ARC
entrez
23237
canonical
uniprot
Q7LC44
canonical
ensembl
ENSG00000198576
resolver
ensp
ENSP00000349022
resolver
enst
ENST00000356613
resolver
genesymbol
ARC
resolver
genesymbol_syn
KIAA0278
resolver
hgnc
HGNC:648
resolver
uniprot
Q9UJW6
resolver
uniprot
Q9Y469
resolver
uniprot_entry
ARC_HUMAN
resolver
uniprot_sec
Q9UJW6
resolver
uniprot_sec
Q9Y469
resolver
amino_acid_sequence
MELDHRTSGGLHAYPGPRGGQVAKPNVILQIGKCRAEMLEHVRRTHRHLLAEVSKQVERELKGLHRSVGKLESNLDGYVPTSDSQRWKKSIKACLCRCQETIANLERWVKREMHVWREVFYRLERWADRLESTGGKYPVGSESARHTVSVGVGGPESYCHEADGYDYTVSPYAITPPPAAGELPGQEPAEAQQYQPWVPGEDGQPSPGVDTQIFEDPREFLSHLEEYLRQVGGSEEYWLSQIQNHMNGPAKKWWEFKQGSVKNWVEFKKEFLQYSEGTLSREAIQRELDLPQKQGEPLDQFLWRKRDLYQTLYVDADEEEIIQYVVGTLQPKLKRFLRHPLPKTLEQLIQRGMEVQDDLEQAAEPAGPHLPVEDEAETLTPAPNSESVASDRTQPE
uniprot
proteins
function
FUNCTION: Master regulator of synaptic plasticity that self-assembles into virion-like capsids that encapsulate RNAs and mediate intercellular RNA transfer in the nervous system. ARC protein is released from neurons in extracellular vesicles that mediate the transfer of ARC mRNA into new target cells, where ARC mRNA can undergo activity-dependent translation. ARC capsids are endocytosed and are able to transfer ARC mRNA into the cytoplasm of neurons. Acts as a key regulator of synaptic plasticity: required for protein synthesis-dependent forms of long-term potentiation (LTP) and depression (LTD) and for the formation of long-term memory. Regulates synaptic plasticity by promoting endocytosis of AMPA receptors (AMPARs) in response to synaptic activity: this endocytic pathway maintains levels of surface AMPARs in response to chronic changes in neuronal activity through synaptic scaling, thereby contributing to neuronal homeostasis. Acts as a postsynaptic mediator of activity-dependent synapse elimination in the developing cerebellum by mediating elimination of surplus climbing fiber synapses. Accumulates at weaker synapses, probably to prevent their undesired enhancement. This suggests that ARC-containing virion-like capsids may be required to eliminate synaptic material. Required to transduce experience into long-lasting changes in visual cortex plasticity and for long-term memory (By similarity). Involved in postsynaptic trafficking and processing of amyloid-beta A4 (APP) via interaction with PSEN1 (By similarity). In addition to its role in synapses, also involved in the regulation of the immune system: specifically expressed in skin-migratory dendritic cells and regulates fast dendritic cell migration, thereby regulating T-cell activation (By similarity). {ECO:0000250|UniProtKB:Q63053, ECO:0000250|UniProtKB:Q9WV31}.
uniprot
proteins
mass_dalton
45316
uniprot
proteins
mutagenesis
MUTAGEN 268; /note="K->A: Complete loss of RNF216-mediated ubiquitination; when associated by A-269."; /evidence="ECO:0000269|PubMed:24945773"; MUTAGEN 269; /note="K->A: Complete loss of RNF216-mediated ubiquitination; when associated by A-268."; /evidence="ECO:0000269|PubMed:24945773
uniprot
proteins
post_translational_modification
PTM: Palmitoylation anchors the protein into the membrane by allowing direct insertion into the hydrophobic core of the lipid bilayer. {ECO:0000250|UniProtKB:Q9WV31}.; PTM: Ubiquitinated by UBE3A, leading to its degradation by the proteasome, thereby promoting AMPA receptors (AMPARs) expression at synapses (By similarity). Ubiquitinated by RNF216 at Lys-268 and Lys-269 limiting ARC protein levels induced by synaptic activity and thus regulating ARC-dependent forms of synaptic plasticity (PubMed:24945773). {ECO:0000250|UniProtKB:Q9WV31, ECO:0000269|PubMed:24945773}.; PTM: Phosphorylation at Ser-260 by CaMK2 prevents homooligomerization into virion-like capsids by disrupting an interaction surface essential for high-order oligomerization. Phosphorylation by CaMK2 inhibits synaptic activity. {ECO:0000250|UniProtKB:Q9WV31}.
uniprot
proteins
protein_family
ARC/ARG3.1 family
uniprot
proteins
pubmed
10970730
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
21834987
uniprot
proteins
pubmed
24945773
uniprot
proteins
pubmed
25748042
uniprot
proteins
pubmed
39390519
uniprot
proteins
pubmed
9039502
uniprot
proteins
sequence_length
396
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Extracellular vesicle membrane {ECO:0000250|UniProtKB:Q63053}; Lipid-anchor {ECO:0000250|UniProtKB:Q9WV31}. Postsynaptic cell membrane {ECO:0000250|UniProtKB:Q9WV31}; Lipid-anchor {ECO:0000250|UniProtKB:Q9WV31}. Synapse {ECO:0000250|UniProtKB:Q63053}. Postsynaptic density {ECO:0000250|UniProtKB:Q63053}. Early endosome membrane {ECO:0000250|UniProtKB:Q63053}. Cell projection, dendrite {ECO:0000250|UniProtKB:Q63053}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:21834987}. Cytoplasm, cell cortex {ECO:0000250|UniProtKB:Q63053}. Cell projection, dendritic spine {ECO:0000250|UniProtKB:Q63053}. Cytoplasmic vesicle, secretory vesicle, acrosome {ECO:0000250|UniProtKB:Q9WV31}. Cytoplasmic vesicle, clathrin-coated vesicle membrane {ECO:0000269|PubMed:24945773}. Note=Forms virion-like extracellular vesicles that are released from neurons. Enriched in postsynaptic density of dendritic spines. Targeted to inactive synapses following interaction with CAMK2B in the kinase inactive state. Accumulation at weaker synapses may be required to prevent their undesired enhancement. Associated with the cell cortex of neuronal soma and dendrites (By similarity). Associated with the sperm tail (By similarity). {ECO:0000250|UniProtKB:Q63053, ECO:0000250|UniProtKB:Q9WV31}.
uniprot
proteins