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Protein

Tau-tubulin kinase 1

Gene

TTBK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

Catalytic activityi

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

Cofactori

Mg2+1 Publication, Mn2+1 PublicationNote: Divalent metal cations. Mg2+ or, to a lesser extent, Mn2+, but not Ca2+ or Zn2+.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei63ATPPROSITE-ProRule annotation1
Active sitei154Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi40 – 48ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS07332-MONOMER.
SignaLinkiQ5TCY1.
SIGNORiQ5TCY1.

Names & Taxonomyi

Protein namesi
Recommended name:
Tau-tubulin kinase 1 (EC:2.7.11.1)
Alternative name(s):
Brain-derived tau kinase
Gene namesi
Name:TTBK1
Synonyms:BDTK, KIAA1855
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:19140. TTBK1.

Subcellular locationi

  • Cytoplasm 1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi84630.
OpenTargetsiENSG00000146216.
PharmGKBiPA134866142.

Chemistry databases

ChEMBLiCHEMBL1926492.

Polymorphism and mutation databases

BioMutaiTTBK1.
DMDMi97203020.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002343411 – 1321Tau-tubulin kinase 1Add BLAST1321

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei441PhosphoserineBy similarity1
Modified residuei540PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ5TCY1.
PaxDbiQ5TCY1.
PeptideAtlasiQ5TCY1.
PRIDEiQ5TCY1.

PTM databases

iPTMnetiQ5TCY1.
PhosphoSitePlusiQ5TCY1.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

BgeeiENSG00000146216.
CleanExiHS_TTBK1.
ExpressionAtlasiQ5TCY1. baseline and differential.
GenevisibleiQ5TCY1. HS.

Organism-specific databases

HPAiHPA031736.

Interactioni

Protein-protein interaction databases

BioGridi124159. 5 interactors.
STRINGi9606.ENSP00000259750.

Structurei

Secondary structure

11321
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni31 – 33Combined sources3
Beta strandi34 – 42Combined sources9
Beta strandi43 – 45Combined sources3
Beta strandi47 – 53Combined sources7
Turni54 – 56Combined sources3
Beta strandi58 – 66Combined sources9
Helixi74 – 83Combined sources10
Turni84 – 86Combined sources3
Beta strandi93 – 98Combined sources6
Beta strandi100 – 108Combined sources9
Helixi114 – 119Combined sources6
Helixi128 – 147Combined sources20
Helixi157 – 159Combined sources3
Beta strandi160 – 162Combined sources3
Turni166 – 170Combined sources5
Beta strandi172 – 174Combined sources3
Beta strandi188 – 190Combined sources3
Helixi203 – 205Combined sources3
Helixi208 – 211Combined sources4
Helixi218 – 234Combined sources17
Turni238 – 241Combined sources4
Helixi245 – 254Combined sources10
Helixi257 – 261Combined sources5
Beta strandi262 – 264Combined sources3
Helixi268 – 277Combined sources10
Beta strandi280 – 282Combined sources3
Helixi286 – 299Combined sources14
Turni309 – 311Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliQ5TCY1.
SMRiQ5TCY1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 297Protein kinasePROSITE-ProRule annotationAdd BLAST264

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili685 – 781Sequence analysisAdd BLAST97

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi733 – 771Glu-richAdd BLAST39
Compositional biasi772 – 777Poly-Ala6
Compositional biasi1110 – 1114Poly-Ser5
Compositional biasi1197 – 1289Pro-richAdd BLAST93

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG1164. Eukaryota.
ENOG410XPGP. LUCA.
GeneTreeiENSGT00760000119040.
HOGENOMiHOG000154701.
HOVERGENiHBG094095.
InParanoidiQ5TCY1.
KOiK08815.
OMAiATTKGRA.
OrthoDBiEOG091G03H8.
PhylomeDBiQ5TCY1.
TreeFamiTF351646.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5TCY1-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MQCLAAALKD ETNMSGGGEQ ADILPANYVV KDRWKVLKKI GGGGFGEIYE
60 70 80 90 100
AMDLLTRENV ALKVESAQQP KQVLKMEVAV LKKLQGKDHV CRFIGCGRNE
110 120 130 140 150
KFNYVVMQLQ GRNLADLRRS QPRGTFTLST TLRLGKQILE SIEAIHSVGF
160 170 180 190 200
LHRDIKPSNF AMGRLPSTYR KCYMLDFGLA RQYTNTTGDV RPPRNVAGFR
210 220 230 240 250
GTVRYASVNA HKNREMGRHD DLWSLFYMLV EFAVGQLPWR KIKDKEQVGM
260 270 280 290 300
IKEKYEHRML LKHMPSEFHL FLDHIASLDY FTKPDYQLIM SVFENSMKER
310 320 330 340 350
GIAENEAFDW EKAGTDALLS TSTSTPPQQN TRQTAAMFGV VNVTPVPGDL
360 370 380 390 400
LRENTEDVLQ GEHLSDQENA PPILPGRPSE GLGPSPHLVP HPGGPEAEVW
410 420 430 440 450
EETDVNRNKL RINIGKSPCV EEEQSRGMGV PSSPVRAPPD SPTTPVRSLR
460 470 480 490 500
YRRVNSPESE RLSTADGRVE LPERRSRMDL PGSPSRQACS SQPAQMLSVD
510 520 530 540 550
TGHADRQASG RMDVSASVEQ EALSNAFRSV PLAEEEDFDS KEWVIIDKET
560 570 580 590 600
ELKDFPPGAE PSTSGTTDEE PEELRPLPEE GEERRRLGAE PTVRPRGRSM
610 620 630 640 650
QALAEEDLQH LPPQPLPPQL SQGDGRSETS QPPTPGSPSH SPLHSGPRPR
660 670 680 690 700
RRESDPTGPQ RQVFSVAPPF EVNGLPRAVP LSLPYQDFKR DLSDYRERAR
710 720 730 740 750
LLNRVRRVGF SHMLLTTPQV PLAPVQPQAN GKEEEEEEEE DEEEEEEDEE
760 770 780 790 800
EEEEEEEEEE EEEEEEEEEE EAAAAVALGE VLGPRSGSSS EGSERSTDRS
810 820 830 840 850
QEGAPSTLLA DDQKESRGRA SMADGDLEPE EGSKTLVLVS PGDMKKSPVT
860 870 880 890 900
AELAPDPDLG TLAALTPQHE RPQPTGSQLD VSEPGTLSSV LKSEPKPPGP
910 920 930 940 950
GAGLGAGTVT TGVGGVAVTS SPFTKVERTF VHIAEKTHLN VMSSGGQALR
960 970 980 990 1000
SEEFSAGGEL GLELASDGGA VEEGARAPLE NGLALSGLNG AEIEGSALSG
1010 1020 1030 1040 1050
APRETPSEMA TNSLPNGPAL ADGPAPVSPL EPSPEKVATI SPRRHAMPGS
1060 1070 1080 1090 1100
RPRSRIPVLL SEEDTGSEPS GSLSAKERWS KRARPQQDLA RLVMEKRQGR
1110 1120 1130 1140 1150
LLLRLASGAS SSSSEEQRRA SETLSGTGSE EDTPASEPAA ALPRKSGRAA
1160 1170 1180 1190 1200
ATRSRIPRPI GLRMPMPVAA QQPASRSHGA APALDTAITS RLQLQTPPGS
1210 1220 1230 1240 1250
ATAADLRPKQ PPGRGLGPGR AQAGARPPAP RSPRLPASTS AARNASASPR
1260 1270 1280 1290 1300
SQSLSRRESP SPSHQARPGV PPPRGVPPAR AQPDGTPSPG GSKKGPRGKL
1310 1320
QAQRATTKGR AGGAEGRAGA R
Length:1,321
Mass (Da):142,737
Last modified:May 16, 2006 - v2
Checksum:i844FAA1EB7A45DE2
GO
Isoform 2 (identifier: Q5TCY1-2) [UniParc]FASTAAdd to basket

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.
Show »
Length:621
Mass (Da):69,084
Checksum:i4A99A34F76D7DD59
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti37L → V in BAE78660 (PubMed:16923168).Curated1
Sequence conflicti402E → G in BAD18405 (PubMed:14702039).Curated1
Sequence conflicti1190S → SS in AAH36764 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041252613P → L.1 PublicationCorresponds to variant rs34993661dbSNPEnsembl.1
Natural variantiVAR_041253623G → A.1 PublicationCorresponds to variant rs3800294dbSNPEnsembl.1
Natural variantiVAR_041254649P → R.1 PublicationCorresponds to variant rs35175743dbSNPEnsembl.1
Natural variantiVAR_041255741D → E.1 PublicationCorresponds to variant rs56377340dbSNPEnsembl.1
Natural variantiVAR_041256744E → D.1 PublicationCorresponds to variant rs3800295dbSNPEnsembl.1
Natural variantiVAR_041257806S → F in a lung large cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041258855P → S in a metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant rs267601046dbSNPEnsembl.1
Natural variantiVAR_0412591145K → R.1 PublicationCorresponds to variant rs3800297dbSNPEnsembl.1
Natural variantiVAR_0412601184L → S.1 PublicationCorresponds to variant rs3800298dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0264971 – 51Missing in isoform 2. 1 PublicationAdd BLAST51
Alternative sequenceiVSP_026498592 – 672TVRPR…PPFEV → FPLTPALGTPPSTERVGPHR PTETVGGGQTLGALPPAVQP PATTGVLRVLLLHAGDGALP SPRRRRLLGLLRFPHSAQPL G in isoform 2. 1 PublicationAdd BLAST81
Alternative sequenceiVSP_026499673 – 1321Missing in isoform 2. 1 PublicationAdd BLAST649

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS34455.1. [Q5TCY1-1]
RefSeqiNP_115927.1. NM_032538.2. [Q5TCY1-1]
UniGeneiHs.485436.

Genome annotation databases

EnsembliENST00000259750; ENSP00000259750; ENSG00000146216. [Q5TCY1-1]
GeneIDi84630.
KEGGihsa:84630.
UCSCiuc003ouq.2. human. [Q5TCY1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS34455.1. [Q5TCY1-1]
RefSeqiNP_115927.1. NM_032538.2. [Q5TCY1-1]
UniGeneiHs.485436.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliQ5TCY1.
SMRiQ5TCY1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124159. 5 interactors.
STRINGi9606.ENSP00000259750.

Chemistry databases

ChEMBLiCHEMBL1926492.

PTM databases

iPTMnetiQ5TCY1.
PhosphoSitePlusiQ5TCY1.

Polymorphism and mutation databases

BioMutaiTTBK1.
DMDMi97203020.

Proteomic databases

EPDiQ5TCY1.
PaxDbiQ5TCY1.
PeptideAtlasiQ5TCY1.
PRIDEiQ5TCY1.

Protocols and materials databases

DNASUi84630.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000259750; ENSP00000259750; ENSG00000146216. [Q5TCY1-1]
GeneIDi84630.
KEGGihsa:84630.
UCSCiuc003ouq.2. human. [Q5TCY1-1]

Organism-specific databases

CTDi84630.
DisGeNETi84630.
GeneCardsiTTBK1.
H-InvDBHIX0005900.
HGNCiHGNC:19140. TTBK1.
HPAiHPA031736.
neXtProtiNX_Q5TCY1.
OpenTargetsiENSG00000146216.
PharmGKBiPA134866142.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1164. Eukaryota.
ENOG410XPGP. LUCA.
GeneTreeiENSGT00760000119040.
HOGENOMiHOG000154701.
HOVERGENiHBG094095.
InParanoidiQ5TCY1.
KOiK08815.
OMAiATTKGRA.
OrthoDBiEOG091G03H8.
PhylomeDBiQ5TCY1.
TreeFamiTF351646.

Enzyme and pathway databases

BioCyciZFISH:HS07332-MONOMER.
SignaLinkiQ5TCY1.
SIGNORiQ5TCY1.

Miscellaneous databases

ChiTaRSiTTBK1. human.
GenomeRNAii84630.
PROiQ5TCY1.

Gene expression databases

BgeeiENSG00000146216.
CleanExiHS_TTBK1.
ExpressionAtlasiQ5TCY1. baseline and differential.
GenevisibleiQ5TCY1. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTTBK1_HUMAN
AccessioniPrimary (citable) accession number: Q5TCY1
Secondary accession number(s): A2A2U5
, Q2L6C6, Q6ZNH0, Q8N444, Q96JH2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 16, 2006
Last modified: November 2, 2016
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Caution

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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.