Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q5TCY1 (TTBK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tau-tubulin kinase 1

EC=2.7.11.1
Alternative name(s):
Brain-derived tau kinase
Gene names
Name:TTBK1
Synonyms:BDTK, KIAA1855
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1321 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU. Ref.1

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.1

Cofactor

Divalent cations. Magnesium or, to a lesser extent, manganese, but not calcium or zinc. Ref.1

Subcellular location

Cytoplasm Ref.1.

Tissue specificity

Expressed in the brain, particularly in cortical and hippocampal neurons. Weakly expressed in spinal cord and testis. No expression in adipose tissue, bladder, cervix, colon, esophagus, heart, kidney, liver, lung, ovary, placenta, prostate, skeletal muscle, small intestine, spleen, testis, thymus, thyroid or trachea. Ref.1

Sequence similarities

Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family.

Contains 1 protein kinase domain.

Caution

It is uncertain whether Met-1 or Met-14 is the initiator.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainCoiled coil
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processsubstantia nigra development

Inferred from expression pattern PubMed 22926577. Source: UniProt

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5TCY1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q5TCY1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-51: Missing.
     592-672: TVRPRGRSMQ...VFSVAPPFEV → FPLTPALGTP...RFPHSAQPLG
     673-1321: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 13211321Tau-tubulin kinase 1
PRO_0000234341

Regions

Domain34 – 297264Protein kinase
Nucleotide binding40 – 489ATP By similarity
Coiled coil685 – 78197 Potential
Compositional bias733 – 77139Glu-rich
Compositional bias772 – 7776Poly-Ala
Compositional bias1110 – 11145Poly-Ser
Compositional bias1197 – 128993Pro-rich

Sites

Active site1541Proton acceptor By similarity
Binding site631ATP By similarity

Natural variations

Alternative sequence1 – 5151Missing in isoform 2.
VSP_026497
Alternative sequence592 – 67281TVRPR…PPFEV → FPLTPALGTPPSTERVGPHR PTETVGGGQTLGALPPAVQP PATTGVLRVLLLHAGDGALP SPRRRRLLGLLRFPHSAQPL G in isoform 2.
VSP_026498
Alternative sequence673 – 1321649Missing in isoform 2.
VSP_026499
Natural variant6131P → L. Ref.6
Corresponds to variant rs34993661 [ dbSNP | Ensembl ].
VAR_041252
Natural variant6231G → A. Ref.6
Corresponds to variant rs3800294 [ dbSNP | Ensembl ].
VAR_041253
Natural variant6491P → R. Ref.6
Corresponds to variant rs35175743 [ dbSNP | Ensembl ].
VAR_041254
Natural variant7411D → E. Ref.6
Corresponds to variant rs56377340 [ dbSNP | Ensembl ].
VAR_041255
Natural variant7441E → D. Ref.6
Corresponds to variant rs3800295 [ dbSNP | Ensembl ].
VAR_041256
Natural variant8061S → F in a lung large cell carcinoma sample; somatic mutation. Ref.6
VAR_041257
Natural variant8551P → S in a metastatic melanoma sample; somatic mutation. Ref.6
VAR_041258
Natural variant11451K → R. Ref.6
Corresponds to variant rs3800297 [ dbSNP | Ensembl ].
VAR_041259
Natural variant11841L → S. Ref.6
Corresponds to variant rs3800298 [ dbSNP | Ensembl ].
VAR_041260

Experimental info

Sequence conflict371L → V in BAE78660. Ref.1
Sequence conflict4021E → G in BAD18405. Ref.2
Sequence conflict11901S → SS in AAH36764. Ref.5

Secondary structure

................................................... 1321
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 16, 2006. Version 2.
Checksum: 844FAA1EB7A45DE2

FASTA1,321142,737
        10         20         30         40         50         60 
MQCLAAALKD ETNMSGGGEQ ADILPANYVV KDRWKVLKKI GGGGFGEIYE AMDLLTRENV 

        70         80         90        100        110        120 
ALKVESAQQP KQVLKMEVAV LKKLQGKDHV CRFIGCGRNE KFNYVVMQLQ GRNLADLRRS 

       130        140        150        160        170        180 
QPRGTFTLST TLRLGKQILE SIEAIHSVGF LHRDIKPSNF AMGRLPSTYR KCYMLDFGLA 

       190        200        210        220        230        240 
RQYTNTTGDV RPPRNVAGFR GTVRYASVNA HKNREMGRHD DLWSLFYMLV EFAVGQLPWR 

       250        260        270        280        290        300 
KIKDKEQVGM IKEKYEHRML LKHMPSEFHL FLDHIASLDY FTKPDYQLIM SVFENSMKER 

       310        320        330        340        350        360 
GIAENEAFDW EKAGTDALLS TSTSTPPQQN TRQTAAMFGV VNVTPVPGDL LRENTEDVLQ 

       370        380        390        400        410        420 
GEHLSDQENA PPILPGRPSE GLGPSPHLVP HPGGPEAEVW EETDVNRNKL RINIGKSPCV 

       430        440        450        460        470        480 
EEEQSRGMGV PSSPVRAPPD SPTTPVRSLR YRRVNSPESE RLSTADGRVE LPERRSRMDL 

       490        500        510        520        530        540 
PGSPSRQACS SQPAQMLSVD TGHADRQASG RMDVSASVEQ EALSNAFRSV PLAEEEDFDS 

       550        560        570        580        590        600 
KEWVIIDKET ELKDFPPGAE PSTSGTTDEE PEELRPLPEE GEERRRLGAE PTVRPRGRSM 

       610        620        630        640        650        660 
QALAEEDLQH LPPQPLPPQL SQGDGRSETS QPPTPGSPSH SPLHSGPRPR RRESDPTGPQ 

       670        680        690        700        710        720 
RQVFSVAPPF EVNGLPRAVP LSLPYQDFKR DLSDYRERAR LLNRVRRVGF SHMLLTTPQV 

       730        740        750        760        770        780 
PLAPVQPQAN GKEEEEEEEE DEEEEEEDEE EEEEEEEEEE EEEEEEEEEE EAAAAVALGE 

       790        800        810        820        830        840 
VLGPRSGSSS EGSERSTDRS QEGAPSTLLA DDQKESRGRA SMADGDLEPE EGSKTLVLVS 

       850        860        870        880        890        900 
PGDMKKSPVT AELAPDPDLG TLAALTPQHE RPQPTGSQLD VSEPGTLSSV LKSEPKPPGP 

       910        920        930        940        950        960 
GAGLGAGTVT TGVGGVAVTS SPFTKVERTF VHIAEKTHLN VMSSGGQALR SEEFSAGGEL 

       970        980        990       1000       1010       1020 
GLELASDGGA VEEGARAPLE NGLALSGLNG AEIEGSALSG APRETPSEMA TNSLPNGPAL 

      1030       1040       1050       1060       1070       1080 
ADGPAPVSPL EPSPEKVATI SPRRHAMPGS RPRSRIPVLL SEEDTGSEPS GSLSAKERWS 

      1090       1100       1110       1120       1130       1140 
KRARPQQDLA RLVMEKRQGR LLLRLASGAS SSSSEEQRRA SETLSGTGSE EDTPASEPAA 

      1150       1160       1170       1180       1190       1200 
ALPRKSGRAA ATRSRIPRPI GLRMPMPVAA QQPASRSHGA APALDTAITS RLQLQTPPGS 

      1210       1220       1230       1240       1250       1260 
ATAADLRPKQ PPGRGLGPGR AQAGARPPAP RSPRLPASTS AARNASASPR SQSLSRRESP 

      1270       1280       1290       1300       1310       1320 
SPSHQARPGV PPPRGVPPAR AQPDGTPSPG GSKKGPRGKL QAQRATTKGR AGGAEGRAGA 


R 

« Hide

Isoform 2 [UniParc].

Checksum: 4A99A34F76D7DD59
Show »

FASTA62169,084

References

« Hide 'large scale' references
[1]"Tau-tubulin kinase 1 (TTBK1), a neuron-specific tau kinase candidate, is involved in tau phosphorylation and aggregation."
Sato S., Cerny R.L., Buescher J.L., Ikezu T.
J. Neurochem. 98:1573-1584(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Brain.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Testis.
[3]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.
DNA Res. 8:85-95(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 52-1321 (ISOFORM 1).
Tissue: Brain.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 979-1321 (ISOFORM 1).
Tissue: Brain.
[6]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-613; ALA-623; ARG-649; GLU-741; ASP-744; PHE-806; SER-855; ARG-1145 AND SER-1184.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB218664 mRNA. Translation: BAE78660.1.
AK131217 mRNA. Translation: BAD18405.1.
AL133375 Genomic DNA. Translation: CAI20206.2.
AL133375 Genomic DNA. Translation: CAM28234.1.
AB058758 mRNA. Translation: BAB47484.1.
BC036764 mRNA. Translation: AAH36764.1.
CCDSCCDS34455.1. [Q5TCY1-1]
RefSeqNP_115927.1. NM_032538.1. [Q5TCY1-1]
UniGeneHs.485436.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4BTJX-ray2.16A/B1-313[»]
4BTKX-ray2.00A1-313[»]
4BTMX-ray2.54A/B1-313[»]
4NFMX-ray2.12A14-343[»]
4NFNX-ray1.42A14-320[»]
ProteinModelPortalQ5TCY1.
SMRQ5TCY1. Positions 22-314.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124159. 4 interactions.
STRING9606.ENSP00000259750.

Chemistry

ChEMBLCHEMBL1926492.

PTM databases

PhosphoSiteQ5TCY1.

Polymorphism databases

DMDM97203020.

Proteomic databases

PaxDbQ5TCY1.
PRIDEQ5TCY1.

Protocols and materials databases

DNASU84630.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000259750; ENSP00000259750; ENSG00000146216. [Q5TCY1-1]
GeneID84630.
KEGGhsa:84630.
UCSCuc003ouq.1. human. [Q5TCY1-1]

Organism-specific databases

CTD84630.
GeneCardsGC06P043259.
H-InvDBHIX0005900.
HGNCHGNC:19140. TTBK1.
HPAHPA031736.
neXtProtNX_Q5TCY1.
PharmGKBPA134866142.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000154701.
HOVERGENHBG094095.
InParanoidQ5TCY1.
KOK08815.
OMAFEMNGLP.
OrthoDBEOG7RFTGM.
PhylomeDBQ5TCY1.
TreeFamTF351646.

Enzyme and pathway databases

SignaLinkQ5TCY1.

Gene expression databases

BgeeQ5TCY1.
CleanExHS_TTBK1.
GenevestigatorQ5TCY1.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi84630.
NextBio74547.
PROQ5TCY1.

Entry information

Entry nameTTBK1_HUMAN
AccessionPrimary (citable) accession number: Q5TCY1
Secondary accession number(s): A2A2U5 expand/collapse secondary AC list , Q2L6C6, Q6ZNH0, Q8N444, Q96JH2
Entry history
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 16, 2006
Last modified: July 9, 2014
This is version 92 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM