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P49638 (TTPA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alpha-tocopherol transfer protein

Short name=Alpha-TTP
Gene names
Name:TTPA
Synonyms:TPP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length278 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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.

Subcellular location

Cytoplasm.

Involvement in disease

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. Ref.2 Ref.4 Ref.5 Ref.8 Ref.9 Ref.10

Sequence similarities

Contains 1 CRAL-TRIO domain.

Ontologies

Keywords
   Biological processTransport
   Cellular componentCytoplasm
   DiseaseDisease mutation
   LigandLipid-binding
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processembryonic placenta development

Inferred from electronic annotation. Source: Ensembl

intermembrane transport

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular pH reduction

Inferred from electronic annotation. Source: Ensembl

lipid metabolic process

Traceable author statement Ref.1. Source: ProtInc

negative regulation of cell death

Inferred from electronic annotation. Source: Ensembl

negative regulation of establishment of blood-brain barrier

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

response to pH

Inferred from electronic annotation. Source: Ensembl

response to toxic substance

Inferred from electronic annotation. Source: Ensembl

transport

Traceable author statement Ref.1. Source: ProtInc

vitamin E metabolic process

Inferred from electronic annotation. Source: Ensembl

vitamin transport

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytosol

Inferred from electronic annotation. Source: Ensembl

late endosome

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionphosphatidylinositol-3,4-bisphosphate binding

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol-4,5-bisphosphate binding

Inferred from sequence or structural similarity. Source: UniProtKB

transporter activity

Inferred from electronic annotation. Source: InterPro

vitamin E binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 278278Alpha-tocopherol transfer protein
PRO_0000210764

Regions

Domain88 – 253166CRAL-TRIO

Sites

Binding site1901Phosphatidylinositol lipid headgroup By similarity
Binding site1921Phosphatidylinositol lipid headgroup By similarity
Binding site2171Phosphatidylinositol lipid headgroup By similarity
Binding site2211Phosphatidylinositol lipid headgroup By similarity

Natural variations

Natural variant591R → W in AVED. Ref.4 Ref.9
VAR_022388
Natural variant1011H → Q in AVED. Ref.8 Ref.9
VAR_005668
Natural variant1201A → T in AVED. Ref.4 Ref.9
VAR_022389
Natural variant1411E → K in AVED. Ref.4 Ref.9
VAR_022390
Natural variant1721T → S.
Corresponds to variant rs34647756 [ dbSNP | Ensembl ].
VAR_037973
Natural variant1921R → H in AVED. Ref.2 Ref.9
Corresponds to variant rs28936369 [ dbSNP | Ensembl ].
VAR_007858
Natural variant2211R → W in AVED. Ref.4 Ref.9
Corresponds to variant rs35916840 [ dbSNP | Ensembl ].
VAR_022391
Natural variant2461G → R in AVED; mild and slowly progressive form of the disease. Ref.10
VAR_022392

Experimental info

Sequence conflict2711S → R in AAA64309. Ref.2

Secondary structure

........................................................... 278
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P49638 [UniParc].

Last modified February 1, 1996. Version 1.
Checksum: 64D1551CC155071E

FASTA27831,750
        10         20         30         40         50         60 
MAEARSQPSA GPQLNALPDH SPLLQPGLAA LRRRAREAGV PLAPLPLTDS FLLRFLRARD 

        70         80         90        100        110        120 
FDLDLAWRLL KNYYKWRAEC PEISADLHPR SIIGLLKAGY HGVLRSRDPT GSKVLIYRIA 

       130        140        150        160        170        180 
HWDPKVFTAY DVFRVSLITS ELIVQEVETQ RNGIKAIFDL EGWQFSHAFQ ITPSVAKKIA 

       190        200        210        220        230        240 
AVLTDSFPLK VRGIHLINEP VIFHAVFSMI KPFLTEKIKE RIHMHGNNYK QSLLQHFPDI 

       250        260        270 
LPLEYGGEEF SMEDICQEWT NFIMKSEDYL SSISESIQ 

« Hide

References

« Hide 'large scale' references
[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]"Molecular determinants of heritable vitamin E deficiency."
Morley S., Panagabko C., Shineman D., Mani B., Stocker A., Atkinson J., Manor D.
Biochemistry 43:4143-4149(2004) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D49488 mRNA. Translation: BAA08449.1.
U21938 mRNA. Translation: AAA64309.1.
BC058000 mRNA. Translation: AAH58000.1.
AH006950 Genomic DNA. Translation: AAC67490.1.
CCDSCCDS6178.1.
PIRS54352.
RefSeqNP_000361.1. NM_000370.3.
UniGeneHs.69049.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1OIPX-ray1.95A1-278[»]
1OIZX-ray1.88A/B1-278[»]
1R5LX-ray1.50A21-278[»]
ProteinModelPortalP49638.
SMRP49638. Positions 9-273.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113125. 2 interactions.
STRING9606.ENSP00000260116.

Chemistry

DrugBankDB00163. Vitamin E.

PTM databases

PhosphoSiteP49638.

Polymorphism databases

DMDM1351322.

Proteomic databases

MaxQBP49638.
PaxDbP49638.
PRIDEP49638.

Protocols and materials databases

DNASU7274.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000260116; ENSP00000260116; ENSG00000137561.
GeneID7274.
KEGGhsa:7274.
UCSCuc003xux.2. human.

Organism-specific databases

CTD7274.
GeneCardsGC08M064022.
GeneReviewsTTPA.
HGNCHGNC:12404. TTPA.
MIM277460. phenotype.
600415. gene.
neXtProtNX_P49638.
Orphanet96. Ataxia with vitamin E deficiency.
PharmGKBPA37068.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG250577.
HOGENOMHOG000231534.
HOVERGENHBG018009.
InParanoidP49638.
OMAHLINEPI.
OrthoDBEOG7H4DTZ.
PhylomeDBP49638.

Gene expression databases

BgeeP49638.
CleanExHS_TPP1.
HS_TTPA.
GenevestigatorP49638.

Family and domain databases

Gene3D3.40.525.10. 1 hit.
InterProIPR001071. CRAL-bd_toc_tran.
IPR001251. CRAL-TRIO_dom.
IPR011074. CRAL/TRIO_N_dom.
[Graphical view]
PfamPF00650. CRAL_TRIO. 1 hit.
PF03765. CRAL_TRIO_N. 1 hit.
[Graphical view]
PRINTSPR00180. CRETINALDHBP.
SMARTSM01100. CRAL_TRIO_N. 1 hit.
SM00516. SEC14. 1 hit.
[Graphical view]
SUPFAMSSF46938. SSF46938. 1 hit.
SSF52087. SSF52087. 1 hit.
PROSITEPS50191. CRAL_TRIO. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP49638.
GeneWikiAlpha-tocopherol_transfer_protein.
GenomeRNAi7274.
NextBio28443.
PROP49638.
SOURCESearch...

Entry information

Entry nameTTPA_HUMAN
AccessionPrimary (citable) accession number: P49638
Secondary accession number(s): Q71V64
Entry history
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 statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM