General Information of the Ferroptosis Regulator (ID: REG10428)
Regulator Name Transportin-1 (TNPO1)
Synonyms
KPNB2; MIP1; TRN; Importin beta-2; Karyopherin beta-2; M9 region interaction protein
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Gene Name TNPO1
Gene ID 3842
Regulator Type Protein coding
Uniprot ID Q92973
Sequence
MVWDRQTKMEYEWKPDEQGLQQILQLLKESQSPDTTIQRTVQQKLEQLNQYPDFNNYLIF
VLTKLKSEDEPTRSLSGLILKNNVKAHFQNFPNGVTDFIKSECLNNIGDSSPLIRATVGI
LITTIASKGELQNWPDLLPKLCSLLDSEDYNTCEGAFGALQKICEDSAEILDSDVLDRPL
NIMIPKFLQFFKHSSPKIRSHAVACVNQFIISRTQALMLHIDSFIENLFALAGDEEPEVR
KNVCRALVMLLEVRMDRLLPHMHNIVEYMLQRTQDQDENVALEACEFWLTLAEQPICKDV
LVRHLPKLIPVLVNGMKYSDIDIILLKGDVEEDETIPDSEQDIRPRFHRSRTVAQQHDED
GIEEEDDDDDEIDDDDTISDWNLRKCSAAALDVLANVYRDELLPHILPLLKELLFHHEWV
VKESGILVLGAIAEGCMQGMIPYLPELIPHLIQCLSDKKALVRSITCWTLSRYAHWVVSQ
PPDTYLKPLMTELLKRILDSNKRVQEAACSAFATLEEEACTELVPYLAYILDTLVFAFSK
YQHKNLLILYDAIGTLADSVGHHLNKPEYIQMLMPPLIQKWNMLKDEDKDLFPLLECLSS
VATALQSGFLPYCEPVYQRCVNLVQKTLAQAMLNNAQPDQYEAPDKDFMIVALDLLSGLA
EGLGGNIEQLVARSNILTLMYQCMQDKMPEVRQSSFALLGDLTKACFQHVKPCIADFMPI
LGTNLNPEFISVCNNATWAIGEISIQMGIEMQPYIPMVLHQLVEIINRPNTPKTLLENTA
ITIGRLGYVCPQEVAPMLQQFIRPWCTSLRNIRDNEEKDSAFRGICTMISVNPSGVIQDF
IFFCDAVASWINPKDDLRDMFCKILHGFKNQVGDENWRRFSDQFPLPLKERLAAFYGV

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Family Importin beta family
Function
Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. May mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). Involved in nuclear import of M9-containing proteins. In vitro, binds directly to the M9 region of the heterogeneous nuclear ribonucleoproteins (hnRNP), A1 and A2 and mediates their nuclear import. Involved in hnRNP A1/A2 nuclear export. Mediates the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5. In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones (By similarity). In vitro, mediates nuclear import of SRP19. Mediates nuclear import of ADAR/ADAR1 isoform 1 and isoform 5 in a RanGTP-dependent manner.; (Microbial infection) In case of HIV-1 infection, binds and mediates the nuclear import of HIV-1 Rev.

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HGNC ID
HGNC:6401
KEGG ID hsa:3842
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
TNPO1 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
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Oesophageal cancer ICD-11: 2B70
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
Eca-109 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_6898
In Vivo Model
Nude mice of both sexes (age: 6-8 weeks, weight: 22-25 g) were purchased from HUNAN SJA LABRATORY ANIMAL CO., LTD (Hunan, China). The EC109 cells stably expressing sh-circBCAR3 or sh-nc were established by infection with corresponding lentivirus vectors. 1 x 106 mL-1 (100 uL) cells were subcutaneously inoculated into the nude mice. The tumor volumes had been measured from day 5 to day 25. On day 25, the xenograft tumors were removed surgically, and the tumor weight was detected.

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Response regulation CircBCAR3 binds with miR-27a-3p to promote TNPO1 expression. GPX4 protein levels were increased by silencing of circBCAR3. And circBCAR3 promoted the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells by miR-27a-3p.
Oesophageal cancer [ICD-11: 2B70]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Transportin-1 (TNPO1) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
Eca-109 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_6898
In Vivo Model
Nude mice of both sexes (age: 6-8 weeks, weight: 22-25 g) were purchased from HUNAN SJA LABRATORY ANIMAL CO., LTD (Hunan, China). The EC109 cells stably expressing sh-circBCAR3 or sh-nc were established by infection with corresponding lentivirus vectors. 1 x 106 mL-1 (100 uL) cells were subcutaneously inoculated into the nude mice. The tumor volumes had been measured from day 5 to day 25. On day 25, the xenograft tumors were removed surgically, and the tumor weight was detected.

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Response regulation CircBCAR3 binds with miR-27a-3p to promote TNPO1 expression. GPX4 protein levels were increased by silencing of circBCAR3. And circBCAR3 promoted the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells by miR-27a-3p.
References
Ref 1 CircBCAR3 accelerates esophageal cancer tumorigenesis and metastasis via sponging miR-27a-3p. Mol Cancer. 2022 Jul 15;21(1):145. doi: 10.1186/s12943-022-01615-8.