ARRD3_MOUSE
ID ARRD3_MOUSE Reviewed; 414 AA.
AC Q7TPQ9; Q4KMN0; Q80TE6; Q8K0L7;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Arrestin domain-containing protein 3;
GN Name=Arrdc3; Synonyms=Kiaa1376;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=CD-1, and FVB/N; TISSUE=Eye, Kidney, and Neural stem cell;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, INDUCTION BY FASTING, AND TISSUE
RP SPECIFICITY.
RX PubMed=21982743; DOI=10.1016/j.cmet.2011.08.011;
RA Patwari P., Emilsson V., Schadt E.E., Chutkow W.A., Lee S., Marsili A.,
RA Zhang Y., Dobrin R., Cohen D.E., Larsen P.R., Zavacki A.M., Fong L.G.,
RA Young S.G., Lee R.T.;
RT "The arrestin domain-containing 3 protein regulates body mass and energy
RT expenditure.";
RL Cell Metab. 14:671-683(2011).
CC -!- FUNCTION: Adapter protein that plays a role in regulating cell-surface
CC expression of adrenergic receptors and probably also other G protein-
CC coupled receptors (PubMed:21982743). Plays a role in NEDD4-mediated
CC ubiquitination and endocytosis af activated ADRB2 and subsequent ADRB2
CC degradation. May recruit NEDD4 to ADRB2. Alternatively, may function as
CC adapter protein that does not play a major role in recruiting NEDD4 to
CC ADRB2, but rather plays a role in a targeting ADRB2 to endosomes.
CC {ECO:0000250|UniProtKB:Q96B67, ECO:0000305|PubMed:21982743}.
CC -!- SUBUNIT: Interacts (via PPxY motifs) with NEDD4 (via WW domains).
CC Interacts with ADRB2. Interacts with ADRB3. Interacts with HGS (via
CC PPxY motifs). Does not bind TXN (thioredoxin). Interacts with ITCH.
CC {ECO:0000250|UniProtKB:Q96B67}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96B67}. Cell
CC membrane {ECO:0000250|UniProtKB:Q96B67}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q96B67}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q96B67}. Lysosome
CC {ECO:0000250|UniProtKB:Q96B67}. Endosome
CC {ECO:0000250|UniProtKB:Q96B67}. Early endosome
CC {ECO:0000250|UniProtKB:Q96B67}. Note=Associated with plasma membrane,
CC as well as with endosomes and lysosomes during endocytosis.
CC {ECO:0000250|UniProtKB:Q96B67}.
CC -!- TISSUE SPECIFICITY: Detected in visceral fat, subcutaneous fat, brown
CC fat and skeletal muscle, and at lower levels in kidney.
CC {ECO:0000269|PubMed:21982743}.
CC -!- INDUCTION: Up-regulated by fasting. Transiently up-regulated during the
CC differentiation of pre-adipocytes. {ECO:0000269|PubMed:21982743}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate, but
CC there is important perinatal lethality and the majority do not survive
CC till weaning. Mutant mice have considerably less body mass and
CC accumulate less body fat than wild-type, in spite of normal food
CC intake. Heterozygous mice display higher oxygen uptake, increased
CC activity levels and higher energy expenditure than wild-type. In
CC addition, they display increased expression of genes required for
CC thermogenesis, increased activation of signaling cascades downstream of
CC beta-adrenergic receptors, more rapid readjustment of body temperature
CC when exposed to cold and increased heat production.
CC {ECO:0000269|PubMed:21982743}.
CC -!- SIMILARITY: Belongs to the arrestin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC65781.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK122499; BAC65781.1; ALT_INIT; mRNA.
DR EMBL; BC031125; AAH31125.1; -; mRNA.
DR EMBL; BC054844; AAH54844.1; -; mRNA.
DR EMBL; BC098474; AAH98474.1; -; mRNA.
DR CCDS; CCDS36736.1; -.
DR RefSeq; NP_001036056.1; NM_001042591.1.
DR AlphaFoldDB; Q7TPQ9; -.
DR SMR; Q7TPQ9; -.
DR STRING; 10090.ENSMUSP00000096957; -.
DR iPTMnet; Q7TPQ9; -.
DR PhosphoSitePlus; Q7TPQ9; -.
DR PaxDb; Q7TPQ9; -.
DR PRIDE; Q7TPQ9; -.
DR ProteomicsDB; 283176; -.
DR Antibodypedia; 57571; 150 antibodies from 27 providers.
DR DNASU; 105171; -.
DR Ensembl; ENSMUST00000099356; ENSMUSP00000096957; ENSMUSG00000074794.
DR GeneID; 105171; -.
DR KEGG; mmu:105171; -.
DR UCSC; uc007rhi.2; mouse.
DR CTD; 57561; -.
DR MGI; MGI:2145242; Arrdc3.
DR VEuPathDB; HostDB:ENSMUSG00000074794; -.
DR eggNOG; KOG3780; Eukaryota.
DR GeneTree; ENSGT00940000155411; -.
DR HOGENOM; CLU_039221_1_1_1; -.
DR InParanoid; Q7TPQ9; -.
DR OMA; WFLPVKL; -.
DR OrthoDB; 817924at2759; -.
DR PhylomeDB; Q7TPQ9; -.
DR TreeFam; TF313650; -.
DR BioGRID-ORCS; 105171; 6 hits in 73 CRISPR screens.
DR ChiTaRS; Arrdc3; mouse.
DR PRO; PR:Q7TPQ9; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q7TPQ9; protein.
DR Bgee; ENSMUSG00000074794; Expressed in manus and 234 other tissues.
DR ExpressionAtlas; Q7TPQ9; baseline and differential.
DR Genevisible; Q7TPQ9; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0031699; F:beta-3 adrenergic receptor binding; ISO:MGI.
DR GO; GO:0060613; P:fat pad development; IMP:MGI.
DR GO; GO:0031649; P:heat generation; IMP:MGI.
DR GO; GO:0071878; P:negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway; IMP:MGI.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0031651; P:negative regulation of heat generation; IMP:MGI.
DR GO; GO:0090327; P:negative regulation of locomotion involved in locomotory behavior; IMP:MGI.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; ISO:MGI.
DR GO; GO:0015031; P:protein transport; IBA:GO_Central.
DR GO; GO:0043588; P:skin development; IMP:MGI.
DR GO; GO:0001659; P:temperature homeostasis; IMP:MGI.
DR Gene3D; 2.60.40.640; -; 2.
DR InterPro; IPR014752; Arrestin-like_C.
DR InterPro; IPR011021; Arrestin-like_N.
DR InterPro; IPR011022; Arrestin_C-like.
DR InterPro; IPR014756; Ig_E-set.
DR Pfam; PF02752; Arrestin_C; 1.
DR Pfam; PF00339; Arrestin_N; 1.
DR SMART; SM01017; Arrestin_C; 1.
DR SUPFAM; SSF81296; SSF81296; 2.
PE 2: Evidence at transcript level;
KW Cell membrane; Cytoplasm; Endosome; Lysosome; Membrane; Reference proteome;
KW Repeat.
FT CHAIN 1..414
FT /note="Arrestin domain-containing protein 3"
FT /id="PRO_0000244350"
FT REGION 393..414
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 346..349
FT /note="PPxY motif 1"
FT /evidence="ECO:0000305"
FT MOTIF 391..394
FT /note="PPxY motif 2"
FT /evidence="ECO:0000305"
FT COMPBIAS 398..414
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 352
FT /note="V -> A (in Ref. 2; AAH98474)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 414 AA; 46275 MW; A9F5EA3A2D701F42 CRC64;
MVLGKVKSLT ISFDCLNDSN VPVYSSGDTV SGRVNLEVTG EIRVKSLKIH ARGHAKVRWT
ESRNAGSNTA YTQNYTEEVE YFNHKDILIG HERDDDNSEE GFHTIHSGRH EYAFSFELPQ
TPLATSFEGR HGSVRYWVKA ELHRPWLLPV KLKKEFTVFE HIDINTPSLL SPQAGTKEKT
LCCWFCTSGP ISLSAKIERK GYTPGESIQI FAEIENCSSR MVVPKAAIYQ TQAFYAKGKM
KEVKQLVANL RGESLSSGKT ETWNGKLLKI PPVSPSILDC SIIRVEYSLM VYVDIPGAMD
LLLSLPLVIG TIPLHPFGSR TSSVSSQCSM SMNWLALALP ERPEAPPSYA EVVTEEQRRN
NLAPVGACDD FERALQGPLF AYIQEFRFLP PPLYSEIDPN PDQSSEDRPS CPSR
