TTLL9_HUMAN
ID TTLL9_HUMAN Reviewed; 439 AA.
AC Q3SXZ7; A6NH06; A6NIS5; B3KSG8; Q3SXZ8; Q5JYS3; Q5JYS4;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 3.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Probable tubulin polyglutamylase TTLL9 {ECO:0000250|UniProtKB:A2APC3};
DE EC=6.3.2.- {ECO:0000250|UniProtKB:A2APC3};
DE AltName: Full=Tubulin--tyrosine ligase-like protein 9;
GN Name=TTLL9 {ECO:0000312|HGNC:HGNC:16118}; Synonyms=C20orf125;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
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).
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. Similar to TTLL1, may
CC acquire enzymatic activity only in complex with other proteins as it is
CC most likely lacking domains important for autonomous activity. Mediates
CC tubulin polyglutamylation which induces establishment of microtubule
CC heterogeneity in sperm flagella, thereby playing a role in normal
CC motile flagella axoneme structure and sperm flagella beating pattern.
CC {ECO:0000250|UniProtKB:A2APC3}.
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:A2APC3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60149;
CC Evidence={ECO:0000250|UniProtKB:A2APC3};
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:0000250|UniProtKB:A2APC3}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:A2APC3}. Cytoplasm, cytoskeleton, flagellum
CC axoneme {ECO:0000250|UniProtKB:A2APC3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q3SXZ7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3SXZ7-2; Sequence=VSP_035765, VSP_035767, VSP_035769;
CC Name=3;
CC IsoId=Q3SXZ7-3; Sequence=VSP_035765, VSP_035766, VSP_035767,
CC VSP_035768;
CC -!- DOMAIN: Gln-173 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 -!- SEQUENCE CAUTION:
CC Sequence=EAW76401.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AK093491; BAG52730.1; -; mRNA.
DR EMBL; AL031658; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359765; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW76401.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471077; EAW76403.1; -; Genomic_DNA.
DR EMBL; BC104024; AAI04025.1; -; mRNA.
DR EMBL; BC104025; AAI04026.1; -; mRNA.
DR CCDS; CCDS42863.1; -. [Q3SXZ7-1]
DR RefSeq; NP_001008409.1; NM_001008409.2. [Q3SXZ7-1]
DR RefSeq; XP_006723787.1; XM_006723724.2.
DR RefSeq; XP_011526948.1; XM_011528646.1.
DR AlphaFoldDB; Q3SXZ7; -.
DR SMR; Q3SXZ7; -.
DR BioGRID; 127895; 14.
DR IntAct; Q3SXZ7; 5.
DR STRING; 9606.ENSP00000442515; -.
DR iPTMnet; Q3SXZ7; -.
DR PhosphoSitePlus; Q3SXZ7; -.
DR BioMuta; TTLL9; -.
DR DMDM; 215274204; -.
DR MassIVE; Q3SXZ7; -.
DR MaxQB; Q3SXZ7; -.
DR PaxDb; Q3SXZ7; -.
DR PeptideAtlas; Q3SXZ7; -.
DR PRIDE; Q3SXZ7; -.
DR Antibodypedia; 49885; 46 antibodies from 12 providers.
DR DNASU; 164395; -.
DR Ensembl; ENST00000375922.8; ENSP00000495141.1; ENSG00000131044.18. [Q3SXZ7-2]
DR Ensembl; ENST00000375938.8; ENSP00000365105.4; ENSG00000131044.18. [Q3SXZ7-1]
DR Ensembl; ENST00000535842.6; ENSP00000442515.1; ENSG00000131044.18. [Q3SXZ7-1]
DR GeneID; 164395; -.
DR KEGG; hsa:164395; -.
DR MANE-Select; ENST00000535842.6; ENSP00000442515.1; NM_001008409.5; NP_001008409.1.
DR UCSC; uc002wwy.2; human. [Q3SXZ7-1]
DR CTD; 164395; -.
DR DisGeNET; 164395; -.
DR GeneCards; TTLL9; -.
DR HGNC; HGNC:16118; TTLL9.
DR HPA; ENSG00000131044; Group enriched (brain, choroid plexus, epididymis, fallopian tube, testis).
DR MIM; 619838; gene.
DR neXtProt; NX_Q3SXZ7; -.
DR OpenTargets; ENSG00000131044; -.
DR PharmGKB; PA25666; -.
DR VEuPathDB; HostDB:ENSG00000131044; -.
DR eggNOG; KOG2157; Eukaryota.
DR GeneTree; ENSGT00940000159879; -.
DR HOGENOM; CLU_010131_0_1_1; -.
DR InParanoid; Q3SXZ7; -.
DR OMA; LIWANGP; -.
DR OrthoDB; 584228at2759; -.
DR PhylomeDB; Q3SXZ7; -.
DR TreeFam; TF313087; -.
DR PathwayCommons; Q3SXZ7; -.
DR Reactome; R-HSA-8955332; Carboxyterminal post-translational modifications of tubulin.
DR SignaLink; Q3SXZ7; -.
DR BioGRID-ORCS; 164395; 10 hits in 1013 CRISPR screens.
DR ChiTaRS; TTLL9; human.
DR GenomeRNAi; 164395; -.
DR Pharos; Q3SXZ7; Tdark.
DR PRO; PR:Q3SXZ7; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q3SXZ7; protein.
DR Bgee; ENSG00000131044; Expressed in right uterine tube and 132 other tissues.
DR ExpressionAtlas; Q3SXZ7; baseline and differential.
DR Genevisible; Q3SXZ7; HS.
DR GO; GO:0036064; C:ciliary basal body; IEA:Ensembl.
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; ISS:UniProtKB.
DR GO; GO:0030317; P:flagellated sperm motility; IEA:Ensembl.
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 InterPro; IPR027751; TTLL9.
DR PANTHER; PTHR12241:SF39; PTHR12241:SF39; 1.
DR Pfam; PF03133; TTL; 1.
DR PROSITE; PS51221; TTL; 1.
PE 2: Evidence at transcript 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..439
FT /note="Probable tubulin polyglutamylase TTLL9"
FT /id="PRO_0000324517"
FT DOMAIN 40..380
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 256..257
FT /note="L-glutamate"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 167
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 173..174
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 173
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 211..214
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 224..226
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 248
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 254..255
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 272
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 326
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 339
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 339
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 341
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 357
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 173
FT /note="Essential for specifying alpha-elongation versus
FT initiation step of the polyglutamylase activity"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT VAR_SEQ 1..50
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035765"
FT VAR_SEQ 169..191
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035766"
FT VAR_SEQ 236..250
FT /note="VFAECLLWSGHRRQD -> YIPLRAWLYRDGFARFSNTRFTLNSIDDQY
FT (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035767"
FT VAR_SEQ 270..439
FT /note="GCKWTLQRFRQYLASKHGPEAVETLFRDIDNIFVKSLQSVQKVIISDKHCFE
FT LYGYDILIDQDLKPWLLEVNASPSLTASSQEDYELKTCLLEDTLHVVDMEARLTGREKR
FT VGGFDLMWNDGPVSREEGAPDLSGMGNFVTNTHLGCVNDRKKQLRQLFCSLQVQKKASS
FT -> VAPGGQCVPITDSQQPGRL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035768"
FT VAR_SEQ 374..439
FT /note="LTGREKRVGGFDLMWNDGPVSREEGAPDLSGMGNFVTNTHLGCVNDRKKQLR
FT QLFCSLQVQKKASS -> SLRADSPCW (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035769"
FT VARIANT 76
FT /note="Y -> C (in dbSNP:rs17093689)"
FT /id="VAR_039805"
FT CONFLICT 274
FT /note="T -> M (in Ref. 4; AAI04026)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 439 AA; 51472 MW; ED6172FE902F791C CRC64;
MVPSREALLG PGTTAIRCPK KLQNQNYKGH GLSKGKEREQ RASIRFKTTL MNTLMDVLRH
RPGWVEVKDE GEWDFYWCDV SWLRENFDHT YMDEHVRISH FRNHYELTRK NYMVKNLKRF
RKQLEREAGK LEAAKCDFFP KTFEMPCEYH LFVEEFRKNP GITWIMKPVA RSQGKGIFLF
RRLKDIVDWR KDTRSSDDQK DDIPVENYVA QRYIENPYLI GGRKFDLRVY VLVMSVFAEC
LLWSGHRRQD VHLTNVAVQK TSPDYHPKKG CKWTLQRFRQ YLASKHGPEA VETLFRDIDN
IFVKSLQSVQ KVIISDKHCF ELYGYDILID QDLKPWLLEV NASPSLTASS QEDYELKTCL
LEDTLHVVDM EARLTGREKR VGGFDLMWND GPVSREEGAP DLSGMGNFVT NTHLGCVNDR
KKQLRQLFCS LQVQKKASS
