Host Protein General Information (ID: PT0650)
  Protein Name
MEK kinase kinase 4 (MAP4K4)
  Gene Name
MAP4K4
  Host Species
Homo sapiens
  Uniprot Entry Name
M4K4_HUMAN
  Protein Families
Protein kinase superfamily
  EC Number
2.7.11.1
  Subcellular Location
Cytoplasm
  External Link
NCBI Gene ID
9448
Uniprot ID
O95819
Ensembl ID
ENSG00000189252
HGNC ID
HGNC:6866
  Function in Host
Serine/threonine kinase that may play a role in the responseto environmental stress and cytokines such as TNF-alpha. Appears to actupstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322. [1-2]
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  Related KEGG Pathway
MAPK signaling pathway hsa04010            Pathway Map 
  3D Structure

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Pro-viral [3]
Infected TissueLung Infection Time7-9 Days
Infected CellCalu-3 Cells (Human epithelial cell line) Cellosaurus IDCVCL_0609 
Method DescriptionTo detect the role of host protein MAP4K4 in viral infection, MAP4K4 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.
ResultsIt is reported that knockout of MAP4K4 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 [4]
              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 = 18
              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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Protein Phosphorylation after Virus Infection
S175 [5]
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S580 [5]
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S585 [5]
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S602 [5]
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S629 [5]
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S631 [5]
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S639 [5]
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S656 [5]
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S700 [5]
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S715 [5]
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S800 [5]
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S801 [5]
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S842 [5]
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S900 [5]
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T181 [5]
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T809 [5]
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T834 [5]
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T846 [5]
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Potential Drug(s) that Targets This Protein
Drug Name DrunkBank ID Pubchem ID TTD ID REF
Fostamatinib DB12010  11671467  D0V8HJ  [6]

Protein Sequence Information
MANDSPAKSLVDIDLSSLRDPAGIFELVEVVGNGTYGQVYKGRHVKTGQLAAIKVMDVTEDEEEEIKLEINMLKKYSHHRNIATYYGAFIKKSPPGHDDQLWLVMEFCGAGSITDLVKNTKGNTLKEDWIAYISREILRGLAHLHIHHVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDRTVGRRNTFIGTPYWMAPEVIACDENPDATYDYRSDLWSCGITAIEMAEGAPPLCDMHPMRALFLIPRNPPPRLKSKKWSKKFFSFIEGCLVKNYMQRPSTEQLLKHPFIRDQPNERQVRIQLKDHIDRTRKKRGEKDETEYEYSGSEEEEEEVPEQEGEPSSIVNVPGESTLRRDFLRLQQENKERSEALRRQQLLQEQQLREQEEYKRQLLAERQKRIEQQKEQRRRLEEQQRREREARRQQEREQRRREQEEKRRLEELERRRKEEEERRRAEEEKRRVEREQEYIRRQLEEEQRHLEVLQQQLLQEQAMLLECRWREMEEHRQAERLQRQLQQEQAYLLSLQHDHRRPHPQHSQQPPPPQQERSKPSFHAPEPKAHYEPADRAREVEDRFRKTNHSSPEAQSKQTGRVLEPPVPSRSESFSNGNSESVHPALQRPAEPQVPVRTTSRSPVLSRRDSPLQGSGQQNSQAGQRNSTSIEPRLLWERVEKLVPRPGSGSSSGSSNSGSQPGSHPGSQSGSGERFRVRSSSKSEGSPSQRLENAVKKPEDKKEVFRPLKPADLTALAKELRAVEDVRPPHKVTDYSSSSEESGTTDEEDDDVEQEGADESTSGPEDTRAASSLNLSNGETESVKTMIVHDDVESEPAMTPSKEGTLIVRQTQSASSTLQKHKSSSSFTPFIDPRLLQISPSSGTTVTSVVGFSCDGMRPEAIRQDPTRKGSVVNVNPTNTRPQSDTPEIRKYKKRFNSEILCAALWGVNLLVGTESGLMLLDRSGQGKVYPLINRRRFQQMDVLEGLNVLVTISGKKDKLRVYYLSWLRNKILHNDPEVEKKQGWTTVGDLEGCVHYKVVKYERIKFLVIALKSSVEVYAWAPKPYHKFMAFKSFGELVHKPLLVDLTVEEGQRLKVIYGSCAGFHAVDVDSGSVYDIYLPTHIQCSIKPHAIIILPNTDGMELLVCYEDEGVYVNTYGRITKDVVLQWGEMPTSVAYIRSNQTMGWGEKAIEIRSVETGHLDGVFMHKRAQRLKFLCERNDKVFFASVRSGGSSQVYFMTLGRTSLLSW
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References
1 Smad inhibition by the Ste20 kinase Misshapen. Proc Natl Acad Sci USA. 2011 Jul 5;108(27):11127-32.
2 A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway. J Biol Chem. 1999 Jan 22;274(4):2118-25.
3 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.
4 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.
5 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.
6 DrugBank