TTL10_MOUSE
ID TTL10_MOUSE Reviewed; 704 AA.
AC A4Q9F3; Q3V0K4;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Protein polyglycylase TTLL10 {ECO:0000303|PubMed:19524510};
DE EC=6.3.2.- {ECO:0000269|PubMed:18331838, ECO:0000269|PubMed:19427864, ECO:0000269|PubMed:19524510};
DE AltName: Full=Tubulin--tyrosine ligase-like protein 10;
GN Name=Ttll10 {ECO:0000312|MGI:MGI:1921855};
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), AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Testis;
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] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Testis;
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 FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=19524510; DOI=10.1016/j.cell.2009.05.020;
RA Rogowski K., Juge F., van Dijk J., Wloga D., Strub J.-M., Levilliers N.,
RA Thomas D., Bre M.-H., Van Dorsselaer A., Gaertig J., Janke C.;
RT "Evolutionary divergence of enzymatic mechanisms for posttranslational
RT polyglycylation.";
RL Cell 137:1076-1087(2009).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLU-499.
RX PubMed=18331838; DOI=10.1016/j.febslet.2008.02.079;
RA Ikegami K., Horigome D., Mukai M., Livnat I., MacGregor G.R., Setou M.;
RT "TTLL10 is a protein polyglycylase that can modify nucleosome assembly
RT protein 1.";
RL FEBS Lett. 582:1129-1134(2008).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=19427864; DOI=10.1016/j.febslet.2009.05.003;
RA Ikegami K., Setou M.;
RT "TTLL10 can perform tubulin glycylation when co-expressed with TTLL8.";
RL FEBS Lett. 583:1957-1963(2009).
CC -!- FUNCTION: Polyglycylase which modifies both tubulin and non-tubulin
CC proteins, generating polyglycine side chains of variable lengths on the
CC gamma-carboxyl groups of specific glutamate residues of target proteins
CC (PubMed:19524510, PubMed:18331838, PubMed:19427864). Involved in the
CC elongation step rather than the initiation step of the polyglycylation
CC reaction (PubMed:19524510, PubMed:18331838, PubMed:19427864).
CC Polyglycylates alpha-tubulin and beta-tubulin (PubMed:19524510,
CC PubMed:19427864). Polyglycylates non-tubulin proteins such as
CC nucleosome assembly protein NAP1 (PubMed:18331838).
CC {ECO:0000269|PubMed:18331838, ECO:0000269|PubMed:19427864,
CC ECO:0000269|PubMed:19524510}.
CC -!- CATALYTIC ACTIVITY: [Protein polyglycylase TTLL10]:
CC Reaction=(glycyl)(n)-glycyl-L-glutamyl-[protein] + ATP + glycine =
CC (glycyl)(n+1)-glycyl-L-glutamyl-[protein] + ADP + H(+) + phosphate;
CC Xref=Rhea:RHEA:67184, Rhea:RHEA-COMP:17208, Rhea:RHEA-COMP:17209,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:167891, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:18331838, ECO:0000269|PubMed:19427864,
CC ECO:0000269|PubMed:19524510};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67185;
CC Evidence={ECO:0000305|PubMed:18331838, ECO:0000305|PubMed:19427864,
CC ECO:0000305|PubMed:19524510};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:19427864, ECO:0000269|PubMed:19524510}. Cell
CC projection, cilium {ECO:0000305}. Cytoplasm, cytoskeleton, cilium
CC axoneme {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A4Q9F3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A4Q9F3-2; Sequence=VSP_032265;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis (PubMed:17499049).
CC Expressed in brain, heart, kidney, liver, lung, muscle and trachea
CC (PubMed:17499049). {ECO:0000269|PubMed:17499049}.
CC -!- DOMAIN: Gln-307 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}.
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DR EMBL; AM690754; CAM84331.1; -; mRNA.
DR EMBL; AK133079; BAE21500.1; -; mRNA.
DR CCDS; CCDS19058.1; -. [A4Q9F3-2]
DR CCDS; CCDS89873.1; -. [A4Q9F3-1]
DR RefSeq; NP_083540.1; NM_029264.2.
DR AlphaFoldDB; A4Q9F3; -.
DR SMR; A4Q9F3; -.
DR STRING; 10090.ENSMUSP00000055671; -.
DR iPTMnet; A4Q9F3; -.
DR PhosphoSitePlus; A4Q9F3; -.
DR PaxDb; A4Q9F3; -.
DR PRIDE; A4Q9F3; -.
DR ProteomicsDB; 298335; -. [A4Q9F3-1]
DR ProteomicsDB; 298336; -. [A4Q9F3-2]
DR DNASU; 330010; -.
DR GeneID; 330010; -.
DR KEGG; mmu:330010; -.
DR CTD; 254173; -.
DR MGI; MGI:1921855; Ttll10.
DR eggNOG; KOG2157; Eukaryota.
DR InParanoid; A4Q9F3; -.
DR OrthoDB; 626048at2759; -.
DR PhylomeDB; A4Q9F3; -.
DR Reactome; R-MMU-8955332; Carboxyterminal post-translational modifications of tubulin.
DR BioGRID-ORCS; 330010; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Ttll10; mouse.
DR PRO; PR:A4Q9F3; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; A4Q9F3; protein.
DR GO; GO:0005930; C:axoneme; IDA:UniProtKB.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070735; F:protein-glycine ligase activity; IDA:UniProtKB.
DR GO; GO:0070737; F:protein-glycine ligase activity, elongating; IDA:UniProtKB.
DR GO; GO:0018094; P:protein polyglycylation; IDA:UniProtKB.
DR InterPro; IPR004344; TTL/TTLL_fam.
DR InterPro; IPR027752; TTLL10.
DR PANTHER; PTHR46810; PTHR46810; 1.
DR Pfam; PF03133; TTL; 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..704
FT /note="Protein polyglycylase TTLL10"
FT /id="PRO_0000324522"
FT DOMAIN 169..540
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 46..125
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 137..170
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 565..704
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 574..610
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 650..674
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 683..704
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 301
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 307..308
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 307
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 350..353
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q6ZT98"
FT BINDING 363..365
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q6ZT98"
FT BINDING 406..407
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 486
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 499
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 499
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 501
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 307
FT /note="Essential for specifying elongation versus
FT initiation step of the polyglycylase activity"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT VAR_SEQ 15..44
FT /note="SEAQAEAAAQDLGRLPSPSKVGAAVCRIQG -> R (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_032265"
FT MUTAGEN 499
FT /note="E->V: Loss of NAP1 polyglycylase activity."
FT /evidence="ECO:0000269|PubMed:18331838"
FT CONFLICT 578
FT /note="N -> H (in Ref. 2; BAE21500)"
FT /evidence="ECO:0000305"
FT CONFLICT 585..586
FT /note="AN -> PH (in Ref. 2; BAE21500)"
FT /evidence="ECO:0000305"
FT CONFLICT 596
FT /note="H -> N (in Ref. 2; BAE21500)"
FT /evidence="ECO:0000305"
FT CONFLICT 600
FT /note="N -> H (in Ref. 2; BAE21500)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 704 AA; 79250 MW; 3225E8C26C760B1F CRC64;
MALHPQAGRP HRDGSEAQAE AAAQDLGRLP SPSKVGAAVC RIQGLGHRAA RRPRRGIGTT
SASRVPRPGA LMPATRNRPR FIHCRGQPPR TRVSSKRSKR SRIHPCHTEV PGWTHEKQMG
SSVKERLRPE LSQLDQDADD LEEEEAARLP VTSPDGLLME GDKQPSPGQG PFFYIGGTNG
ASIISNYCES KGWQRTQDSH CEDYKLKWCE IKCRDNYCSF REGQQLLFQL PNNKLLTTKI
GLLSALREHA RTLSKARMLP STQTKVLKME EFFPETYRLD IRDERQAFFA LFDETQMWIC
KPTASNQGKG IFLIRSQEEA AALQAKTQSI EDDPIYRKMP FRAPQARVVQ RYVQNPLLLD
GKKFDVRSYM LIACAMPYMV FFGHGYARLT LSLYNPHSSD LSGHLTNQFM QKKSPLYTLL
KESTVWTMEH LNRYINDKFR KTKGLPRDWV FTTFTKRMQQ IMSHCFLAVK SKLECKLGYF
DLIGCDFLID ENFKVWLLEM NANPALHTNC EVLKAVIPGV VIETLDLALE TCQKSLHSQK
MLPLLSQRRF VLLYNGETTD LWPRLASSRP LNRLPNPNPN PNPNANPHPH PHPNPHPHPN
PHPNANPHPP RPTCEAASSA LSSARAAISE RPGARKSMPS RGAPVCTPRK SRLSDSSGSS
IAESEPSLCS GSLEGSRDTA REPSLGPPEE EREEEQRSTS HRGS
