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Protein

Heme oxygenase 1

Gene

HMOX1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed. Exhibits cytoprotective effects since excess of free heme sensitizes cells to undergo apoptosis.

Catalytic activityi

Protoheme + 3 [reduced NADPH--hemoprotein reductase] + 3 O2 = biliverdin + Fe2+ + CO + 3 [oxidized NADPH--hemoprotein reductase] + 3 H2O.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei18Heme1
Metal bindingi25Iron (heme axial ligand)1
Binding sitei134Heme1
Binding sitei183Heme1

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • heme binding Source: BHF-UCL
  • heme oxygenase (decyclizing) activity Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW
  • phospholipase D activity Source: Ensembl
  • protein homodimerization activity Source: UniProtKB
  • signal transducer activity Source: UniProtKB

GO - Biological processi

  • angiogenesis Source: BHF-UCL
  • cell death Source: BHF-UCL
  • cellular iron ion homeostasis Source: CACAO
  • cellular response to arsenic-containing substance Source: Ensembl
  • cellular response to cadmium ion Source: Ensembl
  • cellular response to cisplatin Source: Ensembl
  • cellular response to heat Source: UniProtKB
  • cellular response to hypoxia Source: UniProtKB
  • cellular response to nutrient Source: Ensembl
  • cytokine-mediated signaling pathway Source: Reactome
  • endothelial cell proliferation Source: BHF-UCL
  • erythrocyte homeostasis Source: BHF-UCL
  • excretion Source: BHF-UCL
  • heme catabolic process Source: BHF-UCL
  • heme oxidation Source: BHF-UCL
  • intracellular signal transduction Source: BHF-UCL
  • intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
  • iron ion homeostasis Source: BHF-UCL
  • liver regeneration Source: Ensembl
  • low-density lipoprotein particle clearance Source: BHF-UCL
  • negative regulation of DNA binding Source: Ensembl
  • negative regulation of DNA binding transcription factor activity Source: Ensembl
  • negative regulation of epithelial cell apoptotic process Source: Ensembl
  • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
  • negative regulation of leukocyte migration Source: BHF-UCL
  • negative regulation of macroautophagy Source: Ensembl
  • negative regulation of mast cell cytokine production Source: Ensembl
  • negative regulation of mast cell degranulation Source: Ensembl
  • negative regulation of muscle cell apoptotic process Source: Ensembl
  • negative regulation of neuron apoptotic process Source: Ensembl
  • negative regulation of smooth muscle cell proliferation Source: UniProtKB
  • negative regulation of vascular smooth muscle cell proliferation Source: Ensembl
  • positive regulation of angiogenesis Source: BHF-UCL
  • positive regulation of apoptotic process Source: Ensembl
  • positive regulation of blood vessel diameter Source: BHF-UCL
  • positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis Source: BHF-UCL
  • positive regulation of cell migration involved in sprouting angiogenesis Source: BHF-UCL
  • positive regulation of chemokine biosynthetic process Source: BHF-UCL
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of macroautophagy Source: Ensembl
  • positive regulation of smooth muscle cell proliferation Source: UniProtKB
  • protein homooligomerization Source: UniProtKB
  • regulation of angiogenesis Source: BHF-UCL
  • regulation of blood pressure Source: Ensembl
  • regulation of DNA binding transcription factor activity Source: BHF-UCL
  • regulation of transcription from RNA polymerase II promoter in response to iron Source: Ensembl
  • regulation of transcription from RNA polymerase II promoter in response to oxidative stress Source: BHF-UCL
  • response to estrogen Source: Ensembl
  • response to hydrogen peroxide Source: BHF-UCL
  • response to nicotine Source: BHF-UCL
  • response to oxidative stress Source: BHF-UCL
  • small GTPase mediated signal transduction Source: Ensembl
  • smooth muscle hyperplasia Source: BHF-UCL
  • wound healing involved in inflammatory response Source: BHF-UCL

Keywordsi

Molecular functionOxidoreductase
Biological processApoptosis
LigandHeme, Iron, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS02027-MONOMER
BRENDAi1.14.99.3 2681
ReactomeiR-HSA-189483 Heme degradation
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-917937 Iron uptake and transport
SIGNORiP09601

Names & Taxonomyi

Protein namesi
Recommended name:
Heme oxygenase 1 (EC:1.14.14.18By similarity)
Short name:
HO-1
Gene namesi
Name:HMOX1
Synonyms:HO, HO1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100292.16
HGNCiHGNC:5013 HMOX1
MIMi141250 gene
neXtProtiNX_P09601

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Involvement in diseasei

Heme oxygenase 1 deficiency (HMOX1D)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by impaired stress hematopoiesis, resulting in marked erythrocyte fragmentation and intravascular hemolysis, coagulation abnormalities, endothelial damage, and iron deposition in renal and hepatic tissues. Clinical features include persistent hemolytic anemia, asplenia, nephritis, generalized erythematous rash, growth retardation and hepatomegaly.
See also OMIM:614034

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi140D → A: Inactive as a heme oxygenase but active as a peroxidase. 1 Publication1

Organism-specific databases

DisGeNETi3162
MalaCardsiHMOX1
MIMi614034 phenotype
OpenTargetsiENSG00000100292
PharmGKBiPA29341

Chemistry databases

ChEMBLiCHEMBL2823
DrugBankiDB07342 1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone
DB02468 12-Phenylheme
DB03906 2-Phenylheme
DB02073 Biliverdine Ix Alpha
DB01942 Formic Acid
DB00157 NADH
DB04912 Stannsoporfin
DB04803 Verdoheme
DB00163 Vitamin E
GuidetoPHARMACOLOGYi1441

Polymorphism and mutation databases

BioMutaiHMOX1
DMDMi123446

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002096871 – 288Heme oxygenase 1Add BLAST288

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei229PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP09601
PaxDbiP09601
PeptideAtlasiP09601
PRIDEiP09601

PTM databases

iPTMnetiP09601
PhosphoSitePlusiP09601

Expressioni

Tissue specificityi

Expressed at higher levels in renal cancer tissue than in normal tissue (at protein level).1 Publication

Inductioni

Heme oxygenase 1 activity is highly inducible by its substrate heme and by various non-heme substances such as heavy metals, bromobenzene, endotoxin, oxidizing agents and UVA.

Gene expression databases

BgeeiENSG00000100292
CleanExiHS_HMOX1
ExpressionAtlasiP09601 baseline and differential
GenevisibleiP09601 HS

Organism-specific databases

HPAiCAB017444
HPA000635

Interactioni

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi109405, 37 interactors
IntActiP09601, 11 interactors
MINTiP09601
STRINGi9606.ENSP00000216117

Chemistry databases

BindingDBiP09601

Structurei

Secondary structure

1288
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi6 – 8Combined sources3
Helixi13 – 20Combined sources8
Helixi22 – 30Combined sources9
Helixi32 – 38Combined sources7
Helixi44 – 68Combined sources25
Turni72 – 74Combined sources3
Helixi75 – 77Combined sources3
Helixi80 – 83Combined sources4
Helixi86 – 97Combined sources12
Helixi101 – 103Combined sources3
Helixi109 – 124Combined sources16
Helixi126 – 128Combined sources3
Helixi129 – 155Combined sources27
Beta strandi159 – 161Combined sources3
Helixi165 – 167Combined sources3
Helixi175 – 188Combined sources14
Helixi193 – 220Combined sources28

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1N3UX-ray2.58A/B1-233[»]
1N45X-ray1.50A/B1-233[»]
1NI6X-ray2.10A/B/C/D1-224[»]
1OYKX-ray2.59A/B1-233[»]
1OYLX-ray1.59A/B1-233[»]
1OZEX-ray2.19A/B1-233[»]
1OZLX-ray1.58A/B1-233[»]
1OZRX-ray1.74A/B1-233[»]
1OZWX-ray1.55A/B1-233[»]
1S13X-ray2.29A/B1-233[»]
1S8CX-ray2.19A/B/C/D1-233[»]
1T5PX-ray2.11A/B1-233[»]
1TWNX-ray2.20A/B1-233[»]
1TWRX-ray2.10A/B1-233[»]
1XJZX-ray1.88A/B1-233[»]
1XK0X-ray2.18A/B1-233[»]
1XK1X-ray2.08A/B1-233[»]
1XK2X-ray2.20A/B1-233[»]
1XK3X-ray2.08A/B1-233[»]
3CZYX-ray1.54A/B1-233[»]
3HOKX-ray2.19A/B1-233[»]
3K4FX-ray2.17A/B1-233[»]
3TGMX-ray2.85A/B1-233[»]
4WD4X-ray2.95A/B/C/D1-288[»]
5BTQX-ray2.08A/B1-233[»]
ProteinModelPortaliP09601
SMRiP09601
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP09601

Family & Domainsi

Sequence similaritiesi

Belongs to the heme oxygenase family.Curated

Phylogenomic databases

eggNOGiKOG4480 Eukaryota
COG5398 LUCA
GeneTreeiENSGT00390000017673
HOGENOMiHOG000233221
HOVERGENiHBG005982
InParanoidiP09601
KOiK00510
OMAiKKSHTMA
OrthoDBiEOG091G0AS0
PhylomeDBiP09601
TreeFamiTF314786

Family and domain databases

CDDicd00232 HemeO, 1 hit
Gene3Di1.20.910.10, 1 hit
InterProiView protein in InterPro
IPR002051 Haem_Oase
IPR016053 Haem_Oase-like
IPR016084 Haem_Oase-like_multi-hlx
IPR018207 Haem_oxygenase_CS
PANTHERiPTHR10720 PTHR10720, 1 hit
PfamiView protein in Pfam
PF01126 Heme_oxygenase, 1 hit
PIRSFiPIRSF000343 Haem_Oase, 1 hit
PRINTSiPR00088 HAEMOXYGNASE
SUPFAMiSSF48613 SSF48613, 1 hit
PROSITEiView protein in PROSITE
PS00593 HEME_OXYGENASE, 1 hit

Sequencei

Sequence statusi: Complete.

P09601-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MERPQPDSMP QDLSEALKEA TKEVHTQAEN AEFMRNFQKG QVTRDGFKLV
60 70 80 90 100
MASLYHIYVA LEEEIERNKE SPVFAPVYFP EELHRKAALE QDLAFWYGPR
110 120 130 140 150
WQEVIPYTPA MQRYVKRLHE VGRTEPELLV AHAYTRYLGD LSGGQVLKKI
160 170 180 190 200
AQKALDLPSS GEGLAFFTFP NIASATKFKQ LYRSRMNSLE MTPAVRQRVI
210 220 230 240 250
EEAKTAFLLN IQLFEELQEL LTHDTKDQSP SRAPGLRQRA SNKVQDSAPV
260 270 280
ETPRGKPPLN TRSQAPLLRW VLTLSFLVAT VAVGLYAM
Length:288
Mass (Da):32,819
Last modified:July 1, 1989 - v1
Checksum:iAB47827778694064
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0191657D → H1 PublicationCorresponds to variant dbSNP:rs2071747Ensembl.1
Natural variantiVAR_022156106P → L. Corresponds to variant dbSNP:rs9282702Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06985 mRNA Translation: CAA30045.1
CR456505 mRNA Translation: CAG30391.1
AY460337 Genomic DNA Translation: AAR23262.1
Z82244 Genomic DNA No translation available.
M23041 mRNA Translation: AAA50403.1
X14782 Genomic DNA Translation: CAA32886.1
CCDSiCCDS13914.1
PIRiS00325
RefSeqiNP_002124.1, NM_002133.2
UniGeneiHs.517581
Hs.727017

Genome annotation databases

EnsembliENST00000216117; ENSP00000216117; ENSG00000100292
GeneIDi3162
KEGGihsa:3162

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHMOX1_HUMAN
AccessioniPrimary (citable) accession number: P09601
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: April 25, 2018
This is version 190 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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