ARC_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: ARC_HUMAN
• UniProt AC: Q7LC44
• Protein Name: Activity-regulated cytoskeleton-associated protein {ECO:0000303|PubMed:10970730}
• Gene Name: ARC {ECO:0000303|PubMed:10970730, ECO:0000312|HGNC:HGNC:648}
• Organism: Homo sapiens (Human).
• Sequence Length: 396
• Subcellular Localization: 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 projecti
• Protein Description: 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)..
• Protein Sequence: MELDHRTSGGLHAYPGPRGGQVAKPNVILQIGKCRAEMLEHVRRTHRHLLAEVSKQVERELKGLHRSVGKLESNLDGYVPTSDSQRWKKSIKACLCRCQETIANLERWVKREMHVWREVFYRLERWADRLESTGGKYPVGSESARHTVSVGVGGPESYCHEADGYDYTVSPYAITPPPAAGELPGQEPAEAQQYQPWVPGEDGQPSPGVDTQIFEDPREFLSHLEEYLRQVGGSEEYWLSQIQNHMNGPAKKWWEFKQGSVKNWVEFKKEFLQYSEGTLSREAIQRELDLPQKQGEPLDQFLWRKRDLYQTLYVDADEEEIIQYVVGTLQPKLKRFLRHPLPKTLEQLIQRGMEVQDDLEQAAEPAGPHLPVEDEAETLTPAPNSESVASDRTQPE

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
24	Ubiquitination	PRGGQVAKPNVILQI CCCCCCCCCCEEEEE	37.96	30230243
55	Ubiquitination	HLLAEVSKQVERELK HHHHHHHHHHHHHHH	64.64	22817900
70	Ubiquitination	GLHRSVGKLESNLDG HHHHHHHHHHHHCCC	47.10	29967540
78	Phosphorylation	LESNLDGYVPTSDSQ HHHHCCCCCCCCHHH	11.70	29083192
81	Phosphorylation	NLDGYVPTSDSQRWK HCCCCCCCCHHHHHH	34.81	29083192
82	Phosphorylation	LDGYVPTSDSQRWKK CCCCCCCCHHHHHHH	29.24	29083192
84	Phosphorylation	GYVPTSDSQRWKKSI CCCCCCHHHHHHHHH	22.78	29083192
110	Sumoylation	ANLERWVKREMHVWR HHHHHHHHHHHHHHH	35.36	-
260	Phosphorylation	WWEFKQGSVKNWVEF CHHHHCCCCCCHHHH	27.68	-
268	Sumoylation	VKNWVEFKKEFLQYS CCCHHHHHHHHHHHC	37.58	-
274	Phosphorylation	FKKEFLQYSEGTLSR HHHHHHHHCCCCCCH	15.73	25884760
278	Phosphorylation	FLQYSEGTLSREAIQ HHHHCCCCCCHHHHH	19.94	-
293	Ubiquitination	RELDLPQKQGEPLDQ HHCCCCHHCCCCHHH	59.33	30230243
343	Ubiquitination	FLRHPLPKTLEQLIQ HHCCCCCHHHHHHHH	73.71	30230243
344	Phosphorylation	LRHPLPKTLEQLIQR HCCCCCHHHHHHHHH	33.32	28978645

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Oops, there are no upstream regulatory protein records of ARC_HUMAN !!

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
260	S	Phosphorylation	Phosphorylation at Ser-260 by CaMK2 prevents homooligomerization into virion-like capsids by disrupting an interaction surface essential for high-order oligomerization.	-

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of ARC_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
UBE3A_HUMAN	UBE3A	physical	23671107
RN216_HUMAN	RNF216	physical	24945773
FER_HUMAN	FER	physical	28514442
PP4P2_HUMAN	TMEM55A	physical	28514442
FA83B_HUMAN	FAM83B	physical	28514442
SSFA2_HUMAN	SSFA2	physical	28514442
NDE1_HUMAN	NDE1	physical	28514442

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• There are no disease associations of PTM sites.
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.