TTLL9_MOUSE
ID TTLL9_MOUSE Reviewed; 461 AA.
AC A2APC3; A2APC4; A2APC5; A2APC6; Q9D570;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Probable tubulin polyglutamylase TTLL9 {ECO:0000303|PubMed:17499049};
DE EC=6.3.2.- {ECO:0000305|PubMed:27257088};
DE AltName: Full=Tubulin--tyrosine ligase-like protein 9;
GN Name=Ttll9 {ECO:0000312|MGI:MGI:1913589};
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, SUBCELLULAR LOCATION, AND
RP 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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
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).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=27257088; DOI=10.1242/jcs.185983;
RA Konno A., Ikegami K., Konishi Y., Yang H.J., Abe M., Yamazaki M.,
RA Sakimura K., Yao I., Shiba K., Inaba K., Setou M.;
RT "Ttll9-/- mice sperm flagella show shortening of doublet 7, reduction of
RT doublet 5 polyglutamylation and a stall in beating.";
RL J. Cell Sci. 129:2757-2766(2016).
CC -!- FUNCTION: Probable tubulin polyglutamylase that generates side chains
CC of glutamate on the gamma-carboxyl group of specific glutamate residues
CC within the C-terminal tail of target proteins (PubMed:27257088).
CC Similar to TTLL1, may acquire enzymatic activity only in complex with
CC other proteins as it is most likely lacking domains important for
CC autonomous activity (Probable). Mediates tubulin polyglutamylation
CC which induces establishment of microtubule heterogeneity in sperm
CC flagella, thereby playing a role in normal motile flagella axoneme
CC structure and sperm flagella beating pattern (PubMed:27257088).
CC {ECO:0000269|PubMed:27257088, 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:0000305|PubMed:27257088};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60149;
CC Evidence={ECO:0000305|PubMed:27257088};
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:0000269|PubMed:17499049}. Cytoplasm, cytoskeleton, flagellum
CC axoneme {ECO:0000305|PubMed:27257088}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A2APC3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A2APC3-2; Sequence=VSP_032261;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and testis
CC (PubMed:17499049). Expressed in heart, kidney and lung
CC (PubMed:17499049). In the brain, expressed in ependymal cilia, cortex,
CC corpus callosum and striatum (PubMed:23897886). In the testis,
CC specifically expressed in the seminiferous tubules (PubMed:27257088).
CC {ECO:0000269|PubMed:17499049, ECO:0000269|PubMed:23897886,
CC ECO:0000269|PubMed:27257088}.
CC -!- DOMAIN: Gln-155 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 -!- DISRUPTION PHENOTYPE: Males are infertile due to a reduction in sperm
CC count and defective sperm motility. Sperm axonemes have shortened
CC microtubule doublet 7 and reduced tubulin polyglutamylation, in
CC particular of doublet 5. Reduced sperm motility is caused by frequent
CC stalls of flagella due to defective switching in the bending direction.
CC {ECO:0000269|PubMed:27257088}.
CC -!- SIMILARITY: Belongs to the tubulin--tyrosine ligase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAM23684.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAM23685.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AM690753; CAM84330.1; -; mRNA.
DR EMBL; AK015740; BAB29950.1; -; mRNA.
DR EMBL; AL833801; CAM23682.1; -; Genomic_DNA.
DR EMBL; AL928862; CAM23682.1; JOINED; Genomic_DNA.
DR EMBL; AL833801; CAM23683.1; -; Genomic_DNA.
DR EMBL; AL928862; CAM23683.1; JOINED; Genomic_DNA.
DR EMBL; AL833801; CAM23684.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL833801; CAM23685.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL928862; CAM27198.1; -; Genomic_DNA.
DR EMBL; AL833801; CAM27198.1; JOINED; Genomic_DNA.
DR EMBL; AL928862; CAM27199.1; -; Genomic_DNA.
DR EMBL; AL833801; CAM27199.1; JOINED; Genomic_DNA.
DR CCDS; CCDS16903.1; -. [A2APC3-2]
DR CCDS; CCDS38283.1; -. [A2APC3-1]
DR RefSeq; NP_001077087.1; NM_001083618.1. [A2APC3-1]
DR RefSeq; NP_083340.2; NM_029064.2. [A2APC3-2]
DR AlphaFoldDB; A2APC3; -.
DR SMR; A2APC3; -.
DR STRING; 10090.ENSMUSP00000099444; -.
DR PhosphoSitePlus; A2APC3; -.
DR PaxDb; A2APC3; -.
DR PRIDE; A2APC3; -.
DR ProteomicsDB; 298156; -. [A2APC3-1]
DR ProteomicsDB; 298157; -. [A2APC3-2]
DR Antibodypedia; 49885; 46 antibodies from 12 providers.
DR DNASU; 74711; -.
DR Ensembl; ENSMUST00000099197; ENSMUSP00000096803; ENSMUSG00000074673. [A2APC3-1]
DR Ensembl; ENSMUST00000103155; ENSMUSP00000099444; ENSMUSG00000074673. [A2APC3-2]
DR GeneID; 74711; -.
DR KEGG; mmu:74711; -.
DR UCSC; uc008ngv.1; mouse. [A2APC3-2]
DR UCSC; uc008ngx.1; mouse. [A2APC3-1]
DR CTD; 164395; -.
DR MGI; MGI:1913589; Ttll9.
DR VEuPathDB; HostDB:ENSMUSG00000074673; -.
DR eggNOG; KOG2157; Eukaryota.
DR GeneTree; ENSGT00940000159879; -.
DR HOGENOM; CLU_010131_0_1_1; -.
DR InParanoid; A2APC3; -.
DR OMA; LIWANGP; -.
DR OrthoDB; 584228at2759; -.
DR PhylomeDB; A2APC3; -.
DR TreeFam; TF313087; -.
DR Reactome; R-MMU-8955332; Carboxyterminal post-translational modifications of tubulin.
DR BioGRID-ORCS; 74711; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Ttll9; mouse.
DR PRO; PR:A2APC3; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; A2APC3; protein.
DR Bgee; ENSMUSG00000074673; Expressed in spermatid and 91 other tissues.
DR ExpressionAtlas; A2APC3; baseline and differential.
DR Genevisible; A2APC3; 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:0031514; C:motile cilium; 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:0030317; P:flagellated sperm motility; IMP:MGI.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0018095; P:protein polyglutamylation; IMP:MGI.
DR Gene3D; 3.30.1490.20; -; 1.
DR InterPro; IPR013815; ATP_grasp_subdomain_1.
DR InterPro; IPR004344; TTL/TTLL_fam.
DR InterPro; IPR027751; TTLL9.
DR PANTHER; PTHR12241:SF39; PTHR12241:SF39; 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; Flagellum; Ligase; Magnesium; Metal-binding; Microtubule;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..461
FT /note="Probable tubulin polyglutamylase TTLL9"
FT /id="PRO_0000324518"
FT DOMAIN 22..402
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 172..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 278..279
FT /note="L-glutamate"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT COMPBIAS 179..199
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 149
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 155..156
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 155
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 218..221
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 231..233
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 257
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 276..277
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 294
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 348
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 361
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 361
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 363
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 379
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 155
FT /note="Essential for specifying alpha-elongation versus
FT initiation step of the polyglutamylase activity"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT VAR_SEQ 438..461
FT /note="CVNDRKEQLRQLFRSLQAQRKAPS -> TLSQTGSEWERNIIGSGGGLGPLG
FT RAV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_032261"
FT CONFLICT 162
FT /note="F -> L (in Ref. 2; BAB29950)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 461 AA; 54107 MW; 6E83E3C9A4788EAD CRC64;
MSRQKNQNSK GHGVSKGKER EQRTLIRFKT TLMNTLMDVL RHRPGWVEVK DEGEWDFYWC
DVSWLRENFD HTYMDEHVRI SHFRNHYELT RKNYMVKNLK RFRKYLERES GKTEAAKCDF
FPKTFEMPCE YHLFVEEFRK NPGITWIMKP VARSQGKGIF LFRRLKDIMD WRKGTSGKKP
TGVETQPARA NMNPSGSHDT RSSDDQKDDL PVENYVAQRY VENPYLIGGR KFDLRVYVLV
MSYIPLRAWL YRDGFARFSN TRFTLNSIDD HYVHLTNVAV QKTSPDYHLK KGCKWMLQRF
RQYLASKHGP KAVETLFSDM DNIFIKSLQS VQKVIISDKH CFELYGYDIL IDQDLKPWLL
EVNASPSLTA SSQEDYELKT CLLEDTLHVV DMEARLTGKE KRVGGFDLMW NDGPVSREDG
PSDLSGMGNF VTNTHLGCVN DRKEQLRQLF RSLQAQRKAP S
