Negative elongation factor A

NELFA
Identifiers
Aliases	NELFA, NELF-A, WHSC2, P/OKcl.15, negative elongation factor complex member A
External IDs	OMIM: 606026; MGI: 1346098; GeneCards: NELFA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5L3X
Gene location (Human) Chr. Chromosome 4 (human) Band 4p16.3 Start 1,982,717 bp End 2,041,903 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5|5 B2 Start 34,055,260 bp End 34,093,757 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in oocyte secondary oocyte right uterine tube right hemisphere of cerebellum mucosa of transverse colon right testis left testis left ovary skin of leg right ovary Top expressed in secondary oocyte zygote primary oocyte tail of embryo genital tubercle epiblast neural tube embryo ventricular zone embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding Cellular component nucleus nucleoplasm cytosol nuclear body NELF complex Biological process multicellular organism development transcription elongation from RNA polymerase II promoter regulation of transcription, DNA-templated transcription by RNA polymerase II transcription, DNA-templated negative regulation of transcription elongation from RNA polymerase II promoter positive regulation of viral transcription Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 7469 24116 Ensembl ENSG00000185049 ENSMUSG00000029111 UniProt Q9H3P2 Q8BG30 RefSeq (mRNA) NM_005663 NM_011914 RefSeq (protein) NP_005654 NP_036044 Location (UCSC) Chr 4: 1.98 – 2.04 Mb Chr 5: 34.06 – 34.09 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Negative elongation factor A (or NELF-A) is a protein that in humans is encoded by the NELFA gene (previously WHSC2). This protein is part of the negative elongation factor (NELF) complex, together with NELF-B, NELF-E, and either the C or D isoform of NELF-C/D. This complex interacts with RNA polymerase II-based transcriptional elongation and triggers transcriptional pausing. Though it was originally called "Wolf-Hirschhorn syndrome candidate 2", later research has indicated that it is actually not involved with Wolf-Hirschhorn syndrome.

Function

This gene is expressed ubiquitously with higher levels in fetal than in adult tissues. It encodes a protein sharing 93% sequence identity with the mouse protein. Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4. This gene is mapped to the 165 kb WHS critical region, and may play a role in the phenotype of the WHS or Pitt-Rogers-Danks syndrome. The encoded protein is found to be capable of reacting with HLA-A2-restricted and tumor-specific cytotoxic T lymphocytes, suggesting a target for use in specific immunotherapy for a large number of cancer patients. This protein has also been shown to be a member of the NELF (negative elongation factor) protein complex that participates in the regulation of RNA polymerase II transcription elongation. NELFA encodes the NELF-A subunit of the NELF complex.

Interactions

NELF-A has been shown to interact with NELF-E.

Further reading

• Gutmajster E, Rokicka A (2003). "[Genetic determination of Wolf-Hirschhorn syndrome ]". Wiadomości Lekarskie. 55 (11–12): 706–10. PMID 12715353.
• Stevens M, De Clercq E, Balzarini J (Sep 2006). "The regulation of HIV-1 transcription: molecular targets for chemotherapeutic intervention". Medicinal Research Reviews. 26 (5): 595–625. doi:10.1002/med.20081. PMC 7168390. PMID 16838299.
• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (Apr 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
• Wright TJ, Ricke DO, Denison K, Abmayr S, Cotter PD, Hirschhorn K, Keinänen M, McDonald-McGinn D, Somer M, Spinner N, Yang-Feng T, Zackai E, Altherr MR (Feb 1997). "A transcript map of the newly defined 165 kb Wolf-Hirschhorn syndrome critical region". Human Molecular Genetics. 6 (2): 317–24. doi:10.1093/hmg/6.2.317. PMID 9063753.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (Apr 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Yamaguchi Y, Takagi T, Wada T, Yano K, Furuya A, Sugimoto S, Hasegawa J, Handa H (Apr 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. S2CID 16855257.
• Ping YH, Rana TM (Apr 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". The Journal of Biological Chemistry. 276 (16): 12951–8. doi:10.1074/jbc.M006130200. PMID 11112772.
• Mariotti M, Manganini M, Maier JA (Dec 2000). "Modulation of WHSC2 expression in human endothelial cells". FEBS Letters. 487 (2): 166–70. doi:10.1016/S0014-5793(00)02335-8. PMID 11150502. S2CID 5862862.
• Ito M, Shichijo S, Tsuda N, Ochi M, Harashima N, Saito N, Itoh K (Mar 2001). "Molecular basis of T cell-mediated recognition of pancreatic cancer cells". Cancer Research. 61 (5): 2038–46. PMID 11280764.
• Yamaguchi Y, Filipovska J, Yano K, Furuya A, Inukai N, Narita T, Wada T, Sugimoto S, Konarska MM, Handa H (Jul 2001). "Stimulation of RNA polymerase II elongation by hepatitis delta antigen". Science. 293 (5527): 124–7. doi:10.1126/science.1057925. PMID 11387440. S2CID 27068661.
• Yamaguchi Y, Inukai N, Narita T, Wada T, Handa H (May 2002). "Evidence that negative elongation factor represses transcription elongation through binding to a DRB sensitivity-inducing factor/RNA polymerase II complex and RNA". Molecular and Cellular Biology. 22 (9): 2918–27. doi:10.1128/MCB.22.9.2918-2927.2002. PMC 133766. PMID 11940650.
• Zollino M, Lecce R, Fischetto R, Murdolo M, Faravelli F, Selicorni A, Buttè C, Memo L, Capovilla G, Neri G (Mar 2003). "Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2". American Journal of Human Genetics. 72 (3): 590–7. doi:10.1086/367925. PMC 1180235. PMID 12563561.
• 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". Molecular and Cellular Biology. 23 (6): 1863–73. doi:10.1128/MCB.23.6.1863-1873.2003. PMC 149481. PMID 12612062.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (Aug 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.