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HMOX2 heme oxygenase 2 [ Homo sapiens (human) ]

Gene ID: 3163, updated on 7-Apr-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
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Genomic context

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Location:
16p13.3
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (4474736..4510347)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (4504257..4539822)
105.20220307 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 (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
  2. 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
  3. Association between a heme oxygenase-2 genetic variant and risk of Parkinson's disease in Han Chinese. Tian S, et al. Neurosci Lett, 2017 Mar 6. PMID 28179208
  4. Heme Oxygenase 2 Binds Myristate to Regulate Retrovirus Assembly and TLR4 Signaling. Zhu Y, et al. Cell Host Microbe, 2017 Feb 8. PMID 28132836, Free PMC Article
  5. HMOX2 Functions as a Modifier Gene for High-Altitude Adaptation in Tibetans. Yang D, et al. Hum Mutat, 2016 Feb. PMID 26781569

See all (123) 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)

Genotypes

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_2023_10

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

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

    UniProtKB/Swiss-Prot
    A8MT35, D3DUD5, I3L430, O60605, P30519

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

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

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

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