TTLL5_PONAB
ID TTLL5_PONAB Reviewed; 1299 AA.
AC Q5R978;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=Tubulin polyglutamylase TTLL5 {ECO:0000250|UniProtKB:Q8CHB8};
DE EC=6.3.2.- {ECO:0000250|UniProtKB:Q8CHB8};
DE AltName: Full=Tubulin--tyrosine ligase-like protein 5;
GN Name=TTLL5;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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 ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CR859514; CAH91682.1; -; mRNA.
DR RefSeq; NP_001125985.1; NM_001132513.1.
DR AlphaFoldDB; Q5R978; -.
DR SMR; Q5R978; -.
DR STRING; 9601.ENSPPYP00000006833; -.
DR GeneID; 100172924; -.
DR KEGG; pon:100172924; -.
DR CTD; 23093; -.
DR eggNOG; KOG2156; Eukaryota.
DR eggNOG; KOG2157; Eukaryota.
DR InParanoid; Q5R978; -.
DR OrthoDB; 219807at2759; -.
DR Proteomes; UP000001595; Unplaced.
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 Reference proteome; Transcription.
FT CHAIN 1..1299
FT /note="Tubulin polyglutamylase TTLL5"
FT /id="PRO_0000223343"
FT DOMAIN 62..407
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 270..271
FT /note="L-glutamate"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT REGION 378..488
FT /note="c-MTBD region"
FT /evidence="ECO:0000250|UniProtKB:Q6EMB2"
FT REGION 589..626
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 832..853
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 918..941
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1088..1130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1217..1275
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 595..617
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 832..849
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1088..1129
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1254..1275
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; 145530 MW; BEFD9E5F3FCDAB02 CRC64;
MPIVMARDLE 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 GFDVLIDSTL
KPWLLEVNLS PSLACDAPLD LKIKASMISD MFTVVGFVCQ DPAQRASTRP IYPTFESSRR
NPFQKPQRCR PLSASDAEMK NLVGSAREKG PGKLGGSVLG LSMEEIKVLR RVKEENDRRG
GFIRIFPTSE TWEIYGSYLE HKTSMNYMLA TRLFQDRGNP RRSLLTGRTR MTADGAPELK
IESLNSKAKL HAALYERKLL SLEVRKRRRR SSRLRAMRPK YPVITQPAEM NVKTETESEE
EEEVALDNEE EEQEASQEES AGFLRENQAK YTPSLTALVE NTPKEHSMKV REWNNKGGHC
CKLETQELEP KFNLVQILQD NGNLSKVQAR IAFSAYLQHV QIRLMKDSGG QTFSASWAAK
EDEQMELVVR FLKRASNNLQ HSLRMVLPSR RLALLERRRI LAHQLGDFII VYNKETEQMA
EKKSKKKVEE EEEDGVNMEN FQEFIRQASE AELEEVLTFY TQKNKSASVF LGTHSKSSKN
NNSYSDSGAK GDHPETIMEE VKIKPPKQQQ TTEIHSDKLS RFTTSAEKEA KLVYSNSSST
PFSGPTATLQ KIPNTHLSSV TTSDLSPGPG HHSSLSQIPS AIPSMPHQPT VLLNTVSASA
SPCLHTGTQN IPNPAGLPRC RSGSHTIGPF SSFQSAAHIY SQKLSRPSSA KAAGSCYLNK
HHSGIAKTQK EGEDASSYSK RYNQSMVTAE LQRLAEKQAA RQYSPSSHIN LLTQQVTNLN
LATGIINRSS ASTPPTLRPI ISPSGPTWST QSDPQAPENH SSPPGSRSLQ TGVFAWEGEV
ENNVYSKATG VVPQHKYHPT AGSYQLHFAL QQLEQQKLQS RQLLDQSRAR HQAIFGSQTL
PNSNLWTMNN GAGCRISSAT ASGQKPTTLP QKVVPPPSSC ASLVPKPPPN HKQVLRRATS
QRASKGSSAE GQLNGLQSSL NPAAFVPITS STDPAHTKI
