Cofactor of BRCA1

Last updated
NELFB
Identifiers
Aliases NELFB , COBRA1, NELF-B, Cofactor of BRCA1, negative elongation factor complex member B
External IDs OMIM: 611180 MGI: 1931035 HomoloGene: 121600 GeneCards: NELFB
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_015456

NM_021393
NM_001310157

RefSeq (protein)

NP_056271

NP_001297086
NP_067368

Location (UCSC) Chr 9: 137.26 – 137.27 Mb Chr 2: 25.09 – 25.1 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Cofactor of BRCA1, also known as COBRA1, is a human gene [5] that encodes NELF-B.

Contents

Function

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]

Interactions

Cofactor of BRCA1 has been shown to interact with:

Related Research Articles

<span class="mw-page-title-main">BRCA1</span> Gene known for its role in breast cancer

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.

<span class="mw-page-title-main">P-TEFb</span>

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.

<span class="mw-page-title-main">POLR2A</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase II subunit RPB1, also known as RPB1, is an enzyme that is encoded by the POLR2A gene in humans.

<span class="mw-page-title-main">SUPT5H</span> Protein-coding gene in the species Homo sapiens

Transcription elongation factor SPT5 is a protein that in humans is encoded by the SUPT5H gene.

<span class="mw-page-title-main">GTF2H4</span> Protein-coding gene in the species Homo sapiens

General transcription factor IIH subunit 4 is a protein that in humans is encoded by the GTF2H4 gene.

<span class="mw-page-title-main">Structure specific recognition protein 1</span> Protein-coding gene in the species Homo sapiens

FACT complex subunit SSRP1 also known as structure specific recognition protein 1 is a protein that in humans is encoded by the SSRP1 gene.

<span class="mw-page-title-main">RDBP</span> Protein

Negative elongation factor E is a protein that in humans is encoded by the RDBP gene.

<span class="mw-page-title-main">HEXIM1</span> Protein-coding gene in the species Homo sapiens

Protein HEXIM1 is a protein that in humans is encoded by the HEXIM1 gene.

<span class="mw-page-title-main">SUPT16H</span> Protein-coding gene in the species Homo sapiens

FACT complex subunit SPT16 is a protein that in humans is encoded by the SUPT16H gene.

<span class="mw-page-title-main">SUPT4H1</span> Protein-coding gene in the species Homo sapiens

Transcription elongation factor SPT4 is a protein that in humans is encoded by the SUPT4H1 gene.

<span class="mw-page-title-main">MED21</span> Protein-coding gene in the species Homo sapiens

Mediator of RNA polymerase II transcription subunit 21 is an enzyme that in humans is encoded by the MED21 gene.

<span class="mw-page-title-main">WHSC2</span> Protein-coding gene in the species Homo sapiens

Negative elongation factor A is a protein that in humans is encoded by the WHSC2 gene.

<span class="mw-page-title-main">TH1L</span> Protein-coding gene in the species Homo sapiens

Negative elongation factor C/D is a protein that in humans is encoded by the TH1L gene.

<span class="mw-page-title-main">BTAF1</span> Protein-coding gene in the species Homo sapiens

TATA-binding protein-associated factor 172 is a protein that in humans is encoded by the BTAF1 gene.

<span class="mw-page-title-main">MTMR6</span> Protein-coding gene in the species Homo sapiens

Myotubularin-related protein 6 is a protein that in humans is encoded by the MTMR6 gene.

<span class="mw-page-title-main">CNOT8</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">GTF2F2</span> Protein-coding gene in the species Homo sapiens

General transcription factor IIF subunit 2 is a protein that in humans is encoded by the GTF2F2 gene.

<span class="mw-page-title-main">BABAM1</span> Protein-coding gene in the species Homo sapiens

BRCA1-A complex subunit MERIT40 is a protein that in humans is encoded by the BABAM1 gene.

5,6-Dichloro-1-β-<small>D</small>-ribofuranosylbenzimidazole Chemical compound

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.

<span class="mw-page-title-main">Negative elongation factor</span> Protein

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).

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000188986 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000013465 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: COBRA1 cofactor of BRCA1".
  6. Narita T, Yamaguchi Y, Yano K, Sugimoto S, Chanarat S, Wada T, Kim DK, Hasegawa J, Omori M, Inukai N, Endoh M, Yamada T, Handa H (2003). "Human Transcription Elongation Factor NELF: Identification of Novel Subunits and Reconstitution of the Functionally Active Complex". Molecular and Cellular Biology. 23 (6): 1863–1873. doi:10.1128/MCB.23.6.1863-1873.2003. PMC   149481 . PMID   12612062.
  7. Ye Q, Hu YF, Zhong H, Nye AC, Belmont AS, Li R (2001). "BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations". The Journal of Cell Biology. 155 (6): 911–922. doi:10.1083/jcb.200108049. PMC   2150890 . PMID   11739404.
  8. Ye Q, Hu YF, Zhong H, Nye AC, Belmont AS, Li R (Dec 2001). "BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations". J. Cell Biol. 155 (6): 911–921. doi:10.1083/jcb.200108049. PMC   2150890 . PMID   11739404.
  9. 1 2 Zhong H, Zhu J, Zhang H, Ding L, Sun Y, Huang C, Ye Q (Dec 2004). "COBRA1 inhibits AP-1 transcriptional activity in transfected cells". Biochem. Biophys. Res. Commun. 325 (2): 568–573. doi:10.1016/j.bbrc.2004.10.079. PMID   15530430.
  10. Aiyar SE, Sun JL, Blair AL, Moskaluk CA, Lu YZ, Ye QN, Yamaguchi Y, Mukherjee A, Ren DM, Handa H, Li R (Sep 2004). "Attenuation of estrogen receptor alpha-mediated transcription through estrogen-stimulated recruitment of a negative elongation factor". Genes Dev. 18 (17): 2134–2146. doi:10.1101/gad.1214104. PMC   515291 . PMID   15342491.
  11. 1 2 Narita T, Yamaguchi Y, Yano K, Sugimoto S, Chanarat S, Wada T, Kim DK, Hasegawa J, Omori M, Inukai N, Endoh M, Yamada T, Handa H (Mar 2003). "Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex". Mol. Cell. Biol. 23 (6): 1863–1873. doi:10.1128/MCB.23.6.1863-1873.2003. PMC   149481 . PMID   12612062.
  12. Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM (Jan 2004). "Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region". Genomics. 83 (1): 153–167. doi:10.1016/S0888-7543(03)00235-0. PMID   14667819.
  13. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3: 89. doi:10.1038/msb4100134. PMC   1847948 . PMID   17353931.

Further reading