TTL11_CAEEL
ID TTL11_CAEEL Reviewed; 707 AA.
AC H2KZM9; Q9N5L6;
DT 18-SEP-2019, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 1.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=Tubulin polyglutamylase ttll-11 {ECO:0000305};
DE EC=6.-.-.- {ECO:0000305|PubMed:27635036, ECO:0000305|PubMed:29129530};
DE AltName: Full=Tubulin--tyrosine ligase-like protein 11 {ECO:0000312|WormBase:H23L24.3b};
GN Name=ttll-11 {ECO:0000312|WormBase:H23L24.3b};
GN ORFNames=H23L24.3 {ECO:0000312|WormBase:H23L24.3b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=20519502; DOI=10.1074/jbc.c110.128280;
RA Kimura Y., Kurabe N., Ikegami K., Tsutsumi K., Konishi Y., Kaplan O.I.,
RA Kunitomo H., Iino Y., Blacque O.E., Setou M.;
RT "Identification of tubulin deglutamylase among Caenorhabditis elegans and
RT mammalian cytosolic carboxypeptidases (CCPs).";
RL J. Biol. Chem. 285:22936-22941(2010).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP 191-THR--LEU-707.
RX PubMed=27635036; DOI=10.1242/bio.017442;
RA Chawla D.G., Shah R.V., Barth Z.K., Lee J.D., Badecker K.E., Naik A.,
RA Brewster M.M., Salmon T.P., Peel N.;
RT "Caenorhabditis elegans glutamylating enzymes function redundantly in male
RT mating.";
RL Biol. Open 5:1290-1298(2016).
RN [4] {ECO:0000305}
RP FUNCTION (ISOFORMS A AND B), CATALYTIC ACTIVITY, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY (ISOFORMS A AND B), AND MUTAGENESIS OF 191-THR--LEU-707.
RX PubMed=29129530; DOI=10.1016/j.cub.2017.09.066;
RA O'Hagan R., Silva M., Nguyen K.C.Q., Zhang W., Bellotti S., Ramadan Y.H.,
RA Hall D.H., Barr M.M.;
RT "Glutamylation Regulates Transport, Specializes Function, and Sculpts the
RT Structure of Cilia.";
RL Curr. Biol. 27:3430-3441.E6(2017).
CC -!- FUNCTION: Polyglutamylase which preferentially modifies tubulin
CC (PubMed:29129530, PubMed:27635036). Involved in the side-chain
CC initiation step of the polyglutamylation reaction (PubMed:29129530,
CC PubMed:27635036). By controlling tubulin glutamylation, regulates
CC ciliary specialization and motor-based transport. Promotes the
CC formation of A and B tubule singlets by splaying microtubule doublets
CC in cilia (PubMed:29129530). Together with ttll-4 and 5, required for
CC male mating (PubMed:27635036). {ECO:0000269|PubMed:27635036,
CC ECO:0000269|PubMed:29129530}.
CC -!- FUNCTION: [Isoform a]: Specifically promotes tubulin glutamylation in a
CC subset of ciliated neurons including amphid, phasmid, CEP and RnA
CC neurons. {ECO:0000269|PubMed:29129530}.
CC -!- FUNCTION: [Isoform b]: Specifically promotes tubulin glutamylation in
CC male ciliated CEM, HOB and RnB neurons that release bioactive
CC extracellular vesicles (PubMed:29129530). Regulates the localization of
CC TRP channel pdk-2 in male CEM, HOB and RnB neurons (PubMed:29129530).
CC Regulates the environmental release of bioactive extracellular vesicles
CC in cilia (PubMed:29129530). {ECO:0000269|PubMed:29129530}.
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:0000269|PubMed:29129530};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60145;
CC Evidence={ECO:0000269|PubMed:29129530};
CC -!- SUBCELLULAR LOCATION: Cell projection, axon
CC {ECO:0000269|PubMed:20519502, ECO:0000269|PubMed:29129530}. Perikaryon
CC {ECO:0000269|PubMed:29129530}. Cell projection, dendrite
CC {ECO:0000269|PubMed:29129530}. Cell projection, cilium
CC {ECO:0000269|PubMed:20519502}. Extracellular vesicle
CC {ECO:0000269|PubMed:29129530}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:H23L24.3b};
CC IsoId=H2KZM9-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:H23L24.3a};
CC IsoId=H2KZM9-2; Sequence=VSP_060273;
CC -!- TISSUE SPECIFICITY: Expressed in amphid sensory neurons
CC (PubMed:20519502, PubMed:29129530). Weakly expressed in body wall
CC muscles (PubMed:20519502). Isoform a: Specifically expressed in
CC ciliated sensory neurons in the head, including the IL1s, OLQ, head
CC CEP, and amphid neurons. In the male tail, expressed in HOA, RnA, and
CC phasmid neurons (PubMed:29129530). Isoform b: Specifically expressed in
CC male and hermaphrodite IL2 ciliated sensory neurons, and in male-
CC specific CEM, HOB and RnB ciliated sensory neurons (PubMed:29129530).
CC {ECO:0000269|PubMed:20519502, ECO:0000269|PubMed:29129530}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos and adults.
CC {ECO:0000269|PubMed:27635036}.
CC -!- SIMILARITY: Belongs to the tubulin--tyrosine ligase family.
CC {ECO:0000305}.
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DR EMBL; BX284604; CCD68978.2; -; Genomic_DNA.
DR EMBL; BX284604; CCD68979.1; -; Genomic_DNA.
DR RefSeq; NP_741471.2; NM_171405.4. [H2KZM9-1]
DR RefSeq; NP_741472.2; NM_171406.2.
DR AlphaFoldDB; H2KZM9; -.
DR SMR; H2KZM9; -.
DR STRING; 6239.H23L24.3b; -.
DR EPD; H2KZM9; -.
DR PaxDb; H2KZM9; -.
DR EnsemblMetazoa; H23L24.3a.1; H23L24.3a.1; WBGene00019230. [H2KZM9-2]
DR EnsemblMetazoa; H23L24.3b.1; H23L24.3b.1; WBGene00019230. [H2KZM9-1]
DR GeneID; 177677; -.
DR KEGG; cel:CELE_H23L24.3; -.
DR UCSC; H23L24.3b; c. elegans.
DR CTD; 177677; -.
DR WormBase; H23L24.3a; CE31706; WBGene00019230; ttll-11. [H2KZM9-2]
DR WormBase; H23L24.3b; CE34905; WBGene00019230; ttll-11. [H2KZM9-1]
DR eggNOG; KOG2158; Eukaryota.
DR GeneTree; ENSGT00940000156689; -.
DR HOGENOM; CLU_010131_6_1_1; -.
DR InParanoid; H2KZM9; -.
DR OMA; SAPDCNA; -.
DR OrthoDB; 1251554at2759; -.
DR PhylomeDB; H2KZM9; -.
DR Reactome; R-CEL-8955332; Carboxyterminal post-translational modifications of tubulin.
DR PRO; PR:H2KZM9; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00019230; Expressed in larva and 3 other tissues.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0015631; F:tubulin binding; IBA:GO_Central.
DR GO; GO:0070740; F:tubulin-glutamic acid ligase activity; IMP:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0018095; P:protein polyglutamylation; IMP:UniProtKB.
DR GO; GO:0034606; P:response to hermaphrodite contact; IGI:UniProtKB.
DR InterPro; IPR004344; TTL/TTLL_fam.
DR Pfam; PF03133; TTL; 1.
DR PROSITE; PS51221; TTL; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell projection; Ligase;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..707
FT /note="Tubulin polyglutamylase ttll-11"
FT /id="PRO_0000447857"
FT DOMAIN 124..488
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 675..707
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 675..699
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 279..282
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q6ZT98"
FT BINDING 293
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q6ZT98"
FT BINDING 295
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q6ZT98"
FT VAR_SEQ 1..100
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_060273"
FT MUTAGEN 191..707
FT /note="Missing: In tm4059; loss of tubulin glutamylation in
FT male CEM and CEP cilia. Defects in cilia axoneme structure.
FT Release of extracellular vesicles via cilia is reduced.
FT Abnormal accumulation of pkd-2 in cilia and dendrites of
FT male CEM, HOB and RnB neurons. Decreases kinesin klp-6
FT velocity in male CEM cilia. Normal klp-6 and osm-3 velocity
FT is restored in a ccpp-1 mutant background. No defect in
FT polar spindle formation in dividing embryonic cells, cilia-
FT dependent osmotic avoidance and in male mating efficiency."
FT /evidence="ECO:0000269|PubMed:27635036,
FT ECO:0000269|PubMed:29129530"
SQ SEQUENCE 707 AA; 81077 MW; DF57624955B32B96 CRC64;
MGCKISTEFC SDNPVGSIST SKVHPTDLST PSYAIKPVEF YEEPLKDDQL FYKVALAKKE
YREKEKDKKE QLSSNRRVSL QVEPNKLPIP LTRSSSLSSI MENRPPSGIS NSSFIRSRNT
ASRRFTIDTS RAKSNQYVVS LCSKKIGIIE YPDGRSDKQP CDVYWHNVVL SDMNKIVTSP
QSRVNKFPGM TELAKKISLT HSISSMQKLF PDEYAFYPNS WFLPAHLADF HAFYRKAQAL
GKTEMWFIVK PDEGAQGTGI YLINSPNQIR NVDQRQLVQE YVADPLLMND KLKFDFRVYG
VIKSINPLSI YVAREGMARF CTEKYEKPDS SNFKNLYAHL TNYSLNKANE AYVHSNTLQD
QTRGSKRLLS TVFHQLESRG VKTKRLWHDI KLILVKTTLA MLPEIMLHYE HHFYDSTGPQ
CFQIMGFDVM IREDGTPILL EVNAAPSLTA DHIVPHPGRT LLEGGQRVRS IVDEVIKIPL
VRDTLLLVLG LMEEEYQNNS LKGETKSLDD MQTIKQRRKP HLSEIFPTRY GAHSGHLLFL
DKAMYIYMQF VQLRSNVNIT NAGLKQFVRK CNLIDIIPVV HVDAKVSEIN YYFTGEKRTN
GNGLPFHAFL MFLFFIAEKK FVLENDLLSK VQRLLSFCDM SLRRYGVRSA RLRRAEVDST
IGNVEIYMLP SRMARNRSGT NGRKQNFTDD NNNPNSFAHL PKINERL
