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Aliases for ARC Gene

Aliases for ARC Gene

  • Activity Regulated Cytoskeleton Associated Protein 2 3 5
  • Activity-Regulated Gene 3.1 Protein Homolog 3 4
  • ARC/ARG3.1 3 4
  • Arg3.1 3 4
  • HArc 3 4
  • Activity-Regulated Cytoskeleton-Associated Protein 3
  • KIAA0278 4

External Ids for ARC Gene

Previous GeneCards Identifiers for ARC Gene

  • GC08U990084
  • GC08M143591
  • GC08M143690
  • GC08M138948

Summaries for ARC Gene

GeneCards Summary for ARC Gene

ARC (Activity Regulated Cytoskeleton Associated Protein) is a Protein Coding gene. Diseases associated with ARC include Amphetamine Abuse and Hepatocellular Carcinoma. Among its related pathways are Cytoskeletal Signaling and BDNF-TrkB Signaling.

UniProtKB/Swiss-Prot for ARC Gene

  • 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).

Additional gene information for ARC Gene

No data available for Entrez Gene Summary , CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ARC Gene

Genomics for ARC Gene

GeneHancer (GH) Regulatory Elements for ARC Gene

Promoters and enhancers for ARC Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH08J142614 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE 656.3 -0.4 -363 1.6 HDGF CLOCK SIN3A GLIS2 ELK1 FOS SP3 YY2 ZNF592 GLIS1 ARC JRK EEF1D ENSG00000261044
GH08J142608 Enhancer 1 Ensembl ENCODE 7.5 +5.5 5528 1.7 ELF3 PKNOX1 SIN3A RAD21 GLIS2 ELK1 SCRT2 ZNF143 SMARCA5 ZNF654 ARC JRK MROH4P
GH08J142599 Enhancer 0.5 ENCODE 0.4 +15.0 14957 0.2 SP1 RFX1 POLR2A SIN3A BMI1 ARC MROH4P
GH08J142597 Enhancer 0.4 ENCODE 0.4 +16.9 16877 0.2 GATA3 EZH2 JRK ARC MROH4P
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around ARC on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the ARC gene promoter:
  • Sp1
  • STAT5A
  • NF-kappaB1
  • NF-kappaB
  • NRSF form 2
  • NRSF form 1

Genomic Locations for ARC Gene

Genomic Locations for ARC Gene
chr8:142,611,044-142,614,472
(GRCh38/hg38)
Size:
3,429 bases
Orientation:
Minus strand
chr8:143,692,405-143,696,833
(GRCh37/hg19)
Size:
4,429 bases
Orientation:
Minus strand

Genomic View for ARC Gene

Genes around ARC on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ARC Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ARC Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ARC Gene

Proteins for ARC Gene

  • Protein details for ARC Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q7LC44-ARC_HUMAN
    Recommended name:
    Activity-regulated cytoskeleton-associated protein
    Protein Accession:
    Q7LC44
    Secondary Accessions:
    • Q9UJW6
    • Q9Y469

    Protein attributes for ARC Gene

    Size:
    396 amino acids
    Molecular mass:
    45316 Da
    Quaternary structure:
    • 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).
    SequenceCaution:
    • Sequence=BAA19667.1; Type=Erroneous initiation; Evidence={ECO:0000305};

neXtProt entry for ARC Gene

Post-translational modifications for ARC Gene

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

Other Protein References for ARC Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for ARC Gene

Domains & Families for ARC Gene

Gene Families for ARC Gene

Protein Domains for ARC Gene

Suggested Antigen Peptide Sequences for ARC Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q7LC44

UniProtKB/Swiss-Prot:

ARC_HUMAN :
  • 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.
  • Belongs to the ARC/ARG3.1 family.
Domain:
  • 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.
Family:
  • Belongs to the ARC/ARG3.1 family.
genes like me logo Genes that share domains with ARC: view

Function for ARC Gene

Molecular function for ARC Gene

UniProtKB/Swiss-Prot 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).

Phenotypes From GWAS Catalog for ARC Gene

Gene Ontology (GO) - Molecular Function for ARC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003729 mRNA binding ISS --
genes like me logo Genes that share ontologies with ARC: view
genes like me logo Genes that share phenotypes with ARC: view

Animal Models for ARC Gene

MGI Knock Outs for ARC:
  • Arc Arc<tm1.1Kuhl>
  • Arc Arc<tm1Stl>
  • Arc Arc<tm1Amt>

Animal Model Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for ARC Gene

Localization for ARC Gene

Subcellular locations from UniProtKB/Swiss-Prot for ARC Gene

Extracellular vesicle membrane; Lipid-anchor. Cell junction, synapse, postsynaptic cell membrane; Lipid-anchor. Cell junction, synapse. Cell junction, synapse, postsynaptic cell membrane, postsynaptic density. Early endosome membrane. Cell projection, dendrite. Cytoplasm, cytoskeleton. Cytoplasm, cell cortex. Cell projection, dendritic spine. Cytoplasmic vesicle, secretory vesicle, acrosome. 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}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ARC gene
Compartment Confidence
plasma membrane 5
cytoskeleton 3
nucleus 3
endosome 3
cytosol 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Microtubules (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ARC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001669 acrosomal vesicle IEA --
GO:0005737 cytoplasm IDA,IEA 21834987
GO:0005768 endosome IEA --
GO:0005856 cytoskeleton IEA --
GO:0005886 plasma membrane IDA,IEA 21834987
genes like me logo Genes that share ontologies with ARC: view

Pathways & Interactions for ARC Gene

genes like me logo Genes that share pathways with ARC: view

Pathways by source for ARC Gene

1 BioSystems pathway for ARC Gene
1 KEGG pathway for ARC Gene
1 Qiagen pathway for ARC Gene
2 Cell Signaling Technology pathways for ARC Gene

Gene Ontology (GO) - Biological Process for ARC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006897 endocytosis IEA --
GO:0007010 cytoskeleton organization IMP 21834987
GO:0007275 multicellular organism development IEA --
GO:0007492 endoderm development IEA --
GO:0007612 learning IEA --
genes like me logo Genes that share ontologies with ARC: view

No data available for SIGNOR curated interactions for ARC Gene

Drugs & Compounds for ARC Gene

(11) Drugs for ARC Gene - From: ClinicalTrials and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Captopril Approved Pharma Inhibition, Inhibitor ACE inhibitor, ACE inhibitor; also inhibits LTA4 hydrolase 37
rituximab Approved Pharma Therapeutic Antibodies 1808
Angiotensin-Converting Enzyme Inhibitors Pharma 746
Antibodies Pharma 7224
Antihypertensive Agents Pharma 4428
genes like me logo Genes that share compounds with ARC: view

Transcripts for ARC Gene

mRNA/cDNA for ARC Gene

(1) REFSEQ mRNAs :
(4) Additional mRNA sequences :
(40) Selected AceView cDNA sequences:
(2) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for ARC Gene

Activity-regulated cytoskeleton-associated protein:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ARC Gene

No ASD Table

Relevant External Links for ARC Gene

GeneLoc Exon Structure for
ARC
ECgene alternative splicing isoforms for
ARC

Expression for ARC Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ARC Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ARC Gene

This gene is overexpressed in Pituitary (x5.7) and Brain - Cortex (x5.1).

Protein differential expression in normal tissues from HIPED for ARC Gene

This gene is overexpressed in Frontal cortex (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for ARC Gene



Protein tissue co-expression partners for ARC Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of ARC Gene:

ARC

SOURCE GeneReport for Unigene cluster for ARC Gene:

Hs.40888

Evidence on tissue expression from TISSUES for ARC Gene

  • Nervous system(2.8)
genes like me logo Genes that share expression patterns with ARC: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for ARC Gene

Orthologs for ARC Gene

This gene was present in the common ancestor of chordates.

Orthologs for ARC Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ARC 34 33
  • 99.43 (n)
OneToOne
cow
(Bos Taurus)
Mammalia ARC 34 33
  • 89.98 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Arc 33
  • 86.2 (n)
mouse
(Mus musculus)
Mammalia Arc 16 34 33
  • 85.77 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia ARC 34
  • 77 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia ARC 34
  • 77 (a)
OneToOne
chicken
(Gallus gallus)
Aves ARC 34 33
  • 70.78 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia ARC 34
  • 68 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia arc 33
  • 54.06 (n)
Species where no ortholog for ARC was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • dog (Canis familiaris)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for ARC Gene

ENSEMBL:
Gene Tree for ARC (if available)
TreeFam:
Gene Tree for ARC (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ARC: view image

Paralogs for ARC Gene

No data available for Paralogs for ARC Gene

Variants for ARC Gene

Sequence variations from dbSNP and Humsavar for ARC Gene

SNP ID Clin Chr 08 pos Variation AA Info Type
rs1000029399 -- 142,614,156(-) A/C coding_sequence_variant, missense_variant
rs1000233723 -- 142,612,799(-) G/C 3_prime_UTR_variant
rs1003170115 -- 142,615,044(-) G/C upstream_transcript_variant
rs1003242235 -- 142,615,412(-) G/A upstream_transcript_variant
rs1003309256 -- 142,614,821(-) C/T upstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for ARC Gene

Variant ID Type Subtype PubMed ID
nsv950002 CNV deletion 24416366
nsv612709 CNV loss 21841781
nsv470245 CNV loss 18288195
esv2661137 CNV deletion 23128226
dgv904n27 CNV loss 19166990
dgv7335n100 CNV gain 25217958
dgv12397n54 CNV loss 21841781

Variation tolerance for ARC Gene

Residual Variation Intolerance Score: 34.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.66; 14.18% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ARC Gene

Human Gene Mutation Database (HGMD)
ARC
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ARC

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ARC Gene

Disorders for ARC Gene

MalaCards: The human disease database

(4) MalaCards diseases for ARC Gene - From: LncRNADisease, HGMD, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
amphetamine abuse
hepatocellular carcinoma
  • hcc
anterograde amnesia
  • amnesia, anterograde
gordon holmes syndrome
  • gdhs
- elite association - COSMIC cancer census association via MalaCards
Search ARC in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with ARC: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ARC Gene

Publications for ARC Gene

  1. Mutation screening of the chromosome 8q24.3-human activity-regulated cytoskeleton-associated gene (ARC) in idiopathic generalized epilepsy. (PMID: 10970730) Haug K … Heils A (Molecular and cellular probes 2000) 2 3 4 22 58
  2. Activity-regulated cytoskeleton-associated protein Arc/Arg3.1 binds to spectrin and associates with nuclear promyelocytic leukemia (PML) bodies. (PMID: 17466953) Bloomer WA … VanDongen AM (Brain research 2007) 2 3 22 58
  3. Arc is a flexible modular protein capable of reversible self-oligomerization. (PMID: 25748042) Myrum C … Bramham CR (The Biochemical journal 2015) 3 4 58
  4. Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration. (PMID: 21834987) Bai SW … Ridley AJ (BMC biology 2011) 3 4 58
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 58

Products for ARC Gene

Sources for ARC Gene

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