P49638 (TTPA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alpha-tocopherol transfer protein
Short name=Alpha-TTP

Gene names

Name:	TTPA
Synonyms:	TPP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	278 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds alpha-tocopherol and enhances its transfer between separate membranes.
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 process	Transport
Cellular component	Cytoplasm
Disease	Disease mutation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	embryonic placenta development Inferred from electronic annotation. Source: Compara lipid metabolic process Traceable author statement Ref.1. Source: ProtInc negative regulation of establishment of blood-brain barrier Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara response to pH Inferred from electronic annotation. Source: Compara response to toxic substance Inferred from electronic annotation. Source: Compara transport Traceable author statement Ref.1. Source: ProtInc vitamin E metabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara late endosome Inferred from electronic annotation. Source: Compara
Molecular_function	transporter activity Inferred from electronic annotation. Source: InterPro vitamin E binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 278

278

Alpha-tocopherol transfer protein

PRO_0000210764

Regions

Domain

88 – 253

166

CRAL-TRIO

Natural variations

Natural variant

59

1

R → W in AVED. Ref.4 Ref.9

VAR_022388

Natural variant

101

1

H → Q in AVED. Ref.8 Ref.9

VAR_005668

Natural variant

120

1

A → T in AVED. Ref.4 Ref.9

VAR_022389

Natural variant

141

1

E → K in AVED. Ref.4 Ref.9

VAR_022390

Natural variant

172

1

T → S.
Corresponds to variant rs34647756 [ dbSNP | Ensembl ].

VAR_037973

Natural variant

192

1

R → H in AVED. Ref.2 Ref.9
Corresponds to variant rs28936369 [ dbSNP | Ensembl ].

VAR_007858

Natural variant

221

1

R → W in AVED. Ref.4 Ref.9
Corresponds to variant rs35916840 [ dbSNP | Ensembl ].

VAR_022391

Natural variant

246

1

G → R in AVED; mild and slowly progressive form of the disease. Ref.10

VAR_022392

Experimental info

Sequence conflict

271

1

S → R in AAA64309. Ref.2

Secondary structure

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278

Helix Strand Turn

Details...

Helix

10 – 15

6

Helix

22 – 24

3

Helix

28 – 38

11

Beta strand

43 – 45

3

Helix

49 – 58

10

Turn

59 – 61

3

Helix

63 – 79

17

Helix

81 – 84

4

Helix

89 – 91

3

Helix

93 – 97

5

Beta strand

101 – 103

3

Beta strand

113 – 118

6

Helix

119 – 121

3

Turn

124 – 126

3

Helix

129 – 143

15

Helix

147 – 152

6

Beta strand

154 – 159

6

Helix

165 – 170

6

Helix

173 – 184

12

Beta strand

186 – 189

4

Beta strand

191 – 198

8

Helix

201 – 203

3

Helix

204 – 210

7

Helix

211 – 213

3

Helix

216 – 219

4

Beta strand

222 – 224

3

Helix

230 – 236

7

Turn

238 – 240

3

Helix

243 – 245

3

Helix

252 – 265

14

Helix

267 – 272

6

Sequences

	Sequence		Length	Mass (Da)
	P49638 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 64D1551CC155071E	FASTA	278	31,750
	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

References

	« Hide 'large scale' referencesShow '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.

Web resources

GeneReviews

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.

IPI

IPI00027692.

PIR

S54352.

RefSeq

NP_000361.1. NM_000370.3.

UniGene

Hs.69049.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P49638.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000260116.

PTM databases

PhosphoSite

P49638.

Polymorphism databases

DMDM

1351322.

Proteomic databases

PaxDb

P49638.

PRIDE

P49638.

Protocols and materials databases

DNASU

7274.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000260116; ENSP00000260116; ENSG00000137561.

GeneID

7274.

KEGG

hsa:7274.

UCSC

uc003xux.2. human.

Organism-specific databases

CTD

7274.

GeneCards

GC08M064022.

HGNC

HGNC:12404. TTPA.

MIM

277460. phenotype.
600415. gene.

neXtProt

NX_P49638.

Orphanet

96. Friedreich-like ataxia with selective vitamin E deficiency.

PharmGKB

PA37068.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG250577.

HOGENOM

HOG000231534.

HOVERGEN

HBG018009.

InParanoid

P49638.

OMA

YRIAHWD.

OrthoDB

EOG42JNSF.

PhylomeDB

P49638.

Gene expression databases

Bgee

P49638.

CleanEx

HS_TPP1.
HS_TTPA.

Genevestigator

P49638.

GermOnline

ENSG00000137561. Homo sapiens.

Family and domain databases

Gene3D

3.40.525.10. 1 hit.

InterPro

IPR001071. CRAL-bd_toc_tran.
IPR001251. CRAL-TRIO_dom.
IPR011074. CRAL/TRIO_N_dom.
[Graphical view]

Pfam

PF00650. CRAL_TRIO. 1 hit.
PF03765. CRAL_TRIO_N. 1 hit.
[Graphical view]

PRINTS

PR00180. CRETINALDHBP.

SMART

SM01100. CRAL_TRIO_N. 1 hit.
SM00516. SEC14. 1 hit.
[Graphical view]

SUPFAM

SSF52087. CRAL_TRIO_C. 1 hit.
SSF46938. Sec14p_like_N. 1 hit.

PROSITE

PS50191. CRAL_TRIO. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00163. Vitamin E.

EvolutionaryTrace

P49638.

GenomeRNAi

7274.

NextBio

28443.

SOURCE

Search...

Entry information

Entry name

TTPA_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 122 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.