ARRD4_MOUSE
ID ARRD4_MOUSE Reviewed; 415 AA.
AC A0A0B4J1F4; Q8VD69;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 04-MAR-2015, sequence version 1.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=Arrestin domain-containing protein 4;
GN Name=Arrdc4 {ECO:0000312|EMBL:EDL07161.1,
GN ECO:0000312|Ensembl:ENSMUSP00000044578};
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 {ECO:0000312|Ensembl:ENSMUSP00000044578};
RN [1] {ECO:0000312|Ensembl:ENSMUSP00000044578, ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Ensembl:ENSMUSP00000044578,
RC ECO:0000312|Proteomes:UP000000589};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND IDENTIFICATION.
RC STRAIN=FVB/N {ECO:0000312|EMBL:AAH17528.1};
RC TISSUE=Salivary gland {ECO:0000312|EMBL:AAH17528.1};
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 [4]
RP SUBCELLULAR LOCATION.
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 FUNCTION, INTERACTION WITH SLC11A2, SUBCELLULAR LOCATION, INDUCTION, AND
RP MUTAGENESIS OF PHE-115.
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:27462458). Plays a role in
CC endocytosis of activated G protein-coupled receptors (GPCRs) (By
CC similarity). Through an ubiquitination-dependent mechanism also plays a
CC role in the incorporation of SLC11A2 into extracellular vesicles
CC (PubMed:27462458). May play a role in glucose uptake (By similarity).
CC {ECO:0000250|UniProtKB:Q8NCT1, ECO:0000269|PubMed:27462458}.
CC -!- SUBUNIT: Interacts with ADRB2. Interacts (via PPxY motifs) with ITCH,
CC NEDD4L and WWP2. Interacts with AVPR2. Identified in a complex
CC containing at least ARRDC4, AVPR2 and HGS (By similarity). Interacts
CC with SLC11A2; controls the incorporation of SLC11A2 into extracellular
CC vesicles through an ubiquitination-dependent mechanism
CC (PubMed:27462458). {ECO:0000250|UniProtKB:Q8NCT1,
CC ECO:0000269|PubMed:27462458}.
CC -!- SUBCELLULAR LOCATION: Early endosome {ECO:0000269|PubMed:19605364}.
CC Cell membrane {ECO:0000269|PubMed:19605364,
CC ECO:0000269|PubMed:27462458}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:19605364}. Note=Also found in extracellular
CC vesicles different from exosomes. {ECO:0000269|PubMed:27462458}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A0A0B4J1F4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A0A0B4J1F4-2; Sequence=VSP_058000, VSP_058001;
CC -!- INDUCTION: Up-regulated by high iron diet.
CC {ECO:0000269|PubMed:27462458}.
CC -!- SIMILARITY: Belongs to the arrestin family. {ECO:0000305}.
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DR EMBL; AC101933; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466543; EDL07161.1; -; Genomic_DNA.
DR EMBL; BC017528; AAH17528.1; -; mRNA.
DR CCDS; CCDS39985.1; -. [A0A0B4J1F4-1]
DR CCDS; CCDS52272.1; -. [A0A0B4J1F4-2]
DR RefSeq; NP_001036057.1; NM_001042592.2. [A0A0B4J1F4-1]
DR RefSeq; NP_079825.2; NM_025549.3. [A0A0B4J1F4-2]
DR AlphaFoldDB; A0A0B4J1F4; -.
DR SMR; A0A0B4J1F4; -.
DR IntAct; A0A0B4J1F4; 1.
DR STRING; 10090.ENSMUSP00000044578; -.
DR PhosphoSitePlus; A0A0B4J1F4; -.
DR PaxDb; A0A0B4J1F4; -.
DR ProteomicsDB; 281838; -. [A0A0B4J1F4-1]
DR ProteomicsDB; 281839; -. [A0A0B4J1F4-2]
DR Antibodypedia; 51203; 122 antibodies from 22 providers.
DR Ensembl; ENSMUST00000048068; ENSMUSP00000044578; ENSMUSG00000042659. [A0A0B4J1F4-1]
DR Ensembl; ENSMUST00000118110; ENSMUSP00000112962; ENSMUSG00000042659. [A0A0B4J1F4-2]
DR GeneID; 66412; -.
DR KEGG; mmu:66412; -.
DR UCSC; uc009hji.1; mouse.
DR CTD; 91947; -.
DR MGI; MGI:1913662; Arrdc4.
DR VEuPathDB; HostDB:ENSMUSG00000042659; -.
DR eggNOG; KOG3780; Eukaryota.
DR GeneTree; ENSGT00940000160523; -.
DR HOGENOM; CLU_039221_1_1_1; -.
DR OMA; LMIEMPL; -.
DR OrthoDB; 817924at2759; -.
DR PhylomeDB; A0A0B4J1F4; -.
DR BioGRID-ORCS; 66412; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Arrdc4; mouse.
DR PRO; PR:A0A0B4J1F4; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; A0A0B4J1F4; protein.
DR Bgee; ENSMUSG00000042659; Expressed in decidua and 201 other tissues.
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:1903561; C:extracellular vesicle; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IMP:UniProtKB.
DR GO; GO:0140112; P:extracellular vesicle biogenesis; IMP:UniProtKB.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; ISO:MGI.
DR GO; GO:0015031; P:protein transport; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; 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; 1.
DR SUPFAM; SSF81296; SSF81296; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasmic vesicle; Endosome;
KW Membrane; Reference proteome; Repeat.
FT CHAIN 1..415
FT /note="Arrestin domain-containing protein 4"
FT /id="PRO_0000435031"
FT MOTIF 347..350
FT /note="PPxY motif 1"
FT /evidence="ECO:0000305"
FT MOTIF 392..395
FT /note="PPxY motif 2"
FT /evidence="ECO:0000305"
FT VAR_SEQ 293..296
FT /note="YIHI -> IQAS (in isoform 2)"
FT /id="VSP_058000"
FT VAR_SEQ 297..415
FT /note="Missing (in isoform 2)"
FT /id="VSP_058001"
FT MUTAGEN 115
FT /note="F->L: Loss of localization to the cell membrane."
FT /evidence="ECO:0000269|PubMed:27462458"
SQ SEQUENCE 415 AA; 44970 MW; 9C3E9AB078E2D074 CRC64;
MGGEAGADGP RGRVKSLGLV FEDESKGCYS SGETVAGHVL LEAAEPVALR GLRLEAQGRA
TSAWGPSAGA RVCIGGGSPA ASSEVEYLNL RLSLLEAPAG EGVTLLQPGK HEFPFRFQLP
SEPLATSFTG KYGSIQYCVR AVLERPQVPD QSVRRELQVV SHVDVNTPPL LTPMLKTQEK
MVGCWLFTSG PVSLSVKIER KGYCNGEAIP IYAEIENCSS RLVVPKAAIF QTQTYLASGK
TKTVRHMVAN VRGNHIGSGS TDTWNGKMLK IPPVTPSILD CCIIRVDYSL AVYIHIPGAK
RLMLELPLVI GTIPYSGFGR RNSSVASQFS MDMCWLALAL PEQPEAPPNY ADVVSEEEFS
RHVPPYPQPS DCDGEACYSM FACIQEFRFQ PPPLYSEVDP HPGDAQETQP VSFIL
