Q80UG8 · TTLL4_MOUSE
- ProteinTubulin monoglutamylase TTLL4
- GeneTtll4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1193 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Monoglutamylase which modifies both tubulin and non-tubulin proteins, adding a single glutamate on the gamma-carboxyl group of specific glutamate residues of target proteins (PubMed:17499049, PubMed:20530212, PubMed:21074048, PubMed:26829768).
Involved in the side-chain initiation step of the polyglutamylation reaction but not in the elongation step (PubMed:17499049, PubMed:21074048).
Preferentially modifies beta-tail tubulin over the alpha-tubulin (PubMed:17499049).
Monoglutamylates nucleosome assembly proteins NAP1L1 and NAP1L4 (PubMed:17499049).
Monoglutamylates nucleotidyltransferase CGAS, leading to inhibition of CGAS catalytic activity, thereby preventing antiviral defense function (PubMed:26829768).
Involved in KLF4 glutamylation which impedes its ubiquitination, thereby leading to somatic cell reprogramming, pluripotency maintenance and embryogenesis (PubMed:29593216).
Involved in the side-chain initiation step of the polyglutamylation reaction but not in the elongation step (PubMed:17499049, PubMed:21074048).
Preferentially modifies beta-tail tubulin over the alpha-tubulin (PubMed:17499049).
Monoglutamylates nucleosome assembly proteins NAP1L1 and NAP1L4 (PubMed:17499049).
Monoglutamylates nucleotidyltransferase CGAS, leading to inhibition of CGAS catalytic activity, thereby preventing antiviral defense function (PubMed:26829768).
Involved in KLF4 glutamylation which impedes its ubiquitination, thereby leading to somatic cell reprogramming, pluripotency maintenance and embryogenesis (PubMed:29593216).
Catalytic activity
- ATP + L-glutamate + L-glutamyl-[protein] = ADP + gamma-L-glutamyl-L-glutamyl-[protein] + H+ + phosphateThis reaction proceeds in the forward direction.
Cofactor
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 716 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 722 | L-glutamate residue (UniProtKB | ChEBI); L-glutamate acceptor residue in protein target of a protein (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Site | 722 | Essential for specifying initiation versus elongation step of the polyglutamylase activity | ||||
Sequence: R | ||||||
Binding site | 722-723 | ATP (UniProtKB | ChEBI) | ||||
Sequence: RG | ||||||
Binding site | 744-747 | ATP (UniProtKB | ChEBI) | ||||
Sequence: QRYL | ||||||
Binding site | 757-759 | ATP (UniProtKB | ChEBI) | ||||
Sequence: KFD | ||||||
Binding site | 783 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 804-805 | ATP (UniProtKB | ChEBI) | ||||
Sequence: TN | ||||||
Binding site | 806 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 807 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 828 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 888 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 901 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 901 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 903 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 919 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: K |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | 9+0 non-motile cilium | |
Cellular Component | ciliary basal body | |
Cellular Component | cilium | |
Cellular Component | cytoplasm | |
Cellular Component | microtubule | |
Molecular Function | ATP binding | |
Molecular Function | metal ion binding | |
Molecular Function | protein-glutamic acid ligase activity | |
Molecular Function | tubulin binding | |
Molecular Function | tubulin-glutamic acid ligase activity | |
Biological Process | microtubule cytoskeleton organization | |
Biological Process | peptidyl-glutamic acid modification | |
Biological Process | protein polyglutamylation | |
Biological Process | regulation of blastocyst development |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTubulin monoglutamylase TTLL4
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ80UG8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Located in cilia. In some cells, also found in basal bodies.
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Knockout mice show hypoglutamylation of KLF4 resulting in KLF4 proteasome-mediated degradation in early-stage embryos and impaired early embryonic development.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 70 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000212443 | 1-1193 | Tubulin monoglutamylase TTLL4 | |||
Sequence: MASAGTEHYSIGLRRGNSFKQRHPSGTVSASPSEKPSEVKVWSQAHQQVKPIWKLEKKHVGTLSAGLGTSFLGVPSQPAYFLCPSTLCSSGTTAVIAGHSNPCYLQSLPNLFSNTLLYRRTNVRQKPYQQLESFCLRSSPSEKRSFSLPQKGLPVSVTANKATSSTVFPMAQPMATSPTDPYLSLAAAGENPSRKSLASAISGKIASPLSYKPMLNNNSFMRPNSTKVPLSQATDGLKPVSSPKIQPVSWHHSGGTGDCVPQPGDHKVPQNIATVLDDVTAPITPSIPSTLNISTASVTSSQCSQSNFRMEAHPCGLDENPDSQSATKEVHFTEAVRKLAEKGLEKMPRQGYQFEQACFVNPSFQWGLLNRSRRWKPLMGQRFPQEDIGLDSAILPGTSDTLGLDSTVFCTKRISIHLLASHVHGLNPSPACGSAVDPQVLGEDRAPVPPSSLQPLGVAEVATRLSSVHLDQPGKEPEEAKDLNSCTKGGGSATDLQPNQVEPEDTEDELGDGLEDSCSHDENEEEEGDSECSSLSVVSPSESVALISRNCVDLMSKSLPNHEKVVRPALIYSLFPNVTPTIYFGTRDERVEKLPWEQRRLLRWKMSTVTPNIVKQTIGRSHFKISKRNDDWLGCWGHHMKSPGFRSIREHQKLNHFPGSFQIGRKDRLWRNLSRMQSRFGKKEFSFFPQSFILPQDSKLLRKAWESSSRQKWIVKPPASARGIGIQVIHKWSQLPKRRPLLVQRYLHKPYLISGSKFDLRIYVYVTSYDPLRIYLFSDGLVRFASCKYSPSMKSLSNKFMHLTNYSVNKKNTEYQANADETACQGHKWALKALWNYLSQKGINSDAIWEKIKDVVVKTIISSEPYVTNLLKLYVRRPYSCHELFGFDIMLDENLKPWVLEVNISPSLHSNSPLDISIKGQMIRDLLNLAGFVLPNMEDIISSSSSPSSSSGSSTSLPSSPRDKCQMTPEHFTAQKMKKAYYLTQKIPDQDFYASVLDVLTPDDVRVLVEMEDEFSRRGQFERIFPSRISSRYLRFFEQPRYFNILTTQWEQKYHGNKLKGVDLLRNWCYKGFHTGIVSDSAPLWSLPTSLMTTSKGDGTPNSASKSRKKSASEGTTLSSEDRSTPKSKKSQAGLSPISRKTLSSRSNENTSKQSKRSTPGLPVLKYSGQSSRLSAASASQSVTDSRLTAVSS | ||||||
Modified residue | 686 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in testis (PubMed:17499049).
Expressed in brain, heart, kidney, liver, lung, muscle and spleen (PubMed:17499049).
In the brain, expressed in ependymal cilia, the cortex and the striatum (PubMed:23897886).
Expressed in blastomere (PubMed:29593216).
Expressed in brain, heart, kidney, liver, lung, muscle and spleen (PubMed:17499049).
In the brain, expressed in ependymal cilia, the cortex and the striatum (PubMed:23897886).
Expressed in blastomere (PubMed:29593216).
Gene expression databases
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-37 | Disordered | ||||
Sequence: MASAGTEHYSIGLRRGNSFKQRHPSGTVSASPSEKPS | ||||||
Compositional bias | 20-37 | Polar residues | ||||
Sequence: KQRHPSGTVSASPSEKPS | ||||||
Region | 468-535 | Disordered | ||||
Sequence: VHLDQPGKEPEEAKDLNSCTKGGGSATDLQPNQVEPEDTEDELGDGLEDSCSHDENEEEEGDSECSSL | ||||||
Compositional bias | 501-531 | Acidic residues | ||||
Sequence: VEPEDTEDELGDGLEDSCSHDENEEEEGDSE | ||||||
Domain | 599-942 | TTL | ||||
Sequence: RRLLRWKMSTVTPNIVKQTIGRSHFKISKRNDDWLGCWGHHMKSPGFRSIREHQKLNHFPGSFQIGRKDRLWRNLSRMQSRFGKKEFSFFPQSFILPQDSKLLRKAWESSSRQKWIVKPPASARGIGIQVIHKWSQLPKRRPLLVQRYLHKPYLISGSKFDLRIYVYVTSYDPLRIYLFSDGLVRFASCKYSPSMKSLSNKFMHLTNYSVNKKNTEYQANADETACQGHKWALKALWNYLSQKGINSDAIWEKIKDVVVKTIISSEPYVTNLLKLYVRRPYSCHELFGFDIMLDENLKPWVLEVNISPSLHSNSPLDISIKGQMIRDLLNLAGFVLPNMEDIIS | ||||||
Region | 913-1027 | c-MTBD region | ||||
Sequence: PLDISIKGQMIRDLLNLAGFVLPNMEDIISSSSSPSSSSGSSTSLPSSPRDKCQMTPEHFTAQKMKKAYYLTQKIPDQDFYASVLDVLTPDDVRVLVEMEDEFSRRGQFERIFPS | ||||||
Compositional bias | 943-963 | Polar residues | ||||
Sequence: SSSSPSSSSGSSTSLPSSPRD | ||||||
Region | 943-966 | Disordered | ||||
Sequence: SSSSPSSSSGSSTSLPSSPRDKCQ | ||||||
Compositional bias | 1092-1122 | Polar residues | ||||
Sequence: MTTSKGDGTPNSASKSRKKSASEGTTLSSED | ||||||
Region | 1092-1193 | Disordered | ||||
Sequence: MTTSKGDGTPNSASKSRKKSASEGTTLSSEDRSTPKSKKSQAGLSPISRKTLSSRSNENTSKQSKRSTPGLPVLKYSGQSSRLSAASASQSVTDSRLTAVSS | ||||||
Compositional bias | 1129-1193 | Polar residues | ||||
Sequence: KKSQAGLSPISRKTLSSRSNENTSKQSKRSTPGLPVLKYSGQSSRLSAASASQSVTDSRLTAVSS |
Domain
The flexible c-MTBD (cationic microtubule binding domain) region mediates binding to microtubules. It is positively charged and becomes ordered when bound to microtubules: it interacts with a negatively charged patch on tubulin. The presence of positive charges in the c-MTBD region is essential for proper binding.
Arg-722 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.
Sequence similarities
Belongs to the tubulin--tyrosine ligase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,193
- Mass (Da)132,530
- Last updated2006-01-10 v3
- ChecksumE3C6FC5653D0E24E
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 20-37 | Polar residues | ||||
Sequence: KQRHPSGTVSASPSEKPS | ||||||
Compositional bias | 501-531 | Acidic residues | ||||
Sequence: VEPEDTEDELGDGLEDSCSHDENEEEEGDSE | ||||||
Compositional bias | 943-963 | Polar residues | ||||
Sequence: SSSSPSSSSGSSTSLPSSPRD | ||||||
Compositional bias | 1092-1122 | Polar residues | ||||
Sequence: MTTSKGDGTPNSASKSRKKSASEGTTLSSED | ||||||
Compositional bias | 1129-1193 | Polar residues | ||||
Sequence: KKSQAGLSPISRKTLSSRSNENTSKQSKRSTPGLPVLKYSGQSSRLSAASASQSVTDSRLTAVSS |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AM690747 EMBL· GenBank· DDBJ | CAM84324.1 EMBL· GenBank· DDBJ | mRNA | ||
BC044790 EMBL· GenBank· DDBJ | AAH44790.1 EMBL· GenBank· DDBJ | mRNA | ||
BC085151 EMBL· GenBank· DDBJ | AAH85151.1 EMBL· GenBank· DDBJ | mRNA | ||
AK129075 EMBL· GenBank· DDBJ | BAC97885.1 EMBL· GenBank· DDBJ | mRNA |