O08601 (MTP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Microsomal triglyceride transfer protein large subunit

Gene names

Name:	Mttp
Synonyms:	Mtp

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	894 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces. Required for the secretion of plasma lipoproteins that contain apolipoprotein B. May be involved in regulating cholesteryl ester biosynthesis in cells that produce lipoproteins. Loads phospholipid into the C1D1 antigen-binding groove. Isoform 2 is critical for the development of natural killer T (NKT) cells. May have a role in the biogenesis of lipid droplets. Ref.2 Ref.9 Ref.10
Subunit structure	Heterodimer composed of MTTP and of protein disulfide isomerase (P4HB/PDI).
Subcellular location	Isoform 1: Endoplasmic reticulum. Note: Localized to the endoplasmic reticulum according to Ref.2. Ref.2 Ref.9 Isoform 2: Endoplasmic reticulum. Golgi apparatus. Note: Localized to the endoplasmic reticulum according to Ref.2. Localized to the Golgi apparatus according to Ref.9. Ref.2 Ref.9
Tissue specificity	Expressed in heart. Isoform 1 is mainly expressed in the intestine and the liver, and at lower levels in white and brown fat cells. Isoform 2 is ubiquitous, and is the major isoform in hematopoietic cells and adipocytes. Ref.2 Ref.6 Ref.9
Developmental stage	Expression in the yolk sac tissues followed by expression in the primordial liver cell nests as early as day 9 post-coitum (E9.5). Intestinal expression is detected around E12.5 and attains full adult expression patterns by E14.5. Ref.8
Induction	Up-regulated by FOXO1. Ref.11
Disruption phenotype	Lowers plasma and tissue triglyceride levels, and increases cellular free cholesterol. Ref.7 Ref.10
Sequence similarities	Contains 1 vitellogenin domain.

Ontologies

Keywords
Biological process	Cholesterol metabolism Lipid metabolism Steroid metabolism Sterol metabolism Transport
Cellular component	Endoplasmic reticulum Golgi apparatus
Coding sequence diversity	Alternative promoter usage
Domain	Signal
Ligand	Lipid-binding
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol homeostasis Inferred from mutant phenotype Ref.7. Source: MGI cholesterol metabolic process Inferred from electronic annotation. Source: UniProtKB-KW lipoprotein transport Inferred from direct assay Ref.9. Source: MGI protein lipidation Inferred from direct assay PubMed 12072432. Source: MGI response to calcium ion Inferred from electronic annotation. Source: Compara triglyceride metabolic process Inferred from direct assay PubMed 12072432. Source: MGI
Cellular_component	Golgi apparatus Inferred from direct assay Ref.9. Source: MGI basolateral plasma membrane Inferred from electronic annotation. Source: Compara brush border membrane Inferred from electronic annotation. Source: Compara endoplasmic reticulum Inferred from direct assay Ref.9. Source: MGI membrane-bounded vesicle Inferred from electronic annotation. Source: Compara microvillus membrane Inferred from electronic annotation. Source: Compara rough endoplasmic reticulum Inferred from electronic annotation. Source: Compara
Molecular_function	lipid binding Inferred from electronic annotation. Source: UniProtKB-KW lipid transporter activity Inferred from direct assay PubMed 12072432. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative promoter usage. [Align] [Select]

Isoform 1 (identifier: O08601-1)

Also known as: MTP-A;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O08601-2)

Also known as: MTPv1; MTP-B;

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: MILLAVLFLCFFSSYSASVK → MTVVMGKCQVSDGRQLLLFYAVLLLFPTLCAMQNS

Note: Cleaved by signal peptidase between residues Gln-33 and Asn-34 (PubMed:17312007 and PubMed:17635917).

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21
	Chain	22 – 894	873	Microsomal triglyceride transfer protein large subunit		PRO_0000041595
Regions
	Domain	28 – 658	631	Vitellogenin
Natural variations
	Alternative sequence	1 – 20	20	MILLA…SASVK → MTVVMGKCQVSDGRQLLLFY AVLLLFPTLCAMQNS in isoform 2.		VSP_038546
Experimental info
	Sequence conflict	654 – 656	3	GKA → KGT in AAB51431. Ref.1
	Sequence conflict	654 – 656	3	GKA → KGT in ACB41497. Ref.2
	Sequence conflict	800	1	V → L in AAB51431. Ref.1
	Sequence conflict	800	1	V → L in ACB41497. Ref.2
	Sequence conflict	800	1	V → L in AAH12686. Ref.4
	Sequence conflict	800	1	V → L in EDL12110. Ref.5
	Sequence conflict	872	1	E → Q in AAB51431. Ref.1
	Sequence conflict	872	1	E → Q in ACB41497. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (MTP-A) [UniParc]. Last modified January 19, 2010. Version 2. Checksum: 3D8E5EB470CAA6FC	FASTA	894	99,099
	10 20 30 40 50 60 MILLAVLFLC FFSSYSASVK GHTTGLSLNN ERLYKLTYST EVFLDGGKGK PQDSVGYKIS 70 80 90 100 110 120 SDVDVVLLWR NPDGDDDQVI QVTITAVNVE NAGQQRGEKS IFQGKSTPKI IGKDNLEALQ 130 140 150 160 170 180 RPMLLHLVRG KVKEFYSYEN EPVGIENLKR GLASLFQMQL SSGTTNEVDI SGDCKVTYQA 190 200 210 220 230 240 QQDKVVKIKA LDTCKIERSG FTTANQVLGV SSKATSVTTY KIEDSFVTAV LAEETRAFAL 250 260 270 280 290 300 NFQQTIAGKI VSKQKLELKT TEAGPRMIPG KQVAGVIKAV DSKYKAIPIV GQVLERVCKG 310 320 330 340 350 360 CPSLAEHWKS IRKNLEPENL SKAEAVQSFL AFIQHLRTSR REEILQILKA EKKEVLPQLV 370 380 390 400 410 420 DAVTSAQTPD SLEAILDFLD FKSDSSIILQ ERFLYACGFA THPDEELLRA LLSKFKGSFA 430 440 450 460 470 480 SNDIRESVMI IIGALVRKLC QNEGCKLKAV VEAKKLILGG LEKPEKKEDT TMYLLALKNA 490 500 510 520 530 540 LLPEGIPLLL KYAEAGEGPV SHLATTVLQR YDVSFITDEV KKTLNRIYHQ NRKVHEKTVR 550 560 570 580 590 600 TTAAAVILKN PSYMDVKNIL LSIGELPKEM NKYMLTVVQD ILHFEMPASK MIRRVLKEMA 610 620 630 640 650 660 VHNYDRFSKS GSSSAYTGYV ERSPRAASTY SLDILYSGSG ILRRSNLNIF QYIGKAELHG 670 680 690 700 710 720 SQVVIEAQGL EGLIAATPDE GEENLDSYAG MSAILFDVQL RPVTFFNGYS DLMSKMLSAS 730 740 750 760 770 780 GDPVSVVKGL ILLIDHSQDI QLQSGLKANM EIQGGLAIDI SGSMEFSLWY RESKTRVKNR 790 800 810 820 830 840 VAVVITSDVT VDASFVKAGV ESRAETEAGL EFISTVQFSQ YPFLVCMQMD KAEAPLRQFE 850 860 870 880 890 TKYERLSTGR GYVSRRRKES LVAGCELPLH QENSEMCNVV FPPQPESDNS GGWF
	Isoform 2 (MTPv1) (MTP-B) [UniParc]. Checksum: 522AD2682867FA4A	FASTA	909	100,751
	10 20 30 40 50 60 MTVVMGKCQV SDGRQLLLFY AVLLLFPTLC AMQNSGHTTG LSLNNERLYK LTYSTEVFLD 70 80 90 100 110 120 GGKGKPQDSV GYKISSDVDV VLLWRNPDGD DDQVIQVTIT AVNVENAGQQ RGEKSIFQGK 130 140 150 160 170 180 STPKIIGKDN LEALQRPMLL HLVRGKVKEF YSYENEPVGI ENLKRGLASL FQMQLSSGTT 190 200 210 220 230 240 NEVDISGDCK VTYQAQQDKV VKIKALDTCK IERSGFTTAN QVLGVSSKAT SVTTYKIEDS 250 260 270 280 290 300 FVTAVLAEET RAFALNFQQT IAGKIVSKQK LELKTTEAGP RMIPGKQVAG VIKAVDSKYK 310 320 330 340 350 360 AIPIVGQVLE RVCKGCPSLA EHWKSIRKNL EPENLSKAEA VQSFLAFIQH LRTSRREEIL 370 380 390 400 410 420 QILKAEKKEV LPQLVDAVTS AQTPDSLEAI LDFLDFKSDS SIILQERFLY ACGFATHPDE 430 440 450 460 470 480 ELLRALLSKF KGSFASNDIR ESVMIIIGAL VRKLCQNEGC KLKAVVEAKK LILGGLEKPE 490 500 510 520 530 540 KKEDTTMYLL ALKNALLPEG IPLLLKYAEA GEGPVSHLAT TVLQRYDVSF ITDEVKKTLN 550 560 570 580 590 600 RIYHQNRKVH EKTVRTTAAA VILKNPSYMD VKNILLSIGE LPKEMNKYML TVVQDILHFE 610 620 630 640 650 660 MPASKMIRRV LKEMAVHNYD RFSKSGSSSA YTGYVERSPR AASTYSLDIL YSGSGILRRS 670 680 690 700 710 720 NLNIFQYIGK AELHGSQVVI EAQGLEGLIA ATPDEGEENL DSYAGMSAIL FDVQLRPVTF 730 740 750 760 770 780 FNGYSDLMSK MLSASGDPVS VVKGLILLID HSQDIQLQSG LKANMEIQGG LAIDISGSME 790 800 810 820 830 840 FSLWYRESKT RVKNRVAVVI TSDVTVDASF VKAGVESRAE TEAGLEFIST VQFSQYPFLV 850 860 870 880 890 900 CMQMDKAEAP LRQFETKYER LSTGRGYVSR RRKESLVAGC ELPLHQENSE MCNVVFPPQP ESDNSGGWF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mouse microsomal triglyceride transfer protein large subunit: cDNA cloning, tissue-specific expression and chromosomal localization." Nakamuta M., Chang B.H., Hoogeveen R., Li W.H., Chan L. Genomics 33:313-316(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver and Small intestine.
[2]	"MTP regulated by an alternate promoter is essential for NKT cell development." Dougan S.K., Rava P., Hussain M.M., Blumberg R.S. J. Exp. Med. 204:533-545(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE PROMOTER USAGE, FUNCTION, SUBCELLULAR LOCATION, PROCESSING, TISSUE SPECIFICITY. Strain: C57BL/6J. Tissue: Thymus.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Amnion.
[4]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: FVB/N. Tissue: Liver.
[6]	"Apo B100-containing lipoproteins are secreted by the heart." Boren J., Veniant M.M., Young S.G. J. Clin. Invest. 101:1197-1202(1998) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"A deficiency of microsomal triglyceride transfer protein reduces apolipoprotein B secretion." Leung G.K., Veniant M.M., Kim S.K., Zlot C.H., Raabe M., Bjorkegren J., Neese R.A., Hellerstein M.K., Young S.G. J. Biol. Chem. 275:7515-7520(2000) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[8]	"Microsomal triglyceride transfer protein expression during mouse development." Shelton J.M., Lee M.H., Richardson J.A., Patel S.B. J. Lipid Res. 41:532-537(2000) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[9]	"Identification of a novel isoform of microsomal triglyceride transfer protein." Mohler P.J., Zhu M.Y., Blade A.M., Ham A.J., Shelness G.S., Swift L.L. J. Biol. Chem. 282:26981-26988(2007) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE PROMOTER USAGE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[10]	"Microsomal triglyceride transfer protein enhances cellular cholesteryl esterification by relieving product inhibition." Iqbal J., Rudel L.L., Hussain M.M. J. Biol. Chem. 283:19967-19980(2008) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[11]	"FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice." Kamagate A., Qu S., Perdomo G., Su D., Kim D.H., Slusher S., Meseck M., Dong H.H. J. Clin. Invest. 118:2347-2364(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY FOXO1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L47970 mRNA. Translation: AAB51431.1. EU553486 mRNA. Translation: ACB41497.1. AK146553 mRNA. Translation: BAE27255.1. CH466532 Genomic DNA. Translation: EDL12110.1. BC012686 mRNA. Translation: AAH12686.1.
IPI	IPI00309073. IPI00943405.
RefSeq	NP_001156929.1. NM_001163457.1. NP_032668.2. NM_008642.2.
UniGene	Mm.2941.
3D structure databases
ProteinModelPortal	O08601.
SMR	O08601. Positions 470-508.
ModBase	Search...
Protein-protein interaction databases
IntAct	O08601. 4 interactions.
MINT	MINT-1864006.
STRING	10090.ENSMUSP00000029805.
PTM databases
PhosphoSite	O08601.
Proteomic databases
PaxDb	O08601.
PRIDE	O08601.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000029805; ENSMUSP00000029805; ENSMUSG00000028158. ENSMUST00000098580; ENSMUSP00000096179; ENSMUSG00000028158.
GeneID	17777.
KEGG	mmu:17777.
UCSC	uc008rmw.2. mouse. uc008rmx.2. mouse.
Organism-specific databases
CTD	4547.
MGI	MGI:106926. Mttp.
Phylogenomic databases
eggNOG	NOG272516.
GeneTree	ENSGT00390000011412.
HOGENOM	HOG000113688.
HOVERGEN	HBG006416.
InParanoid	Q91X33.
KO	K14463.
OMA	RPVTFFN.
OrthoDB	EOG405S0C.
Gene expression databases
ArrayExpress	O08601.
Bgee	O08601.
CleanEx	MM_MTTP.
Genevestigator	O08601.
GermOnline	ENSMUSG00000028158. Mus musculus.
Family and domain databases
Gene3D	1.25.10.20. 1 hit. 2.30.230.10. 1 hit.
InterPro	IPR015819. Lipid_transp_b-sht_shell. IPR001747. Lipid_transpt_N. IPR015816. Vitellinogen_b-sht_N. IPR011030. Vitellinogen_superhlx. [Graphical view]
Pfam	PF01347. Vitellogenin_N. 1 hit. [Graphical view]
SMART	SM00638. LPD_N. 1 hit. [Graphical view]
SUPFAM	SSF56968. Lipid_transp_b-sht_shell. 1 hit. SSF48431. LV_superhelical. 1 hit.
PROSITE	PS51211. VITELLOGENIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MTTP. mouse.
NextBio	292509.
SOURCE	Search...

Entry information

Entry name

MTP_MOUSE

Accession

Primary (citable) accession number: O08601
Secondary accession number(s): B2CXA7, Q3UJA0, Q91X33

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 19, 2010
Last modified:	May 29, 2013
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program