Haptoglobin

NameHaptoglobin
Synonyms
  • Zonulin
Gene NameHP
OrganismHuman
Amino acid sequence
>lcl|BSEQ0008802|Haptoglobin
MSALGAVIALLLWGQLFAVDSGNDVTDIADDGCPKPPEIAHGYVEHSVRYQCKNYYKLRT
EGDGVYTLNDKKQWINKAVGDKLPECEADDGCPKPPEIAHGYVEHSVRYQCKNYYKLRTE
GDGVYTLNNEKQWINKAVGDKLPECEAVCGKPKNPANPVQRILGGHLDAKGSFPWQAKMV
SHHNLTTGATLINEQWLLTTAKNLFLNHSENATAKDIAPTLTLYVGKKQLVEIEKVVLHP
NYSQVDIGLIKLKQKVSVNERVMPICLPSKDYAEVGRVGYVSGWGRNANFKFTDHLKYVM
LPVADQDQCIRHYEGSTVPEKKTPKSPVGVQPILNEHTFCAGMSKYQEDTCYGDAGSAFA
VHDLEEDTWYATGILSFDKSCAVAEYGVYVKVTSIQDWVQKTIAEN
Number of residues406
Molecular Weight45205.065
Theoretical pINot Available
GO Classification
Functions
  • antioxidant activity
  • hemoglobin binding
  • serine-type endopeptidase activity
Processes
  • acute-phase response
  • defense response to bacterium
  • positive regulation of cell death
  • acute inflammatory response
  • response to organic substance
  • immune system process
  • proteolysis
  • negative regulation of oxidoreductase activity
  • negative regulation of hydrogen peroxide catabolic process
  • defense response
  • receptor-mediated endocytosis
  • response to hydrogen peroxide
Components
  • endocytic vesicle lumen
  • haptoglobin-hemoglobin complex
  • extracellular region
  • extracellular space
  • extracellular exosome
  • blood microparticle
General FunctionSerine-type endopeptidase activity
Specific FunctionAs a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an Antimicrobial; Antioxidant, has antibacterial activity and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidely cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway.Uncleaved haptoglogin, also known as zonulin, plays a role in intestinal permeability, allowing intercellular tight junction disassembly, and controlling the equilibrium between tolerance and immunity to non-self antigens.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP00738
UniProtKB Entry NameHPT_HUMAN
Cellular LocationSecreted
Gene sequence
>lcl|BSEQ0019669|Haptoglobin (HP)
ATGAGTGCCCTGGGAGCTGTCATTGCCCTCCTGCTCTGGGGACAGCTTTTTGCAGTGGAC
TCAGGCAATGATGTCACGGATATCGCAGATGACGGCTGCCCGAAGCCCCCCGAGATTGCA
CATGGCTATGTGGAGCACTCGGTTCGCTACCAGTGTAAGAACTACTACAAACTGCGCACA
GAAGGAGATGGAGTGTACACCTTAAACAATGAGAAGCAGTGGATAAATAAGGCTGTTGGA
GATAAACTTCCTGAATGTGAAGCAGTATGTGGGAAGCCCAAGAATCCGGCAAACCCAGTG
CAGCGGATCCTGGGTGGACACCTGGATGCCAAAGGCAGCTTTCCCTGGCAGGCTAAGATG
GTTTCCCACCATAATCTCACCACAGGTGCCACGCTGATCAATGAACAATGGCTGCTGACC
ACGGCTAAAAATCTCTTCCTGAACCATTCAGAAAATGCAACAGCGAAAGACATTGCCCCT
ACTTTAACACTCTATGTGGGGAAAAAGCAGCTTGTAGAGATTGAGAAGGTTGTTCTACAC
CCTAACTACTCCCAGGTAGATATTGGGCTCATCAAACTCAAACAGAAGGTGTCTGTTAAT
GAGAGAGTGATGCCCATCTGCCTACCTTCAAAGGATTATGCAGAAGTAGGGCGTGTGGGT
TATGTTTCTGGCTGGGGGCGAAATGCCAATTTTAAATTTACTGACCATCTGAAGTATGTC
ATGCTGCCTGTGGCTGACCAAGACCAATGCATAAGGCATTATGAAGGCAGCACAGTCCCC
GAAAAGAAGACACCGAAGAGCCCTGTAGGGGTGCAGCCCATACTGAATGAACACACCTTC
TGTGCTGGCATGTCTAAGTACCAAGAAGACACCTGCTATGGCGATGCGGGCAGTGCCTTT
GCCGTTCACGACCTGGAGGAGGACACCTGGTATGCGACTGGGATCTTAAGCTTTGATAAG
AGCTGTGCTGTGGCTGAGTATGGTGTGTATGTGAAGGTGACTTCCATCCAGGACTGGGTT
CAGAAGACCATAGCTGAGAACTAA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:5141
Chromosome Location16
LocusNot Available
References
  1. vander Straten A, Herzog A, Jacobs P, Cabezon T, Bollen A: Molecular cloning of human haptoglobin cDNA: evidence for a single mRNA coding for alpha 2 and beta chains. EMBO J. 1983;2(6):1003-7. 6688992
  2. Yang F, Brune JL, Baldwin WD, Barnett DR, Bowman BH: Identification and characterization of human haptoglobin cDNA. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5875-9. 6310599
  3. van der Straten A, Herzog A, Cabezon T, Bollen A: Characterization of human haptoglobin cDNAs coding for alpha 2FS beta and alpha 1S beta variants. FEBS Lett. 1984 Mar 12;168(1):103-7. 6546723
  4. Brune JL, Yang F, Barnett DR, Bowman BH: Evolution of haptoglobin: comparison of complementary DNA encoding Hp alpha 1S and Hp alpha 2FS. Nucleic Acids Res. 1984 Jun 11;12(11):4531-8. 6330675
  5. Bensi G, Raugei G, Klefenz H, Cortese R: Structure and expression of the human haptoglobin locus. EMBO J. 1985 Jan;4(1):119-26. 4018023
  6. Maeda N: Nucleotide sequence of the haptoglobin and haptoglobin-related gene pair. The haptoglobin-related gene contains a retrovirus-like element. J Biol Chem. 1985 Jun 10;260(11):6698-709. 2987228
  7. Erickson LM, Kim HS, Maeda N: Junctions between genes in the haptoglobin gene cluster of primates. Genomics. 1992 Dec;14(4):948-58. 1478675
  8. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  9. Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M, Couronne O, Aerts A, Bajorek E, Black S, Blumer H, Branscomb E, Brown NC, Bruno WJ, Buckingham JM, Callen DF, Campbell CS, Campbell ML, Campbell EW, Caoile C, Challacombe JF, Chasteen LA, Chertkov O, Chi HC, Christensen M, Clark LM, Cohn JD, Denys M, Detter JC, Dickson M, Dimitrijevic-Bussod M, Escobar J, Fawcett JJ, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Goodwin LA, Grady DL, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Hildebrand CE, Huang W, Israni S, Jett J, Jewett PB, Kadner K, Kimball H, Kobayashi A, Krawczyk MC, Leyba T, Longmire JL, Lopez F, Lou Y, Lowry S, Ludeman T, Manohar CF, Mark GA, McMurray KL, Meincke LJ, Morgan J, Moyzis RK, Mundt MO, Munk AC, Nandkeshwar RD, Pitluck S, Pollard M, Predki P, Parson-Quintana B, Ramirez L, Rash S, Retterer J, Ricke DO, Robinson DL, Rodriguez A, Salamov A, Saunders EH, Scott D, Shough T, Stallings RL, Stalvey M, Sutherland RD, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Torney DC, Tran-Gyamfi M, Tsai M, Ulanovsky LE, Ustaszewska A, Vo N, White PS, Williams AL, Wills PL, Wu JR, Wu K, Yang J, Dejong P, Bruce D, Doggett NA, Deaven L, Schmutz J, Grimwood J, Richardson P, Rokhsar DS, Eichler EE, Gilna P, Lucas SM, Myers RM, Rubin EM, Pennacchio LA: The sequence and analysis of duplication-rich human chromosome 16. Nature. 2004 Dec 23;432(7020):988-94. 15616553
  10. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  11. van der Straten A, Falque JC, Loriau R, Bollen A, Cabezon T: Expression of cloned human haptoglobin and alpha 1-antitrypsin complementary DNAs in Saccharomyces cerevisiae. DNA. 1986 Apr;5(2):129-36. 3519135
  12. Raugei G, Bensi G, Colantuoni V, Romano V, Santoro C, Costanzo F, Cortese R: Sequence of human haptoglobin cDNA: evidence that the alpha and beta subunits are coded by the same mRNA. Nucleic Acids Res. 1983 Sep 10;11(17):5811-9. 6310515
  13. Loftus BJ, Kim UJ, Sneddon VP, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD: Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q. Genomics. 1999 Sep 15;60(3):295-308. 10493829
  14. Maeda N, Yang F, Barnett DR, Bowman BH, Smithies O: Duplication within the haptoglobin Hp2 gene. Nature. 1984 May 10-16;309(5964):131-5. 6325933
  15. Kurosky A, Barnett DR, Lee TH, Touchstone B, Hay RE, Arnott MS, Bowman BH, Fitch WM: Covalent structure of human haptoglobin: a serine protease homolog. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3388-92. 6997877
  16. Kliffen M, de Jong PT, Luider TM: Protein analysis of human maculae in relation to age-related maculopathy. Lab Invest. 1995 Aug;73(2):267-72. 7637327
  17. Malchy B, Dixon GH: Studies on the interchain disulfides of human haptoglobins. Can J Biochem. 1973 Mar;51(3):249-64. 4573324
  18. Zhang H, Li XJ, Martin DB, Aebersold R: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol. 2003 Jun;21(6):660-6. Epub 2003 May 18. 12754519
  19. Bunkenborg J, Pilch BJ, Podtelejnikov AV, Wisniewski JR: Screening for N-glycosylated proteins by liquid chromatography mass spectrometry. Proteomics. 2004 Feb;4(2):454-65. 14760718
  20. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. 16335952
  21. Ramachandran P, Boontheung P, Xie Y, Sondej M, Wong DT, Loo JA: Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry. J Proteome Res. 2006 Jun;5(6):1493-503. 16740002
  22. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. 19159218
  23. Jia W, Lu Z, Fu Y, Wang HP, Wang LH, Chi H, Yuan ZF, Zheng ZB, Song LN, Han HH, Liang YM, Wang JL, Cai Y, Zhang YK, Deng YL, Ying WT, He SM, Qian XH: A strategy for precise and large scale identification of core fucosylated glycoproteins. Mol Cell Proteomics. 2009 May;8(5):913-23. doi: 10.1074/mcp.M800504-MCP200. Epub 2009 Jan 12. 19139490
  24. Nilsson J, Ruetschi U, Halim A, Hesse C, Carlsohn E, Brinkmalm G, Larson G: Enrichment of glycopeptides for glycan structure and attachment site identification. Nat Methods. 2009 Nov;6(11):809-11. doi: 10.1038/nmeth.1392. Epub 2009 Oct 18. 19838169
  25. Tripathi A, Lammers KM, Goldblum S, Shea-Donohue T, Netzel-Arnett S, Buzza MS, Antalis TM, Vogel SN, Zhao A, Yang S, Arrietta MC, Meddings JB, Fasano A: Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16799-804. doi: 10.1073/pnas.0906773106. Epub 2009 Sep 15. 19805376
  26. Levy AP, Asleh R, Blum S, Levy NS, Miller-Lotan R, Kalet-Litman S, Anbinder Y, Lache O, Nakhoul FM, Asaf R, Farbstein D, Pollak M, Soloveichik YZ, Strauss M, Alshiek J, Livshits A, Schwartz A, Awad H, Jad K, Goldenstein H: Haptoglobin: basic and clinical aspects. Antioxid Redox Signal. 2010 Feb;12(2):293-304. doi: 10.1089/ars.2009.2793. 19659435
  27. 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
  28. Fasano A: Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011 Jan;91(1):151-75. doi: 10.1152/physrev.00003.2008. 21248165
  29. Rosenow A, Noben JP, Jocken J, Kallendrusch S, Fischer-Posovszky P, Mariman EC, Renes J: Resveratrol-induced changes of the human adipocyte secretion profile. J Proteome Res. 2012 Sep 7;11(9):4733-43. doi: 10.1021/pr300539b. Epub 2012 Aug 27. 22905912
  30. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  31. Teye K, Quaye IK, Koda Y, Soejima M, Pang H, Tsuneoka M, Amoah AG, Adjei A, Kimura H: A novel I247T missense mutation in the haptoglobin 2 beta-chain decreases the expression of the protein and is associated with ahaptoglobinemia. Hum Genet. 2004 Apr;114(5):499-502. Epub 2004 Mar 4. 14999562