HIF1A
Hypoxia-inducible factor 1-alpha
Also known as: bHLHe78, HIF-1alpha, HIF1, HIF1A_HUMAN, MOP1, PASD8
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q16665
- Gene
- HIF1A
- Ensembl
- ENSG00000100644
- Chromosome
- 14
- Canonical length
- 826 aa
- Protein class
- Cancer-related genes, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Transcription factors
- Subcellular location
- Nucleoplasm,Nuclear bodies
OverviewNCBI Gene
This gene encodes the alpha subunit of transcription factor hypoxia-inducible factor-1 (HIF-1), which is a heterodimer composed of an alpha and a beta subunit. HIF-1 functions as a master regulator of cellular and systemic homeostatic response to hypoxia by activating transcription of many genes, including those involved in energy metabolism, angiogenesis, apoptosis, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. HIF-1 thus plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2011]
Canonical amino-acid sequenceUniProt
826 residues, UniProt reviewed canonical sequence.
>Q16665|HIF1A
1 MEGAGGANDK KKISSERRKE KSRDAARSRR SKESEVFYEL AHQLPLPHNV SSHLDKASVM
61 RLTISYLRVR KLLDAGDLDI EDDMKAQMNC FYLKALDGFV MVLTDDGDMI YISDNVNKYM
121 GLTQFELTGH SVFDFTHPCD HEEMREMLTH RNGLVKKGKE QNTQRSFFLR MKCTLTSRGR
181 TMNIKSATWK VLHCTGHIHV YDTNSNQPQC GYKKPPMTCL VLICEPIPHP SNIEIPLDSK
241 TFLSRHSLDM KFSYCDERIT ELMGYEPEEL LGRSIYEYYH ALDSDHLTKT HHDMFTKGQV
301 TTGQYRMLAK RGGYVWVETQ ATVIYNTKNS QPQCIVCVNY VVSGIIQHDL IFSLQQTECV
361 LKPVESSDMK MTQLFTKVES EDTSSLFDKL KKEPDALTLL APAAGDTIIS LDFGSNDTET
421 DDQQLEEVPL YNDVMLPSPN EKLQNINLAM SPLPTAETPK PLRSSADPAL NQEVALKLEP
481 NPESLELSFT MPQIQDQTPS PSDGSTRQSS PEPNSPSEYC FYVDSDMVNE FKLELVEKLF
541 AEDTEAKNPF STQDTDLDLE MLAPYIPMDD DFQLRSFDQL SPLESSSASP ESASPQSTVT
601 VFQQTQIQEP TANATTTTAT TDELKTVTKD RMEDIKILIA SPSPTHIHKE TTSATSSPYR
661 DTQSRTASPN RAGKGVIEQT EKSHPRSPNV LSVALSQRTT VPEEELNPKI LALQNAQRKR
721 KMEHDGSLFQ AVGIGTLLQQ PDDHAATTSL SWKRVKGCKS SEQNGMEQKT IILIPSDLAC
781 RLLGQSMDES GLPQLTSYDC EVNAPIQGSR NLLQGEELLR ALDQVNLocalizationUniProt · AlphaFold · HPA
Whether an antibody against HIF1A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.52
- Highest tissue expression
- 424 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 424 nTPM
- urinary bladder: 158 nTPM
- appendix: 138 nTPM
- gallbladder: 136 nTPM
- adrenal gland: 126 nTPM
- cervix: 125 nTPM
Single-cell type
- neutrophils: 1,938 nCPM
- monocytes: 643 nCPM
- neutrophil progenitors: 642 nCPM
- renal collecting duct principal cells: 612 nCPM
- cardiomyocytes: 460 nCPM
- endometrial glandular cells: 445 nCPM
Immune cell
- eosinophil: 155 nTPM
- neutrophil: 56 nTPM
- basophil: 44 nTPM
- naive CD4 T-cell: 23 nTPM
- classical monocyte: 22 nTPM
- NK-cell: 20 nTPM
Brain region
- thalamus: 79 nTPM
- pons: 65 nTPM
- medulla oblongata: 58 nTPM
- midbrain: 56 nTPM
- hypothalamus: 54 nTPM
- cerebellum: 53 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about HIF1A.
Disease | GeneticClinVar
6 pathogenic / likely-pathogenic of 139 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
Disease | ImmuneIEDB
Conditions an epitope on HIF1A was assayed in.
- type 1 diabetes mellitus T cell
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.31
- gnomAD pLI
- 0.98
- gnomAD missense Z
- 2.22
- DepMap mean gene effect
- 0.12
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- angiogenesis
- axonal transport of mitochondrion
- B-1 B cell homeostasis
- bone mineralization
- cardiac ventricle morphogenesis
- cellular response to hypoxia
- cellular response to interleukin-1
- cellular response to oxidative stress
- cellular response to virus
- cerebral cortex development
- chondrocyte differentiation
- collagen metabolic process
- connective tissue replacement involved in inflammatory response wound healing
- digestive tract morphogenesis
- dopaminergic neuron differentiation
- elastin metabolic process
- embryonic hemopoiesis
- embryonic placenta development
- epithelial cell differentiation involved in mammary gland alveolus development
- epithelial to mesenchymal transition
- glandular epithelial cell maturation
- heart looping
- hemoglobin biosynthetic process
- hypoxia-inducible factor-1alpha signaling pathway
- insulin secretion involved in cellular response to glucose stimulus
- intestinal epithelial cell maturation
- intracellular glucose homeostasis
- intracellular iron ion homeostasis
- intracellular oxygen homeostasis
- iris morphogenesis
- lactate metabolic process
- lactation
- mesenchymal cell apoptotic process
- muscle cell cellular homeostasis
- negative regulation of bone mineralization
- negative regulation of gene expression
- negative regulation of growth
- negative regulation of mesenchymal cell apoptotic process
- negative regulation of miRNA transcription
- negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
- negative regulation of reactive oxygen species biosynthetic process
- negative regulation of thymocyte apoptotic process
- negative regulation of TOR signaling
- neural crest cell migration
- neural fold elevation formation
- neuroblast proliferation
- neuron apoptotic process
- outflow tract morphogenesis
- positive regulation of angiogenesis
- positive regulation of blood vessel endothelial cell migration
- positive regulation of chemokine production
- positive regulation of chemokine-mediated signaling pathway
- positive regulation of cytokine production involved in inflammatory response
- positive regulation of DNA-templated transcription
- positive regulation of endothelial cell proliferation
- positive regulation of epithelial cell migration
- positive regulation of erythrocyte differentiation
- positive regulation of gene expression
- positive regulation of glycolytic process
- positive regulation of hormone biosynthetic process
- positive regulation of insulin secretion involved in cellular response to glucose stimulus
- positive regulation of macroautophagy
- positive regulation of miRNA transcription
- positive regulation of neuroblast proliferation
- positive regulation of nitric oxide metabolic process
- positive regulation of transcription by RNA polymerase II
- positive regulation of vascular endothelial growth factor production
- positive regulation of vascular endothelial growth factor receptor signaling pathway
- regulation of DNA-templated transcription
- regulation of gene expression
- regulation of glycolytic process
- regulation of protein neddylation
- regulation of transcription by RNA polymerase II
- regulation of transforming growth factor beta2 production
- response to hypoxia
- response to iron ion
- response to muscle activity
- response to reactive oxygen species
- retina vasculature development in camera-type eye
- signal transduction
- TOR signaling
- vascular endothelial growth factor production
- visual learning
Molecular functions
- cis-regulatory region sequence-specific DNA binding
- DNA-binding transcription activator activity
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity
- E-box binding
- enzyme binding
- histone deacetylase binding
- Hsp90 protein binding
- nuclear receptor binding
- p53 binding
- protein domain specific binding
- protein heterodimerization activity
- protein kinase binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- RNA polymerase II transcription regulatory region sequence-specific DNA binding
- RNA polymerase II-specific DNA-binding transcription factor binding
- transcription coactivator binding
- transcription corepressor binding
- transcription regulator activator activity
- ubiquitin protein ligase binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- PAS domain
- PAC motif
- Myc-type, basic helix-loop-helix (bHLH) domain
- PAS fold 3
- PAS fold
- HIF-1 alpha, C-terminal transactivation domain
- Hypoxia-inducible factor, alpha subunit-like
- PAS domain superfamily
- Helix-loop-helix DNA-binding domain superfamily
- PAS fold
- PAS fold
- HIF-1 alpha C terminal transactivation domain
- Hypoxia-inducible factor-1
- Hypoxia-inducible factor 1-alpha bHLH domain
- Hypoxia-inducible factor-1 alpha
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of HIF1A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads HIF1A as an antibody target. Whether an autoantibody or antibody against HIF1A could matter depends on whether native HIF1A is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
HIF1A is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label HIF1A as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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