Major basic protein

Eosinophil major basic protein, often shortened to major basic protein (MBP; also called Proteoglycan 2 (PRG2)) is encoded in humans by the PRG2 gene.^[5]

PRG2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1H8U, 2BRS, 4QXX
Identifiers
Aliases	PRG2, BMPG, MBP, MBP1, proteoglycan 2, bone marrow (natural killer cell activator, eosinophil granule major basic protein), proMBP, proteoglycan 2, pro eosinophil major basic protein
External IDs	OMIM: 605601; MGI: 103294; HomoloGene: 2044; GeneCards: PRG2; OMA:PRG2 - orthologs
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q12.1 Start 57,386,780 bp[1] End 57,390,650 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 D|2 49.45 cM Start 84,810,805 bp[2] End 84,813,976 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in placenta bone marrow bone marrow cells right lobe of liver skin of leg subcutaneous adipose tissue spleen skin of abdomen monocyte blood Top expressed in tibiofemoral joint granulocyte fetal liver hematopoietic progenitor cell bone marrow embryo embryo ankle joint spleen human fetus vestibular membrane of cochlear duct More reference expression data BioGPS More reference expression data
Gene ontology Molecular function heparin binding carbohydrate binding extracellular matrix structural constituent conferring compression resistance Cellular component extracellular region transport vesicle cytoplasmic vesicle extracellular exosome ficolin-1-rich granule lumen collagen-containing extracellular matrix Biological process defense response to bacterium immune system process defense response to nematode negative regulation of interleukin-10 production positive regulation of interleukin-4 production immune response neutrophil degranulation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5553 19074 Ensembl ENSG00000186652 ENSMUSG00000027073 UniProt P13727 Q61878 RefSeq (mRNA) NM_002728 NM_001243245 NM_001302926 NM_001302927 NM_008920 RefSeq (protein) NP_001230174 NP_001289855 NP_001289856 NP_002719 NP_032946 Location (UCSC) Chr 11: 57.39 – 57.39 Mb Chr 2: 84.81 – 84.81 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene is the predominant constituent of the crystalline core of the eosinophil granule. High levels of the proform of this protein are also present in placenta and pregnancy serum, where it exists as a complex with several other proteins including pregnancy-associated plasma protein A (PAPPA), angiotensinogen (AGT), and C3dg. This protein may be involved in antiparasitic defense mechanisms as a cytotoxin and helmintho-toxin, and in immune hypersensitivity reactions. It is directly implicated in epithelial cell damage, exfoliation, and bronchospasm in allergic diseases.^[5]

PRG2 is a 117-residue protein that predominates in eosinophil granules. It is a potent enzyme against helminths and is toxic towards bacteria and mammalian cells in vitro. The eosinophil major basic protein also causes the release of histamine from mast cells and basophils, and activates neutrophils and alveolar macrophages.

Structure

Structurally the major basic protein (MBP) is similar to lectins (sugar-binding proteins), and has a fold similar to that seen in C-type lectins. However, unlike other C-type lectins (those that bind various carbohydrates in the presence of calcium), MBP does not bind either calcium or any of the other carbohydrates that this family recognize.

Instead, MBP recognises heparan sulfate proteoglycans. Two crystallographic structures of MBP have been determined.^[6][7]

Interactions

Major basic protein has been shown to interact with Pregnancy-associated plasma protein A.^[8][9][10]

See also

• Arylsulfatase

References

1. GRCh38: Ensembl release 89: ENSG00000186652 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027073 – Ensembl, May 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.
5. "Entrez Gene: PRG2 proteoglycan 2, bone marrow (natural killer cell activator, eosinophil granule major basic protein)".
6. PDB: 1h8u​; Swaminathan GJ, Weaver AJ, Loegering DA, Checkel JL, Leonidas DD, Gleich GJ, Acharya KR (July 2001). "Crystal structure of the eosinophil major basic protein at 1.8 A. An atypical lectin with a paradigm shift in specificity". J. Biol. Chem. 276 (28): 26197–26203. doi:10.1074/jbc.M100848200. PMID 11319227.
7. PDB: 2brs​; Swaminathan GJ, Myszka DG, Katsamba PS, Ohnuki LE, Gleich GJ, Acharya KR (November 2005). "Eosinophil-granule major basic protein, a C-type lectin, binds heparin". Biochemistry. 44 (43): 14152–14158. doi:10.1021/bi051112b. PMID 16245931.
8. Overgaard MT, Haaning J, Boldt H B, Olsen I M, Laursen L S, Christiansen M, Gleich G J, Sottrup-Jensen L, Conover C A, Oxvig C (October 2000). "Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor". J. Biol. Chem. 275 (40). UNITED STATES: 31128–31133. doi:10.1074/jbc.M001384200. ISSN 0021-9258. PMID 10913121.
9. Overgaard MT, Sorensen ES, Stachowiak D, Boldt HB, Kristensen L, Sottrup-Jensen L, Oxvig C (January 2003). "Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment". J. Biol. Chem. 278 (4). United States: 2106–2117. doi:10.1074/jbc.M208777200. ISSN 0021-9258. PMID 12421832.
10. Oxvig C, Sand O, Kristensen T, Gleich G J, Sottrup-Jensen L (June 1993). "Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein". J. Biol. Chem. 268 (17). UNITED STATES: 12243–6. doi:10.1016/S0021-9258(18)31378-4. ISSN 0021-9258. PMID 7685339.

Further reading

• Vanhaesebroeck B, Alessi DR (2000). "The PI3K-PDK1 connection: more than just a road to PKB". Biochem. J. 346 (3): 561–76. doi:10.1042/0264-6021:3460561. PMC 1220886. PMID 10698680.
• Yoshimatsu K, Ohya Y, Shikata Y, Toshio S, Yoshikazu H, Isao T, Tamio K, Kyousuke K, Satoshi T (1992). "Purification and cDNA cloning of a novel factor produced by a human T-cell hybridoma: sequence homology with animal lectins". Mol. Immunol. 29 (4): 537–546. doi:10.1016/0161-5890(92)90012-M. PMID 1565101.
• Barker RL, Loegering DA, Arakawa KC, Pease LR, Gleich GJ (1990). "Cloning and sequence analysis of the human gene encoding eosinophil major basic protein". Gene. 86 (2): 285–289. doi:10.1016/0378-1119(90)90292-Y. PMID 2323577.
• Gabay JE, Scott RW, Campanelli D, Griffith J, Wilde C, Marra MN, Seeger M, Nathan CF (1989). "Antibiotic proteins of human polymorphonuclear leukocytes". Proc. Natl. Acad. Sci. U.S.A. 86 (14): 5610–5614. Bibcode:1989PNAS...86.5610G. doi:10.1073/pnas.86.14.5610. PMC 297672. PMID 2501794.
• Wasmoen TL, McKean DJ, Benirschke K, Coulam CB, Gleich GJ (1990). "Evidence of eosinophil granule major basic protein in human placenta". J. Exp. Med. 170 (6): 2051–2063. doi:10.1084/jem.170.6.2051. PMC 2189540. PMID 2584934.
• Barker RL, Gleich GJ, Pease LR (1988). "Acidic precursor revealed in human eosinophil granule major basic protein cDNA". J. Exp. Med. 168 (4): 1493–1498. doi:10.1084/jem.168.4.1493. PMC 2189086. PMID 3171483.
• McGrogan M, Simonsen C, Scott R, Griffith J, Ellis N, Kennedy J, Campanelli D, Nathan C, Gabay J (1989). "Isolation of a complementary DNA clone encoding a precursor to human eosinophil major basic protein". J. Exp. Med. 168 (6): 2295–2308. doi:10.1084/jem.168.6.2295. PMC 2189145. PMID 3199069.
• Wasmoen TL, Bell MP, Loegering DA, Gleich GJ, Prendergast FG, McKean DJ (1988). "Biochemical and amino acid sequence analysis of human eosinophil granule major basic protein". J. Biol. Chem. 263 (25): 12559–63. doi:10.1016/S0021-9258(18)37791-3. PMID 3410852.
• Weller PF, Ackerman SJ, Smith JA (1988). "Eosinophil granule cationic proteins: major basic protein is distinct from the smaller subunit of eosinophil peroxidase". J. Leukoc. Biol. 43 (1): 1–4. doi:10.1002/jlb.43.1.1. PMID 3422083. S2CID 42464743.
• Kristensen T, Oxvig C, Sand O, Hundahl Moeller NP, Sottrup-Jensen L (1994). "Amino acid sequence of human pregnancy-associated plasma protein-A derived from cloned cDNA". Biochemistry. 33 (6): 1592–1598. doi:10.1021/bi00172a040. PMID 7508748.
• Oxvig C, Haaning J, Højrup P, Sottrup-Jensen L (1994). "Location and nature of carbohydrate groups in proform of human major basic protein isolated from pregnancy serum". Biochem. Mol. Biol. Int. 33 (2): 329–36. PMID 7524900.
• Bonno M, Oxvig C, Kephart GM, Wagner JM, Kristensen T, Sottrup-Jensen L, Gleich GJ (1994). "Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta". Lab. Invest. 71 (4): 560–6. PMID 7526035.
• Li MS, Sun L, Satoh T, Fisher LM, Spry CJ (1995). "Human eosinophil major basic protein, a mediator of allergic inflammation, is expressed by alternative splicing from two promoters". Biochem. J. 305 (3): 921–7. doi:10.1042/bj3050921. PMC 1136346. PMID 7531438.
• Oxvig C, Haaning J, Kristensen L, Wagner JM, Rubin I, Stigbrand T, Gleich GJ, Sottrup-Jensen L (1995). "Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma". J. Biol. Chem. 270 (23): 13645–13651. doi:10.1074/jbc.270.23.13645. PMID 7539791.
• Oxvig C, Sand O, Kristensen T, Gleich GJ, Sottrup-Jensen L (1993). "Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein". J. Biol. Chem. 268 (17): 12243–6. doi:10.1016/S0021-9258(18)31378-4. PMID 7685339.
• Levi-Schaffer F, Lacy P, Severs NJ, Newman TM, North J, Gomperts B, Kay AB, Moqbel R (1995). "Association of granulocyte-macrophage colony-stimulating factor with the crystalloid granules of human eosinophils". Blood. 85 (9): 2579–86. doi:10.1182/blood.V85.9.2579.bloodjournal8592579. PMID 7727786.
• Oxvig C, Gleich GJ, Sottrup-Jensen L (1994). "Localization of disulfide bridges and free sulfhydryl groups in human eosinophil granule major basic protein" (PDF). FEBS Lett. 341 (2–3): 213–217. doi:10.1016/0014-5793(94)80459-1. PMID 8137941. S2CID 43467769.
• Shikata Y, Hayashi Y, Yoshimatsu K, Ohya Y, Seto T, Fukushima K, Yoshida Y (1993). "Pro-major basic protein has three types of sugar chains at the pro-portion". Biochim. Biophys. Acta. 1163 (3): 243–9. doi:10.1016/0167-4838(93)90158-N. PMID 8507662.
• Nittoh T, Watanabe M, Okayama H, Misawa S, Isobe Y, Hayashi H, Mue S, Ohuchi K (1996). "Cloning of cDNA for rat eosinophil major basic protein". Biochim. Biophys. Acta. 1264 (3): 261–4. doi:10.1016/0167-4781(95)00183-2. PMID 8547309.
• Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, Dedhar S (1998). "Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase". Proc. Natl. Acad. Sci. U.S.A. 95 (19): 11211–11216. Bibcode:1998PNAS...9511211D. doi:10.1073/pnas.95.19.11211. PMC 21621. PMID 9736715.

External links

• Eosinophil+Major+Basic+Protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt: P13727 (Bone marrow proteoglycan) at the PDBe-KB.