TTBK2_HUMAN
ID TTBK2_HUMAN Reviewed; 1244 AA.
AC Q6IQ55; O94932; Q6ZN52; Q8IVV1;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Tau-tubulin kinase 2;
DE EC=2.7.11.1;
GN Name=TTBK2; Synonyms=KIAA0847;
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=Cerebellum;
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 MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP PRO-8.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 600-1244 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [5]
RP INVOLVEMENT IN SCA11.
RX PubMed=18037885; DOI=10.1038/ng.2007.43;
RA Houlden H., Johnson J., Gardner-Thorpe C., Lashley T., Hernandez D.,
RA Worth P., Singleton A.B., Hilton D.A., Holton J., Revesz T., Davis M.B.,
RA Giunti P., Wood N.W.;
RT "Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation,
RT segregate with spinocerebellar ataxia type 11.";
RL Nat. Genet. 39:1434-1436(2007).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF LYS-50; LYS-143; ASP-163; ARG-181 AND ALA-184.
RX PubMed=21548880; DOI=10.1042/bj20110276;
RA Bouskila M., Esoof N., Gay L., Fang E.H., Deak M., Begley M.J.,
RA Cantley L.C., Prescott A., Storey K.G., Alessi D.R.;
RT "TTBK2 kinase substrate specificity and the impact of spinocerebellar-
RT ataxia-causing mutations on expression, activity, localization and
RT development.";
RL Biochem. J. 437:157-167(2011).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-786, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [8]
RP INTERACTION WITH CEP164.
RX PubMed=22863007; DOI=10.1016/j.cell.2012.06.028;
RA Chaki M., Airik R., Ghosh A.K., Giles R.H., Chen R., Slaats G.G., Wang H.,
RA Hurd T.W., Zhou W., Cluckey A., Gee H.Y., Ramaswami G., Hong C.J.,
RA Hamilton B.A., Cervenka I., Ganji R.S., Bryja V., Arts H.H.,
RA van Reeuwijk J., Oud M.M., Letteboer S.J., Roepman R., Husson H.,
RA Ibraghimov-Beskrovnaya O., Yasunaga T., Walz G., Eley L., Sayer J.A.,
RA Schermer B., Liebau M.C., Benzing T., Le Corre S., Drummond I., Janssen S.,
RA Allen S.J., Natarajan S., O'Toole J.F., Attanasio M., Saunier S.,
RA Antignac C., Koenekoop R.K., Ren H., Lopez I., Nayir A., Stoetzel C.,
RA Dollfus H., Massoudi R., Gleeson J.G., Andreoli S.P., Doherty D.G.,
RA Lindstrad A., Golzio C., Katsanis N., Pape L., Abboud E.B., Al-Rajhi A.A.,
RA Lewis R.A., Omran H., Lee E.Y., Wang S., Sekiguchi J.M., Saunders R.,
RA Johnson C.A., Garner E., Vanselow K., Andersen J.S., Shlomai J.,
RA Nurnberg G., Nurnberg P., Levy S., Smogorzewska A., Otto E.A.,
RA Hildebrandt F.;
RT "Exome capture reveals ZNF423 and CEP164 mutations, linking renal
RT ciliopathies to DNA damage response signaling.";
RL Cell 150:533-548(2012).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23141541; DOI=10.1016/j.cell.2012.10.010;
RA Goetz S.C., Liem K.F. Jr., Anderson K.V.;
RT "The spinocerebellar ataxia-associated gene tau tubulin kinase 2 controls
RT the initiation of ciliogenesis.";
RL Cell 151:847-858(2012).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-445 AND SER-1103, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP FUNCTION.
RX PubMed=30375385; DOI=10.1038/s41467-018-06990-9;
RA Huang N., Zhang D., Li F., Chai P., Wang S., Teng J., Chen J.;
RT "M-Phase Phosphoprotein 9 regulates ciliogenesis by modulating CP110-CEP97
RT complex localization at the mother centriole.";
RL Nat. Commun. 9:4511-4511(2018).
RN [12]
RP VARIANTS [LARGE SCALE ANALYSIS] PRO-8; GLN-120; ALA-313; MET-440; PRO-500;
RP GLY-635; ILE-1062; MET-1084; ALA-1097; ARG-1122 AND THR-1241.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [13]
RP VARIANTS PRO-8; GLY-842 AND HIS-1110.
RX PubMed=19533200; DOI=10.1007/s00415-009-5209-0;
RA Edener U., Kurth I., Meiner A., Hoffmann F., Hubner C.A., Bernard V.,
RA Gillessen-Kaesbach G., Zuhlke C.;
RT "Missense exchanges in the TTBK2 gene mutated in SCA11.";
RL J. Neurol. 256:1856-1859(2009).
RN [14]
RP VARIANTS ILE-367 AND GLU-724.
RX PubMed=26063658; DOI=10.1093/brain/awv155;
RA Verdura E., Herve D., Scharrer E., del Mar Amador M., Guyant-Marechal L.,
RA Philippi A., Corlobe A., Bergametti F., Gazal S., Prieto-Morin C.,
RA Beaufort N., Le Bail B., Viakhireva I., Dichgans M., Chabriat H.,
RA Haffner C., Tournier-Lasserve E.;
RT "Heterozygous HTRA1 mutations are associated with autosomal dominant
RT cerebral small vessel disease.";
RL Brain 138:2347-2358(2015).
CC -!- FUNCTION: Serine/threonine kinase that acts as a key regulator of
CC ciliogenesis: controls the initiation of ciliogenesis by binding to the
CC distal end of the basal body and promoting the removal of CCP110, which
CC caps the mother centriole, leading to the recruitment of IFT proteins,
CC which build the ciliary axoneme. Has some substrate preference for
CC proteins that are already phosphorylated on a Tyr residue at the +2
CC position relative to the phosphorylation site. Able to phosphorylate
CC tau on serines in vitro (PubMed:23141541). Phosphorylates MPHOSPH9
CC which promotes its ubiquitination and proteasomal degradation, loss of
CC MPHOSPH9 facilitates the removal of the CP110-CEP97 complex (a negative
CC regulator of ciliogenesis) from the mother centrioles, promoting the
CC initiation of ciliogenesis (PubMed:30375385).
CC {ECO:0000269|PubMed:21548880, ECO:0000269|PubMed:23141541,
CC ECO:0000269|PubMed:30375385}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:21548880};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:21548880};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=18 uM for RRKDLHDDEEDEAMSIYpA peptide
CC {ECO:0000269|PubMed:21548880};
CC KM=141 uM for RRKDLHDDEEDEAMSIYA peptide
CC {ECO:0000269|PubMed:21548880};
CC Vmax=76 umol/min/mg enzyme with RRKDLHDDEEDEAMSIYpA peptide as
CC substrate {ECO:0000269|PubMed:21548880};
CC Vmax=66 umol/min/mg enzyme with RRKDLHDDEEDEAMSIYA peptide as
CC substrate {ECO:0000269|PubMed:21548880};
CC -!- SUBUNIT: Interacts with CEP164. {ECO:0000269|PubMed:22863007}.
CC -!- INTERACTION:
CC Q6IQ55; Q9UPV0: CEP164; NbExp=4; IntAct=EBI-1050303, EBI-3937015;
CC Q6IQ55; Q53G59: KLHL12; NbExp=6; IntAct=EBI-1050303, EBI-740929;
CC Q6IQ55-3; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-25930156, EBI-350590;
CC Q6IQ55-3; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-25930156, EBI-358545;
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium {ECO:0000250}. Cytoplasm,
CC cytoskeleton, cilium basal body {ECO:0000250}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome, centriole. Cytoplasm,
CC cytosol. Nucleus. Note=Localizes to the transition zone in primary
CC cilia in response to cell cycle signals that promote ciliogenesis (By
CC similarity). May also be present in cytosol and, at lower level in the
CC nucleus. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6IQ55-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6IQ55-2; Sequence=VSP_018272, VSP_018275;
CC Name=3;
CC IsoId=Q6IQ55-3; Sequence=VSP_018273, VSP_018274;
CC -!- DISEASE: Spinocerebellar ataxia 11 (SCA11) [MIM:604432]:
CC Spinocerebellar ataxia is a clinically and genetically heterogeneous
CC group of cerebellar disorders. Patients show progressive incoordination
CC of gait and often poor coordination of hands, speech and eye movements,
CC due to degeneration of the cerebellum with variable involvement of the
CC brainstem and spinal cord. SCA11 is an autosomal dominant cerebellar
CC ataxia (ADCA). It is a relatively benign, late-onset, slowly
CC progressive neurologic disorder. {ECO:0000269|PubMed:18037885}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; AK131372; BAD18523.1; -; mRNA.
DR EMBL; AC068727; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090510; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC041876; AAH41876.1; -; mRNA.
DR EMBL; BC071556; AAH71556.1; -; mRNA.
DR EMBL; AB020654; BAA74870.1; -; mRNA.
DR CCDS; CCDS42029.1; -. [Q6IQ55-1]
DR RefSeq; NP_775771.3; NM_173500.3. [Q6IQ55-1]
DR PDB; 6U0K; X-ray; 1.74 A; A/B=1-299.
DR PDB; 6VRF; X-ray; 1.50 A; A/B=1-299.
DR PDB; 7O3B; X-ray; 2.40 A; G/H/I=1074-1087.
DR PDB; 7Q8Y; X-ray; 1.60 A; A/B=1-299.
DR PDB; 7Q8Z; X-ray; 1.57 A; A/B=1-299.
DR PDB; 7Q90; X-ray; 1.60 A; A/B=1-299.
DR PDBsum; 6U0K; -.
DR PDBsum; 6VRF; -.
DR PDBsum; 7O3B; -.
DR PDBsum; 7Q8Y; -.
DR PDBsum; 7Q8Z; -.
DR PDBsum; 7Q90; -.
DR AlphaFoldDB; Q6IQ55; -.
DR SMR; Q6IQ55; -.
DR BioGRID; 126962; 30.
DR CORUM; Q6IQ55; -.
DR IntAct; Q6IQ55; 7.
DR STRING; 9606.ENSP00000267890; -.
DR BindingDB; Q6IQ55; -.
DR ChEMBL; CHEMBL3337327; -.
DR GlyGen; Q6IQ55; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; Q6IQ55; -.
DR PhosphoSitePlus; Q6IQ55; -.
DR BioMuta; TTBK2; -.
DR DMDM; 116242833; -.
DR EPD; Q6IQ55; -.
DR jPOST; Q6IQ55; -.
DR MassIVE; Q6IQ55; -.
DR MaxQB; Q6IQ55; -.
DR PaxDb; Q6IQ55; -.
DR PeptideAtlas; Q6IQ55; -.
DR PRIDE; Q6IQ55; -.
DR ProteomicsDB; 66487; -. [Q6IQ55-1]
DR ProteomicsDB; 66488; -. [Q6IQ55-2]
DR ProteomicsDB; 66489; -. [Q6IQ55-3]
DR Antibodypedia; 6214; 228 antibodies from 30 providers.
DR DNASU; 146057; -.
DR Ensembl; ENST00000267890.11; ENSP00000267890.6; ENSG00000128881.18. [Q6IQ55-1]
DR Ensembl; ENST00000567840.5; ENSP00000455734.1; ENSG00000128881.18. [Q6IQ55-3]
DR GeneID; 146057; -.
DR KEGG; hsa:146057; -.
DR MANE-Select; ENST00000267890.11; ENSP00000267890.6; NM_173500.4; NP_775771.3.
DR UCSC; uc001zqo.4; human. [Q6IQ55-1]
DR CTD; 146057; -.
DR DisGeNET; 146057; -.
DR GeneCards; TTBK2; -.
DR GeneReviews; TTBK2; -.
DR HGNC; HGNC:19141; TTBK2.
DR HPA; ENSG00000128881; Tissue enhanced (testis).
DR MalaCards; TTBK2; -.
DR MIM; 604432; phenotype.
DR MIM; 611695; gene.
DR neXtProt; NX_Q6IQ55; -.
DR OpenTargets; ENSG00000128881; -.
DR Orphanet; 98767; Spinocerebellar ataxia type 11.
DR PharmGKB; PA134913925; -.
DR VEuPathDB; HostDB:ENSG00000128881; -.
DR eggNOG; KOG1164; Eukaryota.
DR GeneTree; ENSGT00940000160367; -.
DR HOGENOM; CLU_003410_0_0_1; -.
DR InParanoid; Q6IQ55; -.
DR OMA; DPLHQRQ; -.
DR OrthoDB; 75271at2759; -.
DR PhylomeDB; Q6IQ55; -.
DR TreeFam; TF351646; -.
DR BRENDA; 2.7.11.26; 2681.
DR PathwayCommons; Q6IQ55; -.
DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane.
DR SABIO-RK; Q6IQ55; -.
DR SignaLink; Q6IQ55; -.
DR SIGNOR; Q6IQ55; -.
DR BioGRID-ORCS; 146057; 10 hits in 1112 CRISPR screens.
DR ChiTaRS; TTBK2; human.
DR GeneWiki; TTBK2; -.
DR GenomeRNAi; 146057; -.
DR Pharos; Q6IQ55; Tbio.
DR PRO; PR:Q6IQ55; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q6IQ55; protein.
DR Bgee; ENSG00000128881; Expressed in lateral nuclear group of thalamus and 191 other tissues.
DR ExpressionAtlas; Q6IQ55; baseline and differential.
DR Genevisible; Q6IQ55; HS.
DR GO; GO:0005814; C:centriole; IDA:GO_Central.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0035869; C:ciliary transition zone; IDA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019894; F:kinesin binding; IPI:ARUK-UCL.
DR GO; GO:0051010; F:microtubule plus-end binding; TAS:ARUK-UCL.
DR GO; GO:0004672; F:protein kinase activity; IDA:ARUK-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0048156; F:tau protein binding; NAS:ARUK-UCL.
DR GO; GO:0050321; F:tau-protein kinase activity; TAS:ARUK-UCL.
DR GO; GO:0021681; P:cerebellar granular layer development; ISS:ARUK-UCL.
DR GO; GO:0021935; P:cerebellar granule cell precursor tangential migration; ISS:ARUK-UCL.
DR GO; GO:0021549; P:cerebellum development; ISS:ARUK-UCL.
DR GO; GO:0060271; P:cilium assembly; IMP:GO_Central.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IGI:ARUK-UCL.
DR GO; GO:1904527; P:negative regulation of microtubule binding; IDA:ARUK-UCL.
DR GO; GO:0007026; P:negative regulation of microtubule depolymerization; IDA:ARUK-UCL.
DR GO; GO:1902817; P:negative regulation of protein localization to microtubule; IMP:ARUK-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; IGI:ARUK-UCL.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0007224; P:smoothened signaling pathway; ISS:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell projection; Cilium;
KW Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton; Kinase;
KW Neurodegeneration; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase;
KW Spinocerebellar ataxia; Transferase.
FT CHAIN 1..1244
FT /note="Tau-tubulin kinase 2"
FT /id="PRO_0000234342"
FT DOMAIN 21..284
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 674..694
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1052..1088
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1116..1244
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1052..1074
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1116..1133
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1134..1148
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1150..1171
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1184..1212
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1219..1244
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 141
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 27..35
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 50
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 445
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 786
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 1103
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..72
FT /note="MSGGGEQLDILSVGILVKERWKVLRKIGGGGFGEIYDALDMLTRENVALKVE
FT SAQQPKQVLKMEVAVLKKLQ -> MES (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_018272"
FT VAR_SEQ 470..478
FT /note="CLEKMQKDT -> WYKIVYFSF (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_018273"
FT VAR_SEQ 479..1244
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_018274"
FT VAR_SEQ 1233..1244
FT /note="QGKSKPASKLSR -> PREE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_018275"
FT VARIANT 8
FT /note="L -> P (in dbSNP:rs6493068)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:19533200"
FT /id="VAR_041261"
FT VARIANT 120
FT /note="R -> Q (in dbSNP:rs35328266)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041262"
FT VARIANT 313
FT /note="T -> A (in dbSNP:rs56017612)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041263"
FT VARIANT 367
FT /note="K -> I (in dbSNP:rs764753481)"
FT /evidence="ECO:0000269|PubMed:26063658"
FT /id="VAR_076383"
FT VARIANT 440
FT /note="V -> M (in dbSNP:rs56311523)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041264"
FT VARIANT 500
FT /note="R -> P (in dbSNP:rs56039839)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041265"
FT VARIANT 635
FT /note="D -> G (in a lung small cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041266"
FT VARIANT 724
FT /note="G -> E (in dbSNP:rs201524659)"
FT /evidence="ECO:0000269|PubMed:26063658"
FT /id="VAR_076384"
FT VARIANT 842
FT /note="E -> G (found in a patient with SCA11; unknown
FT pathological significance; dbSNP:rs202004988)"
FT /evidence="ECO:0000269|PubMed:19533200"
FT /id="VAR_069052"
FT VARIANT 1062
FT /note="T -> I (in dbSNP:rs55833708)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041267"
FT VARIANT 1084
FT /note="T -> M (in dbSNP:rs34348991)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041268"
FT VARIANT 1097
FT /note="V -> A (in dbSNP:rs55796513)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041269"
FT VARIANT 1110
FT /note="R -> H (found in a patient with SCA11; unknown
FT pathological significance; dbSNP:rs146279300)"
FT /evidence="ECO:0000269|PubMed:19533200"
FT /id="VAR_069053"
FT VARIANT 1122
FT /note="P -> R (in dbSNP:rs56142516)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041270"
FT VARIANT 1241
FT /note="K -> T (in dbSNP:rs36104367)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041271"
FT MUTAGEN 50
FT /note="K->E,A: Leads to inactivation/destabilization of the
FT protein."
FT /evidence="ECO:0000269|PubMed:21548880"
FT MUTAGEN 143
FT /note="K->E,A: Leads to inactivation/destabilization of the
FT protein."
FT /evidence="ECO:0000269|PubMed:21548880"
FT MUTAGEN 163
FT /note="D->A: Abolishes serine/threonine-protein kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:21548880"
FT MUTAGEN 181
FT /note="R->E,A: Impaired serine/threonine-protein kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:21548880"
FT MUTAGEN 184
FT /note="A->E,G: Impaired serine/threonine-protein kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:21548880"
FT CONFLICT 309
FT /note="T -> I (in Ref. 1; BAD18523)"
FT /evidence="ECO:0000305"
FT CONFLICT 456
FT /note="T -> A (in Ref. 1; BAD18523)"
FT /evidence="ECO:0000305"
FT CONFLICT 557
FT /note="K -> N (in Ref. 1; BAD18523)"
FT /evidence="ECO:0000305"
FT TURN 18..20
FT /evidence="ECO:0007829|PDB:6VRF"
FT STRAND 21..28
FT /evidence="ECO:0007829|PDB:6VRF"
FT HELIX 30..32
FT /evidence="ECO:0007829|PDB:6U0K"
FT STRAND 34..40
FT /evidence="ECO:0007829|PDB:6VRF"
FT TURN 41..44
FT /evidence="ECO:0007829|PDB:6VRF"
FT STRAND 45..53
FT /evidence="ECO:0007829|PDB:6VRF"
FT HELIX 61..70
FT /evidence="ECO:0007829|PDB:6VRF"
FT TURN 71..73
FT /evidence="ECO:0007829|PDB:6VRF"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:6VRF"
FT STRAND 87..95
FT /evidence="ECO:0007829|PDB:6VRF"
FT HELIX 101..106
FT /evidence="ECO:0007829|PDB:6VRF"
FT HELIX 115..134
FT /evidence="ECO:0007829|PDB:6VRF"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:6VRF"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:6VRF"
FT TURN 153..157
FT /evidence="ECO:0007829|PDB:6VRF"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:6VRF"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:6VRF"
FT HELIX 190..192
FT /evidence="ECO:0007829|PDB:6VRF"
FT HELIX 195..198
FT /evidence="ECO:0007829|PDB:6VRF"
FT HELIX 205..221
FT /evidence="ECO:0007829|PDB:6VRF"
FT TURN 225..228
FT /evidence="ECO:0007829|PDB:6VRF"
FT HELIX 232..241
FT /evidence="ECO:0007829|PDB:6VRF"
FT HELIX 244..250
FT /evidence="ECO:0007829|PDB:6VRF"
FT HELIX 255..264
FT /evidence="ECO:0007829|PDB:6VRF"
FT HELIX 273..286
FT /evidence="ECO:0007829|PDB:6VRF"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:6U0K"
SQ SEQUENCE 1244 AA; 137412 MW; EAB8FC28370966DE CRC64;
MSGGGEQLDI LSVGILVKER WKVLRKIGGG GFGEIYDALD MLTRENVALK VESAQQPKQV
LKMEVAVLKK LQGKDHVCRF IGCGRNDRFN YVVMQLQGRN LADLRRSQSR GTFTISTTLR
LGRQILESIE SIHSVGFLHR DIKPSNFAMG RFPSTCRKCY MLDFGLARQF TNSCGDVRPP
RAVAGFRGTV RYASINAHRN REMGRHDDLW SLFYMLVEFV VGQLPWRKIK DKEQVGSIKE
RYDHRLMLKH LPPEFSIFLD HISSLDYFTK PDYQLLTSVF DNSIKTFGVI ESDPFDWEKT
GNDGSLTTTT TSTTPQLHTR LTPAAIGIAN ATPIPGDLLR ENTDEVFPDE QLSDGENGIP
VGVSPDKLPG SLGHPRPQEK DVWEEMDANK NKIKLGICKA ATEEENSHGQ ANGLLNAPSL
GSPIRVRSEI TQPDRDIPLV RKLRSIHSFE LEKRLTLEPK PDTDKFLETC LEKMQKDTSA
GKESILPALL HKPCVPAVSR TDHIWHYDEE YLPDASKPAS ANTPEQADGG GSNGFIAVNL
SSCKQEIDSK EWVIVDKEQD LQDFRTNEAV GHKTTGSPSD EEPEVLQVLE ASPQDEKLQL
GPWAENDHLK KETSGVVLAL SAEGPPTAAS EQYTDRLELQ PGAASQFIAA TPTSLMEAQA
EGPLTAITIP RPSVASTQST SGSFHCGQQP EKKDLQPMEP TVELYSPREN FSGLVVTEGE
PPSGGSRTDL GLQIDHIGHD MLPNIRESNK SQDLGPKELP DHNRLVVREF ENLPGETEEK
SILLESDNED EKLSRGQHCI EISSLPGDLV IVEKDHSATT EPLDVTKTQT FSVVPNQDKN
NEIMKLLTVG TSEISSRDID PHVEGQIGQV AEMQKNKISK DDDIMSEDLP GHQGDLSTFL
HQEGKREKIT PRNGELFHCV SENEHGAPTR KDMVRSSFVT RHSRIPVLAQ EIDSTLESSS
PVSAKEKLLQ KKAYQPDLVK LLVEKRQFKS FLGDLSSASD KLLEEKLATV PAPFCEEEVL
TPFSRLTVDS HLSRSAEDSF LSPIISQSRK SKIPRPVSWV NTDQVNSSTS SQFFPRPPPG
KPPTRPGVEA RLRRYKVLGS SNSDSDLFSR LAQILQNGSQ KPRSTTQCKS PGSPHNPKTP
PKSPVVPRRS PSASPRSSSL PRTSSSSPSR AGRPHHDQRS SSPHLGRSKS PPSHSGSSSS
RRSCQQEHCK PSKNGLKGSG SLHHHSASTK TPQGKSKPAS KLSR
