TTL13_HUMAN
ID TTL13_HUMAN Reviewed; 815 AA.
AC A6NNM8;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Tubulin polyglutamylase TTLL13;
DE EC=6.3.2.- {ECO:0000250|UniProtKB:A4Q9F6};
DE AltName: Full=Tubulin tyrosine ligase like 13 {ECO:0000312|HGNC:HGNC:32484};
DE AltName: Full=Tubulin tyrosine ligase-like family member 13 pseudogene;
DE AltName: Full=Tubulin--tyrosine ligase-like protein 13;
GN Name=TTLL13 {ECO:0000312|HGNC:HGNC:32484}; Synonyms=TTLL13P;
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=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=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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).
RN [5]
RP DOMAIN, AND MUTAGENESIS OF 425-LYS--LYS-427 AND 451-ARG-LYS-452.
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. Mediates ATP-dependent polyglutamate side-chain elongation of
CC the polyglutamylation reaction but not the initiation step.
CC Preferentially modifies the alpha-tubulin tail over a beta-tail.
CC {ECO:0000250|UniProtKB:A4Q9F6}.
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:A4Q9F6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60149;
CC Evidence={ECO:0000250|UniProtKB:A4Q9F6};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000305};
CC IsoId=A6NNM8-1; Sequence=Displayed;
CC Name=2 {ECO:0000305};
CC IsoId=A6NNM8-2; Sequence=VSP_052720, VSP_052721;
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-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 -!- MISCELLANEOUS: [Isoform 2]: May be due to an intron retention.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the tubulin--tyrosine ligase family.
CC {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BC036668; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK127965; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC091167; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471101; EAX02094.1; -; Genomic_DNA.
DR EMBL; BC036668; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; A6NNM8; -.
DR SMR; A6NNM8; -.
DR IntAct; A6NNM8; 2.
DR iPTMnet; A6NNM8; -.
DR PhosphoSitePlus; A6NNM8; -.
DR BioMuta; TTLL13P; -.
DR EPD; A6NNM8; -.
DR MassIVE; A6NNM8; -.
DR PaxDb; A6NNM8; -.
DR PeptideAtlas; A6NNM8; -.
DR PRIDE; A6NNM8; -.
DR ProteomicsDB; 1621; -. [A6NNM8-1]
DR ProteomicsDB; 1622; -. [A6NNM8-2]
DR Antibodypedia; 64383; 22 antibodies from 7 providers.
DR DNASU; 440307; -.
DR Ensembl; ENST00000438251.3; ENSP00000491066.1; ENSG00000213471.10. [A6NNM8-1]
DR GeneCards; TTLL13P; -.
DR HGNC; HGNC:32484; TTLL13.
DR HPA; ENSG00000213471; Tissue enriched (testis).
DR neXtProt; NX_A6NNM8; -.
DR OpenTargets; ENSG00000213471; -.
DR PharmGKB; PA143485664; -.
DR VEuPathDB; HostDB:ENSG00000213471; -.
DR GeneTree; ENSGT00940000161367; -.
DR InParanoid; A6NNM8; -.
DR OMA; HSWCHLQ; -.
DR PhylomeDB; A6NNM8; -.
DR TreeFam; TF313087; -.
DR PathwayCommons; A6NNM8; -.
DR Reactome; R-HSA-8955332; Carboxyterminal post-translational modifications of tubulin.
DR SignaLink; A6NNM8; -.
DR Pharos; A6NNM8; Tdark.
DR PRO; PR:A6NNM8; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; A6NNM8; protein.
DR Bgee; ENSG00000213471; Expressed in testis and 93 other tissues.
DR ExpressionAtlas; A6NNM8; baseline and differential.
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: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; Coiled coil; Ligase; Magnesium;
KW Metal-binding; Microtubule; Nucleotide-binding; Reference proteome.
FT CHAIN 1..815
FT /note="Tubulin polyglutamylase TTLL13"
FT /id="PRO_0000326167"
FT DOMAIN 85..430
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
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:0000269|PubMed:25959773"
FT REGION 520..556
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 504..528
FT /evidence="ECO:0000255"
FT COMPBIAS 520..545
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 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"
FT VAR_SEQ 452..459
FT /note="KEKTESSH -> CARCLACV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_052720"
FT VAR_SEQ 460..815
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_052721"
FT VARIANT 126
FT /note="A -> T (in dbSNP:rs12912620)"
FT /id="VAR_057318"
FT VARIANT 262
FT /note="T -> I (in dbSNP:rs2063743)"
FT /id="VAR_057319"
FT MUTAGEN 425..427
FT /note="KRK->EEE: Decreased binding to microtubules and
FT polyglutamylase activity; when associated with 451-E-E-
FT 452."
FT /evidence="ECO:0000269|PubMed:25959773"
FT MUTAGEN 451..452
FT /note="RK->EE: Decreased binding to microtubules and
FT polyglutamylase activity; when associated with 425-E--E-
FT 427."
FT /evidence="ECO:0000269|PubMed:25959773"
FT CONFLICT 108
FT /note="G -> S (in Ref. 1; AK127965)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 815 AA; 93645 MW; E9407A6E0DDD9F68 CRC64;
MEPSTCRTME SEEDYVEEKE SEKCVKEGVT NPSNSSQQAL LKADYKALKN GVPSPIMATK
IPKKVIAPVD TGDLEAGRRK RRRKRRSLAI NLTNCKYESV RRAAQMCGLK EVGEDEEWTL
YWTDCAVSLE RVMDMKRFQK INHFPGMTEI CRKDLLARNL NRMYKLYPSE YNIFPRTWCL
PADYGDFQSY GRQRKARTYI CKPDSGCQGR GIFITRNPRE IKPGEHMICQ QYISKPLLID
GFKFDMRVYV LITSCDPLRI FTYEEGLARF ATTPYMEPSH NNLDNVCMHL TNYAINKHNE
NFVRDGAVGS KRKLSTLNIW LQEHSYNPGE LWGDIEDIII KTIISAHSVL RHNYRTCFPQ
YLNGGTCACF EILGFDILLD HKLKPWLLEV NHSPSFTTDS CLDQEVKDAL LCDAMTLVNL
RGCDKRKVME EDKRRVKERL FQCYRQPRES RKEKTESSHV AMLDQERYED SHLGKYRRIY
PGPDTEKYAR FFKHNGSLFQ ETAASKAREE CARQQLEEIR LKQEQQETSG TKRQKARDQN
QGESAGEKSR PRAGLQSLST HLAYRNRNWE KELLPGQLDT MRPQEIVEEE ELERMKALLQ
RETLIRSLGI VEQLTRLQHP GPQGQKKLHE SRDRLGSQEL KSMSLVLLVL LRGAATEQGA
PHFLHPVLPH ESIPRILGAL PSMNAAIPHV PRYHLQPKNF NWTGEPAAIN SCSLSMKKAG
RCYFSSARIR LTSQGQASRR LEAINRVLAG SVPPTLTPKQ GYFLQPERVA SDSWTECTLP
SMVNSEHRAA KVPLCPASAP MLQRSRALLN INQFR
