ID   HMOX2_RAT               Reviewed;         315 AA.
AC   P23711;
DT   01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1991, sequence version 1.
DT   04-NOV-2026, entry version 185.
DE   RecName: Full=Heme oxygenase 2;
DE            Short=HO-2;
DE            EC=1.14.14.18 {ECO:0000269|PubMed:1575508, ECO:0000269|PubMed:2185251};
DE   Contains:
DE     RecName: Full=Heme oxygenase 2 soluble form {ECO:0000250|UniProtKB:P30519};
GN   Name=Hmox2;
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 [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC   TISSUE=Testis;
RX   PubMed=2185251; DOI=10.1016/s0021-9258(19)39141-0;
RA   Rotenberg M.O., Maines M.D.;
RT   "Isolation, characterization, and expression in Escherichia coli of a cDNA
RT   encoding rat heme oxygenase-2.";
RL   J. Biol. Chem. 265:7501-7506(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RX   PubMed=8112599; DOI=10.1016/0378-1119(94)90749-8;
RA   McCoubrey W.K. Jr., Maines M.D.;
RT   "The structure, organization and differential expression of the gene
RT   encoding rat heme oxygenase-2.";
RL   Gene 139:155-161(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Prostate;
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   NUCLEOTIDE SEQUENCE [MRNA] OF 142-232, PARTIAL PROTEIN SEQUENCE, AND
RP   INDUCTION.
RC   TISSUE=Liver, and Testis;
RX   PubMed=3343248; DOI=10.1016/s0021-9258(18)69078-7;
RA   Cruse I., Maines M.D.;
RT   "Evidence suggesting that the two forms of heme oxygenase are products of
RT   different genes.";
RL   J. Biol. Chem. 263:3348-3353(1988).
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   IDENTIFICATION BY 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).
CC   -!- FUNCTION: [Heme oxygenase 2]: 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. {ECO:0000269|PubMed:1575508,
CC       ECO:0000269|PubMed:2185251}.
CC   -!- FUNCTION: [Heme oxygenase 2 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:P30519}.
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:0000269|PubMed:1575508, ECO:0000269|PubMed:2185251};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21765;
CC         Evidence={ECO:0000305|PubMed:2185251};
CC   -!- ACTIVITY REGULATION: Inhibited by metalloporphyrins such as Sn- and Zn-
CC       protoporphyrins. {ECO:0000269|PubMed:1575508}.
CC   -!- INTERACTION:
CC       P23711; P62161: Calm3; NbExp=2; IntAct=EBI-2910092, EBI-397530;
CC       P23711; P62157: CALM; Xeno; NbExp=3; IntAct=EBI-2910092, EBI-397403;
CC   -!- SUBCELLULAR LOCATION: Microsome membrane
CC       {ECO:0000250|UniProtKB:P30519}; Single-pass type IV membrane protein
CC       {ECO:0000255}; Cytoplasmic side {ECO:0000250|UniProtKB:P09601}.
CC       Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P09601}; Single-
CC       pass type IV membrane protein {ECO:0000255}; Cytoplasmic side
CC       {ECO:0000250|UniProtKB:P09601}.
CC   -!- TISSUE SPECIFICITY: Widely distributed in body with a high
CC       concentration in the brain. {ECO:0000269|PubMed:8112599}.
CC   -!- INDUCTION: Heme oxygenase 2 activity is non-inducible.
CC       {ECO:0000269|PubMed:3343248}.
CC   -!- PTM: A soluble form arises by proteolytic removal of the membrane
CC       anchor. {ECO:0000250|UniProtKB:P30519}.
CC   -!- PTM: S-nitrosylated by BLVRB. {ECO:0000250|UniProtKB:P30519}.
CC   -!- SIMILARITY: Belongs to the heme oxygenase family. {ECO:0000305}.
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DR   EMBL; J05405; AAA41340.1; -; mRNA.
DR   EMBL; U05013; AAA19130.1; -; Genomic_DNA.
DR   EMBL; BC062061; AAH62061.1; -; mRNA.
DR   EMBL; M18918; AAA41347.1; -; mRNA.
DR   PIR; A35199; A35199.
DR   RefSeq; NP_001264002.1; NM_001277073.1.
DR   RefSeq; NP_077363.1; NM_024387.2.
DR   RefSeq; XP_006245889.1; XM_006245827.5.
DR   RefSeq; XP_063125986.1; XM_063269916.1.
DR   AlphaFoldDB; P23711; -.
DR   SMR; P23711; -.
DR   FunCoup; P23711; 2189.
DR   IntAct; P23711; 2.
DR   STRING; 10116.ENSRNOP00000005031; -.
DR   BindingDB; P23711; -.
DR   ChEMBL; CHEMBL3348; -.
DR   DrugCentral; P23711; -.
DR   GuidetoPHARMACOLOGY; 1442; -.
DR   iPTMnet; P23711; -.
DR   PhosphoSitePlus; P23711; -.
DR   jPOST; P23711; -.
DR   PaxDb; 10116-ENSRNOP00000005031; -.
DR   Ensembl; ENSRNOT00000077164.3; ENSRNOP00000075102.3; ENSRNOG00000003773.8.
DR   Ensembl; ENSRNOT00055048553; ENSRNOP00055039913; ENSRNOG00055028051.
DR   Ensembl; ENSRNOT00060012904; ENSRNOP00060009780; ENSRNOG00060007820.
DR   Ensembl; ENSRNOT00065016608; ENSRNOP00065012651; ENSRNOG00065010283.
DR   GeneID; 79239; -.
DR   KEGG; rno:79239; -.
DR   UCSC; RGD:67402; rat.
DR   AGR; RGD:67402; -.
DR   CTD; 3163; -.
DR   RGD; 67402; Hmox2.
DR   eggNOG; KOG4480; Eukaryota.
DR   GeneTree; ENSGT00390000017673; -.
DR   InParanoid; P23711; -.
DR   OrthoDB; 27566at9989; -.
DR   PhylomeDB; P23711; -.
DR   BRENDA; 1.14.14.18; 5301.
DR   Reactome; R-RNO-189483; Heme degradation.
DR   Reactome; R-RNO-6798695; Neutrophil degranulation.
DR   Reactome; R-RNO-8980692; RHOA GTPase cycle.
DR   Reactome; R-RNO-917937; Iron uptake and transport.
DR   Reactome; R-RNO-9707564; Cytoprotection by HMOX1.
DR   SABIO-RK; P23711; -.
DR   PRO; PR:P23711; -.
DR   Proteomes; UP000002494; Chromosome 10.
DR   Bgee; ENSRNOG00000003773; Expressed in testis and 20 other cell types or tissues.
DR   ExpressionAtlas; P23711; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR   GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR   GO; GO:0004392; F:heme oxygenase (decyclizing) activity; IDA:UniProtKB.
DR   GO; GO:0042167; P:heme catabolic process; IBA:GO_Central.
DR   GO; GO:0006788; P:heme oxidation; IBA:GO_Central.
DR   GO; GO:0001666; P:response to hypoxia; ISO:RGD.
DR   GO; GO:0006979; P:response to oxidative stress; IDA:RGD.
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:SF2; HEME OXYGENASE 2; 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   Acetylation; Direct protein sequencing; Endoplasmic reticulum; Heme; Iron;
KW   Membrane; Metal-binding; Microsome; Oxidoreductase; Phosphoprotein;
KW   Reference proteome; Repeat; S-nitrosylation; Transmembrane;
KW   Transmembrane helix.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P30519"
FT   CHAIN           2..315
FT                   /note="Heme oxygenase 2"
FT                   /id="PRO_0000209694"
FT   CHAIN           2..294
FT                   /note="Heme oxygenase 2 soluble form"
FT                   /evidence="ECO:0000250|UniProtKB:P30519"
FT                   /id="PRO_0000455628"
FT   TOPO_DOM        2..294
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P09601"
FT   TRANSMEM        295..315
FT                   /note="Helical; Anchor for type IV membrane protein"
FT                   /evidence="ECO:0000255"
FT   REPEAT          263..268
FT                   /note="HRM 1"
FT   REPEAT          280..285
FT                   /note="HRM 2"
FT   REGION          1..29
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..15
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         44
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:P30519"
FT   BINDING         153
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /evidence="ECO:0000250|UniProtKB:P30519"
FT   BINDING         198
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /evidence="ECO:0000250|UniProtKB:P30519"
FT   BINDING         202
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /evidence="ECO:0000250|UniProtKB:P30519"
FT   SITE            159
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250|UniProtKB:P09601"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000250|UniProtKB:P30519"
FT   MOD_RES         2
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P30519"
FT   MOD_RES         264
FT                   /note="S-nitrosocysteine"
FT                   /evidence="ECO:0000250|UniProtKB:P30519"
FT   MOD_RES         281
FT                   /note="S-nitrosocysteine"
FT                   /evidence="ECO:0000250|UniProtKB:P30519"
FT   CONFLICT        142..146
FT                   /note="QNEPE -> EFRNK (in Ref. 4; AAA41347)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        230..232
FT                   /note="MQI -> TEF (in Ref. 4; AAA41347)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   315 AA;  35762 MW;  981AADE01DE1AFCF CRC64;
     MSSEVETSEG VDESENNSTA PEKENHTKMA DLSELLKEGT KEAHDRAENT QFVKDFLKGN
     IKKELFKLAT TALYFTYSAL EEEMDRNKDH PAFAPLYFPT ELHRKEALIK DMEYFFGENW
     EEQVKCSEAA QKYVDRIHYV GQNEPELLVA HAYTRYMGDL SGGQVLKKVA QRALKLPSTG
     EGTQFYLFEH VDNAQQFKQF YRARMNALDL SMKTKERIVE EANKAFEYNM QIFSELDQAG
     SMLTKETLED GLPVHDGKGD VRKCPFYAAQ PDKGTLGGSN CPFRTAMAVL RKPSLQLILA
     ASVALVAGLL AWYYM
//