HMOX1_RAT
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 03-AUG-2022, entry version 183.
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 [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:21764, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17245, ChEBI:CHEBI:29033,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:57991, ChEBI:CHEBI:58210,
CC 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 -!- 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 -!- 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}.
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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; P06762; -.
DR GeneID; 24451; -.
DR KEGG; rno:24451; -.
DR UCSC; RGD:2806; rat.
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 OMA; KKSHTMA; -.
DR OrthoDB; 1424194at2759; -.
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 tissues.
DR Genevisible; P06762; RN.
DR GO; GO:0005901; C:caveola; IDA:RGD.
DR GO; GO:0005829; C:cytosol; 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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005730; C:nucleolus; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; TAS: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:0006879; P:cellular iron ion homeostasis; ISO: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; IEA:Ensembl.
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: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:0055072; P:iron ion homeostasis; ISO:RGD.
DR GO; GO:0097421; P:liver regeneration; IMP:RGD.
DR GO; GO:0016236; P:macroautophagy; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:RGD.
DR GO; GO:0043392; P:negative regulation of DNA binding; IDA:RGD.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; 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:0043065; P:positive regulation of apoptotic process; ISO: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; IEA:Ensembl.
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:0051090; P:regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0034395; P:regulation of transcription from RNA polymerase II promoter in response to iron; ISO:RGD.
DR GO; GO:0043619; P:regulation of transcription from RNA polymerase II promoter in response to oxidative stress; IDA:BHF-UCL.
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; -; 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; PTHR10720; 1.
DR Pfam; PF01126; Heme_oxygenase; 1.
DR PIRSF; PIRSF000343; Haem_Oase; 1.
DR PRINTS; PR00088; HAEMOXYGNASE.
DR SUPFAM; SSF48613; SSF48613; 1.
DR PROSITE; PS00593; HEME_OXYGENASE; 1.
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
