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MGP005135

UniProt Annotations

Entry Information

Gene Name	HECT and RLD domain containing E3 ubiquitin protein ligase 5
Protein Entry	HERC5_HUMAN
UniProt ID	Q9UII4
Species	Human

Comments

Comment type	Description
Caution	Was thought to be a ubiquitin ligase ubiquitinated by UBE2D1, but was confirmed by numerous studies that it's main function is as E3 ISG15 ligase. {ECO:0000305\|PubMed:15331633}.
Function	Major E3 ligase for ISG15 conjugation. Acts as a positive regulator of innate antiviral response in cells induced by interferon. Functions as part of the ISGylation machinery that recognizes target proteins in a broad and relatively non-specific manner. Catalyzes ISGylation of IRF3 which results in sustained activation, it attenuates IRF3-PIN1 interaction, which antagonizes IRF3 ubiquitination and degradation, and boosts the antiviral response. Catalyzes ISGylation of influenza A viral NS1 which attenuates virulence; ISGylated NS1 fails to form homodimers and thus to interact with its RNA targets. Catalyzes ISGylation of papillomavirus type 16 L1 protein which results in dominant- negative effect on virus infectivity. Physically associated with polyribosomes, broadly modifies newly synthesized proteins in a cotranslational manner. In an interferon-stimulated cell, newly translated viral proteins are primary targets of ISG15. {ECO:0000269\|PubMed:16407192, ECO:0000269\|PubMed:16815975, ECO:0000269\|PubMed:16884686, ECO:0000269\|PubMed:20133869, ECO:0000269\|PubMed:20308324, ECO:0000269\|PubMed:20385878, ECO:0000269\|PubMed:20542004}.
Induction	By IFNB1/IFN-beta. In endothelial cells, by TNF, IL1B/interleukin-1B and by bacterial lipopolysaccharides (LPS), hardly induced in other cells of the vascular wall such as primary smooth muscle cells and fibroblasts. By viral infection. {ECO:0000269\|PubMed:15331633, ECO:0000269\|PubMed:16815975}.
Ptm	ISGylated. {ECO:0000305\|PubMed:16815975}.
Similarity	Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain. {ECO:0000255\|PROSITE-ProRule:PRU00104}.
Similarity	Contains 5 RCC1 repeats. {ECO:0000255\|PROSITE- ProRule:PRU00235}.
Subcellular Location	Cytoplasm, perinuclear region {ECO:0000269\|PubMed:20542004}. Note=Associated with the polyribosomes, probably via the 60S subunit.
Subunit	Binds to CCNA1, CCNB1, CCND1 and CCNE1. Interacts with UBE2L6. Interacts with IRF3, this interaction is marginal in resting cells but enhanced upon viral infection. Interacts with influenza A virus NS1. {ECO:0000269\|PubMed:10581175, ECO:0000269\|PubMed:16815975, ECO:0000269\|PubMed:20133869, ECO:0000269\|PubMed:20308324, ECO:0000269\|PubMed:20542004}.
Tissue Specificity	Expressed in testis and to a lesser degree in brain, ovary and placenta. Found in most tissues at low levels. {ECO:0000269\|PubMed:10581175, ECO:0000269\|PubMed:15331633}.