TTLL3_DANRE
ID TTLL3_DANRE Reviewed; 771 AA.
AC Q1ECV4;
DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2006, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Tubulin monoglycylase TTLL3 {ECO:0000250|UniProtKB:A4Q9E5};
DE EC=6.3.2.- {ECO:0000250|UniProtKB:A4Q9E5};
DE AltName: Full=Tubulin--tyrosine ligase-like protein 3;
GN Name=ttll3; ORFNames=zgc:136840;
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 [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP DISRUPTION PHENOTYPE.
RX PubMed=19531357; DOI=10.1016/j.devcel.2009.04.008;
RA Wloga D., Webster D.M., Rogowski K., Bre M.-H., Levilliers N.,
RA Jerka-Dziadosz M., Janke C., Dougan S.T., Gaertig J.;
RT "TTLL3 Is a tubulin glycine ligase that regulates the assembly of cilia.";
RL Dev. Cell 16:867-876(2009).
CC -!- FUNCTION: Monoglycylase which modifies alpha- and beta-tubulin, adding
CC a single glycine on the gamma-carboxyl groups of specific glutamate
CC residues to generate monoglycine side chains within the C-terminal tail
CC of tubulin. Not involved in elongation step of the polyglycylation
CC reaction (By similarity). Preferentially glycylates a beta-tail peptide
CC over the alpha-tail, although shifts its preference toward alpha-tail
CC as beta-tail glutamylation increases (By similarity). Competes with
CC polyglutamylases for modification site on beta-tubulin substrate,
CC thereby creating an anticorrelation between glycylation and
CC glutamylation reactions (By similarity). Not involved in elongation
CC step of the polyglycylation reaction (By similarity).
CC {ECO:0000250|UniProtKB:A4Q9E5, ECO:0000250|UniProtKB:B2GUB3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glycine + L-glutamyl-[protein] = ADP + glycyl-L-
CC glutamyl-[protein] + H(+) + phosphate; Xref=Rhea:RHEA:67180,
CC Rhea:RHEA-COMP:10208, Rhea:RHEA-COMP:17207, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29973, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:167890, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67181;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E5};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:A4Q9E5}. Cell projection, cilium
CC {ECO:0000250|UniProtKB:A4Q9E5}. Cytoplasm, cytoskeleton, cilium axoneme
CC {ECO:0000250|UniProtKB:A4Q9E5}. Cytoplasm, cytoskeleton, flagellum
CC axoneme {ECO:0000250|UniProtKB:A4Q9E5}.
CC -!- DOMAIN: Two conserved structural elements specific among
CC monoglycylases, IS1 and IS2, are involved in glycyl chains initiation.
CC Two conserved structural interfaces likely constitute the binding
CC platforms for tubulin tail and microtubule.
CC {ECO:0000250|UniProtKB:B2GUB3}.
CC -!- DOMAIN: Arg-345 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: Shortening and loss of cilia in several organs,
CC including the Kupffer's vesicle and olfactory placode.
CC {ECO:0000269|PubMed:19531357}.
CC -!- CAUTION: TTLL3 and TTLL8 monoglycylase-mediated glycylation of tubulin
CC was initially reported to play a role in ependymal motile ciliary
CC maintenance (By similarity). However, contradictory results were later
CC observed (By similarity). {ECO:0000250|UniProtKB:A4Q9E5}.
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DR EMBL; BC117656; AAI17657.1; -; mRNA.
DR RefSeq; NP_001038770.1; NM_001045305.1.
DR AlphaFoldDB; Q1ECV4; -.
DR SMR; Q1ECV4; -.
DR STRING; 7955.ENSDARP00000105880; -.
DR PaxDb; Q1ECV4; -.
DR GeneID; 724000; -.
DR KEGG; dre:724000; -.
DR CTD; 26140; -.
DR ZFIN; ZDB-GENE-060616-182; ttll3.
DR eggNOG; KOG2157; Eukaryota.
DR InParanoid; Q1ECV4; -.
DR OrthoDB; 1137333at2759; -.
DR PhylomeDB; Q1ECV4; -.
DR PRO; PR:Q1ECV4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005930; C:axoneme; ISS:UniProtKB.
DR GO; GO:0005929; C:cilium; IDA:ZFIN.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISS:UniProtKB.
DR GO; GO:0031514; C:motile cilium; 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:0070735; F:protein-glycine ligase activity; IMP:UniProtKB.
DR GO; GO:0070736; F:protein-glycine ligase activity, initiating; ISS:UniProtKB.
DR GO; GO:0070738; F:tubulin-glycine ligase activity; IMP:ZFIN.
DR GO; GO:0035082; P:axoneme assembly; IMP:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0003341; P:cilium movement; IGI:ZFIN.
DR GO; GO:0018094; P:protein polyglycylation; IMP:UniProtKB.
DR InterPro; IPR004344; TTL/TTLL_fam.
DR InterPro; IPR027753; TTLL3.
DR PANTHER; PTHR45870:SF1; PTHR45870:SF1; 1.
DR Pfam; PF03133; TTL; 1.
DR PROSITE; PS51221; TTL; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell projection; Cilium; Cytoplasm; Cytoskeleton; Flagellum;
KW Ligase; Magnesium; Metal-binding; Microtubule; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..771
FT /note="Tubulin monoglycylase TTLL3"
FT /id="PRO_0000381794"
FT DOMAIN 220..566
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 70..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 605..640
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 682..713
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 70..87
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 88..106
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 609..633
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 339
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 345..346
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 345
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 377..380
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:B2GUB3"
FT BINDING 390..392
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 434..435
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 512
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 525
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:B2GUB3"
FT BINDING 525
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 525
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 527
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 345
FT /note="Essential for specifying initiation versus
FT elongation step of the polyglycylase activity"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
SQ SEQUENCE 771 AA; 88876 MW; C03BBD7BEBC58621 CRC64;
MHQHIQVPPL EGKSRINYVN LPLINGDKLR TAKTLVDKAI KEKKVFSVQG PYPVIRAGLR
ARGWVERRLP RPSFSQPRRH DHETETTDEG DSSDEDDLGE EVERDDEAED LYDLMSRLVR
HETPYFYWTT RRDSVDCRSL RKEQMTNHYA KAGSFTTKVG LCMHLRNLQW FDAADPDTFF
PRCYRLGAQD EKHAFIDDFR RTACTSLLLY VLEKYEGDSE GEKMGEVHNA KSHGLRKTRK
QHSSQRIETS VIDSALHVCQ EYLNSLEHCD IDNNLETNST ISEQQWKVFL QNYYLVVHEG
INIEGCEYYL ERCKCMLEQM RQVCPQMEND GICNIWIIKP GAKSRGRGIM CMNKLDDMLG
LVDGDHCIMK DSKWVVQKYI ERPLLVHDTK FDVRQWFLVT DWNPLTVWFY RECYLRFSTQ
PYSTHTLDSS VHLCNNSIQK HYQPSPDRSP SLPAECMWSC SQFRSWLAAS GRAALWKAVV
VPGMQKAVIQ TLLTAQDSVE PRKASFELYG ADFMLGRDLR PWLLEINASP TMAPSTGVTA
RLCPAVQEDT LRVVLDRRSE RNTDTGGFQL IYKQAAVDVP QYVGVNLLIE GTSIRRPRAP
VHKSLIQSHP EPLSKSTNHK SSLLSSPCTS GKENQSEEVK RACPNLPNRK ITMDQSLIFH
PKRKRPHRLV LPSTCCVLPN PTELHHPQRL SHTQPQSDRP HTHRTRSNLP TLYRPTPSVE
VINIRPRQAL TSSHYIHKIH TVNLSYPVLR MQQNHRRSKN TFAEREGPKS S
