MTP_HUMAN
ID MTP_HUMAN Reviewed; 894 AA.
AC P55157; A8K428; Q08AM4; Q6P5T3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Microsomal triglyceride transfer protein large subunit;
DE Flags: Precursor;
GN Name=MTTP; Synonyms=MTP;
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] (ISOFORM 1).
RC TISSUE=Small intestine;
RX PubMed=8111381; DOI=10.1093/hmg/2.12.2109;
RA Shoulders C.C., Brett D.J., Bayliss J.D., Narcisi T.M.E., Jarmuz A.,
RA Grantham T.T., Leoni P.R.D., Bhattacharya S., Pease R.J., Cullen P.M.,
RA Levi S., Byfield P.G.H., Purkiss P., Scott J.;
RT "Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa
RT subunit of a microsomal triglyceride transfer protein.";
RL Hum. Mol. Genet. 2:2109-2116(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=8361539; DOI=10.1038/365065a0;
RA Sharp D., Blinderman L., Combs K.A., Kienzle B., Ricci B., Wager-Smith K.,
RA Gil C.M., Turck C.W., Bouma M.-E., Rader D.J., Aggerbeck L.P., Gregg R.E.,
RA Gordon D.A., Wetterau J.R.;
RT "Cloning and gene defects in microsomal triglyceride transfer protein
RT associated with abetalipoproteinaemia.";
RL Nature 365:65-69(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7545943; DOI=10.1021/bi00197a005;
RA Sharp D., Ricci B., Kienzle B., Lin M.C., Wetterau J.R.;
RT "Human microsomal triglyceride transfer protein large subunit gene
RT structure.";
RL Biochemistry 33:9057-9061(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Blood vessel;
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 [7]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=7961826; DOI=10.1016/s0021-9258(19)61967-8;
RA Hagan D.L., Kienzle B., Jamil H., Hariharan N.;
RT "Transcriptional regulation of human and hamster microsomal triglyceride
RT transfer protein genes. Cell type-specific expression and response to
RT metabolic regulators.";
RL J. Biol. Chem. 269:28737-28744(1994).
RN [8]
RP SIMILARITY TO VITELLOGENINS.
RX PubMed=7664034; DOI=10.1038/nsb0594-285;
RA Shoulders C.C., Narcisi T.M.E., Read J., Chester S.A., Brett D.J.,
RA Scott J., Anderson T.A., Levitt D.G., Banaszak L.J.;
RT "The abetalipoproteinemia gene is a member of the vitellogenin family and
RT encodes an alpha-helical domain.";
RL Nat. Struct. Biol. 1:285-286(1994).
RN [9]
RP MUTAGENESIS OF CYS-878.
RX PubMed=8533758;
RA Narcisi T.M.E., Shoulders C.C., Chester S.A., Read J., Brett D.J.,
RA Harrison G.B., Grantham T.T., Fox M.F., Povey S., de Bruin T.W.A.,
RA Erkelens D.W., Muller D.P.R., Lloyd J.K., Scott J.;
RT "Mutations of the microsomal triglyceride-transfer-protein gene in
RT abetalipoproteinemia.";
RL Am. J. Hum. Genet. 57:1298-1310(1995).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8876250; DOI=10.1073/pnas.93.21.11991;
RA Jamil H., Gordon D.A., Eustice D.C., Brooks C.M., Dickson J.K. Jr.,
RA Chen Y., Ricci B., Chu C.H., Harrity T.W., Ciosek C.P. Jr., Biller S.A.,
RA Gregg R.E., Wetterau J.R.;
RT "An inhibitor of the microsomal triglyceride transfer protein inhibits apoB
RT secretion from HepG2 cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:11991-11995(1996).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15897609; DOI=10.1194/jlr.d400043-jlr200;
RA Rava P., Athar H., Johnson C., Hussain M.M.;
RT "Transfer of cholesteryl esters and phospholipids as well as net deposition
RT by microsomal triglyceride transfer protein.";
RL J. Lipid Res. 46:1779-1785(2005).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP P4HB.
RX PubMed=16478722; DOI=10.1074/jbc.m512823200;
RA Rava P., Ojakian G.K., Shelness G.S., Hussain M.M.;
RT "Phospholipid transfer activity of microsomal triacylglycerol transfer
RT protein is sufficient for the assembly and secretion of apolipoprotein B
RT lipoproteins.";
RL J. Biol. Chem. 281:11019-11027(2006).
RN [13]
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 [14]
RP FUNCTION, INTERACTION WITH P4HB, SUBCELLULAR LOCATION, CHARACTERIZATION OF
RP VARIANTS ABL HIS-540; ILE-590; GLU-746 AND TYR-780, AND CHARACTERIZATION OF
RP VARIANT ALA-384.
RX PubMed=23475612; DOI=10.1194/jlr.m031658;
RA Khatun I., Walsh M.T., Hussain M.M.;
RT "Loss of both phospholipid and triglyceride transfer activities of
RT microsomal triglyceride transfer protein in abetalipoproteinemia.";
RL J. Lipid Res. 54:1541-1549(2013).
RN [15]
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 [16]
RP VARIANT ABL HIS-540, VARIANTS GLN-297 AND ALA-384, CHARACTERIZATION OF
RP VARIANT ABL HIS-540, CHARACTERIZATION OF VARIANTS GLN-297 AND ALA-384,
RP MUTAGENESIS OF ARG-540, FUNCTION, AND INVOLVEMENT IN ABL.
RX PubMed=8939939; DOI=10.1074/jbc.271.47.29945;
RA Rehberg E.F., Samson-Bouma M.-E., Kienzle B., Blinderman L., Jamil H.,
RA Wetterau J.R., Aggerbeck L.P., Gordon D.A.;
RT "A novel abetalipoproteinemia genotype. Identification of a missense
RT mutation in the 97-kDa subunit of the microsomal triglyceride transfer
RT protein that prevents complex formation with protein disulfide isomerase.";
RL J. Biol. Chem. 271:29945-29952(1996).
RN [17]
RP VARIANTS ABL HIS-540; ILE-590 AND GLU-746.
RX PubMed=10679949;
RX DOI=10.1002/(sici)1098-1004(200003)15:3<294::aid-humu14>3.0.co;2-e;
RA Wang J., Hegele R.A.;
RT "Microsomal triglyceride transfer protein (MTP) gene mutations in Canadian
RT subjects with abetalipoproteinemia.";
RL Hum. Mutat. 15:294-295(2000).
RN [18]
RP VARIANT ABL TYR-780.
RX PubMed=10946006;
RA Ohashi K., Ishibashi S., Osuga J., Tozawa R., Harada K., Yahagi N.,
RA Shionoiri F., Iizuka Y., Tamura Y., Nagai R., Illingworth D.R., Gotoda T.,
RA Yamada N.;
RT "Novel mutations in the microsomal triglyceride transfer protein gene
RT causing abetalipoproteinemia.";
RL J. Lipid Res. 41:1199-1204(2000).
RN [19]
RP VARIANTS HIS-95; THR-128; GLU-244 AND GLN-297.
RX PubMed=11792722;
RA Ledmyr H., Karpe F., Lundahl B., McKinnon M., Skoglund-Andersson C.,
RA Ehrenborg E.;
RT "Variants of the microsomal triglyceride transfer protein gene are
RT associated with plasma cholesterol levels and body mass index.";
RL J. Lipid Res. 43:51-58(2002).
RN [20]
RP VARIANTS THR-128; ILE-168 AND GLN-297.
RX PubMed=14732481; DOI=10.1016/j.bbadis.2003.11.002;
RA Lancellotti S., Di Leo E., Penacchioni J.Y., Balli F., Viola L.,
RA Bertolini S., Calandra S., Tarugi P.;
RT "Hypobetalipoproteinemia with an apparently recessive inheritance due to a
RT 'de novo' mutation of apolipoprotein B.";
RL Biochim. Biophys. Acta 1688:61-67(2004).
RN [21]
RP VARIANT ABL HIS-435, CHARACTERIZATION OF VARIANT ABL HIS-435, FUNCTION,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-435.
RX PubMed=22236406; DOI=10.1194/jlr.m020024;
RA Di Filippo M., Crehalet H., Samson-Bouma M.E., Bonnet V., Aggerbeck L.P.,
RA Rabes J.P., Gottrand F., Luc G., Bozon D., Sassolas A.;
RT "Molecular and functional analysis of two new MTTP gene mutations in an
RT atypical case of abetalipoproteinemia.";
RL J. Lipid Res. 53:548-555(2012).
RN [22]
RP VARIANTS ABL ARG-264; HIS-528; CYS-540 AND SER-649, CHARACTERIZATION OF
RP VARIANTS ABL ARG-264; HIS-528; CYS-540; HIS-540 AND SER-649, FUNCTION,
RP INTERACTION WITH APOB AND P4HB, AND MUTAGENESIS OF TYR-528.
RX PubMed=25108285; DOI=10.1016/j.bbalip.2014.08.001;
RA Miller S.A., Burnett J.R., Leonis M.A., McKnight C.J., van Bockxmeer F.M.,
RA Hooper A.J.;
RT "Novel missense MTTP gene mutations causing abetalipoproteinemia.";
RL Biochim. Biophys. Acta 1842:1548-1554(2014).
RN [23]
RP VARIANT ABL VAL-169, CHARACTERIZATION OF VARIANT ABL VAL-169, FUNCTION,
RP INTERACTION WITH APOB AND P4HB, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ASP-169; LYS-187 AND LYS-189.
RX PubMed=26224785; DOI=10.1161/circgenetics.115.001106;
RA Walsh M.T., Iqbal J., Josekutty J., Soh J., Di Leo E., Oezaydin E.,
RA Guenduez M., Tarugi P., Hussain M.M.;
RT "A novel abetalipoproteinemia missense mutation highlights the importance
RT of N-Terminal beta-barrel in microsomal triglyceride transfer protein
RT function.";
RL Circ. Cardiovasc. Genet. 8:677-687(2015).
RN [24]
RP INTERACTION WITH APOB.
RX PubMed=27206948; DOI=10.1016/j.jacl.2016.01.006;
RA Miller S.A., Hooper A.J., Mantiri G.A., Marais D., Tanyanyiwa D.M.,
RA McKnight J., Burnett J.R.;
RT "Novel APOB missense variants, A224T and V925L, in a black South African
RT woman with marked hypocholesterolemia.";
RL J. Clin. Lipidol. 10:604-609(2016).
CC -!- FUNCTION: Catalyzes the transport of triglyceride, cholesteryl ester,
CC and phospholipid between phospholipid surfaces (PubMed:23475612,
CC PubMed:8939939, PubMed:26224785, PubMed:25108285, PubMed:22236406,
CC PubMed:16478722, PubMed:15897609, PubMed:8876250). Required for the
CC assembly and secretion of plasma lipoproteins that contain
CC apolipoprotein B (PubMed:23475612, PubMed:8939939, PubMed:26224785,
CC PubMed:8876250, PubMed:16478722). May be involved in regulating
CC cholesteryl ester biosynthesis in cells that produce lipoproteins (By
CC similarity). {ECO:0000250|UniProtKB:O08601,
CC ECO:0000269|PubMed:15897609, ECO:0000269|PubMed:16478722,
CC ECO:0000269|PubMed:22236406, ECO:0000269|PubMed:23475612,
CC ECO:0000269|PubMed:25108285, ECO:0000269|PubMed:26224785,
CC ECO:0000269|PubMed:8876250, ECO:0000269|PubMed:8939939}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-
CC sn-glycero-3-phosphocholine(out); Xref=Rhea:RHEA:38571,
CC ChEBI:CHEBI:57643; Evidence={ECO:0000269|PubMed:16478722,
CC ECO:0000269|PubMed:8876250};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38572;
CC Evidence={ECO:0000305|PubMed:16478722};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) = a 1,2-
CC diacyl-sn-glycero-3-phosphoethanolamine(out); Xref=Rhea:RHEA:38895,
CC ChEBI:CHEBI:64612; Evidence={ECO:0000269|PubMed:15897609,
CC ECO:0000269|PubMed:16478722};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38896;
CC Evidence={ECO:0000305|PubMed:16478722};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a cholesterol ester(in) = a cholesterol ester(out);
CC Xref=Rhea:RHEA:39007, ChEBI:CHEBI:17002;
CC Evidence={ECO:0000269|PubMed:15897609, ECO:0000269|PubMed:16478722,
CC ECO:0000269|PubMed:8876250};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39008;
CC Evidence={ECO:0000305|PubMed:16478722};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a triacyl-sn-glycerol(in) = a triacyl-sn-glycerol(out);
CC Xref=Rhea:RHEA:39011, ChEBI:CHEBI:64615;
CC Evidence={ECO:0000269|PubMed:15897609, ECO:0000269|PubMed:16478722,
CC ECO:0000269|PubMed:8876250};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39012;
CC Evidence={ECO:0000305|PubMed:16478722};
CC -!- SUBUNIT: Heterodimer; heterodimerizes with the protein disulfide
CC isomerase (P4HB/PDI) (PubMed:23475612, PubMed:26224785,
CC PubMed:25108285, PubMed:16478722). Interacts with APOB
CC (PubMed:26224785, PubMed:25108285, PubMed:27206948). Interacts with
CC PRAP1 (By similarity). {ECO:0000250|UniProtKB:O08601,
CC ECO:0000269|PubMed:16478722, ECO:0000269|PubMed:23475612,
CC ECO:0000269|PubMed:25108285, ECO:0000269|PubMed:26224785,
CC ECO:0000269|PubMed:27206948}.
CC -!- INTERACTION:
CC P55157; P04114: APOB; NbExp=4; IntAct=EBI-11614052, EBI-3926040;
CC P55157; Q4VIT4: PDIA3; Xeno; NbExp=5; IntAct=EBI-11614052, EBI-22054129;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:16478722, ECO:0000269|PubMed:22236406,
CC ECO:0000269|PubMed:23475612, ECO:0000269|PubMed:26224785}. Golgi
CC apparatus {ECO:0000269|PubMed:16478722}. Note=Colocalizes with P4HB/PDI
CC in the endoplasmic reticulum (PubMed:23475612, PubMed:26224785).
CC {ECO:0000269|PubMed:23475612, ECO:0000269|PubMed:26224785}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P55157-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P55157-2; Sequence=VSP_056325, VSP_056326;
CC -!- TISSUE SPECIFICITY: Liver and small intestine. Also found in ovary,
CC testis and kidney. {ECO:0000269|PubMed:7961826}.
CC -!- INDUCTION: Positively regulated by cholesterol and negatively regulated
CC by insulin. {ECO:0000269|PubMed:7961826}.
CC -!- DISEASE: Abetalipoproteinemia (ABL) [MIM:200100]: An autosomal
CC recessive disorder of lipoprotein metabolism. Affected individuals
CC produce virtually no circulating apolipoprotein B-containing
CC lipoproteins (chylomicrons, VLDL, LDL, lipoprotein(A)). Malabsorption
CC of the antioxidant vitamin E occurs, leading to spinocerebellar and
CC retinal degeneration. {ECO:0000269|PubMed:10679949,
CC ECO:0000269|PubMed:10946006, ECO:0000269|PubMed:22236406,
CC ECO:0000269|PubMed:23475612, ECO:0000269|PubMed:25108285,
CC ECO:0000269|PubMed:26224785, ECO:0000269|PubMed:8939939}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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DR EMBL; X75500; CAA53217.1; -; mRNA.
DR EMBL; X59657; CAA42200.1; -; mRNA.
DR EMBL; X83013; CAA58142.1; -; Genomic_DNA.
DR EMBL; X83014; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83015; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83016; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83017; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83018; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83019; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83020; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83021; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83022; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83023; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83024; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83025; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83026; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83027; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83028; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83029; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; X83030; CAA58142.1; JOINED; Genomic_DNA.
DR EMBL; AK290793; BAF83482.1; -; mRNA.
DR EMBL; AC083902; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC062696; AAH62696.1; -; mRNA.
DR EMBL; BC125110; AAI25111.1; -; mRNA.
DR EMBL; BC125111; AAI25112.1; -; mRNA.
DR CCDS; CCDS3651.1; -. [P55157-1]
DR PIR; I38047; I38047.
DR RefSeq; NP_000244.2; NM_000253.3. [P55157-1]
DR RefSeq; NP_001287714.1; NM_001300785.1.
DR AlphaFoldDB; P55157; -.
DR SMR; P55157; -.
DR BioGRID; 110641; 7.
DR IntAct; P55157; 4.
DR STRING; 9606.ENSP00000427679; -.
DR BindingDB; P55157; -.
DR ChEMBL; CHEMBL2569; -.
DR DrugBank; DB01094; Hesperetin.
DR DrugBank; DB04852; Implitapide.
DR DrugBank; DB08827; Lomitapide.
DR DrugBank; DB05678; SLx-4090.
DR DrugCentral; P55157; -.
DR SwissLipids; SLP:000000411; -.
DR GlyGen; P55157; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P55157; -.
DR PhosphoSitePlus; P55157; -.
DR BioMuta; MTTP; -.
DR DMDM; 1709167; -.
DR EPD; P55157; -.
DR jPOST; P55157; -.
DR MassIVE; P55157; -.
DR MaxQB; P55157; -.
DR PaxDb; P55157; -.
DR PeptideAtlas; P55157; -.
DR PRIDE; P55157; -.
DR ProteomicsDB; 56794; -. [P55157-1]
DR ProteomicsDB; 67006; -.
DR Antibodypedia; 25923; 247 antibodies from 29 providers.
DR DNASU; 4547; -.
DR Ensembl; ENST00000265517.10; ENSP00000265517.5; ENSG00000138823.14. [P55157-1]
DR Ensembl; ENST00000422897.6; ENSP00000407350.2; ENSG00000138823.14. [P55157-2]
DR Ensembl; ENST00000457717.6; ENSP00000400821.1; ENSG00000138823.14. [P55157-1]
DR GeneID; 4547; -.
DR KEGG; hsa:4547; -.
DR MANE-Select; ENST00000265517.10; ENSP00000265517.5; NM_001386140.1; NP_001373069.1.
DR UCSC; uc003hvb.4; human. [P55157-1]
DR CTD; 4547; -.
DR DisGeNET; 4547; -.
DR GeneCards; MTTP; -.
DR GeneReviews; MTTP; -.
DR HGNC; HGNC:7467; MTTP.
DR HPA; ENSG00000138823; Group enriched (intestine, liver).
DR MalaCards; MTTP; -.
DR MIM; 157147; gene.
DR MIM; 200100; phenotype.
DR neXtProt; NX_P55157; -.
DR OpenTargets; ENSG00000138823; -.
DR Orphanet; 14; Abetalipoproteinemia.
DR Orphanet; 426; NON RARE IN EUROPE: Familial hypobetalipoproteinemia.
DR PharmGKB; PA164742099; -.
DR VEuPathDB; HostDB:ENSG00000138823; -.
DR eggNOG; KOG4337; Eukaryota.
DR GeneTree; ENSGT00390000011412; -.
DR HOGENOM; CLU_014703_0_0_1; -.
DR InParanoid; P55157; -.
DR OMA; HVWGGSA; -.
DR OrthoDB; 1025450at2759; -.
DR PhylomeDB; P55157; -.
DR TreeFam; TF328754; -.
DR PathwayCommons; P55157; -.
DR Reactome; R-HSA-8866423; VLDL assembly.
DR Reactome; R-HSA-8963888; Chylomicron assembly.
DR Reactome; R-HSA-8964041; LDL remodeling.
DR SignaLink; P55157; -.
DR SIGNOR; P55157; -.
DR BioGRID-ORCS; 4547; 8 hits in 1073 CRISPR screens.
DR ChiTaRS; MTTP; human.
DR GeneWiki; Microsomal_triglyceride_transfer_protein; -.
DR GenomeRNAi; 4547; -.
DR Pharos; P55157; Tclin.
DR PRO; PR:P55157; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P55157; protein.
DR Bgee; ENSG00000138823; Expressed in jejunal mucosa and 103 other tissues.
DR ExpressionAtlas; P55157; baseline and differential.
DR Genevisible; P55157; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; IBA:GO_Central.
DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0031528; C:microvillus membrane; IEA:Ensembl.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0031982; C:vesicle; IEA:Ensembl.
DR GO; GO:0034185; F:apolipoprotein binding; IEA:Ensembl.
DR GO; GO:1902388; F:ceramide 1-phosphate transfer activity; IDA:GO_Central.
DR GO; GO:0120020; F:cholesterol transfer activity; IDA:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0005319; F:lipid transporter activity; TAS:Reactome.
DR GO; GO:0120019; F:phosphatidylcholine transfer activity; IDA:UniProtKB.
DR GO; GO:1904121; F:phosphatidylethanolamine transfer activity; IDA:UniProtKB.
DR GO; GO:0120014; F:phospholipid transfer activity; IDA:GO_Central.
DR GO; GO:0005548; F:phospholipid transporter activity; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0140344; F:triglyceride transfer activity; IDA:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IBA:GO_Central.
DR GO; GO:0034378; P:chylomicron assembly; TAS:Reactome.
DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR GO; GO:0042157; P:lipoprotein metabolic process; IBA:GO_Central.
DR GO; GO:0042953; P:lipoprotein transport; IEA:Ensembl.
DR GO; GO:0034374; P:low-density lipoprotein particle remodeling; IEA:Ensembl.
DR GO; GO:0015914; P:phospholipid transport; IDA:UniProtKB.
DR GO; GO:0034377; P:plasma lipoprotein particle assembly; IDA:UniProtKB.
DR GO; GO:0006497; P:protein lipidation; IEA:Ensembl.
DR GO; GO:0009306; P:protein secretion; IDA:UniProtKB.
DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR GO; GO:0006641; P:triglyceride metabolic process; IEA:Ensembl.
DR GO; GO:0034197; P:triglyceride transport; IDA:UniProtKB.
DR GO; GO:0034379; P:very-low-density lipoprotein particle assembly; TAS:Reactome.
DR Gene3D; 1.25.10.20; -; 1.
DR Gene3D; 2.30.230.10; -; 1.
DR InterPro; IPR015819; Lipid_transp_b-sht_shell.
DR InterPro; IPR011030; Lipovitellin_superhlx_dom.
DR InterPro; IPR045811; MTP_lip-bd.
DR InterPro; IPR039988; MTTP.
DR InterPro; IPR015816; Vitellinogen_b-sht_N.
DR InterPro; IPR001747; Vitellogenin_N.
DR PANTHER; PTHR13024; PTHR13024; 1.
DR Pfam; PF19444; MTP_lip_bd; 1.
DR Pfam; PF01347; Vitellogenin_N; 1.
DR SMART; SM00638; LPD_N; 1.
DR SUPFAM; SSF48431; SSF48431; 1.
DR SUPFAM; SSF56968; SSF56968; 1.
DR PROSITE; PS51211; VITELLOGENIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Disulfide bond;
KW Endoplasmic reticulum; Golgi apparatus; Lipid transport; Lipid-binding;
KW Reference proteome; Signal; Transport.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..894
FT /note="Microsomal triglyceride transfer protein large
FT subunit"
FT /id="PRO_0000041593"
FT DOMAIN 28..659
FT /note="Vitellogenin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00557"
FT DISULFID 174..194
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00557"
FT VAR_SEQ 134..151
FT /note="EFYSYQNEAVAIENIKRG -> GRLDSTTFSPTSYFSSLQ (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056325"
FT VAR_SEQ 152..894
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056326"
FT VARIANT 95
FT /note="Q -> H (in dbSNP:rs61733139)"
FT /evidence="ECO:0000269|PubMed:11792722"
FT /id="VAR_014016"
FT VARIANT 98
FT /note="E -> D (in dbSNP:rs2306986)"
FT /id="VAR_052961"
FT VARIANT 128
FT /note="I -> T (in dbSNP:rs3816873)"
FT /evidence="ECO:0000269|PubMed:11792722,
FT ECO:0000269|PubMed:14732481"
FT /id="VAR_014017"
FT VARIANT 166
FT /note="N -> S (in dbSNP:rs3792683)"
FT /id="VAR_052962"
FT VARIANT 168
FT /note="V -> I (in dbSNP:rs61750974)"
FT /evidence="ECO:0000269|PubMed:14732481"
FT /id="VAR_022658"
FT VARIANT 169
FT /note="D -> V (in ABL; no loss on localization to the
FT endoplasmic reticulum; does not reduce interaction with
FT APOB; inhibits interaction with P4HB/PDI; inhibits
FT phospholipid or triglyceride transfer activity; inhibits
FT apolipoprotein B secretion)"
FT /evidence="ECO:0000269|PubMed:26224785"
FT /id="VAR_074553"
FT VARIANT 244
FT /note="Q -> E (in dbSNP:rs17599091)"
FT /evidence="ECO:0000269|PubMed:11792722"
FT /id="VAR_014018"
FT VARIANT 264
FT /note="G -> R (in ABL; unknown pathological significance;
FT does not reduce interaction with P4HB/PDI and APOB; does
FT not reduce triglyceride transfer activity;
FT dbSNP:rs1367079155)"
FT /evidence="ECO:0000269|PubMed:25108285"
FT /id="VAR_074554"
FT VARIANT 297
FT /note="H -> Q (does not inhibit apolipoprotein B secretion;
FT dbSNP:rs2306985)"
FT /evidence="ECO:0000269|PubMed:11792722,
FT ECO:0000269|PubMed:14732481, ECO:0000269|PubMed:8939939"
FT /id="VAR_010640"
FT VARIANT 384
FT /note="D -> A (no loss on localization to the endoplasmic
FT reticulum; does not reduce interaction with P4HB/PDI;
FT reduces phospholipid or triglyceride transfer activity;
FT does not inhibit apolipoprotein B secretion;
FT dbSNP:rs17029215)"
FT /evidence="ECO:0000269|PubMed:23475612,
FT ECO:0000269|PubMed:8939939"
FT /id="VAR_010641"
FT VARIANT 435
FT /note="L -> H (in ABL; no loss on localization to the
FT endoplasmic reticulum; inhibits triglyceride transfer
FT activity)"
FT /evidence="ECO:0000269|PubMed:22236406"
FT /id="VAR_074555"
FT VARIANT 528
FT /note="Y -> H (in ABL; does not reduce interaction with
FT P4HB/PDI and APOB; inhibits triglyceride transfer activity;
FT dbSNP:rs1485375137)"
FT /evidence="ECO:0000269|PubMed:25108285"
FT /id="VAR_074556"
FT VARIANT 540
FT /note="R -> C (in ABL; does not reduce interaction with
FT P4HB/PDI and APOB; inhibits triglyceride transfer activity;
FT dbSNP:rs372321643)"
FT /evidence="ECO:0000269|PubMed:25108285"
FT /id="VAR_074557"
FT VARIANT 540
FT /note="R -> H (in ABL; no loss on localization to the
FT endoplasmic reticulum; reduces interaction with P4HB/PDI;
FT inhibits phospholipid or triglyceride transfer activity;
FT inhibits apolipoprotein B secretion; dbSNP:rs199422220)"
FT /evidence="ECO:0000269|PubMed:10679949,
FT ECO:0000269|PubMed:23475612, ECO:0000269|PubMed:25108285,
FT ECO:0000269|PubMed:8939939"
FT /id="VAR_010642"
FT VARIANT 590
FT /note="S -> I (in ABL; no loss on localization to the
FT endoplasmic reticulum; does not reduce interaction with
FT P4HB/PDI; inhibits phospholipid or triglyceride transfer
FT activity; inhibits apolipoprotein B secretion;
FT dbSNP:rs199422222)"
FT /evidence="ECO:0000269|PubMed:10679949,
FT ECO:0000269|PubMed:23475612"
FT /id="VAR_010643"
FT VARIANT 649
FT /note="N -> S (in ABL; unknown pathological significance;
FT does not reduce interaction with P4HB/PDI and APOB; reduces
FT triglyceride transfer activity)"
FT /evidence="ECO:0000269|PubMed:25108285"
FT /id="VAR_074558"
FT VARIANT 746
FT /note="G -> E (in ABL; no loss on localization to the
FT endoplasmic reticulum; does not reduce interaction with
FT P4HB/PDI; inhibits phospholipid or triglyceride transfer
FT activity; inhibits apolipoprotein B secretion;
FT dbSNP:rs767833468)"
FT /evidence="ECO:0000269|PubMed:10679949,
FT ECO:0000269|PubMed:23475612"
FT /id="VAR_010644"
FT VARIANT 780
FT /note="N -> Y (in ABL; no loss on localization to the
FT endoplasmic reticulum; does not reduce interaction with
FT P4HB/PDI; inhibits phospholipid or triglyceride transfer
FT activity; inhibits apolipoprotein B secretion;
FT dbSNP:rs199422221)"
FT /evidence="ECO:0000269|PubMed:10946006,
FT ECO:0000269|PubMed:23475612"
FT /id="VAR_014019"
FT MUTAGEN 169
FT /note="D->E: No loss on localization to the endoplasmic
FT reticulum and does not reduce interaction with APOB or
FT P4HB/PDI, does partially reduce phospholipid or
FT triglyceride transfer activity and apolipoprotein B
FT secretion."
FT /evidence="ECO:0000269|PubMed:26224785"
FT MUTAGEN 187
FT /note="K->L: No loss on localization to the endoplasmic
FT reticulum and does not reduce interaction with APOB, but
FT inhibits interaction with P4HB/PDI, phospholipid or
FT triglyceride transfer activity and apolipoprotein B
FT secretion."
FT /evidence="ECO:0000269|PubMed:26224785"
FT MUTAGEN 187
FT /note="K->R: No loss on localization to the endoplasmic
FT reticulum, does not reduce interaction with APOB or
FT P4HB/PDI, partially inhibits triglyceride transfer
FT activity, does not inhibit phospholipid transfer activity
FT and apolipoprotein B secretion."
FT /evidence="ECO:0000269|PubMed:26224785"
FT MUTAGEN 189
FT /note="K->L: No loss on localization to the endoplasmic
FT reticulum and does not reduce interaction with APOB, but
FT inhibits interaction with P4HB/PDI, phospholipid or
FT triglyceride transfer activity and apolipoprotein B
FT secretion."
FT /evidence="ECO:0000269|PubMed:26224785"
FT MUTAGEN 189
FT /note="K->R: No loss on localization to the endoplasmic
FT reticulum, does not reduce interaction with APOB or
FT P4HB/PDI, partially inhibits triglyceride transfer
FT activity, does not inhibit phospholipid transfer activity
FT and apolipoprotein B secretion."
FT /evidence="ECO:0000269|PubMed:26224785"
FT MUTAGEN 435
FT /note="L->E: No loss on localization to the endoplasmic
FT reticulum. Inhibits triglyceride transfer activity."
FT /evidence="ECO:0000269|PubMed:22236406"
FT MUTAGEN 435
FT /note="L->V: No loss on localization to the endoplasmic
FT reticulum. Does not inhibit triglyceride transfer
FT activity."
FT /evidence="ECO:0000269|PubMed:22236406"
FT MUTAGEN 528
FT /note="Y->F: Does not inhibit triglyceride transfer
FT activity."
FT /evidence="ECO:0000269|PubMed:25108285"
FT MUTAGEN 528
FT /note="Y->K: Inhibits triglyceride transfer activity."
FT /evidence="ECO:0000269|PubMed:25108285"
FT MUTAGEN 540
FT /note="R->A: Strongly reduces triglyceride transfer
FT activity."
FT /evidence="ECO:0000269|PubMed:25108285"
FT MUTAGEN 540
FT /note="R->K: Does not inhibit triglyceride transfer
FT activity and apolipoprotein B secretion."
FT /evidence="ECO:0000269|PubMed:25108285,
FT ECO:0000269|PubMed:8939939"
FT MUTAGEN 878
FT /note="C->S: Inhibits triglyceride transfer activity."
FT /evidence="ECO:0000269|PubMed:8533758"
FT CONFLICT 585
FT /note="F -> L (in Ref. 2; CAA42200)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 894 AA; 99351 MW; B20260C136BDAB9F CRC64;
MILLAVLFLC FISSYSASVK GHTTGLSLNN DRLYKLTYST EVLLDRGKGK LQDSVGYRIS
SNVDVALLWR NPDGDDDQLI QITMKDVNVE NVNQQRGEKS IFKGKSPSKI MGKENLEALQ
RPTLLHLIHG KVKEFYSYQN EAVAIENIKR GLASLFQTQL SSGTTNEVDI SGNCKVTYQA
HQDKVIKIKA LDSCKIARSG FTTPNQVLGV SSKATSVTTY KIEDSFVIAV LAEETHNFGL
NFLQTIKGKI VSKQKLELKT TEAGPRLMSG KQAAAIIKAV DSKYTAIPIV GQVFQSHCKG
CPSLSELWRS TRKYLQPDNL SKAEAVRNFL AFIQHLRTAK KEEILQILKM ENKEVLPQLV
DAVTSAQTSD SLEAILDFLD FKSDSSIILQ ERFLYACGFA SHPNEELLRA LISKFKGSIG
SSDIRETVMI ITGTLVRKLC QNEGCKLKAV VEAKKLILGG LEKAEKKEDT RMYLLALKNA
LLPEGIPSLL KYAEAGEGPI SHLATTALQR YDLPFITDEV KKTLNRIYHQ NRKVHEKTVR
TAAAAIILNN NPSYMDVKNI LLSIGELPQE MNKYMLAIVQ DILRFEMPAS KIVRRVLKEM
VAHNYDRFSR SGSSSAYTGY IERSPRSAST YSLDILYSGS GILRRSNLNI FQYIGKAGLH
GSQVVIEAQG LEALIAATPD EGEENLDSYA GMSAILFDVQ LRPVTFFNGY SDLMSKMLSA
SGDPISVVKG LILLIDHSQE LQLQSGLKAN IEVQGGLAID ISGAMEFSLW YRESKTRVKN
RVTVVITTDI TVDSSFVKAG LETSTETEAG LEFISTVQFS QYPFLVCMQM DKDEAPFRQF
EKKYERLSTG RGYVSQKRKE SVLAGCEFPL HQENSEMCKV VFAPQPDSTS SGWF
