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Protein

Arrestin domain-containing protein 3

Gene

ARRDC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).2 Publications

GO - Molecular functioni

  • beta-3 adrenergic receptor binding Source: MGI

GO - Biological processi

Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Arrestin domain-containing protein 3
Alternative name(s):
TBP-2-like inducible membrane protein1 Publication
Short name:
TLIMP1 Publication
Gene namesi
Name:ARRDC3
Synonyms:KIAA1376
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:29263. ARRDC3.

Subcellular locationi

GO - Cellular componenti

  • early endosome Source: UniProtKB-SubCell
  • endosome Source: MGI
  • lysosome Source: UniProtKB-SubCell
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endosome, Lysosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi48K → E: Abolishes interaction with ADRB2; when associated with E-52; E-85 and E-139. 1 Publication1
Mutagenesisi52R → E: Abolishes interaction with ADRB2; when associated with E-48; E-85 and E-139. 1 Publication1
Mutagenesisi56K → E: Nearly abolishes interaction with ADRB2; when associated with E-58; E-135 and E-153. 1 Publication1
Mutagenesisi58R → E: Nearly abolishes interaction with ADRB2; when associated with E-56; E-135 and E-153. 1 Publication1
Mutagenesisi85K → E: Abolishes interaction with ADRB2; when associated with E-48; E-52 and E-139. 1 Publication1
Mutagenesisi135R → E: Nearly abolishes interaction with ADRB2; when associated with E-56; E-58 and E-153. 1 Publication1
Mutagenesisi139K → E: Abolishes interaction with ADRB2; when associated with E-48; E-52 and E-85. 1 Publication1
Mutagenesisi153K → E: Nearly abolishes interaction with ADRB2; when associated with E-56; E-58 and E-135. 1 Publication1
Mutagenesisi346 – 349PPSY → AASA: Strongly reduces interaction with NEDD4. Abolishes interaction with NEDD4; when associated with 391-A--A-394. Abolishes interaction with HGS; when associated with 391-A--A-394. 2 Publications4
Mutagenesisi391 – 394PPLY → AALA: Abolishes interaction with NEDD4; when associated with 346-A--A-349. 1 Publication4

Organism-specific databases

DisGeNETi57561.
OpenTargetsiENSG00000113369.
PharmGKBiPA134925765.

Polymorphism and mutation databases

BioMutaiARRDC3.
DMDMi74731205.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002443491 – 414Arrestin domain-containing protein 3Add BLAST414

Proteomic databases

MaxQBiQ96B67.
PaxDbiQ96B67.
PeptideAtlasiQ96B67.
PRIDEiQ96B67.

PTM databases

iPTMnetiQ96B67.
PhosphoSitePlusiQ96B67.

Expressioni

Tissue specificityi

Highly expressed in skeletal muscle, placenta, kidney, lung, liver, blood, adrenal gland, lymph node, mammary gland, thyroid, and trachea (PubMed:16269462, PubMed:21982743). 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).1 Publication

Inductioni

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).2 Publications

Gene expression databases

BgeeiENSG00000113369.
CleanExiHS_ARRDC3.
GenevisibleiQ96B67. HS.

Organism-specific databases

HPAiHPA051921.

Interactioni

Subunit structurei

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).6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ADRB2P075506EBI-2875665,EBI-491169
BAG3O958175EBI-2875665,EBI-747185
DCUN1D1Q96GG95EBI-2875665,EBI-740086
HPGDSO607603EBI-2875665,EBI-10187349
ITGB4P161443EBI-2875665,EBI-948678
MORF4L1Q9UBU83EBI-2875665,EBI-399246
MORF4L1Q9UBU8-23EBI-2875665,EBI-10288852
OTUB2Q96DC93EBI-2875665,EBI-746259
STAM2O758865EBI-2875665,EBI-373258
TNFAIP3P215805EBI-2875665,EBI-527670
TRIM42A1L4B63EBI-2875665,EBI-10172216
UBE2E2Q96LR55EBI-2875665,EBI-2129763
WWP2O003084EBI-2875665,EBI-743923

GO - Molecular functioni

  • beta-3 adrenergic receptor binding Source: MGI

Protein-protein interaction databases

BioGridi121616. 36 interactors.
IntActiQ96B67. 33 interactors.
STRINGi9606.ENSP00000265138.

Structurei

Secondary structure

1414
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 13Combined sources9
Beta strandi29 – 40Combined sources12
Beta strandi42 – 61Combined sources20
Beta strandi73 – 90Combined sources18
Beta strandi103 – 105Combined sources3
Beta strandi107 – 117Combined sources11
Beta strandi130 – 143Combined sources14
Beta strandi150 – 155Combined sources6
Helixi349 – 351Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4N7HX-ray1.70B342-354[»]
4R7VX-ray1.73A1-165[»]
4R7XX-ray2.61A/B1-180[»]
ProteinModelPortaliQ96B67.
SMRiQ96B67.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi346 – 349PPXY 1Curated4
Motifi391 – 394PPXY 2Curated4

Sequence similaritiesi

Belongs to the arrestin family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3780. Eukaryota.
ENOG41102NY. LUCA.
GeneTreeiENSGT00550000074356.
HOGENOMiHOG000237328.
HOVERGENiHBG066469.
InParanoidiQ96B67.
OMAiTEWNEER.
OrthoDBiEOG091G0B0Y.
PhylomeDBiQ96B67.
TreeFamiTF313650.

Family and domain databases

Gene3Di2.60.40.640. 1 hit.
InterProiIPR011021. Arrestin-like_N.
IPR014752. Arrestin_C.
IPR011022. Arrestin_C-like.
IPR014756. Ig_E-set.
[Graphical view]
PfamiPF02752. Arrestin_C. 1 hit.
PF00339. Arrestin_N. 1 hit.
[Graphical view]
SMARTiSM01017. Arrestin_C. 1 hit.
[Graphical view]
SUPFAMiSSF81296. SSF81296. 2 hits.

Sequencei

Sequence statusi: Complete.

Q96B67-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVLGKVKSLT ISFDCLNDSN VPVYSSGDTV SGRVNLEVTG EIRVKSLKIH
60 70 80 90 100
ARGHAKVRWT ESRNAGSNTA YTQNYTEEVE YFNHKDILIG HERDDDNSEE
110 120 130 140 150
GFHTIHSGRH EYAFSFELPQ TPLATSFEGR HGSVRYWVKA ELHRPWLLPV
160 170 180 190 200
KLKKEFTVFE HIDINTPSLL SPQAGTKEKT LCCWFCTSGP ISLSAKIERK
210 220 230 240 250
GYTPGESIQI FAEIENCSSR MVVPKAAIYQ TQAFYAKGKM KEVKQLVANL
260 270 280 290 300
RGESLSSGKT ETWNGKLLKI PPVSPSILDC SIIRVEYSLM VYVDIPGAMD
310 320 330 340 350
LFLNLPLVIG TIPLHPFGSR TSSVSSQCSM NMNWLSLSLP ERPEAPPSYA
360 370 380 390 400
EVVTEEQRRN NLAPVSACDD FERALQGPLF AYIQEFRFLP PPLYSEIDPN
410
PDQSADDRPS CPSR
Length:414
Mass (Da):46,395
Last modified:December 1, 2001 - v1
Checksum:i9B02190E1BA90B1D
GO

Sequence cautioni

The sequence BAA92614 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti12S → G in BAF84442 (PubMed:14702039).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB037797 mRNA. Translation: BAA92614.1. Different initiation.
AK291753 mRNA. Translation: BAF84442.1.
BC015928 mRNA. Translation: AAH15928.1.
BC053619 mRNA. Translation: AAH53619.1.
CCDSiCCDS34202.1.
RefSeqiNP_065852.1. NM_020801.3.
UniGeneiHs.24684.

Genome annotation databases

EnsembliENST00000265138; ENSP00000265138; ENSG00000113369.
GeneIDi57561.
KEGGihsa:57561.
UCSCiuc003kjz.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB037797 mRNA. Translation: BAA92614.1. Different initiation.
AK291753 mRNA. Translation: BAF84442.1.
BC015928 mRNA. Translation: AAH15928.1.
BC053619 mRNA. Translation: AAH53619.1.
CCDSiCCDS34202.1.
RefSeqiNP_065852.1. NM_020801.3.
UniGeneiHs.24684.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4N7HX-ray1.70B342-354[»]
4R7VX-ray1.73A1-165[»]
4R7XX-ray2.61A/B1-180[»]
ProteinModelPortaliQ96B67.
SMRiQ96B67.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121616. 36 interactors.
IntActiQ96B67. 33 interactors.
STRINGi9606.ENSP00000265138.

PTM databases

iPTMnetiQ96B67.
PhosphoSitePlusiQ96B67.

Polymorphism and mutation databases

BioMutaiARRDC3.
DMDMi74731205.

Proteomic databases

MaxQBiQ96B67.
PaxDbiQ96B67.
PeptideAtlasiQ96B67.
PRIDEiQ96B67.

Protocols and materials databases

DNASUi57561.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265138; ENSP00000265138; ENSG00000113369.
GeneIDi57561.
KEGGihsa:57561.
UCSCiuc003kjz.3. human.

Organism-specific databases

CTDi57561.
DisGeNETi57561.
GeneCardsiARRDC3.
HGNCiHGNC:29263. ARRDC3.
HPAiHPA051921.
MIMi612464. gene.
neXtProtiNX_Q96B67.
OpenTargetsiENSG00000113369.
PharmGKBiPA134925765.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3780. Eukaryota.
ENOG41102NY. LUCA.
GeneTreeiENSGT00550000074356.
HOGENOMiHOG000237328.
HOVERGENiHBG066469.
InParanoidiQ96B67.
OMAiTEWNEER.
OrthoDBiEOG091G0B0Y.
PhylomeDBiQ96B67.
TreeFamiTF313650.

Miscellaneous databases

ChiTaRSiARRDC3. human.
GenomeRNAii57561.
PROiQ96B67.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113369.
CleanExiHS_ARRDC3.
GenevisibleiQ96B67. HS.

Family and domain databases

Gene3Di2.60.40.640. 1 hit.
InterProiIPR011021. Arrestin-like_N.
IPR014752. Arrestin_C.
IPR011022. Arrestin_C-like.
IPR014756. Ig_E-set.
[Graphical view]
PfamiPF02752. Arrestin_C. 1 hit.
PF00339. Arrestin_N. 1 hit.
[Graphical view]
SMARTiSM01017. Arrestin_C. 1 hit.
[Graphical view]
SUPFAMiSSF81296. SSF81296. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiARRD3_HUMAN
AccessioniPrimary (citable) accession number: Q96B67
Secondary accession number(s): A8K6T8, Q9P2H1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 27, 2006
Last sequence update: December 1, 2001
Last modified: November 30, 2016
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.