TTLL3_XENTR
ID TTLL3_XENTR Reviewed; 830 AA.
AC B2GUB3;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Tubulin tyrosine ligase 3 {ECO:0000303|PubMed:28576883};
DE EC=6.3.2.- {ECO:0000269|PubMed:28576883};
DE AltName: Full=Tubulin--tyrosine ligase protein 3 {ECO:0000250|UniProtKB:A4Q9E5};
GN Name=ttll3;
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20431018; DOI=10.1126/science.1183670;
RA Hellsten U., Harland R.M., Gilchrist M.J., Hendrix D., Jurka J.,
RA Kapitonov V., Ovcharenko I., Putnam N.H., Shu S., Taher L., Blitz I.L.,
RA Blumberg B., Dichmann D.S., Dubchak I., Amaya E., Detter J.C., Fletcher R.,
RA Gerhard D.S., Goodstein D., Graves T., Grigoriev I.V., Grimwood J.,
RA Kawashima T., Lindquist E., Lucas S.M., Mead P.E., Mitros T., Ogino H.,
RA Ohta Y., Poliakov A.V., Pollet N., Robert J., Salamov A., Sater A.K.,
RA Schmutz J., Terry A., Vize P.D., Warren W.C., Wells D., Wills A.,
RA Wilson R.K., Zimmerman L.B., Zorn A.M., Grainger R., Grammer T.,
RA Khokha M.K., Richardson P.M., Rokhsar D.S.;
RT "The genome of the Western clawed frog Xenopus tropicalis.";
RL Science 328:633-636(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.29 ANGSTROMS) OF 6-569 IN COMPLEX WITH ATP ANALOG,
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-16; LYS-24; LYS-26;
RP LYS-119; ARG-126; LYS-130; LEU-134; LYS-139; SER-142; TRP-158; PHE-159;
RP ASP-265; ASP-267; ARG-389; ARG-411; ARG-556 AND LYS-568.
RX PubMed=28576883; DOI=10.1073/pnas.1617286114;
RA Garnham C.P., Yu I., Li Y., Roll-Mecak A.;
RT "Crystal structure of tubulin tyrosine ligase-like 3 reveals essential
RT architectural elements unique to tubulin monoglycylases.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:6545-6550(2017).
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 (PubMed:28576883). Preferentially glycylates a beta-tail
CC peptide over the alpha-tail, although shifts its preference toward
CC alpha-tail as beta-tail glutamylation increases (PubMed:28576883).
CC Competes with polyglutamylases for modification site on beta-tubulin
CC substrate, thereby creating an anticorrelation between glycylation and
CC glutamylation reactions (PubMed:28576883). Together with TTLL8,
CC mediates microtubule glycylation of primary and motile cilia, which is
CC essential for their stability and maintenance (By similarity).
CC {ECO:0000250|UniProtKB:A4Q9E5, ECO:0000269|PubMed:28576883}.
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:0000269|PubMed:28576883};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67181;
CC Evidence={ECO:0000305|PubMed:28576883};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:28576883}. 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:0000269|PubMed:28576883}.
CC -!- DOMAIN: Arg-340 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 -!- 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; AAMC04000004; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC166209; AAI66209.1; -; mRNA.
DR RefSeq; NP_001121450.1; NM_001127978.2.
DR PDB; 5VLQ; X-ray; 2.29 A; A/B=6-569.
DR PDBsum; 5VLQ; -.
DR SMR; B2GUB3; -.
DR GeneID; 100158544; -.
DR KEGG; xtr:100158544; -.
DR CTD; 100158544; -.
DR Xenbase; XB-GENE-5950142; XB5950141.
DR OrthoDB; 1137333at2759; -.
DR Proteomes; UP000008143; Chromosome 4.
DR Proteomes; UP000790000; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
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:0070736; F:protein-glycine ligase activity, initiating; IDA:UniProtKB.
DR GO; GO:0018094; P:protein polyglycylation; IDA: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 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell projection; Cilium; Cytoplasm;
KW Cytoskeleton; Flagellum; Ligase; Magnesium; Metal-binding; Microtubule;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..830
FT /note="Tubulin tyrosine ligase 3"
FT /id="PRO_0000453203"
FT DOMAIN 211..561
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 52..102
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 52..68
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 69..97
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 334
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 340..341
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 340
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 372..375
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:28576883,
FT ECO:0007744|PDB:5VLQ"
FT BINDING 385..387
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 429..430
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 507
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 520
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:28576883,
FT ECO:0007744|PDB:5VLQ"
FT BINDING 520
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 520
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 522
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 340
FT /note="Essential for specifying initiation versus
FT elongation step of the polyglycylase activity"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT MUTAGEN 16
FT /note="K->A: Decreased monoglycylation activity; when
FT associated with A-134."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 24
FT /note="K->A: Decreased monoglycylation activity; when
FT associated with A-26."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 26
FT /note="K->A: Decreased monoglycylation activity; when
FT associated with A-24."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 119
FT /note="K->E: Decreased monoglycylation activity."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 126
FT /note="R->E: Decreased monoglycylation activity."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 130
FT /note="K->E: Decreased monoglycylation activity."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 134
FT /note="L->A: Decreased monoglycylation activity; when
FT associated with A-16."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 139
FT /note="K->E: Decreased monoglycylation activity."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 142
FT /note="S->A: Increased monoglycylation activity."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 142
FT /note="S->D: Decreased monoglycylation activity."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 158
FT /note="W->A: Decreased monoglycylation activity."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 159
FT /note="F->A: Decreased monoglycylation activity."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 265
FT /note="D->N: Decreased monoglycylation activity; when
FT associated with N-267."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 267
FT /note="D->N: Decreased monoglycylation activity; when
FT associated with N-265."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 389
FT /note="R->E: Decreased monoglycylation activity."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 411
FT /note="R->E: Decreased monoglycylation activity."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 556
FT /note="R->E: Decreased monoglycylation activity."
FT /evidence="ECO:0000269|PubMed:28576883"
FT MUTAGEN 568
FT /note="K->E: Decreased monoglycylation activity."
FT /evidence="ECO:0000269|PubMed:28576883"
FT HELIX 11..24
FT /evidence="ECO:0007829|PDB:5VLQ"
FT STRAND 28..34
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 36..44
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 100..106
FT /evidence="ECO:0007829|PDB:5VLQ"
FT TURN 107..109
FT /evidence="ECO:0007829|PDB:5VLQ"
FT STRAND 113..119
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:5VLQ"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 146..154
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 155..158
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 182..200
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 245..257
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 279..283
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 285..292
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 301..304
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 305..318
FT /evidence="ECO:0007829|PDB:5VLQ"
FT TURN 320..325
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 350..355
FT /evidence="ECO:0007829|PDB:5VLQ"
FT STRAND 371..373
FT /evidence="ECO:0007829|PDB:5VLQ"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:5VLQ"
FT STRAND 381..384
FT /evidence="ECO:0007829|PDB:5VLQ"
FT STRAND 386..396
FT /evidence="ECO:0007829|PDB:5VLQ"
FT TURN 397..400
FT /evidence="ECO:0007829|PDB:5VLQ"
FT STRAND 401..406
FT /evidence="ECO:0007829|PDB:5VLQ"
FT STRAND 409..412
FT /evidence="ECO:0007829|PDB:5VLQ"
FT STRAND 451..454
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 455..464
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 470..473
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 475..488
FT /evidence="ECO:0007829|PDB:5VLQ"
FT STRAND 502..511
FT /evidence="ECO:0007829|PDB:5VLQ"
FT STRAND 516..524
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 532..549
FT /evidence="ECO:0007829|PDB:5VLQ"
FT HELIX 551..554
FT /evidence="ECO:0007829|PDB:5VLQ"
FT STRAND 563..568
FT /evidence="ECO:0007829|PDB:5VLQ"
SQ SEQUENCE 830 AA; 92974 MW; 4C598FFB667956E0 CRC64;
MAHHTAVNPD RLKHAKALVE KAIKQKKIFA IHGPYPVIRS CLRSRGWVEK KFPKSGKAKQ
KKEKASDEDM EDDDGDGSSN DDDDGENSDE EENGDPDGTC DLMSRLLRNE DPNFFWTTKR
DAVDCRFLKK DQMLNHYAKA GSFTTKVGLC LNLRNLHWFD DADPDSFFPR CYRLGAEDEK
QSFKEDFWHT AARSILKRVA NRRDICSPAA TGGAKASHRE PGANNGAQLL AKRGSRKRAE
SVPVQIILTA LEACERYLNS LEHNDIDMET EATPAMTDTQ WEEFLHGYYQ VIHDGATIEH
SEYYVDQCSE VLHKLEAVNP QLDIEGGRNI WIVKPGAKSR GRGIICMDRL EEILKLVDCD
PMIVKDGKWV VQKYIERPLL IFGTKFDVRQ WFLVTDWNPL TIWFYKECYV RFSSQPFSLE
NLDTSIHLCN NSIQKHYENS QSRHPLVPTD NMWSSRQLQV HLHKLGAPHA WEAVIVPGMK
AAIIHAMQSA QDIVEYRKSS FELYGADFMF GENFHPWLIE INASPTMAAS TTVTSRLCAE
VQEDTLRIVL DRKLDRNCDI GAFELIYKQC AVDIPQYLGI NLLVEGSMVK KPRQLQQPNP
NGAFNLSIVQ SNKRSVSLLN AKTSGSNPGV GSQDSVKVAV PTRTAPAVMG NDFWTSRTHG
TIGRAKTTAA GKENKAAEGG QRNSVMVELV RLPSKRALEQ SKEGTNPRQR LFPAPKSCTL
EKPIRVRQPI RLKNGGFVDL KFTSLDSGQV QLLRNMKTGM TDPNKMPCLF CKGPSSLTGL
HAMCSCSRAG KQAAKPTCLK LSKRIIIGKF HGSSAALSAR GTAILTSLLP
