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FLASH GENE
Symbol HMOX1 contributors: mct/npt/pgu - updated : 29-12-2015
HGNC name heme oxygenase (decycling) 1
HGNC id 5013
Corresponding disease
HMOX1D heme oxygenase-1 deficiency
Location 22q12.3      Physical location : 35.777.059 - 35.790.205
Synonym name heat shock protein 32K
Synonym symbol(s) HO-1, bK286B10, HSP32, HO, HMOX1D
EC.number 1.14.99.3
DNA
TYPE functioning gene
STRUCTURE 13.11 kb     5 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked Y status confirmed
Physical map
LOC388895 22 LOC388895 LOC388896 22 hypothetical gene supported by BX537993 COX7BP1 22q13 cytochrome c oxidase subunit VIIb pseudogene 1 HMG2L1 22q13.1 high-mobility group protein 2-like 1 LOC388897 22 LOC388897 TOM1 22q13.1 target of myb1 (chicken) HMOX1 22q13.1 heme oxygenase (decycling) 1 MCM5 22q13.1 MCM5 minichromosome maintenance deficient 5, cell division cycle 46 (S. cerevisiae) RASD2 22q13.1 RASD family, member 2 MB 22q13.1 myoglobin LOC284912 22q13.1 hypothetical gene supported by BC001801 APOL6 22q13.1 apolipoprotein L, 6 MRPS16P3 22q12-q13.1 apolipoprotein L, 6 APOL5 22q13.1 apolipoprotein L, 5 RBM9 22q13.1 RNA binding motif protein 9 RPL41P3 22q13.1 ribosomal protein L41, pseudogene 3 NDUFA9P1 22q12.3 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 9, pseudogene 1 APOL3 22q13.1 apolipoprotein L, 3 APOL4 22q13.1 apolipoprotein L, 4 APOL2 22q13.1 apolipoprotein L, 2 APOL1 22q13.1 apolipoprotein L, 1 MYH9 22q13.1 myosin, heavy polypeptide 9, non-muscle LOC388898 22 LOC388898 TXN2 22q13.1 thioredoxin 2 FLJ23322 22q13.1 hypothetical protein FLJ23322 EIF3S7 22q13.1 eukaryotic translation initiation factor 3, subunit 7 zeta, 66/67kDa
RNA
TRANSCRIPTS type messenger
text Alternative splicing within the HMOX1 5prime untranslated region contributes to translational regulation and is a mechanistic feature involved in the interplay between genetic variations, HMOX1 expression and disease outcome (PMID: 24098580)
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
5 - 1550 - 288 - 1994 8034330
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivesalivary gland   highly
Lymphoid/Immunespleen   highly
Reproductivefemale systemplacenta  highly
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period
Text following induction by several stresses
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • membrane binding region (C-terminal 23 AAs), ssential for maximal catalytic activity
  • HOMOLOGY
    interspecies homolog to rattus Hmox1 (80.2pc)
    homolog to murine Hmox1 (82.3pc)
    Homologene
    FAMILY
  • heme oxygenase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,microsome
    intracellular,nucleus,nucleolus
    text
  • highly active in the spleen
  • is not present in the mitochondria despite the fact that the organelle is the site of heme synthesis and contains multiple heme proteins
  • basic FUNCTION
  • rate limiting enzyme in the degradation of heme to biliverdin, inducible form, potent anti-inflammatory proteins whenever oxidation injury takes place
  • playing a critical role in FOXP3-mediated immune suppression
  • catabolizes heme into products exhibiting potent anti-inflammatory properties
  • supports neoplastic mast cell survival
  • has the potential to incorporate into phospholipid membranes, which can be reconstituted at known concentrations, in combination with other endoplasmic reticulum resident enzymes
  • novel role of BMP6/HMOX1 cascade to relieve breast cancer metastasis by regulating the secretion of growth factors in tumor microenvironment
  • tumorigenic role of HMOX1 and the importance of RNF139-mediated HMOX1 degradation in the control of cancer growth
  • exerts a protective effect in retinal endothelial cells exposed to hyperglycemic and oxidative/nitrosative stress conditions
  • has a critical role in the modulation of peritoneal fibrosis, and, more important, the suppression of EMT
  • emerges as one important modulator of innate immune responses in pregnancy
  • catalyzes the first and rate-limiting enzymatic step of heme degradation and produces carbon monoxide, free iron, and biliverdin
  • catalyzes the oxidative degradation of heme
  • progesterone and HMOX1 promote fetal growth by CD8+ T cell modulation
  • is a mediator of ATF4-dependent anoikis resistance and tumor metastasis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • forms heterodimers with small MAF proteins
  • HMOX1-STC2 complex may represent a eukaryotic ‘stressosome’ in conditions where heme is liberated
  • INTERACTION
    DNA
    RNA
    small molecule other,
  • interacting with NO and CO
  • protein
  • BACH1 acts as a repressor of its main target, HMOX1
  • HMOX1 is a binding partner of STC2
  • HDAC6 plays a crucial role in MAPK14-dependent induction of HMOX1 in response to proteasome inhibition
  • functional link between HMOX1 gene expression and PECAM1 in human endothelial cells, which might play a critical role in the regulation of inflammation
  • BRD4 directly targeting the HMOX1 promoter over the SP1-binding sites
  • in oxidative stress, nuclear HMOX1 interacts with NFE2L2 and stabilizes it from GSK3B-mediated phosphorylation coupled with ubiquitin-proteasomal degradation
  • antitumoral role of HMOX1 and importance of TP53 status in this antitumor activity
  • cell & other
    REGULATION
    induced by its substrate heme and by various non-heme substances such as heavy metals, bromobenzene, endotoxin, oxidizing agents and UVa
    BACH1 inactivation (necessary and sufficient for transcriptional induction of HMOX1)
    nitrolinoleic acid
    stress-inducible protein, is induced by various oxidative and inflammatory signals
    Other induction is mediated by cAMP, AP-1, and E-Box response element interaction
    ASSOCIATED DISORDERS
    corresponding disease(s) HMOX1D
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colorectal cancer (CRC)
    Susceptibility
  • may be to emphysema (chronic obstructive pulmonary disease)
  • hypertension in women
  • to restless legs syndrome (RLS)
  • Variant & Polymorphism other
  • AA genotype associated with an increased incidence of hypertension in women
  • weak association between HMOX1 rs2071746 polymorphism and the risk to develop RLS
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    interesting new therapeutic target in neoplastic mast cells
    cancer  
    ATF4 and HMOX1 are potential targets for therapeutic intervention in solid tumors
    neurosensorialvisualanterior chamber
    upregulation of HMOX1 signaling may therefore be a novel therapeutic strategy for glaucoma
    ANIMAL & CELL MODELS