HIF1A
Encyclopedia
Hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor), also known as HIF1A, is a protein
that in humans is encoded by the HIF1A gene
. Two alternative transcripts
encoding different isoforms have been identified.
), the beta subunit.
- PAS
transcription factor
found in mammalian cells growing at low oxygen concentrations. It plays an essential role in cellular and systemic responses to hypoxia
. This is one of the class of hypoxia inducible factors
, a family that includes Hif1a, Hif2a, and Hif3a
.
s (PHDs) maintain the appropriate balance of HIF-1α protein in the post-translation phase.
PHDs rely on iron among other molecules to phosphorylate HIF-1alpha; as such, iron chelators such as DFO and DMOG have proven successful in HIF-1alpha stabilization. HBO (Hyperbaric oxygen therapy) and HIF-1alpha imitators such as cobalt chloride have also been successfully utilized.
Factors increasing HIF-1α
Factors decreasing HIF-1α
with pVHL, PSMA7
, NR4A
, STAT3
, CREBB
, ARNTL
, ARNT
, P53
, EP300
, HIF1AN
, Mdm2
, VH
and UBC
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the HIF1A gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. Two alternative transcripts
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...
encoding different isoforms have been identified.
Structure
HIF1 is a homodimeric basic helix-loop-helix structure composed of Hif1a, the alpha subunit (this protein), and the aryl hydrocarbon receptor nuclear translocator (ArntAryl hydrocarbon receptor nuclear translocator
The ARNT gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor , and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor,...
), the beta subunit.
Function
The protein encoded by HIF1 is a bHLHBasic-helix-loop-helix
A basic helix-loop-helix is a protein structural motif that characterizes a family of transcription factors.- Structure :The motif is characterized by two α-helices connected by a loop. In general, transcription factors including this domain are dimeric, each with one helix containing basic amino...
- PAS
PAS domain
The PAS domain is a protein domain contained in many signaling proteins where it functions as a signal sensor. PAS domains are found in a large number of organisms from bacteria to humans...
transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
found in mammalian cells growing at low oxygen concentrations. It plays an essential role in cellular and systemic responses to hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
. This is one of the class of hypoxia inducible factors
Hypoxia inducible factors
Hypoxia-inducible factors are transcription factors that respond to changes in available oxygen in the cellular environment, specifically, to decreases in oxygen, or hypoxia.- Structure :...
, a family that includes Hif1a, Hif2a, and Hif3a
HIF3A
Hypoxia-inducible factor 3 alpha is a protein that in humans is encoded by the HIF3A gene.-Further reading:...
.
Regulation
HIF-1alpha abundance (and its subsequent activity) is regulated transcriptionally in an NF-κB-dependent manner. In addition, the coordinated activity of the prolyl hydroxylaseProlyl hydroxylase
Prolyl hydroxylase is an enzyme involved in the production of collagen, acting to hydroxylate proline to hydroxyproline....
s (PHDs) maintain the appropriate balance of HIF-1α protein in the post-translation phase.
PHDs rely on iron among other molecules to phosphorylate HIF-1alpha; as such, iron chelators such as DFO and DMOG have proven successful in HIF-1alpha stabilization. HBO (Hyperbaric oxygen therapy) and HIF-1alpha imitators such as cobalt chloride have also been successfully utilized.
Factors increasing HIF-1α
- Modulator of Degradation:
- Oxygen-Dependent:
- EPF UCP (degrades pHVL)
- VDU2USP20Ubiquitin carboxyl-terminal hydrolase 20 is an enzyme that in humans is encoded by the USP20 gene.-Further reading:...
(de-ubiquitinates HIF-1α) - SUMOylationSUMO proteinSmall Ubiquitin-like Modifier or SUMO proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function...
(via RSUMERWDD3RWD domain-containing protein 3 is a protein that in humans is encoded by the RWDD3 gene.-Further reading:...
) - DeSUMOylation ( via SENP1SENP1Sentrin-specific protease 1 is an enzyme that in humans is encoded by the SENP1 gene.-Further reading:...
)
- Oxygen-independent:
- Calcineurin ACalcineurinCalcineurin is a protein phosphatase also known as protein phosphatase 3, PPP3CA, and calcium-dependent serine-threonine phosphatase, and formerly known as protein phosphatase 2B . It activates the T cells of the immune system and can be blocked by drugs...
( Ca2+-dependent via RACK1GNB2L1Guanine nucleotide-binding protein subunit beta-2-like 1 is a protein that in humans is encoded by the GNB2L1 gene.-Interactions:GNB2L1 has been shown to interact with PDE4D, STAT1, Tyrosine kinase 2, Src, Androgen receptor, AGTRAP, Janus kinase 1, FYN, Cyclin A1, IFNAR2, PRKCE, P73, RAS p21...
)
- Calcineurin A
- Oxygen-Dependent:
- Modulators of translation:
- RNA-binding proteins, PTBPTBP1Polypyrimidine tract-binding protein 1 is a protein that in humans is encoded by the PTBP1 gene.-Interactions:PTBP1 has been shown to interact with HNRPK, PCBP2, SFPQ and HNRNPL.This gene is targeted by the microRNA miR-124...
, and HuRELAVL1ELAV-like protein 1 or HuR is a protein that in humans is encoded by the ELAVL1 gene.-Further reading:... - PtdIns3K and MAPKMAPK/ERK pathwayThe MAPK/ERK pathway is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. The signal starts when a growth factor binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a...
pathways - IRES-mediated translation
- calcium signaling
- miRNAMirnaMirna may refer to:geographical entities* Mirna , a river in Istria, Croatia* Mirna , a river in Slovenia, tributary of the river Sava* Mirna , a settlement in the municipality of Mirna in Southeastern Sloveniapeople...
s
- RNA-binding proteins, PTB
Factors decreasing HIF-1α
- Modulator of Degradation:
- Oxygen-Dependent:
- PHDProlyl hydroxylaseProlyl hydroxylase is an enzyme involved in the production of collagen, acting to hydroxylate proline to hydroxyproline....
, pVHL, OS-9OS-9OS-9 is a family of real-time, process-based, multitasking, multi-user, Unix-like operating systems, developed in the 1980s, originally by Microware Systems Corporation for the Motorola 6809 microprocessor. It is currently owned by RadiSys Corporation....
and SSAT2SAT2Diamine acetyltransferase 2 is an enzyme that in humans is encoded by the SAT2 gene.SAT2 maintains a key metabolic glutamine/glutamate balance underpinning retrograde signaling by dendritic release of the neurotransmitter glutamate.... - SUMOylation
- PHD
- Oxygen-independent
- RACK1 and SSAT1SAT1 (gene)Diamine acetyltransferase 1 is an enzyme that in humans is encoded by the SAT1 gene.An association with Keratosis follicularis spinulosa decalvans has been suggested.-Further reading:...
- GSK3βGSK3BGlycogen synthase kinase 3 beta, also known as GSK3B, is an enzyme that in humans is encoded by the GSK3B gene.- Function :Glycogen synthase kinase-3 is a proline-directed serine-threonine kinase that was initially identified as a phosphorylating and inactivating glycogen synthase. Two isoforms,...
- FOXO4FOXO4Forkhead box protein O4 is a protein that in humans is encoded by the FOXO4 gene.-Interactions:FOXO4 has been shown to interact with PIN1 and Mdm2.-Further reading:...
- RACK1 and SSAT1
- Oxygen-Dependent:
- Modulators of translation:
- Calcium signaling
- miRNAs
Interactions
HIF1A has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with pVHL, PSMA7
PSMA7
Proteasome subunit alpha type-7 is a protein that in humans is encoded by the PSMA7 gene.-Interactions:PSMA7 has been shown to interact with HIF1A and PLK1.-Further reading:...
, NR4A
Nerve Growth factor IB
The nerve Growth factor IB also known as Nur77 or NR4A1 is a protein that in humans is encoded by the NR4A1 gene....
, STAT3
STAT3
Signal transducer and activator of transcription 3 also known as STAT3 is a transcription factor which in humans is encoded by the STAT3 gene.- Function :The protein encoded by this gene is a member of the STAT protein family...
, CREBB
CREB binding protein
CREB-binding protein, also known as CREBBP or CBP, is a protein that in humans is encoded by the CREBBP gene.The CREB protein carries out its function by activating transcription, where interaction with transcription factors is managed by one or more of p300 domains: the nuclear receptor...
, ARNTL
ARNTL
Aryl hydrocarbon receptor nuclear translocator-like, also known as ARNTL, Bmal1, or Mop3, is a gene which is associated with susceptibility to hypertension and type 2 diabetes.-Function:...
, ARNT
Aryl hydrocarbon receptor nuclear translocator
The ARNT gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor , and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor,...
, P53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
, EP300
EP300
E1A binding protein p300 also known as EP300 or p300 is a protein that, in humans, is encoded by the EP300 gene. This protein regulates the activity of many genes in tissues throughout the body...
, HIF1AN
HIF1AN
Hypoxia-inducible factor 1-alpha inhibitor is a protein that in humans is encoded by the HIF1AN gene.-Interactions:HIF1AN has been shown to interact with HIF1A and Von Hippel-Lindau tumor suppressor.-Further reading:...
, Mdm2
Mdm2
Mdm2 is an important negative regulator of the p53 tumor suppressor. It is the name of a gene as well as the protein encoded by that gene. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain of the p53 tumor suppressor and an inhibitor of...
, VH
Von Hippel-Lindau tumor suppressor
The Von Hippel–Lindau tumor suppressor also known as pVHL is a protein that in humans is encoded by the VHL gene. Mutations of the VHL gene are associated with Von Hippel–Lindau disease....
and UBC
Ubiquitin C
Ubiquitin is a protein that in humans is encoded by the UBC gene.-Interactions:Ubiquitin C has been shown to interact with SCNN1A, SCNN1G, Parkin , P70-S6 Kinase 1, TRAF6, HDAC3, SFPQ, S100A10, Mothers against decapentaplegic homolog 3, NOTCH1, HIF1A, Epidermal growth factor receptor, E2F1,...
.