Details of Host Protein

Host Protein General Information (ID: PT1145)
Protein Name	TRAF2 and NCK interacting kinase (TNIK)	Gene Name	TNIK
Host Species	Homo sapiens	Uniprot Entry Name	TNIK_HUMAN
Protein Families	Protein kinase superfamily
EC Number	2.7.11.1
Subcellular Location	Nucleus
External Link
	NCBI Gene ID	23043
	Uniprot ID	Q9UKE5
	Ensembl ID	ENSG00000154310
	HGNC ID	HGNC:30765
Function in Host	Serine/threonine kinase that acts as an essential activatorof the Wnt signaling pathway. Recruited to promoters of Wnt targetgenes and required to activate their expression. May act byphosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmentalstress. Part of a signaling complex composed of NEDD4, RAP2A and TNIKwhich regulates neuronal dendrite extension and arborization duringdevelopment. More generally, it may play a role in cytoskeletalrearrangements and regulate cell spreading. Phosphorylates SMAD1 onThr-322. [1-6] Click to Show/Hide
3D Structure	PDB ID: 2X7F FASTA Download 2D PNG Download PDB File Download

Function of This Protein During Virus Infection
Virus Name	SARS-COV-2	Protein Function	Pro-viral	[7]
Infected Tissue	Lung	Infection Time	7-9 Days
Infected Cell	Calu-3 Cells (Human epithelial cell line)	Cellosaurus ID	CVCL_0609
Method Description	To detect the role of host protein TNIK in viral infection, TNIK protein knockout Calu-3 Cells were infected with SARS-COV-2 for 7 - 9 Days , and the effects on infection was detected through CRISPR-based genome-wide gene-knockout screen.
Results	It is reported that knockout of TNIK leads to the decreased SARS-CoV-2 RNA levels compared with control group.

Full List of Virus RNA Interacting with This Protien
*RNA Region: 3'-UTR (hCoV-19/Wuhan-Hu-1/2019 )*
RNA Region Details	RNA Info Click to show the detail information of this RNA binding region	[8]
Strains Name	hCoV-19/Wuhan-Hu-1/2019
Strains Family	Beta (B.1.351)
RNA Binding Region	3'-UTR
Virus Name	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Infection Cells	HEK293 Cells (Human embryonic kidney cell) (CVCL_0045 )
Cell Originated Tissue	Liver
Infection Time	48 h
Interaction Score	Prot score = 22
Method Description	RNA-protein interaction detection (RaPID) assay; liquid chromatography with tandem mass spectrometry (LC-MS/MS)

Differential Gene Expression During SARS-COV-2 Infection

GEO Accession: GSE152641

Sample Type: Blood

Samples Details: Healthy Control: 24; COVID-19: 62

Platform: GPL24676 Illumina NovaSeq 6000

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GEO Accession: GSE162835

Sample Type: Nasopharyngeal Swabs

Samples Details: COVID-19 (Mild Symptoms): 37; COVID-19 (Moderate Symptoms): 10; COVID-19 (Severe Symptoms): 3

Platform: GPL24676 Illumina NovaSeq 6000

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GEO Accession: GSE175779

Sample Type: Human Bronchial Epithelial Cells

Samples Details: Healthy Control: 4 (0, 24, 48, 72 and 96 h); COVID-19: 4 (24, 48, 72 and 96 h)

Platform: GPL18573 Illumina NextSeq 500

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Protein Phosphorylation after Virus Infection
S680 [9] PNG Download
S707 [9] PNG Download
S769 [9] PNG Download

Potential Drug(s) that Targets This Protein
Drug Name																									DrunkBank ID																				Pubchem ID																				TTD ID																									REF
Fostamatinib																									DB12010																				11671467																				D0V8HJ																									[10]

Protein Sequence Information
MASDSPARSLDEIDLSALRDPAGIFELVELVGNGTYGQVYKGRHVKTGQLAAIKVMDVTGDEEEEIKQEINMLKKYSHHRNIATYYGAFIKKNPPGMDDQLWLVMEFCGAGSVTDLIKNTKGNTLKEEWIAYICREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDRTVGRRNTFIGTPYWMAPEVIACDENPDATYDFKSDLWSLGITAIEMAEGAPPLCDMHPMRALFLIPRNPAPRLKSKKWSKKFQSFIESCLVKNHSQRPATEQLMKHPFIRDQPNERQVRIQLKDHIDRTKKKRGEKDETEYEYSGSEEEEEENDSGEPSSILNLPGESTLRRDFLRLQLANKERSEALRRQQLEQQQRENEEHKRQLLAERQKRIEEQKEQRRRLEEQQRREKELRKQQEREQRRHYEEQMRREEERRRAEHEQEYIRRQLEEEQRQLEILQQQLLHEQALLLEYKRKQLEEQRQAERLQRQLKQERDYLVSLQHQRQEQRPVEKKPLYHYKEGMSPSEKPAWAKEVEERSRLNRQSSPAMPHKVANRISDPNLPPRSESFSISGVQPARTPPMLRPVDPQIPHLVAVKSQGPALTASQSVHEQPTKGLSGFQEALNVTSHRVEMPRQNSDPTSENPPLPTRIEKFDRSSWLRQEEDIPPKVPQRTTSISPALARKNSPGNGSALGPRLGSQPIRASNPDLRRTEPILESPLQRTSSGSSSSSSTPSSQPSSQGGSQPGSQAGSSERTRVRANSKSEGSPVLPHEPAKVKPEESRDITRPSRPASYKKAIDEDLTALAKELRELRIEETNRPMKKVTDYSSSSEESESSEEEEEDGESETHDGTVAVSDIPRLIPTGAPGSNEQYNVGMVGTHGLETSHADSFSGSISREGTLMIRETSGEKKRSGHSDSNGFAGHINLPDLVQQSHSPAGTPTEGLGRVSTHSQEMDSGTEYGMGSSTKASFTPFVDPRVYQTSPTDEDEEDEESSAAALFTSELLRQEQAKLNEARKISVVNVNPTNIRPHSDTPEIRKYKKRFNSEILCAALWGVNLLVGTENGLMLLDRSGQGKVYNLINRRRFQQMDVLEGLNVLVTISGKKNKLRVYYLSWLRNRILHNDPEVEKKQGWITVGDLEGCIHYKVVKYERIKFLVIALKNAVEIYAWAPKPYHKFMAFKSFADLQHKPLLVDLTVEEGQRLKVIFGSHTGFHVIDVDSGNSYDIYIPSHIQGNITPHAIVILPKTDGMEMLVCYEDEGVYVNTYGRITKDVVLQWGEMPTSVAYIHSNQIMGWGEKAIEIRSVETGHLDGVFMHKRAQRLKFLCERNDKVFFASVRSGGSSQVFFMTLNRNSMMNW Click to Show/Hide

References
1	Smad inhibition by the Ste20 kinase Misshapen. Proc Natl Acad Sci USA. 2011 Jul 5;108(27):11127-32.
2	Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. Neuron. 2010 Feb 11;65(3):358-72.
3	The kinase TNIK is an essential activator of Wnt target genes. EMBO J. 2009 Nov 4;28(21):3329-40.
4	Rap2 function requires palmitoylation and recycling endosome localization. Biochem Biophys Res Commun. 2009 Jan 23;378(4):732-7.
5	The Traf2- and Nck-interacting kinase as a putative effector of Rap2 to regulate actin cytoskeleton. J Biol Chem. 2004 Nov 19;279(47):49488-96.
6	TNIK, a novel member of the germinal center kinase family that activates the c-Jun N-terminal kinase pathway and regulates the cytoskeleton. J Biol Chem. 1999 Oct 22;274(43):30729-37.
7	Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2. Nat Commun. 2022 Apr 25;13(1):2237.
8	RNA-Protein Interaction Analysis of SARS-CoV-2 5 and 3 Untranslated Regions Reveals a Role of Lysosome-Associated Membrane Protein-2a during Viral Infection. mSystems. 2021 Aug 31;6(4):e0064321.
9	Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.
10	DrugBank