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Protein

Activity-regulated cytoskeleton-associated protein

Gene

Arc

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Master regulator of synaptic plasticity that self-assembles into virion-like capsids that encapsulate RNAs and mediate intercellular RNA transfer in the nervous system (By similarity). 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 (By similarity). ARC capsids are endocytosed and are able to transfer ARC mRNA into the cytoplasm of neurons (By similarity). 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 (PubMed:29264923, PubMed:24094104). 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 (PubMed:17088213, PubMed:20211139, PubMed:20228806). Acts as a postsynaptic mediator of activity-dependent synapse elimination in the developing cerebellum by mediating elimination of surplus climbing fiber synapses (PubMed:23791196). Accumulates at weaker synapses, probably to prevent their undesired enhancement (By similarity). This suggests that ARC-containing virion-like capsids may be required to eliminate synaptic material (By similarity). Required to transduce experience into long-lasting changes in visual cortex plasticity and for long-term memory (PubMed:17088210, PubMed:20228806). Involved in postsynaptic trafficking and processing of amyloid-beta A4 (APP) via interaction with PSEN1 (PubMed:22036569). 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 (PubMed:28783680).By similarity8 Publications

Miscellaneous

Widely used as activity-dependent neuronal marker to identify recently activated neurons in behavioral studies.1 Publication

Caution

Genetic disruption of the protein-coding gene was initially reported to cause early embryonic lethality (PubMed:10727859). However, only a partial deletion of the coding region was performed, leading to dominant-negative effects (PubMed:10727859). A complete deletion of the coding region later showed that mice are viable and display deficits in several forms of long-term memory formation (PubMed:17088210).2 Publications

GO - Molecular functioni

  • actin binding Source: MGI
  • mRNA binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, RNA-binding
Biological processEndocytosis, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Activity-regulated cytoskeleton-associated proteinCurated
Short name:
mArc1 Publication
Alternative name(s):
Activity-regulated gene 3.1 protein1 Publication
Short name:
ARC/ARG3.11 Publication
Short name:
Arg3.11 Publication
Gene namesi
Name:ArcImported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:88067 Arc

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Endosome, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Disruption phenotypei

Mice show deficits in several forms of long-term memory formation including spatial and fear-related learning, conditioned taste aversion as well as long-term object recognition (PubMed:17088210). They show enhanced early-phase but impaired late-phase long-term potentiation (LTP) as well as impaired long-term depression (LTD). Neurons lacking Arc show an increase in surface levels of AMPA receptors (PubMed:17088210). In the visual cortex, mice are impervious to the effects of deprivation or experience: mice do not exhibit depression of deprived-eye responses or a shift in ocular dominance after brief monocular deprivation (PubMed:20228806). Although mice exhibit normal visual acuity, baseline ocular dominance is abnormal and resemble that observed after dark-rearing (PubMed:20228806). Mice also show schizophrenia-related phenotypes characterized by deficits in sensorimotor gating, cognitive functions, social behaviors and amphetamine-induced psychomotor responses (PubMed:27524619). Divergent alterations between the prefrontal cortex and striatal dopaminergic system that capture aspects of schizophrenia-related neuropathophysiology are observed (PubMed:27524619). Knockout mice show a relative loss of high-frequency electroencephalogram activity in hippocampus, as well as a decrease in phase locking of spikes to electroencephalogram oscillations (PubMed:27038743).4 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi94 – 98CLCRC → SLSRS: Abolished palmitoylation, leading to impaired ability mediate synaptic long-term depression (LTD). 1 Publication5

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002732861 – 396Activity-regulated cytoskeleton-associated proteinAdd BLAST396

Post-translational modificationi

Ubiquitinated by UBE3A, leading to its degradation by the proteasome, thereby promoting AMPA receptors (AMPARs) expression at synapses.1 Publication
Palmitoylation anchors the protein into the membrane by allowing direct insertion into the hydrophobic core of the lipid bilayer.1 Publication

Keywords - PTMi

Lipoprotein, Palmitate, Ubl conjugation

Proteomic databases

PaxDbiQ9WV31
PeptideAtlasiQ9WV31
PRIDEiQ9WV31

PTM databases

iPTMnetiQ9WV31
PhosphoSitePlusiQ9WV31
SwissPalmiQ9WV31

Expressioni

Tissue specificityi

Expressed in brain and testis (PubMed:12493697). In primary visual cortex, detected in all cortical layers with the exception of layer 5: present at highest level in layers 2/3 and 4, the predominant sites of ocular dominance plasticity (at protein level) (PubMed:20228806). Also expressed in skin-migratory dendritic cells (PubMed:28783680).3 Publications

Developmental stagei

Ubiquitously expressed in early mouse embryos (PubMed:10727859). Detectable in brain from postnatal week 1, in testis from postnatal week 3.2 Publications

Inductioni

Arc expression is regulated at transcription, post-transcription and translation levels (PubMed:19116276, PubMed:24094104). Expression is induced by neuronal and synaptic activity (PubMed:19116276, PubMed:24094104).2 Publications

Gene expression databases

BgeeiENSMUSG00000022602
GenevisibleiQ9WV31 MM

Interactioni

Subunit structurei

Homooligomer; homooligomerizes into virion-like capsids (By similarity). Interacts with SH3GL1/endophilin-2, SH3GL3/endophilin-3 and DNM2/DYN2 (By similarity). Interacts with CAMK2B (in the kinase inactive state); leading to target ARC to inactive synapses (By similarity). Interacts with PSEN1 (PubMed:22036569).By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • actin binding Source: MGI

Protein-protein interaction databases

BioGridi198182, 7 interactors
DIPiDIP-31565N
IntActiQ9WV31, 11 interactors
MINTiQ9WV31
STRINGi10090.ENSMUSP00000023268

Structurei

3D structure databases

ProteinModelPortaliQ9WV31
SMRiQ9WV31
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni89 – 100Interaction with SH3GL1 or SH3GL3By similarityAdd BLAST12
Regioni195 – 214Interaction with DNM2By similarityAdd BLAST20

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili54 – 78Sequence analysisAdd BLAST25

Sequence similaritiesi

Belongs to the ARC/ARG3.1 family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IIAZ Eukaryota
ENOG410YF34 LUCA
GeneTreeiENSGT00390000003914
HOGENOMiHOG000034037
HOVERGENiHBG080862
InParanoidiQ9WV31
KOiK15867
OMAiHMNGPAK
OrthoDBiEOG091G07HQ
PhylomeDBiQ9WV31
TreeFamiTF335604

Family and domain databases

InterProiView protein in InterPro
IPR023263 Activity-reg_cytoskelet-assoc
PANTHERiPTHR15962 PTHR15962, 1 hit
PRINTSiPR02027 ARCARG31

Sequencei

Sequence statusi: Complete.

Q9WV31-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELDHMTTGG LHAYPAPRGG PAAKPNVILQ IGKCRAEMLE HVRRTHRHLL
60 70 80 90 100
TEVSKQVERE LKGLHRSVGK LENNLDGYVP TGDSQRWKKS IKACLCRCQE
110 120 130 140 150
TIANLERWVK REMHVWREVF YRLERWADRL ESMGGKYPVG SEPARHTVSV
160 170 180 190 200
GVGGPEPYCQ EADGYDYTVS PYAITPPPAA GELPEQESVE AQQYQSWGPG
210 220 230 240 250
EDGQPSPGVD TQIFEDPREF LSHLEEYLRQ VGGSEEYWLS QIQNHMNGPA
260 270 280 290 300
KKWWEFKQGS VKNWVEFKKE FLQYSEGTLS REAIQRELEL PQKQGEPLDQ
310 320 330 340 350
FLWRKRDLYQ TLYVDAEEEE IIQYVVGTLQ PKLKRFLRHP LPKTLEQLIQ
360 370 380 390
RGMEVQDGLE QAAEPSGTPL PTEDETEALT PALTSESVAS DRTQPE
Length:396
Mass (Da):45,321
Last modified:November 1, 1999 - v1
Checksum:iF4D3505FD477D18A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF177701 Genomic DNA Translation: AAK91587.1
AF162777 mRNA Translation: AAD43586.1
AK157822 mRNA Translation: BAE34212.1
AK170446 mRNA Translation: BAE41804.1
BC023127 mRNA Translation: AAH23127.1
AF254662 Genomic DNA Translation: AAG10254.1
CCDSiCCDS37102.1
RefSeqiNP_001263613.1, NM_001276684.1
NP_061260.1, NM_018790.3
UniGeneiMm.491310

Genome annotation databases

EnsembliENSMUST00000023268; ENSMUSP00000023268; ENSMUSG00000022602
ENSMUST00000110009; ENSMUSP00000105636; ENSMUSG00000022602
GeneIDi11838
KEGGimmu:11838
UCSCiuc007wfn.2 mouse

Similar proteinsi

Entry informationi

Entry nameiARC_MOUSE
AccessioniPrimary (citable) accession number: Q9WV31
Secondary accession number(s): Q9ES15
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 23, 2007
Last sequence update: November 1, 1999
Last modified: May 23, 2018
This is version 117 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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