TTLL6_DANRE
ID TTLL6_DANRE Reviewed; 778 AA.
AC A8CVX7;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 1.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Tubulin polyglutamylase ttll6 {ECO:0000303|PubMed:22246503};
DE EC=6.3.2.- {ECO:0000250|UniProtKB:A4Q9E8};
DE AltName: Full=Protein polyglutamylase TTLL6 {ECO:0000250|UniProtKB:A4Q9E8};
DE AltName: Full=Tubulin tyrosine ligase-like family member 6;
GN Name=ttll6 {ECO:0000312|EMBL:ABV26100.1};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17761526; DOI=10.1091/mbc.e07-06-0537;
RA Pathak N.H., Obara T., Mangos S., Liu Y., Drummond I.A.;
RT "The zebrafish fleer gene encodes an essential regulator of cilia tubulin
RT polyglutamylation.";
RL Mol. Biol. Cell 18:4353-4364(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22246503; DOI=10.1038/ng.1078;
RA Lee J.E., Silhavy J.L., Zaki M.S., Schroth J., Bielas S.L., Marsh S.E.,
RA Olvera J., Brancati F., Iannicelli M., Ikegami K., Schlossman A.M.,
RA Merriman B., Attie-Bitach T., Logan C.V., Glass I.A., Cluckey A.,
RA Louie C.M., Lee J.H., Raynes H.R., Rapin I., Castroviejo I.P., Setou M.,
RA Barbot C., Boltshauser E., Nelson S.F., Hildebrandt F., Johnson C.A.,
RA Doherty D.A., Valente E.M., Gleeson J.G.;
RT "CEP41 is mutated in Joubert syndrome and is required for tubulin
RT glutamylation at the cilium.";
RL Nat. Genet. 44:193-199(2012).
CC -!- FUNCTION: Polyglutamylase which modifies both tubulin and non-tubulin
CC proteins, generating alpha-linked polyglutamate side chains on the
CC gamma-carboxyl group of specific glutamate residues of target proteins
CC (By similarity). Preferentially mediates ATP-dependent long
CC polyglutamate chain elongation over the initiation step of the
CC polyglutamylation reaction (By similarity). Preferentially modifies the
CC alpha-tubulin tail over a beta-tail (By similarity). Mediates
CC microtubule polyglutamylation in cilia axoneme, which is important for
CC ciliary structural formation and motility (PubMed:17761526,
CC PubMed:22246503). Polyglutamylates olfactory cilia, necessary for the
CC regulation of ciliary sructure and beating (PubMed:17761526).
CC {ECO:0000250|UniProtKB:A4Q9E8, ECO:0000269|PubMed:17761526,
CC ECO:0000269|PubMed:22246503}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-glutamate + L-glutamyl-[protein] = ADP + gamma-L-
CC glutamyl-L-glutamyl-[protein] + H(+) + phosphate;
CC Xref=Rhea:RHEA:60144, Rhea:RHEA-COMP:10208, Rhea:RHEA-COMP:15517,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29973, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:143622,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60145;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(L-glutamyl)(n)-gamma-L-glutamyl-L-glutamyl-[protein] + ATP +
CC L-glutamate = (L-glutamyl)(n+1)-gamma-L-glutamyl-L-glutamyl-[protein]
CC + ADP + H(+) + phosphate; Xref=Rhea:RHEA:60148, Rhea:RHEA-COMP:15519,
CC Rhea:RHEA-COMP:15675, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:143623,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60149;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:A4Q9E8}.
CC Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:A4Q9E8}. Cytoplasm,
CC cytoskeleton, cilium axoneme {ECO:0000269|PubMed:22246503}. Cytoplasm,
CC cytoskeleton, cilium basal body {ECO:0000269|PubMed:22246503}.
CC Note=CEP41 is required for its transport between the basal body and the
CC cilium axoneme. {ECO:0000269|PubMed:22246503}.
CC -!- DOMAIN: The flexible c-MTBD (cationic microtubule binding domain)
CC region mediates binding to microtubules. It is positively charged and
CC becomes ordered when bound to microtubules: it interacts with a
CC negatively charged patch on tubulin. The presence of positive charges
CC in the c-MTBD region is essential for proper binding.
CC {ECO:0000250|UniProtKB:Q6ZT98, ECO:0000250|UniProtKB:Q8N841}.
CC -!- DOMAIN: Gln-174 is the main determinant for regioselectivity, which
CC segregates between initiases and elongases in all tubulin--tyrosine
CC ligase family. A glutamine residue at this position is found in
CC elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-
CC chain elongation, whereas an arginine residue is found in initiases
CC TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.
CC {ECO:0000250|UniProtKB:A4Q9E8}.
CC -!- DISRUPTION PHENOTYPE: Fish display a lack of tubulin polyglutamylation
CC and cilia formation in olfactory placodes.
CC {ECO:0000269|PubMed:17761526}.
CC -!- SIMILARITY: Belongs to the tubulin--tyrosine ligase family.
CC {ECO:0000255}.
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DR EMBL; EU124004; ABV26100.1; -; mRNA.
DR EMBL; BX001014; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001098994.1; NM_001105524.1.
DR AlphaFoldDB; A8CVX7; -.
DR SMR; A8CVX7; -.
DR STRING; 7955.ENSDARP00000124416; -.
DR PaxDb; A8CVX7; -.
DR GeneID; 564075; -.
DR KEGG; dre:564075; -.
DR CTD; 284076; -.
DR ZFIN; ZDB-GENE-080107-1; ttll6.
DR eggNOG; KOG2158; Eukaryota.
DR InParanoid; A8CVX7; -.
DR OrthoDB; 1251554at2759; -.
DR PhylomeDB; A8CVX7; -.
DR BRENDA; 6.3.2.B3; 928.
DR PRO; PR:A8CVX7; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0005929; C:cilium; IDA:ZFIN.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070739; F:protein-glutamic acid ligase activity; ISS:UniProtKB.
DR GO; GO:0015631; F:tubulin binding; ISS:UniProtKB.
DR GO; GO:0070740; F:tubulin-glutamic acid ligase activity; IMP:ZFIN.
DR GO; GO:0035082; P:axoneme assembly; IMP:ZFIN.
DR GO; GO:0003341; P:cilium movement; IGI:ZFIN.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0018095; P:protein polyglutamylation; IMP:UniProtKB.
DR GO; GO:0060296; P:regulation of cilium beat frequency involved in ciliary motility; ISS:UniProtKB.
DR InterPro; IPR004344; TTL/TTLL_fam.
DR Pfam; PF03133; TTL; 1.
DR PROSITE; PS51221; TTL; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell projection; Cilium; Cilium biogenesis/degradation;
KW Cytoplasm; Cytoskeleton; Ligase; Magnesium; Metal-binding; Microtubule;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..778
FT /note="Tubulin polyglutamylase ttll6"
FT /id="PRO_0000326162"
FT DOMAIN 51..393
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 259..260
FT /note="L-glutamate"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT REGION 365..445
FT /note="c-MTBD region"
FT /evidence="ECO:0000250|UniProtKB:Q8N841"
FT REGION 402..422
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 485..542
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 758..778
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 402..417
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 485..515
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 759..778
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 168
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 174..175
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 174
FT /ligand="a protein"
FT /ligand_id="ChEBI:CHEBI:16541"
FT /ligand_part="L-glutamate residue"
FT /ligand_part_id="ChEBI:CHEBI:29973"
FT /ligand_part_note="L-glutamate acceptor residue in protein
FT target"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 196..199
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 209..211
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 235
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 257..258
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 277
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 340
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 353
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 353
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 355
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 356
FT /ligand="a protein"
FT /ligand_id="ChEBI:CHEBI:16541"
FT /ligand_part="L-glutamate residue"
FT /ligand_part_id="ChEBI:CHEBI:29973"
FT /ligand_part_note="L-glutamate acceptor residue in protein
FT target"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 371
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 174
FT /note="Essential for specifying alpha-elongation versus
FT initiation step of the polyglutamylase activity"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 356
FT /note="Important for specifying alpha-elongation versus
FT initiation step of the polyglutamylase activity"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
SQ SEQUENCE 778 AA; 89875 MW; 56A7DD1C4B1A5BFB CRC64;
MGTPAERSVS EVCRCEPDPG LEGEGWGSDT HAEPSNTPIP LPVANKKKKR KKKLWINLTN
CKYESVRRAA RRYGIREAAE GEDWTLYWTD CSVSLDRVMD MKRYQKINHF PGMNEICRKD
LLARNMNRML KLFPKEYNIF PRTWCLPADY SDFQAYTRAK KHKTFICKPD SGCQGRGIYL
TKSSKDIRPG EHMICQVYMS KPFIIDGFKF DLRIYVLVTS CDPFRVFMYD EGLVRFCTTH
YTEPTVSNLE DVCMHLTNYA INKHSENFVR DEDTGSKRKL SSFKKHMEDM SYDTEKLWTD
IEDAIIKTLI SAHPILKHNY QTCFPNHASG SACFEILGFD VLLDRRLKPW LLEVNHSPSF
TTDSRLDREV KDSLLYDTLV LINLGACDRR KITEEEKRRV KERLQQNRSR EARNEEPRQS
QAASMELMQK YEAKHMGGFR RIFPRDGGEK YEKYFQHSSS LFQETAASKA REECARQQLQ
ELRLKQEQKE RDKKGSRKQD LQGESAGEKV KPRKSQPPHK TSNSLPAMLE LSSVREETPV
SLERIEKEEA ERVRELQQRE TLLLNMGVVN QVRQLLQSAN RLTQCINHSH EQASFPPHCR
HDHKLDTLAE ISWRQKNIYS TMQHQILARN RPSLPNVHSQ TLQNRKPWPS LEHGLLQPVQ
TQAAALKHYG LEEMVASNAE EQANLIKATS AQQIPLTING SFIWRQGSLS SSLAESRARA
TMLAMPPLGP GRLHRPTIFH DPNSLSIIST PAPLVPRPHL SHDLRKAPRR VLPHEHSL
