Details of the Target

General Information of Target

Target ID LDTP06601
Target Name Hypoxia-inducible factor 1-alpha (HIF1A)
Gene Name HIF1A
Gene ID 3091
Synonyms
BHLHE78; MOP1; PASD8; Hypoxia-inducible factor 1-alpha; HIF-1-alpha; HIF1-alpha; ARNT-interacting protein; Basic-helix-loop-helix-PAS protein MOP1; Class E basic helix-loop-helix protein 78; bHLHe78; Member of PAS protein 1; PAS domain-containing protein 8
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVM
RLTISYLRVRKLLDAGDLDIEDDMKAQMNCFYLKALDGFVMVLTDDGDMIYISDNVNKYM
GLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKEQNTQRSFFLRMKCTLTSRGR
TMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSK
TFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQV
TTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIVCVNYVVSGIIQHDLIFSLQQTECV
LKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTET
DDQQLEEVPLYNDVMLPSPNEKLQNINLAMSPLPTAETPKPLRSSADPALNQEVALKLEP
NPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSPSEYCFYVDSDMVNEFKLELVEKLF
AEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVT
VFQQTQIQEPTANATTTTATTDELKTVTKDRMEDIKILIASPSPTHIHKETTSATSSPYR
DTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALSQRTTVPEEELNPKILALQNAQRKR
KMEHDGSLFQAVGIGTLLQQPDDHAATTSLSWKRVKGCKSSEQNGMEQKTIILIPSDLAC
RLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN
Target Type
Clinical trial
Target Bioclass
Transcription factor
Subcellular location
Cytoplasm
Function
Functions as a master transcriptional regulator of the adaptive response to hypoxia . 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 NCOA1 and/or NCOA2. Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.; (Microbial infection) Upon infection by human coronavirus SARS-CoV-2, is required for induction of glycolysis in monocytes and the consequent pro-inflammatory state. In monocytes, induces expression of ACE2 and cytokines such as IL1B, TNF, IL6, and interferons. Promotes human coronavirus SARS-CoV-2 replication and monocyte inflammatory response.
TTD ID
T51748
Uniprot ID
Q16665
DrugMap ID
TTQHWNA
Ensemble ID
ENST00000323441.10
HGNC ID
HGNC:4910
ChEMBL ID
CHEMBL4261

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CAL27 SNV: p.D283H .
COLO679 SNV: p.P236S .
FTC133 SNV: p.P45Q .
HCT15 SNV: p.S790N .
HT SNV: p.H744R .
JURKAT SNV: p.R463Q .
KMRC20 Insertion: p.L169SfsTer9 .
MFE319 SNV: p.L430S .
NCIH446 SNV: p.I677V .
OVK18 SNV: p.S58F .
RL SNV: p.S465T .
SH4 SNV: p.I198N .
SNU478 SNV: p.P452S .
SUIT2 SNV: p.R463Ter .
TOV21G SNV: p.L795P .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C90(3.59)  LDD3369  [1]
IA-alkyne
 Probe Info  		C780(17.76)  LDD1706  [2]
CY4
 Probe Info  		N.A.  LDD0247  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 AN3-CA C90(3.02)  LDD2264  [1]
 LDCM0023  KB03 AN3-CA C90(4.68)  LDD2681  [1]
 LDCM0024  KB05 OAW-42 C90(3.59)  LDD3369  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 13 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Histone acetyltransferase KAT2B (KAT2B) Acetyltransferase family Q92831
Fructose-1,6-bisphosphatase 1 (FBP1) FBPase class 1 family P09467
Ubiquitin carboxyl-terminal hydrolase 8 (USP8) Peptidase C19 family P40818
Proteasome subunit alpha type-4 (PSMA4) Peptidase T1A family P25789
E3 SUMO-protein ligase PIAS4 (PIAS4) PIAS family Q8N2W9
von Hippel-Lindau disease tumor suppressor (VHL) VHL family P40337
CREB-binding protein (CREBBP) . Q92793
E3 SUMO-protein ligase CBX4 (CBX4) . O00257
Egl nine homolog 1 (EGLN1) . Q9GZT9
Histone acetyltransferase p300 (EP300) . Q09472
Hypoxia-inducible factor 1-alpha inhibitor (HIF1AN) . Q9NWT6
Prolyl hydroxylase EGLN2 (EGLN2) . Q96KS0
Prolyl hydroxylase EGLN3 (EGLN3) . Q9H6Z9
Transporter and channel
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Beta-arrestin-1 (ARRB1) Arrestin family P49407
Neurogenic locus notch homolog protein 1 (NOTCH1) NOTCH family P46531
Protein OS-9 (OS9) OS-9 family Q13438
Transcription factor
Click To Hide/Show 9 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
X-box-binding protein 1 (XBP1) BZIP family P17861
Mothers against decapentaplegic homolog 3 (SMAD3) Dwarfin/SMAD family P84022
Androgen receptor (AR) Nuclear hormone receptor family P10275
Steroid hormone receptor ERR1 (ESRRA) Nuclear hormone receptor family P11474
Transcription factor Sp1 (SP1) Sp1 C2H2-type zinc-finger protein family P08047
Aryl hydrocarbon receptor nuclear translocator (ARNT) . P27540
Class E basic helix-loop-helix protein 41 (BHLHE41) . Q9C0J9
Metastasis-associated protein MTA1 (MTA1) . Q13330
Trans-acting T-cell-specific transcription factor GATA-3 (GATA3) . P23771
Other
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Catenin beta-1 (CTNNB1) Beta-catenin family P35222
ELL-associated factor 2 (EAF2) EAF family Q96CJ1
Small ubiquitin-related modifier 1 (SUMO1) Ubiquitin family P63165
UBX domain-containing protein 7 (UBXN7) . O94888

The Drug(s) Related To This Target

Approved
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Carvedilol Small molecular drug DB01136
Hydralazine Small molecular drug DB01275
Phase 4
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Hif-1alpha Small molecular drug D0B0AX
Phase 3
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
It-101 . D06PEW
Phase 2
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
2-methoxyestradiol Small molecular drug D06NYA
Phase 1
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Enmd-1198 Small molecular drug D0Y5QD
Px-478 Small molecular drug D06ZVO
Ezn-2968 . D0NF5J
Investigative
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Fg-2216 . DB08687
Vadadustat . DB12255
Patented
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Pyrrolidine Carboxamide Derivative 1 Small molecular drug D0Q2SE

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell. 2020 Aug 20;182(4):1009-1026.e29. doi: 10.1016/j.cell.2020.07.001. Epub 2020 Jul 29.
3 Cyclopropenone, Cyclopropeniminium Ion, and Cyclopropenethione as Novel Electrophilic Warheads for Potential Target Discovery of Triple-Negative Breast Cancer. J Med Chem. 2023 Feb 23;66(4):2851-2864. doi: 10.1021/acs.jmedchem.2c01889. Epub 2023 Feb 10.