Q63053 (ARC_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Activity-regulated cytoskeleton-associated protein

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

Gene names

Name:

Arc

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	396 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the stress fiber dynamics and cell migration By similarity. 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
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: Enriched on the plasma membrane By similarity. Associated with the cell cortex of neuronal soma and dendrites. Enriched in postsynaptic density of dendritic spines. Associated with the sperm tail. Ref.1 Ref.2 Ref.3
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
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anterior/posterior pattern specification Inferred from electronic annotation. Source: Compara cell migration Inferred from sequence or structural similarity. Source: UniProtKB cytoskeleton organization Inferred from sequence or structural similarity. Source: UniProtKB endocytosis Inferred from electronic annotation. Source: UniProtKB-KW endoderm development Inferred from electronic annotation. Source: Compara learning Inferred from expression pattern PubMed 20111591. Source: RGD regulation of cell morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB regulation of neuronal synaptic plasticity Inferred from expression pattern Ref.1. Source: RGD
Cellular_component	acrosomal vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell actin cytoskeleton Inferred from direct assay Ref.1. Source: RGD cell cortex Inferred from electronic annotation. Source: UniProtKB-SubCell cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytoplasm Traceable author statement PubMed 12451105. Source: RGD endosome Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW postsynaptic density Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Camk2b	P08413	6	EBI-5275794,EBI-916155
PSEN1	P49768	3	EBI-5275794,EBI-2606326	From a different organism.

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 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U19866 mRNA. Translation: AAA68695.1. Z46925 mRNA. Translation: CAA87033.1.
IPI	IPI00208151.
PIR	I58168.
RefSeq	NP_062234.1. NM_019361.1.
UniGene	Rn.10086.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q63053. 6 interactions.
PTM databases
PhosphoSite	Q63053.
Proteomic databases
PaxDb	Q63053.
PRIDE	Q63053.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000067442; ENSRNOP00000063719; ENSRNOG00000043465.
GeneID	54323.
KEGG	rno:54323.
UCSC	RGD:62037. rat.
Organism-specific databases
CTD	23237.
RGD	62037. Arc.
Phylogenomic databases
eggNOG	NOG81608.
GeneTree	ENSGT00390000003914.
HOGENOM	HOG000034037.
HOVERGEN	HBG080862.
KO	K15867.
OrthoDB	EOG49S66B.
Gene expression databases
Genevestigator	Q63053.
Family and domain databases
InterPro	IPR023263. Activity-reg_cytoskelet-assoc. [Graphical view]
PRINTS	PR02027. ARCARG31.
ProtoNet	Search...
Other
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:	April 3, 2013
This is version 65 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program