Protein: Activity-regulated cytoskeleton-associated protein (hArc) (Activity-regulated gene 3.1 protein homolog) (ARC/ARG3.1) (Arg3.1) (Q7LC44)
Organism: Homo sapiens (Human)
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).
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}.
Sequence: MELDHRTSGGLHAYPGPRGGQVAKPNVILQIGKCRAEMLEHVRRTHRHLLAEVSKQVERELKGLHRSVGKLESNLDGYVPTSDSQRWKKSIKACLCRCQETIANLERWVKREMHVWREVFYRLERWADRLESTGGKYPVGSESARHTVSVGVGGPESYCHEADGYDYTVSPYAITPPPAAGELPGQEPAEAQQYQPWVPGEDGQPSPGVDTQIFEDPREFLSHLEEYLRQVGGSEEYWLSQIQNHMNGPAKKWWEFKQGSVKNWVEFKKEFLQYSEGTLSREAIQRELDLPQKQGEPLDQFLWRKRDLYQTLYVDADEEEIIQYVVGTLQPKLKRFLRHPLPKTLEQLIQRGMEVQDDLEQAAEPAGPHLPVEDEAETLTPAPNSESVASDRTQPE
InterPro domains: - IPR045557: Activity-regulated cytoskeleton-associated protein, N-terminal domain (domain) [46-154]
- IPR048965: Activity-regulated cytoskeleton-associated protein, capsid domain (domain) [214-275]
- IPR040814: Activity-regulated cytoskeleton-associated protein, C-terminal domain (domain) [278-359]
- IPR023263: Activity-regulated cytoskeleton-associated protein (family) [1-396]
Interaction partners: - Dynamin-2
- Endophilin-A3
- Early growth response protein 1
- Protein c-Fos
- Glutamate receptor 1
- Disks large homolog 4
- Calcium/calmodulin-dependent protein kinase type II subunit beta
- Cyclic AMP-responsive element-binding protein 1
- Endophilin-A2
- Fragile X messenger ribonucleoprotein 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0032502 (developmental process), GO:0032501 (multicellular organismal process), GO:0065008 (regulation of biological quality), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0032879 (regulation of localization), GO:0007389 (pattern specification process), GO:0050794 (regulation of cellular process), GO:0023051 (regulation of signaling), GO:0003008 (system process), GO:0007610 (behavior), GO:0048167 (regulation of synaptic plasticity), GO:0099149 (regulation of postsynaptic neurotransmitter receptor internalization), GO:0051049 (regulation of transport), GO:0009888 (tissue development), GO:0003002 (regionalization), GO:0010646 (regulation of cell communication), GO:0007611 (learning or memory), GO:0060627 (regulation of vesicle-mediated transport), GO:0050877 (nervous system process), GO:0099177 (regulation of trans-synaptic signaling), GO:0051128 (regulation of cellular component organization), GO:0007613 (memory), GO:0007492 (endoderm development), GO:0030100 (regulation of endocytosis), GO:0050890 (cognition), GO:1900452 (regulation of long-term synaptic depression), GO:0050804 (modulation of chemical synaptic transmission), GO:1900271 (regulation of long-term synaptic potentiation), GO:0009952 (anterior/posterior pattern specification), GO:0048259 (regulation of receptor-mediated endocytosis), GO:0007616 (long-term memory), GO:0002090 (regulation of receptor internalization)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0005829 (cytosol), GO:0071944 (cell periphery), GO:0030054 (cell junction), GO:0005576 (extracellular region), GO:0005615 (extracellular space), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0043230 (extracellular organelle), GO:0043228 (non-membrane-bounded organelle), GO:0098797 (plasma membrane protein complex), GO:0070062 (extracellular exosome), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0043231 (intracellular membrane-bounded organelle), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0065010 (extracellular membrane-bounded organelle), GO:0031982 (vesicle), GO:1903561 (extracellular vesicle), GO:0097708 (intracellular vesicle), GO:0005856 (cytoskeleton), GO:0015629 (actin cytoskeleton)