DegronMD - Q16665(HIF1A)

FUNCTION: Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:20624928, PubMed:22009797, PubMed:9887100, PubMed:30125331). 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 (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:20624928, PubMed:22009797, PubMed:9887100, PubMed:30125331). Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease (PubMed:22009797). Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300 (PubMed:9887100, PubMed:16543236). Activity is enhanced by interaction with NCOA1 and/or NCOA2 (PubMed:10594042). Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP (PubMed:10202154, PubMed:10594042). Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia (PubMed:19528298). {ECO:0000250|UniProtKB:Q61221, ECO:0000269|PubMed:10202154, ECO:0000269|PubMed:10594042, ECO:0000269|PubMed:11292861, ECO:0000269|PubMed:11566883, ECO:0000269|PubMed:15465032, ECO:0000269|PubMed:16543236, ECO:0000269|PubMed:16973622, ECO:0000269|PubMed:17610843, ECO:0000269|PubMed:18658046, ECO:0000269|PubMed:19528298, ECO:0000269|PubMed:20624928, ECO:0000269|PubMed:22009797, ECO:0000269|PubMed:30125331, ECO:0000269|PubMed:9887100}.; FUNCTION: (Microbial infection) Upon infection by human coronavirus SARS-CoV-2, is required for induction of glycolysis in monocytes and the consequent pro-inflammatory state (PubMed:32697943). In monocytes, induces expression of ACE2 and cytokines such as IL1B, TNF, IL6, and interferons (PubMed:32697943). Promotes human coronavirus SARS-CoV-2 replication and monocyte inflammatory response (PubMed:32697943). {ECO:0000269|PubMed:32697943}. View more >>

GO - Biological processes (BP): angiogenesis [GO:0001525]; axonal transport of mitochondrion [GO:0019896]; B-1 B cell homeostasis [GO:0001922]; cardiac ventricle morphogenesis [GO:0003208]; cartilage development [GO:0051216]; cellular glucose homeostasis [GO:0001678]; cellular iron ion homeostasis [GO:0006879]; cellular response to hypoxia [GO:0071456]; cellular response to interleukin-1 [GO:0071347]; cellular response to virus [GO:0098586]; cerebral cortex development [GO:0021987]; collagen metabolic process [GO:0032963]; connective tissue replacement involved in inflammatory response wound healing [GO:0002248]; digestive tract morphogenesis [GO:0048546]; dopaminergic neuron differentiation [GO:0071542]; elastin metabolic process [GO:0051541]; embryonic hemopoiesis [GO:0035162]; embryonic placenta development [GO:0001892]; epithelial cell differentiation involved in mammary gland alveolus development [GO:0061030]; epithelial to mesenchymal transition [GO:0001837]; heart looping [GO:0001947]; hemoglobin biosynthetic process [GO:0042541]; hypoxia-inducible factor-1alpha signaling pathway [GO:0097411]; intestinal epithelial cell maturation [GO:0060574]; iris morphogenesis [GO:0061072]; lactate metabolic process [GO:0006089]; lactation [GO:0007595]; muscle cell cellular homeostasis [GO:0046716]; negative regulation of bone mineralization [GO:0030502]; negative regulation of gene expression [GO:0010629]; negative regulation of growth [GO:0045926]; negative regulation of mesenchymal cell apoptotic process [GO:2001054]; negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway [GO:1903377]; negative regulation of reactive oxygen species metabolic process [GO:2000378]; negative regulation of thymocyte apoptotic process [GO:0070244]; negative regulation of TOR signaling [GO:0032007]; neural crest cell migration [GO:0001755]; neural fold elevation formation [GO:0021502]; outflow tract morphogenesis [GO:0003151]; oxygen homeostasis [GO:0032364]; positive regulation of angiogenesis [GO:0045766]; positive regulation of autophagy of mitochondrion [GO:1903599]; positive regulation of blood vessel endothelial cell migration [GO:0043536]; positive regulation of chemokine-mediated signaling pathway [GO:0070101]; positive regulation of chemokine production [GO:0032722]; positive regulation of cytokine production involved in inflammatory response [GO:1900017]; positive regulation of endothelial cell proliferation [GO:0001938]; positive regulation of epithelial cell migration [GO:0010634]; positive regulation of erythrocyte differentiation [GO:0045648]; positive regulation of gene expression [GO:0010628]; positive regulation of glycolytic process [GO:0045821]; positive regulation of hormone biosynthetic process [GO:0046886]; positive regulation of insulin secretion involved in cellular response to glucose stimulus [GO:0035774]; positive regulation of macroautophagy [GO:0016239]; positive regulation of miRNA transcription [GO:1902895]; positive regulation of neuroblast proliferation [GO:0002052]; positive regulation of nitric-oxide synthase activity [GO:0051000]; positive regulation of signaling receptor activity [GO:2000273]; positive regulation of transcription, DNA-templated [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of transcription from RNA polymerase II promoter in response to hypoxia [GO:0061419]; positive regulation of vascular endothelial growth factor production [GO:0010575]; positive regulation of vascular endothelial growth factor receptor signaling pathway [GO:0030949]; regulation of aerobic respiration [GO:1903715]; regulation of gene expression [GO:0010468]; regulation of glycolytic process [GO:0006110]; regulation of protein neddylation [GO:2000434]; regulation of transcription, DNA-templated [GO:0006355]; regulation of transcription by RNA polymerase II [GO:0006357]; regulation of transcription from RNA polymerase II promoter in response to oxidative stress [GO:0043619]; regulation of transforming growth factor beta2 production [GO:0032909]; response to hypoxia [GO:0001666]; response to iron ion [GO:0010039]; response to muscle activity [GO:0014850]; response to reactive oxygen species [GO:0000302]; retina vasculature development in camera-type eye [GO:0061298]; signal transduction [GO:0007165]; vascular endothelial growth factor production [GO:0010573]; visual learning [GO:0008542] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.K571N	TCGA-AN-A046	BRCA	TCGA	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation altering degron motif	0.6918
p.K571N	TCGA-BS-A0UV	UCEC	TCGA	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation altering degron motif	0.6918
p.K571N	SIDM01611	Endometrial Carcinoma	GDSC	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation altering degron motif	0.6918
p.E584D	TCGA-AN-A046	BRCA	TCGA	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation rewiring degron network	0.0556
p.D412N	TCGA-AP-A059	UCEC	TCGA	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation altering degron motif	0.5821
p.K745N	TCGA-B5-A11E	UCEC	TCGA	AATTS	DEG_SPOP_SBC_1	745:749	Mutation altering degron motif	0.6918
p.S409I	TCGA-B5-A3FA	UCEC	TCGA	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation altering degron motif	0.7341
p.S409I	DO52402	UCEC	ICGC	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation altering degron motif	0.7341
p.A428T	TCGA-B5-A3FC	UCEC	TCGA	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation altering degron motif	0.7139
p.Q620E	TCGA-CN-4731	HNSC	TCGA	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation rewiring degron network	0.2778
p.Q620E	DO15886	HNSC	ICGC	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation rewiring degron network	0.2778
p.I432V	TCGA-CR-6477	HNSC	TCGA	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation altering degron motif	0.7076
p.I432V	DO14216	HNSC	ICGC	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation altering degron motif	0.7076
p.E403K	TCGA-D5-6928	COAD	TCGA	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation altering degron motif	0.7022
p.E403K	DO7776	COAD	ICGC	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation altering degron motif	0.7022
p.S621N	TCGA-EB-A431	SKCM	TCGA	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation rewiring degron network	0.25
p.S621N	DO37671	SKCM	ICGC	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation rewiring degron network	0.25
p.G750D	TCGA-EY-A1GQ	UCEC	TCGA	AATTS	DEG_SPOP_SBC_1	745:749	Mutation rewiring degron network	0.3056
p.G750D	SIDM00526	Chronic Myelogenous Leukemia	GDSC	AATTS	DEG_SPOP_SBC_1	745:749	Mutation rewiring degron network	0.3056
p.G750D	MEG-01	haematopoietic and lymphoid tissue	COSMIC	AATTS	DEG_SPOP_SBC_1	745:749	Mutation rewiring degron network	0.3056
p.D441N	TCGA-IR-A3LA	CESC	TCGA	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation rewiring degron network	0.1111
p.D441N	DO44377	CESC	ICGC	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation rewiring degron network	0.1111
p.K415R	TCGA-KS-A4IB	THCA	TCGA	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation rewiring degron network	0.2778
p.K415R	DO40033	THCA	ICGC	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation rewiring degron network	0.2778
p.P614S	TCGA-V5-A7RE	ESCA	TCGA	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation altering degron motif	0.6752
p.Q438H	DO474	BLCA	ICGC	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation rewiring degron network	0.1944
p.P746A	DO5207	BRCA	ICGC	AATTS	DEG_SPOP_SBC_1	745:749	Mutation altering degron motif	0.7503
p.H625D	DO6320	CESC	ICGC	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation substituting flanking lysine	0.25
p.K743Q	DO223417	CLLE	ICGC	AATTS	DEG_SPOP_SBC_1	745:749	Mutation rewiring degron network	0.2778
p.E622D	DO8842	COAD	ICGC	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation rewiring degron network	0.2222
p.I432L	DO8264	COAD	ICGC	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation altering degron motif	0.7174
p.Q436R	DO222576	COCA	ICGC	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation rewiring degron network	0.25
p.G438D	DO222765	COCA	ICGC	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation rewiring degron network	0.1944
p.P606S	DO229013	COCA	ICGC	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation rewiring degron network	0.1111
p.P606S	DO225404	LAML	ICGC	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation rewiring degron network	0.1111
p.A553S	DO228952	LICA	ICGC	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation rewiring degron network	0.0833
p.A755V	DO229050	LICA	ICGC	AATTS	DEG_SPOP_SBC_1	745:749	Mutation rewiring degron network	0.1667
p.I576F	DO22857	LIHC	ICGC	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation blocking phosphorylation signal	0.7222
p.A397S	DO51189	LUAD	ICGC	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation rewiring degron network	0.25
p.I747V	DO26842	LUSC	ICGC	AATTS	DEG_SPOP_SBC_1	745:749	Mutation altering degron motif	0.7076
p.Q577H	DO46483	OV	ICGC	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation rewiring degron network	0.25
p.P626Q	DO47469	SKCM	ICGC	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation rewiring degron network	0.1111
p.L736P	DO38599	STAD	ICGC	AATTS	DEG_SPOP_SBC_1	745:749	Mutation rewiring degron network	0.0833
p.L736P	TOV-21G	ovary	COSMIC	AATTS	DEG_SPOP_SBC_1	745:749	Mutation rewiring degron network	0.0833
p.P423Q	DO42280	UCEC	ICGC	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation rewiring degron network	0.0556
p.P423Q	DO42280	UCEC	ICGC	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation rewiring degron network	0.1944
p.R404Q	DO42472	UCEC	ICGC	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation altering degron motif	0.7329
p.R404Q	Jurkat	haematopoietic and lymphoid tissue	COSMIC	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation altering degron motif	0.7329
p.T431A	DO41133	UCEC	ICGC	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation altering degron motif	0.7139
p.L563R	SIDM01043	Other Sarcomas	GDSC	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation altering degron motif	0.8428
p.L563R	ESS-1	endometrium	COSMIC	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation altering degron motif	0.8428
p.A617P	SIDM00299	Other Sarcomas	GDSC	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation altering degron motif	0.7503
p.A617P	MFH-ino	soft tissue	COSMIC	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation altering degron motif	0.7503
p.V560A	SIDM00537	Colorectal Carcinoma	GDSC	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation rewiring degron network	0.2778
p.V560A	GP5d	large intestine	COSMIC	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation rewiring degron network	0.2778
p.M393T	SIDM00870	Breast Carcinoma	GDSC	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation rewiring degron network	0.1389
p.M393T	HCC202	breast	COSMIC	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation rewiring degron network	0.1389
p.H745R	ACH-000914	Lymphoma	CCLE	AATTS	DEG_SPOP_SBC_1	745:749	Mutation altering degron motif	0.8244
p.H745R	HT	haematopoietic and lymphoid tissue	COSMIC	AATTS	DEG_SPOP_SBC_1	745:749	Mutation altering degron motif	0.8244
p.R755C	ACH-000984	Endometrial/Uterine Cancer	CCLE	AATTS	DEG_SPOP_SBC_1	745:749	Mutation rewiring degron network	0.1667
p.L431S	ACH-000988	Endometrial/Uterine Cancer	CCLE	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation altering degron motif	0.7667
p.L431S	MFE-319	endometrium	COSMIC	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation altering degron motif	0.7667
p.R755H	ACH-000996	Endometrial/Uterine Cancer	CCLE	AATTS	DEG_SPOP_SBC_1	745:749	Mutation rewiring degron network	0.1667
p.D623E	ACH-002282	Neuroblastoma	CCLE	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation rewiring degron network	0.1944
p.D623E	NB17	autonomic ganglia	COSMIC	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation rewiring degron network	0.1944
p.L430S	MFE-319	endometrium	COSMIC	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation altering degron motif	0.7667
p.A581P	NCI-H650	lung	COSMIC	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation rewiring degron network	0.1389
p.P626S	NCI-H1304	lung	COSMIC	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation rewiring degron network	0.1111
p.S406T	RL	haematopoietic and lymphoid tissue	COSMIC	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation altering degron motif	0.7116
p.R572P	KMH-2	thyroid	COSMIC	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation altering degron motif	0.7512
p.R572H	SNU-283	large intestine	COSMIC	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation altering degron motif	0.8244
p.R572H	NCI-H187	lung	COSMIC	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation altering degron motif	0.8244
p.I618V	NCI-H446	lung	COSMIC	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation altering degron motif	0.7076
p.K615N	HN	upper aerodigestive tract	COSMIC	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation altering degron motif	0.6918
p.E420Q	PCI-4B	upper aerodigestive tract	COSMIC	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation rewiring degron network	0.1389
p.E420Q	PCI-4B	upper aerodigestive tract	COSMIC	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation rewiring degron network	0.1111
p.R572C	KMH-2	thyroid	COSMIC	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation altering degron motif	0.8301
p.K759T	23132-87	stomach	COSMIC	AATTS	DEG_SPOP_SBC_1	745:749	Mutation substituting flanking lysine	0.1667
p.H744R	HT	haematopoietic and lymphoid tissue	COSMIC	AATTS	DEG_SPOP_SBC_1	745:749	Mutation rewiring degron network	0.3056
p.L443S	EN	endometrium	COSMIC	VPLYND	LIG_APCC_ABBA_1	428:433	Mutation rewiring degron network	0.0556
p.D622E	NB17	autonomic ganglia	COSMIC	ATTTT	DEG_SPOP_SBC_1	614:618	Mutation rewiring degron network	0.2222
p.M573I	SNU-1040	large intestine	COSMIC	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation altering degron motif	0.7618
p.A410V	SNU-1040	large intestine	COSMIC	LAPAAGDTIISLDF	DEG_ODPH_VHL_1	400:413	Mutation altering degron motif	0.6936
p.D563E	NB17	autonomic ganglia	COSMIC	LAPYIPMDDDFQL	DEG_ODPH_VHL_1	562:574	Mutation altering degron motif	0.6758

Kaplan plot for HIF1A in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

HIF1A

UniProt ID: Q16665

Entrez ID: 3091

Protein name: 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)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for HIF1A in