HMOX2_RAT
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 03-AUG-2022, entry version 170.
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 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: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 -!- 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_006245827.3.
DR AlphaFoldDB; P23711; -.
DR SMR; P23711; -.
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; P23711; -.
DR PRIDE; P23711; -.
DR Ensembl; ENSRNOT00000005031; ENSRNOP00000005031; ENSRNOG00000003773.
DR GeneID; 79239; -.
DR KEGG; rno:79239; -.
DR UCSC; RGD:67402; rat.
DR CTD; 3163; -.
DR RGD; 67402; Hmox2.
DR eggNOG; KOG4480; Eukaryota.
DR GeneTree; ENSGT00390000017673; -.
DR InParanoid; P23711; -.
DR OMA; ANRAFEY; -.
DR OrthoDB; 1424194at2759; -.
DR PhylomeDB; P23711; -.
DR TreeFam; TF314786; -.
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 tissues.
DR Genevisible; P23711; RN.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042167; P:heme catabolic process; IBA:GO_Central.
DR GO; GO:0006788; P:heme oxidation; IBA:GO_Central.
DR GO; GO:0055072; P:iron ion homeostasis; 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 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 PRINTS; PR00088; HAEMOXYGNASE.
DR SUPFAM; SSF48613; SSF48613; 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; Transmembrane; 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 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
