TTL13_MOUSE
ID TTL13_MOUSE Reviewed; 804 AA.
AC A4Q9F6; Q8C0W9;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Tubulin polyglutamylase TTLL13 {ECO:0000303|PubMed:17499049};
DE EC=6.3.2.- {ECO:0000269|PubMed:17499049};
DE AltName: Full=Tubulin--tyrosine ligase-like protein 13;
GN Name=Ttll13 {ECO:0000312|EMBL:CAM84334.1, ECO:0000312|MGI:MGI:1920845};
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], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:CAM84334.1};
RC TISSUE=Testis {ECO:0000312|EMBL:CAM84334.1};
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].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC26514.1};
RC TISSUE=Testis {ECO:0000312|EMBL:BAC26514.1};
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 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). Mediates ATP-dependent polyglutamate side-
CC chain elongation of the polyglutamylation reaction but not the
CC initiation step (PubMed:17499049). Preferentially modifies the alpha-
CC tubulin tail over a beta-tail (PubMed:17499049).
CC {ECO:0000269|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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60149;
CC Evidence={ECO:0000305|PubMed:17499049};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC -!- TISSUE SPECIFICITY: Highly expressed in heart and testis
CC (PubMed:17499049). Expressed in brain, kidney, liver, lung, muscle 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:A6NNM8, ECO:0000250|UniProtKB:Q6ZT98}.
CC -!- DOMAIN: Gln-208 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=BAC26514.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AM690757; CAM84334.1; -; mRNA.
DR EMBL; AK029565; BAC26514.1; ALT_FRAME; mRNA.
DR CCDS; CCDS39996.1; -.
DR RefSeq; NP_808433.2; NM_177765.3.
DR AlphaFoldDB; A4Q9F6; -.
DR SMR; A4Q9F6; -.
DR STRING; 10090.ENSMUSP00000062795; -.
DR iPTMnet; A4Q9F6; -.
DR PhosphoSitePlus; A4Q9F6; -.
DR PaxDb; A4Q9F6; -.
DR PRIDE; A4Q9F6; -.
DR ProteomicsDB; 297681; -.
DR DNASU; 269954; -.
DR Ensembl; ENSMUST00000058266; ENSMUSP00000062795; ENSMUSG00000045467.
DR GeneID; 269954; -.
DR KEGG; mmu:269954; -.
DR UCSC; uc009hzv.1; mouse.
DR CTD; 440307; -.
DR MGI; MGI:1920845; Ttll13.
DR VEuPathDB; HostDB:ENSMUSG00000045467; -.
DR eggNOG; KOG2158; Eukaryota.
DR GeneTree; ENSGT00940000161367; -.
DR HOGENOM; CLU_010131_7_3_1; -.
DR InParanoid; A4Q9F6; -.
DR OMA; HSWCHLQ; -.
DR OrthoDB; 1251554at2759; -.
DR PhylomeDB; A4Q9F6; -.
DR TreeFam; TF313087; -.
DR BRENDA; 6.3.2.B3; 3474.
DR Reactome; R-MMU-8955332; Carboxyterminal post-translational modifications of tubulin.
DR BioGRID-ORCS; 269954; 1 hit in 71 CRISPR screens.
DR PRO; PR:A4Q9F6; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; A4Q9F6; protein.
DR Bgee; ENSMUSG00000045467; Expressed in spermatid and 55 other tissues.
DR ExpressionAtlas; A4Q9F6; baseline and differential.
DR Genevisible; A4Q9F6; MM.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
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:0018095; P:protein polyglutamylation; IBA:GO_Central.
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; Coiled coil; Ligase; Magnesium; Metal-binding; Microtubule;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..804
FT /note="Tubulin polyglutamylase TTLL13"
FT /id="PRO_0000326168"
FT DOMAIN 85..430
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 1..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 293..294
FT /note="L-glutamate"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT REGION 401..482
FT /note="c-MTBD region"
FT /evidence="ECO:0000250|UniProtKB:A6NNM8"
FT REGION 519..556
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 4..30
FT /evidence="ECO:0000255"
FT COILED 504..541
FT /evidence="ECO:0000255"
FT COILED 585..609
FT /evidence="ECO:0000255"
FT COMPBIAS 11..26
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 519..546
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 202
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 208..209
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 208
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 230..233
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 243..245
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 269
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 291..292
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 311
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 376
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 389
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 389
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 391
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 392
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 407
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 208
FT /note="Essential for specifying alpha-elongation versus
FT initiation step of the polyglutamylase activity"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
SQ SEQUENCE 804 AA; 93463 MW; 6AC312D46973DC1A CRC64;
MEPNNCKTSE SEEDDIEEEE SEEECVREES TTPNSTQQAL RKADYKEFEN GVALSVVAKK
IPKKILSATD TDDLEVGRRR RKRKRRPLAI NLTNCKYESV RRAAQMCGLK EVGEDEEWTV
YWTDCSVSLE RVMDMKRFQK INHFPGMTEI CRKDLLARNL NRMQKLYPTE YNIFPRTWCL
PADYGDFQAY GRQRKTRTYI CKPDSGCQGR GIFITRTPKE IKPGEHMICQ QYITKPFLID
GFKFDMRIYV LITSCDPLRI FMYEEGLARF ATMPYVEPSH NNLEEVCMHL TNYAINKHNE
NFVRDDAVGS KRKLSTLNAW LREHSHDPQE LWGDIEDIII KTIISAHSVL RHNYRTCFPQ
YLCGGTCACF EILGFDILLD HKLKPWLLEV NHSPSFTTDS RLDREVKDAL LCDAMNLVNL
RGCDKKKVIE EDKRRVKERL FPCHQQPRET RREQFELSQA AMHDQERYED SHLGGYRRIY
PGPDSEKYAP FFKHNGSLFQ ETAASKAREE CARQQLEEIR LKQEQQENPG TKKRKENKEQ
NQGESAGEKS RSRTATRVLA TSLAYRNRNR EKELLPVQLD TTQPQDIVEE EELERMKLLL
QRENLIRSLG IVEQLTRMLY PSHRSHRKLH EYRPRFHQDG LSSQELQPVN LVPLVLLRGA
ASEQIPPHFL QPLRPHELIP RILGPLSSIN PAIAQHSRYH LQPKNFNWIG DSAATGPCSL
SMKKSGRHYI SSSRVRLTSR KRRKAQHSTK TANGLQSLLI ERLPTSSRLK SSGQDLCLQK
AKNTETPRVL QHSKILWGSV KTKR
