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    HMOX2 heme oxygenase 2 [ Homo sapiens (human) ]

    Gene ID: 3163, updated on 10-Dec-2024

    Summary

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    Official Symbol
    HMOX2provided by HGNC
    Official Full Name
    heme oxygenase 2provided by HGNC
    Primary source
    HGNC:HGNC:5014
    See related
    Ensembl:ENSG00000103415 MIM:141251; AllianceGenome:HGNC:5014
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HO-2
    Summary
    Heme oxygenase, an essential enzyme in heme catabolism, cleaves heme to form biliverdin, which is subsequently converted to bilirubin by biliverdin reductase, and carbon monoxide, a putative neurotransmitter. Heme oxygenase activity is induced by its substrate heme and by various nonheme substances. Heme oxygenase occurs as 2 isozymes, an inducible heme oxygenase-1 and a constitutive heme oxygenase-2. HMOX1 and HMOX2 belong to the heme oxygenase family. Several alternatively spliced transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]
    Expression
    Ubiquitous expression in testis (RPKM 23.0), brain (RPKM 16.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HMOX2 in Genome Data Viewer
    Location:
    16p13.3
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (4474736..4510347)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (4504257..4539822)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (4524737..4560348)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124903635 Neighboring gene DnaJ heat shock protein family (Hsp40) member A3 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:4499977-4500772 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:4505719-4506689 Neighboring gene MPRA-validated peak2472 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:4516031-4516532 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:4526195-4526696 Neighboring gene NmrA like redox sensor 1 Neighboring gene uncharacterized LOC124903636 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:4543888-4544077 Neighboring gene Sharpr-MPRA regulatory region 9698 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:4563218-4563745 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:4563746-4564272 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:4564273-4564800 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:4571909-4572773 Neighboring gene cell death inducing p53 target 1 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:4579080-4579732 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:4579733-4580384 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10340 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7152 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7153 Neighboring gene chromosome 16 open reading frame 96 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:4604203-4604813 Neighboring gene SUB1 pseudogene 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Heme oxygenase-2 is post-translationally regulated by heme occupancy in the catalytic site. Liu L, et al. J Biol Chem, 2020 Dec 11. PMID 33051205, Free PMC Article
    2. Evidence that the heme regulatory motifs in heme oxygenase-2 serve as a thiol/disulfide redox switch regulating heme binding. Yi L, et al. J Biol Chem, 2007 Jul 20. PMID 17540772, Free PMC Article
    3. Heme oxygenase-2 (HO-2) binds and buffers labile ferric heme in human embryonic kidney cells. Hanna DA, et al. J Biol Chem, 2022 Feb. PMID 34973332, Free PMC Article
    4. Comparison of apo- and heme-bound crystal structures of a truncated human heme oxygenase-2. Bianchetti CM, et al. J Biol Chem, 2007 Dec 28. PMID 17965015, Free PMC Article
    5. Inhibitors of heme oxygenase reduce invasion of human primary cytotrophoblast cells in vitro. McCaig D, et al. Placenta, 2009 Jun. PMID 19345412

    See all (138) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Heme oxygenase-2 (HO-2) binds and buffers labile ferric heme in human embryonic kidney cells.
      Title: Heme oxygenase-2 (HO-2) binds and buffers labile ferric heme in human embryonic kidney cells.
    2. Heme oxygenase-1 & 2 and their potential contribution in heme induced colorectal carcinogenesis.
      Title: Heme oxygenase-1 & 2 and their potential contribution in heme induced colorectal carcinogenesis.
    3. Immune Modulation by Inhibitors of the HO System.
      Title: Immune Modulation by Inhibitors of the HO System.
    4. Heme oxygenase promotes B-Raf-dependent melanosphere formation.
      Title: Heme oxygenase promotes B-Raf-dependent melanosphere formation.
    5. Heme oxygenase-2 is post-translationally regulated by heme occupancy in the catalytic site.
      Title: Heme oxygenase-2 is post-translationally regulated by heme occupancy in the catalytic site.
    6. results highlight significant dynamic and structural differences between HO2 and HO1 and indicate that their dissimilar C-terminal regions play a major role in controlling the structural dynamics of these two proteins.
      Title: Dynamic and structural differences between heme oxygenase-1 and -2 are due to differences in their C-terminal regions.
    7. REVIEW: Redox Regulation of Heme Oxygenase-2 and the Transcription Factor, Rev-Erb, Through Heme Regulatory Motifs
      Title: Redox Regulation of Heme Oxygenase-2 and the Transcription Factor, Rev-Erb, Through Heme Regulatory Motifs.
    8. The frequencies of genotype and allelic variants of ALAD rs1800435 did not differ significantly between patients with essential tremor (ET) and controls, and were not influenced by gender. Subjects carrying the ALAD rs1800435CC genotype (wild-type) and the HMOX2 rs1051308GG genotype or the HMOX2 rs1051308G allele had significantly decreased risk for ET.
      Title: Delta-amino-levulinic acid dehydratase gene and essential tremor.
    9. The domains involved in HO-1 translocation have been identified, and it was shown that SPP-mediated HO-1 cleavage is isoform-specific (HO-1 vs HO-2) and independent of heme oxygenase activity.
      Title: Insights into the mechanism of isoenzyme-specific signal peptide peptidase-mediated translocation of heme oxygenase.
    10. HO-2 is a cellular myristate-binding protein that negatively regulates both virus replication and host inflammatory responses.
      Title: Heme Oxygenase 2 Binds Myristate to Regulate Retrovirus Assembly and TLR4 Signaling.
    Submit: New GeneRIF Correction See all GeneRIFs (50)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Genes, including GABRP, ADF, HINT, PRSS2, SDCBP, PTK9, PPP2R5B, ITGA3, PRKCBP1, HMOX2, HAT1, PPP1cB, and ICAM-1, are upregulated after treatment of human astrocytes with HIV-1 gp120 PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables heme binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables heme oxygenase (decyclizing) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables heme oxygenase (decyclizing) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in heme catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in heme oxidation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in response to hypoxia IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to oxidative stress IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in membrane HDA PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in specific granule membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    heme oxygenase 2
    Names
    heme oxygenase (decycling) 2
    NP_001120676.1
    NP_001120677.1
    NP_001120678.1
    NP_001273196.1
    NP_001273197.1
    NP_001273198.1
    NP_001273199.1
    NP_001273200.1
    NP_002125.3
    XP_016878685.1
    XP_024306018.1
    XP_054185152.1
    XP_054185153.1
    XP_054236180.1
    XP_054236181.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001127204.2 → NP_001120676.1  heme oxygenase 2 isoform b

      See identical proteins and their annotated locations for NP_001120676.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) differs in the 5' UTR and coding sequence compared to variant 5. The resulting isoform (b) is shorter at the N-terminus compared to isoform a. Variants 1, 2, 3, 4, 6, 7, and 8 all encode the same isoform (b).
      Source sequence(s)
      BC002396, D21243, DA141643, DA694137
      Consensus CDS
      CCDS10517.1
      UniProtKB/Swiss-Prot
      A8MT35, D3DUD5, I3L430, O60605, P30519
      UniProtKB/TrEMBL
      B3KSE0, Q6FHB5, Q6IBP2
      Related
      ENSP00000394103.3, ENST00000458134.7
      Conserved Domains (2) summary
      cd19165
      Location:147 → 174
      HemeO; kinked helix [structural motif]
      pfam01126
      Location:31 → 236
      Heme_oxygenase; Heme oxygenase

    2. NM_001127205.2 → NP_001120677.1  heme oxygenase 2 isoform b

      See identical proteins and their annotated locations for NP_001120677.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 5. The resulting isoform (b) is shorter at the N-terminus compared to isoform a. Variants 1, 2, 3, 4, 6, 7, and 8 all encode the same isoform (b).
      Source sequence(s)
      BC002396, BP368949, D21243
      Consensus CDS
      CCDS10517.1
      UniProtKB/Swiss-Prot
      A8MT35, D3DUD5, I3L430, O60605, P30519
      UniProtKB/TrEMBL
      B3KSE0, Q6FHB5, Q6IBP2
      Related
      ENSP00000391637.1, ENST00000414777.5
      Conserved Domains (2) summary
      cd19165
      Location:147 → 174
      HemeO; kinked helix [structural motif]
      pfam01126
      Location:31 → 236
      Heme_oxygenase; Heme oxygenase

    3. NM_001127206.3 → NP_001120678.1  heme oxygenase 2 isoform b

      See identical proteins and their annotated locations for NP_001120678.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and coding sequence compared to variant 5. The resulting isoform (b) is shorter at the N-terminus compared to isoform a. Variants 1, 2, 3, 4, 6, 7, and 8 all encode the same isoform (b).
      Source sequence(s)
      BC002396, BE561721
      Consensus CDS
      CCDS10517.1
      UniProtKB/Swiss-Prot
      A8MT35, D3DUD5, I3L430, O60605, P30519
      UniProtKB/TrEMBL
      B3KSE0, Q6FHB5, Q6IBP2
      Related
      ENSP00000385100.2, ENST00000406590.6
      Conserved Domains (2) summary
      cd19165
      Location:147 → 174
      HemeO; kinked helix [structural motif]
      pfam01126
      Location:31 → 236
      Heme_oxygenase; Heme oxygenase

    4. NM_001286267.2 → NP_001273196.1  heme oxygenase 2 isoform a

      See identical proteins and their annotated locations for NP_001273196.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) encodes the longest isoform (a).
      Source sequence(s)
      BC002396, DA141643
      Consensus CDS
      CCDS73818.1
      UniProtKB/TrEMBL
      A0A087WT44, B3KSE0, Q6FHB5, Q6IBP2
      Related
      ENSP00000477572.1, ENST00000613539.1
      Conserved Domains (1) summary
      pfam01126
      Location:85 → 290
      Heme_oxygenase; Heme oxygenase

    5. NM_001286268.2 → NP_001273197.1  heme oxygenase 2 isoform b

      See identical proteins and their annotated locations for NP_001273197.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR and coding sequence compared to variant 5. The resulting isoform (b) is shorter at the N-terminus compared to isoform a. Variants 1, 2, 3, 4, 6, 7, and 8 all encode the same isoform (b).
      Source sequence(s)
      BC002396, DA141643, DB184091
      Consensus CDS
      CCDS10517.1
      UniProtKB/Swiss-Prot
      A8MT35, D3DUD5, I3L430, O60605, P30519
      UniProtKB/TrEMBL
      B3KSE0, Q6FHB5, Q6IBP2
      Related
      ENSP00000484467.1, ENST00000619913.4
      Conserved Domains (2) summary
      cd19165
      Location:147 → 174
      HemeO; kinked helix [structural motif]
      pfam01126
      Location:31 → 236
      Heme_oxygenase; Heme oxygenase

    6. NM_001286269.2 → NP_001273198.1  heme oxygenase 2 isoform b

      See identical proteins and their annotated locations for NP_001273198.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) differs in the 5' UTR and coding sequence compared to variant 5. The resulting isoform (b) is shorter at the N-terminus compared to isoform a. Variants 1, 2, 3, 4, 6, 7, and 8 all encode the same isoform (b).
      Source sequence(s)
      BC002396, BP329113, DA141643
      Consensus CDS
      CCDS10517.1
      UniProtKB/Swiss-Prot
      A8MT35, D3DUD5, I3L430, O60605, P30519
      UniProtKB/TrEMBL
      B3KSE0, Q6FHB5, Q6IBP2
      Related
      ENSP00000484423.1, ENST00000619528.4
      Conserved Domains (2) summary
      cd19165
      Location:147 → 174
      HemeO; kinked helix [structural motif]
      pfam01126
      Location:31 → 236
      Heme_oxygenase; Heme oxygenase

    7. NM_001286270.2 → NP_001273199.1  heme oxygenase 2 isoform b

      See identical proteins and their annotated locations for NP_001273199.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) differs in the 5' UTR and coding sequence compared to variant 5. The resulting isoform (b) is shorter at the N-terminus compared to isoform a. Variants 1, 2, 3, 4, 6, 7, and 8 all encode the same isoform (b).
      Source sequence(s)
      AK093388, BC002396
      Consensus CDS
      CCDS10517.1
      UniProtKB/Swiss-Prot
      A8MT35, D3DUD5, I3L430, O60605, P30519
      UniProtKB/TrEMBL
      B3KSE0, Q6FHB5, Q6IBP2
      Related
      ENSP00000381595.3, ENST00000398595.7
      Conserved Domains (2) summary
      cd19165
      Location:147 → 174
      HemeO; kinked helix [structural motif]
      pfam01126
      Location:31 → 236
      Heme_oxygenase; Heme oxygenase

    8. NM_001286271.2 → NP_001273200.1  heme oxygenase 2 isoform c

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9) differs in the 5' UTR and coding sequence compared to variant 5. The resulting isoform (c) is shorter at the N-terminus compared to isoform a.
      Source sequence(s)
      BC002396, BM905872, DA141643
      Consensus CDS
      CCDS66931.1
      UniProtKB/TrEMBL
      B3KSE0, Q6FHB5, Q6IBP2
      Related
      ENSP00000460926.1, ENST00000575120.5
      Conserved Domains (1) summary
      pfam01126
      Location:2 → 207
      Heme_oxygenase; Heme oxygenase

    9. NM_002134.4 → NP_002125.3  heme oxygenase 2 isoform b

      See identical proteins and their annotated locations for NP_002125.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 5. The resulting isoform (b) is shorter at the N-terminus compared to isoform a. Variants 1, 2, 3, 4, 6, 7, and 8 all encode the same isoform (b).
      Source sequence(s)
      BC002396, DA141643
      Consensus CDS
      CCDS10517.1
      UniProtKB/Swiss-Prot
      A8MT35, D3DUD5, I3L430, O60605, P30519
      UniProtKB/TrEMBL
      B3KSE0, Q6FHB5, Q6IBP2
      Related
      ENSP00000459214.1, ENST00000570646.6
      Conserved Domains (2) summary
      cd19165
      Location:147 → 174
      HemeO; kinked helix [structural motif]
      pfam01126
      Location:31 → 236
      Heme_oxygenase; Heme oxygenase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      4474736..4510347
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017023196.3 → XP_016878685.1  heme oxygenase 2 isoform X1

      UniProtKB/Swiss-Prot
      A8MT35, D3DUD5, I3L430, O60605, P30519
      UniProtKB/TrEMBL
      B3KSE0, Q6FHB5, Q6IBP2
      Conserved Domains (2) summary
      cd19165
      Location:147 → 174
      HemeO; kinked helix [structural motif]
      pfam01126
      Location:31 → 236
      Heme_oxygenase; Heme oxygenase

    2. XM_024450250.2 → XP_024306018.1  heme oxygenase 2 isoform X1

      UniProtKB/Swiss-Prot
      A8MT35, D3DUD5, I3L430, O60605, P30519
      UniProtKB/TrEMBL
      B3KSE0, Q6FHB5, Q6IBP2
      Conserved Domains (2) summary
      cd19165
      Location:147 → 174
      HemeO; kinked helix [structural motif]
      pfam01126
      Location:31 → 236
      Heme_oxygenase; Heme oxygenase

    Reference GRCh38.p14 ALT_REF_LOCI_1

    Genomic

    1. NT_187608.1 Reference GRCh38.p14 ALT_REF_LOCI_1

      Range
      177059..212670
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054329177.1 → XP_054185152.1  heme oxygenase 2 isoform X1

      UniProtKB/Swiss-Prot
      A8MT35, D3DUD5, I3L430, O60605, P30519
      UniProtKB/TrEMBL
      B3KSE0, Q6FHB5, Q6IBP2

    2. XM_054329178.1 → XP_054185153.1  heme oxygenase 2 isoform X1

      UniProtKB/Swiss-Prot
      A8MT35, D3DUD5, I3L430, O60605, P30519
      UniProtKB/TrEMBL
      B3KSE0, Q6FHB5, Q6IBP2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      4504257..4539822
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054380205.1 → XP_054236180.1  heme oxygenase 2 isoform X1

      UniProtKB/Swiss-Prot
      A8MT35, D3DUD5, I3L430, O60605, P30519
      UniProtKB/TrEMBL
      B3KSE0, Q6FHB5, Q6IBP2

    2. XM_054380206.1 → XP_054236181.1  heme oxygenase 2 isoform X1

      UniProtKB/Swiss-Prot
      A8MT35, D3DUD5, I3L430, O60605, P30519
      UniProtKB/TrEMBL
      B3KSE0, Q6FHB5, Q6IBP2
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P30519.2 GenPept UniProtKB/Swiss-Prot:P30519

    Gene LinkOut

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