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Protein

Activity-regulated cytoskeleton-associated protein

Gene

ARC

Organism
Homo sapiens (Human)
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. 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).By similarity

GO - Molecular functioni

GO - Biological processi

  • anterior/posterior pattern specification Source: Ensembl
  • cell migration Source: UniProtKB
  • cytoskeleton organization Source: UniProtKB
  • dendritic spine morphogenesis Source: ARUK-UCL
  • endocytosis Source: UniProtKB-KW
  • endoderm development Source: Ensembl
  • learning Source: Ensembl
  • long-term memory Source: UniProtKB
  • long-term synaptic potentiation Source: ARUK-UCL
  • mRNA transport Source: UniProtKB
  • positive regulation of AMPA receptor activity Source: Ensembl
  • protein homooligomerization Source: UniProtKB
  • regulation of cell morphogenesis Source: UniProtKB
  • regulation of dendritic spine morphogenesis Source: ARUK-UCL
  • regulation of long term synaptic depression Source: UniProtKB
  • regulation of long-term synaptic potentiation Source: UniProtKB
  • regulation of neuronal synaptic plasticity Source: Ensembl
  • vesicle-mediated intercellular transport Source: UniProtKB

Keywordsi

Molecular functionDevelopmental protein, RNA-binding
Biological processEndocytosis, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Activity-regulated cytoskeleton-associated protein1 Publication
Short name:
hArc1 Publication
Alternative name(s):
Activity-regulated gene 3.1 protein homologBy similarity
Short name:
ARC/ARG3.1By similarity
Short name:
Arg3.1By similarity
Gene namesi
Name:ARC1 PublicationImported
Synonyms:KIAA02781 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000198576.3
HGNCiHGNC:648 ARC
MIMi612461 gene
neXtProtiNX_Q7LC44

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

Organism-specific databases

DisGeNETi23237
OpenTargetsiENSG00000198576
PharmGKBiPA24930

Polymorphism and mutation databases

DMDMi74738627

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002732851 – 396Activity-regulated cytoskeleton-associated proteinAdd BLAST396

Post-translational modificationi

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

Keywords - PTMi

Lipoprotein, Palmitate, Ubl conjugation

Proteomic databases

PaxDbiQ7LC44
PeptideAtlasiQ7LC44
PRIDEiQ7LC44

PTM databases

iPTMnetiQ7LC44
PhosphoSitePlusiQ7LC44

Expressioni

Gene expression databases

BgeeiENSG00000198576
CleanExiHS_ARC
GenevisibleiQ7LC44 HS

Organism-specific databases

HPAiHPA056430

Interactioni

Subunit structurei

Homooligomer; homooligomerizes into virion-like capsids (PubMed:25748042). 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 (By similarity).By similarity1 Publication

Protein-protein interaction databases

BioGridi116842, 9 interactors
DIPiDIP-60107N
IntActiQ7LC44, 7 interactors
STRINGi9606.ENSP00000349022

Structurei

3D structure databases

ProteinModelPortaliQ7LC44
SMRiQ7LC44
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

Domaini

The protein is evolutionarily related to retrotransposon Gag proteins: it contains large N- and C-terminal domains that form a bi-lobar architecture similar to the capsid domain of human immunodeficiency virus (HIV) gag protein. It contains structural elements found within viral Gag polyproteins originated from the Ty3/gypsy retrotransposon family and retains the ability to form virion-like capsid structures that can mediate mRNA transfer between cells. Tetrapod and fly Arc protein-coding genes originated independently from distinct lineages of Ty3/gypsy retrotransposons.By similarity

Sequence similaritiesi

Belongs to the ARC/ARG3.1 family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IIAZ Eukaryota
ENOG410YF34 LUCA
GeneTreeiENSGT00390000003914
HOGENOMiHOG000034037
HOVERGENiHBG080862
InParanoidiQ7LC44
KOiK15867
OMAiHMNGPAK
OrthoDBiEOG091G07HQ
PhylomeDBiQ7LC44
TreeFamiTF335604

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

Q7LC44-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELDHRTSGG LHAYPGPRGG QVAKPNVILQ IGKCRAEMLE HVRRTHRHLL
60 70 80 90 100
AEVSKQVERE LKGLHRSVGK LESNLDGYVP TSDSQRWKKS IKACLCRCQE
110 120 130 140 150
TIANLERWVK REMHVWREVF YRLERWADRL ESTGGKYPVG SESARHTVSV
160 170 180 190 200
GVGGPESYCH EADGYDYTVS PYAITPPPAA GELPGQEPAE AQQYQPWVPG
210 220 230 240 250
EDGQPSPGVD TQIFEDPREF LSHLEEYLRQ VGGSEEYWLS QIQNHMNGPA
260 270 280 290 300
KKWWEFKQGS VKNWVEFKKE FLQYSEGTLS REAIQRELDL PQKQGEPLDQ
310 320 330 340 350
FLWRKRDLYQ TLYVDADEEE IIQYVVGTLQ PKLKRFLRHP LPKTLEQLIQ
360 370 380 390
RGMEVQDDLE QAAEPAGPHL PVEDEAETLT PAPNSESVAS DRTQPE
Length:396
Mass (Da):45,316
Last modified:July 5, 2004 - v1
Checksum:iD5C8A8A07FE9615D
GO

Sequence cautioni

The sequence BAA19667 differs from that shown. Reason: Erroneous initiation.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF193421 mRNA Translation: AAF07185.1
AF248637 Genomic DNA Translation: AAG33705.1
D87468 mRNA Translation: BAA19667.1 Different initiation.
BC012321 mRNA Translation: AAH12321.1
BC075802 mRNA Translation: AAH75802.1
CCDSiCCDS34950.1
RefSeqiNP_056008.1, NM_015193.4
UniGeneiHs.40888
Hs.743662

Genome annotation databases

EnsembliENST00000356613; ENSP00000349022; ENSG00000198576
GeneIDi23237
KEGGihsa:23237
UCSCiuc003ywn.2 human

Similar proteinsi

Entry informationi

Entry nameiARC_HUMAN
AccessioniPrimary (citable) accession number: Q7LC44
Secondary accession number(s): Q9UJW6, Q9Y469
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 23, 2007
Last sequence update: July 5, 2004
Last modified: May 23, 2018
This is version 113 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

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