TTL

Protein identityUniProt · HPA

UniProt accession

Q8NG68

Gene

TTL

Ensembl

ENSG00000114999

Chromosome

2

Canonical length

377 aa

Protein class

Enzymes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Vesicles

OverviewNCBI Gene

TTL is a cytosolic enzyme involved in the posttranslational modification of alpha-tubulin (see MIM 602529). Alpha-tubulin within assembled microtubules is detyrosinated over time at the C terminus. After microtubule disassembly, TTL restores the tyrosine residues and consequently participates in a cycle of tubulin detyrosination and tyrosination (Erck et al., 2003 [PubMed 14571137]).[supplied by OMIM, Mar 2008]

Canonical amino-acid sequenceUniProt

377 residues, UniProt reviewed canonical sequence.

>Q8NG68|TTL
     1  MYTFVVRDEN SSVYAEVSRL LLATGHWKRL RRDNPRFNLM LGERNRLPFG RLGHEPGLVQ
    61  LVNYYRGADK LCRKASLVKL IKTSPELAES CTWFPESYVI YPTNLKTPVA PAQNGIQPPI
   121  SNSRTDEREF FLASYNRKKE DGEGNVWIAK SSAGAKGEGI LISSEASELL DFIDNQGQVH
   181  VIQKYLEHPL LLEPGHRKFD IRSWVLVDHQ YNIYLYREGV LRTASEPYHV DNFQDKTCHL
   241  TNHCIQKEYS KNYGKYEEGN EMFFKEFNQY LTSALNITLE SSILLQIKHI IRNCLLSVEP
   301  AISTKHLPYQ SFQLFGFDFM VDEELKVWLI EVNGAPACAQ KLYAELCQGI VDIAISSVFP
   361  PPDVEQPQTQ PAAFIKL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TTL 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)

0.25

Highest tissue expression

3.5 nTPM

Expression across tissuesHPA

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)

0.52

gnomAD pLI

0.36

gnomAD missense Z

1.71

DepMap mean gene effect

-0.07

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

• microtubule cytoskeleton organization
• positive regulation of mitotic cell cycle
• post-translational protein modification
• regulation of axon extension
• regulation of metaphase plate congression

Molecular functions

• ATP binding
• tubulin-tyrosine ligase activity

Cellular components

• spindle microtubule

Protein domainsUniProt · Pfam · InterPro

• Tubulin-tyrosine ligase/Tubulin polyglutamylase
• Tubulin-tyrosine ligase family
• Tubulin--tyrosine ligase

KeywordsUniProt

• ATP-binding
• Ligase
• Magnesium
• Nucleotide-binding
• Potassium