dbPTM

DDX58_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	DDX58_HUMAN
UniProt AC	O95786
Protein Name	Probable ATP-dependent RNA helicase DDX58
Gene Name	DDX58
Organism	Homo sapiens (Human).
Sequence Length	925
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: Human respiratory syncytial virus and measles virus (MeV), 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 reovirus. 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	MTTEQRRSLQAFQDYIRKTLDPTYILSYMAPWFREEEVQYIQAEKNNKGPMEAATLFLKFLLELQEEGWFRGFLDALDHAGYSGLYEAIESWDFKKIEKLEEYRLLLKRLQPEFKTRIIPTDIISDLSECLINQECEEILQICSTKGMMAGAEKLVECLLRSDKENWPKTLKLALEKERNKFSELWIVEKGIKDVETEDLEDKMETSDIQIFYQEDPECQNLSENSCPPSEVSDTNLYSPFKPRNYQLELALPAMKGKNTIICAPTGCGKTFVSLLICEHHLKKFPQGQKGKVVFFANQIPVYEQQKSVFSKYFERHGYRVTGISGATAENVPVEQIVENNDIIILTPQILVNNLKKGTIPSLSIFTLMIFDECHNTSKQHPYNMIMFNYLDQKLGGSSGPLPQVIGLTASVGVGDAKNTDEALDYICKLCASLDASVIATVKHNLEELEQVVYKPQKFFRKVESRISDKFKYIIAQLMRDTESLAKRICKDLENLSQIQNREFGTQKYEQWIVTVQKACMVFQMPDKDEESRICKALFLYTSHLRKYNDALIISEHARMKDALDYLKDFFSNVRAAGFDEIEQDLTQRFEEKLQELESVSRDPSNENPKLEDLCFILQEEYHLNPETITILFVKTRALVDALKNWIEGNPKLSFLKPGILTGRGKTNQNTGMTLPAQKCILDAFKASGDHNILIATSVADEGIDIAQCNLVILYEYVGNVIKMIQTRGRGRARGSKCFLLTSNAGVIEKEQINMYKEKMMNDSILRLQTWDEAVFREKILHIQTHEKFIRDSQEKPKPVPDKENKKLLCRKCKALACYTADVRVIEECHYTVLGDAFKECFVSRPHPKPKQFSSFEKRAKIFCARQNCSHDWGIHVKYKTFEIPVIKIESFVVEDIATGVQTLYSKWKDFHFEKIPFDPAEMSK

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
8	Phosphorylation	MTTEQRRSLQAFQDY CCHHHHHHHHHHHHH	27.33	20406818
15	Phosphorylation	SLQAFQDYIRKTLDP HHHHHHHHHHHHCCC	7.58	28111955
40	Phosphorylation	FREEEVQYIQAEKNN CCHHHHHHHHHHHCC	10.52	27642862
45	Ubiquitination	VQYIQAEKNNKGPME HHHHHHHHCCCCHHH	69.69	29967540
95	Ubiquitination	AIESWDFKKIEKLEE HHHHCCCHHHHHHHH	50.82	22817900
96	Ubiquitination	IESWDFKKIEKLEEY HHHCCCHHHHHHHHH	56.97	22817900
96	Sumoylation	IESWDFKKIEKLEEY HHHCCCHHHHHHHHH	56.97	-
99	Ubiquitination	WDFKKIEKLEEYRLL CCCHHHHHHHHHHHH	65.75	26471729
104	Ubiquitination	IEKLEEYRLLLKRLQ HHHHHHHHHHHHHHC	23.34	30230243
115	Ubiquitination	KRLQPEFKTRIIPTD HHHCHHHHCCCCCHH	34.92	29967540
146	Ubiquitination	ILQICSTKGMMAGAE HHHHHCCCCHHHCHH	28.63	-
154	Ubiquitination	GMMAGAEKLVECLLR CHHHCHHHHHHHHHH	58.25	22817900
159	Ubiquitination	AEKLVECLLRSDKEN HHHHHHHHHHCCCCC	2.56	30230243
160	Ubiquitination	EKLVECLLRSDKENW HHHHHHHHHCCCCCC	8.13	30230243
164	Ubiquitination	ECLLRSDKENWPKTL HHHHHCCCCCCCHHH	54.94	19484123
169	Ubiquitination	SDKENWPKTLKLALE CCCCCCCHHHHHHHH	59.09	22817900
170	Phosphorylation	DKENWPKTLKLALEK CCCCCCHHHHHHHHH	25.66	22817900
172	Ubiquitination	ENWPKTLKLALEKER CCCCHHHHHHHHHHH	36.62	22817900
177	Ubiquitination	TLKLALEKERNKFSE HHHHHHHHHHCCHHH	63.92	22817900
181	Ubiquitination	ALEKERNKFSELWIV HHHHHHCCHHHEEEE	57.39	PubMed
190	Ubiquitination	SELWIVEKGIKDVET HHEEEEECCCCCCCC	55.85	22817900
193	Ubiquitination	WIVEKGIKDVETEDL EEEECCCCCCCCCCH	65.47	PubMed
197	Phosphorylation	KGIKDVETEDLEDKM CCCCCCCCCCHHHHH	34.35	22817900
256	Ubiquitination	ELALPAMKGKNTIIC EEECCHHCCCCEEEE	69.69	29967540
258	Ubiquitination	ALPAMKGKNTIICAP ECCHHCCCCEEEECC	45.45	29967540
292	Ubiquitination	FPQGQKGKVVFFANQ CCCCCCCEEEEEECC	42.11	29967540
302	Ubiquitination	FFANQIPVYEQQKSV EEECCCCCHHHHHHH	9.80	30230243
307	Ubiquitination	IPVYEQQKSVFSKYF CCCHHHHHHHHHHHH	48.56	30230243
308	Phosphorylation	PVYEQQKSVFSKYFE CCHHHHHHHHHHHHH	24.85	28857561
311	Phosphorylation	EQQKSVFSKYFERHG HHHHHHHHHHHHHHC	25.04	28857561
312	Ubiquitination	QQKSVFSKYFERHGY HHHHHHHHHHHHHCC	42.36	-
455	Ubiquitination	ELEQVVYKPQKFFRK HHHHHHCCHHHHHHH	29.39	29967540
458	Ubiquitination	QVVYKPQKFFRKVES HHHCCHHHHHHHHHH	55.80	29967540
468	Phosphorylation	RKVESRISDKFKYII HHHHHHHHHHHHHHH	33.37	24719451
473	Phosphorylation	RISDKFKYIIAQLMR HHHHHHHHHHHHHHC	10.74	24719451
482	Phosphorylation	IAQLMRDTESLAKRI HHHHHCCHHHHHHHH	19.67	29083192
484	Phosphorylation	QLMRDTESLAKRICK HHHCCHHHHHHHHHH	35.40	29083192
491	Ubiquitination	SLAKRICKDLENLSQ HHHHHHHHHHHHHHH	64.08	29967540
495	Deamidation	RICKDLENLSQIQNR HHHHHHHHHHHHCCC	52.90	27866900
549	Deamidation	TSHLRKYNDALIISE HHHHHHHCCEEEECC	30.98	27866900
561	Ubiquitination	ISEHARMKDALDYLK ECCHHHHHHHHHHHH	34.01	29967540
568	Ubiquitination	KDALDYLKDFFSNVR HHHHHHHHHHHHHHH	46.38	29967540
593	Ubiquitination	LTQRFEEKLQELESV HHHHHHHHHHHHHHC	48.55	29967540
599 (in isoform 2)	Ubiquitination	-	37.71	21906983
644	Ubiquitination	RALVDALKNWIEGNP HHHHHHHHHHHCCCC	52.54	23000965
644 (in isoform 1)	Ubiquitination	-	52.54	21906983
652	Acetylation	NWIEGNPKLSFLKPG HHHCCCCCCCCCCCC	61.84	25953088
652	Ubiquitination	NWIEGNPKLSFLKPG HHHCCCCCCCCCCCC	61.84	29967540
654	Phosphorylation	IEGNPKLSFLKPGIL HCCCCCCCCCCCCEE	34.36	24719451
657	Ubiquitination	NPKLSFLKPGILTGR CCCCCCCCCCEEECC	38.91	29967540
666	Ubiquitination	GILTGRGKTNQNTGM CEEECCCCCCCCCCC	42.83	29967540
667	Phosphorylation	ILTGRGKTNQNTGMT EEECCCCCCCCCCCC	44.88	-
671	Phosphorylation	RGKTNQNTGMTLPAQ CCCCCCCCCCCCCHH	20.68	-
674	Phosphorylation	TNQNTGMTLPAQKCI CCCCCCCCCCHHHHH	30.82	-
679	Ubiquitination	GMTLPAQKCILDAFK CCCCCHHHHHHHHHH	25.91	29967540
757	Ubiquitination	KEQINMYKEKMMNDS HHHHHHHHHHHCCCH	39.84	-
759	Ubiquitination	QINMYKEKMMNDSIL HHHHHHHHHCCCHHH	39.02	29967540
764	Phosphorylation	KEKMMNDSILRLQTW HHHHCCCHHHHHCCC	20.65	24719451
770	Phosphorylation	DSILRLQTWDEAVFR CHHHHHCCCCHHHHH	39.20	28857561
779	Ubiquitination	DEAVFREKILHIQTH CHHHHHHHCHHHHHH	46.44	29967540
785	Phosphorylation	EKILHIQTHEKFIRD HHCHHHHHHHHHHHC	31.25	29396449
785	O-linked_Glycosylation	EKILHIQTHEKFIRD HHCHHHHHHHHHHHC	31.25	30379171
788	Ubiquitination	LHIQTHEKFIRDSQE HHHHHHHHHHHCCCC	38.19	29967540
796	Ubiquitination	FIRDSQEKPKPVPDK HHHCCCCCCCCCCCH	51.18	29967540
798	Ubiquitination	RDSQEKPKPVPDKEN HCCCCCCCCCCCHHH	70.48	29967540
812	Ubiquitination	NKKLLCRKCKALACY HHHHHHHHCCHHHHE	38.81	-
851	Ubiquitination	SRPHPKPKQFSSFEK CCCCCCCCCCCCHHH	70.83	29967540
854	Phosphorylation	HPKPKQFSSFEKRAK CCCCCCCCCHHHHHH	31.46	30108239
855	Phosphorylation	PKPKQFSSFEKRAKI CCCCCCCCHHHHHHH	38.42	30108239
858	Ubiquitination	KQFSSFEKRAKIFCA CCCCCHHHHHHHEEE	56.50	19608861
858	Acetylation	KQFSSFEKRAKIFCA CCCCCHHHHHHHEEE	56.50	19608861
861	Malonylation	SSFEKRAKIFCARQN CCHHHHHHHEEECCC	40.11	26320211
879	Phosphorylation	DWGIHVKYKTFEIPV CCCEEEEEEEEECCE	17.74	-
880	Ubiquitination	WGIHVKYKTFEIPVI CCEEEEEEEEECCEE	40.81	29967540
888	Sumoylation	TFEIPVIKIESFVVE EEECCEEEEEEEEHH	40.43	-
909	Malonylation	QTLYSKWKDFHFEKI HHHHHHHCCCCCCCC	55.01	26320211
909	Ubiquitination	QTLYSKWKDFHFEKI HHHHHHHCCCCCCCC	55.01	19608861
909	Acetylation	QTLYSKWKDFHFEKI HHHHHHHCCCCCCCC	55.01	19608861
915	Ubiquitination	WKDFHFEKIPFDPAE HCCCCCCCCCCCHHH	55.52	29967540
924	Phosphorylation	PFDPAEMSK------ CCCHHHHCC------	27.07	28857561

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
8	S	Phosphorylation	Kinase	DAPK1	P53355	PSP
8	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
170	T	Phosphorylation	Kinase	PRKCA	P17252	GPS
654	S	Phosphorylation	Kinase	DAPK1	P53355	PSP
667	T	Phosphorylation	Kinase	DAPK1	P53355	PSP
671	T	Phosphorylation	Kinase	DAPK1	P53355	PSP
674	T	Phosphorylation	Kinase	DAPK1	P53355	PSP
764	S	Phosphorylation	Kinase	DAPK1	P53355	PSP
770	T	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
770	T	Phosphorylation	Kinase	DAPK1	P53355	PSP
770	T	Phosphorylation	Kinase	CK2	-	Uniprot
854	S	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
854	S	Phosphorylation	Kinase	CK2	-	Uniprot
855	S	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
855	S	Phosphorylation	Kinase	IKBKE	Q14164	GPS
855	S	Phosphorylation	Kinase	CK2	-	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	TRIM25	Q14258	PMID:17392790
-	K	Ubiquitination	E3 ubiquitin ligase	RNF135	Q8IUD6	PMID:19017631
-	K	Ubiquitination	E3 ubiquitin ligase	RNF125	Q96EQ8	PMID:17460044
-	K	Ubiquitination	E3 ubiquitin ligase	RNF31	Q96EP0	PMID:21292167

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
48	K	ubiquitylation	28469175
'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.
48	K	ubiquitylation	28469175
Also undergoes 'Lys-48' ubiquitination at Lys-181 by RNF125 that leads to proteasomal degradation.
48	K	ubiquitylation	28469175
Within a negative feedback loop involving SIGLEC10 and PTPN11, 'Lys-48' ubiquitination at Lys-812 by CBL also elicits the proteasomal degradation of DDX58 (By similarity).
48	K	ubiquitylation	28469175
Also probably deubiquitinated by USP17L2/USP17 that cleaves 'Lys-48'- and 'Lys-63'-linked ubiquitin chains and positively regulates the receptor.
63	K	ubiquitylation	23950712
'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.
154	K	ubiquitylation	19484123
Lys-154, Lys-164 and Lys-172 are shared sites for RNF135-mediated and TRIM4-mediated ubiquitination.
164	K	ubiquitylation	19484123
Lys-154, Lys-164 and Lys-172 are shared sites for RNF135-mediated and TRIM4-mediated ubiquitination.
172	K	ubiquitylation	17392790
Lys-154, Lys-164 and Lys-172 are shared sites for RNF135-mediated and TRIM4-mediated ubiquitination.
172	K	ubiquitylation	17392790
Lys-172 is the critical site of ubiquitination for MAVS/IPS1 binding and to induce anti-viral signal transduction.
181	K	ubiquitylation	17392790
Also undergoes 'Lys-48' ubiquitination at Lys-181 by RNF125 that leads to proteasomal degradation.
495	N	Amidation	27866900
(Microbial infection) Deamidated on 'Asn-495' and 'Asn-549' by herpes simplex virus 1 protein UL37.
549	N	Amidation	27866900
(Microbial infection) Deamidated on 'Asn-495' and 'Asn-549' by herpes simplex virus 1 protein UL37.
770	T	Phosphorylation	21068236
Phosphorylation at Thr-770, Ser-854 and Ser-855 results in inhibition of its activity while dephosphorylation at these sites results in its activation.
812	K	ubiquitylation	19017631
Within a negative feedback loop involving SIGLEC10 and PTPN11, 'Lys-48' ubiquitination at Lys-812 by CBL also elicits the proteasomal degradation of DDX58 (By similarity).
854	S	Phosphorylation	21068236
Phosphorylation at Thr-770, Ser-854 and Ser-855 results in inhibition of its activity while dephosphorylation at these sites results in its activation.
855	S	Phosphorylation	21068236
Phosphorylation at Thr-770, Ser-854 and Ser-855 results in inhibition of its activity while dephosphorylation at these sites results in its activation.

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of DDX58_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CYLD_HUMAN	CYLD	physical	18636086
IRF3_HUMAN	IRF3	physical	18636086
TRI25_HUMAN	TRIM25	physical	17392790
MAVS_HUMAN	MAVS	physical	20071582
TRI25_HUMAN	TRIM25	physical	20071582
MAVS_HUMAN	MAVS	physical	19454348
TRI25_HUMAN	TRIM25	physical	20406818
MAVS_HUMAN	MAVS	physical	20406818
MAVS_HUMAN	MAVS	physical	21903422
RAI14_HUMAN	RAI14	physical	21903422
WRIP1_HUMAN	WRNIP1	physical	21903422
HOIL1_HUMAN	RBCK1	physical	21292167
RNF31_HUMAN	RNF31	physical	21292167
MAVS_HUMAN	MAVS	physical	21292167
TRI25_HUMAN	TRIM25	physical	21292167
TRI25_HUMAN	TRIM25	physical	22114345
MAVS_HUMAN	MAVS	physical	22114345
KPCA_HUMAN	PRKCA	physical	22114345
KPCB_HUMAN	PRKCB	physical	22114345
ISG15_HUMAN	ISG15	physical	16009940
TSN6_HUMAN	TSPAN6	physical	22908223
MAVS_HUMAN	MAVS	physical	16177806
SRC_HUMAN	SRC	physical	19419966
MAVS_HUMAN	MAVS	physical	16153868
IRF3_HUMAN	IRF3	physical	16153868
DDX58_HUMAN	DDX58	physical	23264040
MBP_HUMAN	MBP	physical	23264040
UBP4_HUMAN	USP4	physical	23388719
TRI25_MOUSE	Trim25	physical	20818395
CASPC_MOUSE	Casp12	physical	20818395
RN135_HUMAN	RNF135	physical	23950712
TBK1_HUMAN	TBK1	physical	23950712
TRI25_HUMAN	TRIM25	physical	23950712
IKKE_HUMAN	IKBKE	physical	23950712
NEMO_HUMAN	IKBKG	physical	23950712
UBP21_HUMAN	USP21	physical	24493797
UBP3_HUMAN	USP3	physical	24366338
MEX3C_HUMAN	MEX3C	physical	24706898
RN135_HUMAN	RNF135	physical	19484123
MAVS_HUMAN	MAVS	physical	20554965
UBC_HUMAN	UBC	physical	23264040
TRI25_HUMAN	TRIM25	physical	19484123
UBC_HUMAN	UBC	physical	20403326
IFIT3_HUMAN	IFIT3	physical	21813773
MAVS_HUMAN	MAVS	physical	26061460
UBP15_HUMAN	USP15	physical	26061460
TIA1_HUMAN	TIA1	physical	26344197
RN135_HUMAN	RNF135	physical	19017631
IRGM_HUMAN	IRGM	physical	25891078
TRI25_HUMAN	TRIM25	physical	27122586
UBD_HUMAN	UBD	physical	26996158
TRI25_HUMAN	TRIM25	physical	28148787
HDAC6_HUMAN	HDAC6	physical	26746851
RN122_HUMAN	RNF122	physical	27506794

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
616298	Singleton-Merten syndrome 2 (SGMRT2)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of DDX58_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions."; Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.; Science 325:834-840(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-858 AND LYS-909, AND MASSSPECTROMETRY.	19608861 [Abstract]
Phosphorylation
Reference	PubMed
"Phosphorylation of RIG-I by casein kinase II inhibits its antiviralresponse."; Sun Z., Ren H., Liu Y., Teeling J.L., Gu J.; J. Virol. 85:1036-1047(2011). Cited for: PHOSPHORYLATION AT THR-770; SER-854 AND SER-855.	21068236 [Abstract]

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