Details of Protein

General Information of Protein (ID: PRT01085)
Name Hypoxia-inducible factor 1-alpha (HIF1A)
Synonyms   Click to Show/Hide Synonyms of This Protein
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; HIF1A; BHLHE78; MOP1; PASD8
Gene Name HIF1A Gene ID
3091
UniProt ID
Q16665
Family Transcription factor (TF)
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVM
RLTISYLRVRKLLDAGDLDIEDDMKAQMNCFYLKALDGFVMVLTDDGDMIYISDNVNKYM
GLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKEQNTQRSFFLRMKCTLTSRGR
TMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSK
TFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQV
TTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIVCVNYVVSGIIQHDLIFSLQQTECV
LKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTET
DDQQLEEVPLYNDVMLPSPNEKLQNINLAMSPLPTAETPKPLRSSADPALNQEVALKLEP
NPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSPSEYCFYVDSDMVNEFKLELVEKLF
AEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVT
VFQQTQIQEPTANATTTTATTDELKTVTKDRMEDIKILIASPSPTHIHKETTSATSSPYR
DTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALSQRTTVPEEELNPKILALQNAQRKR
KMEHDGSLFQAVGIGTLLQQPDDHAATTSLSWKRVKGCKSSEQNGMEQKTIILIPSDLAC
RLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN
Structure
1D7G ; 1H2K ; 1H2L ; 1H2M ; 1L3E ; 1L8C ; 1LM8 ; 1LQB ; 2ILM ; 3HQR ; 3HQU ; 4AJY ; 4H6J ; 5JWP ; 5L9B ; 5L9V ; 5LA9 ; 5LAS ; 6GFX ; 6GMR ; 6YW3
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 both, NCOA1 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 proinflammatory 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.
Regulatory Network
Full List of Metabolite(s) Regulated by This Protein
      Nucleosides, nucleotides, and analogues
            ATP Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Inhibition (YC-1) of HIF1A
                      Induced Change ATP concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hepatocellular carcinoma [ICD-11: 2C12]
                      Details It is reported that inhibition of HIF1A leads to the decrease of ATP levels compared with control group.
      Lipids and lipid-like molecules
            DG(18:3n3/0:0/18:3n3) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of HIF1A
                      Induced Change DG(18:3n3/0:0/18:3n3) concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockout of HIF1A leads to the increase of DG(18:3n3/0:0/18:3n3) levels compared with control group.
            Glycerol 3-phosphate Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of HIF1A
                      Induced Change Glycerol 3-phosphate concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockout of HIF1A leads to the decrease of glycerol 3-phosphate levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of HIF1A
                      Induced Change Glycerol 3-phosphate concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockout of HIF1A leads to the increase of glycerol 3-phosphate levels compared with control group.
            MG(24:1(15Z)/0:0/0:0) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of HIF1A
                      Induced Change MG(24:1(15Z)/0:0/0:0) concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockout of HIF1A leads to the increase of MG(24:1(15Z)/0:0/0:0) levels compared with control group.
            Oleic acid Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of HIF1A
                      Induced Change Oleic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockout of HIF1A leads to the increase of oleic acid levels compared with control group.
            Palmitic acid Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of HIF1A
                      Induced Change Palmitic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockout of HIF1A leads to the increase of palmitic acid levels compared with control group.
            Stearic acid Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of HIF1A
                      Induced Change Stearic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockout of HIF1A leads to the increase of stearic acid levels compared with control group.
            TG(15:0/15:0/21:0) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of HIF1A
                      Induced Change TG(15:0/15:0/21:0) concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockout of HIF1A leads to the increase of TG(15:0/15:0/21:0) levels compared with control group.
      Organic acids and derivatives
            Phosphatidylcholine O-34:2 Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of HIF1A
                      Induced Change Phosphatidylcholine O-34:2 concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockout of HIF1A leads to the increase of phosphatidylcholine O-34:2 levels compared with control group.
      Organic nitrogen compounds
            Choline Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of HIF1A
                      Induced Change Choline concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockout of HIF1A leads to the increase of choline levels compared with control group.
            Phosphorylcholine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of HIF1A
                      Induced Change Phosphorylcholine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockout of HIF1A leads to the increase of phosphorylcholine levels compared with control group.
      Organic oxygen compounds
            Glucose Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Inhibition (YC-1) of HIF1A
                      Induced Change Glucose concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hepatocellular carcinoma [ICD-11: 2C12]
                      Details It is reported that inhibition of HIF1A leads to the decrease of glucose levels compared with control group.
            Glycerol Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of HIF1A
                      Induced Change Glycerol concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockout of HIF1A leads to the decrease of glycerol levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of HIF1A
                      Induced Change Glycerol concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockout of HIF1A leads to the increase of glycerol levels compared with control group.
Full List of Metabolite(s) Regulating This Protein
      Organic acids and derivatives
            Lactic acid Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Lactic acid addition (6 hours)
                      Induced Change HIF1A protein expression levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Cervical Cancer [ICD-11: 2C77]
                      Details It is reported that lactic acid addition causes the increase of HIF1A protein expression compared with control group.
References
1 Orexin A affects HepG2 human hepatocellular carcinoma cells glucose metabolism via HIF-1-dependent and -independent mechanism. PLoS One. 2017 Sep 8;12(9):e0184213.
2 Hypoxia induces a lipogenic cancer cell phenotype via HIF1-dependent and -independent pathways. Oncotarget. 2015 Feb 10;6(4):1920-41.
3 Lactate promotes glutamine uptake and metabolism in oxidative cancer cells. Cell Cycle. 2016;15(1):72-83.

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