UniProt functional annotation for Q9UII4



	UniProt functional annotation for Q9UII4

UniProt code: Q9UII4.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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}.

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}.

Subcellular location: Cytoplasm, perinuclear region {ECO:0000269|PubMed:20542004}. Note=Associated with the polyribosomes, probably via the 60S subunit.

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}.

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}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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}.


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}.
Subcellular location:		Cytoplasm, perinuclear region {ECO:0000269\|PubMed:20542004}. Note=Associated with the polyribosomes, probably via the 60S subunit.
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}.
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}.