ARRD1_HUMAN
ID ARRD1_HUMAN Reviewed; 433 AA.
AC Q8N5I2;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Arrestin domain-containing protein 1 {ECO:0000305};
DE AltName: Full=Alpha-arrestin 1 {ECO:0000303|PubMed:23886940};
GN Name=ARRDC1 {ECO:0000312|HGNC:HGNC:28633};
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=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Blood;
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 WWP1; WWP2; NEDD4; ITCH; TSG101 AND PDCD6IP, AND
RP UBIQUITINATION BY WWP1.
RX PubMed=21191027; DOI=10.1128/jvi.02045-10;
RA Rauch S., Martin-Serrano J.;
RT "Multiple interactions between the ESCRT machinery and arrestin-related
RT proteins: implications for PPXY-dependent budding.";
RL J. Virol. 85:3546-3556(2011).
RN [4]
RP FUNCTION, INTERACTION WITH TSG101 AND WWP2, SUBCELLULAR LOCATION,
RP UBIQUITINATION BY WWP2, MUTAGENESIS OF PHE-88; GLY-180; ASN-191 AND
RP SER-310, AND MOTIF.
RX PubMed=22315426; DOI=10.1073/pnas.1200448109;
RA Nabhan J.F., Hu R., Oh R.S., Cohen S.N., Lu Q.;
RT "Formation and release of arrestin domain-containing protein 1-mediated
RT microvesicles (ARMMs) at plasma membrane by recruitment of TSG101
RT protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:4146-4151(2012).
RN [5]
RP FUNCTION, INTERACTION WITH ARRB1; ARRB2 AND ITCH, MUTAGENESIS OF PRO-403
RP AND PRO-416, AND MOTIF.
RX PubMed=23886940; DOI=10.1242/jcs.130500;
RA Puca L., Chastagner P., Meas-Yedid V., Israel A., Brou C.;
RT "Alpha-arrestin 1 (ARRDC1) and beta-arrestins cooperate to mediate Notch
RT degradation in mammals.";
RL J. Cell Sci. 126:4457-4468(2013).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [7]
RP FUNCTION, INTERACTION WITH SLC11A2, AND SUBCELLULAR LOCATION.
RX PubMed=27462458; DOI=10.1038/celldisc.2016.11;
RA Mackenzie K., Foot N.J., Anand S., Dalton H.E., Chaudhary N., Collins B.M.,
RA Mathivanan S., Kumar S.;
RT "Regulation of the divalent metal ion transporter via membrane budding.";
RL Cell Discov. 2:16011-16011(2016).
CC -!- FUNCTION: Functions as an adapter recruiting ubiquitin-protein ligases
CC to their specific substrates (PubMed:23886940, PubMed:27462458).
CC Through an ubiquitination-dependent mechanism plays for instance a role
CC in the incorporation of SLC11A2 into extracellular vesicles
CC (PubMed:27462458). More generally, plays a role in the extracellular
CC transport of proteins between cells through the release in the
CC extracellular space of microvesicles (PubMed:22315426). By
CC participating in the ITCH-mediated ubiquitination and subsequent
CC degradation of NOTCH1, negatively regulates the NOTCH signaling pathway
CC (PubMed:23886940). {ECO:0000269|PubMed:22315426,
CC ECO:0000269|PubMed:23886940, ECO:0000269|PubMed:27462458}.
CC -!- SUBUNIT: Interacts (via PPxY motifs) with ITCH (via WW domains); the
CC interaction is direct and participates in the recruitment of the
CC ubiquitin-protein ligase ITCH to the NOTCH1 receptor (PubMed:21191027,
CC PubMed:23886940). Interacts with ARRB1 and ARRB2; the interaction is
CC direct (PubMed:23886940). Interacts with TSG101; may recruit TSG101 to
CC the plasma membrane (PubMed:21191027, PubMed:22315426). Interacts (via
CC PPxY motifs) with WWP2 (via WW domains); ubiquitinates ARRDC1
CC (PubMed:21191027, PubMed:22315426). Interacts with SLC11A2; controls
CC the incorporation of SLC11A2 into extracellular vesicles through an
CC ubiquitination-dependent mechanism (PubMed:27462458). Interacts with
CC WWP1 (via WW domains) (PubMed:21191027). Interacts with NEDD4 (via WW
CC domains) (PubMed:21191027). Interacts with PDCD6IP (PubMed:21191027).
CC {ECO:0000269|PubMed:21191027, ECO:0000269|PubMed:22315426,
CC ECO:0000269|PubMed:23886940, ECO:0000269|PubMed:27462458}.
CC -!- INTERACTION:
CC Q8N5I2; O95208-2: EPN2; NbExp=3; IntAct=EBI-2339564, EBI-12135243;
CC Q8N5I2; Q53G59: KLHL12; NbExp=3; IntAct=EBI-2339564, EBI-740929;
CC Q8N5I2; Q8N3F0: MTURN; NbExp=3; IntAct=EBI-2339564, EBI-11980301;
CC Q8N5I2; P57075-2: UBASH3A; NbExp=3; IntAct=EBI-2339564, EBI-7353612;
CC Q8N5I2; Q9H0M0: WWP1; NbExp=3; IntAct=EBI-2339564, EBI-742157;
CC Q8N5I2; O00308: WWP2; NbExp=5; IntAct=EBI-2339564, EBI-743923;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22315426,
CC ECO:0000269|PubMed:27462458}. Note=Also found in extracellular vesicles
CC different from exosomes. {ECO:0000269|PubMed:22315426,
CC ECO:0000269|PubMed:27462458}.
CC -!- DOMAIN: The PPxY motifs mediate interaction with WW domain-containing
CC ubiquitin-protein ligases. {ECO:0000269|PubMed:22315426,
CC ECO:0000269|PubMed:23886940}.
CC -!- PTM: Ubiquitinated (PubMed:21191027, PubMed:22315426). Ubiquitination
CC by WWP2; promotes localization to extracellular microvesicles
CC (PubMed:22315426). Ubiquitinated by WWP1 (PubMed:21191027).
CC {ECO:0000269|PubMed:21191027, ECO:0000269|PubMed:22315426}.
CC -!- SIMILARITY: Belongs to the arrestin family. {ECO:0000305}.
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DR EMBL; BC032346; AAH32346.1; -; mRNA.
DR EMBL; AL365502; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS7049.1; -.
DR RefSeq; NP_689498.1; NM_152285.3.
DR AlphaFoldDB; Q8N5I2; -.
DR SMR; Q8N5I2; -.
DR BioGRID; 124970; 46.
DR IntAct; Q8N5I2; 35.
DR STRING; 9606.ENSP00000360475; -.
DR iPTMnet; Q8N5I2; -.
DR PhosphoSitePlus; Q8N5I2; -.
DR BioMuta; ARRDC1; -.
DR DMDM; 74751028; -.
DR EPD; Q8N5I2; -.
DR jPOST; Q8N5I2; -.
DR MassIVE; Q8N5I2; -.
DR MaxQB; Q8N5I2; -.
DR PaxDb; Q8N5I2; -.
DR PeptideAtlas; Q8N5I2; -.
DR PRIDE; Q8N5I2; -.
DR ProteomicsDB; 72059; -.
DR Antibodypedia; 49444; 153 antibodies from 25 providers.
DR DNASU; 92714; -.
DR Ensembl; ENST00000371421.9; ENSP00000360475.4; ENSG00000197070.14.
DR GeneID; 92714; -.
DR KEGG; hsa:92714; -.
DR MANE-Select; ENST00000371421.9; ENSP00000360475.4; NM_152285.4; NP_689498.1.
DR UCSC; uc004cns.4; human.
DR CTD; 92714; -.
DR DisGeNET; 92714; -.
DR GeneCards; ARRDC1; -.
DR HGNC; HGNC:28633; ARRDC1.
DR HPA; ENSG00000197070; Low tissue specificity.
DR MIM; 619768; gene.
DR neXtProt; NX_Q8N5I2; -.
DR OpenTargets; ENSG00000197070; -.
DR PharmGKB; PA134938267; -.
DR VEuPathDB; HostDB:ENSG00000197070; -.
DR eggNOG; KOG3780; Eukaryota.
DR GeneTree; ENSGT00940000159652; -.
DR HOGENOM; CLU_051966_0_0_1; -.
DR InParanoid; Q8N5I2; -.
DR OMA; VRYNNTF; -.
DR OrthoDB; 647994at2759; -.
DR PhylomeDB; Q8N5I2; -.
DR TreeFam; TF313650; -.
DR PathwayCommons; Q8N5I2; -.
DR SignaLink; Q8N5I2; -.
DR BioGRID-ORCS; 92714; 11 hits in 1076 CRISPR screens.
DR ChiTaRS; ARRDC1; human.
DR GenomeRNAi; 92714; -.
DR Pharos; Q8N5I2; Tbio.
DR PRO; PR:Q8N5I2; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q8N5I2; protein.
DR Bgee; ENSG00000197070; Expressed in lower esophagus mucosa and 172 other tissues.
DR ExpressionAtlas; Q8N5I2; baseline and differential.
DR Genevisible; Q8N5I2; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:1903561; C:extracellular vesicle; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:1990763; F:arrestin family protein binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IMP:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0006858; P:extracellular transport; IMP:UniProtKB.
DR GO; GO:0140112; P:extracellular vesicle biogenesis; IMP:UniProtKB.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP: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; 2.
DR SUPFAM; SSF81296; SSF81296; 2.
PE 1: Evidence at protein level;
KW Cell membrane; Membrane; Reference proteome; Ubl conjugation.
FT CHAIN 1..433
FT /note="Arrestin domain-containing protein 1"
FT /id="PRO_0000244345"
FT REGION 296..322
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 402..405
FT /note="PPxY motif 1"
FT /evidence="ECO:0000269|PubMed:23886940"
FT MOTIF 415..418
FT /note="PPxY motif 2"
FT /evidence="ECO:0000269|PubMed:23886940"
FT COMPBIAS 296..311
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 363
FT /note="G -> C (in dbSNP:rs35018943)"
FT /id="VAR_048335"
FT MUTAGEN 88
FT /note="F->L: Loss of localization to the cell membrane and
FT extracellular vesicles. Localizes to the cytoplasm."
FT /evidence="ECO:0000269|PubMed:22315426"
FT MUTAGEN 180
FT /note="G->A: Decreased localization to the cell membrane
FT and extracellular vesicles."
FT /evidence="ECO:0000269|PubMed:22315426"
FT MUTAGEN 191
FT /note="N->D: Decreased localization to the cell membrane
FT and extracellular vesicles."
FT /evidence="ECO:0000269|PubMed:22315426"
FT MUTAGEN 310
FT /note="S->A: Decreased interaction with TSG101. No effect
FT on localization to the cell membrane. Loss of localization
FT to extracellular vesicles."
FT /evidence="ECO:0000269|PubMed:22315426"
FT MUTAGEN 403
FT /note="P->A: Loss of interaction with ITCH; when associated
FT with A-416."
FT /evidence="ECO:0000269|PubMed:23886940"
FT MUTAGEN 416
FT /note="P->A: Loss of interaction with ITCH; when associated
FT with A-403."
FT /evidence="ECO:0000269|PubMed:23886940"
SQ SEQUENCE 433 AA; 45981 MW; 5B52A79EE27B5DDB CRC64;
MGRVQLFEIS LSHGRVVYSP GEPLAGTVRV RLGAPLPFRA IRVTCIGSCG VSNKANDTAW
VVEEGYFNSS LSLADKGSLP AGEHSFPFQF LLPATAPTSF EGPFGKIVHQ VRAAIHTPRF
SKDHKCSLVF YILSPLNLNS IPDIEQPNVA SATKKFSYKL VKTGSVVLTA STDLRGYVVG
QALQLHADVE NQSGKDTSPV VASLLQKVSY KAKRWIHDVR TIAEVEGAGV KAWRRAQWHE
QILVPALPQS ALPGCSLIHI DYYLQVSLKA PEATVTLPVF IGNIAVNHAP VSPRPGLGLP
PGAPPLVVPS APPQEEAEAE AAAGGPHFLD PVFLSTKSHS QRQPLLATLS SVPGAPEPCP
QDGSPASHPL HPPLCISTGA TVPYFAEGSG GPVPTTSTLI LPPEYSSWGY PYEAPPSYEQ
SCGGVEPSLT PES
