ARC_MOUSE
ID ARC_MOUSE Reviewed; 396 AA.
AC Q9WV31; Q9ES15;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Activity-regulated cytoskeleton-associated protein {ECO:0000305};
DE Short=mArc {ECO:0000303|Ref.2};
DE AltName: Full=Activity-regulated gene 3.1 protein {ECO:0000303|PubMed:11466419};
DE Short=ARC/ARG3.1 {ECO:0000303|PubMed:11466419};
DE Short=Arg3.1 {ECO:0000303|PubMed:11466419};
GN Name=Arc {ECO:0000312|MGI:MGI:88067};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/Sv {ECO:0000312|EMBL:AAK91587.1};
RX PubMed=11466419; DOI=10.1523/jneurosci.21-15-05484.2001;
RA Waltereit R., Dammermann B., Wulff P., Scafidi J., Staubli U.,
RA Kauselmann G., Bundman M., Kuhl D.;
RT "Arg3.1/Arc mRNA induction by Ca2+ and cAMP requires protein kinase A and
RT mitogen-activated protein kinase/extracellular regulated kinase
RT activation.";
RL J. Neurosci. 21:5484-5493(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAD43586.1};
RC TISSUE=Forebrain {ECO:0000312|EMBL:AAD43586.1};
RA Chowdhury S., Lanahan A.A., Worley P.F.;
RT "The mArc gene, a mouse homolog of rat Arc.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Dendritic cell, and Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland {ECO:0000312|EMBL:AAH23127.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-242.
RC STRAIN=C57BL/6 X CBA {ECO:0000312|EMBL:AAG10254.1};
RA Medrano S., Worley P.F., Chowdhury S., Lanahan A., Steward O., Scrable H.;
RT "Characterization of the promoter region of the immediate early gene Arc.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=10727859; DOI=10.1016/s0925-4773(99)00340-8;
RA Liu D., Bei D., Parmar H., Matus A.;
RT "Activity-regulated, cytoskeleton-associated protein (Arc) is essential for
RT visceral endoderm organization during early embryogenesis.";
RL Mech. Dev. 92:207-215(2000).
RN [7]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=12493697; DOI=10.1095/biolreprod.102.004143;
RA Maier B., Medrano S., Sleight S.B., Visconti P.E., Scrable H.;
RT "Developmental association of the synaptic activity-regulated protein arc
RT with the mouse acrosomal organelle and the sperm tail.";
RL Biol. Reprod. 68:67-76(2003).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17088210; DOI=10.1016/j.neuron.2006.08.024;
RA Plath N., Ohana O., Dammermann B., Errington M.L., Schmitz D., Gross C.,
RA Mao X., Engelsberg A., Mahlke C., Welzl H., Kobalz U., Stawrakakis A.,
RA Fernandez E., Waltereit R., Bick-Sander A., Therstappen E., Cooke S.F.,
RA Blanquet V., Wurst W., Salmen B., Bosl M.R., Lipp H.P., Grant S.G.,
RA Bliss T.V., Wolfer D.P., Kuhl D.;
RT "Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and
RT memories.";
RL Neuron 52:437-444(2006).
RN [9]
RP FUNCTION.
RX PubMed=17088213; DOI=10.1016/j.neuron.2006.08.034;
RA Shepherd J.D., Rumbaugh G., Wu J., Chowdhury S., Plath N., Kuhl D.,
RA Huganir R.L., Worley P.F.;
RT "Arc/Arg3.1 mediates homeostatic synaptic scaling of AMPA Receptors.";
RL Neuron 52:475-484(2006).
RN [10]
RP INDUCTION.
RX PubMed=19116276; DOI=10.1073/pnas.0806518106;
RA Kawashima T., Okuno H., Nonaka M., Adachi-Morishima A., Kyo N., Okamura M.,
RA Takemoto-Kimura S., Worley P.F., Bito H.;
RT "Synaptic activity-responsive element in the Arc/Arg3.1 promoter essential
RT for synapse-to-nucleus signaling in activated neurons.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:316-321(2009).
RN [11]
RP FUNCTION, AND UBIQUITINATION.
RX PubMed=20211139; DOI=10.1016/j.cell.2010.01.026;
RA Greer P.L., Hanayama R., Bloodgood B.L., Mardinly A.R., Lipton D.M.,
RA Flavell S.W., Kim T.K., Griffith E.C., Waldon Z., Maehr R., Ploegh H.L.,
RA Chowdhury S., Worley P.F., Steen J., Greenberg M.E.;
RT "The Angelman syndrome protein Ube3A regulates synapse development by
RT ubiquitinating Arc.";
RL Cell 140:704-716(2010).
RN [12]
RP FUNCTION, AND INTERACTION WITH PSEN1.
RX PubMed=22036569; DOI=10.1016/j.cell.2011.09.036;
RA Wu J., Petralia R.S., Kurushima H., Patel H., Jung M.Y., Volk L.,
RA Chowdhury S., Shepherd J.D., Dehoff M., Li Y., Kuhl D., Huganir R.L.,
RA Price D.L., Scannevin R., Troncoso J.C., Wong P.C., Worley P.F.;
RT "Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent
RT beta-amyloid generation.";
RL Cell 147:615-628(2011).
RN [13]
RP FUNCTION, AND INDUCTION.
RX PubMed=24094104; DOI=10.1016/j.neuron.2013.07.020;
RA Jakkamsetti V., Tsai N.P., Gross C., Molinaro G., Collins K.A.,
RA Nicoletti F., Wang K.H., Osten P., Bassell G.J., Gibson J.R., Huber K.M.;
RT "Experience-induced Arc/Arg3.1 primes CA1 pyramidal neurons for
RT metabotropic glutamate receptor-dependent long-term synaptic depression.";
RL Neuron 80:72-79(2013).
RN [14]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=20228806; DOI=10.1038/nn.2508;
RA McCurry C.L., Shepherd J.D., Tropea D., Wang K.H., Bear M.F., Sur M.;
RT "Loss of Arc renders the visual cortex impervious to the effects of sensory
RT experience or deprivation.";
RL Nat. Neurosci. 13:450-457(2010).
RN [15]
RP FUNCTION.
RX PubMed=23791196; DOI=10.1016/j.neuron.2013.04.036;
RA Mikuni T., Uesaka N., Okuno H., Hirai H., Deisseroth K., Bito H., Kano M.;
RT "Arc/Arg3.1 is a postsynaptic mediator of activity-dependent synapse
RT elimination in the developing cerebellum.";
RL Neuron 78:1024-1035(2013).
RN [16]
RP DISRUPTION PHENOTYPE.
RX PubMed=27524619; DOI=10.1016/j.celrep.2016.07.044;
RA Manago F., Mereu M., Mastwal S., Mastrogiacomo R., Scheggia D.,
RA Emanuele M., De Luca M.A., Weinberger D.R., Wang K.H., Papaleo F.;
RT "Genetic disruption of Arc/Arg3.1 in mice causes alterations in dopamine
RT and neurobehavioral phenotypes related to schizophrenia.";
RL Cell Rep. 16:2116-2128(2016).
RN [17]
RP DISRUPTION PHENOTYPE.
RX PubMed=27038743; DOI=10.1016/j.nlm.2016.03.021;
RA Malkki H.A., Mertens P.E., Lankelma J.V., Vinck M., van Schalkwijk F.J.,
RA van Mourik-Donga L.B., Battaglia F.P., Mahlke C., Kuhl D., Pennartz C.M.;
RT "Effects of Arc/Arg3.1 gene deletion on rhythmic synchronization of
RT hippocampal CA1 neurons during locomotor activity and sleep.";
RL Neurobiol. Learn. Mem. 131:155-165(2016).
RN [18]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28783680; DOI=10.1126/sciimmunol.aaf8665;
RA Ufer F., Vargas P., Engler J.B., Tintelnot J., Schattling B., Winkler H.,
RA Bauer S., Kursawe N., Willing A., Keminer O., Ohana O., Salinas-Riester G.,
RA Pless O., Kuhl D., Friese M.A.;
RT "Arc/Arg3.1 governs inflammatory dendritic cell migration from the skin and
RT thereby controls T cell activation.";
RL Sci. Immunol. 1:EAAF8665-EAAF8665(2016).
RN [19]
RP FUNCTION, PALMITOYLATION, AND MUTAGENESIS OF 94-CYS--CYS-98.
RX PubMed=29264923; DOI=10.1021/acs.biochem.7b00959;
RA Barylko B., Wilkerson J.R., Cavalier S.H., Binns D.D., James N.G.,
RA Jameson D.M., Huber K.M., Albanesi J.P.;
RT "Palmitoylation and membrane binding of Arc/Arg3.1: a potential role in
RT synaptic depression.";
RL Biochemistry 57:520-524(2018).
RN [20]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, PHOSPHORYLATION AT SER-260 AND
RP THR-278, AND MUTAGENESIS OF GLN-241; LYS-257; SER-260; GLY-277; THR-278 AND
RP ARG-335.
RX PubMed=31151856; DOI=10.1016/j.molcel.2019.05.004;
RA Zhang W., Chuang Y.A., Na Y., Ye Z., Yang L., Lin R., Zhou J., Wu J.,
RA Qiu J., Savonenko A., Leahy D.J., Huganir R., Linden D.J., Worley P.F.;
RT "Arc oligomerization is regulated by CaMKII phosphorylation of the GAG
RT domain: an essential mechanism for plasticity and memory formation.";
RL Mol. Cell 0:0-0(2019).
CC -!- FUNCTION: Master regulator of synaptic plasticity that self-assembles
CC into virion-like capsids that encapsulate RNAs and mediate
CC intercellular RNA transfer in the nervous system (By similarity). ARC
CC protein is released from neurons in extracellular vesicles that mediate
CC the transfer of ARC mRNA into new target cells, where ARC mRNA can
CC undergo activity-dependent translation (By similarity). ARC capsids are
CC endocytosed and are able to transfer ARC mRNA into the cytoplasm of
CC neurons (By similarity). Acts as a key regulator of synaptic
CC plasticity: required for protein synthesis-dependent forms of long-term
CC potentiation (LTP) and depression (LTD) and for the formation of long-
CC term memory (PubMed:29264923, PubMed:24094104, PubMed:31151856).
CC Regulates synaptic plasticity by promoting endocytosis of AMPA
CC receptors (AMPARs) in response to synaptic activity: this endocytic
CC pathway maintains levels of surface AMPARs in response to chronic
CC changes in neuronal activity through synaptic scaling, thereby
CC contributing to neuronal homeostasis (PubMed:17088213, PubMed:20211139,
CC PubMed:20228806). Acts as a postsynaptic mediator of activity-dependent
CC synapse elimination in the developing cerebellum by mediating
CC elimination of surplus climbing fiber synapses (PubMed:23791196).
CC Accumulates at weaker synapses, probably to prevent their undesired
CC enhancement (By similarity). This suggests that ARC-containing virion-
CC like capsids may be required to eliminate synaptic material (By
CC similarity). Required to transduce experience into long-lasting changes
CC in visual cortex plasticity and for long-term memory (PubMed:17088210,
CC PubMed:20228806). Involved in postsynaptic trafficking and processing
CC of amyloid-beta A4 (APP) via interaction with PSEN1 (PubMed:22036569).
CC In addition to its role in synapses, also involved in the regulation of
CC the immune system: specifically expressed in skin-migratory dendritic
CC cells and regulates fast dendritic cell migration, thereby regulating
CC T-cell activation (PubMed:28783680). {ECO:0000250|UniProtKB:Q63053,
CC ECO:0000269|PubMed:17088210, ECO:0000269|PubMed:17088213,
CC ECO:0000269|PubMed:20211139, ECO:0000269|PubMed:20228806,
CC ECO:0000269|PubMed:22036569, ECO:0000269|PubMed:24094104,
CC ECO:0000269|PubMed:28783680, ECO:0000269|PubMed:29264923,
CC ECO:0000269|PubMed:31151856}.
CC -!- SUBUNIT: Homooligomer; homooligomerizes into virion-like capsids
CC (PubMed:31151856). Interacts with SH3GL1/endophilin-2,
CC SH3GL3/endophilin-3 and DNM2/DYN2 (By similarity). Interacts with
CC CAMK2B (in the kinase inactive state); leading to target ARC to
CC inactive synapses (By similarity). Interacts with PSEN1
CC (PubMed:22036569). Interacts with GRIN2A and GRIN2B; inhibiting
CC homooligomerization (By similarity). {ECO:0000250|UniProtKB:Q63053,
CC ECO:0000269|PubMed:22036569, ECO:0000269|PubMed:31151856}.
CC -!- INTERACTION:
CC Q9WV31; P28652: Camk2b; NbExp=2; IntAct=EBI-397779, EBI-397029;
CC Q9WV31; Q62108: Dlg4; NbExp=7; IntAct=EBI-397779, EBI-300895;
CC Q9WV31; PRO_0000025597 [P49769]: Psen1; NbExp=2; IntAct=EBI-397779, EBI-5260983;
CC -!- SUBCELLULAR LOCATION: Extracellular vesicle membrane
CC {ECO:0000250|UniProtKB:Q63053}; Lipid-anchor
CC {ECO:0000269|PubMed:29264923}. Postsynaptic cell membrane
CC {ECO:0000269|PubMed:22036569}; Lipid-anchor
CC {ECO:0000269|PubMed:29264923}. Synapse {ECO:0000250|UniProtKB:Q63053}.
CC Postsynaptic density {ECO:0000250|UniProtKB:Q63053}. Early endosome
CC membrane {ECO:0000305|PubMed:31151856}. Cell projection, dendrite
CC {ECO:0000269|PubMed:31151856}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q63053}. Cytoplasm, cell cortex
CC {ECO:0000250|UniProtKB:Q63053}. Cell projection, dendritic spine
CC {ECO:0000250|UniProtKB:Q63053}. Cytoplasmic vesicle, secretory vesicle,
CC acrosome {ECO:0000269|PubMed:12493697}. Note=Forms virion-like
CC extracellular vesicles that are released from neurons (By similarity).
CC Enriched in postsynaptic density of dendritic spines (By similarity).
CC Targeted to inactive synapses following interaction with CAMK2B in the
CC kinase inactive state (By similarity). Accumulation at weaker synapses
CC may be required to prevent their undesired enhancement (By similarity).
CC Associated with the cell cortex of neuronal soma and dendrites (By
CC similarity). Associated with the sperm tail (PubMed:12493697).
CC {ECO:0000250|UniProtKB:Q63053, ECO:0000269|PubMed:12493697}.
CC -!- TISSUE SPECIFICITY: Expressed in brain and testis (PubMed:12493697). In
CC primary visual cortex, detected in all cortical layers with the
CC exception of layer 5: present at highest level in layers 2/3 and 4, the
CC predominant sites of ocular dominance plasticity (at protein level)
CC (PubMed:20228806). Also expressed in skin-migratory dendritic cells
CC (PubMed:28783680). {ECO:0000269|PubMed:12493697,
CC ECO:0000269|PubMed:20228806, ECO:0000269|PubMed:28783680}.
CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed in early mouse embryos
CC (PubMed:10727859). Detectable in brain from postnatal week 1, in testis
CC from postnatal week 3. {ECO:0000269|PubMed:10727859,
CC ECO:0000269|PubMed:12493697}.
CC -!- INDUCTION: Arc expression is regulated at transcription, post-
CC transcription and translation levels (PubMed:19116276,
CC PubMed:24094104). Expression is induced by neuronal and synaptic
CC activity (PubMed:19116276, PubMed:24094104).
CC {ECO:0000269|PubMed:19116276, ECO:0000269|PubMed:24094104}.
CC -!- PTM: Ubiquitinated by UBE3A, leading to its degradation by the
CC proteasome, thereby promoting AMPA receptors (AMPARs) expression at
CC synapses. {ECO:0000269|PubMed:20211139}.
CC -!- PTM: Palmitoylation anchors the protein into the membrane by allowing
CC direct insertion into the hydrophobic core of the lipid bilayer.
CC {ECO:0000305|PubMed:29264923}.
CC -!- PTM: Phosphorylation at Ser-260 by CaMK2 prevents homooligomerization
CC into virion-like capsids by disrupting an interaction surface essential
CC for high-order oligomerization (PubMed:31151856). Phosphorylation by
CC CaMK2 inhibits synaptic activity (PubMed:31151856).
CC {ECO:0000269|PubMed:31151856}.
CC -!- DISRUPTION PHENOTYPE: Mice show deficits in several forms of long-term
CC memory formation including spatial and fear-related learning,
CC conditioned taste aversion as well as long-term object recognition
CC (PubMed:17088210). They show enhanced early-phase but impaired late-
CC phase long-term potentiation (LTP) as well as impaired long-term
CC depression (LTD). Neurons lacking Arc show an increase in surface
CC levels of AMPA receptors (PubMed:17088210). In the visual cortex, mice
CC are impervious to the effects of deprivation or experience: mice do not
CC exhibit depression of deprived-eye responses or a shift in ocular
CC dominance after brief monocular deprivation (PubMed:20228806). Although
CC mice exhibit normal visual acuity, baseline ocular dominance is
CC abnormal and resemble that observed after dark-rearing
CC (PubMed:20228806). Mice also show schizophrenia-related phenotypes
CC characterized by deficits in sensorimotor gating, cognitive functions,
CC social behaviors and amphetamine-induced psychomotor responses
CC (PubMed:27524619). Divergent alterations between the prefrontal cortex
CC and striatal dopaminergic system that capture aspects of schizophrenia-
CC related neuropathophysiology are observed (PubMed:27524619). Knockout
CC mice show a relative loss of high-frequency electroencephalogram
CC activity in hippocampus, as well as a decrease in phase locking of
CC spikes to electroencephalogram oscillations (PubMed:27038743).
CC {ECO:0000269|PubMed:17088210, ECO:0000269|PubMed:20228806,
CC ECO:0000269|PubMed:27038743, ECO:0000269|PubMed:27524619}.
CC -!- MISCELLANEOUS: Widely used as activity-dependent neuronal marker to
CC identify recently activated neurons in behavioral studies.
CC {ECO:0000269|PubMed:17088210}.
CC -!- SIMILARITY: Belongs to the ARC/ARG3.1 family. {ECO:0000305}.
CC -!- CAUTION: Genetic disruption of the protein-coding gene was initially
CC reported to cause early embryonic lethality (PubMed:10727859). However,
CC only a partial deletion of the coding region was performed, leading to
CC dominant-negative effects (PubMed:10727859). A complete deletion of the
CC coding region later showed that mice are viable and display deficits in
CC several forms of long-term memory formation (PubMed:17088210).
CC {ECO:0000269|PubMed:10727859, ECO:0000269|PubMed:17088210}.
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DR EMBL; AF177701; AAK91587.1; -; Genomic_DNA.
DR EMBL; AF162777; AAD43586.1; -; mRNA.
DR EMBL; AK157822; BAE34212.1; -; mRNA.
DR EMBL; AK170446; BAE41804.1; -; mRNA.
DR EMBL; BC023127; AAH23127.1; -; mRNA.
DR EMBL; AF254662; AAG10254.1; -; Genomic_DNA.
DR CCDS; CCDS37102.1; -.
DR RefSeq; NP_001263613.1; NM_001276684.1.
DR RefSeq; NP_061260.1; NM_018790.3.
DR AlphaFoldDB; Q9WV31; -.
DR SMR; Q9WV31; -.
DR BioGRID; 198182; 7.
DR DIP; DIP-31565N; -.
DR IntAct; Q9WV31; 10.
DR MINT; Q9WV31; -.
DR STRING; 10090.ENSMUSP00000023268; -.
DR iPTMnet; Q9WV31; -.
DR PhosphoSitePlus; Q9WV31; -.
DR SwissPalm; Q9WV31; -.
DR PaxDb; Q9WV31; -.
DR PeptideAtlas; Q9WV31; -.
DR PRIDE; Q9WV31; -.
DR ProteomicsDB; 273918; -.
DR Antibodypedia; 3992; 302 antibodies from 34 providers.
DR DNASU; 11838; -.
DR Ensembl; ENSMUST00000023268; ENSMUSP00000023268; ENSMUSG00000022602.
DR Ensembl; ENSMUST00000110009; ENSMUSP00000105636; ENSMUSG00000022602.
DR GeneID; 11838; -.
DR KEGG; mmu:11838; -.
DR UCSC; uc007wfn.2; mouse.
DR CTD; 23237; -.
DR MGI; MGI:88067; Arc.
DR VEuPathDB; HostDB:ENSMUSG00000022602; -.
DR eggNOG; ENOG502QSPT; Eukaryota.
DR GeneTree; ENSGT00390000003914; -.
DR HOGENOM; CLU_782004_0_0_1; -.
DR InParanoid; Q9WV31; -.
DR OMA; AKKWWEY; -.
DR OrthoDB; 904267at2759; -.
DR PhylomeDB; Q9WV31; -.
DR TreeFam; TF335604; -.
DR BioGRID-ORCS; 11838; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Arc; mouse.
DR PRO; PR:Q9WV31; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q9WV31; protein.
DR Bgee; ENSMUSG00000022602; Expressed in primary visual cortex and 71 other tissues.
DR Genevisible; Q9WV31; MM.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:MGI.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; TAS:MGI.
DR GO; GO:0030425; C:dendrite; IDA:MGI.
DR GO; GO:0043197; C:dendritic spine; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:1903561; C:extracellular vesicle; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0071598; C:neuronal ribonucleoprotein granule; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0098839; C:postsynaptic density membrane; ISO:MGI.
DR GO; GO:0098845; C:postsynaptic endosome; ISO:MGI.
DR GO; GO:0003779; F:actin binding; TAS:MGI.
DR GO; GO:0003729; F:mRNA binding; ISS:UniProtKB.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:MGI.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0007492; P:endoderm development; IMP:MGI.
DR GO; GO:0007612; P:learning; IEA:Ensembl.
DR GO; GO:0007616; P:long-term memory; IMP:UniProtKB.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IMP:UniProtKB.
DR GO; GO:0051028; P:mRNA transport; ISS:UniProtKB.
DR GO; GO:2000969; P:positive regulation of AMPA receptor activity; ISO:MGI.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0022604; P:regulation of cell morphogenesis; ISS:UniProtKB.
DR GO; GO:0061001; P:regulation of dendritic spine morphogenesis; ISO:MGI.
DR GO; GO:1900452; P:regulation of long-term synaptic depression; IDA:UniProtKB.
DR GO; GO:1900271; P:regulation of long-term synaptic potentiation; IMP:UniProtKB.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IBA:GO_Central.
DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IDA:SynGO.
DR GO; GO:0110077; P:vesicle-mediated intercellular transport; ISS:UniProtKB.
DR InterPro; IPR023263; Arc.
DR InterPro; IPR040814; Arc_C.
DR InterPro; IPR045557; Arc_N.
DR PANTHER; PTHR15962; PTHR15962; 1.
DR Pfam; PF18162; Arc_C; 1.
DR Pfam; PF19284; Arc_MA; 1.
DR PRINTS; PR02027; ARCARG31.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Coiled coil; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Developmental protein; Endocytosis;
KW Endosome; Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW Postsynaptic cell membrane; Reference proteome; RNA-binding; Synapse;
KW Transport; Ubl conjugation.
FT CHAIN 1..396
FT /note="Activity-regulated cytoskeleton-associated protein"
FT /id="PRO_0000273286"
FT REGION 89..100
FT /note="Interaction with SH3GL1 or SH3GL3"
FT /evidence="ECO:0000250|UniProtKB:Q63053"
FT REGION 177..207
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 195..214
FT /note="Interaction with DNM2"
FT /evidence="ECO:0000250|UniProtKB:Q63053"
FT REGION 356..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 54..78
FT /evidence="ECO:0000255"
FT COMPBIAS 378..396
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 260
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000269|PubMed:31151856"
FT MOD_RES 278
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:31151856"
FT MUTAGEN 94..98
FT /note="CLCRC->SLSRS: Abolished palmitoylation, leading to
FT impaired ability mediate synaptic long-term depression
FT (LTD)."
FT /evidence="ECO:0000269|PubMed:29264923"
FT MUTAGEN 241
FT /note="Q->A: Impaired ability to homooligomerize at 30
FT degrees Celsius."
FT /evidence="ECO:0000269|PubMed:31151856"
FT MUTAGEN 257
FT /note="K->A: Impaired ability to homooligomerize at 30
FT degrees Celsius."
FT /evidence="ECO:0000269|PubMed:31151856"
FT MUTAGEN 260
FT /note="S->A: Abolished phosphorylation by CaMK2; knockin
FT mice display normal baseline synaptic transmission and
FT long-term potentiation (LTP) in the hippocampus, but
FT metabotropic receptor-LTD is increased; when associated
FT with A-278."
FT /evidence="ECO:0000269|PubMed:31151856"
FT MUTAGEN 260
FT /note="S->D: Phosphomimetic mutant; impaired ability to
FT homooligomerize at 30 degrees Celsius."
FT /evidence="ECO:0000269|PubMed:31151856"
FT MUTAGEN 277
FT /note="G->D: Impaired ability to homooligomerize at 30
FT degrees Celsius."
FT /evidence="ECO:0000269|PubMed:31151856"
FT MUTAGEN 278
FT /note="T->A: Abolished phosphorylation by CaMK2; knockin
FT mice display normal baseline synaptic transmission and
FT long-term potentiation (LTP) in the hippocampus, but
FT metabotropic receptor-LTD is increased; when associated
FT with A-278."
FT /evidence="ECO:0000269|PubMed:31151856"
FT MUTAGEN 278
FT /note="T->D: Phosphomimetic mutant; does not affect ability
FT to homooligomerize."
FT /evidence="ECO:0000269|PubMed:31151856"
FT MUTAGEN 335
FT /note="R->E: Impaired ability to homooligomerize at 30
FT degrees Celsius."
FT /evidence="ECO:0000269|PubMed:31151856"
SQ SEQUENCE 396 AA; 45321 MW; F4D3505FD477D18A CRC64;
MELDHMTTGG LHAYPAPRGG PAAKPNVILQ IGKCRAEMLE HVRRTHRHLL TEVSKQVERE
LKGLHRSVGK LENNLDGYVP TGDSQRWKKS IKACLCRCQE TIANLERWVK REMHVWREVF
YRLERWADRL ESMGGKYPVG SEPARHTVSV GVGGPEPYCQ EADGYDYTVS PYAITPPPAA
GELPEQESVE AQQYQSWGPG EDGQPSPGVD TQIFEDPREF LSHLEEYLRQ VGGSEEYWLS
QIQNHMNGPA KKWWEFKQGS VKNWVEFKKE FLQYSEGTLS REAIQRELEL PQKQGEPLDQ
FLWRKRDLYQ TLYVDAEEEE IIQYVVGTLQ PKLKRFLRHP LPKTLEQLIQ RGMEVQDGLE
QAAEPSGTPL PTEDETEALT PALTSESVAS DRTQPE
