Hemopexin
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| Location (UCSC) | Chr 11: 6.43 – 6.44 Mb | Chr 7: 105.24 – 105.25 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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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 the hemopexin family of proteins.[8] Hemopexin is the plasma protein with the highest binding affinity for heme.[9]
Hemoglobin itself circulating alone in the blood plasma (called free hemoglobin, as opposed to the hemoglobin situated in and circulating with the red blood cell.) will soon be oxidized into
Hemopexin's arrival and subsequent binding to the free heme not only prevent heme's pro-oxidant and pro-inflammatory effects but also promotes free heme's detoxification.[10]
Hemopexin is different from haptoglobin, the latter always binds to free hemoglobin.[11][10] (See Haptoglobin § Differentiation with hemopexin)
Cloning, expression, and discovery
Takahashi et al. (1985) determined that human plasma hemopexin consists of a single polypeptide chain of 439 amino acids residues with six intrachain
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
Mapping of hemopexin gene
Cai and Law (1986) prepared a
Differential transcriptional pattern of hemopexin gene
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.[15]
Function
Hemopexin binds heme with the highest affinity of any known protein.[9] 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, hemopexin releases its bound ligand for internalisation upon interacting with CD91.[16] Hemopexin preserves the body's iron.[17] Hemopexin -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.[18] Hemopexin can downregulate the angiotensin II Type 1 receptor (AT1-R) in vitro.[19]
Clinical significance
The predominant source of circulating hemopexin is the liver with a plasma concentration of 1–2 mg/ml.
HPX is produced in the brain.
Circulating hemopexin can modulate in patients and in mice anthracycline-induced cardiotoxicity (e.g. heart failure).[25]
Relation to haptoglobin
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 hemopexin concentration occurs in situations when haptoglobin (Hp) concentrations are low or depleted as a result of severe or prolonged hemolysis.[20] Both haptoglobin and hemopexin are acute-phase proteins, the synthesis of which are induced during infection and after inflammatory states to minimize tissue injury and facilitate tissue repair.[9] Hp and hemopexin prevent heme toxicity by binding themselves to heme prior to monocyte or macrophage's arrivals and ensuing clearances,[9] which may explain their effects on outcome in several diseases, and underlies the rationale for exogenous haptoglobin and hemopexin as therapeutic proteins in hemolytic or hemorrhagic conditions.[26] Hemopexin is the major vehicle for the transportation of heme in the plasma.[9]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000110169 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030895 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: HPX hemopexin".
- S2CID 11271490.
- PMID 2989777.
- PMID 8590012.
- ^ PMID 12042069.
- ^ a b c "Intravascular hemolysis". eClinpath. Retrieved 2019-05-08.
- ^ "Bilirubin and hemolytic anemia". eClinpath. Retrieved 2019-05-08.
- ^ Online Mendelian Inheritance in Man (OMIM): Orthosatic intolerance - 604715
- PMID 3855550.
- ^ Online Mendelian Inheritance in Man (OMIM): Hemopexin - 142290
- PMID 3026994.
- PMID 15947085.
- PMID 12042069.
- PMID 19433579.
- S2CID 23501030.
- ^ PMID 5687939.
- ISBN 978-1-4051-3649-5.
- ^ PMID 26339767.
- ^ S2CID 11532383.
- PMID 26831741.
- PMID 36563141.
- PMID 25389409.
Further reading
- Piccard H, Van den Steen PE, Opdenakker G (April 2007). "Hemopexin domains as multifunctional liganding modules in matrix metalloproteinases and other proteins". Journal of Leukocyte Biology. 81 (4): 870–92. S2CID 16210789.
- Morgan WT, Muller-Eberhard U, Lamola AA (January 1978). "Interaction of rabbit hemopexin with bilirubin". Biochimica et Biophysica Acta (BBA) - Protein Structure. 532 (1): 57–64. PMID 620056.
- Liu HM, Atack JR, Rapoport SI (1989). "Immunohistochemical localization of intracellular plasma proteins in the human central nervous system". Acta Neuropathologica. 78 (1): 16–21. S2CID 24415663.
- Smith A, Tatum FM, Muster P, Burch MK, Morgan WT (April 1988). "Importance of ligand-induced conformational changes in hemopexin for receptor-mediated heme transport". The Journal of Biological Chemistry. 263 (11): 5224–9. PMID 2833500.
- 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. S2CID 11271490.
- 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. PMID 2989777.
- Taketani S, Kohno H, Naitoh Y, Tokunaga R (June 1987). "Isolation of the hemopexin receptor from human placenta". The Journal of Biological Chemistry. 262 (18): 8668–71. PMID 3036819.
- Law ML, Cai GY, Hartz JA, Jones C, Kao FT (July 1988). "The hemopexin gene maps to the same location as the beta-globin gene cluster on human chromosome 11". Genomics. 3 (1): 48–52. PMID 3220477.
- Morgan WT, Alam J, Deaciuc V, Muster P, Tatum FM, Smith A (June 1988). "Interaction of hemopexin with Sn-protoporphyrin IX, an inhibitor of heme oxygenase. Role for hemopexin in hepatic uptake of Sn-protoporphyrin IX and induction of mRNA for heme oxygenase". The Journal of Biological Chemistry. 263 (17): 8226–31. PMID 3372522.
- 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. PMID 3855550.
- Takahashi N, Takahashi Y, Putnam FW (April 1984). "Structure of human hemopexin: O-glycosyl and N-glycosyl sites and unusual clustering of tryptophan residues". Proceedings of the National Academy of Sciences of the United States of America. 81 (7): 2021–5. PMID 6371807.
- Frantíková V, Borvák J, Kluh I, Morávek L (December 1984). "Amino acid sequence of the N-terminal region of human hemopexin". FEBS Letters. 178 (2): 213–6. S2CID 45009902.
- Smith A, Alam J, Escriba PV, Morgan WT (April 1993). "Regulation of heme oxygenase and metallothionein gene expression by the heme analogs, cobalt-, and tin-protoporphyrin". The Journal of Biological Chemistry. 268 (10): 7365–71. PMID 8463269.
- Morris CM, Candy JM, Edwardson JA, Bloxham CA, Smith A (January 1993). "Evidence for the localization of haemopexin immunoreactivity in neurones in the human brain". Neuroscience Letters. 149 (2): 141–4. S2CID 24743139.
- Hrkal Z, Kuzelová K, Muller-Eberhard U, Stern R (March 1996). "Hyaluronan-binding properties of human serum hemopexin". FEBS Letters. 383 (1–2): 72–4. S2CID 21283343.
- Hunt RC, Hunt DM, Gaur N, Smith A (July 1996). "Hemopexin in the human retina: protection of the retina against heme-mediated toxicity". Journal of Cellular Physiology. 168 (1): 71–80. S2CID 10105569.
- Miller YI, Smith A, Morgan WT, Shaklai N (October 1996). "Role of hemopexin in protection of low-density lipoprotein against hemoglobin-induced oxidation". Biochemistry. 35 (40): 13112–7. PMID 8855948.
- Grinberg LN, O'Brien PJ, Hrkal Z (July 1999). "The effects of heme-binding proteins on the peroxidative and catalatic activities of hemin". Free Radical Biology & Medicine. 27 (1–2): 214–9. PMID 10443938.
- Nakajima S, Moriyama T, Hayashi H, Sakata I, Nakae Y, Takemura T (February 2000). "Hemopexin as a carrier protein of tumor-localizing Ga-metalloporphyrin-ATN-2". Cancer Letters. 149 (1–2): 221–6. PMID 10737728.
- Shipulina N, Smith A, Morgan WT (April 2000). "Heme binding by hemopexin: evidence for multiple modes of binding and functional implications". Journal of Protein Chemistry. 19 (3): 239–48. S2CID 45510572.
External links
- Hemopexin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)