{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q96B67","secondaryAccessions":["A8K6T8","Q9P2H1"],"uniProtkbId":"ARRD3_HUMAN","entryAudit":{"firstPublicDate":"2006-06-27","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2001-12-01","entryVersion":170,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Arrestin domain-containing protein 3"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"16269462"}],"value":"TBP-2-like inducible membrane protein"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"16269462"}],"value":"TLIMP"}]}]},"genes":[{"geneName":{"value":"ARRDC3"},"synonyms":[{"value":"KIAA1376"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20559325"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23208550"}],"value":"Adapter protein that plays a role in regulating cell-surface expression of adrenergic receptors and probably also other G protein-coupled receptors (PubMed:20559325, PubMed:21982743, PubMed:23208550). Plays a role in NEDD4-mediated ubiquitination and endocytosis af activated ADRB2 and subsequent ADRB2 degradation (PubMed:20559325, PubMed:23208550). May recruit NEDD4 to ADRB2 (PubMed:20559325). Alternatively, may function as adapter protein that does not play a major role in recruiting NEDD4 to ADRB2, but rather plays a role in a targeting ADRB2 to endosomes (PubMed:23208550)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16269462"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20559325"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21191027"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21982743"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23208550"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23886940"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24379409"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25220262"}],"value":"Interacts (via PPxY motifs) with NEDD4 (via WW domains) (PubMed:20559325, PubMed:23208550, PubMed:24379409). Interacts with ADRB2 (PubMed:20559325, PubMed:21982743, PubMed:25220262). Interacts with ADRB3 (PubMed:21982743). Interacts with HGS (via PPxY motifs) (PubMed:23208550). Does not bind TXN (thioredoxin) (PubMed:16269462). Interacts with ITCH (PubMed:23886940). Interacts with WWP1 (via WW domains) 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Very low levels in colon, thymus, spleen, small intestine, bladder and bone marrow (PubMed:16269462). Strong expression in differentiated adipocytes compared to preadipocytes (PubMed:16269462). Detected in omental fat and subcutaneous fat tissue (PubMed:21982743)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16269462"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21982743"}],"value":"By troglitazone and pioglitazone (selective PPARG agonists), by prostaglandin J2 (PGJ2) and by L165,041 (a PPARD ligand), by vitamin D3 and, to a lesser extent, by phorbol myristate acetate (PMA) in the promyelocytic leukemia HL-60 cells. No induction by retinoic acid, nor by clofibrate (a specific PPARA agonist) (PubMed:16269462). Up-regulated by fasting (PubMed:21982743)"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the arrestin family"}],"commentType":"SIMILARITY"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"BAA92614.1","note":"Extended N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":414,"modifier":"EXACT"}},"description":"Arrestin domain-containing protein 3","featureId":"PRO_0000244349"},{"type":"Region","location":{"start":{"value":393,"modifier":"EXACT"},"end":{"value":414,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Motif","location":{"start":{"value":346,"modifier":"EXACT"},"end":{"value":349,"modifier":"EXACT"}},"description":"PPxY motif 1","evidences":[{"evidenceCode":"ECO:0000305"}]},{"type":"Motif","location":{"start":{"value":391,"modifier":"EXACT"},"end":{"value":394,"modifier":"EXACT"}},"description":"PPxY motif 2","evidences":[{"evidenceCode":"ECO:0000305"}]},{"type":"Compositional bias","location":{"start":{"value":405,"modifier":"EXACT"},"end":{"value":414,"modifier":"EXACT"}},"description":"Basic and acidic residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Mutagenesis","location":{"start":{"value":48,"modifier":"EXACT"},"end":{"value":48,"modifier":"EXACT"}},"description":"Abolishes interaction with ADRB2; when associated with E-52; E-85 and E-139.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25220262"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["E"]}},{"type":"Mutagenesis","location":{"start":{"value":52,"modifier":"EXACT"},"end":{"value":52,"modifier":"EXACT"}},"description":"Abolishes interaction with ADRB2; when associated with E-48; E-85 and E-139.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25220262"}],"alternativeSequence":{"originalSequence":"R","alternativeSequences":["E"]}},{"type":"Mutagenesis","location":{"start":{"value":56,"modifier":"EXACT"},"end":{"value":56,"modifier":"EXACT"}},"description":"Nearly abolishes interaction with ADRB2; when associated with E-58; E-135 and E-153.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25220262"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["E"]}},{"type":"Mutagenesis","location":{"start":{"value":58,"modifier":"EXACT"},"end":{"value":58,"modifier":"EXACT"}},"description":"Nearly abolishes interaction with ADRB2; when associated with E-56; E-135 and E-153.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25220262"}],"alternativeSequence":{"originalSequence":"R","alternativeSequences":["E"]}},{"type":"Mutagenesis","location":{"start":{"value":85,"modifier":"EXACT"},"end":{"value":85,"modifier":"EXACT"}},"description":"Abolishes interaction with ADRB2; when associated with E-48; E-52 and E-139.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25220262"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["E"]}},{"type":"Mutagenesis","location":{"start":{"value":135,"modifier":"EXACT"},"end":{"value":135,"modifier":"EXACT"}},"description":"Nearly abolishes interaction with ADRB2; when associated with E-56; E-58 and E-153.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25220262"}],"alternativeSequence":{"originalSequence":"R","alternativeSequences":["E"]}},{"type":"Mutagenesis","location":{"start":{"value":139,"modifier":"EXACT"},"end":{"value":139,"modifier":"EXACT"}},"description":"Abolishes interaction with ADRB2; when associated with E-48; E-52 and E-85.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25220262"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["E"]}},{"type":"Mutagenesis","location":{"start":{"value":153,"modifier":"EXACT"},"end":{"value":153,"modifier":"EXACT"}},"description":"Nearly abolishes interaction with ADRB2; when associated with E-56; E-58 and E-135.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25220262"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["E"]}},{"type":"Mutagenesis","location":{"start":{"value":346,"modifier":"EXACT"},"end":{"value":349,"modifier":"EXACT"}},"description":"Strongly reduces interaction with NEDD4. 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