UniProt functional annotation for Q9NYJ8



	UniProt functional annotation for Q9NYJ8

UniProt code: Q9NYJ8.

Organism: Homo sapiens (Human).

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

Function: Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of 'Lys-63'-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF) (PubMed:10882101, PubMed:11460167, PubMed:15327770, PubMed:22158122). Acts as an adapter linking MAP3K7/TAK1 and TRAF6 to 'Lys-63'-linked polyubiquitin chains (PubMed:10882101, PubMed:11460167, PubMed:15327770, PubMed:22158122). The RanBP2-type zinc finger (NZF) specifically recognizes Lys-63'-linked polyubiquitin chains unanchored or anchored to the substrate proteins such as RIPK1/RIP1: this acts as a scaffold to organize a large signaling complex to promote autophosphorylation of MAP3K7/TAK1, and subsequent activation of I- kappa-B-kinase (IKK) core complex by MAP3K7/TAK1 (PubMed:15327770, PubMed:22158122). Regulates the IL1-mediated translocation of NCOR1 out of the nucleus (By similarity). Involved in heart development (PubMed:20493459). {ECO:0000250|UniProtKB:Q99K90, ECO:0000269|PubMed:10882101, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:15327770, ECO:0000269|PubMed:20493459, ECO:0000269|PubMed:22158122}.

Subunit: Interacts with MAP3K7 and TRAF6 (PubMed:10882101). Identified in the TRIKA2 complex composed of MAP3K7, TAB1 and TAB2 (PubMed:11460167). Binds 'Lys-63'-linked polyubiquitin chains (PubMed:19675569, PubMed:19935683). Interacts with NCOR1 and HDAC3 to form a ternary complex (By similarity). Interacts (via C-terminal) with NUMBL (via PTB domain) (PubMed:18299187). Interacts (via the C- terminus) with DYNC2I2 (via WD domains) (PubMed:19521662). Interacts with RBCK1 (PubMed:17449468). Interacts with TRIM5 (PubMed:21512573). {ECO:0000250|UniProtKB:Q99K90, ECO:0000269|PubMed:10882101, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:17449468, ECO:0000269|PubMed:18299187, ECO:0000269|PubMed:19521662, ECO:0000269|PubMed:19675569, ECO:0000269|PubMed:19935683, ECO:0000269|PubMed:21512573}.

Subcellular location: Membrane {ECO:0000269|PubMed:10882101}; Peripheral membrane protein {ECO:0000269|PubMed:10882101}. Cytoplasm, cytosol {ECO:0000269|PubMed:10882101}. Note=Following IL1 stimulation, translocation occurs from the membrane to cytosol. {ECO:0000269|PubMed:10882101}.

Tissue specificity: Widely expressed. In the embryo, expressed in the ventricular trabeculae, endothelial cells of the conotruncal cushions of the outflow tract and in the endothelial cells lining the developing aortic valves. {ECO:0000269|PubMed:10882101, ECO:0000269|PubMed:20493459}.

Domain: The RanBP2-type zinc finger (NZF) mediates binding to two consecutive 'Lys-63'-linked ubiquitins. {ECO:0000269|PubMed:19935683, ECO:0000269|PubMed:22158122}.

Ptm: Ubiquitinated; following IL1 stimulation or TRAF6 overexpression. Ubiquitination involves RBCK1 leading to proteasomal degradation. {ECO:0000269|PubMed:14633987, ECO:0000269|PubMed:17449468}.

Ptm: Phosphorylated. {ECO:0000305|PubMed:10882101}.

Ptm: (Microbial infection) Methylated at Cys-673 by enteropathogenic E.coli protein NleE or S.flexneri protein OspZ: methylation disrupts zinc-binding and ability to bind 'Lys-63'-linked ubiquitin, leading to NF-kappa-B inactivation. {ECO:0000269|PubMed:22158122, ECO:0000269|PubMed:25412445, ECO:0000269|PubMed:27445336}.

Disease: Congenital heart defects, multiple types, 2 (CHTD2) [MIM:614980]: A disease characterized by congenital developmental abnormalities involving structures of the heart. CHTD2 patients have left ventricular outflow tract obstruction, subaortic stenosis, residual aortic regurgitation, atrial fibrillation, bicuspid aortic valve and aortic dilation. {ECO:0000269|PubMed:20493459}. Note=The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving TAB2 has been found in a family with congenital heart disease. Translocation t(2;6)(q21;q25).

Sequence caution: Sequence=BAA34453.2; Type=Erroneous initiation; 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:		Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of 'Lys-63'-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF) (PubMed:10882101, PubMed:11460167, PubMed:15327770, PubMed:22158122). Acts as an adapter linking MAP3K7/TAK1 and TRAF6 to 'Lys-63'-linked polyubiquitin chains (PubMed:10882101, PubMed:11460167, PubMed:15327770, PubMed:22158122). The RanBP2-type zinc finger (NZF) specifically recognizes Lys-63'-linked polyubiquitin chains unanchored or anchored to the substrate proteins such as RIPK1/RIP1: this acts as a scaffold to organize a large signaling complex to promote autophosphorylation of MAP3K7/TAK1, and subsequent activation of I- kappa-B-kinase (IKK) core complex by MAP3K7/TAK1 (PubMed:15327770, PubMed:22158122). Regulates the IL1-mediated translocation of NCOR1 out of the nucleus (By similarity). Involved in heart development (PubMed:20493459). {ECO:0000250\|UniProtKB:Q99K90, ECO:0000269\|PubMed:10882101, ECO:0000269\|PubMed:11460167, ECO:0000269\|PubMed:15327770, ECO:0000269\|PubMed:20493459, ECO:0000269\|PubMed:22158122}.


Subunit:		Interacts with MAP3K7 and TRAF6 (PubMed:10882101). Identified in the TRIKA2 complex composed of MAP3K7, TAB1 and TAB2 (PubMed:11460167). Binds 'Lys-63'-linked polyubiquitin chains (PubMed:19675569, PubMed:19935683). Interacts with NCOR1 and HDAC3 to form a ternary complex (By similarity). Interacts (via C-terminal) with NUMBL (via PTB domain) (PubMed:18299187). Interacts (via the C- terminus) with DYNC2I2 (via WD domains) (PubMed:19521662). Interacts with RBCK1 (PubMed:17449468). Interacts with TRIM5 (PubMed:21512573). {ECO:0000250\|UniProtKB:Q99K90, ECO:0000269\|PubMed:10882101, ECO:0000269\|PubMed:11460167, ECO:0000269\|PubMed:17449468, ECO:0000269\|PubMed:18299187, ECO:0000269\|PubMed:19521662, ECO:0000269\|PubMed:19675569, ECO:0000269\|PubMed:19935683, ECO:0000269\|PubMed:21512573}.
Subcellular location:		Membrane {ECO:0000269\|PubMed:10882101}; Peripheral membrane protein {ECO:0000269\|PubMed:10882101}. Cytoplasm, cytosol {ECO:0000269\|PubMed:10882101}. Note=Following IL1 stimulation, translocation occurs from the membrane to cytosol. {ECO:0000269\|PubMed:10882101}.
Tissue specificity:		Widely expressed. In the embryo, expressed in the ventricular trabeculae, endothelial cells of the conotruncal cushions of the outflow tract and in the endothelial cells lining the developing aortic valves. {ECO:0000269\|PubMed:10882101, ECO:0000269\|PubMed:20493459}.
Domain:		The RanBP2-type zinc finger (NZF) mediates binding to two consecutive 'Lys-63'-linked ubiquitins. {ECO:0000269\|PubMed:19935683, ECO:0000269\|PubMed:22158122}.
Ptm:		Ubiquitinated; following IL1 stimulation or TRAF6 overexpression. Ubiquitination involves RBCK1 leading to proteasomal degradation. {ECO:0000269\|PubMed:14633987, ECO:0000269\|PubMed:17449468}.
Ptm:		Phosphorylated. {ECO:0000305\|PubMed:10882101}.
Ptm:		(Microbial infection) Methylated at Cys-673 by enteropathogenic E.coli protein NleE or S.flexneri protein OspZ: methylation disrupts zinc-binding and ability to bind 'Lys-63'-linked ubiquitin, leading to NF-kappa-B inactivation. {ECO:0000269\|PubMed:22158122, ECO:0000269\|PubMed:25412445, ECO:0000269\|PubMed:27445336}.
Disease:		Congenital heart defects, multiple types, 2 (CHTD2) [MIM:614980]: A disease characterized by congenital developmental abnormalities involving structures of the heart. CHTD2 patients have left ventricular outflow tract obstruction, subaortic stenosis, residual aortic regurgitation, atrial fibrillation, bicuspid aortic valve and aortic dilation. {ECO:0000269\|PubMed:20493459}. Note=The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving TAB2 has been found in a family with congenital heart disease. Translocation t(2;6)(q21;q25).
Sequence caution:		Sequence=BAA34453.2; Type=Erroneous initiation; Evidence={ECO:0000305};