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Aliases HERC5, CEB1, CEBP1, HECT and RLD domain containing E3 ubiquitin protein ligase 5
External IDs HomoloGene: 81848 GeneCards: HERC5
RNA expression pattern
PBB GE HERC5 219863 at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 4: 88.46 – 88.51 Mb n/a
PubMed search [1] n/a
View/Edit Human

Probable E3 ubiquitin-protein ligase HERC5 is an enzyme that in humans is encoded by the HERC5 gene.[2][3]

This gene is a member of the HERC family of ubiquitin ligases and encodes a protein with a HECT domain and five RCC1 repeats. Pro-inflammatory cytokines upregulate expression of this gene in endothelial cells. The protein localizes to the cytoplasm and perinuclear region and functions as an interferon-induced E3 protein ligase that mediates ISGylation of protein targets. The gene lies in a cluster of HERC family genes on chromosome 4.[3] HERC5 has been shown to exhibit antiviral activity towards HIV-1, influenza A virus and human papillomavirus.[4][5][6]


HERC5 has been shown to interact with NME2[7] and Cyclin E1.[2]


  1. ^ "Human PubMed Reference:". 
  2. ^ a b Mitsui K, Nakanishi M, Ohtsuka S, Norwood TH, Okabayashi K, Miyamoto C, Tanaka K, Yoshimura A, Ohtsubo M (Jan 2000). "A novel human gene encoding HECT domain and RCC1-like repeats interacts with cyclins and is potentially regulated by the tumor suppressor proteins". Biochem Biophys Res Commun. 266 (1): 115–22. doi:10.1006/bbrc.1999.1777. PMID 10581175. 
  3. ^ a b "Entrez Gene: HERC5 hect domain and RLD 5". 
  4. ^ Woods MW, Kelly JN, Hattlmann CJ, Tong JG, Xu LS, Coleman MD, Quest GR, Smiley JR, Barr SD (Nov 2011). "Human HERC5 restricts an early stage of HIV-1 assembly by a mechanism correlating with the ISGylation of Gag". Retrovirology. 8: 95. doi:10.1186/1742-4690-8-95. PMID 22093708. 
  5. ^ Tang Y, Zhong G, Zhu L, Liu X, Shan Y, Feng H, Bu Z, Chen H, Wang C (May 2010). "Herc5 attenuates influenza A virus by catalyzing ISGylation of viral NS1 protein". J Immunol. 184 (10): 5777–90. doi:10.4049/jimmunol.0903588. PMID 20385878. 
  6. ^ Durfee LA, Lyon N, Seo K, Huibregtse JM (June 2010). "The ISG15 conjugation system broadly targets newly synthesized proteins: implications for the antiviral function of ISG15". Mol Cell. 38 (5): 722–32. doi:10.1016/j.molcel.2010.05.002. PMID 20542004. 
  7. ^ Hochrainer, K; Kroismayr R; Baranyi U; Binder B R; Lipp J (Jul 2008). "Highly homologous HERC proteins localize to endosomes and exhibit specific interactions with hPLIC and Nm23B". Cell. Mol. Life Sci. Switzerland. 65 (13): 2105–17. doi:10.1007/s00018-008-8148-5. ISSN 1420-682X. PMID 18535780.