ID HMOX1_MOUSE Reviewed; 289 AA. AC P14901; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1990, sequence version 1. DT 02-SEP-2026, entry version 197. DE RecName: Full=Heme oxygenase 1; DE Short=HO-1; DE EC=1.14.14.18 {ECO:0000250|UniProtKB:P09601}; DE AltName: Full=P32 protein; DE Contains: DE RecName: Full=Heme oxygenase 1 soluble form {ECO:0000250|UniProtKB:P09601}; GN Name=Hmox1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION. RC STRAIN=BALB/cJ; TISSUE=Fibroblast; RX PubMed=3409220; RA Kageyama H., Hiwasa T., Tokunaga K., Sakiyama S.; RT "Isolation and characterization of a complementary DNA clone for a Mr RT 32,000 protein which is induced with tumor promoters in BALB/c 3T3 cells."; RL Cancer Res. 48:4795-4798(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INDUCTION. RX PubMed=8288554; DOI=10.1016/s0021-9258(17)42211-3; RA Alam J., Cai J., Smith A.; RT "Isolation and characterization of the mouse heme oxygenase-1 gene. Distal RT 5' sequences are required for induction by heme or heavy metals."; RL J. Biol. Chem. 269:1001-1009(1994). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP INDUCTION BY M.TUBERCULOSIS. RX PubMed=18474359; DOI=10.1016/j.chom.2008.03.007; RA Shiloh M.U., Manzanillo P., Cox J.S.; RT "Mycobacterium tuberculosis senses host-derived carbon monoxide during RT macrophage infection."; RL Cell Host Microbe 3:323-330(2008). RN [5] RP INDUCTION IN MACROPHAGES AND LUNGS BY M.TUBERCULOSIS. RC STRAIN=C3Heb/FeJ, and C57BL/6 X FVB; TISSUE=Lung, and Macrophage; RX PubMed=18400743; DOI=10.1074/jbc.m802274200; RA Kumar A., Deshane J.S., Crossman D.K., Bolisetty S., Yan B.S., Kramnik I., RA Agarwal A., Steyn A.J.; RT "Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium RT tuberculosis dormancy regulon."; RL J. Biol. Chem. 283:18032-18039(2008). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver, Lung, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [7] RP INTERACTION WITH FLVCR2. RX PubMed=32973183; DOI=10.1038/s41467-020-18607-1; RA Li Y., Ivica N.A., Dong T., Papageorgiou D.P., He Y., Brown D.R., RA Kleyman M., Hu G., Chen W.W., Sullivan L.B., Del Rosario A., Hammond P.T., RA Vander Heiden M.G., Chen J.; RT "MFSD7C switches mitochondrial ATP synthesis to thermogenesis in response RT to heme."; RL Nat. Commun. 11:4837-4837(2020). CC -!- FUNCTION: [Heme oxygenase 1]: Catalyzes the oxidative cleavage of heme CC at the alpha-methene bridge carbon, released as carbon monoxide (CO), CC to generate biliverdin IXalpha, while releasing the central heme iron CC chelate as ferrous iron (By similarity) Affords protection against CC programmed cell death and this cytoprotective effect relies on its CC ability to catabolize free heme and prevent it from sensitizing cells CC to undergo apoptosis (By similarity). {ECO:0000250|UniProtKB:P09601}. CC -!- FUNCTION: [Heme oxygenase 1 soluble form]: Catalyzes the oxidative CC cleavage of heme at the alpha-methene bridge carbon, released as carbon CC monoxide (CO), to generate biliverdin IXalpha, while releasing the CC central heme iron chelate as ferrous iron. CC {ECO:0000250|UniProtKB:P09601}. CC -!- CATALYTIC ACTIVITY: CC Reaction=heme b + 3 reduced [NADPH--hemoprotein reductase] + 3 O2 = CC biliverdin IXalpha + CO + Fe(2+) + 3 oxidized [NADPH--hemoprotein CC reductase] + 3 H2O + H(+); Xref=Rhea:RHEA:21764, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17245, CC ChEBI:CHEBI:29033, ChEBI:CHEBI:57618, ChEBI:CHEBI:57991, CC ChEBI:CHEBI:58210, ChEBI:CHEBI:60344; EC=1.14.14.18; CC Evidence={ECO:0000250|UniProtKB:P09601}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21765; CC Evidence={ECO:0000250|UniProtKB:P09601}; CC -!- SUBUNIT: Homodimer and higher order homooligomer. Oligomerization is CC crucial for its stability and function in the endoplasmic reticulum (By CC similarity). Interacts with FLVCR2; this interaction is potentiated in CC the presence of heme. {ECO:0000250|UniProtKB:P09601, CC ECO:0000269|PubMed:32973183}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:P09601}; Single-pass type IV membrane protein CC {ECO:0000255}; Cytoplasmic side {ECO:0000250|UniProtKB:P09601}. CC -!- INDUCTION: Induced by its substrate heme, CdCl2, sodium arsenite and CC 12-O-tetradecanoyl-phorbol-13-acetate (PubMed:3409220, PubMed:8288554). CC It is also induced in macrophages, liver and the lungs upon infection CC with M.tuberculosis (at protein level). Data is conflicting as to CC whether macrophage induction is independent of the nitric oxide (NO) CC signaling pathway (PubMed:18400743), or dependent on NO CC (PubMed:18474359). {ECO:0000269|PubMed:18400743, CC ECO:0000269|PubMed:18474359, ECO:0000269|PubMed:3409220, CC ECO:0000269|PubMed:8288554}. CC -!- DOMAIN: The transmembrane domain is necessary for its oligomerization. CC {ECO:0000250|UniProtKB:P09601}. CC -!- PTM: A soluble form arises by proteolytic removal of the membrane CC anchor. {ECO:0000250|UniProtKB:P09601}. CC -!- SIMILARITY: Belongs to the heme oxygenase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M33203; AAA39872.1; -; mRNA. DR EMBL; X13356; CAA31732.1; -; mRNA. DR EMBL; X56824; CAA40159.1; -; Genomic_DNA. DR EMBL; X56825; CAA40159.1; JOINED; Genomic_DNA. DR EMBL; X56826; CAA40159.1; JOINED; Genomic_DNA. DR EMBL; X56827; CAA40159.1; JOINED; Genomic_DNA. DR EMBL; BC010757; AAH10757.1; -; mRNA. DR CCDS; CCDS22423.1; -. DR PIR; I48409; I48409. DR RefSeq; NP_034572.1; NM_010442.2. DR AlphaFoldDB; P14901; -. DR SMR; P14901; -. DR BioGRID; 200344; 6. DR FunCoup; P14901; 442. DR IntAct; P14901; 3. DR MINT; P14901; -. DR STRING; 10090.ENSMUSP00000005548; -. DR ChEMBL; CHEMBL4434; -. DR GlyGen; P14901; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P14901; -. DR PhosphoSitePlus; P14901; -. DR SwissPalm; P14901; -. DR jPOST; P14901; -. DR PaxDb; 10090-ENSMUSP00000005548; -. DR PeptideAtlas; P14901; -. DR ProteomicsDB; 269605; -. DR Pumba; P14901; -. DR Antibodypedia; 266; 1139 antibodies from 48 providers. DR DNASU; 15368; -. DR Ensembl; ENSMUST00000005548.8; ENSMUSP00000005548.7; ENSMUSG00000005413.9. DR GeneID; 15368; -. DR KEGG; mmu:15368; -. DR UCSC; uc009mhc.2; mouse. DR AGR; MGI:96163; -. DR CTD; 3162; -. DR MGI; MGI:96163; Hmox1. DR VEuPathDB; HostDB:ENSMUSG00000005413; -. DR eggNOG; KOG4480; Eukaryota. DR GeneTree; ENSGT00390000017673; -. DR HOGENOM; CLU_057050_0_1_1; -. DR InParanoid; P14901; -. DR OMA; TEQLWFV; -. DR OrthoDB; 652091at2759; -. DR PhylomeDB; P14901; -. DR BRENDA; 1.14.14.18; 3474. DR Reactome; R-MMU-189483; Heme degradation. DR Reactome; R-MMU-917937; Iron uptake and transport. DR Reactome; R-MMU-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane. DR Reactome; R-MMU-9707564; Cytoprotection by HMOX1. DR Reactome; R-MMU-9707587; Regulation of HMOX1 expression and activity. DR BioGRID-ORCS; 15368; 6 hits in 80 CRISPR screens. DR PRO; PR:P14901; -. DR Proteomes; UP000000589; Chromosome 8. DR RNAct; P14901; protein. DR Bgee; ENSMUSG00000005413; Expressed in ectoplacental cone and 211 other cell types or tissues. DR ExpressionAtlas; P14901; baseline and differential. DR GO; GO:0005901; C:caveola; ISO:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:MGI. DR GO; GO:0005783; C:endoplasmic reticulum; ISO:GO_Central. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:GO_Central. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0052869; F:arachidonate omega-hydroxylase activity; ISO:GO_Central. DR GO; GO:0004630; F:D-type glycerophospholipase activity; ISO:GO_Central. DR GO; GO:0019899; F:enzyme binding; ISO:GO_Central. DR GO; GO:0020037; F:heme binding; ISO:GO_Central. DR GO; GO:0004392; F:heme oxygenase (decyclizing) activity; IDA:MGI. DR GO; GO:0042802; F:identical protein binding; ISO:GO_Central. DR GO; GO:0042803; F:protein homodimerization activity; ISO:GO_Central. DR GO; GO:0005198; F:structural molecule activity; ISO:GO_Central. DR GO; GO:0001525; P:angiogenesis; ISO:GO_Central. DR GO; GO:0071243; P:cellular response to arsenic-containing substance; IDA:MGI. DR GO; GO:0071276; P:cellular response to cadmium ion; IDA:MGI. DR GO; GO:0072719; P:cellular response to cisplatin; IMP:MGI. DR GO; GO:0034605; P:cellular response to heat; ISO:GO_Central. DR GO; GO:0034101; P:erythrocyte homeostasis; ISO:GO_Central. DR GO; GO:0042167; P:heme catabolic process; IMP:MGI. DR GO; GO:0042168; P:heme metabolic process; IDA:MGI. DR GO; GO:0006788; P:heme oxidation; ISO:GO_Central. DR GO; GO:0006879; P:intracellular iron ion homeostasis; ISO:GO_Central. DR GO; GO:0035556; P:intracellular signal transduction; ISO:GO_Central. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISO:GO_Central. DR GO; GO:0097421; P:liver regeneration; ISO:GO_Central. DR GO; GO:0060586; P:multicellular organismal-level iron ion homeostasis; ISO:GO_Central. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:GO_Central. DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; IDA:UniProt. DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; ISO:GO_Central. DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:GO_Central. DR GO; GO:0110076; P:negative regulation of ferroptosis; ISS:UniProtKB. DR GO; GO:0016242; P:negative regulation of macroautophagy; IMP:MGI. DR GO; GO:0032764; P:negative regulation of mast cell cytokine production; ISO:GO_Central. DR GO; GO:0043305; P:negative regulation of mast cell degranulation; ISO:GO_Central. DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; ISO:GO_Central. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:GO_Central. DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:GO_Central. DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; ISO:GO_Central. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:GO_Central. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:MGI. DR GO; GO:1903589; P:positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; ISO:GO_Central. DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; ISO:GO_Central. DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:MGI. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:GO_Central. DR GO; GO:0008217; P:regulation of blood pressure; ISO:GO_Central. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:GO_Central. DR GO; GO:1904550; P:response to arachidonate; ISO:GO_Central. DR GO; GO:0043627; P:response to estrogen; ISO:GO_Central. DR GO; GO:0042542; P:response to hydrogen peroxide; ISO:GO_Central. DR GO; GO:0001666; P:response to hypoxia; ISO:GO_Central. DR GO; GO:0035094; P:response to nicotine; ISO:GO_Central. DR GO; GO:0006979; P:response to oxidative stress; ISO:GO_Central. DR GO; GO:0007264; P:small GTPase-mediated signal transduction; ISO:GO_Central. DR GO; GO:0002246; P:wound healing involved in inflammatory response; ISO:GO_Central. DR CDD; cd19165; HemeO; 1. DR FunFam; 1.20.910.10:FF:000001; Heme oxygenase 1; 1. DR Gene3D; 1.20.910.10; Heme oxygenase-like; 1. DR InterPro; IPR002051; Haem_Oase. DR InterPro; IPR016053; Haem_Oase-like. DR InterPro; IPR016084; Haem_Oase-like_multi-hlx. DR InterPro; IPR018207; Haem_oxygenase_CS. DR PANTHER; PTHR10720; HEME OXYGENASE; 1. DR PANTHER; PTHR10720:SF1; HEME OXYGENASE 1; 1. DR Pfam; PF01126; Heme_oxygenase; 1. DR PIRSF; PIRSF000343; Haem_Oase; 1. DR PRINTS; PR00088; HAEMOXYGNASE. DR SUPFAM; SSF48613; Heme oxygenase-like; 1. DR PROSITE; PS00593; HEME_OXYGENASE; 1. PE 1: Evidence at protein level; KW Apoptosis; Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding; KW Oxidoreductase; Phosphoprotein; Reference proteome; Transmembrane; KW Transmembrane helix. FT CHAIN 1..289 FT /note="Heme oxygenase 1" FT /id="PRO_0000209688" FT CHAIN 1..266 FT /note="Heme oxygenase 1 soluble form" FT /evidence="ECO:0000250|UniProtKB:P09601" FT /id="PRO_0000455622" FT TOPO_DOM 1..266 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P09601" FT TRANSMEM 267..289 FT /note="Helical; Anchor for type IV membrane protein" FT /evidence="ECO:0000255" FT REGION 224..262 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 18 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /evidence="ECO:0000250|UniProtKB:P09601" FT BINDING 25 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /ligand_part="Fe" FT /ligand_part_id="ChEBI:CHEBI:18248" FT /note="axial binding residue" FT /evidence="ECO:0000250|UniProtKB:P09601" FT BINDING 134 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /evidence="ECO:0000250|UniProtKB:P09601" FT BINDING 183 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /evidence="ECO:0000250|UniProtKB:P09601" FT SITE 140 FT /note="Important for catalytic activity" FT /evidence="ECO:0000250|UniProtKB:P09601" FT MOD_RES 229 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09601" FT MOD_RES 242 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P06762" SQ SEQUENCE 289 AA; 32929 MW; 19DB0DCCD574044B CRC64; MERPQPDSMP QDLSEALKEA TKEVHIQAEN AEFMKNFQKG QVSREGFKLV MASLYHIYTA LEEEIERNKQ NPVYAPLYFP EELHRRAALE QDMAFWYGPH WQEIIPCTPA TQHYVKRLHE VGRTHPELLV AHAYTRYLGD LSGGQVLKKI AQKAMALPSS GEGLAFFTFP NIDSPTKFKQ LYRARMNTLE MTPEVKHRVT EEAKTAFLLN IELFEELQVM LTEEHKDQSP SQMASLRQRP ASLVQDTAPA ETPRGKPQIS TSSSQTPLLQ WVLTLSFLLA TVAVGIYAM //