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P49638

- TTPA_HUMAN

UniProt

P49638 - TTPA_HUMAN

Protein

Alpha-tocopherol transfer protein

Gene

TTPA

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 1 (01 Feb 1996)
      Previous versions | rss
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    Functioni

    Binds alpha-tocopherol, enhances its transfer between separate membranes, and stimulates its release from liver cells. Binds both phosphatidylinol 3,4-bisphosphate and phosphatidylinol 4,5-bisphosphate; the resulting conformation change is important for the release of the bound alpha-tocopherol By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei190 – 1901Phosphatidylinositol lipid headgroupBy similarity
    Binding sitei192 – 1921Phosphatidylinositol lipid headgroupBy similarity
    Binding sitei217 – 2171Phosphatidylinositol lipid headgroupBy similarity
    Binding sitei221 – 2211Phosphatidylinositol lipid headgroupBy similarity

    GO - Molecular functioni

    1. phosphatidylinositol-3,4-bisphosphate binding Source: UniProtKB
    2. phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
    3. transporter activity Source: InterPro
    4. vitamin E binding Source: UniProtKB

    GO - Biological processi

    1. embryonic placenta development Source: Ensembl
    2. intermembrane transport Source: UniProtKB
    3. intracellular pH reduction Source: Ensembl
    4. lipid metabolic process Source: ProtInc
    5. negative regulation of cell death Source: Ensembl
    6. negative regulation of establishment of blood-brain barrier Source: Ensembl
    7. response to nutrient Source: Ensembl
    8. response to pH Source: Ensembl
    9. response to toxic substance Source: Ensembl
    10. transport Source: ProtInc
    11. vitamin E metabolic process Source: Ensembl
    12. vitamin transport Source: UniProtKB

    Keywords - Biological processi

    Transport

    Keywords - Ligandi

    Lipid-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Alpha-tocopherol transfer protein
    Short name:
    Alpha-TTP
    Gene namesi
    Name:TTPA
    Synonyms:TPP1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:12404. TTPA.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Ensembl
    2. late endosome Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Ataxia with isolated vitamin E deficiency (AVED) [MIM:277460]: An autosomal recessive disease characterized by undetectable or markedly reduced plasma levels of vitamin E, spinocerebellar degeneration, ataxia, areflexia and proprioception loss.4 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti59 – 591R → W in AVED. 1 Publication
    VAR_022388
    Natural varianti101 – 1011H → Q in AVED. 1 Publication
    VAR_005668
    Natural varianti120 – 1201A → T in AVED. 1 Publication
    VAR_022389
    Natural varianti141 – 1411E → K in AVED. 1 Publication
    VAR_022390
    Natural varianti192 – 1921R → H in AVED. 1 Publication
    Corresponds to variant rs28936369 [ dbSNP | Ensembl ].
    VAR_007858
    Natural varianti221 – 2211R → W in AVED. 1 Publication
    Corresponds to variant rs35916840 [ dbSNP | Ensembl ].
    VAR_022391
    Natural varianti246 – 2461G → R in AVED; mild and slowly progressive form of the disease. 1 Publication
    VAR_022392

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi277460. phenotype.
    Orphaneti96. Ataxia with vitamin E deficiency.
    PharmGKBiPA37068.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 278278Alpha-tocopherol transfer proteinPRO_0000210764Add
    BLAST

    Proteomic databases

    MaxQBiP49638.
    PaxDbiP49638.
    PRIDEiP49638.

    PTM databases

    PhosphoSiteiP49638.

    Expressioni

    Gene expression databases

    BgeeiP49638.
    CleanExiHS_TPP1.
    HS_TTPA.
    GenevestigatoriP49638.

    Interactioni

    Subunit structurei

    Monomer and homotetramer. Phosphatidylinol 4,5-bisphosphate binding induces the formation of homotetramers. Phosphatidylinol 3,4-bisphosphate is less efficient in inducing tetramerization By similarity.By similarity

    Protein-protein interaction databases

    BioGridi113125. 2 interactions.
    STRINGi9606.ENSP00000260116.

    Structurei

    Secondary structure

    1
    278
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi10 – 156
    Helixi22 – 243
    Helixi28 – 3811
    Beta strandi43 – 453
    Helixi49 – 5810
    Turni59 – 613
    Helixi63 – 7917
    Helixi81 – 844
    Helixi89 – 913
    Helixi93 – 975
    Beta strandi101 – 1033
    Beta strandi113 – 1186
    Helixi119 – 1213
    Turni124 – 1263
    Helixi129 – 14315
    Helixi147 – 1526
    Beta strandi154 – 1596
    Helixi165 – 1706
    Helixi173 – 18412
    Beta strandi186 – 1894
    Beta strandi191 – 1988
    Helixi201 – 2033
    Helixi204 – 2107
    Helixi211 – 2133
    Helixi216 – 2194
    Beta strandi222 – 2243
    Helixi230 – 2367
    Turni238 – 2403
    Helixi243 – 2453
    Helixi252 – 26514
    Helixi267 – 2726

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1OIPX-ray1.95A1-278[»]
    1OIZX-ray1.88A/B1-278[»]
    1R5LX-ray1.50A21-278[»]
    ProteinModelPortaliP49638.
    SMRiP49638. Positions 9-273.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP49638.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini88 – 253166CRAL-TRIOPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 CRAL-TRIO domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG250577.
    HOGENOMiHOG000231534.
    HOVERGENiHBG018009.
    InParanoidiP49638.
    OMAiHLINEPI.
    OrthoDBiEOG7H4DTZ.
    PhylomeDBiP49638.

    Family and domain databases

    Gene3Di3.40.525.10. 1 hit.
    InterProiIPR001071. CRAL-bd_toc_tran.
    IPR001251. CRAL-TRIO_dom.
    IPR011074. CRAL/TRIO_N_dom.
    [Graphical view]
    PfamiPF00650. CRAL_TRIO. 1 hit.
    PF03765. CRAL_TRIO_N. 1 hit.
    [Graphical view]
    PRINTSiPR00180. CRETINALDHBP.
    SMARTiSM01100. CRAL_TRIO_N. 1 hit.
    SM00516. SEC14. 1 hit.
    [Graphical view]
    SUPFAMiSSF46938. SSF46938. 1 hit.
    SSF52087. SSF52087. 1 hit.
    PROSITEiPS50191. CRAL_TRIO. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P49638-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAEARSQPSA GPQLNALPDH SPLLQPGLAA LRRRAREAGV PLAPLPLTDS    50
    FLLRFLRARD FDLDLAWRLL KNYYKWRAEC PEISADLHPR SIIGLLKAGY 100
    HGVLRSRDPT GSKVLIYRIA HWDPKVFTAY DVFRVSLITS ELIVQEVETQ 150
    RNGIKAIFDL EGWQFSHAFQ ITPSVAKKIA AVLTDSFPLK VRGIHLINEP 200
    VIFHAVFSMI KPFLTEKIKE RIHMHGNNYK QSLLQHFPDI LPLEYGGEEF 250
    SMEDICQEWT NFIMKSEDYL SSISESIQ 278
    Length:278
    Mass (Da):31,750
    Last modified:February 1, 1996 - v1
    Checksum:i64D1551CC155071E
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti271 – 2711S → R in AAA64309. (PubMed:8602747)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti59 – 591R → W in AVED. 1 Publication
    VAR_022388
    Natural varianti101 – 1011H → Q in AVED. 1 Publication
    VAR_005668
    Natural varianti120 – 1201A → T in AVED. 1 Publication
    VAR_022389
    Natural varianti141 – 1411E → K in AVED. 1 Publication
    VAR_022390
    Natural varianti172 – 1721T → S.
    Corresponds to variant rs34647756 [ dbSNP | Ensembl ].
    VAR_037973
    Natural varianti192 – 1921R → H in AVED. 1 Publication
    Corresponds to variant rs28936369 [ dbSNP | Ensembl ].
    VAR_007858
    Natural varianti221 – 2211R → W in AVED. 1 Publication
    Corresponds to variant rs35916840 [ dbSNP | Ensembl ].
    VAR_022391
    Natural varianti246 – 2461G → R in AVED; mild and slowly progressive form of the disease. 1 Publication
    VAR_022392

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D49488 mRNA. Translation: BAA08449.1.
    U21938 mRNA. Translation: AAA64309.1.
    BC058000 mRNA. Translation: AAH58000.1.
    AH006950 Genomic DNA. Translation: AAC67490.1.
    CCDSiCCDS6178.1.
    PIRiS54352.
    RefSeqiNP_000361.1. NM_000370.3.
    UniGeneiHs.69049.

    Genome annotation databases

    EnsembliENST00000260116; ENSP00000260116; ENSG00000137561.
    GeneIDi7274.
    KEGGihsa:7274.
    UCSCiuc003xux.2. human.

    Polymorphism databases

    DMDMi1351322.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D49488 mRNA. Translation: BAA08449.1 .
    U21938 mRNA. Translation: AAA64309.1 .
    BC058000 mRNA. Translation: AAH58000.1 .
    AH006950 Genomic DNA. Translation: AAC67490.1 .
    CCDSi CCDS6178.1.
    PIRi S54352.
    RefSeqi NP_000361.1. NM_000370.3.
    UniGenei Hs.69049.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1OIP X-ray 1.95 A 1-278 [» ]
    1OIZ X-ray 1.88 A/B 1-278 [» ]
    1R5L X-ray 1.50 A 21-278 [» ]
    ProteinModelPortali P49638.
    SMRi P49638. Positions 9-273.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 113125. 2 interactions.
    STRINGi 9606.ENSP00000260116.

    Chemistry

    DrugBanki DB00163. Vitamin E.

    PTM databases

    PhosphoSitei P49638.

    Polymorphism databases

    DMDMi 1351322.

    Proteomic databases

    MaxQBi P49638.
    PaxDbi P49638.
    PRIDEi P49638.

    Protocols and materials databases

    DNASUi 7274.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000260116 ; ENSP00000260116 ; ENSG00000137561 .
    GeneIDi 7274.
    KEGGi hsa:7274.
    UCSCi uc003xux.2. human.

    Organism-specific databases

    CTDi 7274.
    GeneCardsi GC08M064022.
    GeneReviewsi TTPA.
    HGNCi HGNC:12404. TTPA.
    MIMi 277460. phenotype.
    600415. gene.
    neXtProti NX_P49638.
    Orphaneti 96. Ataxia with vitamin E deficiency.
    PharmGKBi PA37068.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG250577.
    HOGENOMi HOG000231534.
    HOVERGENi HBG018009.
    InParanoidi P49638.
    OMAi HLINEPI.
    OrthoDBi EOG7H4DTZ.
    PhylomeDBi P49638.

    Miscellaneous databases

    EvolutionaryTracei P49638.
    GeneWikii Alpha-tocopherol_transfer_protein.
    GenomeRNAii 7274.
    NextBioi 28443.
    PROi P49638.
    SOURCEi Search...

    Gene expression databases

    Bgeei P49638.
    CleanExi HS_TPP1.
    HS_TTPA.
    Genevestigatori P49638.

    Family and domain databases

    Gene3Di 3.40.525.10. 1 hit.
    InterProi IPR001071. CRAL-bd_toc_tran.
    IPR001251. CRAL-TRIO_dom.
    IPR011074. CRAL/TRIO_N_dom.
    [Graphical view ]
    Pfami PF00650. CRAL_TRIO. 1 hit.
    PF03765. CRAL_TRIO_N. 1 hit.
    [Graphical view ]
    PRINTSi PR00180. CRETINALDHBP.
    SMARTi SM01100. CRAL_TRIO_N. 1 hit.
    SM00516. SEC14. 1 hit.
    [Graphical view ]
    SUPFAMi SSF46938. SSF46938. 1 hit.
    SSF52087. SSF52087. 1 hit.
    PROSITEi PS50191. CRAL_TRIO. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Human alpha-tocopherol transfer protein: cDNA cloning, expression and chromosomal localization."
      Arita M., Sato Y., Miyata A., Tanabe T., Takahashi E., Kayden H.J., Arai H., Inoue K.
      Biochem. J. 306:437-443(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Liver.
    2. "Human alpha-tocopherol transfer protein: gene structure and mutations in familial vitamin E deficiency."
      Hentati A., Deng H.-X., Hung W.-Y., Nayer M., Ahmed M.S., He X., Tim R., Stumpf D.A., Siddique T.
      Ann. Neurol. 39:295-300(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT AVED HIS-192.
    3. "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].
      Tissue: Kidney.
    4. "Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families."
      Cavalier L., Ouahchi K., Kayden H.J., Di Donato S., Reutenauer L., Mandel J.-L., Koenig M.
      Am. J. Hum. Genet. 62:301-310(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-119, VARIANTS AVED TRP-59; THR-120; LYS-141 AND TRP-221.
    5. "Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein."
      Ouahchi K., Arita M., Kayden H., Hentati F., Ben-Hamida M., Sokol R., Arai H., Inoue K., Mandel J.-L., Koenig M.
      Nat. Genet. 9:141-145(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 170-180 AND 246-265, DISEASE.
    6. "The molecular basis of vitamin E retention: structure of human alpha-tocopherol transfer protein."
      Meier R., Tomizaki T., Schulze-Briese C., Baumann U., Stocker A.
      J. Mol. Biol. 331:725-734(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
    7. "Crystal structure of human alpha-tocopherol transfer protein bound to its ligand: implications for ataxia with vitamin E deficiency."
      Min K.C., Kovall R.A., Hendrickson W.A.
      Proc. Natl. Acad. Sci. U.S.A. 100:14713-14718(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 21-278.
    8. "Adult-onset spinocerebellar dysfunction caused by a mutation in the gene for the alpha-tocopherol-transfer protein."
      Gotoda T., Arita M., Arai H., Inoue K., Yokota T., Fukuo Y., Yazaki Y., Yamada N.
      N. Engl. J. Med. 333:1313-1318(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT AVED GLN-101.
    9. Cited for: CHARACTERIZATION OF VARIANTS AVED TRP-59; GLN-101; THR-120; LYS-141; HIS-192 AND TRP-221.
    10. "Ataxia with isolated vitamin E deficiency: neurological phenotype, clinical follow-up and novel mutations in TTPA gene in Italian families."
      Mariotti C., Gellera C., Rimoldi M., Mineri R., Uziel G., Zorzi G., Pareyson D., Piccolo G., Gambi D., Piacentini S., Squitieri F., Capra R., Castellotti B., Di Donato S.
      Neurol. Sci. 25:130-137(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT AVED ARG-246.

    Entry informationi

    Entry nameiTTPA_HUMAN
    AccessioniPrimary (citable) accession number: P49638
    Secondary accession number(s): Q71V64
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: February 1, 1996
    Last modified: October 1, 2014
    This is version 134 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 8
      Human chromosome 8: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3