HIF1A

Protein HIF1A

Identifiers
HUGO:SETD2 HGNC:18420
HUGO:HIF1A
hypoxia inducible factor 1 alpha subunit
HUGO:HIF1A hgnc_id:HGNC:4910 HGNC:4910 ENTREZ:3091 UNIPROT:Q16665
hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
HUGO:HIF1A, HGNC:4910, ENTREZ:3091, GENECARDS:GC14P062162, UNIPROT:Q16665
HUGO:HIF1A HGNC:4910 ENTREZ:3091 UNIPROT:Q16665

Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Adaptive Immune Response / INHIBITING_CHECKPOINTS
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / METABOLIC
EMT Senescence / EMT_REGULATORS
EMT Senescence / SENESCENCE
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
Regulated Cell Death / ANTIOXIDANT_RESPONSE
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / STARVATION_AUTOPHAGY
Regulated Cell Death / DEATH_RECEPTOR_PATHWAYS
Regulated Cell Death / FATTY_ACID_BIOSYNTHESIS
Regulated Cell Death / GLUCOSE_METABOLISM
Regulated Cell Death / RCD_GENES
Innate Immunity / IMMUNOSUPPPRESSIVE_CORE_PATHWAYS
Innate Immunity / MIRNA_TF_IMMUNOSUPPRESSIVE

References
PMID:10804084
PMID:16110315 PMID:22988108
CASCADE:TGFB
PMID:22850421
Protein level of MCT4 (SLC16A4) in CAFs is redox and HIF1 dependent.
PMID:20855962
HIF-1?? drives Cav-1 degradation in CAFs and provides CAFs autophagy
Autophagy in cancer associated fibroblasts promotes tumor cell survival:
PMID:21051947
fibroblasts expressing activated HIF1?? increased tumor mass by ???2-fold and tumor volume by ???3-fold, without an increase in angiogenesis.5 Similarly, HIF1??-transfected fibroblasts increased the lymph node metastasis of cancer cells.
PMID:20535745
junD???/??? fibroblasts exhibit features of carcinoma-associated myofibroblasts.
The expression of the chemokine CXCL12 was increased in junD???/??? fibroblasts
HIF-1?? protein accumulates in junD???/??? fibroblasts and mice (Gerald et al, 2004; Laurent et al, 2008), the up-regulation of CXCL12 in junD???/??? fibroblasts could be mediated, at least partly, through HIF. Specific inhibition of HIF-1?? by siRNA strongly reduced HIF-1?? mRNA levels (Fig S3A) and decreased the expression of its target gene, CXCL12
PMID:25732824
expression of HIF-1?? was increased in CAFs, with no significant changes for HIF-2?? or HIF-3??
Stabilization of HIF-1?? protein in induced CAF cells downstream of tgfb 5mRNA level is the same)
The gene HIF1A gives rise to 3 different isoforms: HIF1_alpha_, HIF2_alpha_ and HIF3_alpha
PMID:17533374
HIF-1 and NF-kappaB upregulates CXCR1 and CXCR2 expression
NATURAL_KILLER
MACROPHAGE
CASCADE:IL4
CASCADE:LACTIC
CASCADE:IL13
CASCADE:CSF2
CASCADE:IFNG
PMID:22006996
Hypoxia-induced expression of ADAM10 is HIF-1-dependent.
PMID:25103413
Hypoxia downregulates MICA, MICB surface expression via HIF1A.
PMID:24006507
HIF1A expression is assotiated with classical activation of macrophages
PMID:20427344
HIF1 expression is assotiated with classical activation of macrophages
HIF1A upregulates expression of: TNF, IL6, HIF1A downregulates expression of M2 markers CD206 and STAB1.
PMID_24006507
IL4 downregulates HIF1a translation.
PMID:21765015
CSF2 upregulates VEGF expression via HIF1a specific inhibition of PHD2 increases VEGF production
HIF1a induces MIF expression of macrophages after hypoxia.
IL4+IL13 inhibit MIF expression via inhibition of HIF1a expression.
PMID:16127144
HIF-1A and HIF-2A are up-regulated by human macrophages exposed to hypoxia??in vitro??and by TAMs in hypoxic/necrotic areas of human tumors.
PMID:25043024
Lactic acid is sufficient to induce Vegf and Arg1 via HIF1??.
Lactic acid, probably via HIF1A polarizes macrophages to an M2-Iike state that is critical for tumour growth
HIF1A upregulates expression of: TNF, IL6 and downregulates expression of M2 markers CD206 and STAB1
HIF1A upregulates expression of EGLN1, EGLN3, PDK1, Pfkfb3, GLUT1, VEGF, FGF2 Mif, Ccr2, Cxcl2

HIF1A|ubi@Nucleus

Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
Regulated Cell Death / ANTIOXIDANT_RESPONSE
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / STARVATION_AUTOPHAGY
Regulated Cell Death / DEATH_RECEPTOR_PATHWAYS
Regulated Cell Death / FATTY_ACID_BIOSYNTHESIS
Regulated Cell Death / GLUCOSE_METABOLISM
Regulated Cell Death / RCD_GENES

References
rc_re398:( Regulated Cell Death ) PMID:18838541

HIF1A|ubi|P564_hyd@Cytosol

References
rc_re386( Regulated Cell Death ):
PMID:10973499
in vitro reconstitution of the E3-ligase activity, with VHL, elonginB/C, RBX1,CUL2
PMID:18985005
in COS monkey kidney cells and Caki-I human renal carcinoma cells, inhibition of VHL-mediated HIF1A ubiquitinylation and degradation by ectopically expressed constitutively active STAT3

HIF1A|P564_hyd@Cytosol

References
rc_re387( Regulated Cell Death ):
PMID:12351678
identification of PHD2 as a HIF1A prolyl hydroxylase
PMID:15652751
inhibition of HIF1A prolyl hydroxylation by succinate and fumarate
PMID:15721254
in 293 cells, OS9 interacts with HIF1 and PHD and promotes HIF1A prolylhydroxylation and degradation
rc_re386( Regulated Cell Death ):
PMID:10973499
in vitro reconstitution of the E3-ligase activity, with VHL, elonginB/C, RBX1,CUL2
PMID:18985005
in COS monkey kidney cells and Caki-I human renal carcinoma cells, inhibition of VHL-mediated HIF1A ubiquitinylation and degradation by ectopically expressed constitutively active STAT3

HIF1A@Nucleus

References
rc_re401:( Regulated Cell Death ) reactionType:is.a
rc_re98( Regulated Cell Death ):
PMID:18056423
p53 mediated upregulation of IGFBP1
in mouse liver
PMID:9707622
in HepG2, by HIF1
PMID:10102273
in 293T, by FOXO3, EMSA
rc_re126( Regulated Cell Death ):
PMID:14699081
in Saos-2, direct transactivation of NOXA by HIF1A during hypoxia, role of NOXA in hypoxia-induced cell death
PMID:16888645
in SH-EP, in NB15 neuroblastoma cell lines expressing a FOXO3-ER fusion, upon 4OHT. PMAIP knock down protects from apoptosis
PMID:12676992
in MEF by CTBP1 and CTBP2 (RT-PCR, double knocked out)
PMID:14684737
in NIH3T3, by E2F1
rc_re130( Regulated Cell Death ):
PMID:12402042
in mouse splenic red pulp and colonic epithelium, upon irradiation
in human, the p53 binding element is conserved
PMID:15024076
in HT29 and CHO, HIF1-dependent hypoxia-induced repression of BID expression
in SW480 upon hypoxia, interaction between HIF1 and BID promoter, by EMSA
PMID:15240700
in mouse T cells, by E2F1
rc_re158( Regulated Cell Death ):
Reaction (id=re340, name=; 10 01 04.xml)
PMID:11557773
by HIF1
PMID:14672622
in liver tumors by HIF1
PMID:16782875
by MLX:MLXIP
rc_re160( Regulated Cell Death ):
PMID:11744734
in renal carcinoma 786-0 cells (VHL deficient), in HIF1 KO MEFs
PMID:17143338
in pancreatic and gastric cancer cell lines (correlation HIF stabilisation and gene expression)
rc_re162( Regulated Cell Death ):
PMID:16517405
HIF
PMID:16517406
PMID:17785433
by MYC
rc_re164( Regulated Cell Death ):
PMID:17418790
in Hela cells, in RCC4 renal carcinoma human cells, in mouse
rc_re170( Regulated Cell Death ):
PMID:8955077
in HepG3
PMID:8089148
in Hela and HepG3
rc_re172( Regulated Cell Death ):
PMID:16126909
in human breast carcinoma BT-549 cells, by HIF1
PMID:10823814
in rat1a rat fibroblasts upon c-myc overexpression
rc_re174( Regulated Cell Death ):
PMID:7493931
in HepG2 by HIF1 (EMSA, reporter plasmids)
PMID:9525945
in chinese hamster ovary cells by HIF1
PMID:15059920
in Saos2, in human embryonal rhabdomyosarcoma derived RD (ATCC no. CCL-136), in murine skeletal muscle-derived C2C12 myoblasts (ATCC no. CRL-1772), by TP53 (luciferase reporter)
rc_re176( Regulated Cell Death ):
PMID:15379897
in CCF-STTG1 human glial cells (EMSA + supershift with HRE derived from the PKM2 promoter)
rc_re178( Regulated Cell Death ):
PMID:14762718
in MEFs upon hypoxia, not in HIF1 KO cells
PMID:15199147
MYC
rc_re180( Regulated Cell Death ):
PMID:16585195
in Hela cells, BNIP3 expression upon hypoxia is impaired by siRNA against HIF1
PMID:18054315
PMID:11559532
rc_re182( Regulated Cell Death ):
in Hela cells, PGK1 expression upon hypoxia is impaired by siRNA against HIF1
PMID:8702901
in mouse hepatoma cell line Hepa1c1c7, but not in an ARNT defective conterpart
rc_re184( Regulated Cell Death ):
in Hela cells, CA9 expression upon hypoxia is impaired by siRNA against HIF1
rc_re186:( Regulated Cell Death ) PMID:18718909
rc_re189( Regulated Cell Death ):
PMID:7508926
in murine RAW 264.7 macrophage cell line, by NFKB
PMID:7500013
in murine macrophage derived from C57BL/6 mice and transformed with J2 (v-raf1v-myc) recombinant retrovirus, by HIF1
PMID:9486205
in rat lung epithelia, by hypoxia
in bovine pulmonary artery endothelial cells, HIF1 regulates the murine iNOS promoter (supershifted EMSA + gene reporter)
rc_re190( Regulated Cell Death ):
PMID:19211554
in PC-3 human prostate cancer cell line by HIF, transactivation of the promoter (ChIP, EMSA, reporter gene assay)
PMID:10435632
in murine immortalized bone marrow-derived pro-B-cell BA/F3, by STAT5 upon IL3
PMID:10428780 AND PMID:10428030
in murine erythroleukemia HCD-57 cells, by STAT5 upon EPO (HGNC:3415) treatment
PMID:11756417
in UT-7/TPO human TPO-dependent megakaryocytic cell line, by STAT5 and NF-kappaB, upon TPO
rc_re192( Regulated Cell Death ):
PMID:18158893
in MEFs, in MCF7
rc_re194( Regulated Cell Death ):
PMID:15545625
PMID:11884613
rc_re196( Regulated Cell Death ):
prototypical HIF1 target
PMID:15369676
rc_re199:( Regulated Cell Death ) PMID:20028863
rc_re876:( Regulated Cell Death ) PMID:15312748
rc_re992( Regulated Cell Death ):
PMID:12743597
in 786-O human carcinoma cell line
rc_re1993:( Regulated Cell Death ) PMID:22841746

Modifications:
In compartment: Cytosol

HIF1A@Cytosol
HIF1A|P564_hyd@Cytosol
HIF1A|ubi|P564_hyd@Cytosol

In compartment: INNATE_IMMUNE_CELL_Cytosol

HIF1A@INNATE_IMMUNE_CELL_Cytosol

In compartment: Nucleus

HIF1A@Nucleus
HIF1A|ubi@Nucleus

In compartment: TUMOR_CELL_AS_INDUCTOR

HIF1A@TUMOR_CELL_AS_INDUCTOR

In compartment: T_cell

HIF1A@T_cell

Participates in complexes:
In compartment: Nucleus

Participates in reactions:
As Reactant or Product:

As Catalyser: