Q8N5I2 · ARRD1_HUMAN
- ProteinArrestin domain-containing protein 1
- GeneARRDC1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids433 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Functions as an adapter recruiting ubiquitin-protein ligases to their specific substrates (PubMed:23886940, PubMed:27462458).
Through an ubiquitination-dependent mechanism plays for instance a role in the incorporation of SLC11A2 into extracellular vesicles (PubMed:27462458).
More generally, plays a role in the extracellular transport of proteins between cells through the release in the extracellular space of microvesicles (PubMed:22315426).
By participating in the ITCH-mediated ubiquitination and subsequent degradation of NOTCH1, negatively regulates the NOTCH signaling pathway (PubMed:23886940).
Through an ubiquitination-dependent mechanism plays for instance a role in the incorporation of SLC11A2 into extracellular vesicles (PubMed:27462458).
More generally, plays a role in the extracellular transport of proteins between cells through the release in the extracellular space of microvesicles (PubMed:22315426).
By participating in the ITCH-mediated ubiquitination and subsequent degradation of NOTCH1, negatively regulates the NOTCH signaling pathway (PubMed:23886940).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytoplasmic vesicle | |
Cellular Component | extracellular exosome | |
Cellular Component | extracellular vesicle | |
Cellular Component | plasma membrane | |
Molecular Function | arrestin family protein binding | |
Molecular Function | identical protein binding | |
Molecular Function | ubiquitin protein ligase binding | |
Molecular Function | ubiquitin-like ligase-substrate adaptor activity | |
Biological Process | extracellular transport | |
Biological Process | extracellular vesicle biogenesis | |
Biological Process | negative regulation of Notch signaling pathway | |
Biological Process | protein transport | |
Biological Process | protein ubiquitination | |
Biological Process | ubiquitin-dependent protein catabolic process |
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameArrestin domain-containing protein 1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ8N5I2
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Also found in extracellular vesicles different from exosomes.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 88 | Loss of localization to the cell membrane and extracellular vesicles. Localizes to the cytoplasm. | ||||
Sequence: F → L | ||||||
Mutagenesis | 180 | Decreased localization to the cell membrane and extracellular vesicles. | ||||
Sequence: G → A | ||||||
Mutagenesis | 191 | Decreased localization to the cell membrane and extracellular vesicles. | ||||
Sequence: N → D | ||||||
Mutagenesis | 310 | Decreased interaction with TSG101. No effect on localization to the cell membrane. Loss of localization to extracellular vesicles. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_048335 | 363 | in dbSNP:rs35018943 | |||
Sequence: G → C | ||||||
Mutagenesis | 403 | Loss of interaction with ITCH; when associated with A-416. | ||||
Sequence: P → A | ||||||
Mutagenesis | 416 | Loss of interaction with ITCH; when associated with A-403. | ||||
Sequence: P → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 568 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000244345 | 1-433 | UniProt | Arrestin domain-containing protein 1 | |||
Sequence: MGRVQLFEISLSHGRVVYSPGEPLAGTVRVRLGAPLPFRAIRVTCIGSCGVSNKANDTAWVVEEGYFNSSLSLADKGSLPAGEHSFPFQFLLPATAPTSFEGPFGKIVHQVRAAIHTPRFSKDHKCSLVFYILSPLNLNSIPDIEQPNVASATKKFSYKLVKTGSVVLTASTDLRGYVVGQALQLHADVENQSGKDTSPVVASLLQKVSYKAKRWIHDVRTIAEVEGAGVKAWRRAQWHEQILVPALPQSALPGCSLIHIDYYLQVSLKAPEATVTLPVFIGNIAVNHAPVSPRPGLGLPPGAPPLVVPSAPPQEEAEAEAAAGGPHFLDPVFLSTKSHSQRQPLLATLSSVPGAPEPCPQDGSPASHPLHPPLCISTGATVPYFAEGSGGPVPTTSTLILPPEYSSWGYPYEAPPSYEQSCGGVEPSLTPES | |||||||
Modified residue (large scale data) | 292 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Ubiquitinated (PubMed:21191027, PubMed:22315426).
Ubiquitination by WWP2; promotes localization to extracellular microvesicles (PubMed:22315426).
Ubiquitinated by WWP1 (PubMed:21191027).
Ubiquitination by WWP2; promotes localization to extracellular microvesicles (PubMed:22315426).
Ubiquitinated by WWP1 (PubMed:21191027).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Interacts (via PPxY motifs) with ITCH (via WW domains); the interaction is direct and participates in the recruitment of the ubiquitin-protein ligase ITCH to the NOTCH1 receptor (PubMed:21191027, PubMed:23886940).
Interacts with ARRB1 and ARRB2; the interaction is direct (PubMed:23886940).
Interacts with TSG101; may recruit TSG101 to the plasma membrane (PubMed:21191027, PubMed:22315426).
Interacts (via PPxY motifs) with WWP2 (via WW domains); ubiquitinates ARRDC1 (PubMed:21191027, PubMed:22315426).
Interacts with SLC11A2; controls the incorporation of SLC11A2 into extracellular vesicles through an ubiquitination-dependent mechanism (PubMed:27462458).
Interacts with WWP1 (via WW domains) (PubMed:21191027).
Interacts with NEDD4 (via WW domains) (PubMed:21191027).
Interacts with PDCD6IP (PubMed:21191027).
Interacts with ARRB1 and ARRB2; the interaction is direct (PubMed:23886940).
Interacts with TSG101; may recruit TSG101 to the plasma membrane (PubMed:21191027, PubMed:22315426).
Interacts (via PPxY motifs) with WWP2 (via WW domains); ubiquitinates ARRDC1 (PubMed:21191027, PubMed:22315426).
Interacts with SLC11A2; controls the incorporation of SLC11A2 into extracellular vesicles through an ubiquitination-dependent mechanism (PubMed:27462458).
Interacts with WWP1 (via WW domains) (PubMed:21191027).
Interacts with NEDD4 (via WW domains) (PubMed:21191027).
Interacts with PDCD6IP (PubMed:21191027).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q8N5I2 | EPN2 O95208-2 | 3 | EBI-2339564, EBI-12135243 | |
BINARY | Q8N5I2 | ITCH Q96J02 | 5 | EBI-2339564, EBI-1564678 | |
BINARY | Q8N5I2 | KLHL12 Q53G59 | 4 | EBI-2339564, EBI-740929 | |
BINARY | Q8N5I2 | MTURN Q8N3F0 | 3 | EBI-2339564, EBI-11980301 | |
BINARY | Q8N5I2 | NCAPG Q9BPX3 | 2 | EBI-2339564, EBI-970214 | |
BINARY | Q8N5I2 | UBASH3A P57075-2 | 3 | EBI-2339564, EBI-7353612 | |
BINARY | Q8N5I2 | WWP1 Q9H0M0 | 5 | EBI-2339564, EBI-742157 | |
BINARY | Q8N5I2 | WWP2 O00308 | 8 | EBI-2339564, EBI-743923 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for compositional bias, region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 296-311 | Pro residues | ||||
Sequence: GLGLPPGAPPLVVPSA | ||||||
Region | 296-322 | Disordered | ||||
Sequence: GLGLPPGAPPLVVPSAPPQEEAEAEAA | ||||||
Region | 349-372 | Disordered | ||||
Sequence: LSSVPGAPEPCPQDGSPASHPLHP | ||||||
Motif | 402-405 | PPxY motif 1 | ||||
Sequence: PPEY | ||||||
Motif | 415-418 | PPxY motif 2 | ||||
Sequence: PPSY |
Domain
The PPxY motifs mediate interaction with WW domain-containing ubiquitin-protein ligases.
Sequence similarities
Belongs to the arrestin family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length433
- Mass (Da)45,981
- Last updated2002-10-01 v1
- Checksum5B52A79EE27B5DDB
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 296-311 | Pro residues | ||||
Sequence: GLGLPPGAPPLVVPSA |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
BC032346 EMBL· GenBank· DDBJ | AAH32346.1 EMBL· GenBank· DDBJ | mRNA | ||
AL365502 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |