Vitro Model: Panc 0504 cells; Pancreas; Homo sapiens (Human); CVCL_1637
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: HEC59 cells; Endometrium; Homo sapiens (Human); CVCL_2930
• In Vitro Model: ESS-1 cells; Endometrium; Homo sapiens (Human); CVCL_1205
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Spliceostatin A

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Pancreatic ductal adenocarcinoma [3]

• Sensitive Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Sensitive Drug: Spliceostatin A
• Molecule Alteration: Missense mutation; p.K700E (c.2098A>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: Capan-1 cells; Pancreas; Homo sapiens (Human); CVCL_0237
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: HEC1A cells; Uterus; Homo sapiens (Human); CVCL_0293
• In Vitro Model: Capan-1 cells; Pancreas; Homo sapiens (Human); CVCL_0237
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: Pancreatic Panc 0504 cells; Pancreas; Homo sapiens (Human); CVCL_1637
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: HEC59 cells; Endometrium; Homo sapiens (Human); CVCL_2930
• In Vitro Model: ESS-1 cells; Endometrium; Homo sapiens (Human); CVCL_1205
• In Vitro Model: DSMZ cells; N.A.; .; N.A.
• In Vitro Model: ESS-1 cells; Endometrium; Homo sapiens (Human); CVCL_1205
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CellTiter-Glo assay

Disease Class: Breast adenocarcinoma [3]

• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Sensitive Drug: Spliceostatin A
• Molecule Alteration: Missense mutation; p.K666N (c.1998G>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: Capan-1 cells; Pancreas; Homo sapiens (Human); CVCL_0237
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: HEC1A cells; Uterus; Homo sapiens (Human); CVCL_0293
• In Vitro Model: Capan-1 cells; Pancreas; Homo sapiens (Human); CVCL_0237
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: Pancreatic Panc 0504 cells; Pancreas; Homo sapiens (Human); CVCL_1637
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: HEC59 cells; Endometrium; Homo sapiens (Human); CVCL_2930
• In Vitro Model: ESS-1 cells; Endometrium; Homo sapiens (Human); CVCL_1205
• In Vitro Model: DSMZ cells; N.A.; .; N.A.
• In Vitro Model: ESS-1 cells; Endometrium; Homo sapiens (Human); CVCL_1205
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CellTiter-Glo assay

Disease Class: Breast adenocarcinoma [3]

• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Sensitive Drug: Spliceostatin A
• Molecule Alteration: Missense mutation; p.K700E (c.2098A>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: Capan-1 cells; Pancreas; Homo sapiens (Human); CVCL_0237
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: HEC1A cells; Uterus; Homo sapiens (Human); CVCL_0293
• In Vitro Model: Capan-1 cells; Pancreas; Homo sapiens (Human); CVCL_0237
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: Pancreatic Panc 0504 cells; Pancreas; Homo sapiens (Human); CVCL_1637
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: HEC59 cells; Endometrium; Homo sapiens (Human); CVCL_2930
• In Vitro Model: ESS-1 cells; Endometrium; Homo sapiens (Human); CVCL_1205
• In Vitro Model: DSMZ cells; N.A.; .; N.A.
• In Vitro Model: ESS-1 cells; Endometrium; Homo sapiens (Human); CVCL_1205
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CellTiter-Glo assay

Disease Class: Endometrial adenocarcinoma [3]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: Spliceostatin A
• Molecule Alteration: Missense mutation; p.K666N (c.1998G>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: Capan-1 cells; Pancreas; Homo sapiens (Human); CVCL_0237
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: HEC1A cells; Uterus; Homo sapiens (Human); CVCL_0293
• In Vitro Model: Capan-1 cells; Pancreas; Homo sapiens (Human); CVCL_0237
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: Pancreatic Panc 0504 cells; Pancreas; Homo sapiens (Human); CVCL_1637
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: HEC59 cells; Endometrium; Homo sapiens (Human); CVCL_2930
• In Vitro Model: ESS-1 cells; Endometrium; Homo sapiens (Human); CVCL_1205
• In Vitro Model: DSMZ cells; N.A.; .; N.A.
• In Vitro Model: ESS-1 cells; Endometrium; Homo sapiens (Human); CVCL_1205
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CellTiter-Glo assay

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Pancreatic cancer [ICD-11: 2C10]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Pancreas
• The Specified Disease: Pancreatic cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.41E-03; Fold-change: 6.14E-01; Z-score: 1.40E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.44E-02; Fold-change: -2.37E-01; Z-score: -3.66E-01

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.21E-02; Fold-change: -1.31E-02; Z-score: -1.76E-02
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.92E-04; Fold-change: -5.30E-01; Z-score: -5.62E-01

References

• Ref 1: Physiologic Expression of Sf3b1(K700E) Causes Impaired Erythropoiesis, Aberrant Splicing, and Sensitivity to Therapeutic Spliceosome ModulationCancer Cell. 2016 Sep 12;30(3):404-417. doi: 10.1016/j.ccell.2016.08.006.
• Ref 2: STATISTICS/DATA TYPE - iGMDR.
• Ref 3: SF3B1 mutations constitute a novel therapeutic target in breast cancerJ Pathol. 2015 Mar;235(4):571-80. doi: 10.1002/path.4483. Epub 2014 Dec 22.