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Database: UniProt
Entry: P55157
LinkDB: P55157
Original site: P55157 
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   02-JUN-2021, entry version 183.
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;
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   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   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; 240 antibodies.
DR   DNASU; 4547; -.
DR   Ensembl; ENST00000265517; ENSP00000265517; ENSG00000138823. [P55157-1]
DR   Ensembl; ENST00000422897; ENSP00000407350; ENSG00000138823. [P55157-2]
DR   Ensembl; ENST00000457717; ENSP00000400821; ENSG00000138823. [P55157-1]
DR   GeneID; 4547; -.
DR   KEGG; hsa:4547; -.
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:ENSG00000138823.12; -.
DR   eggNOG; KOG4337; Eukaryota.
DR   GeneTree; ENSGT00390000011412; -.
DR   HOGENOM; CLU_014703_0_0_1; -.
DR   InParanoid; P55157; -.
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   SIGNOR; P55157; -.
DR   BioGRID-ORCS; 4547; 4 hits in 986 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 119 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: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: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: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; IPR001747; Lipid_transpt_N.
DR   InterPro; IPR011030; Lipovitellin_superhlx_dom.
DR   InterPro; IPR039988; MTTP.
DR   InterPro; IPR015816; Vitellinogen_b-sht_N.
DR   PANTHER; PTHR13024; PTHR13024; 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
//
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