Cofactor of BRCA1, also known as COBRA1, is a human gene [5] that encodes NELF-B.
NELF-B is a subunit of negative elongation factor (NELF), which also includes NELF-A (WHSC2; MIM 606026), either NELF-C or NELF-D (TH1L; MIM 605297), and NELF-E (RDBP; MIM 154040). NELF acts with DRB sensitivity-inducing factor (DSIF), a heterodimer of SPT4 (SUPT4H1; MIM 603555) and SPT5 (SUPT5H; MIM 602102), to cause transcriptional pausing of RNA polymerase II (see MIM 180660). [6] COBRA1 was initially identified in a yeast two-hybrid screen using the BRCT1 domain of BRCA1 as bait. [7]
Cofactor of BRCA1 has been shown to interact with:
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the BRCA1 gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. BRCA1 is a human tumor suppressor gene and is responsible for repairing DNA.
The positive transcription elongation factor, P-TEFb, is a multiprotein complex that plays an essential role in the regulation of transcription by RNA polymerase II in eukaryotes. Immediately following initiation Pol II becomes trapped in promoter proximal paused positions on the majority of human genes. P-TEFb is a cyclin dependent kinase that can phosphorylate the DRB sensitivity inducing factor (DSIF) and negative elongation factor (NELF), as well as the carboxyl terminal domain of the large subunit of Pol II and this causes the transition into productive elongation leading to the synthesis of mRNAs. P-TEFb is regulated in part by a reversible association with the 7SK snRNP. Treatment of cells with the P-TEFb inhibitors DRB or flavopidirol leads to loss of mRNA production and ultimately cell death.
DNA-directed RNA polymerase II subunit RPB1, also known as RPB1, is an enzyme that is encoded by the POLR2A gene in humans.
Transcription elongation factor SPT5 is a protein that in humans is encoded by the SUPT5H gene.
General transcription factor IIH subunit 4 is a protein that in humans is encoded by the GTF2H4 gene.
FACT complex subunit SSRP1 also known as structure specific recognition protein 1 is a protein that in humans is encoded by the SSRP1 gene.
Negative elongation factor E is a protein that in humans is encoded by the RDBP gene.
Protein HEXIM1 is a protein that in humans is encoded by the HEXIM1 gene.
FACT complex subunit SPT16 is a protein that in humans is encoded by the SUPT16H gene.
Transcription elongation factor SPT4 is a protein that in humans is encoded by the SUPT4H1 gene.
Mediator of RNA polymerase II transcription subunit 21 is an enzyme that in humans is encoded by the MED21 gene.
Negative elongation factor A is a protein that in humans is encoded by the WHSC2 gene.
Negative elongation factor C/D is a protein that in humans is encoded by the TH1L gene.
TATA-binding protein-associated factor 172 is a protein that in humans is encoded by the BTAF1 gene.
Myotubularin-related protein 6 is a protein that in humans is encoded by the MTMR6 gene.
CCR4-NOT transcription complex subunit 8 is a protein that in humans is encoded by the CNOT8 gene. It is a subunit of the CCR4-Not deadenylase complex.
General transcription factor IIF subunit 2 is a protein that in humans is encoded by the GTF2F2 gene.
BRCA1-A complex subunit MERIT40 is a protein that in humans is encoded by the BABAM1 gene.
5,6-Dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) is a chemical compound that inhibits transcription elongation by RNA Polymerase II. Sensitivity to DRB is dependent on DRB sensitivity inducing factor (DSIF), negative elongation factor (NELF), and positive transcription elongation factor b (P-TEFb). DRB is a nucleoside analog and also inhibits some protein kinases.
In molecular biology, the NELF is a four-subunit protein complex that negatively impacts transcription by RNA polymerase II by pausing about 20-60 nucleotides downstream from the transcription start site (TSS).