Molecule Details

General Information of the Molecule

Name

Hypoxia-inducible factor 1 alpha (HIF-1A)

Synonyms

bHLHe78; Transcription factor HIF-1; PASD8; PAS domain-containing protein 8; Member of PAS protein 1; MOP1; Hypoxia-inducible transcription factor (HIF)-1; Hypoxia-inducible factor 1-alpha; Hypoxia-inducible factor 1 A; Hypoxia inducible factor 1; HIF1-alpha; HIF1 alpha; HIF-1alpha; HIF-1-alpha; HIF-1 alpha; Class E basic helix-loop-helix protein 78; Basic-helix-loop-helix-PAS protein MOP1; ARNT-interacting protein; ARNT interacting protein

Gene Name

HIF1A

Gene ID

3091

Sequence

MEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVM
RLTISYLRVRKLLDAGDLDIEDDMKAQMNCFYLKALDGFVMVLTDDGDMIYISDNVNKYM
GLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKEQNTQRSFFLRMKCTLTSRGR
TMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSK
TFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQV
TTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIVCVNYVVSGIIQHDLIFSLQQTECV
LKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTET
DDQQLEEVPLYNDVMLPSPNEKLQNINLAMSPLPTAETPKPLRSSADPALNQEVALKLEP
NPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSPSEYCFYVDSDMVNEFKLELVEKLF
AEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVT
VFQQTQIQEPTANATTTTATTDELKTVTKDRMEDIKILIASPSPTHIHKETTSATSSPYR
DTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALSQRTTVPEEELNPKILALQNAQRKR
KMEHDGSLFQAVGIGTLLQQPDDHAATTSLSWKRVKGCKSSEQNGMEQKTIILIPSDLAC
RLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN

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Function

Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia. Functions as a master transcriptional regulator of the adaptive response to hypoxia.

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Uniprot ID

HIF1A_HUMAN

Pfam

PF11413 ; PF08778 ; PF00989 ; PF08447

KEGG ID

hsa3091

TTD ID

T55610

A List of Drug Combination(s) Able to Regulate This Molecule

Expression Regulation

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Down-regulation

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Drug Combination 1 Down-regulating the Expression of This Molecule

[1]

Detail(s)

Combination Info

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Name

Pterostilbene NP Info

Vorinostat Drug Info

Structure

Drug Combination 2 Down-regulating the Expression of This Molecule

[2]

Detail(s)

Combination Info

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Name

Apigenin NP Info

Gefitinib Drug Info

Structure

Drug Combination 3 Down-regulating the Expression of This Molecule

[3]

Detail(s)

Combination Info

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Name

Curcumin NP Info

Sorafenib Drug Info

Structure

Drug Combination 4 Down-regulating the Expression of This Molecule

[4]

Detail(s)

Combination Info

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Name

Curcumin NP Info

Cisplatin Drug Info

Structure

Drug Combination 5 Down-regulating the Expression of This Molecule

[5]

Detail(s)

Combination Info

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Name

Noscapine NP Info

Cisplatin Drug Info

Structure

Drug Combination 6 Down-regulating the Expression of This Molecule

[6]

Detail(s)

Combination Info

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Name

Ursolic acid NP Info

Cisplatin Drug Info

Structure

Up-regulation

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Drug Combination 1 Up-regulating the Expression of This Molecule

[7]

Detail(s)

Combination Info

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Name

Arsenic trioxide NP Info

PX-478 Drug Info

Structure

Drug Combination 2 Up-regulating the Expression of This Molecule

[8]

Detail(s)

Combination Info

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Name

Arsenic trioxide NP Info

Cisplatin Drug Info

Structure

Natural Product(s) of This Target

Cardamonin

NP Info

Investigative

Alpinia zerumbet

Drug(s) of This Target

2-methoxyestradiol

Drug Info

Phase 2

Pulmonary hypertension

PX-478

Drug Info

Phase 1

Solid tumour/cancer

References

Reference 1

Targeting MTA1/HIF-1Alpha signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression. Cancer Med. 2017 Nov;6(11):2673-2685.

Reference 2

Apigenin Combined With Gefitinib Blocks Autophagy Flux and Induces Apoptotic Cell Death Through Inhibition of HIF-1alpha, c-Myc, p-EGFR, and Glucose Metabolism in EGFR L858R+T790M-Mutated H1975 Cells. Front Pharmacol. 2019 Mar 22;10:260.

Reference 3

Combinatorial anticancer effects of curcumin and sorafenib towards thyroid cancer cells via PI3K/Akt and ERK pathways. Nat Prod Res. 2016 Aug;30(16):1858-61.

Reference 4

Curcumin sensitizes lung cancer cells to cisplatin-induced apoptosis through superoxide anion-mediated Bcl-2 degradation. Cancer Invest. 2009 Jul;27(6):624-35.

Reference 5

Noscapine sensitizes chemoresistant ovarian cancer cells to cisplatin through inhibition of HIF-1Alpha. Cancer Lett. 2011 Jun 1;305(1):94-9.

Reference 6

Ursolic acid inhibits proliferation and reverses drug resistance of ovarian cancer stem cells by downregulating ABCG2 through suppressing the expression of hypoxia-inducible factor-1alpha in vitro. Oncol Rep. 2016 Jul;36(1):428-40.

Reference 7

Arsenic trioxide plus PX-478 achieves effective treatment in pancreatic ductal adenocarcinoma. Cancer Lett. 2016 Aug 10;378(2):87-96.

Reference 8

Co-application of arsenic trioxide (As2O3) and cisplatin (CDDP) on human SY-5Y neuroblastoma cells has differential effects on the intracellular calcium concentration ([Ca2+]i) and cytotoxicity. Neurotoxicology. 2009 Mar;30(2):194-202.

Reference 9

Cardamonin inhibits breast cancer growth by repressing HIF-1Alpha-dependent metabolic reprogramming. J Exp Clin Cancer Res. 2019 Aug 27;38(1):377.

Reference 10

2-methoxyestradiol inhibits hypoxia-inducible factor 1alpha, tumor growth, and angiogenesis and augments paclitaxel efficacy in head and neck squam... Clin Cancer Res. 2004 Dec 15;10(24):8665-73.

Reference 11

The selective hypoxia inducible factor-1 inhibitor PX-478 provides in vivo radiosensitization through tumor stromal effects. Mol Cancer Ther. 2009 Apr;8(4):947-58.

Molecule Details

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Correspondence

Prof. Feng ZHU (zhufeng@zju.edu.cn)

Prof. Xinbing SUI (hzzju@hznu.edu.cn)