HMOX1_MOUSE
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 03-AUG-2022, entry version 178.
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).
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 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:0000250|UniProtKB:P09601};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21765;
CC Evidence={ECO:0000250|UniProtKB:P09601};
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 -!- 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}.
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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; 4.
DR IntAct; P14901; 3.
DR MINT; P14901; -.
DR STRING; 10090.ENSMUSP00000005548; -.
DR ChEMBL; CHEMBL4434; -.
DR iPTMnet; P14901; -.
DR PhosphoSitePlus; P14901; -.
DR SwissPalm; P14901; -.
DR EPD; P14901; -.
DR jPOST; P14901; -.
DR PaxDb; P14901; -.
DR PeptideAtlas; P14901; -.
DR PRIDE; P14901; -.
DR ProteomicsDB; 269605; -.
DR Antibodypedia; 266; 1132 antibodies from 45 providers.
DR DNASU; 15368; -.
DR Ensembl; ENSMUST00000005548; ENSMUSP00000005548; ENSMUSG00000005413.
DR GeneID; 15368; -.
DR KEGG; mmu:15368; -.
DR UCSC; uc009mhc.2; mouse.
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; KKSHTMA; -.
DR OrthoDB; 1424194at2759; -.
DR PhylomeDB; P14901; -.
DR TreeFam; TF314786; -.
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 75 CRISPR screens.
DR ChiTaRS; Hmox1; mouse.
DR PRO; PR:P14901; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P14901; protein.
DR Bgee; ENSMUSG00000005413; Expressed in ectoplacental cone and 207 other tissues.
DR ExpressionAtlas; P14901; baseline and differential.
DR Genevisible; P14901; MM.
DR GO; GO:0005901; C:caveola; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0020037; F:heme binding; ISO:MGI.
DR GO; GO:0004392; F:heme oxygenase (decyclizing) activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004630; F:phospholipase D activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0005198; F:structural molecule activity; ISO:MGI.
DR GO; GO:0001525; P:angiogenesis; ISO:MGI.
DR GO; GO:0008219; P:cell death; ISO:MGI.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISO:MGI.
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:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0031670; P:cellular response to nutrient; IEA:Ensembl.
DR GO; GO:1904019; P:epithelial cell apoptotic process; IMP:MGI.
DR GO; GO:0034101; P:erythrocyte homeostasis; ISO:MGI.
DR GO; GO:0042167; P:heme catabolic process; ISO:MGI.
DR GO; GO:0042168; P:heme metabolic process; IDA:MGI.
DR GO; GO:0006788; P:heme oxidation; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISO:MGI.
DR GO; GO:0055072; P:iron ion homeostasis; ISO:MGI.
DR GO; GO:0097421; P:liver regeneration; ISO:MGI.
DR GO; GO:0016236; P:macroautophagy; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0043392; P:negative regulation of DNA binding; ISO:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; ISO:MGI.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:MGI.
DR GO; GO:0016242; P:negative regulation of macroautophagy; IMP:MGI.
DR GO; GO:0032764; P:negative regulation of mast cell cytokine production; ISO:MGI.
DR GO; GO:0043305; P:negative regulation of mast cell degranulation; ISO:MGI.
DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI.
DR GO; GO:1903589; P:positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; ISO:MGI.
DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; ISO:MGI.
DR GO; GO:1904037; P:positive regulation of epithelial cell apoptotic process; IMP:MGI.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0008217; P:regulation of blood pressure; ISO:MGI.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0034395; P:regulation of transcription from RNA polymerase II promoter in response to iron; IDA:MGI.
DR GO; GO:0043619; P:regulation of transcription from RNA polymerase II promoter in response to oxidative stress; ISO:MGI.
DR GO; GO:0043627; P:response to estrogen; ISO:MGI.
DR GO; GO:0042542; P:response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR GO; GO:0035094; P:response to nicotine; ISO:MGI.
DR GO; GO:0006979; P:response to oxidative stress; ISO:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; ISO:MGI.
DR GO; GO:0002246; P:wound healing involved in inflammatory response; ISO:MGI.
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 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 COMPBIAS 224..242
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: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
