Cofactor of BRCA1

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

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
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q34.3 Start 137,255,327 bp[1] End 137,273,542 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 A3 Start 25,199,712 bp[2] End 25,211,489 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • RNA binding Cellular component • cell nucleus • cytoplasm • NELF complex • nucleoplasm Biological process • transcription elongation from RNA polymerase II promoter • regulation of transcription, DNA-templated • transcription from RNA polymerase II promoter • negative regulation of transcription elongation from RNA polymerase II promoter • transcription, DNA-templated • negative regulation of transcription, DNA-templated • cellular proliferation • stem cell differentiation • negative regulation of stem cell differentiation • positive regulation of viral transcription Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	25920	58202
Ensembl	ENSG00000188986	ENSMUSG00000013465
UniProt	Q8WX92	Q8C4Y3
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: 25.2 – 25.21 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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:

• BRCA1[8]
• C-Fos,[9]
• C-jun,[9]
• Estrogen receptor alpha,[10]
• RDBP,[11][12] and
• TH1L.[11][13]

References

1. GRCh38: Ensembl release 89: ENSG00000188986 - Ensembl, May 2017
2. 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. 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. 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

• Stevens M, De Clercq E, Balzarini J (2007). "The regulation of HIV-1 transcription: molecular targets for chemotherapeutic intervention". Med Res Rev. 26 (5): 595–625. doi:10.1002/med.20081. PMC 7168390. PMID 16838299.
• Yamaguchi Y, Takagi T, Wada T, Yano K, Furuya A, Sugimoto S, Hasegawa J, Handa H (1999). "NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation". Cell. 97 (1): 41–51. doi:10.1016/S0092-8674(00)80713-8. PMID 10199401.
• Hirosawa M, Nagase T, Ishikawa K, Kikuno R, Nomura N, Ohara O (2000). "Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain". DNA Res. 6 (5): 329–336. doi:10.1093/dnares/6.5.329. PMID 10574461.
• Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–1795. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Ping YH, Rana TM (2001). "DSIF and NELF interact with RNA polymerase II elongation complex and HIV-1 Tat stimulates P-TEFb-mediated phosphorylation of RNA polymerase II and DSIF during transcription elongation". J. Biol. Chem. 276 (16): 12951–12958. doi:10.1074/jbc.M006130200. PMID 11112772.
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (2001). "Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs". Genome Res. 11 (3): 422–435. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–292. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
• Ye Q, Hu YF, Zhong H, Nye AC, Belmont AS, Li R (2002). "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.
• 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". Mol. Cell. Biol. 23 (6): 1863–1873. doi:10.1128/MCB.23.6.1863-1873.2003. PMC 149481. PMID 12612062.
• Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM (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.
• Zhu J, Song S, Jiang Z, Yan J, Lu Q, Huang C, Ye Q (2005). "Characterization of COBRA1 in human breast cancer cell lines using a new polyclonal antibody against COBRA1". IUBMB Life. 56 (3): 161–166. doi:10.1080/15216540410001699826. PMID 15185750.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–12135. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Aiyar SE, Sun JL, Blair AL, Moskaluk CA, Lu YZ, Ye QN, Yamaguchi Y, Mukherjee A, Ren DM, Handa H, Li R (2004). "Attenuation of estrogen receptor α-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.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (2004). "From ORFeome to Biology: A Functional Genomics Pipeline". Genome Res. 14 (10B): 2136–2144. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• Zhong H, Zhu J, Zhang H, Ding L, Sun Y, Huang C, Ye Q (2005). "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.
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
• McChesney PA, Aiyar SE, Lee OJ, Zaika A, Moskaluk C, Li R, El-Rifai W (2006). "Cofactor of BRCA1: a novel transcription factor regulator in upper gastrointestinal adenocarcinomas". Cancer Res. 66 (3): 1346–1353. doi:10.1158/0008-5472.CAN-05-3593. PMID 16452188.