ID TTL11_MOUSE Reviewed; 727 AA.
AC A4Q9F4; Q1LZJ9; Q9D4E7;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 1.
DT 24-JAN-2024, entry version 110.
DE RecName: Full=Tubulin polyglutamylase TTLL11 {ECO:0000303|PubMed:17499049};
DE EC=6.3.2.- {ECO:0000269|PubMed:17499049, ECO:0000269|PubMed:20530212};
DE AltName: Full=Tubulin--tyrosine ligase-like protein 11;
GN Name=Ttll11 {ECO:0000312|EMBL:CAM84332.1, ECO:0000312|MGI:MGI:1921660};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:CAM84332.1};
RC TISSUE=Testis {ECO:0000312|EMBL:CAM84332.1};
RX PubMed=17499049; DOI=10.1016/j.molcel.2007.04.012;
RA van Dijk J., Rogowski K., Miro J., Lacroix B., Edde B., Janke C.;
RT "A targeted multienzyme mechanism for selective microtubule
RT polyglutamylation.";
RL Mol. Cell 26:437-448(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 110-727 (ISOFORM 3).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAB30318.1};
RC TISSUE=Testis {ECO:0000312|EMBL:BAB30318.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 185-727 (ISOFORM 2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20530212; DOI=10.1083/jcb.201001024;
RA Lacroix B., van Dijk J., Gold N.D., Guizetti J., Aldrian-Herrada G.,
RA Rogowski K., Gerlich D.W., Janke C.;
RT "Tubulin polyglutamylation stimulates spastin-mediated microtubule
RT severing.";
RL J. Cell Biol. 189:945-954(2010).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=23897886; DOI=10.1083/jcb.201305041;
RA Bosch Grau M., Gonzalez Curto G., Rocha C., Magiera M.M., Marques Sousa P.,
RA Giordano T., Spassky N., Janke C.;
RT "Tubulin glycylases and glutamylases have distinct functions in
RT stabilization and motility of ependymal cilia.";
RL J. Cell Biol. 202:441-451(2013).
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:17499049, PubMed:20530212). Preferentially mediates
CC ATP-dependent polyglutamate long side-chain elongation over the
CC initiation step of the polyglutamylation reaction (PubMed:17499049,
CC PubMed:20530212). Preferentially modifies the alpha-tubulin tail over a
CC beta-tail (PubMed:17499049). Required for CCSAP localization to both
CC spindle and cilia microtubules (By similarity). Promotes tubulin
CC polyglutamylation which stimulates spastin/SPAST-mediated microtubule
CC severing, thereby regulating microtubule functions (PubMed:20530212).
CC {ECO:0000250|UniProtKB:Q8NHH1, ECO:0000269|PubMed:17499049,
CC ECO:0000269|PubMed:20530212}.
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:17499049};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60145;
CC Evidence={ECO:0000305|PubMed:17499049};
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:17499049,
CC ECO:0000269|PubMed:20530212};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60149;
CC Evidence={ECO:0000305|PubMed:17499049, ECO:0000305|PubMed:20530212};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000269|PubMed:17499049}. Cytoplasm, cytoskeleton
CC {ECO:0000305|PubMed:20530212}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1 {ECO:0000269|PubMed:17499049};
CC IsoId=A4Q9F4-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:15489334};
CC IsoId=A4Q9F4-2; Sequence=VSP_052719;
CC Name=3 {ECO:0000269|PubMed:16141072};
CC IsoId=A4Q9F4-3; Sequence=VSP_052718, VSP_052719;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, kidney, liver, lung,
CC muscle and testis (PubMed:17499049). Expressed in heart, spleen and
CC trachea (PubMed:17499049). In the brain, expressed in ependymal cilia,
CC cortex, corpus callosum and striatum (PubMed:23897886).
CC {ECO:0000269|PubMed:17499049, ECO:0000269|PubMed:23897886}.
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:Q6ZT98, ECO:0000250|UniProtKB:Q8NHH1}.
CC -!- DOMAIN: Gln-252 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:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB30318.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB30318.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB30318.1; Type=Frameshift; Evidence={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; AM690755; CAM84332.1; -; mRNA.
DR EMBL; AK016577; BAB30318.1; ALT_SEQ; mRNA.
DR EMBL; BC115858; AAI15859.1; -; mRNA.
DR CCDS; CCDS50579.1; -. [A4Q9F4-1]
DR RefSeq; NP_084050.1; NM_029774.2. [A4Q9F4-1]
DR AlphaFoldDB; A4Q9F4; -.
DR SMR; A4Q9F4; -.
DR BioGRID; 216728; 1.
DR STRING; 10090.ENSMUSP00000028248; -.
DR PhosphoSitePlus; A4Q9F4; -.
DR PaxDb; 10090-ENSMUSP00000028248; -.
DR ProteomicsDB; 300049; -. [A4Q9F4-1]
DR ProteomicsDB; 300050; -. [A4Q9F4-2]
DR ProteomicsDB; 300051; -. [A4Q9F4-3]
DR Antibodypedia; 53016; 19 antibodies from 9 providers.
DR Ensembl; ENSMUST00000028248.11; ENSMUSP00000028248.5; ENSMUSG00000026885.14. [A4Q9F4-1]
DR Ensembl; ENSMUST00000112976.9; ENSMUSP00000108600.3; ENSMUSG00000026885.14. [A4Q9F4-2]
DR GeneID; 74410; -.
DR KEGG; mmu:74410; -.
DR UCSC; uc008jkz.3; mouse. [A4Q9F4-1]
DR AGR; MGI:1921660; -.
DR CTD; 158135; -.
DR MGI; MGI:1921660; Ttll11.
DR VEuPathDB; HostDB:ENSMUSG00000026885; -.
DR eggNOG; KOG2158; Eukaryota.
DR GeneTree; ENSGT00940000156689; -.
DR HOGENOM; CLU_010131_6_0_1; -.
DR InParanoid; A4Q9F4; -.
DR OMA; QMKSFGE; -.
DR OrthoDB; 7265at2759; -.
DR PhylomeDB; A4Q9F4; -.
DR TreeFam; TF313087; -.
DR BRENDA; 6.3.2.B3; 3474.
DR Reactome; R-MMU-8955332; Carboxyterminal post-translational modifications of tubulin.
DR BioGRID-ORCS; 74410; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Ttll11; mouse.
DR PRO; PR:A4Q9F4; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; A4Q9F4; Protein.
DR Bgee; ENSMUSG00000026885; Expressed in gastrula and 119 other cell types or tissues.
DR ExpressionAtlas; A4Q9F4; baseline and differential.
DR Genevisible; A4Q9F4; MM.
DR GO; GO:0036064; C:ciliary basal body; IDA:MGI.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005874; C:microtubule; 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: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:0051013; P:microtubule severing; IDA:MGI.
DR GO; GO:0036211; P:protein modification process; IEA:InterPro.
DR Gene3D; 3.30.470.20; ATP-grasp fold, B domain; 1.
DR InterPro; IPR004344; TTL/TTLL_fam.
DR PANTHER; PTHR12241; TUBULIN POLYGLUTAMYLASE; 1.
DR PANTHER; PTHR12241:SF154; TUBULIN POLYGLUTAMYLASE TTLL11; 1.
DR Pfam; PF03133; TTL; 1.
DR SUPFAM; SSF56059; Glutathione synthetase ATP-binding domain-like; 1.
DR PROSITE; PS51221; TTL; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell projection; Cilium; Cytoplasm;
KW Cytoskeleton; Ligase; Magnesium; Metal-binding; Microtubule;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..727
FT /note="Tubulin polyglutamylase TTLL11"
FT /id="PRO_0000326165"
FT DOMAIN 125..477
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 1..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 464..566
FT /note="c-MTBD region"
FT /evidence="ECO:0000250|UniProtKB:Q8NHH1"
FT REGION 530..551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 694..727
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..82
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 702..727
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 246
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 252..253
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 252
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 279..282
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 292..294
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 318
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
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 342
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 343
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
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 425
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 438
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 438
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 440
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 470
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 252
FT /note="Essential for specifying alpha-elongation versus
FT initiation step of the polyglutamylase activity"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT VAR_SEQ 210..281
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_052718"
FT VAR_SEQ 491..524
FT /note="HFPDIYMDRKHRIPPVSDRMSSWKHKGSSLSIVR -> Q (in isoform
FT 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_052719"
FT CONFLICT 110
FT /note="R -> G (in Ref. 2; BAB30318)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="S -> G (in Ref. 2; BAB30318)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="S -> D (in Ref. 2; BAB30318)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 727 AA; 82361 MW; 661A7FB585BB9EDB CRC64;
MRRSSPEKKP EAEWEADAAA AAAATAAATE SLPAETEKQQ GVDAGAAGDP ERLELEEQPK
DVGRIPTPTR RHAPEEGEAR VVRRLPPALP LAQPRPAARA LSQLVKARGR SRSRVYRRSA
GSMRPVTVDS SKARTSLDAL KISLRQLRWK EFPFGRRLPC DIYWHGVSFR DSDILSGQVN
KFPGMTEMVR KVTLSRALRI MQNLFPEEYN FYPRSWILPE EFQLFVSQVQ TVKEGDPSWK
PTFIVKPDSG CQGDGIYLIK DPCDGRLTGT LHNRPAVVQE YIRKPLLIDK LKFDIRLYVL
LKSLDPLEIY IAKDGLSRFC TEPYQEPNPQ NLHHVFMHLT NYSLNIHSGK FVHSDSASTG
SKRTFSSILC RLSSKGVDIK KVWSDIISLV IKTVIALTPE LKVFYQSDIP TGRPGPTCFQ
ILGFDILLMK NLKPMLLEVN ANPSMRIEHE YELSPGVFEN IPSLVDEEVK VAVIRDTLRL
MDPLKKKKEI HFPDIYMDRK HRIPPVSDRM SSWKHKGSSL SIVRSQQMEK SFTSKEDLNC
DPTGGDSEPN PEAHLPSICL KQVFPKYAKQ FNYLRLVDRM ANLFIRFLGI KGTMKLGPTG
FRTFIRNCKL SSSSLSMAAV DILYIDITRR WNSVTVDQRD SGMCLQAFVE AFFFLAQRKF
KLQPLHEQVA SLIDLCEYHL SVLDEKRLLC HRGRPLQRNP PQMNRPEHSA TGSSAPRVIG
ASKLSQS
//
