Heme oxygenase 1

NameHeme oxygenase 1
Synonyms
  • 1.14.14.18
  • HO
  • HO-1
  • HO1
Gene NameHMOX1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0021270|Heme oxygenase 1
MERPQPDSMPQDLSEALKEATKEVHTQAENAEFMRNFQKGQVTRDGFKLVMASLYHIYVA
LEEEIERNKESPVFAPVYFPEELHRKAALEQDLAFWYGPRWQEVIPYTPAMQRYVKRLHE
VGRTEPELLVAHAYTRYLGDLSGGQVLKKIAQKALDLPSSGEGLAFFTFPNIASATKFKQ
LYRSRMNSLEMTPAVRQRVIEEAKTAFLLNIQLFEELQELLTHDTKDQSPSRAPGLRQRA
SNKVQDSAPVETPRGKPPLNTRSQAPLLRWVLTLSFLVATVAVGLYAM
Number of residues288
Molecular Weight32818.345
Theoretical pI8.68
GO Classification
Functions
  • heme oxygenase (decyclizing) activity
  • metal ion binding
  • enzyme binding
  • heme binding
  • protein homodimerization activity
  • signal transducer activity
  • phospholipase D activity
Processes
  • response to nicotine
  • transmembrane transport
  • cellular response to arsenic-containing substance
  • cell death
  • negative regulation of leukocyte migration
  • response to hydrogen peroxide
  • negative regulation of mast cell degranulation
  • response to oxidative stress
  • porphyrin-containing compound metabolic process
  • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
  • negative regulation of sequence-specific DNA binding transcription factor activity
  • intracellular signal transduction
  • cellular response to cadmium ion
  • positive regulation of vasodilation
  • response to estrogen
  • erythrocyte homeostasis
  • smooth muscle hyperplasia
  • negative regulation of DNA binding
  • heme oxidation
  • negative regulation of smooth muscle cell proliferation
  • angiogenesis
  • cellular response to nutrient
  • regulation of transcription from RNA polymerase II promoter in response to iron
  • small GTPase mediated signal transduction
  • cellular iron ion homeostasis
  • low-density lipoprotein particle clearance
  • wound healing involved in inflammatory response
  • heme catabolic process
  • positive regulation of smooth muscle cell proliferation
  • negative regulation of mast cell cytokine production
  • positive regulation of I-kappaB kinase/NF-kappaB signaling
  • cellular response to hypoxia
  • regulation of transcription from RNA polymerase II promoter in response to oxidative stress
  • small molecule metabolic process
  • negative regulation of muscle cell apoptotic process
  • regulation of angiogenesis
  • positive regulation of angiogenesis
  • cellular response to heat
  • excretion
  • regulation of sequence-specific DNA binding transcription factor activity
  • regulation of blood pressure
  • positive regulation of chemokine biosynthetic process
  • negative regulation of neuron apoptotic process
  • endothelial cell proliferation
  • iron ion homeostasis
  • protein homooligomerization
  • intrinsic apoptotic signaling pathway in response to DNA damage
Components
  • endoplasmic reticulum
  • extracellular space
  • endoplasmic reticulum membrane
  • caveola
  • cytosol
  • membrane
  • nucleolus
  • nucleus
  • perinuclear region of cytoplasm
General FunctionSignal transducer activity
Specific FunctionHeme 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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID35173
UniProtKB IDP09601
UniProtKB Entry NameHMOX1_HUMAN
Cellular LocationMicrosome
Gene sequence
>lcl|BSEQ0021271|Heme oxygenase 1 (HMOX1)
ATGGAGCGTCCGCAACCCGACAGCATGCCCCAGGATTTGTCAGAGGCCCTGAAGGAGGCC
ACCAAGGAGGTGCACACCCAGGCAGAGAATGCTGAGTTCATGAGGAACTTTCAGAAGGGC
CAGGTGACCCGAGACGGCTTCAAGCTGGTGATGGCCTCCCTGTACCACATCTATGTGGCC
CTGGAGGAGGAGATTGAGCGCAACAAGGAGAGCCCAGTCTTCGCCCCTGTCTACTTCCCA
GAAGAGCTGCACCGCAAGGCTGCCCTGGAGCAGGACCTGGCCTTCTGGTACGGGCCCCGC
TGGCAGGAGGTCATCCCCTACACACCAGCCATGCAGCGCTATGTGAAGCGGCTCCACGAG
GTGGGGCGCACAGAGCCCGAGCTGCTGGTGGCCCACGCCTACACCCGCTACCTGGGTGAC
CTGTCTGGGGGCCAGGTGCTCAAAAAGATTGCCCAGAAAGCCCTGGACCTGCCCAGCTCT
GGCGAGGGCCTGGCCTTCTTCACCTTCCCCAACATTGCCAGTGCCACCAAGTTCAAGCAG
CTCTACCGCTCCCGCATGAACTCCCTGGAGATGACTCCCGCAGTCAGGCAGAGGGTGATA
GAAGAGGCCAAGACTGCGTTCCTGCTCAACATCCAGCTCTTTGAGGAGTTGCAGGAGCTG
CTGACCCATGACACCAAGGACCAGAGCCCCTCACGGGCACCAGGGCTTCGCCAGCGGGCC
AGCAACAAAGTGCAAGATTCTGCCCCCGTGGAGACTCCCAGAGGGAAGCCCCCACTCAAC
ACCCGCTCCCAGGCTCCGCTTCTCCGATGGGTCCTTACACTCAGCTTTCTGGTGGCGACA
GTTGCTGTAGGGCTTTATGCCATGTGA
GenBank Gene IDX06985
GeneCard IDNot Available
GenAtlas IDHMOX1
HGNC IDHGNC:5013
Chromosome Location22
Locus22q12|22q13.1
References
  1. Yoshida T, Biro P, Cohen T, Muller RM, Shibahara S: Human heme oxygenase cDNA and induction of its mRNA by hemin. Eur J Biochem. 1988 Feb 1;171(3):457-61. 3345742
  2. Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I: A genome annotation-driven approach to cloning the human ORFeome. Genome Biol. 2004;5(10):R84. Epub 2004 Sep 30. 15461802
  3. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. 10591208
  4. Keyse SM, Tyrrell RM: Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc Natl Acad Sci U S A. 1989 Jan;86(1):99-103. 2911585
  5. Shibahara S, Sato M, Muller RM, Yoshida T: Structural organization of the human heme oxygenase gene and the function of its promoter. Eur J Biochem. 1989 Feb 15;179(3):557-63. 2537723
  6. Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T, Ohta K, Kasahara Y, Koizumi S: Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest. 1999 Jan;103(1):129-35. 9884342
  7. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. 17081983
  8. Gozzelino R, Jeney V, Soares MP: Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol. 2010;50:323-54. doi: 10.1146/annurev.pharmtox.010909.105600. 20055707
  9. Datta D, Banerjee P, Gasser M, Waaga-Gasser AM, Pal S: CXCR3-B can mediate growth-inhibitory signals in human renal cancer cells by down-regulating the expression of heme oxygenase-1. J Biol Chem. 2010 Nov 19;285(47):36842-8. doi: 10.1074/jbc.M110.170324. Epub 2010 Sep 20. 20855888
  10. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  11. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  12. Gottlieb Y, Truman M, Cohen LA, Leichtmann-Bardoogo Y, Meyron-Holtz EG: Endoplasmic reticulum anchored heme-oxygenase 1 faces the cytosol. Haematologica. 2012 Oct;97(10):1489-93. doi: 10.3324/haematol.2012.063651. Epub 2012 Mar 14. 22419571
  13. Schuller DJ, Wilks A, Ortiz de Montellano PR, Poulos TL: Crystal structure of human heme oxygenase-1. Nat Struct Biol. 1999 Sep;6(9):860-7. 10467099
  14. Lad L, Wang J, Li H, Friedman J, Bhaskar B, Ortiz de Montellano PR, Poulos TL: Crystal structures of the ferric, ferrous, and ferrous-NO forms of the Asp140Ala mutant of human heme oxygenase-1: catalytic implications. J Mol Biol. 2003 Jul 11;330(3):527-38. 12842469