Reviewed, UniProtKB/Swiss-Prot Q63053 (ARC_RAT)

Names and origin

Protein names

Recommended name:
    Activity-regulated cytoskeleton-associated protein
Alternative name(s):
    Activity-regulated gene 3.1 protein
      Short name=Arg3.1
    ARC/ARG3.1

Gene names

Name:

Arc

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	396 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for consolidation of synaptic plasticity as well as formation of long-term memory. Regulates endocytosis of AMPA receptors in response to synaptic activity. Required for homeostatic synaptic scaling of AMPA receptors. Ref.4 Ref.5 UniProtKB Q9WV31
Subunit structure	Interacts with SH3GL1/endophilin-2, SH3GL3/endophilin-3 and DNM2/DYN2. Ref.3
Subcellular location	Cytoplasm › cytoskeleton. Endosome. Cytoplasmic vesicle › secretory vesicle › acrosome By similarity. Cytoplasm › cell cortex. Cell projection › dendrite. Cell projection › dendritic spine. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density. Cell junction › synapse. Note: Associated with the cell cortex of neuronal soma and dendrites. Enriched in postsynaptic density of dendritic spines. Associated with the sperm tail.
Tissue specificity	Expressed exclusively in certain parts of the brain including cortex and molecular layer of the hippocampus. Typically expressed at high level in a minority of neurons. Basal expression higher in cortex than in hippocampus, highest in visual cortex. Ref.1 Ref.2
Developmental stage	Expressed during postnatal development from day 8. Highest expression around day 23 with moderate levels expressed to adulthood. Ref.1
Induction	By synaptic activity in hippocampus, cerebral cortex, amygdala and hypothalamus. Highest level in hippocampus within 30 min, dropping to basal levels within 24 hours. By NGF and EGF in fibroblasts. Ref.1 Ref.2
Miscellaneous	Widely used as activity-dependent neuronal marker to identify recently activated neurons in behavioral studies By similarity. UniProtKB Q9WV31 Neurons overexpressing Arc show reduced AMPA receptor-dependent synaptic transmission associated with reduced surface levels of AMPA receptor. This effect is dependent on NMDA receptor activity. Ref.4 Ref.5 Transcripts enriched in dendrites may be translated locally. Ref.2
Sequence similarities	Belongs to the ARC/ARG3.1 family.

Ontologies

Keywords
Biological process	Endocytosis
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Cytoplasmic vesicle Cytoskeleton Endosome Membrane Postsynaptic cell membrane Synapse
Domain	Coiled coil
Molecular function	Developmental protein
Gene Ontology (GO)
Biological process	endocytosis Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW regulation of neuronal synaptic plasticity Ref.1 Inferred from expression pattern. Source: RGD
Cellular component	acrosomal vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell actin cytoskeleton Ref.1 Inferred from direct assay. Source: RGD cell cortex Inferred from electronic annotation. Source: UniProtKB-SubCell cell junction Inferred from electronic annotation. Source: UniProtKB-KW dendritic spine Inferred from electronic annotation. Source: UniProtKB-SubCell endosome Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic density Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 396	396	Activity-regulated cytoskeleton-associated protein		PRO_0000273287
Regions
	Region	89 – 100	12	Binds SH3GL1 or SH3GL3 Ref.3
	Region	195 – 214	20	Required for binding DNM2 Ref.3
	Coiled coil	54 – 78	25	Potential
Experimental info
	Sequence conflict	209	1	V → L in AAA68695. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q63053-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 4E95B46B75853CA5	FASTA	396	45,353
	10 20 30 40 50 60 MELDHMTTGG LHAYPAPRGG PAAKPNVILQ IGKCRAEMLE HVRRTHRHLL TEVSKQVERE 70 80 90 100 110 120 LKGLHRSVGK LENNLDGYVP TGDSQRWKKS IKACLCRCQE TIANLERWVK REMHVWREVF 130 140 150 160 170 180 YRLERWADRL ESMGGKYPVG SEPARHTVSV GVGGPEPYCQ EADGYDYTVS PYAITPPPAA 190 200 210 220 230 240 GELPEQESVG AQQYQSWVPG EDGQPSPGVD TQIFEDPREF LSHLEEYLRQ VGGSEEYWLS 250 260 270 280 290 300 QIQNHMNGPA KKWWEFKQGS VKNWVEFKKE FLQYSEGTLS REAIQRELDL PQKQGEPLDQ 310 320 330 340 350 360 FLWRKRDLYQ TLYVDAEEEE IIQYVVGTLQ PKFKRFLRHP LPKTLEQLIQ RGMEVQDGLE 370 380 390 QAAEPSVTPL PTEDETEALT PALTSESVAS DRTQPE

References

[1]	"Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites." Lyford G.L., Yamagata K., Kaufmann W.E., Barnes C.A., Sanders L.K., Copeland N.G., Gilbert D.J., Jenkins N.A., Lanahan A.A., Worley P.F. Neuron 14:433-445(1995) [PubMed: 7857651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION. Tissue: Hippocampus.
[2]	"Somatodendritic expression of an immediate early gene is regulated by synaptic activity." Link W., Konietzko U., Kauselmann G., Krug M., Schwanke B., Frey U., Kuhl D. Proc. Natl. Acad. Sci. U.S.A. 92:5734-5738(1995) [PubMed: 7777577] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION. Strain: Sprague-Dawley. Tissue: Hippocampus.
[3]	"Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking." Chowdhury S., Shepherd J.D., Okuno H., Lyford G., Petralia R.S., Plath N., Kuhl D., Huganir R.L., Worley P.F. Neuron 52:445-459(2006) [PubMed: 17088211] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH DNM2; SH3GL1 AND SH3GL3.
[4]	"Increased expression of the immediate-early gene arc/arg3.1 reduces AMPA receptor-mediated synaptic transmission." Rial Verde E.M., Lee-Osbourne J., Worley P.F., Malinow R., Cline H.T. Neuron 52:461-474(2006) [PubMed: 17088212] [Abstract] Cited for: FUNCTION.
[5]	"Arc/Arg3.1 mediates homeostatic synaptic scaling of AMPA Receptors." Shepherd J.D., Rumbaugh G., Wu J., Chowdhury S., Plath N., Kuhl D., Huganir R.L., Worley P.F. Neuron 52:475-484(2006) [PubMed: 17088213] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U19866 mRNA. Translation: AAA68695.1. Z46925 mRNA. Translation: CAA87033.1.
IPI	IPI00208151.
PIR	I58168.
RefSeq	NP_062234.1.
UniGene	Rn.10086
3D structure databases
ModBase	Search...
Genome annotation databases
GeneID	54323.
KEGG	rno:54323.
UCSC	NM_019361. rat.
Organism-specific databases
CTD	54323.
RGD	62037. Arc.
Phylogenomic databases
HOVERGEN	Q63053.
OMA	RCQETIA.
Gene expression databases
Genevestigator	Q63053.
Family and domain databases
ProtoNet	Search...
Other Resources
NextBio	611018.

Entry information

Entry name

ARC_RAT

Accession

Primary (citable) accession number: Q63053
Secondary accession number(s): Q62743

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 23, 2007
Last sequence update:	November 1, 1996
Last modified:	November 3, 2009
This is version 43 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)