MTP_DANRE
ID MTP_DANRE Reviewed; 884 AA.
AC A0A0R4IVV0; A4IGB9; Q8AXV7;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Microsomal triglyceride transfer protein large subunit {ECO:0000303|PubMed:15614773};
DE Flags: Precursor;
GN Name=mttp {ECO:0000305}; Synonyms=mtp {ECO:0000312|ZFIN:ZDB-GENE-040419-2};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP INDUCTION.
RC TISSUE=Intestine;
RX PubMed=15614773; DOI=10.1002/dvdy.20251;
RA Marza E., Barthe C., Andre M., Villeneuve L., Helou C., Babin P.J.;
RT "Developmental expression and nutritional regulation of a zebrafish gene
RT homologous to mammalian microsomal triglyceride transfer protein large
RT subunit.";
RL Dev. Dyn. 232:506-518(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Singapore {ECO:0000305}; TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP ACTIVITY REGULATION, INDUCTION, DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17176039; DOI=10.1021/bi0619268;
RA Schlegel A., Stainier D.Y.;
RT "Microsomal triglyceride transfer protein is required for yolk lipid
RT utilization and absorption of dietary lipids in zebrafish larvae.";
RL Biochemistry 45:15179-15187(2006).
RN [5] {ECO:0000305}
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=17924655; DOI=10.1021/bi700762z;
RA Rava P., Hussain M.M.;
RT "Acquisition of triacylglycerol transfer activity by microsomal
RT triglyceride transfer protein during evolution.";
RL Biochemistry 46:12263-12274(2007).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=22581286; DOI=10.1038/nm.2759;
RA Avraham-Davidi I., Ely Y., Pham V.N., Castranova D., Grunspan M.,
RA Malkinson G., Gibbs-Bar L., Mayseless O., Allmog G., Lo B., Warren C.M.,
RA Chen T.T., Ungos J., Kidd K., Shaw K., Rogachev I., Wan W., Murphy P.M.,
RA Farber S.A., Carmel L., Shelness G.S., Iruela-Arispe M.L., Weinstein B.M.,
RA Yaniv K.;
RT "ApoB-containing lipoproteins regulate angiogenesis by modulating
RT expression of VEGF receptor 1.";
RL Nat. Med. 18:967-973(2012).
CC -!- FUNCTION: Catalyzes the transport of triglyceride between phospholipid
CC surfaces (PubMed:17924655). Catalyzes the transport of cholesteryl
CC ester, and phospholipid between phospholipid surfaces (By similarity).
CC Required for the assembly and secretion of plasma lipoproteins that
CC contain apolipoprotein B (PubMed:22581286, PubMed:17924655). Required
CC for yolk lipid utilization and absorption of dietary lipids in larvae
CC (PubMed:17176039). {ECO:0000250|UniProtKB:P55157,
CC ECO:0000269|PubMed:17176039, ECO:0000269|PubMed:17924655,
CC ECO:0000269|PubMed:22581286}.
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:0000250|UniProtKB:P55157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38572;
CC Evidence={ECO:0000250|UniProtKB:P55157};
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:0000250|UniProtKB:P55157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38896;
CC Evidence={ECO:0000250|UniProtKB:P55157};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a cholesterol ester(in) = a cholesterol ester(out);
CC Xref=Rhea:RHEA:39007, ChEBI:CHEBI:17002;
CC Evidence={ECO:0000250|UniProtKB:P55157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39008;
CC Evidence={ECO:0000250|UniProtKB:P55157};
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:0000250|UniProtKB:P55157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39012;
CC Evidence={ECO:0000250|UniProtKB:P55157};
CC -!- ACTIVITY REGULATION: Inhibited by naringenin.
CC {ECO:0000269|PubMed:17176039}.
CC -!- SUBUNIT: Heterodimer; heterodimerizes with the protein disulfide
CC isomerase. {ECO:0000269|PubMed:17924655}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:17924655}. Golgi apparatus
CC {ECO:0000250|UniProtKB:P55157}. Note=Colocalizes with P4HB/PDI in the
CC endoplasmic reticulum. {ECO:0000269|PubMed:17924655}.
CC -!- TISSUE SPECIFICITY: Highest expression in the proximal part of the
CC anterior intestine. Lower expression in the distal part of the anterior
CC intestine, in the posterior portion of the intestinal tube and liver.
CC Very low expression levels in heart, brain, ovary, testis and kidney.
CC {ECO:0000269|PubMed:15614773}.
CC -!- DEVELOPMENTAL STAGE: Detected in the blastoderm margin by 4 hours post-
CC fertilization (hpf). Expressed in the yolk syncytial layer (YSL) from 9
CC hpf to 24 hpf. By 48 hpf expression decreases in the extraembryonic YSL
CC and is detected in the embryonic liver primordium and intestinal tube
CC in which strongly expressed by 4 days post-fertilization (dpf). At 6
CC and 15 dpf expression is restricted to the two main liver lobes and the
CC anterior part of the intestine including the intestinal bulb, but not
CC detected in the pharynx or posterior intestine. Expressed in the
CC enterocytes of the anterior part of intestine as well as in the hepatic
CC cells in 15 dpf larvae. The total level of expression is very small
CC before 2 hpf, increasing significantly between 2 and 5 hpf, and
CC remaining high at 6 and 9 hpf. A significant decrease in the expression
CC level is detected at 12 hpf and low level remains until the end of
CC embryogenesis, which occurs by 72 hpf. {ECO:0000269|PubMed:15614773}.
CC -!- INDUCTION: Expression is strongly up-regulated in the anterior
CC intestine and to a lesser extent in liver in response to feeding in
CC both larvae and adults (at protein level) (PubMed:15614773). Protein
CC levels are not changed in 1 or 6 hours after feeding (PubMed:17176039).
CC {ECO:0000269|PubMed:15614773, ECO:0000269|PubMed:17176039}.
CC -!- DISRUPTION PHENOTYPE: Larvae do not absorb dietary neutral lipids,
CC consume very little yolk, are small and die by 6 days post-
CC fertilization (dpf) with pronounced edema. No defects in intestinal
CC absorption of short chain fatty acids. Loss of visualization of neutral
CC lipids in the vasculature, heart and head structures by oil red o
CC staining. Levels of apolipoprotein B, vitellogenin and lipovitellin
CC unchanged. No cardiovascular defects or global intestinal function
CC impairment. Increased expression of Foza2 and Pgc1 proteins
CC (PubMed:17176039). Leads to excess angiogenesis and yolk absorption
CC defects. Decreased mRNA levels of flt1 at 24 hours post-fertilization
CC (hpf) with no change in the mRNA levels of kdrl or flt4 or in other
CC vascular genes (PubMed:22581286). {ECO:0000269|PubMed:17176039,
CC ECO:0000269|PubMed:22581286}.
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DR EMBL; AJ428850; CAD21747.1; -; mRNA.
DR EMBL; BX908747; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CABZ01049941; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CABZ01050432; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU914777; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FO704847; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC135020; AAI35021.1; -; mRNA.
DR RefSeq; NP_998135.1; NM_212970.1.
DR AlphaFoldDB; A0A0R4IVV0; -.
DR SMR; A0A0R4IVV0; -.
DR STRING; 7955.ENSDARP00000024667; -.
DR PaxDb; A0A0R4IVV0; -.
DR Ensembl; ENSDART00000015251; ENSDARP00000024667; ENSDARG00000008637.
DR GeneID; 406207; -.
DR KEGG; dre:406207; -.
DR CTD; 4547; -.
DR ZFIN; ZDB-GENE-040419-2; mttp.
DR eggNOG; KOG4337; Eukaryota.
DR GeneTree; ENSGT00390000011412; -.
DR OMA; HVWGGSA; -.
DR OrthoDB; 673565at2759; -.
DR Reactome; R-DRE-8866423; VLDL assembly.
DR Reactome; R-DRE-8963888; Chylomicron assembly.
DR Reactome; R-DRE-8964041; LDL remodeling.
DR PRO; PR:A0A0R4IVV0; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 1.
DR Bgee; ENSDARG00000008637; Expressed in intestine and 21 other tissues.
DR ExpressionAtlas; A0A0R4IVV0; baseline.
DR GO; GO:0016323; C:basolateral plasma membrane; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0120013; F:lipid transfer activity; IDA:UniProtKB.
DR GO; GO:0005319; F:lipid transporter activity; ISS:ZFIN.
DR GO; GO:1904121; F:phosphatidylethanolamine transfer activity; ISS:UniProtKB.
DR GO; GO:0005548; F:phospholipid transporter activity; IBA:GO_Central.
DR GO; GO:0042632; P:cholesterol homeostasis; IBA:GO_Central.
DR GO; GO:0007586; P:digestion; IEP:ZFIN.
DR GO; GO:0006629; P:lipid metabolic process; IMP:ZFIN.
DR GO; GO:0006869; P:lipid transport; ISS:ZFIN.
DR GO; GO:0042158; P:lipoprotein biosynthetic process; IMP:ZFIN.
DR GO; GO:0042157; P:lipoprotein metabolic process; IBA:GO_Central.
DR GO; GO:0042953; P:lipoprotein transport; IDA:UniProtKB.
DR GO; GO:0015909; P:long-chain fatty acid transport; IMP:ZFIN.
DR GO; GO:0001579; P:medium-chain fatty acid transport; IMP:ZFIN.
DR GO; GO:0034377; P:plasma lipoprotein particle assembly; ISS:UniProtKB.
DR GO; GO:0009306; P:protein secretion; ISS:UniProtKB.
DR GO; GO:0002040; P:sprouting angiogenesis; IMP:ZFIN.
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 Disulfide bond; Endoplasmic reticulum; Glycoprotein; Golgi apparatus;
KW Lipid transport; Lipid-binding; Reference proteome; Signal; Transport.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..884
FT /note="Microsomal triglyceride transfer protein large
FT subunit"
FT /evidence="ECO:0000255"
FT /id="PRO_5006451763"
FT DOMAIN 26..660
FT /note="Vitellogenin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00557"
FT CARBOHYD 348
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 787
FT /note="N-linked (GlcNAc...) asparagine"
FT DISULFID 172..192
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00557"
FT DISULFID 438..443
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00557"
FT CONFLICT 37
FT /note="S -> G (in Ref. 1; CAD21747)"
FT /evidence="ECO:0000305"
FT CONFLICT 50
FT /note="G -> E (in Ref. 1; CAD21747 and 3; AAI35021)"
FT /evidence="ECO:0000305"
FT CONFLICT 81
FT /note="K -> Q (in Ref. 1; CAD21747 and 3; AAI35021)"
FT /evidence="ECO:0000305"
FT CONFLICT 447
FT /note="A -> V (in Ref. 1; CAD21747)"
FT /evidence="ECO:0000305"
FT CONFLICT 488
FT /note="A -> T (in Ref. 1; CAD21747)"
FT /evidence="ECO:0000305"
FT CONFLICT 672
FT /note="L -> P (in Ref. 1; CAD21747)"
FT /evidence="ECO:0000305"
FT CONFLICT 718
FT /note="M -> T (in Ref. 1; CAD21747)"
FT /evidence="ECO:0000305"
FT CONFLICT 850
FT /note="M -> T (in Ref. 3; AAI35021)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 884 AA; 96988 MW; F152B03F919EA752 CRC64;
MMPVAGLLLC VTAVLCTSAL GAGPRLDNGK LYRYSYSTEV GLNRPTGSPG GNVGFRISSD
VDINLAWRNP EIQDEQLLQV KISNIQVESA GKHSRKNNIF HGSSAESILG KVRLEALQRP
FLVLWKMGKI RSLYAQKAEP ATVKNLKRGV ASMLMMQLKS GKMSEADASG KCLVEYKVNK
HQVIRTKHLE TCKSQETGFT THSPVLGISG KCAAETVITL ENGIIKSADA KETHVLSINA
RHKAATKVLS RQSLTLKAIE AGPAEVAGKD VAGVVKALDD KFLSVGVIVE KTKPKCKGCP
NLMETWKAVR SQLEPNSLSK AEAPRSFLTL VHSLRKSSKS EILTVLQNCS KTALPQLVDA
VTSAQTPSSL SAILEFLDFS KKDGLILQER FLYACGFASH PTESMLQSLL EVSQGKIGST
EIKESVVIIM GALLRKLCLK GACDLPAVLK VKELLLAGPD STQEESEVQM YLLALKNALL
PEGIPVLAKY AESEVGAYST IAITALQRYD PALITAEVKK ALNRIYHQNQ RIYEKNVRAA
AADVIMSSNP SYMEVKNLLL SIGHLPHEMN KYMLSKIQDV LRFQMPAYKL VRQVMKDMIS
HNYDRFSKTG SSSAYSGFMA ETVDVTCTYN LDILYSGSGV LRRSNMNIYG QSNNALLHGL
QVTIEAQGLE SLIAATPDEG EEELESFAGM SALLFDVQLR PVTFFKGYSD LMSKMFSMSG
DPINVVKGLI LLTDHSQVIP LQSGLRASAE FQAGLSIDIS GGMEFSLWYR ESKTSVNNRG
ALVIIGNMTV DTDFVSAGVE VGFETEATLD FITTVQFSEY PFLVCMQMDK TTFPFRETVS
KQEKLPTGQM FSRKRSRDQV VPGSEFPLHQ ENSNMCKKVF EPAW
