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P49638

- TTPA_HUMAN

UniProt

P49638 - TTPA_HUMAN

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Protein
Alpha-tocopherol transfer protein
Gene
TTPA, TPP1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei190 – 1901Phosphatidylinositol lipid headgroup By similarity
Binding sitei192 – 1921Phosphatidylinositol lipid headgroup By similarity
Binding sitei217 – 2171Phosphatidylinositol lipid headgroup By similarity
Binding sitei221 – 2211Phosphatidylinositol lipid headgroup By 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
Complete GO annotation...

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
Complete GO annotation...

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.
Note: The disease is caused by mutations affecting the gene represented in this entry.6 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti59 – 591R → W in AVED. 2 Publications
VAR_022388
Natural varianti101 – 1011H → Q in AVED. 2 Publications
VAR_005668
Natural varianti120 – 1201A → T in AVED. 2 Publications
VAR_022389
Natural varianti141 – 1411E → K in AVED. 2 Publications
VAR_022390
Natural varianti192 – 1921R → H in AVED. 2 Publications
Corresponds to variant rs28936369 [ dbSNP | Ensembl ].
VAR_007858
Natural varianti221 – 2211R → W in AVED. 2 Publications
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 protein
PRO_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.

Protein-protein interaction databases

BioGridi113125. 2 interactions.
STRINGi9606.ENSP00000260116.

Structurei

Secondary structure

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.

Miscellaneous databases

EvolutionaryTraceiP49638.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini88 – 253166CRAL-TRIO
Add
BLAST

Sequence similaritiesi

Contains 1 CRAL-TRIO domain.

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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti59 – 591R → W in AVED. 2 Publications
VAR_022388
Natural varianti101 – 1011H → Q in AVED. 2 Publications
VAR_005668
Natural varianti120 – 1201A → T in AVED. 2 Publications
VAR_022389
Natural varianti141 – 1411E → K in AVED. 2 Publications
VAR_022390
Natural varianti172 – 1721T → S.
Corresponds to variant rs34647756 [ dbSNP | Ensembl ].
VAR_037973
Natural varianti192 – 1921R → H in AVED. 2 Publications
Corresponds to variant rs28936369 [ dbSNP | Ensembl ].
VAR_007858
Natural varianti221 – 2211R → W in AVED. 2 Publications
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 conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti271 – 2711S → R in AAA64309. 1 Publication

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

« Hide 'large scale' publications
  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: July 9, 2014
This is version 133 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

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