Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

1.14.99.3

Official Name

heme oxygenase

Name from literature

Heme oxygenase

Pathway from literature

CO generation,degrades heme/ production of bilirubin/ heme degradation pathway

Pathway from KEGG

Metabolism of Cofactors and Vitamins; Porphyrin and chlorophyll metabolism; map00860

Organisms

Human (9606)

Genome localization

22q12|22q13.1[3162 ], 16p13.3[3163 ],

Comments

Requires NAD(P)H and EC 1.6.2.4, NADPH---hemoprotein reductase. The terminal oxygen atoms that are incorporated into the carbonyl groups of pyrrole rings A and B of biliverdin are derived from two separate oxygen molecules [4]. The third oxygen molecule provides the oxygen atom that converts the alpha-carbon to CO. The central iron is kept in the reduced state by NAD(P)H.

Rate-limiting Description

"Heme oxygenase-1 (HO-1), which is the rate-limiting enzyme in heme catabolism, was also associated with activated macrophages." (10353745)

"Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme catabolism and presumably is involved in cellular iron homeostasis." (10644516)

"Heme oxygenase is a rate-limiting enzyme in heme catabolism that cleaves heme to form biliverdin, carbon monoxide, and iron." (10349844)

Regulatory Information

Upstream transcription factor

1432;3297;3162;6720

Regulatory type

Detail

phosphorylation;

"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." (17081983)

transcriptional factor;TGF-beta1(7040)

"TGF-beta1 is a potent inducer of HO-1; the signaling pathway by which TGF-beta1 regulates HO-1 expression in human lung epithelial cells" (12376363)

transcriptional factor;HSF-1(3297)

"It is possible that HSF-1 negatively regulates HO-1 gene expression, and that the consensus heat shock element present in the -389 to -362 region mediates HSF-1-induced repression of HO-1 gene expression." (15618017)

transcriptional factor;AEBSF(1432)

"transcriptional induction of HO-1 gene expression by AEBSF is mediated via activation of a PKB, p38 MAPK signaling pathway" (15833736)

signal pathway;p38(1432)

"up-regulation of HO-1 by non-steroidal anti-inflammatory drugs (NSAIDs) is mediated through NSAID-dependent activation (phosphorylation) of p38 mitogen-activated protein kinase" (16945925)

transcriptional factor;HSF1(3297)

"HSF1 is directly involved in the regulation of HO-1 with an anti-oxidative role" (17244614)

transcriptional factor;SREBP-1(6720)

"We have identified novel nonclassical mediators of the SREBP-1 response, including HMOX1, supporting the hypothesis that SREBP-1 regulates stress response and signaling genes." (17452746)

signal pathway;

"Isothiocyanates activate antioxidant response element(ARE)-mediated HO-1 gene transcription through Nrf2/ARE signaling pathway." (17657593)

phosphorylation;

P09601

phosphorylation;

P09601:from_uniprot:229_Phosphoserine

transcriptional factor;HMOX1(3162)

"Comparison of the heme-free and -bound crystal structures of human heme oxygenase-1." (12500973)

transcriptional factor;HMOX1(3162)

"Comparison of the heme-free and -bound crystal structures of human heme oxygenase-1." (12500973#16189514)

Gene ontology

Gene ontology

GO:0005615 (C) extracellular space [P09601 ];
GO:0019899 (F) enzyme binding [P09601 ];
GO:0005515 (F) protein binding [P30519 ];
GO:0043123 (P) positive regulation of I-kappaB kinase/NF-k... [P09601 ];
GO:0043619 (P) regulation of transcription from RNA polyme... [P09601 ];
GO:0042167 (P) heme catabolic process [P09601 ];
GO:0002246 (P) healing during inflammatory response [P09601 ];
GO:0034101 (P) erythrocyte homeostasis [P09601 ];
GO:0001935 (P) endothelial cell proliferation [P09601 ];
GO:0005634 (C) nucleus [P09601 ];
GO:0034383 (P) low-density lipoprotein particle clearance [P09601 ];
GO:0004392 (F) heme oxygenase (decyclizing) activity [P09601, P30519 ];
GO:0045080 (P) positive regulation of chemokine biosynthet... [P09601 ];
GO:0035094 (P) response to nicotine [P09601 ];
GO:0014806 (P) smooth muscle hyperplasia [P09601 ];
GO:0055072 (P) iron ion homeostasis [P09601 ];
GO:0020037 (F) heme binding [P09601 ];
GO:0042542 (P) response to hydrogen peroxide [P09601 ];
GO:0051090 (P) regulation of transcription factor activity [P09601 ];
GO:0009055 (F) electron carrier activity [P30519 ];
GO:0002686 (P) negative regulation of leukocyte migration [P09601 ];
GO:0007588 (P) excretion [P09601 ];
GO:0045909 (P) positive regulation of vasodilation [P09601 ];
GO:0005783 (C) endoplasmic reticulum [P09601, P30519 ];
GO:0045765 (P) regulation of angiogenesis [P09601 ];
GO:0001666 (P) response to hypoxia [P30519 ];
GO:0005886 (C) plasma membrane [P30519 ];
GO:0005506 (F) iron ion binding [P09601, P30519 ];
GO:0006788 (P) heme oxidation [P09601, P30519 ];
GO:0004871 (F) signal transducer activity [P09601 ];
GO:0005792 (C) microsome [P09601, P30519 ];
GO:0006916 (P) anti-apoptosis [P09601 ];
GO:0055114 (P) oxidation reduction [P09601, P30519 ];

Subcellular localization

Localization

endoplasmic reticulum [P09601, P30519 ];

microsome [P09601, P30519 ];

Links

SwissProt

P09601; P30519

Entrez Gene

3162; 3163

HPRD

00782; 00783



  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min