ID   TTPA_MOUSE              Reviewed;         278 AA.
AC   Q8BWP5; Q9CW51; Q9JL07;
DT   26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   24-JAN-2024, entry version 145.
DE   RecName: Full=Alpha-tocopherol transfer protein;
DE            Short=Alpha-TTP;
GN   Name=Ttpa;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Liver;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-271.
RC   STRAIN=C57BL/6J;
RA   Fechner H.;
RL   Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 21-278 IN COMPLEXES WITH
RP   ALPHA-TOCOPHEROL; PHOSPHATIDYLINOSITOL-3,4-BISPHOSPHATE AND
RP   PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE, FUNCTION, SUBUNIT, AND MUTAGENESIS
RP   OF ARG-59; LYS-217 AND ARG-221.
RX   PubMed=23599266; DOI=10.1126/science.1233508;
RA   Kono N., Ohto U., Hiramatsu T., Urabe M., Uchida Y., Satow Y., Arai H.;
RT   "Impaired alpha-TTP-PIPs interaction underlies familial vitamin E
RT   deficiency.";
RL   Science 340:1106-1110(2013).
CC   -!- FUNCTION: Binds (+)-alpha-tocopherol, enhances its transfer between
CC       separate membranes, and stimulates its release from liver cells. Binds
CC       both phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol
CC       4,5-bisphosphate; the resulting conformation change is important for
CC       the release of the bound alpha-tocopherol.
CC       {ECO:0000269|PubMed:23599266}.
CC   -!- SUBUNIT: Monomer and homotetramer. Phosphatidylinositol 4,5-
CC       bisphosphate binding induces the formation of homotetramers.
CC       Phosphatidylinositol 3,4-bisphosphate is less efficient in inducing
CC       tetramerization. {ECO:0000269|PubMed:23599266}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
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DR   EMBL; AK004882; BAB23640.1; -; mRNA.
DR   EMBL; AK050374; BAC34218.1; -; mRNA.
DR   EMBL; AF218416; AAF25956.1; -; mRNA.
DR   CCDS; CCDS17995.1; -.
DR   RefSeq; NP_056582.1; NM_015767.4.
DR   PDB; 3W67; X-ray; 2.61 A; A/B/C/D=21-278.
DR   PDB; 3W68; X-ray; 2.05 A; A/B/C/D=21-278.
DR   PDBsum; 3W67; -.
DR   PDBsum; 3W68; -.
DR   AlphaFoldDB; Q8BWP5; -.
DR   SMR; Q8BWP5; -.
DR   STRING; 10090.ENSMUSP00000095845; -.
DR   iPTMnet; Q8BWP5; -.
DR   PhosphoSitePlus; Q8BWP5; -.
DR   jPOST; Q8BWP5; -.
DR   MaxQB; Q8BWP5; -.
DR   PaxDb; 10090-ENSMUSP00000095845; -.
DR   ProteomicsDB; 298025; -.
DR   Antibodypedia; 55595; 133 antibodies from 17 providers.
DR   DNASU; 50500; -.
DR   Ensembl; ENSMUST00000098244.2; ENSMUSP00000095845.2; ENSMUSG00000073988.14.
DR   GeneID; 50500; -.
DR   KEGG; mmu:50500; -.
DR   UCSC; uc008sci.1; mouse.
DR   AGR; MGI:1354168; -.
DR   CTD; 7274; -.
DR   MGI; MGI:1354168; Ttpa.
DR   VEuPathDB; HostDB:ENSMUSG00000073988; -.
DR   eggNOG; KOG1471; Eukaryota.
DR   GeneTree; ENSGT00940000159203; -.
DR   InParanoid; Q8BWP5; -.
DR   OMA; KQRVYMH; -.
DR   OrthoDB; 522503at2759; -.
DR   PhylomeDB; Q8BWP5; -.
DR   Reactome; R-MMU-8877627; Vitamin E.
DR   BioGRID-ORCS; 50500; 1 hit in 80 CRISPR screens.
DR   ChiTaRS; Ttpa; mouse.
DR   PRO; PR:Q8BWP5; -.
DR   Proteomes; UP000000589; Chromosome 4.
DR   RNAct; Q8BWP5; Protein.
DR   Bgee; ENSMUSG00000073988; Expressed in left lobe of liver and 137 other cell types or tissues.
DR   ExpressionAtlas; Q8BWP5; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; TAS:MGI.
DR   GO; GO:0005770; C:late endosome; ISO:MGI.
DR   GO; GO:0120013; F:lipid transfer activity; IDA:UniProtKB.
DR   GO; GO:1902936; F:phosphatidylinositol bisphosphate binding; IBA:GO_Central.
DR   GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:UniProtKB.
DR   GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR   GO; GO:0019842; F:vitamin binding; ISO:MGI.
DR   GO; GO:0008431; F:vitamin E binding; IDA:UniProtKB.
DR   GO; GO:0001892; P:embryonic placenta development; IMP:MGI.
DR   GO; GO:0120009; P:intermembrane lipid transfer; IDA:UniProtKB.
DR   GO; GO:0051452; P:intracellular pH reduction; ISO:MGI.
DR   GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; ISO:MGI.
DR   GO; GO:0090212; P:negative regulation of establishment of blood-brain barrier; IMP:BHF-UCL.
DR   GO; GO:0001890; P:placenta development; IMP:MGI.
DR   GO; GO:1900223; P:positive regulation of amyloid-beta clearance; IMP:MGI.
DR   GO; GO:0009268; P:response to pH; ISO:MGI.
DR   GO; GO:0009636; P:response to toxic substance; IMP:BHF-UCL.
DR   GO; GO:0042360; P:vitamin E metabolic process; IMP:BHF-UCL.
DR   GO; GO:0051180; P:vitamin transport; IDA:UniProtKB.
DR   CDD; cd00170; SEC14; 1.
DR   Gene3D; 1.20.5.1200; Alpha-tocopherol transfer; 1.
DR   Gene3D; 3.40.525.10; CRAL-TRIO lipid binding domain; 1.
DR   Gene3D; 1.10.8.20; N-terminal domain of phosphatidylinositol transfer protein sec14p; 1.
DR   InterPro; IPR001251; CRAL-TRIO_dom.
DR   InterPro; IPR036865; CRAL-TRIO_dom_sf.
DR   InterPro; IPR011074; CRAL/TRIO_N_dom.
DR   InterPro; IPR036273; CRAL/TRIO_N_dom_sf.
DR   PANTHER; PTHR10174:SF225; ALPHA-TOCOPHEROL TRANSFER PROTEIN; 1.
DR   PANTHER; PTHR10174; ALPHA-TOCOPHEROL TRANSFER PROTEIN-RELATED; 1.
DR   Pfam; PF00650; CRAL_TRIO; 1.
DR   Pfam; PF03765; CRAL_TRIO_N; 1.
DR   PRINTS; PR00180; CRETINALDHBP.
DR   SMART; SM01100; CRAL_TRIO_N; 1.
DR   SMART; SM00516; SEC14; 1.
DR   SUPFAM; SSF52087; CRAL/TRIO domain; 1.
DR   SUPFAM; SSF46938; CRAL/TRIO N-terminal domain; 1.
DR   PROSITE; PS50191; CRAL_TRIO; 1.
DR   Genevisible; Q8BWP5; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Lipid-binding; Reference proteome; Transport.
FT   CHAIN           1..278
FT                   /note="Alpha-tocopherol transfer protein"
FT                   /id="PRO_0000210765"
FT   DOMAIN          88..253
FT                   /note="CRAL-TRIO"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00056"
FT   BINDING         185
FT                   /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT                   inositol-3,4-bisphosphate)"
FT                   /ligand_id="ChEBI:CHEBI:57658"
FT                   /evidence="ECO:0000269|PubMed:23599266,
FT                   ECO:0007744|PDB:3W67"
FT   BINDING         187
FT                   /ligand="(+)-alpha-tocopherol"
FT                   /ligand_id="ChEBI:CHEBI:18145"
FT                   /evidence="ECO:0000269|PubMed:23599266,
FT                   ECO:0007744|PDB:3W68"
FT   BINDING         190..192
FT                   /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT                   inositol-3,4-bisphosphate)"
FT                   /ligand_id="ChEBI:CHEBI:57658"
FT                   /evidence="ECO:0000269|PubMed:23599266,
FT                   ECO:0007744|PDB:3W67"
FT   BINDING         208..211
FT                   /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT                   inositol-4,5-bisphosphate)"
FT                   /ligand_id="ChEBI:CHEBI:58456"
FT                   /evidence="ECO:0000269|PubMed:23599266,
FT                   ECO:0007744|PDB:3W68"
FT   BINDING         217
FT                   /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT                   inositol-3,4-bisphosphate)"
FT                   /ligand_id="ChEBI:CHEBI:57658"
FT                   /evidence="ECO:0000269|PubMed:23599266,
FT                   ECO:0007744|PDB:3W67"
FT   BINDING         221
FT                   /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT                   inositol-3,4-bisphosphate)"
FT                   /ligand_id="ChEBI:CHEBI:57658"
FT                   /evidence="ECO:0000269|PubMed:23599266,
FT                   ECO:0007744|PDB:3W67"
FT   MUTAGEN         59
FT                   /note="R->W: Abolishes binding to phosphatidylinositol
FT                   3,4-bisphosphate and phosphatidylinositol
FT                   4,5-bisphosphate."
FT                   /evidence="ECO:0000269|PubMed:23599266"
FT   MUTAGEN         217
FT                   /note="K->A: Loss of tocopherol secretion (in vivo). No
FT                   effect on tocopherol binding and intermembrane transfer (in
FT                   vitro)."
FT                   /evidence="ECO:0000269|PubMed:23599266"
FT   MUTAGEN         221
FT                   /note="R->W: Loss of tocopherol secretion (in vivo). No
FT                   effect on tocopherol binding and intermembrane transfer (in
FT                   vitro)."
FT                   /evidence="ECO:0000269|PubMed:23599266"
FT   HELIX           28..38
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   STRAND          43..45
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           49..58
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   TURN            59..61
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           63..79
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           81..84
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           90..92
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           93..98
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   STRAND          101..103
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   STRAND          113..118
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           119..121
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   TURN            124..126
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           129..143
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           147..152
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   STRAND          154..159
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           165..169
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           173..183
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   STRAND          186..189
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   STRAND          191..198
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           202..210
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           211..213
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           216..219
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   STRAND          222..224
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           230..236
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   TURN            238..240
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           243..245
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           252..265
FT                   /evidence="ECO:0007829|PDB:3W68"
FT   HELIX           267..272
FT                   /evidence="ECO:0007829|PDB:3W68"
SQ   SEQUENCE   278 AA;  32014 MW;  BC913ADA7FB606D3 CRC64;
     MAEMRPGPLV GKQLNELPDH SPLLQPGLAE LRRRVQEAGV PQTPQPLTDA FLLRFLRARD
     FDLDLAWRLM KNYYKWRAEC PELSADLRPR SILGLLKAGY HGVLRSRDST GSRVLIYRIA
     YWDPKVFTAY DVFRVSLITS ELIVQEVETQ RNGVKAIFDL EGWQVSHAFQ ITPSVAKKIA
     AVLTDSFPLK VRGIHLINEP VIFHAVFSMI KPFLTEKIKD RIHLHGNNYK SSMLQHFPDI
     LPREYGGKEF SMEDICQEWT NFIMKSEDYL SSISETIQ
//