KEGG   PATHWAY: bom04066
Entry
bom04066                    Pathway                                
Name
HIF-1 signaling pathway - Bos mutus (wild yak)
Description
Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. It consists of two subunits: an inducibly-expressed HIF-1alpha subunit and a constitutively-expressed HIF-1beta subunit. Under normoxia, HIF-1 alpha undergoes hydroxylation at specific prolyl residues which leads to an immediate ubiquitination and subsequent proteasomal degradation of the subunit. In contrast, under hypoxia, HIF-1 alpha subunit becomes stable and interacts with coactivators such as p300/CBP to modulate its transcriptional activity. Eventually, HIF-1 acts as a master regulator of numerous hypoxia-inducible genes under hypoxic conditions. The target genes of HIF-1 encode proteins that increase O2 delivery and mediate adaptive responses to O2 deprivation. Despite its name, HIF-1 is induced not only in response to reduced oxygen availability but also by other stimulants, such as nitric oxide, or various growth factors.
Class
Environmental Information Processing; Signal transduction
Pathway map
bom04066  HIF-1 signaling pathway
bom04066

Organism
Bos mutus (wild yak) [GN:bom]
Gene
102287919  IL6; interleukin 6 [KO:K05405]
102287439  IL6R; interleukin 6 receptor [KO:K05055]
102282282  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
102288174  TLR4; toll like receptor 4 [KO:K10160]
102267095  IFNG; interferon gamma [KO:K04687]
102275527  IFNGR1; interferon gamma receptor 1 [KO:K05132]
102281523  IFNGR2; interferon gamma receptor 2 [KO:K05133]
102268417  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102286969  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102274400  INS; insulin [KO:K04526]
102285914  EGF; epidermal growth factor [KO:K04357]
102272009  IGF1; insulin like growth factor 1 [KO:K05459]
102285317  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
102269868  epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102278105  IGF1R; insulin like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
102267975  ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
102280670  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102271710  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102272368  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102284931  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102269500  MKNK2; MAP kinase interacting serine/threonine kinase 2 [KO:K04372] [EC:2.7.11.1]
102284499  MKNK1; MAP kinase interacting serine/threonine kinase 1 [KO:K04372] [EC:2.7.11.1]
102274553  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
102274461  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102277548  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102266922  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102280296  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102286868  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102275199  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102265427  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102283212  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102281727  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
102278368  EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205]
102275213  EIF4E1B; eukaryotic translation initiation factor 4E family member 1B [KO:K03259]
102266436  EIF4E2; eukaryotic translation initiation factor 4E family member 2 [KO:K03259]
102282841  EIF4E; eukaryotic translation initiation factor 4E [KO:K03259]
102285710  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
102271079  RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:2.7.11.1]
102278820  RPS6; ribosomal protein S6 [KO:K02991]
102288255  HIF1A; hypoxia inducible factor 1 alpha subunit [KO:K08268]
102274048  VHL; von Hippel-Lindau tumor suppressor [KO:K03871]
102272719  RBX1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
102267084  ELOC; elongin C [KO:K03872]
102265644  transcription elongation factor B polypeptide 2 [KO:K03873]
102288128  ELOB; elongin B [KO:K03873]
102276684  CUL2; cullin 2 [KO:K03870]
102280646  EGLN2; egl-9 family hypoxia inducible factor 2 [KO:K09592] [EC:1.14.11.29]
102287116  EGLN1; egl-9 family hypoxia inducible factor 1 [KO:K09592] [EC:1.14.11.29]
102280498  EGLN3; egl-9 family hypoxia inducible factor 3 [KO:K09592] [EC:1.14.11.29]
102287994  ARNT; aryl hydrocarbon receptor nuclear translocator [KO:K09097]
102264880  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
102273007  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
102288244  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
102265099  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
102285300  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
102278724  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102274116  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
102265831  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
102281822  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
102271451  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
102279381  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
102280002  calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
102285540  TIMP1; TIMP metallopeptidase inhibitor 1 [KO:K16451]
102286430  LTBR; lymphotoxin beta receptor [KO:K03159]
102279821  EPO; erythropoietin [KO:K05437]
102276879  TF; transferrin [KO:K14736]
102276607  inhibitor of carbonic anhydrase [KO:K14736]
102278238  TFRC; transferrin receptor [KO:K06503]
102270607  VEGFA; vascular endothelial growth factor A [KO:K05448]
102269660  FLT1; fms related tyrosine kinase 1 [KO:K05096] [EC:2.7.10.1]
102275884  SERPINE1; serpin family E member 1 [KO:K03982]
102267130  ANGPT1; angiopoietin 1 [KO:K05465]
102272495  ANGPT2; angiopoietin 2 [KO:K05466]
102281947  ANGPT4; angiopoietin 4 [KO:K05467]
102283049  TEK; TEK receptor tyrosine kinase [KO:K05121] [EC:2.7.10.1]
102272983  EDN1; endothelin 1 [KO:K16366]
102265893  NOS2; nitric oxide synthase 2 [KO:K13241] [EC:1.14.13.39]
102267556  NOS3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
102281265  HMOX1; heme oxygenase 1 [KO:K00510] [EC:1.14.14.18]
102287668  NPPA; natriuretic peptide A [KO:K12334]
102278454  SLC2A1; solute carrier family 2 member 1 [KO:K07299]
102265648  PDK1; pyruvate dehydrogenase kinase 1 [KO:K12077] [EC:2.7.11.2]
102270322  HK1; hexokinase 1 [KO:K00844] [EC:2.7.1.1]
102268099  HKDC1; hexokinase domain containing 1 [KO:K00844] [EC:2.7.1.1]
102275095  HK3; hexokinase 3 [KO:K00844] [EC:2.7.1.1]
102274810  HK2; hexokinase 2 [KO:K00844] [EC:2.7.1.1]
102269659  PFKP; phosphofructokinase, platelet [KO:K00850] [EC:2.7.1.11]
102285285  PFKM; phosphofructokinase, muscle [KO:K00850] [EC:2.7.1.11]
102268656  PFKL; phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
102275759  GAPDH; glyceraldehyde-3-phosphate dehydrogenase [KO:K00134] [EC:1.2.1.12]
102267185  ALDOC; aldolase, fructose-bisphosphate C [KO:K01623] [EC:4.1.2.13]
102270580  ALDOA; aldolase, fructose-bisphosphate A [KO:K01623] [EC:4.1.2.13]
102287742  ALDOB; aldolase, fructose-bisphosphate B [KO:K01623] [EC:4.1.2.13]
102265407  ENO1; enolase 1 [KO:K01689] [EC:4.2.1.11]
102283349  ENO2; enolase 2 [KO:K01689] [EC:4.2.1.11]
102267910  ENO3; enolase 3 [KO:K01689] [EC:4.2.1.11]
102276694  PGK1; phosphoglycerate kinase 1 [KO:K00927] [EC:2.7.2.3]
102268739  PGK2; phosphoglycerate kinase 2 [KO:K00927] [EC:2.7.2.3]
102276469  PFKFB3; 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 [KO:K01103] [EC:2.7.1.105 3.1.3.46]
102265127  LDHB; lactate dehydrogenase B [KO:K00016] [EC:1.1.1.27]
102274962  LDHA; L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
102274105  LDHC; L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
102282411  LDHAL6B; lactate dehydrogenase A like 6B [KO:K00016] [EC:1.1.1.27]
102268592  BCL2; BCL2, apoptosis regulator [KO:K02161]
102268672  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
102276245  CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624]
102286090  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
102275901  PDHA1; pyruvate dehydrogenase (lipoamide) alpha 1 [KO:K00161] [EC:1.2.4.1]
102287624  PDHB; pyruvate dehydrogenase (lipoamide) beta [KO:K00162] [EC:1.2.4.1]
Compound
C00002  ATP
C00007  Oxygen
C00022  Pyruvate
C00024  Acetyl-CoA
C00026  2-Oxoglutarate
C00031  D-Glucose
C00072  Ascorbate
C00076  Calcium cation
C00165  Diacylglycerol
C00186  (S)-Lactate
C00338  Lipopolysaccharide
C00533  Nitric oxide
C00704  Superoxide
C01245  D-myo-Inositol 1,4,5-trisphosphate
C14818  Fe2+
Reference
PMID:20836033
  Authors
Semenza GL
  Title
Oxygen homeostasis.
  Journal
Wiley Interdiscip Rev Syst Biol Med 2:336-61 (2010)
DOI:10.1002/wsbm.69
Reference
PMID:17955264
  Authors
Mole DR, Ratcliffe PJ
  Title
Cellular oxygen sensing in health and disease.
  Journal
Pediatr Nephrol 23:681-94 (2008)
DOI:10.1007/s00467-007-0632-x
Reference
PMID:18498744
  Authors
Kaelin WG Jr, Ratcliffe PJ
  Title
Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.
  Journal
Mol Cell 30:393-402 (2008)
DOI:10.1016/j.molcel.2008.04.009
Reference
PMID:22205687
  Authors
Palazon A, Aragones J, Morales-Kastresana A, de Landazuri MO, Melero I
  Title
Molecular pathways: hypoxia response in immune cells fighting or promoting cancer.
  Journal
Clin Cancer Res 18:1207-13 (2012)
DOI:10.1158/1078-0432.CCR-11-1591
Reference
PMID:20965423
  Authors
Majmundar AJ, Wong WJ, Simon MC
  Title
Hypoxia-inducible factors and the response to hypoxic stress.
  Journal
Mol Cell 40:294-309 (2010)
DOI:10.1016/j.molcel.2010.09.022
Reference
PMID:22562152
  Authors
Greer SN, Metcalf JL, Wang Y, Ohh M
  Title
The updated biology of hypoxia-inducible factor.
  Journal
EMBO J 31:2448-60 (2012)
DOI:10.1038/emboj.2012.125
Reference
PMID:15448722
  Authors
Zagorska A, Dulak J
  Title
HIF-1: the knowns and unknowns of hypoxia sensing.
  Journal
Acta Biochim Pol 51:563-85 (2004)
Reference
PMID:19364912
  Authors
Semenza GL
  Title
Regulation of oxygen homeostasis by hypoxia-inducible factor 1.
  Journal
Physiology (Bethesda) 24:97-106 (2009)
DOI:10.1152/physiol.00045.2008
Reference
PMID:16234508
  Authors
Wenger RH, Stiehl DP, Camenisch G
  Title
Integration of oxygen signaling at the consensus HRE.
  Journal
Sci STKE 2005:re12 (2005)
DOI:10.1126/stke.3062005re12
Reference
PMID:15031665
  Authors
Lee JW, Bae SH, Jeong JW, Kim SH, Kim KW
  Title
Hypoxia-inducible factor (HIF-1)alpha: its protein stability and biological functions.
  Journal
Exp Mol Med 36:1-12 (2004)
DOI:10.1038/emm.2004.1
Reference
PMID:18259201
  Authors
Weidemann A, Johnson RS
  Title
Biology of HIF-1alpha.
  Journal
Cell Death Differ 15:621-7 (2008)
DOI:10.1038/cdd.2008.12
Reference
PMID:11902584
  Authors
Harris AL
  Title
Hypoxia--a key regulatory factor in tumour growth.
  Journal
Nat Rev Cancer 2:38-47 (2002)
DOI:10.1038/nrc704
Reference
PMID:19147540
  Authors
Knaup KX, Jozefowski K, Schmidt R, Bernhardt WM, Weidemann A, Juergensen JS, Warnecke C, Eckardt KU, Wiesener MS
  Title
Mutual regulation of hypoxia-inducible factor and mammalian target of rapamycin as a function of oxygen availability.
  Journal
Mol Cancer Res 7:88-98 (2009)
DOI:10.1158/1541-7786.MCR-08-0288
Reference
PMID:18505681
  Authors
Kaluz S, Kaluzova M, Stanbridge EJ
  Title
Regulation of gene expression by hypoxia: integration of the HIF-transduced hypoxic signal at the hypoxia-responsive element.
  Journal
Clin Chim Acta 395:6-13 (2008)
DOI:10.1016/j.cca.2008.05.002
Reference
PMID:20679415
  Authors
Cadenas S, Aragones J, Landazuri MO
  Title
Mitochondrial reprogramming through cardiac oxygen sensors in ischaemic heart disease.
  Journal
Cardiovasc Res 88:219-28 (2010)
DOI:10.1093/cvr/cvq256
Reference
PMID:19861159
  Authors
Berchner-Pfannschmidt U, Tug S, Kirsch M, Fandrey J
  Title
Oxygen-sensing under the influence of nitric oxide.
  Journal
Cell Signal 22:349-56 (2010)
DOI:10.1016/j.cellsig.2009.10.004
Related
pathway
bom00020  Citrate cycle (TCA cycle)
bom04010  MAPK signaling pathway
bom04020  Calcium signaling pathway
bom04120  Ubiquitin mediated proteolysis
bom04150  mTOR signaling pathway
bom04151  PI3K-Akt signaling pathway
bom04370  VEGF signaling pathway
KO pathway
ko04066   
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