UniProt functional annotation for Q9NWF9



	UniProt functional annotation for Q9NWF9

UniProt code: Q9NWF9.

Organism: Homo sapiens (Human).

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

Function: Isoform 1 acts as an E3 ubiquitin ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Promotes degradation of TRAF3, TLR4 and TLR9. Contributes to the regulation of antiviral responses. Down-regulates activation of NF-kappa-B, IRF3 activation and IFNB production. Isoform 3 inhibits TNF and IL-1 mediated activation of NF-kappa-B. Promotes TNF and RIP mediated apoptosis. {ECO:0000269|PubMed:15107846, ECO:0000269|PubMed:19893624}.

Catalytic activity: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;

Pathway: Protein modification; protein ubiquitination.

Subunit: Interacts with UBE2L3 and to some extent with UBE2L6. Interacts with TRAF3, TLR3, TLR4, TLR5 and TLR9. Isoform 3/ZIN binds RIPK1. {ECO:0000269|PubMed:11854271, ECO:0000269|PubMed:15107846, ECO:0000269|PubMed:19893624}.

Subunit: (Microbial infection) Isoform 3/ZIN binds RIPK1 and HIV Vif. {ECO:0000269|PubMed:15367624}.

Subcellular location: Cytoplasm.

Tissue specificity: Ubiquitous, with the highest levels of expression in testis and peripheral blood leukocytes.

Domain: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme. {ECO:0000250}.

Ptm: Auto-ubiquitinated.

Disease: Gordon Holmes syndrome (GDHS) [MIM:212840]: A disease characterized by cerebellar symptoms and signs of sex steroid deficiency. Clinical features include cerebellar and brain stem atrophy, cerebellar ataxia, hypothalamic LHRH deficiency, hypogonadotrophic hypogonadism, lack of secondary sexual characteristics, and infertility. {ECO:0000269|PubMed:23656588}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform 3]: 4 different alternatively spliced mRNAs code for this protein isoform. {ECO:0000305}.

Sequence caution: Sequence=BAA91422.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

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:		Isoform 1 acts as an E3 ubiquitin ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Promotes degradation of TRAF3, TLR4 and TLR9. Contributes to the regulation of antiviral responses. Down-regulates activation of NF-kappa-B, IRF3 activation and IFNB production. Isoform 3 inhibits TNF and IL-1 mediated activation of NF-kappa-B. Promotes TNF and RIP mediated apoptosis. {ECO:0000269\|PubMed:15107846, ECO:0000269\|PubMed:19893624}.


Catalytic activity:		Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;
Pathway:		Protein modification; protein ubiquitination.
Subunit:		Interacts with UBE2L3 and to some extent with UBE2L6. Interacts with TRAF3, TLR3, TLR4, TLR5 and TLR9. Isoform 3/ZIN binds RIPK1. {ECO:0000269\|PubMed:11854271, ECO:0000269\|PubMed:15107846, ECO:0000269\|PubMed:19893624}.
Subunit:		(Microbial infection) Isoform 3/ZIN binds RIPK1 and HIV Vif. {ECO:0000269\|PubMed:15367624}.
Subcellular location:		Cytoplasm.
Tissue specificity:		Ubiquitous, with the highest levels of expression in testis and peripheral blood leukocytes.
Domain:		The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme. {ECO:0000250}.
Ptm:		Auto-ubiquitinated.
Disease:		Gordon Holmes syndrome (GDHS) [MIM:212840]: A disease characterized by cerebellar symptoms and signs of sex steroid deficiency. Clinical features include cerebellar and brain stem atrophy, cerebellar ataxia, hypothalamic LHRH deficiency, hypogonadotrophic hypogonadism, lack of secondary sexual characteristics, and infertility. {ECO:0000269\|PubMed:23656588}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform 3]: 4 different alternatively spliced mRNAs code for this protein isoform. {ECO:0000305}.
Sequence caution:		Sequence=BAA91422.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};