Protein:HIF1A |
Protein Summary |
 Gene summary |
| Gene name: HIF1A | ASpdb.0 ID: 3091 | Gene | Gene symbol | HIF1A | Gene ID | 3091 |
| Gene name | hypoxia inducible factor 1 subunit alpha |
| Synonyms | HIF-1-alpha|HIF-1A|HIF-1alpha|HIF1|HIF1-ALPHA|MOP1|PASD8|bHLHe78 |
| Cytomap | 14q23.2 |
| Type of gene | protein-coding |
| Description | hypoxia-inducible factor 1-alphaARNT interacting proteinPAS domain-containing protein 8basic-helix-loop-helix-PAS protein MOP1class E basic helix-loop-helix protein 78hypoxia inducible factor 1 alpha subunithypoxia inducible factor 1, alpha subunit |
| Modification date | 20240416 |
| UniProtAcc | Q16665 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | HIF1A | GO:0000302 | response to reactive oxygen species | 32697943 |
| Gene | HIF1A | GO:0000785 | chromatin | 19782034 |
| Gene | HIF1A | GO:0000977 | RNA polymerase II transcription regulatory region sequence-specific DNA binding | 19782034 |
| Gene | HIF1A | GO:0000981 | DNA-binding transcription factor activity, RNA polymerase II-specific | 7539918|8756616 |
| Gene | HIF1A | GO:0000981 | DNA-binding transcription factor activity, RNA polymerase II-specific | 8387214|9079689 |
| Gene | HIF1A | GO:0001228 | DNA-binding transcription activator activity, RNA polymerase II-specific | 19782034 |
| Gene | HIF1A | GO:0001666 | response to hypoxia | 11782478 |
| Gene | HIF1A | GO:0001666 | response to hypoxia | 8756616|9887100|15261140|18419598 |
| Gene | HIF1A | GO:0001678 | intracellular glucose homeostasis | 30125331 |
| Gene | HIF1A | GO:0002039 | p53 binding | 15629713 |
| Gene | HIF1A | GO:0003700 | DNA-binding transcription factor activity | 11782478|15261140|18658046|25043030|30125331 |
| Gene | HIF1A | GO:0005634 | nucleus | 8089148|15261140|18658046|20810912|20972335|22848707|24048733|25043030 |
| Gene | HIF1A | GO:0005654 | nucleoplasm | - |
| Gene | HIF1A | GO:0005737 | cytoplasm | 19651758|24048733 |
| Gene | HIF1A | GO:0005829 | cytosol | 24681946 |
| Gene | HIF1A | GO:0006110 | regulation of glycolytic process | 32697943 |
| Gene | HIF1A | GO:0006355 | regulation of DNA-templated transcription | 11782478 |
| Gene | HIF1A | GO:0006355 | regulation of DNA-templated transcription | 15261140 |
| Gene | HIF1A | GO:0010468 | regulation of gene expression | 18419598|32697943 |
| Gene | HIF1A | GO:0010573 | vascular endothelial growth factor production | 12958148 |
| Gene | HIF1A | GO:0010575 | positive regulation of vascular endothelial growth factor production | 8756616 |
| Gene | HIF1A | GO:0010628 | positive regulation of gene expression | 15459207|24244340 |
| Gene | HIF1A | GO:0016604 | nuclear body | - |
| Gene | HIF1A | GO:0032364 | intracellular oxygen homeostasis | 16956324 |
| Gene | HIF1A | GO:0034599 | cellular response to oxidative stress | 8089148|8387214 |
| Gene | HIF1A | GO:0043565 | sequence-specific DNA binding | 7539918|8756616|9079689 |
| Gene | HIF1A | GO:0045893 | positive regulation of DNA-templated transcription | 9887100|25043030 |
| Gene | HIF1A | GO:0045944 | positive regulation of transcription by RNA polymerase II | 7539918|8089148|8387214|11573933|22735262|32697943 |
| Gene | HIF1A | GO:0046886 | positive regulation of hormone biosynthetic process | 1448077 |
| Gene | HIF1A | GO:0051879 | Hsp90 protein binding | 9079689 |
| Gene | HIF1A | GO:0070101 | positive regulation of chemokine-mediated signaling pathway | 17178876 |
| Gene | HIF1A | GO:0071456 | cellular response to hypoxia | 11573933|19528298|20889502|22735262 |
| Gene | HIF1A | GO:0090575 | RNA polymerase II transcription regulator complex | 7539918|8756616 |
| Gene | HIF1A | GO:0098586 | cellular response to virus | 32697943 |
| Gene | HIF1A | GO:1900017 | positive regulation of cytokine production involved in inflammatory response | 32697943 |
| Gene | HIF1A | GO:1902895 | positive regulation of miRNA transcription | 19782034 |
| Gene | HIF1A | GO:1903377 | negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway | 24899725 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| Q16665-1 | Q16665-1_4h6j_A.pdb | 4H6J | X-ray | 1.52 | A | 238 | 343 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| Q16665 | HIF1A | Q16665-1 | Q16665-2 | 826 | 735 | 735 | 735 | Substitution | G | I | 735 | 735 |
| Q16665 | HIF1A | Q16665-1 | Q16665-2 | 826 | 735 | 736 | 826 | Deletion | none | none | 735 | 735 |
| Q16665 | HIF1A | Q16665-1 | Q16665-3 | 826 | 850 | 1 | 12 | Substitution | MEGAGGANDKKK | MSSQCRSLENKFVFLKEGLGNSKPEELEEIRIENGR | 1 | 36 |
| Multiple sequence alignment of our canonical and alternatively spliced HIF1A |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of HIF1A |
| UniProt-id | ENSG | ENST | ENSP |
| Q16665-1 | ENSG00000100644.17 | ENST00000337138.9 | ENSP00000338018.4 |
| Q16665-2 | ENSG00000100644.17 | ENST00000323441.10 | ENSP00000323326.6 |
| Q16665-3 | ENSG00000100644.17 | ENST00000539097.2 | ENSP00000437955.1 |
| UniProt-id | NM ID | NP ID |
| Q16665-1 | NM_001530.3 | NP_001521.1 |
| Q16665-2 | NM_181054.2 | NP_851397.1 |
| Q16665-3 | NM_001243084.1 | NP_001230013.1 |
| Amino acid sequences of our canonical and alternatively spliced HIF1A |
| accession_id | Protein sequence |
| Q16665-1 | MEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDAGDLDIEDDMKAQMNC FYLKALDGFVMVLTDDGDMIYISDNVNKYMGLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKEQNTQRSFFLRMKCTLTSRGR TMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSKTFLSRHSLDMKFSYCDERITELMGYEPEEL LGRSIYEYYHALDSDHLTKTHHDMFTKGQVTTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIVCVNYVVSGIIQHDLIFSLQQTECV LKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTETDDQQLEEVPLYNDVMLPSPNEKLQNINLAM SPLPTAETPKPLRSSADPALNQEVALKLEPNPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSPSEYCFYVDSDMVNEFKLELVEKLF AEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVTVFQQTQIQEPTANATTTTATTDELKTVTKD RMEDIKILIASPSPTHIHKETTSATSSPYRDTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALSQRTTVPEEELNPKILALQNAQRKR KMEHDGSLFQAVGIGTLLQQPDDHAATTSLSWKRVKGCKSSEQNGMEQKTIILIPSDLACRLLGQSMDESGLPQLTSYDCEVNAPIQGSR |
| Q16665-2 | MEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDAGDLDIEDDMKAQMNC FYLKALDGFVMVLTDDGDMIYISDNVNKYMGLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKEQNTQRSFFLRMKCTLTSRGR TMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSKTFLSRHSLDMKFSYCDERITELMGYEPEEL LGRSIYEYYHALDSDHLTKTHHDMFTKGQVTTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIVCVNYVVSGIIQHDLIFSLQQTECV LKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTETDDQQLEEVPLYNDVMLPSPNEKLQNINLAM SPLPTAETPKPLRSSADPALNQEVALKLEPNPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSPSEYCFYVDSDMVNEFKLELVEKLF AEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVTVFQQTQIQEPTANATTTTATTDELKTVTKD RMEDIKILIASPSPTHIHKETTSATSSPYRDTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALSQRTTVPEEELNPKILALQNAQRKR |
| Q16665-3 | MSSQCRSLENKFVFLKEGLGNSKPEELEEIRIENGRISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISY LRVRKLLDAGDLDIEDDMKAQMNCFYLKALDGFVMVLTDDGDMIYISDNVNKYMGLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVK KGKEQNTQRSFFLRMKCTLTSRGRTMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSKTFLSRH SLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQVTTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIV CVNYVVSGIIQHDLIFSLQQTECVLKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTETDDQQLE EVPLYNDVMLPSPNEKLQNINLAMSPLPTAETPKPLRSSADPALNQEVALKLEPNPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSP SEYCFYVDSDMVNEFKLELVEKLFAEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVTVFQQTQ IQEPTANATTTTATTDELKTVTKDRMEDIKILIASPSPTHIHKETTSATSSPYRDTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALS QRTTVPEEELNPKILALQNAQRKRKMEHDGSLFQAVGIGTLLQQPDDHAATTSLSWKRVKGCKSSEQNGMEQKTIILIPSDLACRLLGQS |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| HIF1A (go to UniProt):Q16665 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Q16665 | Region | 1 | 401 | Note=Interaction with TSGA10;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q61221 | Type=Substitution;Start=1;End=12 |
| Q16665 | Region | 1 | 30 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=1;End=12 |
| Q16665 | Region | 576 | 785 | Note=ID | Type=Substitution;Start=735;End=735 |
| Q16665 | Region | 576 | 785 | Note=ID | Type=Deletion;Start=736;End=826 |
| Q16665 | Region | 786 | 826 | "Note=CTAD;Ontology_term=ECO:0000303 | ECO:0000303;evidence=ECO:0000303|PubMed:10202154 |
Gene Isoform Structures and Expression Levels for HIF1A |
| Gene structures of our canonical and alternative spliced genes of HIF1A * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
 |
| Expression levels of gene isoforms across TCGA. |
 |
Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of Q16665-1 |
| 3D view using mol* of Q16665-2 |
| 3D view using mol* of Q16665-3 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of Q16665-1 |
 |
| pLDDT distribution across the protein length of Q16665-2 |
 |
| pLDDT distribution across the protein length of Q16665-3 |
 |
Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of Q16665-1 |
 |
| Ramachandran plot of Q16665-2 |
 |
| Ramachandran plot of Q16665-3 |
 |
Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| Q16665-1 | 1.047 | 112 | 1.108 | 266.511 | 0.559 | 0.681 | 0.883 | 0.945 | 0.738 | 1.281 | 1.103 | 233,234,235,236,237,239,243,254,256,257,258,261,52 7,529,530,531,532,533,535,536,537,539 |
| Q16665-2 | 1.089 | 357 | 1.151 | 1095.199 | 0.505 | 0.736 | 0.954 | 1.438 | 0.709 | 2.028 | 1.194 | 44,45,46,62,65,66,69,70,72,73,76,77,78,79,84,85,88 ,89,90,92,93,94,96,97,100,102,110,111,112,113,114, 115,116,117,118,119,123,124,125,128,164,195,196,19 7,199,201,221,222,223,635,636,637,638,639,640,641, 642,643,735 |
| Q16665-3 | 1.136 | 116 | 1.203 | 292.922 | 0.465 | 0.788 | 1.095 | 2.003 | 0.645 | 3.107 | 1.2 | 116,117,119,120,124,188,219,220,221,223,245,246,24 7,794,795,796,797,798,800,802,803,806 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
 |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of Q16665-1_Q16665-1_4h6j_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q16665-1_4h6j_A_Q16665-2.pdb |
| 3D view using mol* of Q16665-1_4h6j_A_Q16665-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q16665-1_Q16665-2.pdb |
| 3D view using mol* of Q16665-1_Q16665-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q16665-1_vs_Q16665-2.png |
 < |
| ./stats/secondary_structure/figure/Q16665-1_vs_Q16665-3.png |
 < |
| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q16665-1_vs_Q16665-2.png |
 < |
| ./stats/relative_asa/Q16665-1_vs_Q16665-3.png |
 < |
Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Q16665 | Region | 1 | 401 | Note=Interaction with TSGA10;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q61221 | Type=Substitution;Start=1;End=12 |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to HIF1A |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| Q16665 | HIF1A | DB01136 | Carvedilol | approved, investigational | modulator |
| Q16665 | HIF1A | DB02342 | 2-Methoxyestradiol | investigational | |
| Q16665 | HIF1A | DB05959 | ENMD-1198 | investigational | |
| Q16665 | HIF1A | DB08687 | FG-2216 | investigational | |
| Q16665 | HIF1A | DB01275 | Hydralazine | approved | inducer |
| Q16665 | HIF1A | DB06082 | PX-478 | investigational | inhibitor |
| Q16665 | HIF1A | DB12255 | Vadadustat | approved, investigational | stabilization |
Related Diseases to HIF1A |
| Previous studies relating to the alternative splicing of HIF1A and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| HIF1A | 20416395 | Hypoxia-inducible factor (HIF)-3alpha is subject to extensive alternative splicing in human tissues and cancer cells and is regulated by HIF-1 but not HIF-2. | The hypoxia-inducible transcription factors (HIFs) play a central role in the response of cells to hypoxia. HIFs are alphabeta dimers, the human alpha subunit having three isoforms. HIF-3alpha is unique among the HIF-alpha isoforms in that its gene is subject to extensive alternative splicing. Database analyses have predicted the generation of six HIF-3alpha splice variants that utilize three alternative transcription initiation sites. None of these variants is likely to act as an efficient transcription factor, but some of them have been reported to inhibit HIF-1 and HIF-2 functions. We analyzed here for the first time in detail whether these six variants are indeed generated in various human tissues and cell lines. We identified four novel variants, named here HIF-3alpha7 to HIF-3alpha10, whereas we obtained no evidence for the predicted HIF-3alpha3 and HIF-3alpha5. Distinct differences in the expression patterns of the variants were found between human tissues, the levels being particularly low in many cancer cell lines. Hypoxia upregulated transcription from all three alternative HIF-3alpha promoters. siRNA experiments showed that this induction is mediated specifically by HIF-1 and not by HIF-2. The tissue-specific differences in the expression patterns and levels of the HIF-3alpha variants can be expected to modulate the hypoxia response of various tissues and cell types to different extents during development and in pathological situations. A further level of regulation is brought about by the fact that the levels of the HIF-3alpha transcripts themselves are regulated by hypoxia and by changes in HIF-1 levels. | D009369 | Neoplasms |
Clinically important variants in HIF1A |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
Copyright 2024-PresentThe University of Texas Health Science Center at Houston (UTHealth Houston) Web File Viewing | Emergency Information |