TTPA_MOUSE
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 03-AUG-2022, entry version 137.
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; Q8BWP5; -.
DR PRIDE; Q8BWP5; -.
DR ProteomicsDB; 298025; -.
DR Antibodypedia; 55595; 122 antibodies from 17 providers.
DR DNASU; 50500; -.
DR Ensembl; ENSMUST00000098244; ENSMUSP00000095845; ENSMUSG00000073988.
DR GeneID; 50500; -.
DR KEGG; mmu:50500; -.
DR UCSC; uc008sci.1; mouse.
DR CTD; 7274; -.
DR MGI; MGI:1354168; Ttpa.
DR VEuPathDB; HostDB:ENSMUSG00000073988; -.
DR eggNOG; KOG1471; Eukaryota.
DR GeneTree; ENSGT00940000159203; -.
DR InParanoid; Q8BWP5; -.
DR OMA; WTDFIMA; -.
DR OrthoDB; 1053004at2759; -.
DR PhylomeDB; Q8BWP5; -.
DR Reactome; R-MMU-8877627; Vitamin E.
DR BioGRID-ORCS; 50500; 1 hit in 75 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 135 other tissues.
DR ExpressionAtlas; Q8BWP5; baseline and differential.
DR Genevisible; Q8BWP5; MM.
DR GO; GO:0005737; C:cytoplasm; TAS:MGI.
DR GO; GO:0005829; C:cytosol; ISO: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:0060548; P:negative regulation of cell death; 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:0007584; P:response to nutrient; IEA:Ensembl.
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; 3.40.525.10; -; 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 Pfam; PF00650; CRAL_TRIO; 1.
DR Pfam; PF03765; CRAL_TRIO_N; 1.
DR SMART; SM01100; CRAL_TRIO_N; 1.
DR SMART; SM00516; SEC14; 1.
DR SUPFAM; SSF46938; SSF46938; 1.
DR SUPFAM; SSF52087; SSF52087; 1.
DR PROSITE; PS50191; CRAL_TRIO; 1.
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 3,4-
FT bisphosphate and phosphatidylinositol 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
