ARRD4_HUMAN
ID ARRD4_HUMAN Reviewed; 418 AA.
AC Q8NCT1; Q6NSI9;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Arrestin domain-containing protein 4;
GN Name=ARRDC4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ALA-79; SER-347 AND
RP PRO-358.
RC TISSUE=Placenta, and Testis;
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 INTERACTION WITH ADRB2, AND SUBCELLULAR LOCATION.
RX PubMed=23208550; DOI=10.1038/embor.2012.187;
RA Han S.O., Kommaddi R.P., Shenoy S.K.;
RT "Distinct roles for beta-arrestin2 and arrestin-domain-containing proteins
RT in beta2 adrenergic receptor trafficking.";
RL EMBO Rep. 14:164-171(2013).
RN [4]
RP FUNCTION.
RX PubMed=19605364; DOI=10.1074/jbc.m109.018093;
RA Patwari P., Chutkow W.A., Cummings K., Verstraeten V.L., Lammerding J.,
RA Schreiter E.R., Lee R.T.;
RT "Thioredoxin-independent regulation of metabolism by the alpha-arrestin
RT proteins.";
RL J. Biol. Chem. 284:24996-25003(2009).
RN [5]
RP INTERACTION WITH ADRB2.
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).
RN [6]
RP SUBCELLULAR LOCATION, INTERACTION WITH AVPR2; ITCH; NEDD4L AND WWP2, AND
RP IDENTIFICATION IN A COMPLEX WITH AVPR2 AND HGS.
RX PubMed=23236378; DOI=10.1371/journal.pone.0050557;
RA Shea F.F., Rowell J.L., Li Y., Chang T.H., Alvarez C.E.;
RT "Mammalian alpha arrestins link activated seven transmembrane receptors to
RT Nedd4 family e3 ubiquitin ligases and interact with beta arrestins.";
RL PLoS ONE 7:E50557-E50557(2012).
CC -!- FUNCTION: Functions as an adapter recruiting ubiquitin-protein ligases
CC to their specific substrates (By similarity). Plays a role in
CC endocytosis of activated G protein-coupled receptors (GPCRs)
CC (Probable). Through an ubiquitination-dependent mechanism also plays a
CC role in the incorporation of SLC11A2 into extracellular vesicles (By
CC similarity). May play a role in glucose uptake (PubMed:19605364).
CC {ECO:0000250|UniProtKB:A0A0B4J1F4, ECO:0000269|PubMed:19605364,
CC ECO:0000305}.
CC -!- SUBUNIT: Interacts with ADRB2 (PubMed:21982743, PubMed:23208550).
CC Interacts (via PPxY motifs) with ITCH, NEDD4L and WWP2
CC (PubMed:23236378). Interacts with AVPR2. Identified in a complex
CC containing at least ARRDC4, AVPR2 and HGS (PubMed:23236378). Interacts
CC with SLC11A2; controls the incorporation of SLC11A2 into extracellular
CC vesicles through an ubiquitination-dependent mechanism (By similarity).
CC {ECO:0000250|UniProtKB:A0A0B4J1F4, ECO:0000269|PubMed:21982743,
CC ECO:0000269|PubMed:23208550, ECO:0000269|PubMed:23236378}.
CC -!- INTERACTION:
CC Q8NCT1; P30518: AVPR2; NbExp=2; IntAct=EBI-11673273, EBI-11675746;
CC -!- SUBCELLULAR LOCATION: Early endosome {ECO:0000269|PubMed:23208550}.
CC Cell membrane {ECO:0000269|PubMed:23208550,
CC ECO:0000269|PubMed:23236378}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:23236378}. Note=Also found in extracellular
CC vesicles different from exosomes. {ECO:0000250|UniProtKB:A0A0B4J1F4}.
CC -!- SIMILARITY: Belongs to the arrestin family. {ECO:0000305}.
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DR EMBL; AC024651; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC028704; AAH28704.2; -; mRNA.
DR EMBL; BC070100; AAH70100.1; -; mRNA.
DR CCDS; CCDS10377.1; -.
DR RefSeq; NP_899232.2; NM_183376.2.
DR AlphaFoldDB; Q8NCT1; -.
DR SMR; Q8NCT1; -.
DR BioGRID; 124894; 11.
DR IntAct; Q8NCT1; 5.
DR STRING; 9606.ENSP00000268042; -.
DR iPTMnet; Q8NCT1; -.
DR PhosphoSitePlus; Q8NCT1; -.
DR BioMuta; ARRDC4; -.
DR DMDM; 296439437; -.
DR MassIVE; Q8NCT1; -.
DR PaxDb; Q8NCT1; -.
DR PeptideAtlas; Q8NCT1; -.
DR PRIDE; Q8NCT1; -.
DR Antibodypedia; 51203; 122 antibodies from 22 providers.
DR DNASU; 91947; -.
DR Ensembl; ENST00000268042.7; ENSP00000268042.6; ENSG00000140450.9.
DR GeneID; 91947; -.
DR KEGG; hsa:91947; -.
DR MANE-Select; ENST00000268042.7; ENSP00000268042.6; NM_183376.3; NP_899232.2.
DR UCSC; uc010bom.4; human.
DR CTD; 91947; -.
DR DisGeNET; 91947; -.
DR GeneCards; ARRDC4; -.
DR HGNC; HGNC:28087; ARRDC4.
DR HPA; ENSG00000140450; Tissue enhanced (brain).
DR MIM; 619788; gene.
DR neXtProt; NX_Q8NCT1; -.
DR OpenTargets; ENSG00000140450; -.
DR PharmGKB; PA134895338; -.
DR VEuPathDB; HostDB:ENSG00000140450; -.
DR eggNOG; KOG3780; Eukaryota.
DR GeneTree; ENSGT00940000160523; -.
DR HOGENOM; CLU_039221_1_1_1; -.
DR InParanoid; Q8NCT1; -.
DR OMA; LMIEMPL; -.
DR OrthoDB; 817924at2759; -.
DR PhylomeDB; Q8NCT1; -.
DR TreeFam; TF313650; -.
DR PathwayCommons; Q8NCT1; -.
DR SignaLink; Q8NCT1; -.
DR BioGRID-ORCS; 91947; 13 hits in 1072 CRISPR screens.
DR GenomeRNAi; 91947; -.
DR Pharos; Q8NCT1; Tbio.
DR PRO; PR:Q8NCT1; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q8NCT1; protein.
DR Bgee; ENSG00000140450; Expressed in upper leg skin and 186 other tissues.
DR ExpressionAtlas; Q8NCT1; baseline and differential.
DR Genevisible; Q8NCT1; HS.
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; IDA:MGI.
DR GO; GO:1903561; C:extracellular vesicle; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; ISS:UniProtKB.
DR GO; GO:0140112; P:extracellular vesicle biogenesis; ISS:UniProtKB.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; IPI:MGI.
DR GO; GO:0015031; P:protein transport; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
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 1: Evidence at protein level;
KW Cell membrane; Cytoplasmic vesicle; Endosome; Membrane; Reference proteome;
KW Repeat.
FT CHAIN 1..418
FT /note="Arrestin domain-containing protein 4"
FT /id="PRO_0000244353"
FT MOTIF 350..353
FT /note="PPxY motif 1"
FT /evidence="ECO:0000305"
FT MOTIF 395..398
FT /note="PPxY motif 2"
FT /evidence="ECO:0000305"
FT VARIANT 79
FT /note="T -> A (in dbSNP:rs12101554)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_026899"
FT VARIANT 347
FT /note="P -> S (in dbSNP:rs17856817)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_026900"
FT VARIANT 358
FT /note="S -> P (in dbSNP:rs2130882)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_026901"
SQ SEQUENCE 418 AA; 45479 MW; 32E37F8AD2450074 CRC64;
MGGEAGCAAA VGAEGRVKSL GLVFEDERKG CYSSGETVAG HVLLEASEPV ALRALRLEAQ
GRATAAWGPS TCPRASASTA ALAVFSEVEY LNVRLSLREP PAGEGIILLQ PGKHEFPFRF
QLPSEPLVTS FTGKYGSIQY CVRAVLERPK VPDQSVKREL QVVSHVDVNT PALLTPVLKT
QEKMVGCWFF TSGPVSLSAK IERKGYCNGE AIPIYAEIEN CSSRLIVPKA AIFQTQTYLA
SGKTKTIRHM VANVRGNHIA SGSTDTWNGK TLKIPPVTPS ILDCCIIRVD YSLAVYIHIP
GAKKLMLELP LVIGTIPYNG FGSRNSSIAS QFSMDMSWLT LTLPEQPEAP PNYADVVSEE
EFSRHIPPYP QPPNCEGEVC CPVFACIQEF RFQPPPLYSE VDPHPSDVEE SQPVSFIL
