TTL_HUMAN
ID TTL_HUMAN Reviewed; 377 AA.
AC Q8NG68; Q585T3; Q7Z302; Q8N426;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Tubulin--tyrosine ligase;
DE Short=TTL;
DE EC=6.3.2.25 {ECO:0000250|UniProtKB:Q9QXJ0};
GN Name=TTL;
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 [MRNA].
RA Miyazaki K., Okamoto Y., Kato C., Sakamoto M., Ohira M., Morohashi A.,
RA Nakagawara A.;
RT "Homo sapiens tubulin tyrosine ligase mRNA, complete cds.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
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].
RC TISSUE=Brain;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 205-377.
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [8]
RP FUNCTION.
RX PubMed=25908662; DOI=10.1126/science.aaa5175;
RA Barisic M., Silva e Sousa R., Tripathy S.K., Magiera M.M., Zaytsev A.V.,
RA Pereira A.L., Janke C., Grishchuk E.L., Maiato H.;
RT "Mitosis. Microtubule detyrosination guides chromosomes during mitosis.";
RL Science 348:799-803(2015).
CC -!- FUNCTION: Catalyzes the post-translational addition of a tyrosine to
CC the C-terminal end of detyrosinated alpha-tubulin.
CC {ECO:0000269|PubMed:25908662}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-
CC [tubulin] + L-tyrosine = ADP + C-terminal L-alpha-aminoacyl-L-
CC glutamyl-L-glutamyl-L-tyrosyl-[tubulin] + H(+) + phosphate;
CC Xref=Rhea:RHEA:17605, Rhea:RHEA-COMP:16434, Rhea:RHEA-COMP:16435,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58315, ChEBI:CHEBI:149554, ChEBI:CHEBI:149555,
CC ChEBI:CHEBI:456216; EC=6.3.2.25;
CC Evidence={ECO:0000250|UniProtKB:Q9QXJ0};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P38584};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Evidence={ECO:0000250|UniProtKB:P38584};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P38584}.
CC -!- SIMILARITY: Belongs to the tubulin--tyrosine ligase family.
CC {ECO:0000305}.
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DR EMBL; AB071393; BAC06832.2; -; mRNA.
DR EMBL; AC012442; AAX81998.1; -; Genomic_DNA.
DR EMBL; CH471217; EAW73589.1; -; Genomic_DNA.
DR EMBL; BC036819; AAH36819.1; -; mRNA.
DR EMBL; BX538316; CAD98091.1; -; mRNA.
DR CCDS; CCDS2096.1; -.
DR RefSeq; NP_714923.1; NM_153712.4.
DR AlphaFoldDB; Q8NG68; -.
DR SMR; Q8NG68; -.
DR BioGRID; 127297; 13.
DR IntAct; Q8NG68; 5.
DR STRING; 9606.ENSP00000233336; -.
DR BindingDB; Q8NG68; -.
DR ChEMBL; CHEMBL5549; -.
DR iPTMnet; Q8NG68; -.
DR PhosphoSitePlus; Q8NG68; -.
DR BioMuta; TTL; -.
DR DMDM; 47117358; -.
DR EPD; Q8NG68; -.
DR jPOST; Q8NG68; -.
DR MassIVE; Q8NG68; -.
DR MaxQB; Q8NG68; -.
DR PaxDb; Q8NG68; -.
DR PeptideAtlas; Q8NG68; -.
DR PRIDE; Q8NG68; -.
DR ProteomicsDB; 73442; -.
DR Antibodypedia; 33272; 177 antibodies from 25 providers.
DR DNASU; 150465; -.
DR Ensembl; ENST00000233336.7; ENSP00000233336.5; ENSG00000114999.8.
DR GeneID; 150465; -.
DR KEGG; hsa:150465; -.
DR MANE-Select; ENST00000233336.7; ENSP00000233336.5; NM_153712.5; NP_714923.1.
DR UCSC; uc002thu.4; human.
DR CTD; 150465; -.
DR DisGeNET; 150465; -.
DR GeneCards; TTL; -.
DR HGNC; HGNC:21586; TTL.
DR HPA; ENSG00000114999; Low tissue specificity.
DR MIM; 608291; gene.
DR neXtProt; NX_Q8NG68; -.
DR OpenTargets; ENSG00000114999; -.
DR PharmGKB; PA134934330; -.
DR VEuPathDB; HostDB:ENSG00000114999; -.
DR eggNOG; KOG2157; Eukaryota.
DR GeneTree; ENSGT00940000161907; -.
DR HOGENOM; CLU_010131_2_0_1; -.
DR InParanoid; Q8NG68; -.
DR OMA; LAQLVNY; -.
DR OrthoDB; 626048at2759; -.
DR PhylomeDB; Q8NG68; -.
DR TreeFam; TF350555; -.
DR BRENDA; 6.3.2.25; 2681.
DR PathwayCommons; Q8NG68; -.
DR Reactome; R-HSA-8955332; Carboxyterminal post-translational modifications of tubulin.
DR SignaLink; Q8NG68; -.
DR SIGNOR; Q8NG68; -.
DR BioGRID-ORCS; 150465; 11 hits in 1079 CRISPR screens.
DR ChiTaRS; TTL; human.
DR GenomeRNAi; 150465; -.
DR Pharos; Q8NG68; Tchem.
DR PRO; PR:Q8NG68; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8NG68; protein.
DR Bgee; ENSG00000114999; Expressed in dorsal root ganglion and 189 other tissues.
DR Genevisible; Q8NG68; HS.
DR GO; GO:0005876; C:spindle microtubule; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004835; F:tubulin-tyrosine ligase activity; IMP:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; IMP:UniProtKB.
DR GO; GO:0030516; P:regulation of axon extension; IEA:Ensembl.
DR GO; GO:0090235; P:regulation of metaphase plate congression; IMP:UniProtKB.
DR InterPro; IPR004344; TTL/TTLL_fam.
DR Pfam; PF03133; TTL; 1.
DR PROSITE; PS51221; TTL; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Ligase; Magnesium; Nucleotide-binding; Potassium;
KW Reference proteome.
FT CHAIN 1..377
FT /note="Tubulin--tyrosine ligase"
FT /id="PRO_0000212434"
FT DOMAIN 3..370
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT CONFLICT 245
FT /note="I -> V (in Ref. 5; CAD98091)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 377 AA; 43212 MW; 7A13E2C28E1AD6EA CRC64;
MYTFVVRDEN SSVYAEVSRL LLATGHWKRL RRDNPRFNLM LGERNRLPFG RLGHEPGLVQ
LVNYYRGADK LCRKASLVKL IKTSPELAES CTWFPESYVI YPTNLKTPVA PAQNGIQPPI
SNSRTDEREF FLASYNRKKE DGEGNVWIAK SSAGAKGEGI LISSEASELL DFIDNQGQVH
VIQKYLEHPL LLEPGHRKFD IRSWVLVDHQ YNIYLYREGV LRTASEPYHV DNFQDKTCHL
TNHCIQKEYS KNYGKYEEGN EMFFKEFNQY LTSALNITLE SSILLQIKHI IRNCLLSVEP
AISTKHLPYQ SFQLFGFDFM VDEELKVWLI EVNGAPACAQ KLYAELCQGI VDIAISSVFP
PPDVEQPQTQ PAAFIKL
