Heme oxygenase 1

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityⁱ

• heme b

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  + 3 O₂

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  + 3 reduced [NADPH—hemoprotein reductase]

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  = biliverdin IXα

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  + CO

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  + Fe²⁺

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  + H⁺

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  + 3 H₂O

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  + 3 oxidized [NADPH—hemoprotein reductase]

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  By similarity

  <p>Manually curated information which has been propagated from a related experimentally characterized protein.</p> <p><a href="/manual/evidences#ECO:0000250">More...</a></p> Manual assertion inferred from sequence similarity toⁱ

  • UniProtKB:O48782 (HMOX1_ARATH)
  EC:1.14.14.18
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  By similarity

  Manual assertion inferred from sequence similarity toⁱ

  • UniProtKB:O48782 (HMOX1_ARATH)
  Source: Rhea

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  • See the description of this reaction in Rhea.

  . Show »« Hide
  heme b

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  zoom

  +

  3

  O₂

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  +

  3

  reduced [NADPH—hemoprotein reductase]

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  FMNH₂

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  =

  biliverdin IXα

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  zoom

  +

  CO

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  +

  Fe²⁺

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  zoom

  +

  H⁺

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  +

  3

  H₂O

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  +

  3

  oxidized [NADPH—hemoprotein reductase]

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  FMN

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Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• enzyme binding Source: BHF-UCL <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Involvement of NADPH in the interaction between heme oxygenase-1 and cytochrome P450 reductase."
    Higashimoto Y., Sakamoto H., Hayashi S., Sugishima M., Fukuyama K., Palmer G., Noguchi M.
    J Biol Chem 280:729-737(2005) [PubMed] [Europe PMC] [Abstract]
• heme binding Source: RGD <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "Crystal structure of rat apo-heme oxygenase-1 (HO-1): mechanism of heme binding in HO-1 inferred from structural comparison of the apo and heme complex forms."
    Sugishima M., Sakamoto H., Kakuta Y., Omata Y., Hayashi S., Noguchi M., Fukuyama K.
    Biochemistry 41:7293-7300(2002) [PubMed] [Europe PMC] [Abstract]
• heme oxygenase (decyclizing) activity Source: BHF-UCLInferred from direct assayⁱ
  • Ref.2

    "Cloning and expression of cDNA for rat heme oxygenase."
    Shibahara S., Mueller R., Taguchi H., Yoshida T.
    Proc. Natl. Acad. Sci. U.S.A. 82:7865-7869(1985) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
• identical protein binding Source: RGD
• metal ion binding Source: UniProtKB-KW
• phospholipase D activity Source: RGDInferred from direct assayⁱ
  • "Heme oxygenase inhibitor restores arteriolar nitric oxide function in dahl rats."
    Johnson F.K., Durante W., Peyton K.J., Johnson R.A.
    Hypertension 41:149-155(2003) [PubMed] [Europe PMC] [Abstract]
• protein homodimerization activity Source: RGD
• structural molecule activity Source: RGD

GO - Biological processⁱ

• angiogenesis Source: RGDInferred from direct assayⁱ
  • "Facilitated angiogenesis induced by heme oxygenase-1 gene transfer in a rat model of hindlimb ischemia."
    Suzuki M., Iso-o N., Takeshita S., Tsukamoto K., Mori I., Sato T., Ohno M., Nagai R., Ishizaka N.
    Biochem Biophys Res Commun 302:138-143(2003) [PubMed] [Europe PMC] [Abstract]
• cell death Source: BHF-UCLInferred from direct assayⁱ
  • "Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress."
    Lin Q., Weis S., Yang G., Weng Y.H., Helston R., Rish K., Smith A., Bordner J., Polte T., Gaunitz F., Dennery P.A.
    J Biol Chem 282:20621-20633(2007) [PubMed] [Europe PMC] [Abstract]
• cellular iron ion homeostasis Source: RGD
• cellular response to arsenic-containing substance Source: RGD
• cellular response to cadmium ion Source: RGD
• cellular response to cisplatin Source: RGD
• cellular response to heat Source: RGD
• cellular response to hypoxia Source: RGD
• cellular response to nutrient Source: RGD <p>Inferred from Expression Pattern</p> <p>Covers cases where the annotation is inferred from the timing or location of expression of a gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iep">GO evidence code guide</a></p> Inferred from expression patternⁱ
  • "Effects of 1alpha,25 dihydroxyvitamin D3 on the expression of HO-1 and GFAP in glial cells of the photothrombotically lesioned cerebral cortex."
    Oermann E., Bidmon H.J., Witte O.W., Zilles K.
    J Chem Neuroanat 28:225-238(2004) [PubMed] [Europe PMC] [Abstract]
• erythrocyte homeostasis Source: RGD
• heme catabolic process Source: RGDInferred from direct assayⁱ
  • "Caveolae compartmentalization of heme oxygenase-1 in endothelial cells."
    Kim H.P., Wang X., Galbiati F., Ryter S.W., Choi A.M.
    FASEB J 18:1080-1089(2004) [PubMed] [Europe PMC] [Abstract]
• heme metabolic process Source: RGD
• heme oxidation Source: RGD
• intracellular signal transduction Source: RGDInferred from direct assayⁱ
  • "Mitogen-activated protein kinases regulate HO-1 gene transcription after ischemia-reperfusion lung injury."
    Zhang X., Bedard E.L., Potter R., Zhong R., Alam J., Choi A.M., Lee P.J.
    Am J Physiol Lung Cell Mol Physiol 283:L815-29(2002) [PubMed] [Europe PMC] [Abstract]
• intrinsic apoptotic signaling pathway in response to DNA damage Source: RGDInferred from direct assayⁱ
  • "Leydig cell-derived heme oxygenase-1 regulates apoptosis of premeiotic germ cells in response to stress."
    Ozawa N., Goda N., Makino N., Yamaguchi T., Yoshimura Y., Suematsu M.
    J Clin Invest 109:457-467(2002) [PubMed] [Europe PMC] [Abstract]
• iron ion homeostasis Source: RGD
• liver regeneration Source: RGD <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Regulation of heme oxygenase 1 expression by miR-27b with stem cell therapy for liver regeneration in rats."
    Chen K.D., Hsu L.W., Goto S., Huang K.T., Nakano T., Weng W.T., Lai C.Y., Kuo Y.R., Chiu K.W., Wang C.C., Cheng Y.F., Lin C.C., Ma Y.Y., Chen C.L.
    Transplant Proc 46:1198-1200(2014) [PubMed] [Europe PMC] [Abstract]
• negative regulation of cell population proliferation Source: RGDInferred from direct assayⁱ
  • "Heme oxygenase-1 inhibits rat and human breast cancer cell proliferation: mutual cross inhibition with indoleamine 2,3-dioxygenase."
    Hill M., Pereira V., Chauveau C., Zagani R., Remy S., Tesson L., Mazal D., Ubillos L., Brion R., Asghar K., Ashgar K., Mashreghi M.F., Kotsch K., Moffett J., Doebis C., Seifert M., Boczkowski J., Osinaga E., Anegon I.
    FASEB J 19:1957-1968(2005) [PubMed] [Europe PMC] [Abstract]
• negative regulation of DNA binding Source: RGDInferred from direct assayⁱ
  • "Heme oxygenase-1 inhibits cytokine production by activated mast cells."
    Yasui Y., Nakamura M., Onda T., Uehara T., Murata S., Matsui N., Fukuishi N., Akagi R., Suematsu M., Akagi M.
    Biochem Biophys Res Commun 354:485-490(2007) [PubMed] [Europe PMC] [Abstract]
• negative regulation of DNA-binding transcription factor activity Source: RGDInferred from direct assayⁱ
  • "Heme oxygenase-1 inhibits cytokine production by activated mast cells."
    Yasui Y., Nakamura M., Onda T., Uehara T., Murata S., Matsui N., Fukuishi N., Akagi R., Suematsu M., Akagi M.
    Biochem Biophys Res Commun 354:485-490(2007) [PubMed] [Europe PMC] [Abstract]
• negative regulation of epithelial cell apoptotic process Source: RGDInferred from mutant phenotypeⁱ
  • "[The role of heme oxygenase 1 in hydrogen peroxide induced apoptosis and mitochondrial trans membrane potential change in rat primary type II alveolar epithelium cells]."
    Wu Y., Chen M., Wu S., Wang H.M., Qian M.J., Wang Y.H., Fu X.Y.
    Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 23:658-660(2011) [PubMed] [Europe PMC] [Abstract]
• negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: RGD
• negative regulation of macroautophagy Source: RGD
• negative regulation of mast cell cytokine production Source: RGDInferred from direct assayⁱ
  • "Heme oxygenase-1 inhibits cytokine production by activated mast cells."
    Yasui Y., Nakamura M., Onda T., Uehara T., Murata S., Matsui N., Fukuishi N., Akagi R., Suematsu M., Akagi M.
    Biochem Biophys Res Commun 354:485-490(2007) [PubMed] [Europe PMC] [Abstract]
• negative regulation of mast cell degranulation Source: RGDInferred from direct assayⁱ
  • "Heme oxygenase-1 inhibits cytokine production by activated mast cells."
    Yasui Y., Nakamura M., Onda T., Uehara T., Murata S., Matsui N., Fukuishi N., Akagi R., Suematsu M., Akagi M.
    Biochem Biophys Res Commun 354:485-490(2007) [PubMed] [Europe PMC] [Abstract]
• negative regulation of muscle cell apoptotic process Source: RGDInferred from direct assayⁱ
  • "Heme oxygenase 1 mediates the immunomodulatory and antiapoptotic effects of interleukin 13 gene therapy in vivo and in vitro."
    Ke B., Shen X.D., Zhai Y., Gao F., Busuttil R.W., Volk H.D., Kupiec-Weglinski J.W.
    Hum Gene Ther 13:1845-1857(2002) [PubMed] [Europe PMC] [Abstract]
• negative regulation of neuron apoptotic process Source: RGDInferred from mutant phenotypeⁱ
  • "Neuroprotective role of heme-oxygenase 1 against iodoacetate-induced toxicity in rat cerebellar granule neurons: Role of bilirubin."
    Gonzalez-Reyes S., Orozco-Ibarra M., Guzman-Beltran S., Molina-Jijon E., Massieu L., Pedraza-Chaverri J.
    Free Radic Res 43:214-223(2009) [PubMed] [Europe PMC] [Abstract]
• negative regulation of smooth muscle cell proliferation Source: RGDInferred from mutant phenotypeⁱ
  • "Aprotinin Inhibits Vascular Smooth Muscle Cell Inflammation and Proliferation via Induction of HO-1."
    Lee D.H., Choi H.C., Lee K.Y., Kang Y.J.
    Korean J Physiol Pharmacol 13:123-129(2009) [PubMed] [Europe PMC] [Abstract]
• negative regulation of vascular associated smooth muscle cell proliferation Source: RGDInferred from mutant phenotypeⁱ
  • "Naringenin inhibits TNF-alpha induced VSMC proliferation and migration via induction of HO-1."
    Chen S., Ding Y., Tao W., Zhang W., Liang T., Liu C.
    Food Chem Toxicol 50:3025-3031(2012) [PubMed] [Europe PMC] [Abstract]
• phospholipid metabolic process Source: RGD <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#tas">GO evidence code guide</a></p> Traceable author statementⁱ
  • "Heme oxygenase inhibitor restores arteriolar nitric oxide function in dahl rats."
    Johnson F.K., Durante W., Peyton K.J., Johnson R.A.
    Hypertension 41:149-155(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of angiogenesis Source: RGDInferred from mutant phenotypeⁱ
  • "Over-expression of HO-1 on mesenchymal stem cells promotes angiogenesis and improves myocardial function in infarcted myocardium."
    Zeng B., Lin G., Ren X., Zhang Y., Chen H.
    J Biomed Sci 17:80-80(2010) [PubMed] [Europe PMC] [Abstract]
• positive regulation of apoptotic process Source: RGD
• positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis Source: RGD
• positive regulation of cell migration involved in sprouting angiogenesis Source: RGD
• positive regulation of macroautophagy Source: RGD
• positive regulation of smooth muscle cell proliferation Source: RGD
• regulation of blood pressure Source: RGDInferred from direct assayⁱ
  • "Selective regulation of blood pressure by heme oxygenase-1 in hypertension."
    Ndisang J.F., Zhao W., Wang R.
    Hypertension 40:315-321(2002) [PubMed] [Europe PMC] [Abstract]
• regulation of DNA-binding transcription factor activity Source: BHF-UCLInferred from direct assayⁱ
  • "Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress."
    Lin Q., Weis S., Yang G., Weng Y.H., Helston R., Rish K., Smith A., Bordner J., Polte T., Gaunitz F., Dennery P.A.
    J Biol Chem 282:20621-20633(2007) [PubMed] [Europe PMC] [Abstract]
• regulation of transcription from RNA polymerase II promoter in response to iron Source: RGD
• regulation of transcription from RNA polymerase II promoter in response to oxidative stress Source: BHF-UCLInferred from direct assayⁱ
  • "Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress."
    Lin Q., Weis S., Yang G., Weng Y.H., Helston R., Rish K., Smith A., Bordner J., Polte T., Gaunitz F., Dennery P.A.
    J Biol Chem 282:20621-20633(2007) [PubMed] [Europe PMC] [Abstract]
• response to drug Source: RGDInferred from expression patternⁱ
  • "Protective effect of dioscin against thioacetamide-induced acute liver injury via FXR/AMPK signaling pathway in vivo."
    Zheng L., Yin L., Xu L., Qi Y., Li H., Xu Y., Han X., Liu K., Peng J.
    Biomed Pharmacother 97:481-488(2018) [PubMed] [Europe PMC] [Abstract]
• response to estrogen Source: RGDInferred from direct assayⁱ
  • "Mechanism of salutary effects of estradiol on organ function after trauma-hemorrhage: upregulation of heme oxygenase."
    Szalay L., Shimizu T., Schwacha M.G., Choudhry M.A., Rue L.W., Bland K.I., Chaudry I.H.
    Am J Physiol Heart Circ Physiol 289:H92-8(2005) [PubMed] [Europe PMC] [Abstract]
• response to hydrogen peroxide Source: BHF-UCLInferred from direct assayⁱ
  • "Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress."
    Lin Q., Weis S., Yang G., Weng Y.H., Helston R., Rish K., Smith A., Bordner J., Polte T., Gaunitz F., Dennery P.A.
    J Biol Chem 282:20621-20633(2007) [PubMed] [Europe PMC] [Abstract]
• response to hypoxia Source: RGDInferred from mutant phenotypeⁱ
  • "Regulation of heme oxygenase-1 by nitric oxide during hepatopulmonary syndrome."
    Carter E.P., Hartsfield C.L., Miyazono M., Jakkula M., Morris K.G. Jr., McMurtry I.F.
    Am J Physiol Lung Cell Mol Physiol 283:L346-53(2002) [PubMed] [Europe PMC] [Abstract]
• response to nicotine Source: RGD
• response to oxidative stress Source: RGDInferred from direct assayⁱ
  • "Resistance to nitric oxide-induced necrosis in heme oxygenase-1 overexpressing pulmonary epithelial cells associated with decreased lipid peroxidation."
    Reiter T.A., Pang B., Dedon P., Demple B.
    J Biol Chem 281:36603-36612(2006) [PubMed] [Europe PMC] [Abstract]
• small GTPase mediated signal transduction Source: RGDInferred from direct assayⁱ
  • "Heme oxygenase inhibitor restores arteriolar nitric oxide function in dahl rats."
    Johnson F.K., Durante W., Peyton K.J., Johnson R.A.
    Hypertension 41:149-155(2003) [PubMed] [Europe PMC] [Abstract]
• wound healing involved in inflammatory response Source: RGD

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

Chemistry databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductionⁱ

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

GO - Molecular functionⁱ

• enzyme binding Source: BHF-UCLInferred from physical interactionⁱ
  • "Involvement of NADPH in the interaction between heme oxygenase-1 and cytochrome P450 reductase."
    Higashimoto Y., Sakamoto H., Hayashi S., Sugishima M., Fukuyama K., Palmer G., Noguchi M.
    J Biol Chem 280:729-737(2005) [PubMed] [Europe PMC] [Abstract]
• identical protein binding Source: RGD
• protein homodimerization activity Source: RGD

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequenceⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

        10         20         30         40         50
MERPQLDSMS QDLSEALKEA TKEVHIRAEN SEFMRNFQKG QVSREGFKLV 
        60         70         80         90        100
MASLYHIYTA LEEEIERNKQ NPVYAPLYFP EELHRRAALE QDMAFWYGPH 
       110        120        130        140        150
WQEAIPYTPA TQHYVKRLHE VGGTHPELLV AHAYTRYLGD LSGGQVLKKI 
       160        170        180        190        200
AQKAMALPSS GEGLAFFTFP SIDNPTKFKQ LYRARMNTLE MTPEVKHRVT 
       210        220        230        240        250
EEAKTAFLLN IELFEELQAL LTEEHKDQSP SQTEFLRQRP ASLVQDTTSA 
       260        270        280 
ETPRGKSQIS TSSSQTPLLR WVLTLSFLLA TVAVGIYAM             

Sequence databases

Genome annotation databases

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. PDB cross-references
   Index of Protein Data Bank (PDB) cross-references
2. SIMILARITY comments
   Index of protein domains and families