E2AK2_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: E2AK2_MOUSE
• UniProt AC: Q03963
• Protein Name: Interferon-induced, double-stranded RNA-activated protein kinase
• Gene Name: Eif2ak2
• Organism: Mus musculus (Mouse).
• Sequence Length: 515
• Subcellular Localization: Cytoplasm. Nucleus. Cytoplasm, perinuclear region.
• Protein Description: IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. Exerts its antiviral activity on a wide range of DNA and RNA viruses including west nile virus (WNV), sindbis virus (SV), foot-and-mouth virus (FMDV), semliki Forest virus (SFV) and lymphocytic choriomeningitis virus (LCMV). Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (EIF2S1), this phosphorylation impairs the recycling of EIF2S1 between successive rounds of initiation leading to inhibition of translation which eventually results in shutdown of cellular and viral protein synthesis. Also phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3 and IRS1. In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteosomal degradation. Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding proinflammatory cytokines and IFNs. Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6. Can act as both a positive and negative regulator of the insulin signaling pathway (ISP). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes. Can trigger apoptosis via FADD-mediated activation of CASP8. Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin. Regulates proliferation, differentiation and survival of hematopoietic stem/progenitor cells, induction of cytokines and chemokines and plays a role in cortex-dependent memory consolidation..
• Protein Sequence: MASDTPGFYMDKLNKYRQMHGVAITYKELSTSGPPHDRRFTFQVLIDEKEFPEAKGRSKQEARNAAAKLAVDILDNENKVDCHTSASEQGLFVGNYIGLVNSFAQKKKLSVNYEQCEPNSELPQRFICKCKIGQTMYGTGSGVTKQEAKQLAAKEAYQKLLKSPPKTAGTSSSVVTSTFSGFSSSSSMTSNGVSQSAPGSFSSENVFTNGLGENKRKSGVKVSPDDVQRNKYTLDARFNSDFEDIEEIGLGGFGQVFKAKHRIDGKRYAIKRVKYNTEKAEHEVQALAELNHVNIVQYHSCWEGVDYDPEHSMSDTSRYKTRCLFIQMEFCDKGTLEQWMRNRNQSKVDKALILDLYEQIVTGVEYIHSKGLIHRDLKPGNIFLVDERHIKIGDFGLATALENDGKSRTRRTGTLQYMSPEQLFLKHYGKEVDIFALGLILAELLHTCFTESEKIKFFESLRKGDFSNDIFDNKEKSLLKKLLSEKPKDRPETSEILKTLAEWRNISEKKKRNTC

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
2	Acetylation	------MASDTPGFY ------CCCCCCCCC	19.00	-
30	Phosphorylation	AITYKELSTSGPPHD EEEEEEHHCCCCCCC	22.94	25266776
31	Phosphorylation	ITYKELSTSGPPHDR EEEEEHHCCCCCCCC	50.78	28418008
32	Phosphorylation	TYKELSTSGPPHDRR EEEEHHCCCCCCCCE	46.02	26824392
68	Acetylation	EARNAAAKLAVDILD HHHHHHHHHHHHHHC	32.05	19857117
84	Phosphorylation	ENKVDCHTSASEQGL CCCCCCCCCHHHCCC	32.11	-
87	Phosphorylation	VDCHTSASEQGLFVG CCCCCCHHHCCCCHH	30.16	30352176
96	Phosphorylation	QGLFVGNYIGLVNSF CCCCHHHHHHHHHHH	7.16	-
110	Phosphorylation	FAQKKKLSVNYEQCE HHHHCCCCCCHHHCC	19.73	22942356
113	Phosphorylation	KKKLSVNYEQCEPNS HCCCCCCHHHCCCCC	12.76	26160508
157	Phosphorylation	QLAAKEAYQKLLKSP HHHHHHHHHHHHCCC	13.79	-
162	Ubiquitination	EAYQKLLKSPPKTAG HHHHHHHCCCCCCCC	71.94	27667366
163	Phosphorylation	AYQKLLKSPPKTAGT HHHHHHCCCCCCCCC	46.53	22942356
176	Ubiquitination	GTSSSVVTSTFSGFS CCCCCEEEEECCCCC	21.64	27667366
218	Phosphorylation	LGENKRKSGVKVSPD CCCCCCCCCCCCCHH	53.50	29472430
221	Ubiquitination	NKRKSGVKVSPDDVQ CCCCCCCCCCHHHHH	40.29	27667366
223	Phosphorylation	RKSGVKVSPDDVQRN CCCCCCCCHHHHHCC	19.52	26824392
232	Phosphorylation	DDVQRNKYTLDARFN HHHHCCCEEEEECCC	18.98	26643407
233	Phosphorylation	DVQRNKYTLDARFNS HHHCCCEEEEECCCC	21.55	26643407
235	Ubiquitination	QRNKYTLDARFNSDF HCCCEEEEECCCCCC	28.09	27667366
240	Phosphorylation	TLDARFNSDFEDIEE EEEECCCCCCHHHHH	40.75	26643407
268	Phosphorylation	HRIDGKRYAIKRVKY ECCCCEEEEEEEEEE	19.03	-
378	Ubiquitination	GLIHRDLKPGNIFLV CCCCCCCCCCCEEEE	55.99	22790023
407	Phosphorylation	ALENDGKSRTRRTGT HHCCCCCCCCCCCEE	44.40	29514104
409	Phosphorylation	ENDGKSRTRRTGTLQ CCCCCCCCCCCEEEC	31.43	22817900
414	Phosphorylation	SRTRRTGTLQYMSPE CCCCCCEEECCCCHH	15.29	-
419	Phosphorylation	TGTLQYMSPEQLFLK CEEECCCCHHHHHHH	21.98	-

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

Oops, there are no upstream regulatory protein records of E2AK2_MOUSE !!

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
409	T	Phosphorylation	Autophosphorylation of Thr-414 is dependent on Thr-409 and is stimulated by dsRNA binding and dimerization.	-
414	T	Phosphorylation	Autophosphorylation of Thr-414 is dependent on Thr-409 and is stimulated by dsRNA binding and dimerization.	-

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of E2AK2_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NPM_MOUSE	Npm1	physical	12882984

Drug and Disease Associations

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