KEGG   PATHWAY: ajm04066
Entry
ajm04066                    Pathway                                
Name
HIF-1 signaling pathway - Artibeus jamaicensis (Jamaican fruit-eating bat)
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
ajm04066  HIF-1 signaling pathway
ajm04066

Organism
Artibeus jamaicensis (Jamaican fruit-eating bat) [GN:ajm]
Gene
119042560  IL6; interleukin-6 isoform X1 [KO:K05405]
119061811  IL6R; interleukin-6 receptor subunit alpha [KO:K05055]
119052142  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
119056324  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
119042309  IFNG; interferon gamma [KO:K04687]
119051850  IFNGR1; interferon gamma receptor 1 [KO:K05132]
119035735  IFNGR2; interferon gamma receptor 2 [KO:K05133]
119050282  RELA; transcription factor p65 [KO:K04735]
119057921  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
119057541  INS; insulin [KO:K04526]
119057431  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
119060308  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
119045329  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
119057339  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
119049802  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
119057101  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
119063754  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
119040930  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119059157  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
119045082  MAP kinase-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K04372] [EC:2.7.11.1]
119043820  MKNK2; MAP kinase-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K04372] [EC:2.7.11.1]
119043036  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
119044861  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119064089  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119052227  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
119053288  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
119046830  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
119040479  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119053408  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119063115  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119064071  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
119065028  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
119045012  LOW QUALITY PROTEIN: eukaryotic translation initiation factor 4E type 2-like [KO:K03259]
119046526  EIF4E; LOW QUALITY PROTEIN: eukaryotic translation initiation factor 4E [KO:K03259]
119054312  EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
119062958  EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
119065424  LOW QUALITY PROTEIN: eukaryotic translation initiation factor 4E-like [KO:K03259]
119041842  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
119062679  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
119035211  LOW QUALITY PROTEIN: 40S ribosomal protein S6-like [KO:K02991]
119039580  RPS6; LOW QUALITY PROTEIN: 40S ribosomal protein S6 [KO:K02991]
119042644  40S ribosomal protein S6-like [KO:K02991]
119064525  LOW QUALITY PROTEIN: 40S ribosomal protein S6-like [KO:K02991]
119039594  HIF1A; hypoxia-inducible factor 1-alpha [KO:K08268]
119038335  von Hippel-Lindau disease tumor suppressor [KO:K03871]
119041442  von Hippel-Lindau disease tumor suppressor-like [KO:K03871]
119058834  von Hippel-Lindau disease tumor suppressor-like [KO:K03871]
119060371  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
119053416  ELOC; elongin-C [KO:K03872]
119058208  ELOB; elongin-B isoform X1 [KO:K03873]
119038940  CUL2; cullin-2 [KO:K03870]
119040737  EGLN2; prolyl hydroxylase EGLN2 [KO:K09592] [EC:1.14.11.29]
119042924  EGLN1; egl nine homolog 1 isoform X1 [KO:K09592] [EC:1.14.11.29]
119061156  EGLN3; prolyl hydroxylase EGLN3 [KO:K09592] [EC:1.14.11.29]
119034693  ARNT; aryl hydrocarbon receptor nuclear translocator isoform X1 [KO:K09097]
119060587  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
119056235  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
119063653  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
119063199  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
119047103  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
119036326  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
119043241  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
119036009  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
119037697  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
119038077  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
119052888  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
119061401  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
119060159  TIMP1; metalloproteinase inhibitor 1 [KO:K16451]
119060191  LTBR; tumor necrosis factor receptor superfamily member 3 [KO:K03159]
119041558  EPO; erythropoietin isoform X1 [KO:K05437]
119048276  serotransferrin-like [KO:K14736]
119048279  inhibitor of carbonic anhydrase-like [KO:K14736]
119050880  serotransferrin-like [KO:K14736]
119050872  TFRC; transferrin receptor protein 1 [KO:K06503]
119055590  VEGFA; vascular endothelial growth factor A [KO:K05448]
119041773  vascular endothelial growth factor receptor kdr-like [KO:K05096] [EC:2.7.10.1]
119064949  FLT1; vascular endothelial growth factor receptor 1 [KO:K05096] [EC:2.7.10.1]
119044724  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
119054343  ANGPT1; angiopoietin-1 [KO:K05465]
119040807  ANGPT2; angiopoietin-2 isoform X1 [KO:K05466]
119047700  ANGPT4; angiopoietin-4 [KO:K05467]
119046176  TEK; angiopoietin-1 receptor [KO:K05121] [EC:2.7.10.1]
119054876  EDN1; endothelin-1 [KO:K16366]
119062015  NOS2; LOW QUALITY PROTEIN: nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
119039263  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
119060410  HMOX1; heme oxygenase 1 [KO:K00510] [EC:1.14.14.18]
119064118  NPPA; natriuretic peptides A [KO:K12334]
119052239  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
119053640  PDK1; pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial isoform X1 [KO:K12077] [EC:2.7.11.2]
119038115  HK1; hexokinase-1 isoform X1 [KO:K00844] [EC:2.7.1.1]
119038131  HKDC1; hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
119038386  HK2; hexokinase-2 isoform X1 [KO:K00844] [EC:2.7.1.1]
119062960  HK3; hexokinase-3 isoform X1 [KO:K00844] [EC:2.7.1.1]
119042065  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
119057685  ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
119058740  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
119043154  LOW QUALITY PROTEIN: glyceraldehyde-3-phosphate dehydrogenase-like [KO:K00134] [EC:1.2.1.12]
119059345  LOW QUALITY PROTEIN: glyceraldehyde-3-phosphate dehydrogenase-like [KO:K00134] [EC:1.2.1.12]
119060182  GAPDH; glyceraldehyde-3-phosphate dehydrogenase [KO:K00134] [EC:1.2.1.12]
119045596  glyceraldehyde-3-phosphate dehydrogenase 2, cytosolic [KO:K00134] [EC:1.2.1.12]
119048587  glyceraldehyde-3-phosphate dehydrogenase 2-like [KO:K00134] [EC:1.2.1.12]
119056868  LOW QUALITY PROTEIN: glyceraldehyde-3-phosphate dehydrogenase-like [KO:K00134] [EC:1.2.1.12]
119065099  glyceraldehyde-3-phosphate dehydrogenase 1, cytosolic isoform X1 [KO:K00134] [EC:1.2.1.12]
119050287  glyceraldehyde-3-phosphate dehydrogenase-like [KO:K00134] [EC:1.2.1.12]
119040430  fructose-bisphosphate aldolase 1, cytoplasmic [KO:K01623] [EC:4.1.2.13]
119040954  ALDOA; fructose-bisphosphate aldolase A isoform X1 [KO:K01623] [EC:4.1.2.13]
119045950  ALDOB; fructose-bisphosphate aldolase B [KO:K01623] [EC:4.1.2.13]
119062042  ALDOC; fructose-bisphosphate aldolase C [KO:K01623] [EC:4.1.2.13]
119038816  enolase 1 [KO:K01689] [EC:4.2.1.11]
119039101  enolase-related protein 1 [KO:K01689] [EC:4.2.1.11]
119042697  enolase-like [KO:K01689] [EC:4.2.1.11]
119059809  LOW QUALITY PROTEIN: beta-enolase-like [KO:K01689] [EC:4.2.1.11]
119060546  ENO2; gamma-enolase [KO:K01689] [EC:4.2.1.11]
119046917  alpha-enolase-like [KO:K01689] [EC:4.2.1.11]
119048599  ENO3; LOW QUALITY PROTEIN: beta-enolase [KO:K01689] [EC:4.2.1.11]
119055926  ENO1; alpha-enolase [KO:K01689] [EC:4.2.1.11]
119039453  PGK1; phosphoglycerate kinase 1 [KO:K00927] [EC:2.7.2.3]
119053621  PGK2; phosphoglycerate kinase 2 [KO:K00927] [EC:2.7.2.3]
119039559  6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase-like [KO:K01103] [EC:2.7.1.105 3.1.3.46]
119056680  PFKFB3; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 isoform X1 [KO:K01103] [EC:2.7.1.105 3.1.3.46]
119034900  L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
119042839  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
119053090  L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
119053093  LDHA; L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
119057575  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
119050063  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
119042826  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
119043051  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial-like isoform X1 [KO:K00161] [EC:1.2.4.1]
119044419  pyruvate dehydrogenase E1 component subunit alpha-1, mitochondrial [KO:K00161] [EC:1.2.4.1]
119064190  pyruvate dehydrogenase E1 component subunit alpha-3, chloroplastic [KO:K00161] [EC:1.2.4.1]
119058337  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
119043350  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
119049306  pyruvate dehydrogenase E1 component subunit beta-1, mitochondrial [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
ajm00020  Citrate cycle (TCA cycle)
ajm04010  MAPK signaling pathway
ajm04020  Calcium signaling pathway
ajm04120  Ubiquitin mediated proteolysis
ajm04150  mTOR signaling pathway
ajm04151  PI3K-Akt signaling pathway
ajm04370  VEGF signaling pathway
KO pathway
ko04066   
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