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Haem oxygenase 1

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Target id: 1441

Nomenclature: Haem oxygenase 1

Abbreviated Name: HO1

Family: Haem oxygenase

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 288 22q12.3 HMOX1 heme oxygenase 1
Mouse - 289 8 C1 Hmox1 heme oxygenase 1
Rat - 289 19p11 Hmox1 heme oxygenase 1
Previous and Unofficial Names Click here for help
hsp32 | heme oxygenase 1 | Heox | HEOXG | Hmox | HO-1 | heme oxygenase (decycling) 1
Database Links Click here for help
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BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
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Enzyme Reaction Click here for help
EC Number: 1.14.14.18
Description Reaction Reference
Protoheme + 3 [reduced NADPH-hemoprotein reductase] + 3 O(2) <=> biliverdin + Fe(2+) + CO + 3 [oxidized NADPH-hemoprotein reductase] + 3 H(2)O

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 1 [PMID: 16821802] Small molecule or natural product Hs Inhibition 5.8 pKi 4
pKi 5.8 (Ki 1.5x10-6 M) [4]
Description: Enzyme isolated from human spleen.
compound 1 [PMID: 16821802] Small molecule or natural product Click here for species-specific activity table Rn Inhibition 6.1 pIC50 4
pIC50 6.1 (IC50 8x10-7 M) [4]
Description: Enzyme isolated from rat spleen.
View species-specific inhibitor tables
Immunopharmacology Comments
Heme oxygenase (HO) is a rate-limiting enzyme in the catabolism of heme, catalyzing the oxidative cleavage of heme (Fe-protoporphyrin-IX) to render equimolar amounts of biliverdin, ferrous iron (Fe2+), and carbon monoxide (CO).

Heme oxygenase 1 (HO1) is a Nrf2-regulated gene, whose expression is upregulated as a cytoprotective mechanism in response to cellular stresses including inflammation, ischemia, hypoxia, hyperoxia, hyperthermia, or radiation.

HO1 has antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, playing an important role in the prevention of vascular inflammation and atherogenesis (reviewed in [2]). HO1 may also be involved in macrophage differentiation and polarization to certain subtypes, and studies in animals and in human aortic endothelial cells suggest a protective role in prevention of allograft rejection [1,3].
Cell Type Associations
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   immature conventional dendritic cell (CL:0000840)
Comment:  HO1 expression inhibits dendritic cell maturation and secretion of proinflammatory cytokines.
References:  2
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   macrophage (CL:0000235)
monocyte (CL:0000576)
References:  2
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 3 GO processes
GO:0002246 wound healing involved in inflammatory response IMP
GO:0002686 negative regulation of leukocyte migration TAS
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GO:0043305 negative regulation of mast cell degranulation IEA
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 1 GO processes
GO:0034383 low-density lipoprotein particle clearance TAS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 4 GO processes
GO:0002686 negative regulation of leukocyte migration TAS
GO:0034101 erythrocyte homeostasis IMP
click arrow to show/hide IEA associations
GO:0032764 negative regulation of mast cell cytokine production IEA
GO:0043305 negative regulation of mast cell degranulation IEA
Immuno Process:  Tissue repair
GO Annotations:  Associated to 1 GO processes
GO:0002246 wound healing involved in inflammatory response IMP
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 2 GO processes
GO:0032722 positive regulation of chemokine production TAS
click arrow to show/hide IEA associations
GO:0032764 negative regulation of mast cell cytokine production IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 2 GO processes
GO:0002686 negative regulation of leukocyte migration TAS
GO:0032722 positive regulation of chemokine production TAS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0043305 negative regulation of mast cell degranulation IEA

References

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1. Araujo JA, Meng L, Tward AD, Hancock WW, Zhai Y, Lee A, Ishikawa K, Iyer S, Buelow R, Busuttil RW et al.. (2003) Systemic rather than local heme oxygenase-1 overexpression improves cardiac allograft outcomes in a new transgenic mouse. J Immunol, 171 (3): 1572-80. [PMID:12874251]

2. Araujo JA, Zhang M, Yin F. (2012) Heme oxygenase-1, oxidation, inflammation, and atherosclerosis. Front Pharmacol, 3: 119. [PMID:22833723]

3. Romanoski CE, Che N, Yin F, Mai N, Pouldar D, Civelek M, Pan C, Lee S, Vakili L, Yang WP et al.. (2011) Network for activation of human endothelial cells by oxidized phospholipids: a critical role of heme oxygenase 1. Circ Res, 109 (5): e27-41. [PMID:21737788]

4. Vlahakis JZ, Kinobe RT, Bowers RJ, Brien JF, Nakatsu K, Szarek WA. (2006) Imidazole-dioxolane compounds as isozyme-selective heme oxygenase inhibitors. J Med Chem, 49 (14): 4437-41. [PMID:16821802]

Contributors

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