TTLL4_CAEEL
ID TTLL4_CAEEL Reviewed; 601 AA.
AC Q09647; Q5FC81;
DT 11-JAN-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 3.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Tubulin polyglutamylase ttll-4;
DE EC=6.3.2.- {ECO:0000269|PubMed:32747782};
DE AltName: Full=Tubulin--tyrosine ligase-like protein 4 {ECO:0000303|PubMed:32747782};
GN Name=ttll-4 {ECO:0000312|WormBase:ZK1128.6a};
GN ORFNames=ZK1128.6 {ECO:0000312|WormBase:ZK1128.6a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
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]
RP FUNCTION, 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]
RP DISRUPTION PHENOTYPE.
RX PubMed=24780738; DOI=10.1016/j.devcel.2014.03.007;
RA Lacroix B., Bourdages K.G., Dorn J.F., Ihara S., Sherwood D.R.,
RA Maddox P.S., Maddox A.S.;
RT "In situ imaging in C. elegans reveals developmental regulation of
RT microtubule dynamics.";
RL Dev. Cell 29:203-216(2014).
RN [4]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
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 [5]
RP FUNCTION, AND MUTAGENESIS OF THR-446.
RX PubMed=29849065; DOI=10.1038/s41598-018-26694-w;
RA Kimura Y., Tsutsumi K., Konno A., Ikegami K., Hameed S., Kaneko T.,
RA Kaplan O.I., Teramoto T., Fujiwara M., Ishihara T., Blacque O.E., Setou M.;
RT "Environmental responsiveness of tubulin glutamylation in sensory cilia is
RT regulated by the p38 MAPK pathway.";
RL Sci. Rep. 8:8392-8392(2018).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=32747782; DOI=10.1038/s41594-020-0462-0;
RA Mahalingan K.K., Keith Keenan E., Strickland M., Li Y., Liu Y., Ball H.L.,
RA Tanner M.E., Tjandra N., Roll-Mecak A.;
RT "Structural basis for polyglutamate chain initiation and elongation by TTLL
RT family enzymes.";
RL Nat. Struct. Mol. Biol. 27:802-813(2020).
CC -!- FUNCTION: Monoglutamylase which modifies tubulin, adding a single
CC glutamate on the gamma-carboxyl group of specific glutamate residues of
CC target proteins (PubMed:32747782). Involved in the side-chain
CC initiation step of the polyglutamylation reaction but not in the
CC elongation step. Preferentially modifies beta-tail tubulin over the
CC alpha-tubulin (PubMed:32747782). Involved in side-chain glutamylation
CC of tubulin in sensory cilia (PubMed:20519502, PubMed:27635036,
CC PubMed:29849065). Together with ttll-5 and ttll-11, required for male
CC mating (PubMed:27635036). {ECO:0000269|PubMed:20519502,
CC ECO:0000269|PubMed:27635036, ECO:0000269|PubMed:29849065,
CC ECO:0000269|PubMed:32747782}.
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:32747782};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60145;
CC Evidence={ECO:0000305|PubMed:32747782};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.66 uM for non-glutamylated tubulin
CC {ECO:0000269|PubMed:32747782};
CC KM=5.35 uM for glutamylated tubulin {ECO:0000269|PubMed:32747782};
CC Note=kcat is 0.102 min(-1) non-glutamylated tubulin as substrate
CC (PubMed:32747782). kcat is 0.027 min(-1) glutamylated tubulin as
CC substrate (PubMed:32747782). {ECO:0000269|PubMed:32747782};
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:ZK1128.6a};
CC IsoId=Q09647-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:ZK1128.6b};
CC IsoId=Q09647-2; Sequence=VSP_040444;
CC -!- TISSUE SPECIFICITY: Expressed in many sensory neurons in amphid.
CC {ECO:0000269|PubMed:20519502}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos and adults.
CC {ECO:0000269|PubMed:27635036}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown at the L1 or L4 larval
CC stages causes a defect in egg-laying. {ECO:0000269|PubMed:24780738}.
CC -!- SIMILARITY: Belongs to the tubulin--tyrosine ligase family.
CC {ECO:0000305}.
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DR EMBL; BX284603; CAA87425.3; -; Genomic_DNA.
DR EMBL; BX284603; CAI46580.1; -; Genomic_DNA.
DR PIR; E88575; E88575.
DR PIR; T27699; T27699.
DR RefSeq; NP_001022985.1; NM_001027814.2. [Q09647-1]
DR RefSeq; NP_001022986.1; NM_001027815.3. [Q09647-2]
DR AlphaFoldDB; Q09647; -.
DR SMR; Q09647; -.
DR BioGRID; 41621; 3.
DR STRING; 6239.ZK1128.6a; -.
DR EPD; Q09647; -.
DR PaxDb; Q09647; -.
DR PeptideAtlas; Q09647; -.
DR PRIDE; Q09647; -.
DR EnsemblMetazoa; ZK1128.6a.1; ZK1128.6a.1; WBGene00014232. [Q09647-1]
DR EnsemblMetazoa; ZK1128.6b.1; ZK1128.6b.1; WBGene00014232. [Q09647-2]
DR EnsemblMetazoa; ZK1128.6b.2; ZK1128.6b.2; WBGene00014232. [Q09647-2]
DR EnsemblMetazoa; ZK1128.6b.3; ZK1128.6b.3; WBGene00014232. [Q09647-2]
DR GeneID; 176427; -.
DR KEGG; cel:CELE_ZK1128.6; -.
DR UCSC; ZK1128.6a; c. elegans.
DR CTD; 176427; -.
DR WormBase; ZK1128.6a; CE29940; WBGene00014232; ttll-4. [Q09647-1]
DR WormBase; ZK1128.6b; CE38015; WBGene00014232; ttll-4. [Q09647-2]
DR eggNOG; KOG2156; Eukaryota.
DR GeneTree; ENSGT00940000157916; -.
DR InParanoid; Q09647; -.
DR OMA; HRWSQIP; -.
DR OrthoDB; 219807at2759; -.
DR PhylomeDB; Q09647; -.
DR Reactome; R-CEL-8955332; Carboxyterminal post-translational modifications of tubulin.
DR PRO; PR:Q09647; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00014232; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
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; IDA:UniProtKB.
DR GO; GO:0015631; F:tubulin binding; IBA:GO_Central.
DR GO; GO:0070740; F:tubulin-glutamic acid ligase activity; IDA: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 InterPro; IPR027748; TTLL-4.
DR PANTHER; PTHR12241:SF145; PTHR12241:SF145; 1.
DR Pfam; PF03133; TTL; 1.
DR PROSITE; PS51221; TTL; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Ligase; Magnesium; Metal-binding;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..601
FT /note="Tubulin polyglutamylase ttll-4"
FT /id="PRO_0000403767"
FT DOMAIN 138..476
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 344..345
FT /note="L-glutamate"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 20..37
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 254
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 260..261
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 260
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 282..285
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 295..297
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 321
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 342..343
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 362
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 422
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 435
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 435
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 437
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 453
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 260
FT /note="Essential for specifying initiation versus
FT elongation step of the polyglutamylase activity"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT VAR_SEQ 1..38
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_040444"
FT MUTAGEN 446
FT /note="T->A: Impairs increase in tubulin glutamylation
FT levels in sensory cilia in response to starvation. Has no
FT effect on basal tubulin glutamylation levels in sensory
FT cilia."
FT /evidence="ECO:0000269|PubMed:29849065"
FT MUTAGEN 446
FT /note="T->E: Increases basal tubulin glutamylation levels
FT in sensory cilia."
FT /evidence="ECO:0000269|PubMed:29849065"
SQ SEQUENCE 601 AA; 69188 MW; 8EF1E33096CD5756 CRC64;
MSSGYSSAPS VSHTSSDTDL NRIDSYDDGA EETTDEQRMC GLSELVTSCL TSSRLKAIDE
EDEEENCNDI EIVGLSKTTT KVKRSKKVLS CPIVSSSTKK ENGNAAPFLK SSQFTDVPPT
IRFYTKGTKV TKPARKIQAR LTWCHNSLLP IVMRQTLAAS HFTVVDESLF YVGYWGRHLK
SAQYRALQPH QKVNHFPGAF HIGRKDRLWM HIRKQQERFE GEFDIMPFTY ILPTDRQELL
KYLETDASRH VIVKPPASAR GTGISVTRKP KDFPTTATLV AQHYIERPLT INRAKFDLRL
YAYVPTFEPL RVYIYDQGLV RFASVPYSHS VSTISNKYMH LTNYSINKLA EADGVANKPV
PKWTLHHLWE HFDEMGVDRE KIQREIEEVI IKAFISTEKP IREHMSRFLE QEFICYELFG
IDIILDEDYK PWLLEVNISP SLHSGTPLDV SVKAPLAKDV LNLAGVYVPP SFDKLSDADY
STRPRNGRKN REQLIKEASW VAAYKDQLGV IDNRIFKRLT PEDTRALVEF EDELERIGDF
KLVFPTAHTS HYQKYFAETI YMNILLQQWQ IAQEDDRSIG INRLEQLCRQ KHMQSDQETS
F
