Q6ZT98 · TTLL7_HUMAN
- ProteinTubulin polyglutamylase TTLL7
- GeneTTLL7
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids887 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Polyglutamylase which modifies tubulin, generating polyglutamate side chains of variable lengths on the gamma-carboxyl group of specific glutamate residues within the C-terminal tail of tubulin (PubMed:16901895, PubMed:25959773).
Mediates both ATP-dependent initiation and elongation steps of the polyglutamylation reaction (PubMed:16901895, PubMed:25959773).
Preferentially modifies the beta-tubulin tail over an alpha-tail (PubMed:16901895, PubMed:25959773).
Competes with monoglycylase TTLL3 for modification site on beta-tubulin substrate, thereby creating an anticorrelation between glycylation and glutamylation reactions (By similarity).
Required for neurite growth; responsible for the strong increase in tubulin polyglutamylation during postnatal neuronal maturation (By similarity).
Mediates both ATP-dependent initiation and elongation steps of the polyglutamylation reaction (PubMed:16901895, PubMed:25959773).
Preferentially modifies the beta-tubulin tail over an alpha-tail (PubMed:16901895, PubMed:25959773).
Competes with monoglycylase TTLL3 for modification site on beta-tubulin substrate, thereby creating an anticorrelation between glycylation and glutamylation reactions (By similarity).
Required for neurite growth; responsible for the strong increase in tubulin polyglutamylation during postnatal neuronal maturation (By similarity).
Catalytic activity
Tubulin polyglutamylase TTLL7
ATP + L-glutamate + L-glutamyl-[protein] = ADP + gamma-L-glutamyl-L-glutamyl-[protein] + H+ + phosphateThis reaction proceeds in the forward direction.Tubulin polyglutamylase TTLL7
(L-glutamyl)(n)-gamma-L-glutamyl-L-glutamyl-[protein] + ATP + L-glutamate = (L-glutamyl)(n+1)-gamma-L-glutamyl-L-glutamyl-[protein] + ADP + H+ + phosphateThis reaction proceeds in the forward direction.
Cofactor
Features
Showing features for site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 106 | Binds negatively charged residues of beta-tubulin C-terminal tails | ||||
Sequence: R | ||||||
Binding site | 160 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 166-167 | ATP (UniProtKB | ChEBI) | ||||
Sequence: MG | ||||||
Binding site | 188-191 | ATP (UniProtKB | ChEBI) | ||||
Sequence: QEYI | ||||||
Binding site | 201-203 | ATP (UniProtKB | ChEBI) | ||||
Sequence: KFD | ||||||
Binding site | 227 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 249-250 | ATP (UniProtKB | ChEBI) | ||||
Sequence: TN | ||||||
Binding site | 251 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 252 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 271 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 336 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 349 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 349 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 351 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Site | 352 | Binds negatively charged residues of beta-tubulin C-terminal tails | ||||
Sequence: R | ||||||
Binding site | 367 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: K |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cilium | |
Cellular Component | cytosol | |
Cellular Component | dendrite | |
Cellular Component | microtubule | |
Cellular Component | perikaryon | |
Molecular Function | alpha-tubulin binding | |
Molecular Function | ATP binding | |
Molecular Function | beta-tubulin binding | |
Molecular Function | metal ion binding | |
Molecular Function | tubulin binding | |
Molecular Function | tubulin-glutamic acid ligase activity | |
Biological Process | cell differentiation | |
Biological Process | microtubule cytoskeleton organization | |
Biological Process | nervous system development | |
Biological Process | protein polyglutamylation |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTubulin polyglutamylase TTLL7
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ6ZT98
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: In cells with primary cilia, found in both cilia and basal bodies. In neuronal cells, found in dendrites and perikaryon.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 106 | Nearly abolished polyglutamylase activity. | ||||
Sequence: R → E | ||||||
Mutagenesis | 143-146 | 70% decreased polyglutamylase activity. | ||||
Sequence: NYVK → EYVE | ||||||
Mutagenesis | 178 | Decreased polyglutamylase activity. | ||||
Sequence: K → E | ||||||
Mutagenesis | 205 | Nearly abolished polyglutamylase activity. | ||||
Sequence: R → E | ||||||
Mutagenesis | 227 | Nearly abolished polyglutamylase activity. | ||||
Sequence: R → E | ||||||
Mutagenesis | 271 | Nearly abolished polyglutamylase activity. | ||||
Sequence: K → E | ||||||
Mutagenesis | 349 | Loss of polyglutamylase activity. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 352 | Nearly abolished polyglutamylase activity. | ||||
Sequence: R → A or E | ||||||
Mutagenesis | 385-393 | 45% decreased binding to microtubules. Decreased polyglutamylase activity. 76% decreased binding to microtubules; when associated with 425-E--E-427. | ||||
Sequence: KRRNLAKQK → EEENLAEQE | ||||||
Mutagenesis | 425-427 | 76% decreased binding to microtubules; when associated with 385-E--E-393. | ||||
Sequence: RRK → EEE | ||||||
Mutagenesis | 477-480 | 40% decreased polyglutamylase activity. | ||||
Sequence: FQTF → AQTA | ||||||
Mutagenesis | 490-500 | 69% decreased polyglutamylase activity. | ||||
Sequence: RELNNPLKRMK → DELNNPLDDMD |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 829 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000212444 | 1-887 | Tubulin polyglutamylase TTLL7 | |||
Sequence: MPSLPQEGVIQGPSPLDLNTELPYQSTMKRKVRKKKKKGTITANVAGTKFEIVRLVIDEMGFMKTPDEDETSNLIWCDSAVQQEKISELQNYQRINHFPGMGEICRKDFLARNMTKMIKSRPLDYTFVPRTWIFPAEYTQFQNYVKELKKKRKQKTFIVKPANGAMGHGISLIRNGDKLPSQDHLIVQEYIEKPFLMEGYKFDLRIYILVTSCDPLKIFLYHDGLVRMGTEKYIPPNESNLTQLYMHLTNYSVNKHNEHFERDETENKGSKRSIKWFTEFLQANQHDVAKFWSDISELVVKTLIVAEPHVLHAYRMCRPGQPPGSESVCFEVLGFDILLDRKLKPWLLEINRAPSFGTDQKIDYDVKRGVLLNALKLLNIRTSDKRRNLAKQKAEAQRRLYGQNSIKRLLPGSSDWEQQRHQLERRKEELKERLAQVRKQISREEHENRHMGNYRRIYPPEDKALLEKYENLLAVAFQTFLSGRAASFQRELNNPLKRMKEEDILDLLEQCEIDDEKLMGKTTKTRGPKPLCSMPESTEIMKRPKYCSSDSSYDSSSSSSESDENEKEEYQNKKREKQVTYNLKPSNHYKLIQQPSSIRRSVSCPRSISAQSPSSGDTRPFSAQQMISVSRPTSASRSHSLNRASSYMRHLPHSNDACSTNSQVSESLRQLKTKEQEDDLTSQTLFVLKDMKIRFPGKSDAESELLIEDIIDNWKYHKTKVASYWLIKLDSVKQRKVLDIVKTSIRTVLPRIWKVPDVEEVNLYRIFNRVFNRLLWSRGQGLWNCFCDSGSSWESIFNKSPEVVTPLQLQCCQRLVELCKQCLLVVYKYATDKRGSLSGIGPDWGNSRYLLPGSTQFFLRTPTYNLKYNSPGMTRSNVLFTSRYGHL |
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in the nervous system including spinal cord, thalamus, hippocampus, hypothalamus and cerebellum.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with both alpha- and beta-tubulin (via C-terminal tubulin tails).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q6ZT98-3 | LMO4 P61968 | 3 | EBI-13339851, EBI-2798728 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-21 | Disordered | ||||
Sequence: MPSLPQEGVIQGPSPLDLNTE | ||||||
Domain | 38-390 | TTL | ||||
Sequence: KGTITANVAGTKFEIVRLVIDEMGFMKTPDEDETSNLIWCDSAVQQEKISELQNYQRINHFPGMGEICRKDFLARNMTKMIKSRPLDYTFVPRTWIFPAEYTQFQNYVKELKKKRKQKTFIVKPANGAMGHGISLIRNGDKLPSQDHLIVQEYIEKPFLMEGYKFDLRIYILVTSCDPLKIFLYHDGLVRMGTEKYIPPNESNLTQLYMHLTNYSVNKHNEHFERDETENKGSKRSIKWFTEFLQANQHDVAKFWSDISELVVKTLIVAEPHVLHAYRMCRPGQPPGSESVCFEVLGFDILLDRKLKPWLLEINRAPSFGTDQKIDYDVKRGVLLNALKLLNIRTSDKRRNLA | ||||||
Region | 388-450 | c-MTBD region | ||||
Sequence: NLAKQKAEAQRRLYGQNSIKRLLPGSSDWEQQRHQLERRKEELKERLAQVRKQISREEHENRH | ||||||
Region | 519-621 | Disordered | ||||
Sequence: MGKTTKTRGPKPLCSMPESTEIMKRPKYCSSDSSYDSSSSSSESDENEKEEYQNKKREKQVTYNLKPSNHYKLIQQPSSIRRSVSCPRSISAQSPSSGDTRPF | ||||||
Compositional bias | 544-559 | Polar residues | ||||
Sequence: PKYCSSDSSYDSSSSS | ||||||
Compositional bias | 560-581 | Basic and acidic residues | ||||
Sequence: SESDENEKEEYQNKKREKQVTY | ||||||
Compositional bias | 582-621 | Polar residues | ||||
Sequence: NLKPSNHYKLIQQPSSIRRSVSCPRSISAQSPSSGDTRPF | ||||||
Compositional bias | 651-669 | Polar residues | ||||
Sequence: LPHSNDACSTNSQVSESLR | ||||||
Region | 651-676 | Disordered | ||||
Sequence: LPHSNDACSTNSQVSESLRQLKTKEQ |
Domain
The enzyme uses its core to engage the disordered anionic tails of alpha- and beta-tubulin and the flexible c-MTBD (cationic microtubule binding domain) region to bind the microtubule and position itself for beta-tail modification. The c-MTBD region is positively charged and becomes ordered when bound to microtubules: it interacts with a negatively charged patch on alpha-tubulin. The presence of positive charges in the c-MTBD region is essential for proper binding.
Sequence similarities
Belongs to the tubulin--tyrosine ligase family.
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q6ZT98-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length887
- Mass (Da)102,999
- Last updated2005-08-30 v2
- Checksum881C46437FB385EA
Q6ZT98-2
- Name2
Q6ZT98-3
- Name3
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A087X234 | A0A087X234_HUMAN | TTLL7 | 543 | ||
F2Z2X2 | F2Z2X2_HUMAN | TTLL7 | 553 | ||
F2Z2J7 | F2Z2J7_HUMAN | TTLL7 | 477 |
Features
Showing features for sequence conflict, compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 13 | in Ref. 1; AAO37763 | ||||
Sequence: P → S | ||||||
Sequence conflict | 48 | in Ref. 2; BAC86695 | ||||
Sequence: T → A | ||||||
Sequence conflict | 298 | in Ref. 4; AAH60878 | ||||
Sequence: L → M | ||||||
Sequence conflict | 489 | in Ref. 4; AAH60878 | ||||
Sequence: Q → R | ||||||
Sequence conflict | 493 | in Ref. 4; AAH60878 | ||||
Sequence: N → D | ||||||
Compositional bias | 544-559 | Polar residues | ||||
Sequence: PKYCSSDSSYDSSSSS | ||||||
Compositional bias | 560-581 | Basic and acidic residues | ||||
Sequence: SESDENEKEEYQNKKREKQVTY | ||||||
Sequence conflict | 575 | in Ref. 4; AAH60878 | ||||
Sequence: R → G | ||||||
Compositional bias | 582-621 | Polar residues | ||||
Sequence: NLKPSNHYKLIQQPSSIRRSVSCPRSISAQSPSSGDTRPF | ||||||
Sequence conflict | 609 | in Ref. 2; BAB15526 | ||||
Sequence: S → F | ||||||
Compositional bias | 651-669 | Polar residues | ||||
Sequence: LPHSNDACSTNSQVSESLR | ||||||
Alternative sequence | VSP_015199 | 665-669 | in isoform 2 | |||
Sequence: SESLR → IILAQ | ||||||
Alternative sequence | VSP_015200 | 670-887 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 677 | in Ref. 4; AAH60878 | ||||
Sequence: E → G | ||||||
Alternative sequence | VSP_015201 | 791-792 | in isoform 3 | |||
Sequence: SS → YV | ||||||
Alternative sequence | VSP_015202 | 793-887 | in isoform 3 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY170843 EMBL· GenBank· DDBJ | AAO37763.1 EMBL· GenBank· DDBJ | mRNA | ||
AK026686 EMBL· GenBank· DDBJ | BAB15526.1 EMBL· GenBank· DDBJ | mRNA | ||
AK126792 EMBL· GenBank· DDBJ | BAC86695.1 EMBL· GenBank· DDBJ | mRNA | ||
AC104454 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL138844 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC060878 EMBL· GenBank· DDBJ | AAH60878.1 EMBL· GenBank· DDBJ | mRNA |