UniProt functional annotation for Q9WUB0



	UniProt functional annotation for Q9WUB0

UniProt code: Q9WUB0.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, such as UBE2L3/UBCM4, and then transfers it to substrates. Functions as an E3 ligase for oxidized IREB2 and both heme and oxygen are necessary for IREB2 ubiquitination. Promotes ubiquitination of TAB2 and IRF3 and their degradation by the proteasome. Component of the LUBAC complex which conjugates linear ('Met-1'-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways. Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex. Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis. Binds polyubiquitin of different linkage types (By similarity). {ECO:0000250|UniProtKB:Q9BYM8}.

Catalytic activity: Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine.; EC=2.3.2.31; Evidence={ECO:0000250|UniProtKB:Q9BYM8};

Subunit: Component of the LUBAC complex (linear ubiquitin chain assembly complex) which consists of SHARPIN, RBCK1 and RNF31 (By similarity). LUBAC has a MW of approximately 600 kDa suggesting a heteromultimeric assembly of its subunits (By similarity). Interacts with beta-I-type (PRKCB1) and zeta-type protein kinase C (PRKCZ) and with UBE2L3 (By similarity). Interacts with IREB2 only in iron-rich conditions (By similarity). Associates with the TNF-R1 signaling complex (TNF-RSC) in a stimulation-dependent manner (By similarity). Interacts with EYA1, TAB2, TAB3, MAP3K7 TRAF6 and RIPK1 (PubMed:20956555). Interacts with IRF3 (By similarity). {ECO:0000250|UniProtKB:Q9BYM8, ECO:0000269|PubMed:20956555}.

Domain: The RanBP2-type zinc finger, also called Npl4 zinc finger (NZF), mediates binding to 'Met-1'-linked polyubiquitins. {ECO:0000269|PubMed:22139374}.

Domain: The UBL domain mediates association with RNF31 via interaction with its UBA domain. {ECO:0000250|UniProtKB:Q9BYM8}.

Ptm: Auto-ubiquitinated. Auto-ubiquitination leads to degradation by the proteasome (By similarity). {ECO:0000250|UniProtKB:Q62921}.

Ptm: Phosphorylated. In vitro, phosphorylation inhibits auto- ubiquitination activity (By similarity). {ECO:0000250|UniProtKB:Q62921}.

Disruption phenotype: Impaired TNF-alpha-mediated NF-kappa-B activation and enhanced JNK-mediated apoptosis. {ECO:0000269|PubMed:19136968}.

Similarity: Belongs to the RBR family. {ECO:0000305}.

Sequence caution: Sequence=AAD24572.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAH34555.1; Type=Erroneous initiation; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, such as UBE2L3/UBCM4, and then transfers it to substrates. Functions as an E3 ligase for oxidized IREB2 and both heme and oxygen are necessary for IREB2 ubiquitination. Promotes ubiquitination of TAB2 and IRF3 and their degradation by the proteasome. Component of the LUBAC complex which conjugates linear ('Met-1'-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways. Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex. Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis. Binds polyubiquitin of different linkage types (By similarity). {ECO:0000250\|UniProtKB:Q9BYM8}.


Catalytic activity:		Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine.; EC=2.3.2.31; Evidence={ECO:0000250\|UniProtKB:Q9BYM8};
Subunit:		Component of the LUBAC complex (linear ubiquitin chain assembly complex) which consists of SHARPIN, RBCK1 and RNF31 (By similarity). LUBAC has a MW of approximately 600 kDa suggesting a heteromultimeric assembly of its subunits (By similarity). Interacts with beta-I-type (PRKCB1) and zeta-type protein kinase C (PRKCZ) and with UBE2L3 (By similarity). Interacts with IREB2 only in iron-rich conditions (By similarity). Associates with the TNF-R1 signaling complex (TNF-RSC) in a stimulation-dependent manner (By similarity). Interacts with EYA1, TAB2, TAB3, MAP3K7 TRAF6 and RIPK1 (PubMed:20956555). Interacts with IRF3 (By similarity). {ECO:0000250\|UniProtKB:Q9BYM8, ECO:0000269\|PubMed:20956555}.
Domain:		The RanBP2-type zinc finger, also called Npl4 zinc finger (NZF), mediates binding to 'Met-1'-linked polyubiquitins. {ECO:0000269\|PubMed:22139374}.
Domain:		The UBL domain mediates association with RNF31 via interaction with its UBA domain. {ECO:0000250\|UniProtKB:Q9BYM8}.
Ptm:		Auto-ubiquitinated. Auto-ubiquitination leads to degradation by the proteasome (By similarity). {ECO:0000250\|UniProtKB:Q62921}.
Ptm:		Phosphorylated. In vitro, phosphorylation inhibits auto- ubiquitination activity (By similarity). {ECO:0000250\|UniProtKB:Q62921}.
Disruption phenotype:		Impaired TNF-alpha-mediated NF-kappa-B activation and enhanced JNK-mediated apoptosis. {ECO:0000269\|PubMed:19136968}.
Similarity:		Belongs to the RBR family. {ECO:0000305}.
Sequence caution:		Sequence=AAD24572.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAH34555.1; Type=Erroneous initiation; Evidence={ECO:0000305};