ID HMOX1_RAT Reviewed; 289 AA. AC P06762; Q5BK87; DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1988, sequence version 1. DT 27-MAR-2024, entry version 192. DE RecName: Full=Heme oxygenase 1; DE Short=HO-1; DE EC=1.14.14.18 {ECO:0000269|PubMed:1575508, ECO:0000269|PubMed:1935972, ECO:0000269|PubMed:3865203}; DE AltName: Full=HSP32; DE Contains: DE RecName: Full=Heme oxygenase 1 soluble form {ECO:0000303|PubMed:1935972}; GN Name=Hmox1; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3032976; DOI=10.1016/s0021-9258(18)48315-9; RA Mueller R.M., Taguchi H., Shibahara S.; RT "Nucleotide sequence and organization of the rat heme oxygenase gene."; RL J. Biol. Chem. 262:6795-6802(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, RP SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=3865203; DOI=10.1073/pnas.82.23.7865; RA Shibahara S., Mueller R., Taguchi H., Yoshida T.; RT "Cloning and expression of cDNA for rat heme oxygenase."; RL Proc. Natl. Acad. Sci. U.S.A. 82:7865-7869(1985). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Thymus; 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 FUNCTION, CATALYTIC ACTIVITY, AND PROTEOLYTIC CLEAVAGE. RX PubMed=1935972; DOI=10.1111/j.1432-1033.1991.tb16357.x; RA Ishikawa K., Sato M., Yoshida T.; RT "Expression of rat heme oxygenase in Escherichia coli as a catalytically RT active, full-length form that binds to bacterial membranes."; RL Eur. J. Biochem. 202:161-165(1991). RN [5] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=1575508; DOI=10.1016/0003-9861(92)90481-b; RA McCoubrey W.K. Jr., Ewing J.F., Maines M.D.; RT "Human heme oxygenase-2: characterization and expression of a full-length RT cDNA and evidence suggesting that the two HO-2 transcripts may differ by RT choice of polyadenylation signal."; RL Arch. Biochem. Biophys. 295:13-20(1992). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-242, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-267. RX PubMed=10760513; DOI=10.1016/s0014-5793(00)01353-3; RA Sugishima M., Omata Y., Kakuta Y., Sakamoto H., Noguchi M., Fukuyama K.; RT "Crystal structure of rat heme oxygenase-1 in complex with heme."; RL FEBS Lett. 471:61-66(2000). 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 (PubMed:3865203, PubMed:1935972, CC PubMed:1575508). Affords protection against programmed cell death and CC this cytoprotective effect relies on its ability to catabolize free CC heme and prevent it from sensitizing cells to undergo apoptosis (By CC similarity). {ECO:0000250|UniProtKB:P09601, ECO:0000269|PubMed:1575508, CC ECO:0000269|PubMed:1935972, ECO:0000269|PubMed:3865203}. 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:0000269|PubMed:1935972}. CC -!- CATALYTIC ACTIVITY: CC Reaction=heme b + 3 O2 + 3 reduced [NADPH--hemoprotein reductase] = CC biliverdin IXalpha + CO + Fe(2+) + H(+) + 3 H2O + 3 oxidized CC [NADPH--hemoprotein reductase]; 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:0000269|PubMed:1575508, ECO:0000269|PubMed:1935972, CC ECO:0000269|PubMed:3865203}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21765; CC Evidence={ECO:0000305|PubMed:1935972}; CC -!- ACTIVITY REGULATION: Inhibited by metalloporphyrins such as Sn- and Zn- CC protoporphyrins. {ECO:0000269|PubMed:1575508}. CC -!- SUBUNIT: Homodimer and higher order homooligomer. Oligomerization is CC crucial for its stability and function in the endoplasmic reticulum. CC Interacts with FLVCR2; this interaction is potentiated in the presence CC of heme. {ECO:0000250|UniProtKB:P14901}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000305|PubMed:3865203}; Single-pass type IV membrane protein CC {ECO:0000255}; Cytoplasmic side {ECO:0000250|UniProtKB:P09601}. CC -!- INDUCTION: Induced by its substrate heme and CoCl2. CC {ECO:0000269|PubMed:3865203}. 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:0000305|PubMed:1935972}. 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; J02722; AAA41346.1; -; Genomic_DNA. DR EMBL; BC091164; AAH91164.1; -; mRNA. DR PIR; A92645; OHRTD. DR RefSeq; NP_036712.1; NM_012580.2. DR PDB; 1DVE; X-ray; 2.40 A; A=1-267. DR PDB; 1DVG; X-ray; 2.20 A; A/B=1-267. DR PDB; 1IRM; X-ray; 2.55 A; A/B/C=1-267. DR PDB; 1IVJ; X-ray; 1.90 A; A=1-267. DR PDB; 1IX3; X-ray; 2.00 A; A=1-267. DR PDB; 1IX4; X-ray; 1.80 A; A=1-267. DR PDB; 1J02; X-ray; 1.70 A; A=1-267. DR PDB; 1J2C; X-ray; 2.40 A; A=1-267. DR PDB; 1UBB; X-ray; 2.30 A; A=1-267. DR PDB; 1ULX; X-ray; 2.00 A; A=1-267. DR PDB; 1VGI; X-ray; 1.90 A; A=1-267. DR PDB; 2DY5; X-ray; 2.70 A; A=1-267. DR PDB; 2E7E; X-ray; 1.85 A; A=1-267. DR PDB; 2ZVU; X-ray; 2.20 A; A=1-267. DR PDB; 3I9T; X-ray; 2.15 A; A=1-261. DR PDB; 3I9U; X-ray; 2.25 A; A=1-261. DR PDB; 3WKT; X-ray; 4.30 A; C/D=1-267. DR PDB; 4G7L; X-ray; 1.80 A; A=1-267. DR PDB; 4G7P; X-ray; 1.90 A; A=1-267. DR PDB; 4G7T; X-ray; 1.90 A; A=1-267. DR PDB; 4G7U; X-ray; 1.90 A; A=1-267. DR PDB; 4G8P; X-ray; 1.90 A; A=1-267. DR PDB; 4G8U; X-ray; 2.10 A; A=1-267. DR PDB; 4G8W; X-ray; 2.40 A; A=1-267. DR PDB; 4G98; X-ray; 2.30 A; A=1-267. DR PDB; 4G99; X-ray; 2.30 A; A=1-267. DR PDB; 4MEC; X-ray; 3.20 A; A/B/C/D/E/F/G=1-232. DR PDB; 6J79; X-ray; 3.33 A; A/B=1-233. DR PDB; 6J7A; X-ray; 3.27 A; A/B=1-238. DR PDB; 6J7I; X-ray; 3.30 A; A/B=1-235. DR PDBsum; 1DVE; -. DR PDBsum; 1DVG; -. DR PDBsum; 1IRM; -. DR PDBsum; 1IVJ; -. DR PDBsum; 1IX3; -. DR PDBsum; 1IX4; -. DR PDBsum; 1J02; -. DR PDBsum; 1J2C; -. DR PDBsum; 1UBB; -. DR PDBsum; 1ULX; -. DR PDBsum; 1VGI; -. DR PDBsum; 2DY5; -. DR PDBsum; 2E7E; -. DR PDBsum; 2ZVU; -. DR PDBsum; 3I9T; -. DR PDBsum; 3I9U; -. DR PDBsum; 3WKT; -. DR PDBsum; 4G7L; -. DR PDBsum; 4G7P; -. DR PDBsum; 4G7T; -. DR PDBsum; 4G7U; -. DR PDBsum; 4G8P; -. DR PDBsum; 4G8U; -. DR PDBsum; 4G8W; -. DR PDBsum; 4G98; -. DR PDBsum; 4G99; -. DR PDBsum; 4MEC; -. DR PDBsum; 6J79; -. DR PDBsum; 6J7A; -. DR PDBsum; 6J7I; -. DR AlphaFoldDB; P06762; -. DR BMRB; P06762; -. DR SMR; P06762; -. DR BioGRID; 246615; 1. DR MINT; P06762; -. DR STRING; 10116.ENSRNOP00000019192; -. DR BindingDB; P06762; -. DR ChEMBL; CHEMBL5035; -. DR GuidetoPHARMACOLOGY; 1441; -. DR iPTMnet; P06762; -. DR PhosphoSitePlus; P06762; -. DR jPOST; P06762; -. DR PaxDb; 10116-ENSRNOP00000019192; -. DR Ensembl; ENSRNOT00055037437; ENSRNOP00055030521; ENSRNOG00055021832. DR Ensembl; ENSRNOT00060027191; ENSRNOP00060021805; ENSRNOG00060015875. DR Ensembl; ENSRNOT00065005841; ENSRNOP00065004199; ENSRNOG00065004008. DR GeneID; 24451; -. DR KEGG; rno:24451; -. DR UCSC; RGD:2806; rat. DR AGR; RGD:2806; -. DR CTD; 3162; -. DR RGD; 2806; Hmox1. DR VEuPathDB; HostDB:ENSRNOG00000014117; -. DR eggNOG; KOG4480; Eukaryota. DR HOGENOM; CLU_057050_0_1_1; -. DR InParanoid; P06762; -. DR OrthoDB; 1366343at2759; -. DR PhylomeDB; P06762; -. DR TreeFam; TF314786; -. DR BRENDA; 1.14.14.18; 5301. DR BRENDA; 1.3.1.24; 5301. DR Reactome; R-RNO-189483; Heme degradation. DR Reactome; R-RNO-917937; Iron uptake and transport. DR Reactome; R-RNO-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane. DR Reactome; R-RNO-9707564; Cytoprotection by HMOX1. DR Reactome; R-RNO-9707587; Regulation of HMOX1 expression and activity. DR SABIO-RK; P06762; -. DR EvolutionaryTrace; P06762; -. DR PRO; PR:P06762; -. DR Proteomes; UP000002494; Chromosome 19. DR Bgee; ENSRNOG00000014117; Expressed in spleen and 18 other cell types or tissues. DR GO; GO:0005901; C:caveola; IDA:RGD. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL. 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:RGD. DR GO; GO:0052869; F:arachidonic acid omega-hydroxylase activity; IMP:RGD. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0020037; F:heme binding; IDA:RGD. DR GO; GO:0004392; F:heme oxygenase (decyclizing) activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISO:RGD. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004630; F:phospholipase D activity; IDA:RGD. DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD. DR GO; GO:0005198; F:structural molecule activity; ISO:RGD. DR GO; GO:0001525; P:angiogenesis; IDA:RGD. DR GO; GO:0071243; P:cellular response to arsenic-containing substance; ISO:RGD. DR GO; GO:0071276; P:cellular response to cadmium ion; ISO:RGD. DR GO; GO:0072719; P:cellular response to cisplatin; ISO:RGD. DR GO; GO:0034605; P:cellular response to heat; ISO:RGD. DR GO; GO:0071456; P:cellular response to hypoxia; ISO:RGD. DR GO; GO:0031670; P:cellular response to nutrient; IEP:RGD. DR GO; GO:1904019; P:epithelial cell apoptotic process; ISO:RGD. DR GO; GO:0034101; P:erythrocyte homeostasis; ISO:RGD. DR GO; GO:0042167; P:heme catabolic process; IDA:RGD. DR GO; GO:0042168; P:heme metabolic process; ISO:RGD. DR GO; GO:0006788; P:heme oxidation; ISO:RGD. DR GO; GO:0006879; P:intracellular iron ion homeostasis; ISO:RGD. DR GO; GO:0035556; P:intracellular signal transduction; IDA:RGD. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:RGD. DR GO; GO:0097421; P:liver regeneration; IMP:RGD. DR GO; GO:0016236; P:macroautophagy; ISO:RGD. DR GO; GO:0060586; P:multicellular organismal-level iron ion homeostasis; ISO:RGD. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:RGD. DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IMP:RGD. DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:RGD. DR GO; GO:0016242; P:negative regulation of macroautophagy; ISO:RGD. DR GO; GO:0032764; P:negative regulation of mast cell cytokine production; IDA:RGD. DR GO; GO:0043305; P:negative regulation of mast cell degranulation; IDA:RGD. DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; IDA:RGD. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:RGD. DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IMP:RGD. DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IMP:RGD. DR GO; GO:0006644; P:phospholipid metabolic process; TAS:RGD. DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:RGD. DR GO; GO:1903589; P:positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; ISO:RGD. DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; ISO:RGD. DR GO; GO:1904037; P:positive regulation of epithelial cell apoptotic process; ISO:RGD. DR GO; GO:0016239; P:positive regulation of macroautophagy; ISO:RGD. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:RGD. DR GO; GO:0008217; P:regulation of blood pressure; IDA:RGD. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:1904681; P:response to 3-methylcholanthrene; IEP:RGD. DR GO; GO:1904550; P:response to arachidonic acid; IMP:RGD. DR GO; GO:0043627; P:response to estrogen; IDA:RGD. DR GO; GO:0042542; P:response to hydrogen peroxide; IDA:BHF-UCL. DR GO; GO:0001666; P:response to hypoxia; IMP:RGD. DR GO; GO:0035094; P:response to nicotine; ISO:RGD. DR GO; GO:0006979; P:response to oxidative stress; IDA:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD. DR GO; GO:0007264; P:small GTPase mediated signal transduction; IDA:RGD. DR GO; GO:0002246; P:wound healing involved in inflammatory response; ISO:RGD. DR CDD; cd19165; HemeO; 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. DR Genevisible; P06762; RN. PE 1: Evidence at protein level; KW 3D-structure; Apoptosis; Endoplasmic reticulum; Heme; Iron; Membrane; KW Metal-binding; Oxidoreductase; Phosphoprotein; Reference proteome; KW Transmembrane; Transmembrane helix. FT CHAIN 1..289 FT /note="Heme oxygenase 1" FT /id="PRO_0000209690" FT CHAIN 1..266 FT /note="Heme oxygenase 1 soluble form" FT /evidence="ECO:0000305|PubMed:1935972" FT /id="PRO_0000455625" 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 225..261 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 233..261 FT /note="Polar residues" 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:0007744|PubMed:22673903" FT HELIX 13..29 FT /evidence="ECO:0007829|PDB:1J02" FT HELIX 32..39 FT /evidence="ECO:0007829|PDB:1J02" FT HELIX 44..67 FT /evidence="ECO:0007829|PDB:1J02" FT TURN 68..70 FT /evidence="ECO:0007829|PDB:1J02" FT TURN 72..74 FT /evidence="ECO:0007829|PDB:1J02" FT HELIX 75..77 FT /evidence="ECO:0007829|PDB:1J02" FT HELIX 80..83 FT /evidence="ECO:0007829|PDB:1J02" FT HELIX 86..97 FT /evidence="ECO:0007829|PDB:1J02" FT HELIX 101..103 FT /evidence="ECO:0007829|PDB:1J02" FT HELIX 109..124 FT /evidence="ECO:0007829|PDB:1J02" FT HELIX 126..128 FT /evidence="ECO:0007829|PDB:1J02" FT HELIX 129..140 FT /evidence="ECO:0007829|PDB:1J02" FT HELIX 143..155 FT /evidence="ECO:0007829|PDB:1J02" FT HELIX 165..167 FT /evidence="ECO:0007829|PDB:1J02" FT HELIX 175..186 FT /evidence="ECO:0007829|PDB:1J02" FT HELIX 193..221 FT /evidence="ECO:0007829|PDB:1J02" SQ SEQUENCE 289 AA; 33006 MW; EF7D2B98048AF44D CRC64; MERPQLDSMS QDLSEALKEA TKEVHIRAEN SEFMRNFQKG QVSREGFKLV MASLYHIYTA LEEEIERNKQ NPVYAPLYFP EELHRRAALE QDMAFWYGPH WQEAIPYTPA TQHYVKRLHE VGGTHPELLV AHAYTRYLGD LSGGQVLKKI AQKAMALPSS GEGLAFFTFP SIDNPTKFKQ LYRARMNTLE MTPEVKHRVT EEAKTAFLLN IELFEELQAL LTEEHKDQSP SQTEFLRQRP ASLVQDTTSA ETPRGKSQIS TSSSQTPLLR WVLTLSFLLA TVAVGIYAM //