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Aliases HPX, HX, hemopexin
External IDs OMIM: 142290 MGI: 105112 HomoloGene: 511 GeneCards: HPX
Gene location (Human)
Chromosome 11 (human)
Chr. Chromosome 11 (human)[1]
Chromosome 11 (human)
Genomic location for HPX
Genomic location for HPX
Band 11p15.4 Start 6,431,049 bp[1]
End 6,442,617 bp[1]
RNA expression pattern
PBB GE HPX 39763 at fs.png

PBB GE HPX 210013 at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 11: 6.43 – 6.44 Mb Chr 11: 105.59 – 105.6 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse

Hemopexin (or haemopexin; Hpx; Hx), also known as beta-1B-glycoprotein, is a glycoprotein that in humans is encoded by the HPX gene[5][6][7] and belongs to hemopexin family of proteins.[8] Heme released during degradation of hemoglobin is bound by albumin and rapidly transferred to Hx, the plasma protein with the highest binding affinity for heme. Hx prevents heme's pro-oxidant and pro-inflammatory effects and it also promotes its detoxification. The Hx-heme complex is cleared by the receptor CD91.

Cloning, expression, and discovery[edit]

Takahashi et al. (1985) determined that human plasma Hx consists of a single polypeptide chain of 439 amino acids residues with six intrachain disulfide bridges and has a molecular mass of approximately 63 kD. The amino-terminal threonine residue is blocked by an O-linked galactosamine oligosaccharide, and the protein has five glucosamine oligosaccharides N-linked to the acceptor sequence Asn-X-Ser/Thr. The 18 tryptophan residues are arranged in four clusters, and 12 of the tryptophans are conserved in homologous positions. Computer-assisted analysis of the internal homology in amino acid sequence suggested duplication of an ancestral gene thus indicating that Hx consists of two similar halves.[9]

Altruda et al. (1988) demonstrated that the HPX gene spans approximately 12 kb and is interrupted by 9 exons. The demonstration shows direct correspondence between exons and the 10 repeating units in the protein. The introns were not placed randomly; they fell in the center of the region of amino acid sequence homology in strikingly similar locations in 6 of the 10 units and in a symmetric position in each half of the coding sequence. From these observations, Altruda et al. (1988) concluded that the gene evolved through intron-mediated duplications of a primordial sequence to a 5-exon cluster.[10]

Mapping of hemopexin gene[edit]

Cai and Law (1986) prepared a cDNA clone for Hx, by Southern blot analysis of human/hamster hybrids containing different combinations of human chromosomes, assigned the HPX gene to human chromosome 11. Law et al. (1988) assigned the HPX gene to 11p15.5-p15.4, the same location as that of the beta-globin gene complex by in situ hybridization.[11]

Differential transcriptional pattern of hemopexin gene[edit]

In 1986, the expression of the human HPX gene in different human tissues and cell lines was carried out by using a specific cDNA probe. From the results obtained it was concluded that this gene was expressed in the liver and it was below the level of detection in other tissues or cell lines examined. By S1 mapping, the transcription initiation site in hepatic cells was located 28 base pairs upstream from the AUG initiation codon of the hemopexin gene.[12]


Hx binds heme with the highest affinity of any known protein. Its main function is scavenging the heme released or lost by the turnover of heme proteins such as hemoglobin and thus protects the body from the oxidative damage that free heme can cause. In addition, Hx releases its bound ligand for internalisation upon interacting with CD91[13]. Hx preserves the body's iron.[14] Hx-dependent uptake of extracellular heme can lead to the deactivation of Bach1 repression which leads to the transcriptional activation of antioxidant heme oxygenase-1 gene. Hemoglobin, haptoglobin (Hp) and Hx associate with high density lipoprotein (HDL) and influence the inflammatory properties of HDL.[15] Hx can downregulate the angiotensin II Type 1 receptor (AT1-R) in vitro.[16]

Clinical significance[edit]

The predominant source of circulating Hx is the liver with a plasma concentration of 1–2 mg/ml.[17] Serum Hx level reflects how much heme is present in the blood. Therefore, a low Hx level indicates that there has been significant degradation of heme containing compounds. A low Hx level is one of the diagnostic features of an intravascular hemolytic anemia.[18] Hx has been implicated in cardiovascular disease, septic shock, cerebral ischemic injury, and experimental autoimmune encephalomyelitis.[19][20] The circulating level of Hx is associated with prognosis in patients with septic shock.[19]

HPX is produced in the brain[21]. Deletion of the HPX gene can aggravate brain injury followed by stroma-free hemoglobin-induced intracerebral haemorrhage.[22] High Hx level in the cerebrospinal fluid is associated with poor outcome after subarachnoid hemorrhage.[21]

Relation to haptoglobin[edit]

In past there have been reports showing that in patients with sickle cell disease, spherocytosis, autoimmune hemolytic anemia, erythropoietic protoporphyria and pyruvate kinase deficiency, a decline in Hx concentration occurs in situations when Hp concentrations are low or depleted as a result of severe or prolonged hemolysis.[17] Both Hp and Hx are acute-phase proteins, induced during infection and inflammatory states to minimize tissue injury and facilitate tissue repair. Hp and Hx prevent heme toxicity prior to monocyte or macrophage clearance, which may explain their effect on outcome in several diseases, and underlies the rationale for exogenous Hp and Hx as therapeutic proteins in hemolytic or hemorrhagic conditions.[23]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000110169 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030895 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ "Entrez Gene: HPX hemopexin". 
  6. ^ Altruda F, Poli V, Restagno G, Silengo L (1988). "Structure of the human hemopexin gene and evidence for intron-mediated evolution". Journal of Molecular Evolution. 27 (2): 102–8. doi:10.1007/BF02138368. PMID 2842511. 
  7. ^ Altruda F, Poli V, Restagno G, Argos P, Cortese R, Silengo L (June 1985). "The primary structure of human hemopexin deduced from cDNA sequence: evidence for internal, repeating homology". Nucleic Acids Research. 13 (11): 3841–59. doi:10.1093/nar/13.11.3841. PMC 341281Freely accessible. PMID 2989777. 
  8. ^ Bode W (June 1995). "A helping hand for collagenases: the haemopexin-like domain". Structure. 3 (6): 527–30. doi:10.1016/s0969-2126(01)00185-x. PMID 8590012. 
  9. ^ Online Mendelian Inheritance in Man (OMIM) Orthosatic intolerance -604715
  10. ^ Takahashi N, Takahashi Y, Putnam FW (January 1985). "Complete amino acid sequence of human hemopexin, the heme-binding protein of serum". Proceedings of the National Academy of Sciences of the United States of America. 82 (1): 73–7. doi:10.1073/pnas.82.1.73. PMC 396973Freely accessible. PMID 3855550. 
  11. ^ Online Mendelian Inheritance in Man (OMIM) Hemopexin -142290
  12. ^ Poli V, Altruda F, Silengo L (1986). "Differential transcriptional pattern of the hemopexin gene". The Italian Journal of Biochemistry. 35 (5): 355–60. PMID 3026994. 
  13. ^ Hvidberg V, Maniecki MB, Jacobsen C, Højrup P, Møller HJ, Moestrup SK (October 2005). "Identification of the receptor scavenging hemopexin-heme complexes". Blood. 106 (7): 2572–9. doi:10.1182/blood-2005-03-1185. PMID 15947085. 
  14. ^ Tolosano E, Altruda F (April 2002). "Hemopexin: structure, function, and regulation". DNA and Cell Biology. 21 (4): 297–306. doi:10.1089/104454902753759717. PMID 12042069. 
  15. ^ Watanabe J, Grijalva V, Hama S, Barbour K, Berger FG, Navab M, Fogelman AM, Reddy ST (July 2009). "Hemoglobin and its scavenger protein haptoglobin associate with apoA-1-containing particles and influence the inflammatory properties and function of high density lipoprotein". The Journal of Biological Chemistry. 284 (27): 18292–301. doi:10.1074/jbc.m109.017202. PMID 19433579. 
  16. ^ Krikken JA, Lely AT, Bakker SJ, Borghuis T, Faas MM, van Goor H, Navis G, Bakker WW (March 2013). "Hemopexin activity is associated with angiotensin II responsiveness in humans". Journal of Hypertension. 31 (3): 537–41; discussion 542. doi:10.1097/HJH.0b013e32835c1727. PMID 23254305. 
  17. ^ a b Muller-Eberhard U, Javid J, Liem HH, Hanstein A, Hanna M (November 1968). "Plasma concentrations of hemopexin, haptoglobin and heme in patients with various hemolytic diseases". Blood. 32 (5): 811–5. PMID 5687939. 
  18. ^ Hoffbrand A, Moss P, Pettit J (2006). Essential Haematology (5th ed.). Oxford: Blackwell Publishing. p. 60. ISBN 978-1-4051-3649-5. 
  19. ^ a b Mehta NU, Reddy ST (October 2015). "Role of hemoglobin/heme scavenger protein hemopexin in atherosclerosis and inflammatory diseases". Current Opinion in Lipidology. 26 (5): 384–7. doi:10.1097/MOL.0000000000000208. PMC 4826275Freely accessible. PMID 26339767. 
  20. ^ "Role of hemoglobin/heme scavenger protein hemopexin in atherosclerosis and inflammatory diseases". PMID 26339767. 
  21. ^ a b Garland P, Durnford AJ, Okemefuna AI, Dunbar J, Nicoll JA, Galea J, Boche D, Bulters DO, Galea I (March 2016). "Heme-Hemopexin Scavenging Is Active in the Brain and Associates With Outcome After Subarachnoid Hemorrhage". Stroke. 47 (3): 872–6. doi:10.1161/strokeaha.115.011956. PMID 26768209. 
  22. ^ Ma B, Day JP, Phillips H, Slootsky B, Tolosano E, Doré S (February 2016). "Deletion of the hemopexin or heme oxygenase-2 gene aggravates brain injury following stroma-free hemoglobin-induced intracerebral hemorrhage". Journal of Neuroinflammation. 13: 26. doi:10.1186/s12974-016-0490-1. PMC 4736638Freely accessible. PMID 26831741. 
  23. ^ Schaer DJ, Vinchi F, Ingoglia G, Tolosano E, Buehler PW (2014). "Haptoglobin, hemopexin, and related defense pathways-basic science, clinical perspectives, and drug development". Frontiers in Physiology. 5: 415. doi:10.3389/fphys.2014.00415. PMC 4211382Freely accessible. PMID 25389409. 

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