TTL11_HUMAN
ID TTL11_HUMAN Reviewed; 800 AA.
AC Q8NHH1; F8W6M1;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-SEP-2015, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Tubulin polyglutamylase TTLL11 {ECO:0000250|UniProtKB:A4Q9F4};
DE EC=6.3.2.- {ECO:0000250|UniProtKB:A4Q9F4};
DE AltName: Full=Tubulin--tyrosine ligase-like protein 11;
GN Name=TTLL11 {ECO:0000312|HGNC:HGNC:18113}; Synonyms=C9orf20;
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 2).
RC TISSUE=Brain;
RA Guo J.H., Yu L.;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP FUNCTION.
RX PubMed=22493317; DOI=10.1091/mbc.e11-11-0931;
RA Backer C.B., Gutzman J.H., Pearson C.G., Cheeseman I.M.;
RT "CSAP localizes to polyglutamylated microtubules and promotes proper cilia
RT function and zebrafish development.";
RL Mol. Biol. Cell 23:2122-2130(2012).
RN [4]
RP DOMAIN, AND MUTAGENESIS OF 578-LYS--ARG-581.
RX PubMed=25959773; DOI=10.1016/j.cell.2015.04.003;
RA Garnham C.P., Vemu A., Wilson-Kubalek E.M., Yu I., Szyk A., Lander G.C.,
RA Milligan R.A., Roll-Mecak A.;
RT "Multivalent microtubule recognition by tubulin tyrosine ligase-like family
RT glutamylases.";
RL Cell 161:1112-1123(2015).
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. Preferentially mediates ATP-dependent polyglutamate long side-
CC chain elongation over the initiation step of the polyglutamylation
CC reaction. Preferentially modifies the alpha-tubulin tail over a beta-
CC tail (By similarity). Required for CCSAP localization to both spindle
CC and cilia microtubules (PubMed:22493317). Promotes tubulin
CC polyglutamylation which stimulates spastin/SPAST-mediated microtubule
CC severing, thereby regulating microtubule functions (By similarity).
CC {ECO:0000250|UniProtKB:A4Q9F4, ECO:0000269|PubMed:22493317}.
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:0000250|UniProtKB:A4Q9F4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60145;
CC Evidence={ECO:0000250|UniProtKB:A4Q9F4};
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:A4Q9F4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60149;
CC Evidence={ECO:0000250|UniProtKB:A4Q9F4};
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:A4Q9F4}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:A4Q9F4}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8NHH1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NHH1-2; Sequence=VSP_057853, VSP_057854;
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:0000269|PubMed:25959773}.
CC -!- DOMAIN: Gln-345 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}.
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DR EMBL; AF521886; AAM81328.1; -; mRNA.
DR EMBL; AL162423; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL442634; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL445587; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001132914.1; NM_001139442.1.
DR RefSeq; NP_919228.2; NM_194252.2.
DR AlphaFoldDB; Q8NHH1; -.
DR SMR; Q8NHH1; -.
DR BioGRID; 127650; 7.
DR IntAct; Q8NHH1; 2.
DR MINT; Q8NHH1; -.
DR STRING; 9606.ENSP00000321346; -.
DR iPTMnet; Q8NHH1; -.
DR PhosphoSitePlus; Q8NHH1; -.
DR BioMuta; TTLL11; -.
DR DMDM; 73920150; -.
DR jPOST; Q8NHH1; -.
DR MassIVE; Q8NHH1; -.
DR PaxDb; Q8NHH1; -.
DR PeptideAtlas; Q8NHH1; -.
DR PRIDE; Q8NHH1; -.
DR ProteomicsDB; 29811; -.
DR ProteomicsDB; 73708; -.
DR Antibodypedia; 53016; 16 antibodies from 8 providers.
DR DNASU; 158135; -.
DR Ensembl; ENST00000321582.11; ENSP00000321346.6; ENSG00000175764.17.
DR Ensembl; ENST00000373776.5; ENSP00000362881.4; ENSG00000175764.17.
DR GeneID; 158135; -.
DR KEGG; hsa:158135; -.
DR UCSC; uc004blt.2; human. [Q8NHH1-1]
DR UCSC; uc011lyl.3; human.
DR CTD; 158135; -.
DR DisGeNET; 158135; -.
DR GeneCards; TTLL11; -.
DR HGNC; HGNC:18113; TTLL11.
DR HPA; ENSG00000175764; Tissue enhanced (skeletal).
DR neXtProt; NX_Q8NHH1; -.
DR PharmGKB; PA25977; -.
DR VEuPathDB; HostDB:ENSG00000175764; -.
DR eggNOG; KOG2158; Eukaryota.
DR HOGENOM; CLU_532730_0_0_1; -.
DR InParanoid; Q8NHH1; -.
DR OMA; SAPDCNA; -.
DR PhylomeDB; Q8NHH1; -.
DR TreeFam; TF313087; -.
DR PathwayCommons; Q8NHH1; -.
DR Reactome; R-HSA-8955332; Carboxyterminal post-translational modifications of tubulin.
DR SignaLink; Q8NHH1; -.
DR BioGRID-ORCS; 158135; 8 hits in 1077 CRISPR screens.
DR ChiTaRS; TTLL11; human.
DR GenomeRNAi; 158135; -.
DR Pharos; Q8NHH1; Tdark.
DR PRO; PR:Q8NHH1; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q8NHH1; protein.
DR Bgee; ENSG00000175764; Expressed in C1 segment of cervical spinal cord and 109 other tissues.
DR ExpressionAtlas; Q8NHH1; baseline and differential.
DR Genevisible; Q8NHH1; HS.
DR GO; GO:0036064; C:ciliary basal body; IEA:Ensembl.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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; ISS:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0051013; P:microtubule severing; IEA:Ensembl.
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 Alternative splicing; ATP-binding; Cell projection; Cilium; Cytoplasm;
KW Cytoskeleton; Ligase; Magnesium; Metal-binding; Microtubule;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..800
FT /note="Tubulin polyglutamylase TTLL11"
FT /id="PRO_0000212445"
FT DOMAIN 218..570
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 138..225
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 435..436
FT /note="L-glutamate"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT REGION 557..628
FT /note="c-MTBD region"
FT /evidence="ECO:0000269|PubMed:25959773"
FT REGION 755..800
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 191..205
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 206..225
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 761..780
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 781..800
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 339
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 345..346
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 345
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 372..375
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 385..387
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 411
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 433..434
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 455
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 518
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 531
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 531
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 533
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 563
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 345
FT /note="Essential for specifying alpha-elongation versus
FT initiation step of the polyglutamylase activity"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT VAR_SEQ 514..538
FT /note="ILGFDILLMKNLKPILLEVNANPSM -> VTIASSQPAFPALTGLKRALWLR
FT VG (in isoform 2)"
FT /id="VSP_057853"
FT VAR_SEQ 539..800
FT /note="Missing (in isoform 2)"
FT /id="VSP_057854"
FT MUTAGEN 578..581
FT /note="KKKR->EEEE: Decreased binding to microtubules and
FT polyglutamylase activity; when associated with E-416 and E-
FT 419."
FT /evidence="ECO:0000269|PubMed:25959773"
SQ SEQUENCE 800 AA; 87612 MW; DB9C75CC06124C27 CRC64;
MAAAASVTGR VTWAASPMRS LGLGRRLSLP GPRLDAVTAA VNPSLSDHGN GLGRGTRGSG
CSGGSLVADW GGGAAAAAAV ALALAPALST MRRGSSESEL AARWEAEAVA AAKAAAKAEA
EATAETVAEQ VRVDAGAAGE PECKAGEEQP KVLAPAPAQP SAAEEGNTQV LQRPPPTLPP
SKPKPVQGLC PHGKPRDKGR SCKRSSGHGS GENGSQRPVT VDSSKARTSL DALKISIRQL
KWKEFPFGRR LPCDIYWHGV SFHDNDIFSG QVNKFPGMTE MVRKITLSRA VRTMQNLFPE
EYNFYPRSWI LPDEFQLFVA QVQMVKDDDP SWKPTFIVKP DGGCQGDGIY LIKDPSDIRL
AGTLQSRPAV VQEYICKPLL IDKLKFDIRL YVLLKSLDPL EIYIAKDGLS RFCTEPYQEP
TPKNLHRIFM HLTNYSLNIH SGNFIHSDSA STGSKRTFSS ILCRLSSKGV DIKKVWSDII
SVVIKTVIAL TPELKVFYQS DIPTGRPGPT CFQILGFDIL LMKNLKPILL EVNANPSMRI
EHEHELSPGV FENVPSLVDE EVKVAVIRDT LRLMDPLKKK RENQSQQLEK PFAGKEDALD
GELTSAPDCN ANPEAHLPSI CLKQVFPKYA KQFNYLRLVD RMANLFIRFL GIKGTMKLGP
TGFRTFIRSC KLSSSSLSMA AVDILYIDIT RRWNSMTLDQ RDSGMCLQAF VEAFFFLAQR
KFKMLPLHEQ VASLIDLCEY HLSLLDEKRL VCGRGVPSGG RPPHRGPPQE PSPSAQPAGD
NPPPRTSCAN KLSHPRHTLS
