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Gene Review

MTTP  -  microsomal triglyceride transfer protein

Homo sapiens

Synonyms: ABL, MTP, Microsomal triglyceride transfer protein large subunit
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Disease relevance of MTTP

  • Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia [1].
  • We recently observed that a polymorphism in the MTTP promoter (-493G>T), which is in allelic association with an isoleucine-to-theronine substitution at position 128 (Ile128Thr) in the expressed protein, confers an increased risk of coronary heart disease [2].
  • In these studies we show that transcriptional co-repression of the two lipid transfer proteins, liver fatty acid-binding protein (L-FABP) and MTP, which cooperatively shunt fatty acids into de novo synthesized glycerolipids and the transfer of lipids into VLDL, respectively, act together to maintain hepatic lipid homeostasis [3].
  • Studies carried out in a variety of heterologous expression systems, as well as the use of microsomal triglyceride transfer protein inhibitors in hepatoma cell lines, have been critical to this progress [4].
  • These complex regulations may represent a means to fine-tuning MTP gene transcription in response to a diverse set of environmental stimuli and may have important implications for the onset and development of diabetes-associated dyslipidemia [5].
  • MTP -493 G/T polymorphism may impact NASH by modulating postprandial lipemia and lipoprotein metabolism; homozygous GG carriers have a more atherogenic postprandial lipid profile than the other genotypes, independently of adipokines and insulin resistance [6].

Psychiatry related information on MTTP

  • "Among women attending the MTP [medical termination of pregnancy] clinic of the National Institute of Health and Family Welfare, New Delhi [India], during 1985-86, 135 were interviewed to ascertain the psychosocial factors indluencing their decision to accept MTP [7].

High impact information on MTTP

  • A conserved tyrosine residue (Y88) in the Cdk-binding domain of p27 can be phosphorylated by the Src-family kinase Lyn and the oncogene product BCR-ABL [8].
  • The microsomal triglyceride transfer protein (MTP), which catalyses the transport of triglyceride, cholesteryl ester and phospholipid between phospholipid surfaces, is a heterodimer composed of the multifunctional protein, protein disulphide isomerase, and a unique large subunit with an apparent M(r) of 88K (refs 1-3) [9].
  • This finding suggests that a defect in MTP is the basis for abetalipoproteinemia and that MTP is indeed required for lipoprotein assembly [10].
  • The microsomal triglyceride transfer protein (MTP), which is located in the lumen of microsomes isolated from the liver and intestine, has been proposed to function in lipoprotein assembly [10].
  • MTP and MTPv1 efficiently transferred phosphatidylethanolamine to CD1d in vitro [11].

Chemical compound and disease context of MTTP


Biological context of MTTP


Anatomical context of MTTP


Associations of MTTP with chemical compounds


Regulatory relationships of MTTP


Other interactions of MTTP

  • These results indicate that two nuclear receptors, HNF-4 and FXR, are closely involved in MTP gene expression, and the results provide evidence for a novel interaction between bile acids and lipoprotein metabolism [17].
  • These results suggest that CYP17A1 and MTP are susceptibility loci for increased BMD in postmenopausal and premenopausal Japanese women, respectively, and that VLDLR constitutes such a locus in Japanese men [20].
  • Expression of ABCG5 and ABCG8 mRNA was lower in the diabetic patients (p<0.05) and MTTP expression was increased (p<0.05) [27].
  • There was a positive correlation between NPLC1L1 and MTTP mRNA (p<0.01) and a negative correlation between NPC1L1 and ABCG5 mRNA (p<0.001) [27].
  • Furthermore, IL-1 and IL-6 significantly decreased MTP mRNA levels in HepG2 cells [28].

Analytical, diagnostic and therapeutic context of MTTP


  1. Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia. Ohashi, K., Ishibashi, S., Osuga, J., Tozawa, R., Harada, K., Yahagi, N., Shionoiri, F., Iizuka, Y., Tamura, Y., Nagai, R., Illingworth, D.R., Gotoda, T., Yamada, N. J. Lipid Res. (2000) [Pubmed]
  2. The Ile128Thr polymorphism influences stability and ligand binding properties of the microsomal triglyceride transfer protein. Ledmyr, H., Ottosson, L., Sunnerhagen, M., Ehrenborg, E. J. Lipid Res. (2006) [Pubmed]
  3. Coordinate Transcriptional Repression of Liver Fatty Acid-binding Protein and Microsomal Triglyceride Transfer Protein Blocks Hepatic Very Low Density Lipoprotein Secretion without Hepatosteatosis. Spann, N.J., Kang, S., Li, A.C., Chen, A.Z., Newberry, E.P., Davidson, N.O., Hui, S.T., Davis, R.A. J. Biol. Chem. (2006) [Pubmed]
  4. Recent advances in elucidating the role of the microsomal triglyceride transfer protein in apolipoprotein B lipoprotein assembly. Gordon, D.A. Curr. Opin. Lipidol. (1997) [Pubmed]
  5. Regulation of microsomal triglyceride transfer protein gene by insulin in HepG2 cells: roles of MAPKerk and MAPKp38. Au, W.S., Kung, H.F., Lin, M.C. Diabetes (2003) [Pubmed]
  6. Polymorphism in microsomal triglyceride transfer protein: a link between liver disease and atherogenic postprandial lipid profile in NASH? Gambino, R., Cassader, M., Pagano, G., Durazzo, M., Musso, G. Hepatology (2007) [Pubmed]
  7. Psycho-social factors influencing decisions to accept termination of pregnancy in Delhi. Sarkar, N.N. Biology and society : the journal of the Eugenics Society. (1990) [Pubmed]
  8. Cdk-Inhibitory Activity and Stability of p27(Kip1) Are Directly Regulated by Oncogenic Tyrosine Kinases. Grimmler, M., Wang, Y., Mund, T., Cilensek, Z., Keidel, E.M., Waddell, M.B., Jäkel, H., Kullmann, M., Kriwacki, R.W., Hengst, L. Cell (2007) [Pubmed]
  9. Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia. Sharp, D., Blinderman, L., Combs, K.A., Kienzle, B., Ricci, B., Wager-Smith, K., Gil, C.M., Turck, C.W., Bouma, M.E., Rader, D.J. Nature (1993) [Pubmed]
  10. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Wetterau, J.R., Aggerbeck, L.P., Bouma, M.E., Eisenberg, C., Munck, A., Hermier, M., Schmitz, J., Gay, G., Rader, D.J., Gregg, R.E. Science (1992) [Pubmed]
  11. MTP regulated by an alternate promoter is essential for NKT cell development. Dougan, S.K., Rava, P., Hussain, M.M., Blumberg, R.S. J. Exp. Med. (2007) [Pubmed]
  12. The microsomal triglyceride transfer protein gene-493T variant lowers cholesterol but increases the risk of coronary heart disease. Ledmyr, H., McMahon, A.D., Ehrenborg, E., Nielsen, L.B., Neville, M., Lithell, H., MacFarlane, P.W., Packard, C.J., Karpe, F. Circulation (2004) [Pubmed]
  13. Oncogenic signaling: new insights and controversies from chronic myeloid leukemia. Van Etten, R.A. J. Exp. Med. (2007) [Pubmed]
  14. Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance. Azam, M., Nardi, V., Shakespeare, W.C., Metcalf, C.A., Bohacek, R.S., Wang, Y., Sundaramoorthi, R., Sliz, P., Veach, D.R., Bornmann, W.G., Clarkson, B., Dalgarno, D.C., Sawyer, T.K., Daley, G.Q. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  15. Bcr-Abl resistance screening predicts a limited spectrum of point mutations to be associated with clinical resistance to the Abl kinase inhibitor nilotinib (AMN107). von Bubnoff, N., Manley, P.W., Mestan, J., Sanger, J., Peschel, C., Duyster, J. Blood (2006) [Pubmed]
  16. A mechanism of membrane neutral lipid acquisition by the microsomal triglyceride transfer protein. Read, J., Anderson, T.A., Ritchie, P.J., Vanloo, B., Amey, J., Levitt, D., Rosseneu, M., Scott, J., Shoulders, C.C. J. Biol. Chem. (2000) [Pubmed]
  17. Bile acid reduces the secretion of very low density lipoprotein by repressing microsomal triglyceride transfer protein gene expression mediated by hepatocyte nuclear factor-4. Hirokane, H., Nakahara, M., Tachibana, S., Shimizu, M., Sato, R. J. Biol. Chem. (2004) [Pubmed]
  18. A common binding site on the microsomal triglyceride transfer protein for apolipoprotein B and protein disulfide isomerase. Bradbury, P., Mann, C.J., Köchl, S., Anderson, T.A., Chester, S.A., Hancock, J.M., Ritchie, P.J., Amey, J., Harrison, G.B., Levitt, D.G., Banaszak, L.J., Scott, J., Shoulders, C.C. J. Biol. Chem. (1999) [Pubmed]
  19. Transcriptional regulation of human and hamster microsomal triglyceride transfer protein genes. Cell type-specific expression and response to metabolic regulators. Hagan, D.L., Kienzle, B., Jamil, H., Hariharan, N. J. Biol. Chem. (1994) [Pubmed]
  20. Association of polymorphisms in CYP17A1, MTP, and VLDLR with bone mineral density in community-dwelling Japanese women and men. Yamada, Y., Ando, F., Shimokata, H. Genomics (2005) [Pubmed]
  21. Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein. Shoulders, C.C., Brett, D.J., Bayliss, J.D., Narcisi, T.M., Jarmuz, A., Grantham, T.T., Leoni, P.R., Bhattacharya, S., Pease, R.J., Cullen, P.M. Hum. Mol. Genet. (1993) [Pubmed]
  22. Dual PPARalpha/gamma ligand TZD18 either alone or in combination with imatinib inhibits proliferation and induces apoptosis of human CML cell lines. Zang, C., Liu, H., Waechter, M., Eucker, J., Bertz, J., Possinger, K., Koeffler, H.P., Elstner, E. Cell Cycle (2006) [Pubmed]
  23. Bifonazole (Mycospor cream) in the treatment of moccasin-type tinea pedis. Comparison between combination therapy of bifonazole cream + 10% urea ointment (Urepearl) and occlusive dressing therapy with the same agents. Tanuma, H., Doi, M., Sato, N., Nishiyama, S., Abe, M., Kume, H., Katsuoka, K. Mycoses (2000) [Pubmed]
  24. Mutations of the microsomal triglyceride-transfer-protein gene in abetalipoproteinemia. Narcisi, T.M., Shoulders, C.C., Chester, S.A., Read, J., Brett, D.J., Harrison, G.B., Grantham, T.T., Fox, M.F., Povey, S., de Bruin, T.W. Am. J. Hum. Genet. (1995) [Pubmed]
  25. Increased activity of hepatic microsomal triglyceride transfer protein and bile acid synthesis in gallstone disease. Castro, J., Amigo, L., Miquel, J.F., Gälman, C., Crovari, F., Raddatz, A., Zanlungo, S., Jalil, R., Rudling, M., Nervi, F. Hepatology (2007) [Pubmed]
  26. Sterol regulatory element-binding protein negatively regulates microsomal triglyceride transfer protein gene transcription. Sato, R., Miyamoto, W., Inoue, J., Terada, T., Imanaka, T., Maeda, M. J. Biol. Chem. (1999) [Pubmed]
  27. Messenger RNA levels of genes involved in dysregulation of postprandial lipoproteins in type 2 diabetes: the role of Niemann-Pick C1-like 1, ATP-binding cassette, transporters G5 and G8, and of microsomal triglyceride transfer protein. Lally, S., Tan, C.Y., Owens, D., Tomkin, G.H. Diabetologia (2006) [Pubmed]
  28. Regulation of microsomal triglyceride transfer protein mRNA expression by endotoxin and cytokines. Navasa, M., Gordon, D.A., Hariharan, N., Jamil, H., Shigenaga, J.K., Moser, A., Fiers, W., Pollock, A., Grunfeld, C., Feingold, K.R. J. Lipid Res. (1998) [Pubmed]
  29. Apo B100-containing lipoproteins are secreted by the heart. Borén, J., Véniant, M.M., Young, S.G. J. Clin. Invest. (1998) [Pubmed]
  30. Variants of the microsomal triglyceride transfer protein gene are associated with plasma cholesterol levels and body mass index. Ledmyr, H., Karpe, F., Lundahl, B., McKinnon, M., Skoglund-Andersson, C., Ehrenborg, E. J. Lipid Res. (2002) [Pubmed]
  31. Human microsomal triglyceride transfer protein large subunit gene structure. Sharp, D., Ricci, B., Kienzle, B., Lin, M.C., Wetterau, J.R. Biochemistry (1994) [Pubmed]
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