Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Thioredoxin-binding protein-2-like inducible membrane protein is a novel vitamin D3 and peroxisome proliferator-activated receptor (PPAR)gamma ligand target protein that regulates PPARgamma signaling.
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TLIMP (ARRDC3) is at membranes, endosomes and lysosomes.
"TLIMP exhibited an inner membrane-associated pattern of distribution and also colocalized with transferrin and low-density lipoprotein, indicating endosome- and lysosome-associated functions."
Arrestin domain-containing protein 3 recruits the NEDD4 E3 ligase to mediate ubiquitination of the beta2-adrenergic receptor.
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ARRDC3 recruits NEDD4 to activated beta2AR via PPxY motifs.
"The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."
ARRDC3 suppresses breast cancer progression by negatively regulating integrin beta4.
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ARRDC3 binds phosphorylated ITGB4 and drives its degradation.
"Our data indicates ARRDC3 directly binds to a phosphorylated form of ITGbeta4 leading to its internalization, ubiquitination and ultimate degradation."
The arrestin domain-containing 3 protein regulates body mass and energy expenditure.
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ARRDC3 binds beta-adrenergic receptors and regulates energy expenditure.
"ARRDC3 interacted directly with β-adrenergic receptors, and loss of ARRDC3 increased the response to β-adrenergic stimulation in isolated adipose tissue."
Distinct roles for β-arrestin2 and arrestin-domain-containing proteins in β2 adrenergic receptor trafficking.
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ARRDC proteins are secondary adaptors trafficking Nedd4-beta2AR complexes to early endosomes.
"The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized β(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of β-arrestin2."
Mammalian α arrestins link activated seven transmembrane receptors to Nedd4 family e3 ubiquitin ligases and interact with β arrestins.
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Alpha-arrestins recruit Nedd4 E3s to activated receptors.
"[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."
Α-arrestin 1 (ARRDC1) and β-arrestins cooperate to mediate Notch degradation in mammals.
The Hippo signaling pathway interactome.
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Mammalian Arrdc1 or Arrdc3 expression reduces Yki-reporter activity.
"Expression of Arrdc1 or Arrdc3 reduced Yki-reporter activity"
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Leash binds Nedd4 and other HECT ligases.
"We also identified additional Leash interactors by AP/MS (tables S8 and S9) and found that Leash strongly binds to Nedd4 and a few other HECT (homologous to E6-AP carboxyl terminus) ubiquitin ligases (Fig."
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Leash lowers Yki through lysosomal degradation.
"4D), indicating that Leash decreases Yki abundance through the lysosomal degradation pathway."
A proteome-scale map of the human interactome network.
Architecture of the human interactome defines protein communities and disease networks.
ARRDC3 suppresses colorectal cancer progression through destabilizing the oncoprotein YAP.
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ARRDC3 binds YAP and decreases its levels.
"Mechanistically, we reveal that ARRDC3 binds and decreases expression of the oncoprotein YAP, the cotranscription factor of the Hippo pathway."
A reference map of the human binary protein interactome.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Comparative interactome analysis of α-arrestin families in human and Drosophila.
Multimodal cell maps as a foundation for structural and functional genomics.
Insights into β2-adrenergic receptor binding from structures of the N-terminal lobe of ARRDC3.
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Basic-patch residues of the ARRDC3 N-lobe are needed for beta2AR binding.
"Residues within the basic patch were shown to be important for binding to β2AR, similar to the situation with β-arrestins."
The α-Arrestin ARRDC3 Regulates the Endosomal Residence Time and Intracellular Signaling of the β2-Adrenergic Receptor.
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ARRDC3 binds beta2AR ligand-independently and sits on EEA1 early endosomes.
"We find that ARRDC3 primarily localizes to EEA1-positive early endosomes and directly interacts with the β2AR in a ligand-independent manner."
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ARRDC3 restrains beta2AR entry into SNX27 tubules without affecting degradation.
"Although ARRDC3 has no effect on β2AR endocytosis or degradation, it negatively regulates β2AR entry into SNX27-occupied endosomal tubules."
The α-arrestin ARRDC3 mediates ALIX ubiquitination and G protein-coupled receptor lysosomal sorting.
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ARRDC3 regulates ALIX in GPCR sorting via ubiquitination.
"Here we show that the mammalian α-arrestin arrestin domain-containing protein-3 (ARRDC3) regulates ALIX function in GPCR sorting via ubiquitination."
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ARRDC3 is required for PAR1-induced ALIX ubiquitination.
"We found that ARRDC3 is required for ALIX ubiquitination induced by activation of PAR1."
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ALIX ubiquitination depends on ARRDC3 and WWP2.
"Moreover, activation of PAR1 increases ALIX ubiquitination that is dependent on ARRDC3 and WW domain–containing E3 ubiquitin protein ligase 2 (WWP2)."
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ARRDC3 is required for PAR1 sorting and degradation.
"ARRDC3 colocalizes with ALIX and is required for PAR1 sorting at late endosomes and degradation."
The α-arrestin ARRDC3 suppresses breast carcinoma invasion by regulating G protein-coupled receptor lysosomal sorting and signaling.
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ARRDC3 re-expression restores ALIX-dependent PAR1 lysosomal trafficking in breast carcinoma.
"Using a lentiviral doxycycline-inducible system, we demonstrate that re-expression of ARRDC3 in invasive breast carcinoma is sufficient to restore normal PAR1 trafficking through the ALG-interacting protein X (ALIX)-dependent lysosomal degradative pathway."
Structural and biochemical basis for ubiquitin ligase recruitment by arrestin-related domain-containing protein-3 (ARRDC3).
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ARRDC3 PPXY1 binds Nedd4 WW3 with Kd about 3 uM.
"ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 μM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."
Divergent regulation of α-arrestin ARRDC3 function by ubiquitination.
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ARRDC3 ubiquitination via PPxY motifs governs its degradation, localization and WWP2 binding.
"Additionally, ubiquitination and the PPXY motifs mediate ARRDC3 protein degradation, dictate ARRDC3 subcellular localization, and are required for interaction with the NEDD4-family E3 ubiquitin ligase WWP2."
ARRDC3 tyrosine phosphorylation functions as a switch to control c-Src versus WWP2 interactions and distinct scaffolding functions.
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Y394 phosphorylation switches ARRDC3 from WWP2 to c-Src binding.
"We found that ARRDC3 Y394 phosphorylation promotes interaction with c-Src via its SH2 domain, whereas the non-phosphorylated form binds to WWP2."
ARRDC1 and ARRDC3 act as tumor suppressors in renal cell carcinoma by facilitating YAP1 degradation.
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ARRDC3 promotes ITCH-mediated YAP1 ubiquitination and degradation.
"Mechanically, ARRDC1/3 negatively regulates YAP1 protein stability by facilitating E3 ubiquitin ligase Itch-mediated ubiquitination and degradation of YAP1."
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YAP1 binding uses ARRDC3 PPxY motifs.
"Binding of ARRDC1/3 to YAP1 is mediated through the WW domains of YAP1 and the PPXY motifs of ARRDC1/3."
α-Arrestin ARRDC3 tumor suppressor function is linked to GPCR-induced TAZ activation and breast cancer metastasis.
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ARRDC3 sequesters TAZ independently of PAR1 trafficking.
"Additionally, ARRDC3 suppresses PAR1-induced Hippo signaling via sequestration of TAZ, which occurs independently of ARRDC3-regulated PAR1 trafficking."
Adipocyte arrestin domain-containing 3 protein (Arrdc3) regulates uncoupling protein 1 (Ucp1) expression in white adipose independently of canonical changes in β-adrenergic receptor signaling.
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Adipocyte Arrdc3 deletion raises Ucp1.
"We generated a mouse with conditional deletion of Arrdc3, and here we present evidence that genetic ablation of Arrdc3 specifically in adipocytes results in increased Ucp1 expression in subcutaneous and parametrial adipose tissue."
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Canonical beta-adrenergic signalling is unchanged in Arrdc3-null adipocytes.
"Additionally, canonical β-adrenergic receptor signaling was not different in Arrdc3-null adipocytes."
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Agonist-treated null adipocytes show decreased Ucp1.
"It was previously hypothesized that Arrdc3 ablation leads to increased β-adrenergic receptor sensitivity; however, in vitro experiments show that Arrdc3-null adipocytes responded to β-adrenergic receptor agonist with decreased Ucp1 levels."
UniProt entry Q96B67 (ARRD3_HUMAN)
Affinage mechanistic annotation for ARRDC3 (human)