UniProt functional annotation for Q3TTA7



	UniProt functional annotation for Q3TTA7

UniProt code: Q3TTA7.

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, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBL, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (PubMed:29237719). {ECO:0000269|PubMed:10646608, ECO:0000269|PubMed:10646609, ECO:0000269|PubMed:11070165, ECO:0000269|PubMed:11526404, ECO:0000269|PubMed:12771181, ECO:0000269|PubMed:15308098, ECO:0000269|PubMed:29237719}.

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; Evidence={ECO:0000250|UniProtKB:Q13191};

Pathway: Protein modification; protein ubiquitination.

Subunit: Interacts with SH3 domain-containing proteins LCK, CRK and SORBS1. Interacts with LCP2 and ZAP70. Interacts with CBL. Interacts with SH3 domain-containing proteins VAV1, FYN, FGR, PLCG1, GRB2, CRKL, PIK3R1 and SH3KBP1/CIN85. Identified in heterotrimeric complexes with SH3KBP1/CIN85, CD2AP and ARHGEF7, where one CBLB peptide binds two copies of the other protein. Interacts with poly-ubiquitinated proteins. Dimerization is required for the binding of poly-ubiquitin, but not for the binding of mono-ubiquitin. Interacts with EGFR (phosphorylated). Interacts with IFT20 (By similarity). {ECO:0000250|UniProtKB:Q13191, ECO:0000269|PubMed:10646608, ECO:0000269|PubMed:12842890}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:12842890}. Note=In adipocytes, translocates to the plasma membrane upon insulin stimulation.

Induction: By serum starvation. {ECO:0000269|PubMed:29237719}.

Domain: The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain.

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

Domain: The UBA domain interacts with poly-ubiquitinated proteins. {ECO:0000250|UniProtKB:Q13191}.

Ptm: Phosphorylated on tyrosine and serine residues upon TCR or BCR activation. Phosphorylated on Tyr-664 and Tyr-708 in adipocytes following insulin stimulation. {ECO:0000269|PubMed:12771181, ECO:0000269|PubMed:12842890}.

Ptm: Auto-ubiquitinated upon EGF-mediated cell activation or upon T- cell costimulation by CD28; which promotes proteasomal degradation. {ECO:0000269|PubMed:12193687}.

Disruption phenotype: Mice are fertile and grossly normal. However, they show a high sensitivity to autoimmune diseases and may develop a spontaneous generalized autoimmune disorder characterized by auto- antibody production, infiltration of activated T- and B-lymphocytes into various organs and parenchymal damage. {ECO:0000269|PubMed:10646609}.

Miscellaneous: This protein has one functional calcium-binding site. {ECO:0000250}.

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, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBL, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (PubMed:29237719). {ECO:0000269\|PubMed:10646608, ECO:0000269\|PubMed:10646609, ECO:0000269\|PubMed:11070165, ECO:0000269\|PubMed:11526404, ECO:0000269\|PubMed:12771181, ECO:0000269\|PubMed:15308098, ECO:0000269\|PubMed:29237719}.


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; Evidence={ECO:0000250\|UniProtKB:Q13191};
Pathway:		Protein modification; protein ubiquitination.
Subunit:		Interacts with SH3 domain-containing proteins LCK, CRK and SORBS1. Interacts with LCP2 and ZAP70. Interacts with CBL. Interacts with SH3 domain-containing proteins VAV1, FYN, FGR, PLCG1, GRB2, CRKL, PIK3R1 and SH3KBP1/CIN85. Identified in heterotrimeric complexes with SH3KBP1/CIN85, CD2AP and ARHGEF7, where one CBLB peptide binds two copies of the other protein. Interacts with poly-ubiquitinated proteins. Dimerization is required for the binding of poly-ubiquitin, but not for the binding of mono-ubiquitin. Interacts with EGFR (phosphorylated). Interacts with IFT20 (By similarity). {ECO:0000250\|UniProtKB:Q13191, ECO:0000269\|PubMed:10646608, ECO:0000269\|PubMed:12842890}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:12842890}. Note=In adipocytes, translocates to the plasma membrane upon insulin stimulation.
Induction:		By serum starvation. {ECO:0000269\|PubMed:29237719}.
Domain:		The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain.
Domain:		The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.
Domain:		The UBA domain interacts with poly-ubiquitinated proteins. {ECO:0000250\|UniProtKB:Q13191}.
Ptm:		Phosphorylated on tyrosine and serine residues upon TCR or BCR activation. Phosphorylated on Tyr-664 and Tyr-708 in adipocytes following insulin stimulation. {ECO:0000269\|PubMed:12771181, ECO:0000269\|PubMed:12842890}.
Ptm:		Auto-ubiquitinated upon EGF-mediated cell activation or upon T- cell costimulation by CD28; which promotes proteasomal degradation. {ECO:0000269\|PubMed:12193687}.
Disruption phenotype:		Mice are fertile and grossly normal. However, they show a high sensitivity to autoimmune diseases and may develop a spontaneous generalized autoimmune disorder characterized by auto- antibody production, infiltration of activated T- and B-lymphocytes into various organs and parenchymal damage. {ECO:0000269\|PubMed:10646609}.
Miscellaneous:		This protein has one functional calcium-binding site. {ECO:0000250}.