Haptoglobin

HP
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	4X0L, 4WJG, 5HU6
Identifikatori
Aliasi	HP
Vanjski ID-jevi	OMIM: 140100 MGI: 96211 HomoloGene: 121756 GeneCards: HP
Lokacija gena (čovjek)
Hrom.	Hromosom 16 (čovjek)
Kraj	72,061,055 bp
Lokacija gena (miš)
Hrom.	Hromosom 8 (miš)
Kraj	110,305,804 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• antioxidant activity; • GO:0001948, GO:0016582 vezivanje za proteine; • hemoglobin binding; • serine-type endopeptidase activity;
Ćelijska komponenta	• extracellular region; • endocytic vesicle lumen; • Egzosom; • blood microparticle; • haptoglobin-hemoglobin complex; • Vanćelijsko; • specific granule lumen; • tertiary granule lumen;
Biološki proces	• cellular oxidant detoxification; • defense response; • positive regulation of cell death; • acute-phase response; • receptor-mediated endocytosis; • defense response to bacterium; • response to hydrogen peroxide; • GO:2001216 negative regulation of oxidoreductase activity; • negative regulation of hydrogen peroxide catabolic process; • immune system process; • neutrophil degranulation; • acute inflammatory response; • Proteoliza; • response to organic substance;
	Izvori:Amigo / QuickGO
Ortolozi
	3240
	15439
	ENSG00000257017
	ENSMUSG00000031722
	P00738
	Q61646
	NM_001126102; NM_005143; NM_001318138
	NM_017370; NM_001329965
	NP_001119574; NP_001305067; NP_005134
	NP_001316894; NP_059066
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Haptoglobin (skr. Hp) jest protein koji je kod ljudi kodiran genom HP sa hromosoma 16.^[5]^[6] U krvnoj plazmi, haptoglobin se veže sa visokim afinitetom na slobodni hemoglobin,^[7] oslobađa se iz eritrocita i na taj način inhibira njegovu štetnu oksidacijsku aktivnost. U poređenju sa Hp, hemopeksin se vezuje za slobodni hem.^[8] Kompleks haptoglobin-hemoglobin tada biva uklonjen putem retikuloendotelnog sistema (uglavnom slezine).

U kliničkim uslovima, analiza haptoglobina se koristi za skrining i praćenje unutarvaskularne hemolitse anemije. U unutarvaskularnoj hemolizi, slobodni hemoglobin će se osloboditi u cirkulaciju i stoga će haptoglobin vezati hemoglobin. Ovo uzrokuje pad nivoa haptoglobina.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 406 aminokiselina, a molekulska težina Da.^[9]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MSALGAVIAL	LLWGQLFAVD	SGNDVTDIAD	DGCPKPPEIA	HGYVEHSVRY
QCKNYYKLRT	EGDGVYTLND	KKQWINKAVG	DKLPECEADD	GCPKPPEIAH
GYVEHSVRYQ	CKNYYKLRTE	GDGVYTLNNE	KQWINKAVGD	KLPECEAVCG
KPKNPANPVQ	RILGGHLDAK	GSFPWQAKMV	SHHNLTTGAT	LINEQWLLTT
AKNLFLNHSE	NATAKDIAPT	LTLYVGKKQL	VEIEKVVLHP	NYSQVDIGLI
KLKQKVSVNE	RVMPICLPSK	DYAEVGRVGY	VSGWGRNANF	KFTDHLKYVM
LPVADQDQCI	RHYEGSTVPE	KKTPKSPVGV	QPILNEHTFC	AGMSKYQEDT
CYGDAGSAFA	VHDLEEDTWY	ATGILSFDKS	CAVAEYGVYV	KVTSIQDWVQ
KTIAEN

Funkcija

Hemoglobin koji oštećena crvena krvna zrnca ispuštaju u krvnu plazmu ima štetne učinke. „HP“ gen kodira preproprotein koji se obrađuje kako bi se dobili i alfa i beta lanci, koji se zatim kombinuju kao tetramer da bi se proizveo haptoglobin. Haptoglobin funkcionira tako da veže slobodnu plazmu hemoglobina, što omogućava degradacijskim enzimima da dobiju pristup hemoglobinu, dok istovremeno sprječava gubitak željeza kroz bubrege i štiti ih od oštećenja hemoglobinom.^[9]

Cilj ćelijskog receptora za Hp je receptor za čišćenje monocita/makrofaga, CD163.^[7] Nakon vezivanja Hb-Hp za CD163, ćelijska internalizacija kompleksa dovodi do metabolizma globina i hema, što je praćeno adaptivnim promjenama u putevima metabolizama antioksidansa i željeza i polarizacijom makrofagnog fenotipa.^[7]

Sinteza

Haptoglobin proizvode uglavnom ćelije hepatocita, ali i druga tkiva kao što su koža, pluća i bubrezi. Pored toga, gen za haptoglobin eksprimiran je u mišjem i ljudskom masnom tkivu.^[10]

Pokazalo se da se haptoglobin eksprimira i u masnom tkivu goveda.^[11]

Struktura

Haptoglobin, u svom najjednostavnijem obliku, sastoji se od dva alfa i dva beta lanca, povezanih disulfidnim mostovima. Lanci potiču od uobičajenog proteinskog prekursora, koji se proteolitski cijepa tokom sinteza proteina.

Hp postoji u dva alelna oblika u ljudskoj populaciji, takozvani Hp1 i Hp2, pri čemu je potonji nastao zbog djelimične duplikacije Hp1 gena. Stoga se kod ljudi nalaze tri genotipa Hp: Hp1-1, Hp2-1 i Hp2-2. Pokazalo se da Hp različitih genotipova veže hemoglobin sa različitim afinitetima, pri čemu je Hp2-2 najslabije vezivo.

Kod ostalih vrsta

HP je pronađen kod svih do sada proučavanih sisara, nekih ptica, npr. kormoran i noj, ali i, u jednostavnijem obliku, košljoribe, npr. zebrica. Hp je odsutan barem kod nekih vodozemaca (Xenopus) i neognatnih ptica (kokoši i guske).

Klinički značaj

Mutacije ovog gena ili njegovih regulatornih regija uzrokuju haptoglobinemiju ili hipohaptoglobinemiju. Ovaj gen je takođe povezan sa dijabetesno mnefropatijom,^[12] učestalost koronarne arterijske bolesti kod dijabetesa tipa 1,^[13] Crohnove bolesti,^[14] ponašanje upalne bolesti, primarni sklerozirajući holangitis, sklonost idiopatskoj Parkinsonovoj bolesti,^[15] i smanjena incidencija malarije preko Plasmodium falciparum.^[16]

Pošto će retikuloendotelni sistem ukloniti kompleks haptoglobin-hemoglobin iz tijela,^[8] nivo haptoglobina će biti smanjen u slučaju vaskularne hemolize ili „teške“ vanvaskularne hemolize. U procesu vezivanja za slobodni hemoglobin, haptoglobin sekvestrira željezo unutar hemoglobina, sprječavajući bakterije koje ga koriste da imaju koristi od hemolize. Pretpostavlja se da je zbog toga haptoglobin evoluirao u protein akutne faze. HP ima zaštitni učinak na hemolitski bubreg.^[17]^[18]

Različiti fenotipovi haptoglobina razlikuju se po svojim antioksidansnim svojstvima, čišćenju i imunomodulacijskim svojstvima. Ovaj aspekt haptoglobina može dobiti na značaju u imunosupresiranim stanjima (kao što je jetrena ciroza), a različiti fenotipovi mogu rezultirati različitim nivoima osjetljivosti na bakterijske infekcije.^[19]

Neke studije povezuju određene fenotipove haptoglobina sa rizikom od razvoja shizofrenije.

Također pogledajte

Reference

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000257017 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000031722 - Ensembl, maj 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.
^ Dobryszycka W (septembar 1997). "Biological functions of haptoglobin--new pieces to an old puzzle". European Journal of Clinical Chemistry and Clinical Biochemistry. 35 (9): 647–654. PMID 9352226.
^ Wassell J (2000). "Haptoglobin: function and polymorphism". Clinical Laboratory. 46 (11–12): 547–552. PMID 11109501.
^ ^a ^b ^c Schaer DJ, Vinchi F, Ingoglia G, Tolosano E, Buehler PW (28. 10. 2014). "Haptoglobin, hemopexin, and related defense pathways-basic science, clinical perspectives, and drug development". Frontiers in Physiology. Frontiers Media SA. 5: 415. doi:10.3389/fphys.2014.00415. PMC 4211382. PMID 25389409.
^ ^a ^b "Intravascular hemolysis". eClinpath. Pristupljeno 8. 5. 2019.
^ ^a ^b "Entrez Gene: HP".
^ Trayhurn P, Wood IS (septembar 2004). "Adipokines: inflammation and the pleiotropic role of white adipose tissue". The British Journal of Nutrition. 92 (3): 347–355. doi:10.1079/BJN20041213. PMID 15469638.
^ Saremi B, Al-Dawood A, Winand S, Müller U, Pappritz J, von Soosten D, et al. (maj 2012). "Bovine haptoglobin as an adipokine: serum concentrations and tissue expression in dairy cows receiving a conjugated linoleic acids supplement throughout lactation". Veterinary Immunology and Immunopathology. 146 (3–4): 201–211. doi:10.1016/j.vetimm.2012.03.011. PMID 22498004.
^ Asleh R, Levy AP (2005). "In vivo and in vitro studies establishing haptoglobin as a major susceptibility gene for diabetic vascular disease". Vascular Health and Risk Management. 1 (1): 19–28. doi:10.2147/vhrm.1.1.19.58930. PMC 1993923. PMID 17319095.
^ Sadrzadeh SM, Bozorgmehr J (juni 2004). "Haptoglobin phenotypes in health and disorders". American Journal of Clinical Pathology. 121 (Suppl): S97-104. doi:10.1309/8GLX5798Y5XHQ0VW. PMID 15298155.
^ Papp M, Lakatos PL, Palatka K, Foldi I, Udvardy M, Harsfalvi J, et al. (maj 2007). "Haptoglobin polymorphisms are associated with Crohn's disease, disease behavior, and extraintestinal manifestations in Hungarian patients". Digestive Diseases and Sciences. 52 (5): 1279–1284. doi:10.1007/s10620-006-9615-1. PMID 17357835. S2CID 35999438.
^ Costa-Mallen P, Checkoway H, Zabeti A, Edenfield MJ, Swanson PD, Longstreth WT, et al. (mart 2008). "The functional polymorphism of the hemoglobin-binding protein haptoglobin influences susceptibility to idiopathic Parkinson's disease". American Journal of Medical Genetics. 147B (2): 216–222. doi:10.1002/ajmg.b.30593. PMID 17918239. S2CID 21568460. Zanemaren tekst "Part B, Neuropsychiatric Genetics" (pomoć)
^ Prentice AM, Ghattas H, Doherty C, Cox SE (decembar 2007). "Iron metabolism and malaria". Food and Nutrition Bulletin. 28 (4 Suppl): S524–S539. doi:10.1177/15648265070284S406. PMID 18297891.
^ Pintera J (1968). "The protective influence of haptoglobin on hemoglobinuric kidney. I. Bioch- emical and macroscopic observations". Folia Haematologica. 90 (1): 82–91. PMID 4176393.
^ Miederer SE, Hotz J (decembar 1969). "[Pathogenesis of kidney hemolysis]". Bruns' Beiträge für klinische Chirurgie (jezik: njemački). 217 (7): 661–665. PMID 5404273.
^ Vitalis Z, Altorjay I, Tornai I, Palatka K, Kacska S, Palyu E, et al. (april 2011). "Phenotypic polymorphism of haptoglobin: a novel risk factor for the development of infection in liver cirrhosis". Human Immunology. 72 (4): 348–354. doi:10.1016/j.humimm.2011.01.008. PMID 21262313.

Dopunska literatura

Graversen JH, Madsen M, Moestrup SK (april 2002). "CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma". The International Journal of Biochemistry & Cell Biology. 34 (4): 309–314. doi:10.1016/S1357-2725(01)00144-3. PMID 11854028.
Madsen M, Graversen JH, Moestrup SK (2002). "Haptoglobin and CD163: captor and receptor gating hemoglobin to macrophage lysosomes". Redox Report. 6 (6): 386–388. doi:10.1179/135100001101536490. PMID 11865982.
Erickson LM, Kim HS, Maeda N (decembar 1992). "Junctions between genes in the haptoglobin gene cluster of primates". Genomics. 14 (4): 948–958. doi:10.1016/S0888-7543(05)80116-8. PMID 1478675.
Maeda N (juni 1985). "Nucleotide sequence of the haptoglobin and haptoglobin-related gene pair. The haptoglobin-related gene contains a retrovirus-like element". The Journal of Biological Chemistry. 260 (11): 6698–6709. doi:10.1016/S0021-9258(18)88836-6. PMID 2987228.
Simmers RN, Stupans I, Sutherland GR (1986). "Localization of the human haptoglobin genes distal to the fragile site at 16q22 using in situ hybridization". Cytogenetics and Cell Genetics. 41 (1): 38–41. doi:10.1159/000132193. PMID 3455911.
van der Straten A, Falque JC, Loriau R, Bollen A, Cabezón T (april 1986). "Expression of cloned human haptoglobin and alpha 1-antitrypsin complementary DNAs in Saccharomyces cerevisiae". DNA. 5 (2): 129–136. doi:10.1089/dna.1986.5.129. PMID 3519135.
Bensi G, Raugei G, Klefenz H, Cortese R (januar 1985). "Structure and expression of the human haptoglobin locus". The EMBO Journal. 4 (1): 119–126. doi:10.1002/j.1460-2075.1985.tb02325.x. PMC 554159. PMID 4018023.
Malchy B, Dixon GH (mart 1973). "Studies on the interchain disulfides of human haptoglobins". Canadian Journal of Biochemistry. 51 (3): 249–264. doi:10.1139/o73-032. PMID 4573324.
Raugei G, Bensi G, Colantuoni V, Romano V, Santoro C, Costanzo F, Cortese R (septembar 1983). "Sequence of human haptoglobin cDNA: evidence that the alpha and beta subunits are coded by the same mRNA". Nucleic Acids Research. 11 (17): 5811–5819. doi:10.1093/nar/11.17.5811. PMC 326319. PMID 6310515.
Yang F, Brune JL, Baldwin WD, Barnett DR, Bowman BH (oktobar 1983). "Identification and characterization of human haptoglobin cDNA". Proceedings of the National Academy of Sciences of the United States of America. 80 (19): 5875–5879. Bibcode:1983PNAS...80.5875Y. doi:10.1073/pnas.80.19.5875. PMC 390178. PMID 6310599.
Maeda N, Yang F, Barnett DR, Bowman BH, Smithies O (1984). "Duplication within the haptoglobin Hp2 gene". Nature. 309 (5964): 131–135. Bibcode:1984Natur.309..131M. doi:10.1038/309131a0. PMID 6325933. S2CID 4368535.
Brune JL, Yang F, Barnett DR, Bowman BH (juni 1984). "Evolution of haptoglobin: comparison of complementary DNA encoding Hp alpha 1S and Hp alpha 2FS". Nucleic Acids Research. 12 (11): 4531–4538. doi:10.1093/nar/12.11.4531. PMC 318856. PMID 6330675.
van der Straten A, Herzog A, Cabezón T, Bollen A (mart 1984). "Characterization of human haptoglobin cDNAs coding for alpha 2FS beta and alpha 1S beta variants". FEBS Letters. 168 (1): 103–107. doi:10.1016/0014-5793(84)80215-X. PMID 6546723. S2CID 85082741.
vander Straten A, Herzog A, Jacobs P, Cabezón T, Bollen A (1984). "Molecular cloning of human haptoglobin cDNA: evidence for a single mRNA coding for alpha 2 and beta chains". The EMBO Journal. 2 (6): 1003–1007. doi:10.1002/j.1460-2075.1983.tb01534.x. PMC 555221. PMID 6688992.
Kurosky A, Barnett DR, Lee TH, Touchstone B, Hay RE, Arnott MS, et al. (juni 1980). "Covalent structure of human haptoglobin: a serine protease homolog". Proceedings of the National Academy of Sciences of the United States of America. 77 (6): 3388–3392. Bibcode:1980PNAS...77.3388K. doi:10.1073/pnas.77.6.3388. PMC 349621. PMID 6997877.
Eaton JW, Brandt P, Mahoney JR, Lee JT (februar 1982). "Haptoglobin: a natural bacteriostat". Science. 215 (4533): 691–693. Bibcode:1982Sci...215..691E. doi:10.1126/science.7036344. PMID 7036344.
Kazim AL, Atassi MZ (januar 1980). "Haemoglobin binding with haptoglobin. Unequivocal demonstration that the beta-chains of human haemoglobin bind to haptoglobin". The Biochemical Journal. 185 (1): 285–287. doi:10.1042/bj1850285. PMC 1161299. PMID 7378053.
Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, et al. (septembar 1996). "Generation and analysis of 280,000 human expressed sequence tags". Genome Research. 6 (9): 807–828. doi:10.1101/gr.6.9.807. PMID 8889549.
Tabak S, Lev A, Valansi C, Aker O, Shalitin C (novembar 1996). "Transcriptionally active haptoglobin-related (Hpr) gene in hepatoma G2 and leukemia molt-4 cells". DNA and Cell Biology. 15 (11): 1001–1007. doi:10.1089/dna.1996.15.1001. PMID 8945641.
Koda Y, Soejima M, Yoshioka N, Kimura H (februar 1998). "The haptoglobin-gene deletion responsible for anhaptoglobinemia". American Journal of Human Genetics. 62 (2): 245–252. doi:10.1086/301701. PMC 1376878. PMID 9463309.

Vanjski linkovi

Haptoglobins na US National Library of Medicine Medical Subject Headings (MeSH)
P00738

Šablon:Alfa globulini Šablon:Mukoproteini

Šablon:Mijeloidni krvni testovi

	Portal Biologija
	Portal Medicina

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000257017 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000031722 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9352226-5] Dobryszycka W (septembar 1997). "Biological functions of haptoglobin--new pieces to an old puzzle". European Journal of Clinical Chemistry and Clinical Biochemistry. 35 (9): 647–654. PMID 9352226.

[pmid11109501-6] Wassell J (2000). "Haptoglobin: function and polymorphism". Clinical Laboratory. 46 (11–12): 547–552. PMID 11109501.

[Schaer_Vinchi_Ingoglia_Tolosano_p.-7] Schaer DJ, Vinchi F, Ingoglia G, Tolosano E, Buehler PW (28. 10. 2014). "Haptoglobin, hemopexin, and related defense pathways-basic science, clinical perspectives, and drug development". Frontiers in Physiology. Frontiers Media SA. 5: 415. doi:10.3389/fphys.2014.00415. PMC 4211382. PMID 25389409.

[eClinpath-8] "Intravascular hemolysis". eClinpath. Pristupljeno 8. 5. 2019.

[entrez-9] "Entrez Gene: HP".

[pmid15469638-10] Trayhurn P, Wood IS (septembar 2004). "Adipokines: inflammation and the pleiotropic role of white adipose tissue". The British Journal of Nutrition. 92 (3): 347–355. doi:10.1079/BJN20041213. PMID 15469638.

[pmid22498004-11] Saremi B, Al-Dawood A, Winand S, Müller U, Pappritz J, von Soosten D, et al. (maj 2012). "Bovine haptoglobin as an adipokine: serum concentrations and tissue expression in dairy cows receiving a conjugated linoleic acids supplement throughout lactation". Veterinary Immunology and Immunopathology. 146 (3–4): 201–211. doi:10.1016/j.vetimm.2012.03.011. PMID 22498004.

[pmid17319095-12] Asleh R, Levy AP (2005). "In vivo and in vitro studies establishing haptoglobin as a major susceptibility gene for diabetic vascular disease". Vascular Health and Risk Management. 1 (1): 19–28. doi:10.2147/vhrm.1.1.19.58930. PMC 1993923. PMID 17319095.

[pmid15298155-13] Sadrzadeh SM, Bozorgmehr J (juni 2004). "Haptoglobin phenotypes in health and disorders". American Journal of Clinical Pathology. 121 (Suppl): S97-104. doi:10.1309/8GLX5798Y5XHQ0VW. PMID 15298155.

[pmid17357835-14] Papp M, Lakatos PL, Palatka K, Foldi I, Udvardy M, Harsfalvi J, et al. (maj 2007). "Haptoglobin polymorphisms are associated with Crohn's disease, disease behavior, and extraintestinal manifestations in Hungarian patients". Digestive Diseases and Sciences. 52 (5): 1279–1284. doi:10.1007/s10620-006-9615-1. PMID 17357835. S2CID 35999438.

[pmid17918239-15] Costa-Mallen P, Checkoway H, Zabeti A, Edenfield MJ, Swanson PD, Longstreth WT, et al. (mart 2008). "The functional polymorphism of the hemoglobin-binding protein haptoglobin influences susceptibility to idiopathic Parkinson's disease". American Journal of Medical Genetics. 147B (2): 216–222. doi:10.1002/ajmg.b.30593. PMID 17918239. S2CID 21568460. Zanemaren tekst "Part B, Neuropsychiatric Genetics" (pomoć)

[pmid18297891-16] Prentice AM, Ghattas H, Doherty C, Cox SE (decembar 2007). "Iron metabolism and malaria". Food and Nutrition Bulletin. 28 (4 Suppl): S524–S539. doi:10.1177/15648265070284S406. PMID 18297891.

[pmid4176393-17] Pintera J (1968). "The protective influence of haptoglobin on hemoglobinuric kidney. I. Bioch- emical and macroscopic observations". Folia Haematologica. 90 (1): 82–91. PMID 4176393.

[pmid5404273-18] Miederer SE, Hotz J (decembar 1969). "[Pathogenesis of kidney hemolysis]". Bruns' Beiträge für klinische Chirurgie (jezik: njemački). 217 (7): 661–665. PMID 5404273.

[19] Vitalis Z, Altorjay I, Tornai I, Palatka K, Kacska S, Palyu E, et al. (april 2011). "Phenotypic polymorphism of haptoglobin: a novel risk factor for the development of infection in liver cirrhosis". Human Immunology. 72 (4): 348–354. doi:10.1016/j.humimm.2011.01.008. PMID 21262313.

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p r u Proteini akutne faze
Amiloid	SAP SAA
Ostali pozitivni	Alfa 1-antihimotripsin Alfa 1-antitripsin Alfa-2-Makroglobulin C-reaktivni protein Ceruloplazmin C3 Feritin Fibrin Haptoglobin Hemopeksin Orosomukoid
Negativni	Serumski albumin Transferin