TTLL7_XENTR
ID TTLL7_XENTR Reviewed; 909 AA.
AC F7E540; A7MC53; F6Q5C0; F6S9W5; F6ST33;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 11-MAY-2016, sequence version 2.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=Tubulin polyglutamylase TTLL7 {ECO:0000303|PubMed:28576883};
DE EC=6.3.2.- {ECO:0000269|PubMed:26875866, ECO:0000269|PubMed:28576883};
DE AltName: Full=Tubulin--tyrosine ligase-like protein 7 {ECO:0000303|PubMed:28576883};
GN Name=ttll7 {ECO:0000303|PubMed:26875866};
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] OF 1-389.
RC TISSUE=Brain;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (AUG-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
RX PubMed=26875866; DOI=10.1016/j.cell.2016.01.019;
RA Valenstein M.L., Roll-Mecak A.;
RT "Graded control of microtubule severing by tubulin glutamylation.";
RL Cell 164:911-921(2016).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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: Polyglutamylase which modifies tubulin, generating
CC polyglutamate side chains of variable lengths on the gamma-carboxyl
CC group of specific glutamate residues within the C-terminal tail of
CC tubulin (PubMed:26875866, PubMed:28576883). Mediates both ATP-dependent
CC initiation and elongation steps of the polyglutamylation reaction
CC (PubMed:26875866). Preferentially modifies the beta-tubulin tail over
CC an alpha-tail (PubMed:26875866, PubMed:28576883). Competes with
CC monoglycylase TTLL3 for modification site on beta-tubulin substrate,
CC thereby creating an anticorrelation between glycylation and
CC glutamylation reactions (PubMed:28576883).
CC {ECO:0000269|PubMed:26875866, ECO:0000269|PubMed:28576883}.
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:26875866,
CC ECO:0000269|PubMed:28576883};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60145;
CC Evidence={ECO:0000305|PubMed:26875866, ECO:0000305|PubMed:28576883};
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:0000269|PubMed:26875866};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60149;
CC Evidence={ECO:0000305|PubMed:26875866};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC -!- SUBUNIT: Interacts with both alpha- and beta-tubulin (via C-terminal
CC tubulin tails). {ECO:0000250|UniProtKB:Q6ZT98}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000250|UniProtKB:A4Q9F0}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000250|UniProtKB:A4Q9F0}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:A4Q9F0}. Perikaryon
CC {ECO:0000250|UniProtKB:A4Q9F0}. Note=In cells with primary cilia, found
CC in both cilia and basal bodies. In neuronal cells, found in dendrites
CC and perikaryon. {ECO:0000250|UniProtKB:A4Q9F0}.
CC -!- DOMAIN: The enzyme uses its core to engage the disordered anionic tails
CC of alpha- and beta-tubulin and the flexible c-MTBD (cationic
CC microtubule binding domain) region to bind the microtubule and position
CC itself for beta-tail modification. The c-MTBD region is positively
CC charged and becomes ordered when bound to microtubules: it interacts
CC with a negatively charged patch on alpha-tubulin. The presence of
CC positive charges in the c-MTBD region is essential for proper binding.
CC {ECO:0000250|UniProtKB:Q6ZT98}.
CC -!- SIMILARITY: Belongs to the tubulin--tyrosine ligase family.
CC {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI52049.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; AAMC01003218; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01003219; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01003220; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01003221; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01003222; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01003223; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC152048; AAI52049.1; ALT_SEQ; mRNA.
DR AlphaFoldDB; F7E540; -.
DR SMR; F7E540; -.
DR STRING; 8364.ENSXETP00000018940; -.
DR PaxDb; F7E540; -.
DR PRIDE; F7E540; -.
DR eggNOG; KOG2158; Eukaryota.
DR TreeFam; TF313087; -.
DR Proteomes; UP000008143; Genome assembly.
DR Proteomes; UP000790000; Unplaced.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0018095; P:protein polyglutamylation; IDA:UniProtKB.
DR InterPro; IPR004344; TTL/TTLL_fam.
DR Pfam; PF03133; TTL; 1.
DR PROSITE; PS51221; TTL; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell projection; Cilium; Cytoplasm; Cytoskeleton;
KW Developmental protein; Differentiation; Ligase; Magnesium; Metal-binding;
KW Microtubule; Neurogenesis; Nucleotide-binding; Reference proteome.
FT CHAIN 1..909
FT /note="Tubulin polyglutamylase TTLL7"
FT /id="PRO_0000436276"
FT DOMAIN 40..392
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 253..254
FT /note="L-glutamate"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT REGION 390..452
FT /note="c-MTBD region"
FT /evidence="ECO:0000250|UniProtKB:Q6ZT98"
FT REGION 517..580
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 603..688
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 532..561
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 606..688
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 162
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 168..169
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 190..193
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q6ZT98"
FT BINDING 203..205
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q6ZT98"
FT BINDING 229
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 251..252
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 273
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 338
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 351
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 351
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
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 369
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 108
FT /note="Binds negatively charged residues of beta-tubulin C-
FT terminal tails"
FT /evidence="ECO:0000250|UniProtKB:Q6ZT98"
FT SITE 354
FT /note="Binds negatively charged residues of beta-tubulin C-
FT terminal tails"
FT /evidence="ECO:0000250|UniProtKB:Q6ZT98"
SQ SEQUENCE 909 AA; 105304 MW; 90C5FE03CC969E35 CRC64;
MPSLPNESDH QATCSLSLHS DLPYQPSSSI KRKVRKKKKN GAITANVVGT KYEIVRLVTE
EMMFTKARDD DETANLIWND CAVQHEKIAE LRNYQRINHF PGMGEICRKD CLARNMTKMI
KCQPHEYNFI PRTWIFPAEY TQFQTYIKEL KKKRRQKTFI IKPANGAMGH GISLTRNGEK
LQAQDHLIVQ EYLEKPFLLE SYKFDLRIYI LVTSCDPLRI FLYNDGLVRM GTEKYHPPSE
SNLSQLYMHL TNYSVNKHNE NFERDETENR GSKRSIKWFT EFLRANDYDI SKFWNDISDL
VVKTLIVAEP HVLHAYRMCR PGQHPTSESV CFEVLGFDII LDRKLKPWLL EINRAPSFGT
DQKIDHDVKK GVLLNALKLL NIRASDKKKN LAKQKAEAQK RLYGQGSMKR LSPASSDWEK
QRHTLERRKE ELKERLAQVR KQISREEYEN RHLGNYRRIY PPEDKLLLEK YEGLLATAFQ
TFLAGRAASL QREMNNPLKR MKEEDILDLL EQCELDDEKL SGKPTRPKEP RTLSSMPEST
QTLKKLKNYS SHSSSNSTGS SSDTEEEEDE KEGKEKKVSY DLEEHKYKSL ERSSRIHWKP
PLKAARPFSN SSSPSSAASM RRSVSCPRSI TALNTQSPTT DQRPFSSRIS STITRPLSGN
RTNSLNRSSS SNRVPQSGTS GSVYPSISES RLDHLTKEQE EELTKQTLYA LRDMRIRIPG
KGVEEITHSH IDEIMDNWTY HKSKVASYWL IKLDSVKQRK VLDIVRTNIR SVLQRIWKVS
DVECLHIYRS FNRVFNRLLW NHGQGLWSCF SNSGTSWETI FCKSTEVVTP QQFQCCQRLV
QLCKDCLLAV YKYATDSRVA GMSPDWDDSR YLFPVVPQFT MKSSSSGVNC SSSRLPRSSI
LFNPRHNHY
