TTLL5_CHLAE
ID TTLL5_CHLAE Reviewed; 1299 AA.
AC Q6EEF3;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 2.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=Tubulin polyglutamylase TTLL5 {ECO:0000250|UniProtKB:Q8CHB8};
DE EC=6.3.2.- {ECO:0000250|UniProtKB:Q8CHB8};
DE AltName: Full=SRC1 and TIF2-associated modulatory protein {ECO:0000250|UniProtKB:Q6EMB2};
DE Short=STAMP protein {ECO:0000250|UniProtKB:Q6EMB2};
DE AltName: Full=Tubulin--tyrosine ligase-like protein 5;
GN Name=TTLL5; Synonyms=STAMP {ECO:0000250|UniProtKB:Q6EMB2};
OS Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Chlorocebus.
OX NCBI_TaxID=9534;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA He Y., Simons S.S. Jr.;
RT "Cercopithecus aethiops SRC1 and TIF2-associated modulatory protein (STAMP)
RT mRNA.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Polyglutamylase which modifies tubulin, generating
CC polyglutamate side chains on the gamma-carboxyl group of specific
CC glutamate residues within the C-terminal tail of tubulin.
CC Preferentially mediates ATP-dependent initiation step of the
CC polyglutamylation reaction over the elongation step. Preferentially
CC modifies the alpha-tubulin tail over a beta-tail (By similarity).
CC Required for CCSAP localization to both polyglutamylated spindle and
CC cilia microtubules. Increases the effects of transcriptional
CC coactivator NCOA2/TIF2 in glucocorticoid receptor-mediated repression
CC and induction and in androgen receptor-mediated induction (By
CC similarity). {ECO:0000250|UniProtKB:Q6EMB2,
CC ECO:0000250|UniProtKB:Q8CHB8}.
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:0000250|UniProtKB:Q8CHB8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60145;
CC Evidence={ECO:0000250|UniProtKB:Q8CHB8};
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:0000250|UniProtKB:Q8CHB8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60149;
CC Evidence={ECO:0000250|UniProtKB:Q8CHB8};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC -!- SUBUNIT: Interacts with the transcriptional coactivators NCOA1/SRC-1
CC and NCOA2/TIF2. {ECO:0000250|UniProtKB:Q6EMB2}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q6EMB2}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000250|UniProtKB:Q8CHB8}. Nucleus
CC {ECO:0000250|UniProtKB:Q6EMB2}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q6EMB2}. Note=Localized to the base of the
CC connecting cilium between the basal body and the adjacent daughter
CC centriole of the cilium. In osteosarcoma cells, found in both cytoplasm
CC and nucleus in the absence of steroid but located exclusively in the
CC nucleus in the presence of steroid. {ECO:0000250|UniProtKB:Q6EMB2,
CC ECO:0000250|UniProtKB:Q8CHB8}.
CC -!- DOMAIN: The flexible c-MTBD (cationic microtubule binding domain)
CC region mediates binding to microtubules. It is positively charged and
CC becomes ordered when bound to microtubules: it interacts with a
CC negatively charged patch on tubulin. The presence of positive charges
CC in the c-MTBD region is essential for proper binding.
CC {ECO:0000250|UniProtKB:Q6EMB2, ECO:0000250|UniProtKB:Q6ZT98}.
CC -!- DOMAIN: Arg-186 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 -!- SIMILARITY: Belongs to the tubulin--tyrosine ligase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ88106.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY383558; AAQ88106.1; ALT_INIT; mRNA.
DR AlphaFoldDB; Q6EEF3; -.
DR SMR; Q6EEF3; -.
DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; 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:0070740; F:tubulin-glutamic acid ligase activity; ISS:UniProtKB.
DR InterPro; IPR004344; TTL/TTLL_fam.
DR Pfam; PF03133; TTL; 1.
DR PROSITE; PS51221; TTL; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell projection; Cilium; Cytoplasm; Cytoskeleton; Ligase;
KW Magnesium; Metal-binding; Microtubule; Nucleotide-binding; Nucleus;
KW Transcription.
FT CHAIN 1..1299
FT /note="Tubulin polyglutamylase TTLL5"
FT /id="PRO_0000223340"
FT DOMAIN 62..407
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 270..271
FT /note="L-glutamate"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT REGION 378..502
FT /note="c-MTBD region"
FT /evidence="ECO:0000250|UniProtKB:Q6EMB2"
FT REGION 410..449
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 591..644
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 833..883
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 919..948
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 960..981
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1090..1131
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1217..1299
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 410..444
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 596..618
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 621..644
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 833..850
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 866..880
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1090..1129
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1254..1299
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 180
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 186..187
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 186
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 208..211
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 221..223
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 247
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 268..269
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 293
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 353
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 366
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 366
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 368
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 384
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 186
FT /note="Essential for specifying initiation versus
FT elongation step of the polyglutamylase activity"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
SQ SEQUENCE 1299 AA; 145553 MW; 639E977EF06CB84F CRC64;
MPVVMARDLE ETASSSEDEE VISQEDHPCI MWTGGCRRIP VLVFHADAIL TKDNNIRVIG
ERYHLSYKIV RTDSRLVRSI LTAHGFHEVH PSSTDYNLMW TGSHLKPFLL RTLSEAQKVN
HFPRSYELTR KDRLYKNIIR MQHTHGFKAF HILPQTFLLP AEYAEFCNSY SKDRGPWIVK
PVASSRGRGV YLINNPNQIS LEENILVSRY INNPLLIDDF KFDVRLYVLV TSYDPLVIYL
YEEGLARFAT VRYDQGAKNI RNQFMHLTNY SVNKKSGDYV SCDDPEVEDY GNKWSMSAML
RYLKQEGRDT TALMAHVEDL IIKTIISAEL AIATACKTFV PHRSSCFELY GFDVLIDATL
KPWLLEVNLS PSLACDAPLD LKIKASMISD MFTVVGFVCQ DPAQRASTRP IYPTFESSRR
NPFQKPQRPL PAQFHSSEPK QRSRPLSASD AEMKNLVGSA REKGPGKLGG SVLGLSMEEI
KVLRRVKEEN DRRGGFIRIF PTSETWEIYG SYLEHKTSMN YMLATRLFQD RMTADGAPEL
KIEGLNSKAK LHAALYERKL LSLEVRKRRR RSSRLRAMRP KYPVITQPAE MNVKTETESE
EEEEVALDNE DEEQEASQEE SAGFLRENQA KDTPSLTTLV ENTPKENSVK VREWSKKGER
CCKLETQELE PKFNLMQVLQ DNGNLSKVQA RIAFSTYLQH VQIRLMKDSG GQTFSASWAA
KEDEQMELVV RFLKRASNNL QQSLRMVLPS RRLALLERRR ILAHQLGDFI IVYNKETEQM
AEKKSKKKVE EEEEDGVNME NFQEFIRQAS EAELEEVLTF YTQKNKSASV FLGTHSKSSK
NNNSYSDSGA KGDHPETVME EAKMKPPKQQ QTTEIHSDKL SRFTTSAEKE AKLVYTSSSS
TPFSGPTATL QKIPNTHLSS VTTSDLSPGP GHHSSLSQIP SAIPSMPHQP TILLNTVSAS
ASPSLHPGTQ NIPSPAGLPR CRSGSHTIGS FSSFQSAAHI YSQKLSRPSS AKAGSCYLNK
HHSGIAKTQQ EGEDASLYSK RYNQSMVTAE LQRLAEKQAA RQYSPSSHIN LLTQQVTNLN
LATGIINRSS ASTPPTLQPI ISPSGPTWLV QSDPQAPENH SSPPRSRSLQ TGGFAWEGEV
ENNVYSKATG VVPQHKYHPT AGSYQLHFAL QQLEQQKLQS RQLLDQSRAR HQAIFGSQTL
PNSNLWTMNN GAGCRISSAT ASGQKPTTLP QKAVPPPSSC ASLVPKPPPN HKQVLRRATS
QRASKGSSAY AQLNGLQSSL NPAASVPITS STDPAHTKR
