ID   HMOX1_BOVIN             Reviewed;         289 AA.
AC   Q5E9F2; Q3ZCK7; Q7M338;
DT   30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2005, sequence version 1.
DT   27-MAR-2024, entry version 119.
DE   RecName: Full=Heme oxygenase 1;
DE            Short=HO-1;
DE            EC=1.14.14.18 {ECO:0000269|PubMed:6806282};
DE   Contains:
DE     RecName: Full=Heme oxygenase 1 soluble form {ECO:0000250|UniProtKB:P09601};
GN   Name=HMOX1;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA   Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA   Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT   "Characterization of 954 bovine full-CDS cDNA sequences.";
RL   BMC Genomics 6:166-166(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   PROTEIN SEQUENCE OF 24-33; 41-49; 88-113; 138-147; 155-158; 187-196 AND
RP   200-205.
RC   TISSUE=Spleen;
RX   PubMed=1700666; DOI=10.1016/0003-9861(90)90136-m;
RA   Schacter B.A., Cripps V., Troxler R.F., Offner G.D.;
RT   "Structural studies on bovine spleen heme oxygenase. Immunological and
RT   structural diversity among mammalian heme oxygenase enzymes.";
RL   Arch. Biochem. Biophys. 282:404-412(1990).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP   REGULATION.
RX   PubMed=6806282; DOI=10.1016/s0021-9258(18)34449-1;
RA   Yoshinaga T., Sassa S., Kappas A.;
RT   "Purification and properties of bovine spleen heme oxygenase. Amino acid
RT   composition and sites of action of inhibitors of heme oxidation.";
RL   J. Biol. Chem. 257:7778-7785(1982).
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:6806282). 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       ECO:0000269|PubMed:6806282}.
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
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:6806282};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21765;
CC         Evidence={ECO:0000305|PubMed:6806282};
CC   -!- ACTIVITY REGULATION: Inhibited by metalloporphyrins such as Sn-, Co-,
CC       Mn- and Zn-protoporphyrins. {ECO:0000269|PubMed:6806282}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.93 uM for heme b {ECO:0000269|PubMed:6806282};
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:0000250|UniProtKB:P09601}; Single-pass type IV membrane protein
CC       {ECO:0000255}; Cytoplasmic side {ECO:0000250|UniProtKB:P09601}.
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}.
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DR   EMBL; BT020968; AAX08985.1; -; mRNA.
DR   EMBL; BC102105; AAI02106.4; -; mRNA.
DR   PIR; S13265; S13265.
DR   RefSeq; NP_001014912.1; NM_001014912.1.
DR   AlphaFoldDB; Q5E9F2; -.
DR   SMR; Q5E9F2; -.
DR   STRING; 9913.ENSBTAP00000061215; -.
DR   ChEMBL; CHEMBL1255146; -.
DR   PaxDb; 9913-ENSBTAP00000020701; -.
DR   Ensembl; ENSBTAT00000020701.6; ENSBTAP00000020701.5; ENSBTAG00000015582.6.
DR   GeneID; 513221; -.
DR   KEGG; bta:513221; -.
DR   CTD; 3162; -.
DR   VEuPathDB; HostDB:ENSBTAG00000015582; -.
DR   VGNC; VGNC:29885; HMOX1.
DR   eggNOG; KOG4480; Eukaryota.
DR   GeneTree; ENSGT00390000017673; -.
DR   HOGENOM; CLU_057050_0_1_1; -.
DR   InParanoid; Q5E9F2; -.
DR   OrthoDB; 1366343at2759; -.
DR   TreeFam; TF314786; -.
DR   BRENDA; 1.14.14.18; 908.
DR   Reactome; R-BTA-189483; Heme degradation.
DR   Reactome; R-BTA-917937; Iron uptake and transport.
DR   Reactome; R-BTA-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR   Reactome; R-BTA-9707564; Cytoprotection by HMOX1.
DR   Reactome; R-BTA-9707587; Regulation of HMOX1 expression and activity.
DR   SABIO-RK; Q5E9F2; -.
DR   Proteomes; UP000009136; Chromosome 5.
DR   ExpressionAtlas; Q5E9F2; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR   GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR   GO; GO:0004392; F:heme oxygenase (decyclizing) activity; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR   GO; GO:0005198; F:structural molecule activity; IEA:Ensembl.
DR   GO; GO:0071243; P:cellular response to arsenic-containing substance; IEA:Ensembl.
DR   GO; GO:0071276; P:cellular response to cadmium ion; IEA:Ensembl.
DR   GO; GO:0072719; P:cellular response to cisplatin; IEA:Ensembl.
DR   GO; GO:0034605; P:cellular response to heat; IEA:Ensembl.
DR   GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR   GO; GO:1904019; P:epithelial cell apoptotic process; IEA:Ensembl.
DR   GO; GO:0034101; P:erythrocyte homeostasis; IEA:Ensembl.
DR   GO; GO:0042167; P:heme catabolic process; IBA:GO_Central.
DR   GO; GO:0006788; P:heme oxidation; IBA:GO_Central.
DR   GO; GO:0006879; P:intracellular iron ion homeostasis; IEA:Ensembl.
DR   GO; GO:0016236; P:macroautophagy; IEA:Ensembl.
DR   GO; GO:0060586; P:multicellular organismal-level iron ion homeostasis; IEA:Ensembl.
DR   GO; GO:0043922; P:negative regulation by host of viral transcription; IMP:AgBase.
DR   GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
DR   GO; GO:0016242; P:negative regulation of macroautophagy; IEA:Ensembl.
DR   GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR   GO; GO:1903901; P:negative regulation of viral life cycle; IMP:AgBase.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR   GO; GO:1903589; P:positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IEA:Ensembl.
DR   GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; IEA:Ensembl.
DR   GO; GO:1904037; P:positive regulation of epithelial cell apoptotic process; IEA:Ensembl.
DR   GO; GO:0016239; P:positive regulation of macroautophagy; IEA:Ensembl.
DR   GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
DR   GO; GO:0006979; P:response to oxidative stress; IBA:GO_Central.
DR   GO; GO:0002246; P:wound healing involved in inflammatory response; IEA:Ensembl.
DR   CDD; cd00232; HemeO-like; 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   PRINTS; PR00088; HAEMOXYGNASE.
DR   SUPFAM; SSF48613; Heme oxygenase-like; 1.
DR   PROSITE; PS00593; HEME_OXYGENASE; 1.
PE   1: Evidence at protein level;
KW   Apoptosis; Direct protein sequencing; Endoplasmic reticulum; Heme; Iron;
KW   Membrane; Metal-binding; Oxidoreductase; Phosphoprotein;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..289
FT                   /note="Heme oxygenase 1"
FT                   /id="PRO_0000209686"
FT   CHAIN           1..266
FT                   /note="Heme oxygenase 1 soluble form"
FT                   /evidence="ECO:0000250|UniProtKB:P09601"
FT                   /id="PRO_0000455620"
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          1..24
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          239..261
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         19
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /evidence="ECO:0000250|UniProtKB:P09601"
FT   BINDING         26
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         135
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /evidence="ECO:0000250|UniProtKB:P09601"
FT   BINDING         184
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /evidence="ECO:0000250|UniProtKB:P09601"
FT   SITE            141
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250|UniProtKB:P09601"
FT   MOD_RES         243
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P06762"
FT   CONFLICT        28
FT                   /note="Q -> E (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        100
FT                   /note="P -> PH (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   289 AA;  32940 MW;  8EAEA06BCCA4B96C CRC64;
     MERPQPDSSM PQDLSEALKE ATKEVHTQAE NAEFMKNFQK GELTQEGFKL VMASLYHIYV
     ALEEEIERNK ENPVYTPLYF PEELHRRASL EQDMAFWYGP RWQEAIPYTQ ATKRYVQRLQ
     EVGRTEPELL VAHAYTRYLG DLSGGQVLKK IAQKALNLPS SGEGLAFFTF PNIASATKFK
     QLYRSRMNTL EMTPEVRQRV LDEAKTAFLL NIQLFEELQG LLTQKAKDHD PLQAPELHRR
     AGSKVQDLAP TKASRGKPQP SVLSQAPLLR WVLTLSFLVA TVAVGLYAM
//