Molecule Information

General Information of the Molecule (ID: Mol01829)

• Name: Janus kinase 1 (JAK-1) ,Homo sapiens
• Synonyms: Janus kinase 1; JAK-1; JAK1; JAK1A; JAK1B
• Molecule Type: Protein
• Gene Name: JAK1
• Gene ID: 3716
• Location: chr1:64,833,22965,067,754[-]
• Sequence:
  MQYLNIKEDCNAMAFCAKMRSSKKTEVNLEAPEPGVEVIFYLSDREPLRLGSGEYTAEEL
  CIRAAQACRISPLCHNLFALYDENTKLWYAPNRTITVDDKMSLRLHYRMRFYFTNWHGTN
  DNEQSVWRHSPKKQKNGYEKKKIPDATPLLDASSLEYLFAQGQYDLVKCLAPIRDPKTEQ
  DGHDIENECLGMAVLAISHYAMMKKMQLPELPKDISYKRYIPETLNKSIRQRNLLTRMRI
  NNVFKDFLKEFNNKTICDSSVSTHDLKVKYLATLETLTKHYGAEIFETSMLLISSENEMN
  WFHSNDGGNVLYYEVMVTGNLGIQWRHKPNVVSVEKEKNKLKRKKLENKHKKDEEKNKIR
  EEWNNFSYFPEITHIVIKESVVSINKQDNKKMELKLSSHEEALSFVSLVDGYFRLTADAH
  HYLCTDVAPPLIVHNIQNGCHGPICTEYAINKLRQEGSEEGMYVLRWSCTDFDNILMTVT
  CFEKSEQVQGAQKQFKNFQIEVQKGRYSLHGSDRSFPSLGDLMSHLKKQILRTDNISFML
  KRCCQPKPREISNLLVATKKAQEWQPVYPMSQLSFDRILKKDLVQGEHLGRGTRTHIYSG
  TLMDYKDDEGTSEEKKIKVILKVLDPSHRDISLAFFEAASMMRQVSHKHIVYLYGVCVRD
  VENIMVEEFVEGGPLDLFMHRKSDVLTTPWKFKVAKQLASALSYLEDKDLVHGNVCTKNL
  LLAREGIDSECGPFIKLSDPGIPITVLSRQECIERIPWIAPECVEDSKNLSVAADKWSFG
  TTLWEICYNGEIPLKDKTLIEKERFYESRCRPVTPSCKELADLMTRCMNYDPNQRPFFRA
  IMRDINKLEEQNPDIVSEKKPATEVDPTHFEKRFLKRIRDLGEGHFGKVELCRYDPEGDN
  TGEQVAVKSLKPESGGNHIADLKKEIEILRNLYHENIVKYKGICTEDGGNGIKLIMEFLP
  SGSLKEYLPKNKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIG
  DFGLTKAIETDKEYYTVKDDRDSPVFWYAPECLMQSKFYIASDVWSFGVTLHELLTYCDS
  DSSPMALFLKMIGPTHGQMTVTRLVNTLKEGKRLPCPPNCPDEVYQLMRKCWEFQPSNRT
  SFQNLIEGFEALLK
• Function: Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor as well as interleukin (IL)-10 receptor.
• Uniprot ID: JAK1_HUMAN
• Ensembl ID: ENSG00000162434
• HGNC ID: HGNC:6190

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Ruxolitinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Cholangiocarcinoma [1]

• Sensitive Disease: Cholangiocarcinoma [ICD-11: 2C12.0]
• Sensitive Drug: Ruxolitinib
• Molecule Alteration: Missense mutation; p.S703I (c.2108G>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: JAK1 cells; N.A.; .; N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Tumor volume measurement assay

Disease Class: Acute lymphocytic leukemia [2]

• Sensitive Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Sensitive Drug: Ruxolitinib
• Molecule Alteration: Missense mutation; p.S646F (c.1937C>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bone marrow; .
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Phosphoflow analysis
• Mechanism Description: The missense mutation p.S646F (c.1937C>T) in gene JAK1 cause the sensitivity of Ruxolitinib by aberration of the drug's therapeutic target

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.35E-01; Fold-change: 2.90E-02; Z-score: 4.42E-02
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 7.63E-01; Fold-change: 1.73E-02; Z-score: 3.11E-02
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 9.55E-01; Fold-change: 1.01E-01; Z-score: 1.35E-01

References

• Ref 1: Activating JAK1 mutation may predict the sensitivity of JAK-STAT inhibition in hepatocellular carcinomaOncotarget. 2016 Feb 2;7(5):5461-9. doi: 10.18632/oncotarget.6684.
• Ref 2: Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemiaBlood. 2012 Oct 25;120(17):3510-8. doi: 10.1182/blood-2012-03-415448. Epub 2012 Sep 6.