TPK1

Protein identityUniProt · HPA

UniProt accession

Q9H3S4

Gene

TPK1

Ensembl

ENSG00000196511

Chromosome

7

Canonical length

243 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Vesicles

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene functions as a homodimer and catalyzes the conversion of thiamine to thiamine pyrophosphate, a cofactor for some enzymes of the glycolytic and energy production pathways. Defects in this gene are a cause of thiamine metabolism dysfunction syndrome-5. [provided by RefSeq, Apr 2017]

Canonical amino-acid sequenceUniProt

243 residues, UniProt reviewed canonical sequence.

>Q9H3S4|TPK1
     1  MEHAFTPLEP LLSTGNLKYC LVILNQPLDN YFRHLWNKAL LRACADGGAN RLYDITEGER
    61  ESFLPEFING DFDSIRPEVR EYYATKGCEL ISTPDQDHTD FTKCLKMLQK KIEEKDLKVD
   121  VIVTLGGLAG RFDQIMASVN TLFQATHITP FPIIIIQEES LIYLLQPGKH RLHVDTGMEG
   181  DWCGLIPVGQ PCMQVTTTGL KWNLTNDVLA FGTLVSTSNT YDGSGVVTVE TDHPLLWTMA
   241  IKS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TPK1 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)

0.24

Highest tissue expression

13 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TPK1.

Disease | AllUniProt

Conditions TPK1 is implicated in, by any mechanism.

• Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type (THMD5) MIM:614458

Disease | GeneticClinVar

31 pathogenic / likely-pathogenic of 308 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Childhood encephalopathy due to thiamine pyrophosphokinase deficiency
• Leigh 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)

0.7

gnomAD pLI

0.09

gnomAD missense Z

0.34

DepMap mean gene effect

-0.08

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• regulation of pyruvate decarboxylation to acetyl-CoA
• thiamine diphosphate biosynthetic process
• thiamine metabolic process

Molecular functions

• ATP binding
• identical protein binding
• kinase activity
• thiamine binding
• thiamine diphosphokinase activity
• UTP thiamine diphosphokinase activity

Cellular components

• cytosol

Protein domainsUniProt · Pfam · InterPro

• Thiamin pyrophosphokinase
• Thiamin pyrophosphokinase, catalytic domain
• Thiamin pyrophosphokinase, thiamin-binding domain
• Thiamin pyrophosphokinase, eukaryotic
• Thiamin pyrophosphokinase, thiamin-binding domain superfamily
• Thiamin pyrophosphokinase, catalytic domain superfamily
• Thiamin pyrophosphokinase, catalytic domain
• Thiamin pyrophosphokinase, vitamin B1 binding domain

KeywordsUniProt

• ATP-binding
• Kinase
• Nucleotide-binding
• Transferase