TTPA

Protein identityUniProt · HPA

UniProt accession

P49638

Gene

TTPA

Ensembl

ENSG00000137561

Chromosome

8

Canonical length

278 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Quaternary structure

Homotetramer

OverviewNCBI Gene

This gene encodes a soluble protein that binds alpha-trocopherol, a form of vitamin E, with high selectivity and affinity. This protein plays an important role in regulating vitamin E levels in the body by transporting vitamin E between membrane vesicles and facilitating the secretion of vitamin E from hepatocytes to circulating lipoproteins. Mutations in this gene cause hereditary vitamin E deficiency (ataxia with vitamin E deficiency, AVED) and retinitis pigmentosa. [provided by RefSeq, Nov 2009]

Canonical amino-acid sequenceUniProt

278 residues, UniProt reviewed canonical sequence.

>P49638|TTPA
     1  MAEARSQPSA GPQLNALPDH SPLLQPGLAA LRRRAREAGV PLAPLPLTDS FLLRFLRARD
    61  FDLDLAWRLL KNYYKWRAEC PEISADLHPR SIIGLLKAGY HGVLRSRDPT GSKVLIYRIA
   121  HWDPKVFTAY DVFRVSLITS ELIVQEVETQ RNGIKAIFDL EGWQFSHAFQ ITPSVAKKIA
   181  AVLTDSFPLK VRGIHLINEP VIFHAVFSMI KPFLTEKIKE RIHMHGNNYK QSLLQHFPDI
   241  LPLEYGGEEF SMEDICQEWT NFIMKSEDYL SSISESIQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TTPA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

154 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TTPA.

Disease | AllUniProt

Conditions TTPA is implicated in, by any mechanism.

• Ataxia with vitamin E deficiency (AVED) MIM:277460

Disease | GeneticClinVar

92 pathogenic / likely-pathogenic of 498 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Familial isolated deficiency of vitamin E
• ATAXIA, FRIEDREICH-LIKE, WITH ISOLATED VITAMIN E DEFICIENCY
• Retinal dystrophy
• TTPA-related disorder
• CHD7-related CHARGE syndrome

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.09

gnomAD pLI

0

gnomAD missense Z

0.3

DepMap mean gene effect

0.05

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• embryonic placenta development
• intermembrane lipid transfer
• lipid metabolic process
• positive regulation of amyloid-beta clearance
• response to toxic substance
• vitamin E metabolic process
• vitamin transport
• negative regulation of establishment of blood-brain barrier

Molecular functions

• lipid transfer activity
• phosphatidylinositol bisphosphate binding
• phosphatidylinositol-3,4-bisphosphate binding
• phosphatidylinositol-4,5-bisphosphate binding
• vitamin E binding

Cellular components

• cytosol
• late endosome

Protein domainsUniProt · Pfam · InterPro

• CRAL-TRIO lipid binding domain
• CRAL/TRIO, N-terminal domain
• CRAL/TRIO, N-terminal domain superfamily
• CRAL-TRIO lipid binding domain superfamily
• CRAL/TRIO domain
• CRAL/TRIO, N-terminal domain

KeywordsUniProt

• Cytoplasm
• Lipid-binding
• Transport