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Protein

Tau-tubulin kinase 2

Gene

Ttbk2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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)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

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCilium biogenesis/degradation
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:2155779 Ttbk2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
Mutagenesisi163D → A: Abolishes serine/threonine-protein kinase activity and ability to initiate ciliogenesis. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002343431 – 1243Tau-tubulin kinase 2Add BLAST1243

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei445PhosphoserineBy similarity1
Modified residuei786PhosphoserineBy similarity1
Modified residuei1102PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ3UVR3
PRIDEiQ3UVR3

PTM databases

iPTMnetiQ3UVR3
PhosphoSitePlusiQ3UVR3

Expressioni

Gene expression databases

BgeeiENSMUSG00000090100 Expressed in 223 organ(s), highest expression level in lumbar subsegment of spinal cord
CleanExiMM_TTBK1
ExpressionAtlasiQ3UVR3 baseline and differential
GenevisibleiQ3UVR3 MM

Interactioni

Subunit structurei

Interacts with CEP164.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000028740

Structurei

3D structure databases

ProteinModelPortaliQ3UVR3
SMRiQ3UVR3
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 – 311Poly-Thr5
Compositional biasi1099 – 1242Ser-richAdd BLAST144

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1164 Eukaryota
ENOG410XPGP LUCA
GeneTreeiENSGT00930000150814
HOVERGENiHBG061812
InParanoidiQ3UVR3
KOiK08815

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A2AW15A2AW15_MOUSE
Tau-tubulin kinase 2
Ttbk2
1,312Annotation score:
A2AW13A2AW13_MOUSE
Tau-tubulin kinase 2
Ttbk2
872Annotation score:
A2AW14A2AW14_MOUSE
Tau-tubulin kinase 2
Ttbk2
436Annotation score:

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti192Y → C in BAB62004 (PubMed:11257498).Curated1
Sequence conflicti196N → D in BAB62004 (PubMed:11257498).Curated1
Sequence conflicti228K → E in BAB62004 (PubMed:11257498).Curated1
Sequence conflicti317 – 320LHTR → CTPA in BAB62004 (PubMed:11257498).Curated4
Sequence conflicti490P → L in BAE28449 (Ref. 2) Curated1
Sequence conflicti500H → R in BAE28449 (Ref. 2) Curated1
Sequence conflicti591G → V in BAE28449 (Ref. 2) Curated1
Sequence conflicti890R → G in BAE28449 (Ref. 2) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0182761091 – 1243LRRYK…SKLSR → PGSPQAVHLITLLQGPGNQR KAPRRPAGLAGWADLPGPPE PHPSRTRPVVQRSIPVAGSA PPGCPWRECACSVASERLHR DGGRFRVAAARRGAGRSRRA VDRAQHPEFGG in isoform 2. CuratedAdd BLAST153

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 No translation available.
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

Similar proteinsi

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 No translation available.
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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000028740

PTM databases

iPTMnetiQ3UVR3
PhosphoSitePlusiQ3UVR3

Proteomic databases

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
GeneTreeiENSGT00930000150814
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
PROiPR:Q3UVR3
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000090100 Expressed in 223 organ(s), highest expression level in lumbar subsegment of spinal cord
CleanExiMM_TTBK1
ExpressionAtlasiQ3UVR3 baseline and differential
GenevisibleiQ3UVR3 MM

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTTBK2_MOUSE
AccessioniPrimary (citable) accession number: Q3UVR3
Secondary accession number(s): A2AW12
, Q3TSR6, Q3UFW0, Q571D1, Q8BKA4, Q924U8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: October 11, 2005
Last modified: November 7, 2018
This is version 105 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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