HPT_HUMAN
ID HPT_HUMAN Reviewed; 406 AA.
AC P00738; B0AZL5; P00737; Q0VAC4; Q0VAC5; Q2PP15; Q3B7J0; Q6LBY9; Q9UC67;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 225.
DE RecName: Full=Haptoglobin;
DE AltName: Full=Zonulin;
DE Contains:
DE RecName: Full=Haptoglobin alpha chain;
DE Contains:
DE RecName: Full=Haptoglobin beta chain;
DE Flags: Precursor;
GN Name=HP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6688992;
RA van der Straten A., Herzog A., Jacobs P., Cabezon T., Bollen A.;
RT "Molecular cloning of human haptoglobin cDNA: evidence for a single mRNA
RT coding for alpha 2 and beta chains.";
RL EMBO J. 2:1003-1007(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6310599; DOI=10.1073/pnas.80.19.5875;
RA Yang F., Brune J.L., Baldwin W.D., Barnett D.R., Bowman B.H.;
RT "Identification and characterization of human haptoglobin cDNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:5875-5879(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS 29-ALA--GLU-87 DEL; ASP-129 AND
RP LYS-130.
RC TISSUE=Liver;
RX PubMed=6546723; DOI=10.1016/0014-5793(84)80215-x;
RA van der Straten A., Herzog A., Cabezon T., Bollen A.;
RT "Characterization of human haptoglobin cDNAs coding for alpha 2FS beta and
RT alpha 1S beta variants.";
RL FEBS Lett. 168:103-107(1984).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT 29-ALA--GLU-87 DEL.
RX PubMed=6330675; DOI=10.1093/nar/12.11.4531;
RA Brune J.L., Yang F., Barnett D.R., Bowman B.H.;
RT "Evolution of haptoglobin: comparison of complementary DNA encoding Hp
RT alpha 1S and Hp alpha 2FS.";
RL Nucleic Acids Res. 12:4531-4538(1984).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-129.
RX PubMed=4018023; DOI=10.1002/j.1460-2075.1985.tb02325.x;
RA Bensi G., Raugei G., Klefenz H., Cortese R.;
RT "Structure and expression of the human haptoglobin locus.";
RL EMBO J. 4:119-126(1985).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2987228; DOI=10.1016/s0021-9258(18)88836-6;
RA Maeda N.;
RT "Nucleotide sequence of the haptoglobin and haptoglobin-related gene pair.
RT The haptoglobin-related gene contains a retrovirus-like element.";
RL J. Biol. Chem. 260:6698-6709(1985).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1478675; DOI=10.1016/s0888-7543(05)80116-8;
RA Erickson L.M., Kim H.S., Maeda N.;
RT "Junctions between genes in the haptoglobin gene cluster of primates.";
RL Genomics 14:948-958(1992).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELES HP*1F AND HP*1S).
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-19.
RX PubMed=3519135; DOI=10.1089/dna.1986.5.129;
RA van der Straten A., Falque J.-C., Loriau R., Bollen A., Cabezon T.;
RT "Expression of cloned human haptoglobin and alpha 1-antitrypsin
RT complementary DNAs in Saccharomyces cerevisiae.";
RL DNA 5:129-136(1986).
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-406.
RX PubMed=6310515; DOI=10.1093/nar/11.17.5811;
RA Raugei G., Bensi G., Colantuoni V., Romano V., Santoro C., Costanzo F.,
RA Cortese R.;
RT "Sequence of human haptoglobin cDNA: evidence that the alpha and beta
RT subunits are coded by the same mRNA.";
RL Nucleic Acids Res. 11:5811-5819(1983).
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 3-406.
RX PubMed=10493829; DOI=10.1006/geno.1999.5927;
RA Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J.,
RA Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X.,
RA Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C.,
RA Adams M.D.;
RT "Genome duplications and other features in 12 Mb of DNA sequence from human
RT chromosome 16p and 16q.";
RL Genomics 60:295-308(1999).
RN [15]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 3-375.
RX PubMed=6325933; DOI=10.1038/309131a0;
RA Maeda N., Yang F., Barnett D.R., Bowman B.H., Smithies O.;
RT "Duplication within the haptoglobin Hp2 gene.";
RL Nature 309:131-135(1984).
RN [16]
RP PROTEIN SEQUENCE OF 19-28; 88-160 AND 162-406, AND DISULFIDE BONDS.
RX PubMed=6997877; DOI=10.1073/pnas.77.6.3388;
RA Kurosky A., Barnett D.R., Lee T.-H., Touchstone B., Hay R.E., Arnott M.S.,
RA Bowman B.H., Fitch W.M.;
RT "Covalent structure of human haptoglobin: a serine protease homolog.";
RL Proc. Natl. Acad. Sci. U.S.A. 77:3388-3392(1980).
RN [17]
RP PROTEIN SEQUENCE OF 162-176.
RC TISSUE=Eye;
RX PubMed=7637327;
RA Kliffen M., de Jong P.T.V.M., Luider T.M.;
RT "Protein analysis of human maculae in relation to age-related
RT maculopathy.";
RL Lab. Invest. 73:267-272(1995).
RN [18]
RP DISULFIDE BONDS.
RX PubMed=4573324; DOI=10.1139/o73-032;
RA Malchy B., Dixon G.H.;
RT "Studies on the interchain disulfides of human haptoglobins.";
RL Can. J. Biochem. 51:249-264(1973).
RN [19]
RP GLYCOSYLATION AT ASN-207 AND ASN-241.
RC TISSUE=Plasma, and Serum;
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [20]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-184; ASN-207; ASN-211 AND
RP ASN-241.
RC TISSUE=Plasma;
RX PubMed=14760718; DOI=10.1002/pmic.200300556;
RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT "Screening for N-glycosylated proteins by liquid chromatography mass
RT spectrometry.";
RL Proteomics 4:454-465(2004).
RN [21]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-184; ASN-207; ASN-211 AND
RP ASN-241.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [22]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-207 AND ASN-211.
RC TISSUE=Saliva;
RX PubMed=16740002; DOI=10.1021/pr050492k;
RA Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A.;
RT "Identification of N-linked glycoproteins in human saliva by glycoprotein
RT capture and mass spectrometry.";
RL J. Proteome Res. 5:1493-1503(2006).
RN [23]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-184; ASN-207; ASN-211 AND
RP ASN-241.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [24]
RP GLYCOSYLATION AT ASN-184 AND ASN-241.
RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [25]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-241, AND STRUCTURE OF
RP CARBOHYDRATE.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=19838169; DOI=10.1038/nmeth.1392;
RA Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G.,
RA Larson G.;
RT "Enrichment of glycopeptides for glycan structure and attachment site
RT identification.";
RL Nat. Methods 6:809-811(2009).
RN [26]
RP IDENTIFICATION AS ZONULIN.
RX PubMed=19805376; DOI=10.1073/pnas.0906773106;
RA Tripathi A., Lammers K.M., Goldblum S., Shea-Donohue T., Netzel-Arnett S.,
RA Buzza M.S., Antalis T.M., Vogel S.N., Zhao A., Yang S., Arrietta M.C.,
RA Meddings J.B., Fasano A.;
RT "Identification of human zonulin, a physiological modulator of tight
RT junctions, as prehaptoglobin-2.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:16799-16804(2009).
RN [27]
RP REVIEW.
RX PubMed=19659435; DOI=10.1089/ars.2009.2793;
RA Levy A.P., Asleh R., Blum S., Levy N.S., Miller-Lotan R., Kalet-Litman S.,
RA Anbinder Y., Lache O., Nakhoul F.M., Asaf R., Farbstein D., Pollak M.,
RA Soloveichik Y.Z., Strauss M., Alshiek J., Livshits A., Schwartz A.,
RA Awad H., Jad K., Goldenstein H.;
RT "Haptoglobin: basic and clinical aspects.";
RL Antioxid. Redox Signal. 12:293-304(2010).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [29]
RP FUNCTION OF ZONULIN.
RX PubMed=21248165; DOI=10.1152/physrev.00003.2008;
RA Fasano A.;
RT "Zonulin and its regulation of intestinal barrier function: the biological
RT door to inflammation, autoimmunity, and cancer.";
RL Physiol. Rev. 91:151-175(2011).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22905912; DOI=10.1021/pr300539b;
RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P.,
RA Mariman E.C., Renes J.;
RT "Resveratrol-induced changes of the human adipocyte secretion profile.";
RL J. Proteome Res. 11:4733-4743(2012).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [32]
RP INTERACTION WITH ERGIC3.
RX PubMed=31142615; DOI=10.1074/jbc.ra119.007435;
RA Yoo W., Cho E.B., Kim S., Yoon J.B.;
RT "The E3 ubiquitin ligase MARCH2 regulates ERGIC3-dependent trafficking of
RT secretory proteins.";
RL J. Biol. Chem. 294:10900-10912(2019).
RN [33]
RP VARIANT AHP THR-247, AND CHARACTERIZATION OF VARIANT AHP THR-247.
RX PubMed=14999562; DOI=10.1007/s00439-004-1098-6;
RA Teye K., Quaye I.K., Koda Y., Soejima M., Pang H., Tsuneoka M., Amoah A.G.,
RA Adjei A., Kimura H.;
RT "A novel I247T missense mutation in the haptoglobin 2 beta-chain decreases
RT the expression of the protein and is associated with ahaptoglobinemia.";
RL Hum. Genet. 114:499-502(2004).
CC -!- FUNCTION: As a result of hemolysis, hemoglobin is found to accumulate
CC in the kidney and is secreted in the urine. Haptoglobin captures, and
CC combines with free plasma hemoglobin to allow hepatic recycling of heme
CC iron and to prevent kidney damage. Haptoglobin also acts as an
CC antioxidant, has antibacterial activity, and plays a role in modulating
CC many aspects of the acute phase response. Hemoglobin/haptoglobin
CC complexes are rapidly cleared by the macrophage CD163 scavenger
CC receptor expressed on the surface of liver Kupfer cells through an
CC endocytic lysosomal degradation pathway. {ECO:0000269|PubMed:21248165}.
CC -!- FUNCTION: The uncleaved form of allele alpha-2 (2-2), known as zonulin,
CC plays a role in intestinal permeability, allowing intercellular tight
CC junction disassembly, and controlling the equilibrium between tolerance
CC and immunity to non-self antigens. {ECO:0000269|PubMed:21248165}.
CC -!- SUBUNIT: Tetramer of two alpha and two beta chains; disulfide-linked
CC (PubMed:6997877, PubMed:4573324). The hemoglobin/haptoglobin complex is
CC composed of a haptoglobin dimer bound to two hemoglobin alpha-beta
CC dimers (By similarity). Interacts with CD163 (By similarity). Interacts
CC with ERGIC3 (PubMed:31142615). {ECO:0000250|UniProtKB:Q8SPS7,
CC ECO:0000269|PubMed:31142615, ECO:0000269|PubMed:4573324,
CC ECO:0000269|PubMed:6997877}.
CC -!- INTERACTION:
CC P00738; P02647: APOA1; NbExp=3; IntAct=EBI-1220767, EBI-701692;
CC P00738; P02649: APOE; NbExp=7; IntAct=EBI-1220767, EBI-1222467;
CC P00738; Q9Y282: ERGIC3; NbExp=2; IntAct=EBI-1220767, EBI-781551;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P00738-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P00738-2; Sequence=VSP_055024;
CC -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
CC -!- POLYMORPHISM: In human populations there are two major allelic forms,
CC alpha-1 (1-1) with 83 residues and alpha-2 (2-2) with 142 residues.
CC These alleles determine 3 possible genotypes, homozygous (1-1 or 2-2)
CC and heterozygous (2-1), and 3 major phenotypes HP*1F/HP*1S and HP*2FS.
CC The two main alleles of HP*1 are called HP*1F (fast) and HP*1S (slow).
CC The alleles exhibit different oligomerization properties. In healthy
CC males, but not in females, the Hp 2-2 phenotype is associated with
CC higher serum iron, decreased antimicrobial and antioxidant capability,
CC and less efficient clearance from the circulation, than Hp 1-1 and 2-1.
CC The sequence displayed in this entry corresponds to allele alpha-2 (2-
CC 2). {ECO:0000269|PubMed:4018023, ECO:0000269|PubMed:6330675,
CC ECO:0000269|PubMed:6546723}.
CC -!- DISEASE: Anhaptoglobinemia (AHP) [MIM:614081]: A condition
CC characterized by the absence of the serum glycoprotein haptoglobin.
CC Serum levels of haptoglobin vary among normal persons: levels are low
CC in the neonatal period and in the elderly, differ by population, and
CC can be influenced by environmental factors, such as infection.
CC Secondary hypohaptoglobinemia can occur as a consequence of hemolysis,
CC during which haptoglobin binds to free hemoglobin. Congenital
CC haptoglobin deficiency is a risk factor for anaphylactic non-hemolytic
CC transfusion reactions. {ECO:0000269|PubMed:14999562}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
CC -!- CAUTION: Although homologous to serine proteases, it has lost all
CC essential catalytic residues and has no enzymatic activity.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Haptoglobin entry;
CC URL="https://en.wikipedia.org/wiki/Haptoglobin";
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DR EMBL; K00422; AAA52687.1; -; mRNA.
DR EMBL; K01763; AAA52684.1; -; mRNA.
DR EMBL; L29394; AAA52685.1; -; mRNA.
DR EMBL; X00637; CAA25267.1; -; mRNA.
DR EMBL; X01793; CAA25926.1; -; Genomic_DNA.
DR EMBL; X01786; CAA25926.1; JOINED; Genomic_DNA.
DR EMBL; X02206; CAA25926.1; JOINED; Genomic_DNA.
DR EMBL; X01789; CAA25926.1; JOINED; Genomic_DNA.
DR EMBL; X01791; CAA25926.1; JOINED; Genomic_DNA.
DR EMBL; M10935; AAA88080.1; -; Genomic_DNA.
DR EMBL; M69197; AAA88078.1; -; Genomic_DNA.
DR EMBL; AK314700; BAF98793.1; -; mRNA.
DR EMBL; DQ314870; ABC40729.1; -; Genomic_DNA.
DR EMBL; AC004682; AAC27432.1; -; Genomic_DNA.
DR EMBL; AC009087; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC107587; AAI07588.1; -; mRNA.
DR EMBL; BC121124; AAI21125.1; -; mRNA.
DR EMBL; BC121125; AAI21126.1; -; mRNA.
DR EMBL; M13192; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; X00606; CAA25248.1; -; Genomic_DNA.
DR CCDS; CCDS45524.1; -. [P00738-1]
DR CCDS; CCDS45525.1; -. [P00738-2]
DR PIR; A92532; HPHU2.
DR PIR; A93521; HPHU1.
DR RefSeq; NP_001119574.1; NM_001126102.2. [P00738-2]
DR RefSeq; NP_001305067.1; NM_001318138.1.
DR RefSeq; NP_005134.1; NM_005143.4. [P00738-1]
DR PDB; 4WJG; X-ray; 3.10 A; 2/C/H/M/R/W=92-406.
DR PDB; 4X0L; X-ray; 2.05 A; C=148-406.
DR PDB; 5HU6; X-ray; 2.90 A; C=148-406.
DR PDB; 6TB2; X-ray; 2.90 A; C=148-406.
DR PDBsum; 4WJG; -.
DR PDBsum; 4X0L; -.
DR PDBsum; 5HU6; -.
DR PDBsum; 6TB2; -.
DR AlphaFoldDB; P00738; -.
DR SMR; P00738; -.
DR BioGRID; 109480; 113.
DR IntAct; P00738; 32.
DR MINT; P00738; -.
DR STRING; 9606.ENSP00000348170; -.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR MEROPS; S01.972; -.
DR CarbonylDB; P00738; -.
DR GlyConnect; 744; 132 N-Linked glycans (4 sites), 1 O-Linked glycan (1 site).
DR GlyGen; P00738; 5 sites, 162 N-linked glycans (4 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P00738; -.
DR PhosphoSitePlus; P00738; -.
DR SwissPalm; P00738; -.
DR BioMuta; HP; -.
DR DMDM; 123508; -.
DR DOSAC-COBS-2DPAGE; P00738; -.
DR SWISS-2DPAGE; P00738; -.
DR CPTAC; CPTAC-671; -.
DR CPTAC; non-CPTAC-1128; -.
DR CPTAC; non-CPTAC-2671; -.
DR EPD; P00738; -.
DR jPOST; P00738; -.
DR MassIVE; P00738; -.
DR MaxQB; P00738; -.
DR PaxDb; P00738; -.
DR PeptideAtlas; P00738; -.
DR PRIDE; P00738; -.
DR ProteomicsDB; 51271; -. [P00738-1]
DR ProteomicsDB; 58792; -.
DR Antibodypedia; 48338; 1221 antibodies from 44 providers.
DR DNASU; 3240; -.
DR Ensembl; ENST00000355906.10; ENSP00000348170.5; ENSG00000257017.10. [P00738-1]
DR Ensembl; ENST00000398131.6; ENSP00000381199.2; ENSG00000257017.10. [P00738-2]
DR Ensembl; ENST00000570083.5; ENSP00000457629.1; ENSG00000257017.10. [P00738-2]
DR GeneID; 3240; -.
DR KEGG; hsa:3240; -.
DR MANE-Select; ENST00000355906.10; ENSP00000348170.5; NM_005143.5; NP_005134.1.
DR UCSC; uc002fbr.5; human. [P00738-1]
DR CTD; 3240; -.
DR DisGeNET; 3240; -.
DR GeneCards; HP; -.
DR HGNC; HGNC:5141; HP.
DR HPA; ENSG00000257017; Tissue enriched (liver).
DR MalaCards; HP; -.
DR MIM; 140100; gene.
DR MIM; 614081; phenotype.
DR neXtProt; NX_P00738; -.
DR OpenTargets; ENSG00000257017; -.
DR PharmGKB; PA29415; -.
DR VEuPathDB; HostDB:ENSG00000257017; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000159903; -.
DR HOGENOM; CLU_006842_0_0_1; -.
DR InParanoid; P00738; -.
DR OMA; EKQWVNK; -.
DR PhylomeDB; P00738; -.
DR TreeFam; TF334326; -.
DR PathwayCommons; P00738; -.
DR Reactome; R-HSA-2168880; Scavenging of heme from plasma.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P00738; -.
DR SIGNOR; P00738; -.
DR BioGRID-ORCS; 3240; 12 hits in 992 CRISPR screens.
DR ChiTaRS; HP; human.
DR GeneWiki; Haptoglobin; -.
DR GenomeRNAi; 3240; -.
DR Pharos; P00738; Tbio.
DR PRO; PR:P00738; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P00738; protein.
DR Bgee; ENSG00000257017; Expressed in pericardium and 165 other tissues.
DR ExpressionAtlas; P00738; baseline and differential.
DR Genevisible; P00738; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0071682; C:endocytic vesicle lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0031838; C:haptoglobin-hemoglobin complex; IDA:BHF-UCL.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR GO; GO:0016209; F:antioxidant activity; IEA:UniProtKB-KW.
DR GO; GO:0030492; F:hemoglobin binding; IDA:BHF-UCL.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0002526; P:acute inflammatory response; IBA:GO_Central.
DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW.
DR GO; GO:0006952; P:defense response; TAS:ProtInc.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:2000296; P:negative regulation of hydrogen peroxide catabolic process; IDA:BHF-UCL.
DR GO; GO:0051354; P:negative regulation of oxidoreductase activity; IDA:BHF-UCL.
DR GO; GO:0010942; P:positive regulation of cell death; IDA:BHF-UCL.
DR GO; GO:0042542; P:response to hydrogen peroxide; IDA:BHF-UCL.
DR GO; GO:0031638; P:zymogen activation; IBA:GO_Central.
DR CDD; cd00033; CCP; 2.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR InterPro; IPR008292; Haptoglobin.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR InterPro; IPR001254; Trypsin_dom.
DR PANTHER; PTHR24255:SF27; PTHR24255:SF27; 2.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57535; SSF57535; 2.
DR PROSITE; PS50923; SUSHI; 2.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acute phase; Alternative splicing; Antibiotic; Antimicrobial;
KW Antioxidant; Direct protein sequencing; Disease variant; Disulfide bond;
KW Glycoprotein; Hemoglobin-binding; Immunity; Reference proteome; Repeat;
KW Secreted; Serine protease homolog; Signal; Sushi.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:6997877"
FT CHAIN 19..406
FT /note="Haptoglobin"
FT /id="PRO_0000028456"
FT CHAIN 19..160
FT /note="Haptoglobin alpha chain"
FT /id="PRO_0000028457"
FT CHAIN 162..406
FT /note="Haptoglobin beta chain"
FT /id="PRO_0000028458"
FT DOMAIN 31..88
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 90..147
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 162..404
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 318..323
FT /note="Interaction with CD163"
FT /evidence="ECO:0000250"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19139490,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:16740002, ECO:0000269|PubMed:19159218"
FT CARBOHYD 211
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:16740002,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:19838169"
FT DISULFID 33
FT /note="Interchain"
FT DISULFID 52..86
FT DISULFID 92
FT /note="Interchain"
FT DISULFID 111..145
FT DISULFID 149..266
FT /note="Interchain (between alpha and beta chains)"
FT DISULFID 309..340
FT DISULFID 351..381
FT VAR_SEQ 38..96
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_055024"
FT VARIANT 29..87
FT /note="Missing (in allele HP*1F and allele HP*1S)"
FT /evidence="ECO:0000269|PubMed:6330675,
FT ECO:0000269|PubMed:6546723"
FT /id="VAR_017112"
FT VARIANT 129
FT /note="N -> D (in allele HP*1F; dbSNP:rs199926732)"
FT /evidence="ECO:0000269|PubMed:4018023,
FT ECO:0000269|PubMed:6546723"
FT /id="VAR_005294"
FT VARIANT 130
FT /note="E -> K (in allele HP*1F; dbSNP:rs200877317)"
FT /evidence="ECO:0000269|PubMed:6546723"
FT /id="VAR_017113"
FT VARIANT 247
FT /note="I -> T (in AHP; causes reduced expression of the
FT protein; dbSNP:rs104894517)"
FT /evidence="ECO:0000269|PubMed:14999562"
FT /id="VAR_066214"
FT VARIANT 397
FT /note="D -> H (in dbSNP:rs189115161)"
FT /id="VAR_017114"
FT CONFLICT 70
FT /note="D -> N (in Ref. 2; AAA52687)"
FT /evidence="ECO:0000305"
FT CONFLICT 130
FT /note="E -> G (in Ref. 11; AAI07588)"
FT /evidence="ECO:0000305"
FT STRAND 101..111
FT /evidence="ECO:0007829|PDB:4WJG"
FT STRAND 115..121
FT /evidence="ECO:0007829|PDB:4WJG"
FT STRAND 123..127
FT /evidence="ECO:0007829|PDB:4WJG"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:4WJG"
FT TURN 136..138
FT /evidence="ECO:0007829|PDB:4WJG"
FT STRAND 144..147
FT /evidence="ECO:0007829|PDB:4WJG"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:4X0L"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:4X0L"
FT STRAND 186..193
FT /evidence="ECO:0007829|PDB:4X0L"
FT STRAND 196..199
FT /evidence="ECO:0007829|PDB:4X0L"
FT HELIX 201..204
FT /evidence="ECO:0007829|PDB:4X0L"
FT TURN 205..207
FT /evidence="ECO:0007829|PDB:4X0L"
FT HELIX 214..217
FT /evidence="ECO:0007829|PDB:4X0L"
FT HELIX 218..220
FT /evidence="ECO:0007829|PDB:4X0L"
FT STRAND 222..225
FT /evidence="ECO:0007829|PDB:4X0L"
FT TURN 226..228
FT /evidence="ECO:0007829|PDB:4X0L"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:4X0L"
FT STRAND 233..238
FT /evidence="ECO:0007829|PDB:4X0L"
FT TURN 240..244
FT /evidence="ECO:0007829|PDB:4X0L"
FT STRAND 248..254
FT /evidence="ECO:0007829|PDB:4X0L"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:5HU6"
FT STRAND 278..283
FT /evidence="ECO:0007829|PDB:4X0L"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:4X0L"
FT STRAND 297..303
FT /evidence="ECO:0007829|PDB:4X0L"
FT HELIX 306..314
FT /evidence="ECO:0007829|PDB:4X0L"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:4X0L"
FT STRAND 327..330
FT /evidence="ECO:0007829|PDB:4WJG"
FT STRAND 338..341
FT /evidence="ECO:0007829|PDB:4X0L"
FT STRAND 345..347
FT /evidence="ECO:0007829|PDB:6TB2"
FT STRAND 358..363
FT /evidence="ECO:0007829|PDB:4X0L"
FT TURN 364..367
FT /evidence="ECO:0007829|PDB:4X0L"
FT STRAND 368..377
FT /evidence="ECO:0007829|PDB:4X0L"
FT TURN 381..383
FT /evidence="ECO:0007829|PDB:4X0L"
FT STRAND 387..391
FT /evidence="ECO:0007829|PDB:4X0L"
FT HELIX 392..394
FT /evidence="ECO:0007829|PDB:4X0L"
FT HELIX 396..405
FT /evidence="ECO:0007829|PDB:4X0L"
SQ SEQUENCE 406 AA; 45205 MW; A98B56B2B1BE891E CRC64;
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
