Details of the Target

General Information of Target

Target ID LDTP07427
Target Name Tau-tubulin kinase 2 (TTBK2)
Gene Name TTBK2
Gene ID 146057
Synonyms
KIAA0847; Tau-tubulin kinase 2; EC 2.7.11.1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSGGGEQLDILSVGILVKERWKVLRKIGGGGFGEIYDALDMLTRENVALKVESAQQPKQV
LKMEVAVLKKLQGKDHVCRFIGCGRNDRFNYVVMQLQGRNLADLRRSQSRGTFTISTTLR
LGRQILESIESIHSVGFLHRDIKPSNFAMGRFPSTCRKCYMLDFGLARQFTNSCGDVRPP
RAVAGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWRKIKDKEQVGSIKE
RYDHRLMLKHLPPEFSIFLDHISSLDYFTKPDYQLLTSVFDNSIKTFGVIESDPFDWEKT
GNDGSLTTTTTSTTPQLHTRLTPAAIGIANATPIPGDLLRENTDEVFPDEQLSDGENGIP
VGVSPDKLPGSLGHPRPQEKDVWEEMDANKNKIKLGICKAATEEENSHGQANGLLNAPSL
GSPIRVRSEITQPDRDIPLVRKLRSIHSFELEKRLTLEPKPDTDKFLETCLEKMQKDTSA
GKESILPALLHKPCVPAVSRTDHIWHYDEEYLPDASKPASANTPEQADGGGSNGFIAVNL
SSCKQEIDSKEWVIVDKEQDLQDFRTNEAVGHKTTGSPSDEEPEVLQVLEASPQDEKLQL
GPWAENDHLKKETSGVVLALSAEGPPTAASEQYTDRLELQPGAASQFIAATPTSLMEAQA
EGPLTAITIPRPSVASTQSTSGSFHCGQQPEKKDLQPMEPTVELYSPRENFSGLVVTEGE
PPSGGSRTDLGLQIDHIGHDMLPNIRESNKSQDLGPKELPDHNRLVVREFENLPGETEEK
SILLESDNEDEKLSRGQHCIEISSLPGDLVIVEKDHSATTEPLDVTKTQTFSVVPNQDKN
NEIMKLLTVGTSEISSRDIDPHVEGQIGQVAEMQKNKISKDDDIMSEDLPGHQGDLSTFL
HQEGKREKITPRNGELFHCVSENEHGAPTRKDMVRSSFVTRHSRIPVLAQEIDSTLESSS
PVSAKEKLLQKKAYQPDLVKLLVEKRQFKSFLGDLSSASDKLLEEKLATVPAPFCEEEVL
TPFSRLTVDSHLSRSAEDSFLSPIISQSRKSKIPRPVSWVNTDQVNSSTSSQFFPRPPPG
KPPTRPGVEARLRRYKVLGSSNSDSDLFSRLAQILQNGSQKPRSTTQCKSPGSPHNPKTP
PKSPVVPRRSPSASPRSSSLPRTSSSSPSRAGRPHHDQRSSSPHLGRSKSPPSHSGSSSS
RRSCQQEHCKPSKNGLKGSGSLHHHSASTKTPQGKSKPASKLSR
Target Bioclass
Enzyme
Family
Protein kinase superfamily, CK1 Ser/Thr protein kinase family
Subcellular location
Cell projection, cilium
Function
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. Phosphorylates MPHOSPH9 which promotes its ubiquitination and proteasomal degradation, loss of MPHOSPH9 facilitates the removal of the CP110-CEP97 complex (a negative regulator of ciliogenesis) from the mother centrioles, promoting the initiation of ciliogenesis.
Uniprot ID
Q6IQ55
Ensemble ID
ENST00000267890.11
HGNC ID
HGNC:19141
ChEMBL ID
CHEMBL3337327

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
22RV1 SNV: p.Y36C .
CAL78 SNV: p.K1230E .
COLO678 SNV: p.T1231N .
FADU SNV: p.R168P .
IGR1 SNV: p.D349N .
Ishikawa (Heraklio) 02 ER SNV: p.S1152N .
KU1919 Deletion: p.E1017RfsTer10 .
LS123 Deletion: p.Q1233PfsTer4 .
NCIH716 Deletion: p.Q1233PfsTer4 .
OVCAR8 SNV: p.V716L .
TE8 SNV: p.Q316L .
TFK1 SNV: p.R425P .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C90(1.91)  LDD3433  [1]
IPM
 Probe Info  		C83(1.21)  LDD1701  [2]
4-Iodoacetamidophenylacetylene
 Probe Info  		N.A.  LDD0038  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0237  AC12 HEK-293T C494(0.88)  LDD1510  [4]
 LDCM0270  AC15 HEK-293T C494(0.87)  LDD1513  [4]
 LDCM0280  AC20 HEK-293T C494(0.96)  LDD1519  [4]
 LDCM0281  AC21 HEK-293T C494(1.48)  LDD1520  [4]
 LDCM0283  AC23 HEK-293T C494(0.83)  LDD1522  [4]
 LDCM0284  AC24 HEK-293T C494(0.91)  LDD1523  [4]
 LDCM0288  AC28 HEK-293T C494(0.92)  LDD1527  [4]
 LDCM0289  AC29 HEK-293T C494(1.14)  LDD1528  [4]
 LDCM0292  AC31 HEK-293T C494(0.85)  LDD1531  [4]
 LDCM0293  AC32 HEK-293T C494(0.93)  LDD1532  [4]
 LDCM0297  AC36 HEK-293T C494(1.14)  LDD1536  [4]
 LDCM0298  AC37 HEK-293T C494(1.31)  LDD1537  [4]
 LDCM0300  AC39 HEK-293T C494(0.84)  LDD1539  [4]
 LDCM0301  AC4 HEK-293T C494(0.88)  LDD1540  [4]
 LDCM0302  AC40 HEK-293T C494(0.93)  LDD1541  [4]
 LDCM0306  AC44 HEK-293T C494(1.00)  LDD1545  [4]
 LDCM0307  AC45 HEK-293T C494(1.31)  LDD1546  [4]
 LDCM0309  AC47 HEK-293T C494(0.80)  LDD1548  [4]
 LDCM0310  AC48 HEK-293T C494(1.22)  LDD1549  [4]
 LDCM0312  AC5 HEK-293T C494(1.43)  LDD1551  [4]
 LDCM0315  AC52 HEK-293T C494(0.93)  LDD1554  [4]
 LDCM0316  AC53 HEK-293T C494(1.22)  LDD1555  [4]
 LDCM0318  AC55 HEK-293T C494(0.78)  LDD1557  [4]
 LDCM0319  AC56 HEK-293T C494(1.16)  LDD1558  [4]
 LDCM0324  AC60 HEK-293T C494(0.96)  LDD1563  [4]
 LDCM0325  AC61 HEK-293T C494(1.31)  LDD1564  [4]
 LDCM0327  AC63 HEK-293T C494(0.83)  LDD1566  [4]
 LDCM0328  AC64 HEK-293T C494(0.83)  LDD1567  [4]
 LDCM0334  AC7 HEK-293T C494(0.82)  LDD1568  [4]
 LDCM0345  AC8 HEK-293T C494(1.16)  LDD1569  [4]
 LDCM0248  AKOS034007472 HEK-293T C494(1.19)  LDD1511  [4]
 LDCM0275  AKOS034007705 HEK-293T C494(0.97)  LDD1514  [4]
 LDCM0367  CL1 HEK-293T C919(1.48)  LDD1571  [4]
 LDCM0370  CL101 HEK-293T C919(0.98)  LDD1574  [4]
 LDCM0371  CL102 HEK-293T C919(0.88); C494(1.04)  LDD1575  [4]
 LDCM0372  CL103 HEK-293T C919(0.77); C494(0.75)  LDD1576  [4]
 LDCM0374  CL105 HEK-293T C919(0.98)  LDD1578  [4]
 LDCM0375  CL106 HEK-293T C919(0.92); C494(0.89)  LDD1579  [4]
 LDCM0376  CL107 HEK-293T C919(0.89); C494(0.91)  LDD1580  [4]
 LDCM0378  CL109 HEK-293T C919(1.08)  LDD1582  [4]
 LDCM0379  CL11 HEK-293T C494(1.07)  LDD1583  [4]
 LDCM0380  CL110 HEK-293T C919(1.00); C494(0.85)  LDD1584  [4]
 LDCM0381  CL111 HEK-293T C919(1.10); C494(1.02)  LDD1585  [4]
 LDCM0383  CL113 HEK-293T C919(1.22)  LDD1587  [4]
 LDCM0384  CL114 HEK-293T C919(1.19); C494(1.28)  LDD1588  [4]
 LDCM0385  CL115 HEK-293T C919(0.78); C494(1.16)  LDD1589  [4]
 LDCM0387  CL117 HEK-293T C919(1.09)  LDD1591  [4]
 LDCM0388  CL118 HEK-293T C919(0.98); C494(1.20)  LDD1592  [4]
 LDCM0389  CL119 HEK-293T C919(1.11); C494(1.12)  LDD1593  [4]
 LDCM0390  CL12 HEK-293T C494(1.06)  LDD1594  [4]
 LDCM0392  CL121 HEK-293T C919(1.37)  LDD1596  [4]
 LDCM0393  CL122 HEK-293T C919(0.91); C494(1.10)  LDD1597  [4]
 LDCM0394  CL123 HEK-293T C919(1.09); C494(0.87)  LDD1598  [4]
 LDCM0396  CL125 HEK-293T C919(1.15)  LDD1600  [4]
 LDCM0397  CL126 HEK-293T C919(0.85); C494(0.98)  LDD1601  [4]
 LDCM0398  CL127 HEK-293T C919(0.83); C494(1.20)  LDD1602  [4]
 LDCM0400  CL13 HEK-293T C919(1.33)  LDD1604  [4]
 LDCM0401  CL14 HEK-293T C919(1.17); C494(1.19)  LDD1605  [4]
 LDCM0402  CL15 HEK-293T C919(1.12); C494(1.21)  LDD1606  [4]
 LDCM0407  CL2 HEK-293T C919(1.01); C494(1.26)  LDD1611  [4]
 LDCM0408  CL20 HEK-293T C494(1.37)  LDD1612  [4]
 LDCM0409  CL21 HEK-293T C494(1.68)  LDD1613  [4]
 LDCM0411  CL23 HEK-293T C494(1.48)  LDD1615  [4]
 LDCM0412  CL24 HEK-293T C494(1.12)  LDD1616  [4]
 LDCM0413  CL25 HEK-293T C919(1.44)  LDD1617  [4]
 LDCM0414  CL26 HEK-293T C919(0.93); C494(0.93)  LDD1618  [4]
 LDCM0415  CL27 HEK-293T C919(0.98); C494(0.83)  LDD1619  [4]
 LDCM0418  CL3 HEK-293T C919(1.08); C494(1.31)  LDD1622  [4]
 LDCM0421  CL32 HEK-293T C494(1.02)  LDD1625  [4]
 LDCM0422  CL33 HEK-293T C494(1.02)  LDD1626  [4]
 LDCM0424  CL35 HEK-293T C494(1.12)  LDD1628  [4]
 LDCM0425  CL36 HEK-293T C494(1.10)  LDD1629  [4]
 LDCM0426  CL37 HEK-293T C919(1.06)  LDD1630  [4]
 LDCM0428  CL39 HEK-293T C919(0.92); C494(1.02)  LDD1632  [4]
 LDCM0434  CL44 HEK-293T C494(0.97)  LDD1638  [4]
 LDCM0435  CL45 HEK-293T C494(1.23)  LDD1639  [4]
 LDCM0437  CL47 HEK-293T C494(0.88)  LDD1641  [4]
 LDCM0438  CL48 HEK-293T C494(1.11)  LDD1642  [4]
 LDCM0439  CL49 HEK-293T C919(1.05)  LDD1643  [4]
 LDCM0441  CL50 HEK-293T C919(1.02); C494(0.97)  LDD1645  [4]
 LDCM0447  CL56 HEK-293T C494(1.27)  LDD1650  [4]
 LDCM0448  CL57 HEK-293T C494(1.25)  LDD1651  [4]
 LDCM0450  CL59 HEK-293T C494(1.06)  LDD1653  [4]
 LDCM0452  CL60 HEK-293T C494(0.99)  LDD1655  [4]
 LDCM0453  CL61 HEK-293T C919(1.00)  LDD1656  [4]
 LDCM0454  CL62 HEK-293T C919(0.91); C494(1.05)  LDD1657  [4]
 LDCM0455  CL63 HEK-293T C919(0.88); C494(1.00)  LDD1658  [4]
 LDCM0460  CL68 HEK-293T C494(0.89)  LDD1663  [4]
 LDCM0461  CL69 HEK-293T C494(1.49)  LDD1664  [4]
 LDCM0464  CL71 HEK-293T C494(0.87)  LDD1667  [4]
 LDCM0465  CL72 HEK-293T C494(1.36)  LDD1668  [4]
 LDCM0466  CL73 HEK-293T C919(0.93)  LDD1669  [4]
 LDCM0467  CL74 HEK-293T C919(1.36); C494(1.05)  LDD1670  [4]
 LDCM0473  CL8 HEK-293T C494(0.85)  LDD1676  [4]
 LDCM0474  CL80 HEK-293T C494(0.95)  LDD1677  [4]
 LDCM0475  CL81 HEK-293T C494(1.22)  LDD1678  [4]
 LDCM0477  CL83 HEK-293T C494(0.93)  LDD1680  [4]
 LDCM0478  CL84 HEK-293T C494(1.10)  LDD1681  [4]
 LDCM0479  CL85 HEK-293T C919(1.06)  LDD1682  [4]
 LDCM0480  CL86 HEK-293T C919(0.90); C494(1.77)  LDD1683  [4]
 LDCM0481  CL87 HEK-293T C919(0.77); C494(1.00)  LDD1684  [4]
 LDCM0484  CL9 HEK-293T C494(1.21)  LDD1687  [4]
 LDCM0487  CL92 HEK-293T C494(1.09)  LDD1690  [4]
 LDCM0488  CL93 HEK-293T C494(1.40)  LDD1691  [4]
 LDCM0490  CL95 HEK-293T C494(1.07)  LDD1693  [4]
 LDCM0491  CL96 HEK-293T C494(0.90)  LDD1694  [4]
 LDCM0492  CL97 HEK-293T C919(1.28)  LDD1695  [4]
 LDCM0493  CL98 HEK-293T C919(1.83); C494(1.11)  LDD1696  [4]
 LDCM0494  CL99 HEK-293T C919(0.85); C494(1.09)  LDD1697  [4]
 LDCM0495  E2913 HEK-293T C919(0.90); C494(1.25)  LDD1698  [4]
 LDCM0468  Fragment33 HEK-293T C919(0.83); C494(1.10)  LDD1671  [4]
 LDCM0427  Fragment51 HEK-293T C919(1.01); C494(1.30)  LDD1631  [4]
 LDCM0022  KB02 Kelly C90(2.32)  LDD2417  [1]
 LDCM0023  KB03 MDA-MB-231 C83(1.21)  LDD1701  [2]
 LDCM0024  KB05 SK-N-AS C90(1.91)  LDD3433  [1]

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
3 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
4 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402