Microsomal triglyceride transfer protein

Large subunit of microsomal triglyceride transfer protein

MTTP

Available structures

PDB

Ortholog search: PDBe RCSB

List of PDB id codes
6I7S, 8EOJ

Identifiers

Aliases

MTTP, ABL, MTP, Microsomal triglyceride transfer protein

External IDs

OMIM: 157147; MGI: 106926; HomoloGene: 212; GeneCards: MTTP; OMA:MTTP - orthologs

Gene location (Human)

Chr.	Chromosome 4 (human)^[1]

Band	4q23	Start	99,564,081 bp^[1]
Band	4q23	End	99,623,997 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 3 (mouse)^[2]

Band	3 G3\|3 64.06 cM	Start	137,795,615 bp^[2]
Band	3 G3\|3 64.06 cM	End	137,850,729 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

jejunal mucosa

liver

duodenum

right lobe of liver

kidney tubule

kidney

testicle

ganglionic eminence

metanephric glomerulus

gallbladder

Top expressed in

jejunum

duodenum

left lobe of liver

ileum

yolk sac

spermatocyte

intestinal epithelium

crypt of lieberkuhn of small intestine

spermatid

sexually immature organism

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	protein heterodimerization activity protein binding phospholipid transporter activity lipid binding lipid transporter activity
Cellular component	receptor complex endoplasmic reticulum lumen endoplasmic reticulum Golgi apparatus basolateral plasma membrane
Biological process	phospholipid transport lipid transport plasma lipoprotein particle assembly lipid metabolism protein secretion triglyceride transport chylomicron assembly very-low-density lipoprotein particle assembly lipoprotein metabolic process cholesterol homeostasis
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


4547


17777

Ensembl


ENSG00000138823


ENSMUSG00000028158

UniProt


P55157


O08601

RefSeq (mRNA)


NM_001300785 NM_000253 NM_001386140


NM_001163457 NM_008642 NM_001355051 NM_001355052

RefSeq (protein)


NP_000244 NP_001287714


NP_001156929 NP_032668 NP_001341980 NP_001341981

Location (UCSC)

Chr 4: 99.56 – 99.62 Mb

Chr 3: 137.8 – 137.85 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Microsomal triglyceride transfer protein large subunit is a protein that in humans is encoded by the MTTP, also known as MTP, gene.^[5]^[6]

MTTP encodes the large subunit of the heterodimeric microsomal triglyceride transfer protein (MTP). Protein disulfide isomerase (PDI) completes the heterodimeric MTP, which has been shown to play a central role in lipoprotein assembly. Mutations in MTTP can cause abetalipoproteinemia.^[6]

Apolipoprotein B48 on chylomicra and Apolipoprotein B100 on LDL, IDL, and VLDL are important for MTP binding.^{[citation needed]}

Structure

The large subunit of MTP, also known as the alpha subunit, contains an N-terminal half beta barrel, an alpha helix and a C-terminal lipid binding site that lies between two beta pleated sheets. It is a member of the large lipid transfer protein family, like apolipoprotein B (apo B), with which it interacts, but unlike apo B, it is not secreted. The heterodimer is instead retained in the endoplasmic reticulum due to the presence of a C-terminal KDEL motif on the PDI beta subunit.^[7]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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|alt=Statin pathway edit]]

Statin pathway edit

^ The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".

Pharmacology

Drugs that inhibit MTTP prevent the assembly of apo B-containing lipoproteins thus inhibiting the synthesis of chylomicrons and VLDL and leading to decrease in plasma levels of LDL-C.

Lomitapide (Juxtapid) was approved by the US FDA for adjunctive treatment of homozygous familial hypercholesterolemia.
Dirlotapide (Slentrol) and mitratapide (Yarvitan) are veterinary drugs for the management of obesity in dogs.

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000138823 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000028158 – Ensembl, May 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.
^ Shoulders CC, Brett DJ, Bayliss JD, Narcisi TM, Jarmuz A, Grantham TT, Leoni PR, Bhattacharya S, Pease RJ, Cullen PM, et al. (Mar 1994). "Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein". Hum Mol Genet. 2 (12): 2109–16. doi:10.1093/hmg/2.12.2109. PMID 8111381.
^ ^a ^b "Entrez Gene: MTTP microsomal triglyceride transfer protein".
^ Biterova EI, Isupov MN, Keegan RM, Lebedev AA, Sohail AA, Liaquat I, Alanen HI, Ruddock LW (2019). "The crystal structure of human microsomal triglyceride transfer protein". Proceedings of the National Academy of Sciences of the United States of America. 116 (35): 17251–17260. Bibcode:2019PNAS..11617251B. doi:10.1073/pnas.1903029116. PMC 6717300. PMID 31395737.

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Wetterau JR, Lin MC, Jamil H (1997). "Microsomal triaglyceride transfer protein". Biochim. Biophys. Acta. 1345 (2): 136–50. doi:10.1016/s0005-2760(96)00168-3. PMID 9106493.
Gordon DA (1997). "Recent advances in elucidating the role of the microsomal triaglyceride transfer protein in apolipoprotein B lipoprotein assembly". Curr. Opin. Lipidol. 8 (3): 131–7. doi:10.1097/00041433-199706000-00002. PMID 9211060.
Ye J (2007). "Reliance of Host Cholesterol Metabolic Pathways for the Life Cycle of Hepatitis C Virus". PLOS Pathog. 3 (8): e108. doi:10.1371/journal.ppat.0030108. PMC 1959368. PMID 17784784.
Wetterau JR, Aggerbeck LP, Bouma ME, et al. (1992). "Absence of microsomal triaglyceride transfer protein in individuals with abetalipoproteinemia". Science. 258 (5084): 999–1001. Bibcode:1992Sci...258..999W. doi:10.1126/science.1439810. PMID 1439810.
Sharp D, Ricci B, Kienzle B, et al. (1994). "Human microsomal triaglyceride transfer protein large subunit gene structure". Biochemistry. 33 (31): 9057–61. doi:10.1021/bi00197a005. PMID 7545943.
Shoulders CC, Narcisi TM, Read J, et al. (1995). "The abetalipoproteinemia gene is a member of the vitellogenin family and encodes an alpha-helical domain". Nat. Struct. Biol. 1 (5): 285–6. doi:10.1038/nsb0594-285. PMID 7664034. S2CID 11860468.
Hagan DL, Kienzle B, Jamil H, Hariharan N (1994). "Transcriptional regulation of human and hamster microsomal triaglyceride transfer protein genes. Cell type-specific expression and response to metabolic regulators". J. Biol. Chem. 269 (46): 28737–44. doi:10.1016/S0021-9258(19)61967-8. PMID 7961826.
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Sharp D, Blinderman L, Combs KA, et al. (1993). "Cloning and gene defects in microsomal triaglyceride transfer protein associated with abetalipoproteinaemia". Nature. 365 (6441): 65–9. Bibcode:1993Natur.365...65S. doi:10.1038/365065a0. PMID 8361539. S2CID 4334532.
Narcisi TM, Shoulders CC, Chester SA, et al. (1996). "Mutations of the Microsomal Triglyceride-Transfer–Protein Gene in Abetalipoproteinemia". Am. J. Hum. Genet. 57 (6): 1298–310. PMC 1801399. PMID 8533758.
Rehberg EF, Samson-Bouma ME, Kienzle B, et al. (1997). "A novel abetalipoproteinemia genotype. Identification of a missense mutation in the 97-kDa subunit of the microsomal triaglyceride transfer protein that prevents complex formation with protein disulfide isomerase". J. Biol. Chem. 271 (47): 29945–52. doi:10.1074/jbc.271.47.29945. PMID 8939939.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
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