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Protein

Tau-tubulin kinase 2

Gene

TTBK2

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

Functioni

Serine/threonine kinase that acts as a key regulator of ciliogenesis: controls the initiation of ciliogenesis by binding to the distal end of the basal body and promoting the removal of CCP110, which caps the mother centriole, leading to the recruitment of IFT proteins, which build the ciliary axoneme. Has some substrate preference for proteins that are already phosphorylated on a Tyr residue at the +2 position relative to the phosphorylation site. Able to phosphorylate tau on serines in vitro.2 Publications

Catalytic activityi

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

Kineticsi

  1. KM=18 µM for RRKDLHDDEEDEAMSIYpA peptide1 Publication
  2. KM=141 µM for RRKDLHDDEEDEAMSIYA peptide1 Publication
  1. Vmax=76 µmol/min/mg enzyme with RRKDLHDDEEDEAMSIYpA peptide as substrate1 Publication
  2. Vmax=66 µmol/min/mg enzyme with RRKDLHDDEEDEAMSIYA peptide as substrate1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei50ATPPROSITE-ProRule annotation1
Active sitei141Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi27 – 35ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cilium biogenesis/degradation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS13280-MONOMER.
ReactomeiR-HSA-5620912. Anchoring of the basal body to the plasma membrane.
SignaLinkiQ6IQ55.

Names & Taxonomyi

Protein namesi
Recommended name:
Tau-tubulin kinase 2 (EC:2.7.11.1)
Gene namesi
Name:TTBK2
Synonyms:KIAA0847
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:19141. TTBK2.

Subcellular locationi

GO - Cellular componenti

  • centriole Source: GO_Central
  • ciliary basal body Source: UniProtKB
  • ciliary transition zone Source: UniProtKB
  • cytosol Source: UniProtKB
  • extracellular space Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cilium, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Involvement in diseasei

Spinocerebellar ataxia 11 (SCA11)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSpinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA11 is an autosomal dominant cerebellar ataxia (ADCA). It is a relatively benign, late-onset, slowly progressive neurologic disorder.
See also OMIM:604432
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069052842E → G Found in a patient with SCA11; unknown pathological significance. 1 PublicationCorresponds to variant rs202004988dbSNPEnsembl.1
Natural variantiVAR_0690531110R → H Found in a patient with SCA11; unknown pathological significance. 1 PublicationCorresponds to variant rs146279300dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi50K → E or A: Leads to inactivation/destabilization of the protein. 1 Publication1
Mutagenesisi143K → E or A: Leads to inactivation/destabilization of the protein. 1 Publication1
Mutagenesisi163D → A: Abolishes serine/threonine-protein kinase activity. 1 Publication1
Mutagenesisi181R → E or A: Impaired serine/threonine-protein kinase activity. 1 Publication1
Mutagenesisi184A → E or G: Impaired serine/threonine-protein kinase activity. 1 Publication1

Keywords - Diseasei

Neurodegeneration, Spinocerebellar ataxia

Organism-specific databases

DisGeNETi146057.
MalaCardsiTTBK2.
MIMi604432. phenotype.
OpenTargetsiENSG00000128881.
Orphaneti98767. Spinocerebellar ataxia type 11.
PharmGKBiPA134913925.

Chemistry databases

ChEMBLiCHEMBL3337327.

Polymorphism and mutation databases

BioMutaiTTBK2.
DMDMi116242833.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002343421 – 1244Tau-tubulin kinase 2Add BLAST1244

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei445PhosphoserineCombined sources1
Modified residuei786PhosphoserineCombined sources1
Modified residuei1103PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ6IQ55.
MaxQBiQ6IQ55.
PaxDbiQ6IQ55.
PeptideAtlasiQ6IQ55.
PRIDEiQ6IQ55.

PTM databases

iPTMnetiQ6IQ55.
PhosphoSitePlusiQ6IQ55.

Expressioni

Gene expression databases

BgeeiENSG00000128881.
CleanExiHS_TTBK2.
ExpressionAtlasiQ6IQ55. baseline and differential.
GenevisibleiQ6IQ55. HS.

Organism-specific databases

HPAiHPA018113.

Interactioni

Subunit structurei

Binary interactionsi

WithEntry#Exp.IntActNotes
CEP164Q9UPV04EBI-1050303,EBI-3937015
KLHL12Q53G595EBI-1050303,EBI-740929

Protein-protein interaction databases

BioGridi126962. 9 interactors.
IntActiQ6IQ55. 4 interactors.
STRINGi9606.ENSP00000267890.

Structurei

3D structure databases

ProteinModelPortaliQ6IQ55.
SMRiQ6IQ55.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini21 – 284Protein kinasePROSITE-ProRule annotationAdd BLAST264

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi307 – 314Poly-Thr8
Compositional biasi1150 – 1203Ser-richAdd BLAST54

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1164. Eukaryota.
ENOG410XPGP. LUCA.
GeneTreeiENSGT00760000119040.
HOGENOMiHOG000232043.
HOVERGENiHBG061812.
InParanoidiQ6IQ55.
KOiK08815.
PhylomeDBiQ6IQ55.
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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6IQ55-1) [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
MSGGGEQLDI LSVGILVKER WKVLRKIGGG GFGEIYDALD MLTRENVALK
60 70 80 90 100
VESAQQPKQV LKMEVAVLKK LQGKDHVCRF IGCGRNDRFN YVVMQLQGRN
110 120 130 140 150
LADLRRSQSR GTFTISTTLR LGRQILESIE SIHSVGFLHR DIKPSNFAMG
160 170 180 190 200
RFPSTCRKCY MLDFGLARQF TNSCGDVRPP RAVAGFRGTV RYASINAHRN
210 220 230 240 250
REMGRHDDLW SLFYMLVEFV VGQLPWRKIK DKEQVGSIKE RYDHRLMLKH
260 270 280 290 300
LPPEFSIFLD HISSLDYFTK PDYQLLTSVF DNSIKTFGVI ESDPFDWEKT
310 320 330 340 350
GNDGSLTTTT TSTTPQLHTR LTPAAIGIAN ATPIPGDLLR ENTDEVFPDE
360 370 380 390 400
QLSDGENGIP VGVSPDKLPG SLGHPRPQEK DVWEEMDANK NKIKLGICKA
410 420 430 440 450
ATEEENSHGQ ANGLLNAPSL GSPIRVRSEI TQPDRDIPLV RKLRSIHSFE
460 470 480 490 500
LEKRLTLEPK PDTDKFLETC LEKMQKDTSA GKESILPALL HKPCVPAVSR
510 520 530 540 550
TDHIWHYDEE YLPDASKPAS ANTPEQADGG GSNGFIAVNL SSCKQEIDSK
560 570 580 590 600
EWVIVDKEQD LQDFRTNEAV GHKTTGSPSD EEPEVLQVLE ASPQDEKLQL
610 620 630 640 650
GPWAENDHLK KETSGVVLAL SAEGPPTAAS EQYTDRLELQ PGAASQFIAA
660 670 680 690 700
TPTSLMEAQA EGPLTAITIP RPSVASTQST SGSFHCGQQP EKKDLQPMEP
710 720 730 740 750
TVELYSPREN FSGLVVTEGE PPSGGSRTDL GLQIDHIGHD MLPNIRESNK
760 770 780 790 800
SQDLGPKELP DHNRLVVREF ENLPGETEEK SILLESDNED EKLSRGQHCI
810 820 830 840 850
EISSLPGDLV IVEKDHSATT EPLDVTKTQT FSVVPNQDKN NEIMKLLTVG
860 870 880 890 900
TSEISSRDID PHVEGQIGQV AEMQKNKISK DDDIMSEDLP GHQGDLSTFL
910 920 930 940 950
HQEGKREKIT PRNGELFHCV SENEHGAPTR KDMVRSSFVT RHSRIPVLAQ
960 970 980 990 1000
EIDSTLESSS PVSAKEKLLQ KKAYQPDLVK LLVEKRQFKS FLGDLSSASD
1010 1020 1030 1040 1050
KLLEEKLATV PAPFCEEEVL TPFSRLTVDS HLSRSAEDSF LSPIISQSRK
1060 1070 1080 1090 1100
SKIPRPVSWV NTDQVNSSTS SQFFPRPPPG KPPTRPGVEA RLRRYKVLGS
1110 1120 1130 1140 1150
SNSDSDLFSR LAQILQNGSQ KPRSTTQCKS PGSPHNPKTP PKSPVVPRRS
1160 1170 1180 1190 1200
PSASPRSSSL PRTSSSSPSR AGRPHHDQRS SSPHLGRSKS PPSHSGSSSS
1210 1220 1230 1240
RRSCQQEHCK PSKNGLKGSG SLHHHSASTK TPQGKSKPAS KLSR
Length:1,244
Mass (Da):137,412
Last modified:October 17, 2006 - v2
Checksum:iEAB8FC28370966DE
GO
Isoform 2 (identifier: Q6IQ55-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-72: MSGGGEQLDILSVGILVKERWKVLRKIGGGGFGEIYDALDMLTRENVALKVESAQQPKQVLKMEVAVLKKLQ → MES
     1233-1244: QGKSKPASKLSR → PREE

Note: No experimental confirmation available.
Show »
Length:1,167
Mass (Da):129,110
Checksum:i5517B88C9E5E86E9
GO
Isoform 3 (identifier: Q6IQ55-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     470-478: CLEKMQKDT → WYKIVYFSF
     479-1244: Missing.

Note: No experimental confirmation available.
Show »
Length:478
Mass (Da):54,037
Checksum:i2F3AF5039B6F021A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti309T → I in BAD18523 (PubMed:14702039).Curated1
Sequence conflicti456T → A in BAD18523 (PubMed:14702039).Curated1
Sequence conflicti557K → N in BAD18523 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0412618L → P.3 PublicationsCorresponds to variant rs6493068dbSNPEnsembl.1
Natural variantiVAR_041262120R → Q.1 PublicationCorresponds to variant rs35328266dbSNPEnsembl.1
Natural variantiVAR_041263313T → A.1 PublicationCorresponds to variant rs56017612dbSNPEnsembl.1
Natural variantiVAR_076383367K → I.1 PublicationCorresponds to variant rs764753481dbSNPEnsembl.1
Natural variantiVAR_041264440V → M.1 PublicationCorresponds to variant rs56311523dbSNPEnsembl.1
Natural variantiVAR_041265500R → P.1 PublicationCorresponds to variant rs56039839dbSNPEnsembl.1
Natural variantiVAR_041266635D → G in a lung small cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_076384724G → E.1 PublicationCorresponds to variant rs201524659dbSNPEnsembl.1
Natural variantiVAR_069052842E → G Found in a patient with SCA11; unknown pathological significance. 1 PublicationCorresponds to variant rs202004988dbSNPEnsembl.1
Natural variantiVAR_0412671062T → I.1 PublicationCorresponds to variant rs55833708dbSNPEnsembl.1
Natural variantiVAR_0412681084T → M.1 PublicationCorresponds to variant rs34348991dbSNPEnsembl.1
Natural variantiVAR_0412691097V → A.1 PublicationCorresponds to variant rs55796513dbSNPEnsembl.1
Natural variantiVAR_0690531110R → H Found in a patient with SCA11; unknown pathological significance. 1 PublicationCorresponds to variant rs146279300dbSNPEnsembl.1
Natural variantiVAR_0412701122P → R.1 PublicationCorresponds to variant rs56142516dbSNPEnsembl.1
Natural variantiVAR_0412711241K → T.1 PublicationCorresponds to variant rs36104367dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0182721 – 72MSGGG…LKKLQ → MES in isoform 2. 1 PublicationAdd BLAST72
Alternative sequenceiVSP_018273470 – 478CLEKMQKDT → WYKIVYFSF in isoform 3. 1 Publication9
Alternative sequenceiVSP_018274479 – 1244Missing in isoform 3. 1 PublicationAdd BLAST766
Alternative sequenceiVSP_0182751233 – 1244QGKSK…SKLSR → PREE in isoform 2. 1 PublicationAdd BLAST12

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK131372 mRNA. Translation: BAD18523.1.
AC068727 Genomic DNA. No translation available.
AC090510 Genomic DNA. No translation available.
BC041876 mRNA. Translation: AAH41876.1.
BC071556 mRNA. Translation: AAH71556.1.
AB020654 mRNA. Translation: BAA74870.1.
CCDSiCCDS42029.1. [Q6IQ55-1]
RefSeqiNP_775771.3. NM_173500.3. [Q6IQ55-1]
UniGeneiHs.646511.
Hs.727864.
Hs.733489.

Genome annotation databases

EnsembliENST00000267890; ENSP00000267890; ENSG00000128881. [Q6IQ55-1]
ENST00000567840; ENSP00000455734; ENSG00000128881. [Q6IQ55-3]
GeneIDi146057.
KEGGihsa:146057.
UCSCiuc001zqo.4. human. [Q6IQ55-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK131372 mRNA. Translation: BAD18523.1.
AC068727 Genomic DNA. No translation available.
AC090510 Genomic DNA. No translation available.
BC041876 mRNA. Translation: AAH41876.1.
BC071556 mRNA. Translation: AAH71556.1.
AB020654 mRNA. Translation: BAA74870.1.
CCDSiCCDS42029.1. [Q6IQ55-1]
RefSeqiNP_775771.3. NM_173500.3. [Q6IQ55-1]
UniGeneiHs.646511.
Hs.727864.
Hs.733489.

3D structure databases

ProteinModelPortaliQ6IQ55.
SMRiQ6IQ55.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126962. 9 interactors.
IntActiQ6IQ55. 4 interactors.
STRINGi9606.ENSP00000267890.

Chemistry databases

ChEMBLiCHEMBL3337327.

PTM databases

iPTMnetiQ6IQ55.
PhosphoSitePlusiQ6IQ55.

Polymorphism and mutation databases

BioMutaiTTBK2.
DMDMi116242833.

Proteomic databases

EPDiQ6IQ55.
MaxQBiQ6IQ55.
PaxDbiQ6IQ55.
PeptideAtlasiQ6IQ55.
PRIDEiQ6IQ55.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000267890; ENSP00000267890; ENSG00000128881. [Q6IQ55-1]
ENST00000567840; ENSP00000455734; ENSG00000128881. [Q6IQ55-3]
GeneIDi146057.
KEGGihsa:146057.
UCSCiuc001zqo.4. human. [Q6IQ55-1]

Organism-specific databases

CTDi146057.
DisGeNETi146057.
GeneCardsiTTBK2.
GeneReviewsiTTBK2.
H-InvDBHIX0012177.
HGNCiHGNC:19141. TTBK2.
HPAiHPA018113.
MalaCardsiTTBK2.
MIMi604432. phenotype.
611695. gene.
neXtProtiNX_Q6IQ55.
OpenTargetsiENSG00000128881.
Orphaneti98767. Spinocerebellar ataxia type 11.
PharmGKBiPA134913925.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1164. Eukaryota.
ENOG410XPGP. LUCA.
GeneTreeiENSGT00760000119040.
HOGENOMiHOG000232043.
HOVERGENiHBG061812.
InParanoidiQ6IQ55.
KOiK08815.
PhylomeDBiQ6IQ55.
TreeFamiTF351646.

Enzyme and pathway databases

BioCyciZFISH:HS13280-MONOMER.
ReactomeiR-HSA-5620912. Anchoring of the basal body to the plasma membrane.
SignaLinkiQ6IQ55.

Miscellaneous databases

GeneWikiiTTBK2.
GenomeRNAii146057.
PROiQ6IQ55.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000128881.
CleanExiHS_TTBK2.
ExpressionAtlasiQ6IQ55. baseline and differential.
GenevisibleiQ6IQ55. 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 nameiTTBK2_HUMAN
AccessioniPrimary (citable) accession number: Q6IQ55
Secondary accession number(s): O94932, Q6ZN52, Q8IVV1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 135 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  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.