Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10127)
Regulator Name Tyrosine-protein phosphatase non-receptor type 6 (PTPN6)
Synonyms
HCP, PTP1C; Hematopoietic cell protein-tyrosine phosphatase; Protein-tyrosine phosphatase 1C; Protein-tyrosine phosphatase SHP-1; SH-PTP1
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Gene Name PTPN6
Gene ID 5777
Regulator Type Protein coding
Uniprot ID P29350
Sequence
MVRWFHRDLSGLDAETLLKGRGVHGSFLARPSRKNQGDFSLSVRVGDQVTHIRIQNSGDF
YDLYGGEKFATLTELVEYYTQQQGVLQDRDGTIIHLKYPLNCSDPTSERWYHGHMSGGQA
ETLLQAKGEPWTFLVRESLSQPGDFVLSVLSDQPKAGPGSPLRVTHIKVMCEGGRYTVGG
LETFDSLTDLVEHFKKTGIEEASGAFVYLRQPYYATRVNAADIENRVLELNKKQESEDTA
KAGFWEEFESLQKQEVKNLHQRLEGQRPENKGKNRYKNILPFDHSRVILQGRDSNIPGSD
YINANYIKNQLLGPDENAKTYIASQGCLEATVNDFWQMAWQENSRVIVMTTREVEKGRNK
CVPYWPEVGMQRAYGPYSVTNCGEHDTTEYKLRTLQVSPLDNGDLIREIWHYQYLSWPDH
GVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMENISTKGLDC
DIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFIETTKKKLEVLQSQKGQESEYGNIT
YPPAMKNAHAKASRTSSKHKEDVYENLHTKNKREEKVKKQRSADKEKSKGSLKRK

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Family Protein-tyrosine phosphatase family
Function
Modulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis.

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HGNC ID
HGNC:9658
KEGG ID hsa:5777
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
PTPN6 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
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Ubiquitin mediated proteolysis hsa04120
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Mahlavu cells Hepatoma Homo sapiens CVCL_0405
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
HA22T/VGH cells Hepatocellular carcinoma Homo sapiens CVCL_7046
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
PDX tumors in cold Dulbeccos Modified Eagles Medium (DMEM) were minced into 1-2 mm3 fragments, and each fragment was subcutaneously transplanted into the dorsal flank of 6-week-old male NSG (non-obese diabetic; severe combined immunodeficiency; interleukin-2 receptor gamma chain null) mice. Tumor growth was monitored by bidimensional tumor measurements with a caliper twice a week until the endpoint.

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Response regulation LIFR and SHP1 (PTPN6) positively regulate ferroptosis while LCN2 negatively regulates ferroptosis. Notably, an LCN2-neutralizing antibody enhances the ferroptosis-inducing and anticancer effects of sorafenib on hepatocellular carcinoma patient-derived xenograft tumors with low LIFR expression and high LCN2 expression.
Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Tyrosine-protein phosphatase non-receptor type 6 (PTPN6) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Ubiquitin mediated proteolysis hsa04120
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Mahlavu cells Hepatoma Homo sapiens CVCL_0405
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
HA22T/VGH cells Hepatocellular carcinoma Homo sapiens CVCL_7046
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
PDX tumors in cold Dulbeccos Modified Eagles Medium (DMEM) were minced into 1-2 mm3 fragments, and each fragment was subcutaneously transplanted into the dorsal flank of 6-week-old male NSG (non-obese diabetic; severe combined immunodeficiency; interleukin-2 receptor gamma chain null) mice. Tumor growth was monitored by bidimensional tumor measurements with a caliper twice a week until the endpoint.

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Response regulation LIFR and SHP1 (PTPN6) positively regulate ferroptosis while LCN2 negatively regulates ferroptosis. Notably, an LCN2-neutralizing antibody enhances the ferroptosis-inducing and anticancer effects of sorafenib on hepatocellular carcinoma patient-derived xenograft tumors with low LIFR expression and high LCN2 expression.
References
Ref 1 A targetable LIFR-NF-B-LCN2 axis controls liver tumorigenesis and vulnerability to ferroptosis. Nat Commun. 2021 Dec 17;12(1):7333. doi: 10.1038/s41467-021-27452-9.