Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10201)
Regulator Name Tyrosine-protein kinase receptor TYRO3 (TYRO3)
Synonyms
BYK, DTK, RSE, SKY, TIF; Tyrosine-protein kinase BYK; Tyrosine-protein kinase DTK; Tyrosine-protein kinase RSE; Tyrosine-protein kinase SKY; Tyrosine-protein kinase TIF
    Click to Show/Hide
Gene Name TYRO3
Gene ID 7301
Regulator Type Protein coding
Uniprot ID Q06418
Sequence
MALRRSMGRPGLPPLPLPPPPRLGLLLAALASLLLPESAAAGLKLMGAPVKLTVSQGQPV
KLNCSVEGMEEPDIQWVKDGAVVQNLDQLYIPVSEQHWIGFLSLKSVERSDAGRYWCQVE
DGGETEISQPVWLTVEGVPFFTVEPKDLAVPPNAPFQLSCEAVGPPEPVTIVWWRGTTKI
GGPAPSPSVLNVTGVTQSTMFSCEAHNLKGLASSRTATVHLQALPAAPFNITVTKLSSSN
ASVAWMPGADGRALLQSCTVQVTQAPGGWEVLAVVVPVPPFTCLLRDLVPATNYSLRVRC
ANALGPSPYADWVPFQTKGLAPASAPQNLHAIRTDSGLILEWEEVIPEAPLEGPLGPYKL
SWVQDNGTQDELTVEGTRANLTGWDPQKDLIVRVCVSNAVGCGPWSQPLVVSSHDRAGQQ
GPPHSRTSWVPVVLGVLTALVTAAALALILLRKRRKETRFGQAFDSVMARGEPAVHFRAA
RSFNRERPERIEATLDSLGISDELKEKLEDVLIPEQQFTLGRMLGKGEFGSVREAQLKQE
DGSFVKVAVKMLKADIIASSDIEEFLREAACMKEFDHPHVAKLVGVSLRSRAKGRLPIPM
VILPFMKHGDLHAFLLASRIGENPFNLPLQTLIRFMVDIACGMEYLSSRNFIHRDLAARN
CMLAEDMTVCVADFGLSRKIYSGDYYRQGCASKLPVKWLALESLADNLYTVQSDVWAFGV
TMWEIMTRGQTPYAGIENAEIYNYLIGGNRLKQPPECMEDVYDLMYQCWSADPKQRPSFT
CLRMELENILGQLSVLSASQDPLYINIERAEEPTAGGSLELPGRDQPYSGAGDGSGMGAV
GGTPSDCRYILTPGGLAEQPGQAEHQPESPLNETQRLLLLQQGLLPHSSC

    Click to Show/Hide
Family Tyr protein kinase family
Function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of TYRO3 on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with PIK3R1 and thereby enhances PI3-kinase activity. Activates the AKT survival pathway, including nuclear translocation of NF-kappa-B and up-regulation of transcription of NF-kappa-B-regulated genes. TYRO3 signaling plays a role in various processes such as neuron protection from excitotoxic injury, platelet aggregation and cytoskeleton reorganization. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.

    Click to Show/Hide
HGNC ID
HGNC:12446
KEGG ID hsa:7301
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
TYRO3 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Nuclear factor erythroid 2-related factor 2 (NFE2L2) [Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 4T1 cells Mammary carcinoma Mus musculus CVCL_0125
HEK-293T cells Normal Homo sapiens CVCL_0063
B16-F10 cells Melanoma Mus musculus CVCL_0159
BT-549 cells Invasive breast carcinoma Homo sapiens CVCL_1092
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
Py8119 cells Breast carcinoma Mus musculus CVCL_AQ09
In Vivo Model
Six-week-old BALB/c mice were purchased from The Jackson Laboratory. Mouse 4T1 cells (5 x 104 cells) in 50 uL of 50% Matrigel (47743-720, Corning) were injected into the mammary fat pad. Three days after inoculation, 100 ug mouse anti-PD-1 antibody (BE0146, Bio X Cell) or IgG control (BE0089, Bio X Cell) was injected intraperitoneally twice a week for a total of 5 injections. For the TYRO3 inhibitor and antimPD-1 combination treatment, mice were also treated daily with vehicle control (90% polyethylene glycol 400 and 10% DMSO) or LDC1267 (20 mg/kg, S7638, Selleck Chemical) for 10 days by intraperitoneal injection.

    Click to Show/Hide
Response regulation The study proposed a model in which high expression of TYRO3 or TYRO3 activation by its ligands on apoptotic cells triggers the downstream AKT/NRF2 pathway, followed by the transcription of genes that inhibit ferroptosis in Mammary carcinoma.
Breast cancer [ICD-11: 2C60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Tyrosine-protein kinase receptor TYRO3 (TYRO3) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 4T1 cells Mammary carcinoma Mus musculus CVCL_0125
HEK-293T cells Normal Homo sapiens CVCL_0063
B16-F10 cells Melanoma Mus musculus CVCL_0159
BT-549 cells Invasive breast carcinoma Homo sapiens CVCL_1092
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
Py8119 cells Breast carcinoma Mus musculus CVCL_AQ09
In Vivo Model
Six-week-old BALB/c mice were purchased from The Jackson Laboratory. Mouse 4T1 cells (5 x 104 cells) in 50 uL of 50% Matrigel (47743-720, Corning) were injected into the mammary fat pad. Three days after inoculation, 100 ug mouse anti-PD-1 antibody (BE0146, Bio X Cell) or IgG control (BE0089, Bio X Cell) was injected intraperitoneally twice a week for a total of 5 injections. For the TYRO3 inhibitor and antimPD-1 combination treatment, mice were also treated daily with vehicle control (90% polyethylene glycol 400 and 10% DMSO) or LDC1267 (20 mg/kg, S7638, Selleck Chemical) for 10 days by intraperitoneal injection.

    Click to Show/Hide
Response regulation The study proposed a model in which high expression of TYRO3 or TYRO3 activation by its ligands on apoptotic cells triggers the downstream AKT/NRF2 pathway, followed by the transcription of genes that inhibit ferroptosis in Mammary carcinoma.
References
Ref 1 TYRO3 induces anti-PD-1/PD-L1 therapy resistance by limiting innate immunity and tumoral ferroptosis. J Clin Invest. 2021 Apr 15;131(8):e139434. doi: 10.1172/JCI139434.