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Protein

Tau-tubulin kinase 2

Gene

Ttbk2

Organism
Mus musculus (Mouse)
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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei50 – 501ATPPROSITE-ProRule annotation
Active sitei141 – 1411Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi27 – 359ATPPROSITE-ProRule annotation

GO - Molecular functioni

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

GO - Biological processi

  • cilium assembly Source: UniProtKB
  • embryonic brain development Source: MGI
  • embryonic digit morphogenesis Source: MGI
  • forebrain development Source: MGI
  • negative regulation of cellular protein localization Source: MGI
  • neural tube development Source: MGI
  • peptidyl-serine phosphorylation Source: UniProtKB
  • positive regulation of nonmotile primary cilium assembly Source: MGI
  • regulation of cell shape Source: GO_Central
  • regulation of smoothened signaling pathway Source: MGI
  • smoothened signaling pathway Source: UniProtKB
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

BRENDAi2.7.11.26. 3474.
ReactomeiR-MMU-5620912. Anchoring of the basal body to the plasma membrane.

Names & Taxonomyi

Protein namesi
Recommended name:
Tau-tubulin kinase 2 (EC:2.7.11.1)
Alternative name(s):
Protein bartleby
Gene namesi
Name:Ttbk2
Synonyms:Bby, Kiaa0847, Ttbk1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:2155779. Ttbk2.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell projection, Cilium, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Disruption phenotypei

Defects in Ttbk2 are the cause of the bartleby (bby) phenotype characterized by defects in sonic hedgehog/SHH signaling and ciliogenesis. Embryos display morphological defects at midgestation similar to those seen in mutants that lack cilia, including holoprosencephaly, twisted body axis, abnormal limb development and randomized laterality of heart looping. Mutants die at midgestation (around E10.5).1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi163 – 1631D → A: Abolishes serine/threonine-protein kinase activity and ability to initiate ciliogenesis. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12431243Tau-tubulin kinase 2PRO_0000234343Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei445 – 4451PhosphoserineBy similarity
Modified residuei786 – 7861PhosphoserineBy similarity
Modified residuei1102 – 11021PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ3UVR3.
PaxDbiQ3UVR3.
PRIDEiQ3UVR3.

PTM databases

iPTMnetiQ3UVR3.
PhosphoSiteiQ3UVR3.

Expressioni

Gene expression databases

BgeeiENSMUSG00000090100.
CleanExiMM_TTBK1.
ExpressionAtlasiQ3UVR3. baseline and differential.
GenevisibleiQ3UVR3. MM.

Interactioni

Subunit structurei

Interacts with CEP164.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000028740.

Structurei

3D structure databases

ProteinModelPortaliQ3UVR3.
SMRiQ3UVR3. Positions 9-301.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini21 – 284264Protein kinasePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi307 – 3115Poly-Thr
Compositional biasi1099 – 1242144Ser-richAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1164. Eukaryota.
ENOG410XPGP. LUCA.
GeneTreeiENSGT00760000119040.
HOVERGENiHBG061812.
InParanoidiQ3UVR3.
KOiK08815.

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: Q3UVR3-1) [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
MSGGGEQPDI LSVGILVKER WKVLRKIGGG GFGEIYDALD MLTRENVALK
60 70 80 90 100
VESAQQPKQV LKMEVAVLKK LQGKDHVCRF IGCGRNDRFN YVVMQLQGRN
110 120 130 140 150
LADLRRSQSR GTFTISTTLR LGKQILESIE SIHSVGFLHR DIKPSNFAMG
160 170 180 190 200
RFPSTCRKCF MLDFGLARQF TNSCGDVRPP RAVAGFRGTV RYASINAHRN
210 220 230 240 250
REMGRHDDLW SLFYMLVEFV VGQLPWRKIK DKEQVGSIKE RYDHRLMLKH
260 270 280 290 300
LPPEFSTFLD HISSLDYFTK PDYQLLTSVF DNSIKTFGVI ESDPFDWEKS
310 320 330 340 350
GTDGSLTTTT TSATPQLHTR LTPAAIGIAN ATPIPGDLLR ENTDEVFPDE
360 370 380 390 400
QLSDGENGIP VGVSPDKLPG SLGHPRPQEK DVWEEMDINK NKIKLGICKA
410 420 430 440 450
ATEEENSHGQ VNGILNAPSL GSPIRVRSEI TQPDRDVPLV RKLRSIHSFE
460 470 480 490 500
LEKRLTLEPK PDTDKFLETC MEKMQKDSSA GKEPVPPALP HKPCVPVVTH
510 520 530 540 550
TDHIWHYDDE YLPDASKPAS ANTPEQADGG GSNGFIAVNL SSCKQEVDSK
560 570 580 590 600
EWVIVDKEQD LQDFRTNEVL GHKTTGSPSD EEPEVLQVLE GSPQDEKIQV
610 620 630 640 650
GPWTDNHHLK KESSGVVLAL SAECPATAAS ELYTDRLDLQ AGAASQFITV
660 670 680 690 700
TPTSPMEAQA EGPLTAITIP RPSVASTQST SGSFHYGPQP EKKDLQPLEP
710 720 730 740 750
TVELYSPREN FSGLVVTEGE LASGGSRVDL GLQIDHTGHD MLPNMRDGDT
760 770 780 790 800
SQDLGPKDPP DHNRLAVKEF EHLPGETEER SLLLGSENED ERLSKGQHCI
810 820 830 840 850
EVSSPGELVT AERAQLAATE PLHVSETQNC SVLPNQDKTH EIMKLLAVGT
860 870 880 890 900
SEISPQAIDP HAEGQIGQMA AMQKNKLFKD DGIQSESLPR QQGDLSAFLH
910 920 930 940 950
QEGKREKVVP RNGELYHCVS ENEHGPPTRK DMLRSSFVTR HSRIPVLAQE
960 970 980 990 1000
IDSTFESSSA ISAKEKLLQK KAYQPEIVKL LVEKRQFKSF LGDLSSASDK
1010 1020 1030 1040 1050
LIEEKLAAVP VPFSEEEVFA PFSRLAADSH LSRSVEDSFL SPIISQARKS
1060 1070 1080 1090 1100
KIPRPVSWVS TDQINGSASP QFLPRPPPGK PPVRPGVEAR LRRYKVLGSS
1110 1120 1130 1140 1150
NSDSDLFSRL AQILQNGSQK SRSTTQCKSP GSPHNPKTPP KSPVVPRRSP
1160 1170 1180 1190 1200
SASPRSSSLP RTSSSSPSRA GRPHHDQRSS SPHLGRSKSP PSHSGSSSSR
1210 1220 1230 1240
RSCQQEHCKP SKNGPKGSGS LHHHSTSSKT PPGKSKPASK LSR
Length:1,243
Mass (Da):136,770
Last modified:October 11, 2005 - v1
Checksum:i978D68D7BC7A535E
GO
Isoform 2 (identifier: Q3UVR3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1091-1243: LRRYKVLGSS...KSKPASKLSR → PGSPQAVHLI...DRAQHPEFGG

Note: No experimental confirmation available.
Show »
Length:1,201
Mass (Da):132,256
Checksum:i5D9A16DC855EF5EB
GO

Sequence cautioni

The sequence BAD90183 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti192 – 1921Y → C in BAB62004 (PubMed:11257498).Curated
Sequence conflicti196 – 1961N → D in BAB62004 (PubMed:11257498).Curated
Sequence conflicti228 – 2281K → E in BAB62004 (PubMed:11257498).Curated
Sequence conflicti317 – 3204LHTR → CTPA in BAB62004 (PubMed:11257498).Curated
Sequence conflicti490 – 4901P → L in BAE28449 (Ref. 2) Curated
Sequence conflicti500 – 5001H → R in BAE28449 (Ref. 2) Curated
Sequence conflicti591 – 5911G → V in BAE28449 (Ref. 2) Curated
Sequence conflicti890 – 8901R → G in BAE28449 (Ref. 2) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1091 – 1243153LRRYK…SKLSR → PGSPQAVHLITLLQGPGNQR KAPRRPAGLAGWADLPGPPE PHPSRTRPVVQRSIPVAGSA PPGCPWRECACSVASERLHR DGGRFRVAAARRGAGRSRRA VDRAQHPEFGG in isoform 2. CuratedVSP_018276Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK053820 mRNA. Translation: BAC35540.1.
AK137024 mRNA. Translation: BAE23206.1.
AK148269 mRNA. Translation: BAE28449.1.
AK161858 mRNA. Translation: BAE36609.1.
AK220258 mRNA. Translation: BAD90183.1. Different initiation.
AL935168 Genomic DNA. Translation: CAM21401.1.
AB046593 mRNA. Translation: BAB62004.2.
CCDSiCCDS16627.1. [Q3UVR3-1]
RefSeqiNP_001020027.1. NM_001024856.2. [Q3UVR3-1]
NP_001020028.1. NM_001024857.2. [Q3UVR3-1]
NP_542966.2. NM_080788.3.
UniGeneiMm.275698.

Genome annotation databases

EnsembliENSMUST00000057135; ENSMUSP00000055032; ENSMUSG00000090100. [Q3UVR3-1]
ENSMUST00000085840; ENSMUSP00000083001; ENSMUSG00000090100. [Q3UVR3-1]
GeneIDi140810.
KEGGimmu:140810.
UCSCiuc008lww.2. mouse. [Q3UVR3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK053820 mRNA. Translation: BAC35540.1.
AK137024 mRNA. Translation: BAE23206.1.
AK148269 mRNA. Translation: BAE28449.1.
AK161858 mRNA. Translation: BAE36609.1.
AK220258 mRNA. Translation: BAD90183.1. Different initiation.
AL935168 Genomic DNA. Translation: CAM21401.1.
AB046593 mRNA. Translation: BAB62004.2.
CCDSiCCDS16627.1. [Q3UVR3-1]
RefSeqiNP_001020027.1. NM_001024856.2. [Q3UVR3-1]
NP_001020028.1. NM_001024857.2. [Q3UVR3-1]
NP_542966.2. NM_080788.3.
UniGeneiMm.275698.

3D structure databases

ProteinModelPortaliQ3UVR3.
SMRiQ3UVR3. Positions 9-301.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000028740.

PTM databases

iPTMnetiQ3UVR3.
PhosphoSiteiQ3UVR3.

Proteomic databases

MaxQBiQ3UVR3.
PaxDbiQ3UVR3.
PRIDEiQ3UVR3.

Protocols and materials databases

DNASUi140810.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000057135; ENSMUSP00000055032; ENSMUSG00000090100. [Q3UVR3-1]
ENSMUST00000085840; ENSMUSP00000083001; ENSMUSG00000090100. [Q3UVR3-1]
GeneIDi140810.
KEGGimmu:140810.
UCSCiuc008lww.2. mouse. [Q3UVR3-1]

Organism-specific databases

CTDi146057.
MGIiMGI:2155779. Ttbk2.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG1164. Eukaryota.
ENOG410XPGP. LUCA.
GeneTreeiENSGT00760000119040.
HOVERGENiHBG061812.
InParanoidiQ3UVR3.
KOiK08815.

Enzyme and pathway databases

BRENDAi2.7.11.26. 3474.
ReactomeiR-MMU-5620912. Anchoring of the basal body to the plasma membrane.

Miscellaneous databases

ChiTaRSiTtbk2. mouse.
PROiQ3UVR3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000090100.
CleanExiMM_TTBK1.
ExpressionAtlasiQ3UVR3. baseline and differential.
GenevisibleiQ3UVR3. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: Q3UVR3
Secondary accession number(s): A2AW12
, Q3TSR6, Q3UFW0, Q571D1, Q8BKA4, Q924U8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: October 11, 2005
Last modified: September 7, 2016
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. 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.