DDX58_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: DDX58_MOUSE
• UniProt AC: Q6Q899
• Protein Name: Probable ATP-dependent RNA helicase DDX58
• Gene Name: Ddx58
• Organism: Mus musculus (Mouse).
• Sequence Length: 926
• Subcellular Localization: Cytoplasm. Cell projection, ruffle membrane. Cytoplasm, cytoskeleton. Cell junction, tight junction. Colocalized with TRIM25 at cytoplasmic perinuclear bodies. Associated with the actin cytoskeleton at membrane ruffles..
• Protein Description: Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include: 5'-triphosphorylated ssRNA and dsRNA and short dsRNA (<1 kb in length). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential. Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity. A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity. Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: newcastle disease virus (NDV) and Sendai virus (SeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV). It also detects rotavirus and orthoreovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration..
• Protein Sequence: MTAEQRQNLQAFRDYIKKILDPTYILSYMSSWLEDEEVQYIQAEKNNKGPMEAASLFLQYLLKLQSEGWFQAFLDALYHAGYCGLCEAIESWDFQKIEKLEEHRLLLRRLEPEFKATVDPNDILSELSECLINQECEEIRQIRDTKGRMAGAEKMAECLIRSDKENWPKVLQLALEKDNSKFSELWIVDKGFKRAESKADEDDGAEASSIQIFIQEEPECQNLSQNPGPPSEASSNNLHSPLKPRNYQLELALPAKKGKNTIICAPTGCGKTFVSLLICEHHLKKFPCGQKGKVVFFANQIPVYEQQATVFSRYFERLGYNIASISGATSDSVSVQHIIEDNDIIILTPQILVNNLNNGAIPSLSVFTLMIFDECHNTSKNHPYNQIMFRYLDHKLGESRDPLPQVVGLTASVGVGDAKTAEEAMQHICKLCAALDASVIATVRDNVAELEQVVYKPQKISRKVASRTSNTFKCIISQLMKETEKLAKDVSEELGKLFQIQNREFGTQKYEQWIVGVHKACSVFQMADKEEESRVCKALFLYTSHLRKYNDALIISEDAQMTDALNYLKAFFHDVREAAFDETERELTRRFEEKLEELEKVSRDPSNENPKLRDLYLVLQEEYHLKPETKTILFVKTRALVDALKKWIEENPALSFLKPGILTGRGRTNRATGMTLPAQKCVLEAFRASGDNNILIATSVADEGIDIAECNLVILYEYVGNVIKMIQTRGRGRARDSKCFLLTSSADVIEKEKANMIKEKIMNESILRLQTWDEMKFGKTVHRIQVNEKLLRDSQHKPQPVPDKENKKLLCGKCKNFACYTADIRVVETSHYTVLGDAFKERFVCKPHPKPKIYDNFEKKAKIFCAKQNCSHDWGIFVRYKTFEIPVIKIESFVVEDIVSGVQNRHSKWKDFHFERIQFDPAEMSV

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
285	Ubiquitination	ICEHHLKKFPCGQKG HHHHHHHCCCCCCCC	61.98	-
293	Ubiquitination	FPCGQKGKVVFFANQ CCCCCCCEEEEEECC	42.11	-
496	Ubiquitination	DVSEELGKLFQIQNR HHHHHHHHHHHEECC	59.77	22790023
600	Ubiquitination	EKLEELEKVSRDPSN HHHHHHHHHCCCCCC	59.12	22790023
645	Ubiquitination	RALVDALKKWIEENP HHHHHHHHHHHHHCC	48.02	22790023
771	Phosphorylation	ESILRLQTWDEMKFG CHHHHHCCCCHHHCC	39.20	-
776	Acetylation	LQTWDEMKFGKTVHR HCCCCHHHCCCEEEE	49.25	23954790
776	Malonylation	LQTWDEMKFGKTVHR HCCCCHHHCCCEEEE	49.25	26320211
794	Phosphorylation	NEKLLRDSQHKPQPV CHHHHHCCCCCCCCC	27.96	-
813	Ubiquitination	NKKLLCGKCKNFACY CCEEECHHCCCEEEE	40.83	PubMed
852	Malonylation	CKPHPKPKIYDNFEK CCCCCCCCCCCCHHH	61.08	26320211
852	Acetylation	CKPHPKPKIYDNFEK CCCCCCCCCCCCHHH	61.08	23806337
854	Phosphorylation	PHPKPKIYDNFEKKA CCCCCCCCCCHHHHH	15.80	25367039
859	Acetylation	KIYDNFEKKAKIFCA CCCCCHHHHHEEEEE	54.62	-
859	Malonylation	KIYDNFEKKAKIFCA CCCCCHHHHHEEEEE	54.62	26320211
860	Acetylation	IYDNFEKKAKIFCAK CCCCHHHHHEEEEEC	47.95	15604057
862	Acetylation	DNFEKKAKIFCAKQN CCHHHHHEEEEECCC	45.24	15604065
862	Malonylation	DNFEKKAKIFCAKQN CCHHHHHEEEEECCC	45.24	26320211
910	Malonylation	QNRHSKWKDFHFERI CCCCCCCCCCEEEEC	55.01	32601280
925	Phosphorylation	QFDPAEMSV------ CCCHHHCCC------	19.04	26525534

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

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
771	T	Phosphorylation	Kinase	CK2	-	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Rnf125	Q9D9R0	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Rnf135	Q9CWS1	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Trim25	Q61510	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Cbl	P22682	PMID:23374343

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
48	K	ubiquitylation	'Lys-48' ubiquitination follows viral infection and is enhanced by 'Lys-63'-linked ubiquitination of the CARD domains that promotes interaction with VCP/p97 and subsequent recruitment of RNF125 (By similarity).	23374343
48	K	ubiquitylation	Also undergoes 'Lys-48' ubiquitination by RNF125 that leads to proteasomal degradation.	23374343
48	K	ubiquitylation	Within a negative feedback loop involving SIGLEC10 and PTPN11, 'Lys-48' ubiquitination at Lys-813 by CBL also elicits the proteasomal degradation of DDX58.	23374343
48	K	ubiquitylation	Also probably deubiquitinated by USP17L2/USP17 that cleaves 'Lys-48'- and 'Lys-63'-linked ubiquitin chains and positively regulates the receptor (By similarity).	23374343
63	K	ubiquitylation	'Lys-63' ubiquitination by RNF135, which occurs after RNA-binding and homodimerization, releases the autoinhibition of the CARD domains by the RLR CTR domain, an essential step in the activation of the RIG-I signaling pathway.	23374343
771	T	Phosphorylation	Phosphorylation at Thr-771 results in inhibition of its activity while dephosphorylation at these sites results in its activation.	-
813	K	ubiquitylation	Within a negative feedback loop involving SIGLEC10 and PTPN11, 'Lys-48' ubiquitination at Lys-813 by CBL also elicits the proteasomal degradation of DDX58.	23374343

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of DDX58_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
TBK1_MOUSE	Tbk1	physical	23950712
TRI25_HUMAN	TRIM25	physical	23209422
TRI25_MOUSE	Trim25	physical	23209422

Drug and Disease Associations

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