Details of the Target

General Information of Target

Target ID LDTP09189
Target Name Dedicator of cytokinesis protein 8 (DOCK8)
Gene Name DOCK8
Gene ID 81704
Synonyms
Dedicator of cytokinesis protein 8
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MATLPSAERRAFALKINRYSSAEIRKQFTLPPNLGQYHRQSISTSGFPSLQLPQFYDPVE
PVDFEGLLMTHLNSLDVQLAQELGDFTDDDLDVVFTPKECRTLQPSLPEEGVELDPHVRD
CVQTYIREWLIVNRKNQGSPEICGFKKTGSRKDFHKTLPKQTFESETLECSEPAAQAGPR
HLNVLCDVSGKGPVTACDFDLRSLQPDKRLENLLQQVSAEDFEKQNEEARRTNRQAELFA
LYPSVDEEDAVEIRPVPECPKEHLGNRILVKLLTLKFEIEIEPLFASIALYDVKERKKIS
ENFHCDLNSDQFKGFLRAHTPSVAASSQARSAVFSVTYPSSDIYLVVKIEKVLQQGEIGD
CAEPYTVIKESDGGKSKEKIEKLKLQAESFCQRLGKYRMPFAWAPISLSSFFNVSTLERE
VTDVDSVVGRSSVGERRTLAQSRRLSERALSLEENGVGSNFKTSTLSVSSFFKQEGDRLS
DEDLFKFLADYKRSSSLQRRVKSIPGLLRLEISTAPEIINCCLTPEMLPVKPFPENRTRP
HKEILEFPTREVYVPHTVYRNLLYVYPQRLNFVNKLASARNITIKIQFMCGEDASNAMPV
IFGKSSGPEFLQEVYTAVTYHNKSPDFYEEVKIKLPAKLTVNHHLLFTFYHISCQQKQGA
SVETLLGYSWLPILLNERLQTGSYCLPVALEKLPPNYSMHSAEKVPLQNPPIKWAEGHKG
VFNIEVQAVSSVHTQDNHLEKFFTLCHSLESQVTFPIRVLDQKISEMALEHELKLSIICL
NSSRLEPLVLFLHLVLDKLFQLSVQPMVIAGQTANFSQFAFESVVAIANSLHNSKDLSKD
QHGRNCLLASYVHYVFRLPEVQRDVPKSGAPTALLDPRSYHTYGRTSAAAVSSKLLQARV
MSSSNPDLAGTHSAADEEVKNIMSSKIADRNCSRMSYYCSGSSDAPSSPAAPRPASKKHF
HEELALQMVVSTGMVRETVFKYAWFFFELLVKSMAQHVHNMDKRDSFRRTRFSDRFMDDI
TTIVNVVTSEIAALLVKPQKENEQAEKMNISLAFFLYDLLSLMDRGFVFNLIRHYCSQLS
AKLSNLPTLISMRLEFLRILCSHEHYLNLNLFFMNADTAPTSPCPSISSQNSSSCSSFQD
QKIASMFDLTSEYRQQHFLTGLLFTELAAALDAEGEGISKVQRKAVSAIHSLLSSHDLDP
RCVKPEVKVKIAALYLPLVGIILDALPQLCDFTVADTRRYRTSGSDEEQEGAGAINQNVA
LAIAGNNFNLKTSGIVLSSLPYKQYNMLNADTTRNLMICFLWIMKNADQSLIRKWIADLP
STQLNRILDLLFICVLCFEYKGKQSSDKVSTQVLQKSRDVKARLEEALLRGEGARGEMMR
RRAPGNDRFPGLNENLRWKKEQTHWRQANEKLDKTKAELDQEALISGNLATEAHLIILDM
QENIIQASSALDCKDSLLGGVLRVLVNSLNCDQSTTYLTHCFATLRALIAKFGDLLFEEE
VEQCFDLCHQVLHHCSSSMDVTRSQACATLYLLMRFSFGATSNFARVKMQVTMSLASLVG
RAPDFNEEHLRRSLRTILAYSEEDTAMQMTPFPTQVEELLCNLNSILYDTVKMREFQEDP
EMLMDLMYRIAKSYQASPDLRLTWLQNMAEKHTKKKCYTEAAMCLVHAAALVAEYLSMLE
DHSYLPVGSVSFQNISSNVLEESVVSEDTLSPDEDGVCAGQYFTESGLVGLLEQAAELFS
TGGLYETVNEVYKLVIPILEAHREFRKLTLTHSKLQRAFDSIVNKDHKRMFGTYFRVGFF
GSKFGDLDEQEFVYKEPAITKLPEISHRLEAFYGQCFGAEFVEVIKDSTPVDKTKLDPNK
AYIQITFVEPYFDEYEMKDRVTYFEKNFNLRRFMYTTPFTLEGRPRGELHEQYRRNTVLT
TMHAFPYIKTRISVIQKEEFVLTPIEVAIEDMKKKTLQLAVAINQEPPDAKMLQMVLQGS
VGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLITADQR
EYQQELKKNYNKLKENLRPMIERKIPELYKPIFRVESQKRDSFHRSSFRKCETQLSQGS
Target Bioclass
Other
Family
DOCK family
Subcellular location
Cytoplasm
Function
Guanine nucleotide exchange factor (GEF) which specifically activates small GTPase CDC42 by exchanging bound GDP for free GTP. During immune responses, required for interstitial dendritic cell (DC) migration by locally activating CDC42 at the leading edge membrane of DC. Required for CD4(+) T-cell migration in response to chemokine stimulation by promoting CDC42 activation at T cell leading edge membrane. Is involved in NK cell cytotoxicity by controlling polarization of microtubule-organizing center (MTOC), and possibly regulating CCDC88B-mediated lytic granule transport to MTOC during cell killing.
Uniprot ID
Q8NF50
Ensemble ID
ENST00000432829.7
HGNC ID
HGNC:19191

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CCSW1 SNV: p.I343S .
CHL1 SNV: p.D207E .
COLO320 SNV: p.S1345I .
HCT116 Deletion: p.K147RfsTer36; p.F1113LfsTer2 .
HT Deletion: p.F1113LfsTer2 .
HT115 SNV: p.K379N; p.I544M; p.R1789I .
Ishikawa (Heraklio) 02 ER Insertion: p.A1483CfsTer16
SNV: p.D1197G		 .
JHH1 SNV: p.V421G .
JURKAT SNV: p.M1534T .
KMS12BM SNV: p.P1087L .
L428 SNV: p.Q801L .
LN18 Deletion: p.S903TfsTer17
SNV: p.S415C		 .
LS180 Deletion: p.V352SfsTer32 .
MDAMB436 Deletion: p.C1471HfsTer23 .
NCIH446 SNV: p.K1815Ter .
NCIH716 SNV: p.E1674G .
P31FUJ SNV: p.V1068L DBIA    Probe Info 
REH SNV: p.A11T DBIA    Probe Info 
SUDHL4 SNV: p.R2089M DBIA    Probe Info 
U87MG SNV: p.Q386Ter .
WM115 SNV: p.P548L .
WM2664 SNV: p.P548L .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 6 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STPyne
 Probe Info  		K156(9.47)  LDD0277  [1]
DBIA
 Probe Info  		C197(1.41); C685(1.27)  LDD3319  [2]
CY4
 Probe Info  		N1887(0.00); N1889(0.00)  LDD0247  [3]
IA-alkyne
 Probe Info  		C197(0.00); C391(0.00); C143(0.00); C846(0.00)  LDD0167  [4]
IPM
 Probe Info  		N.A.  LDD0025  [5]
NAIA_5
 Probe Info  		C143(0.00); C170(0.00)  LDD2224  [6]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0215  AC10 HEK-293T C1202(1.05)  LDD1508  [7]
 LDCM0277  AC18 HEK-293T C1202(0.97)  LDD1516  [7]
 LDCM0279  AC2 HEK-293T C1202(1.09)  LDD1518  [7]
 LDCM0286  AC26 HEK-293T C1202(1.05)  LDD1525  [7]
 LDCM0295  AC34 HEK-293T C1202(1.05)  LDD1534  [7]
 LDCM0304  AC42 HEK-293T C1202(1.02)  LDD1543  [7]
 LDCM0313  AC50 HEK-293T C1202(1.04)  LDD1552  [7]
 LDCM0321  AC58 HEK-293T C1202(1.06)  LDD1560  [7]
 LDCM0367  CL1 HEK-293T C1202(1.13)  LDD1571  [7]
 LDCM0370  CL101 HEK-293T C1202(1.06)  LDD1574  [7]
 LDCM0371  CL102 HEK-293T C1202(0.99)  LDD1575  [7]
 LDCM0374  CL105 HEK-293T C1202(0.96)  LDD1578  [7]
 LDCM0375  CL106 HEK-293T C1202(0.94)  LDD1579  [7]
 LDCM0378  CL109 HEK-293T C1202(0.90)  LDD1582  [7]
 LDCM0380  CL110 HEK-293T C1202(1.04)  LDD1584  [7]
 LDCM0383  CL113 HEK-293T C1202(1.09)  LDD1587  [7]
 LDCM0384  CL114 HEK-293T C1202(1.00)  LDD1588  [7]
 LDCM0387  CL117 HEK-293T C1202(1.09)  LDD1591  [7]
 LDCM0388  CL118 HEK-293T C1202(1.02)  LDD1592  [7]
 LDCM0392  CL121 HEK-293T C1202(1.06)  LDD1596  [7]
 LDCM0393  CL122 HEK-293T C1202(0.92)  LDD1597  [7]
 LDCM0396  CL125 HEK-293T C1202(1.04)  LDD1600  [7]
 LDCM0397  CL126 HEK-293T C1202(0.83)  LDD1601  [7]
 LDCM0400  CL13 HEK-293T C1202(1.10)  LDD1604  [7]
 LDCM0401  CL14 HEK-293T C1202(0.94)  LDD1605  [7]
 LDCM0405  CL18 HEK-293T C1202(1.08)  LDD1609  [7]
 LDCM0407  CL2 HEK-293T C1202(0.94)  LDD1611  [7]
 LDCM0413  CL25 HEK-293T C1202(0.89)  LDD1617  [7]
 LDCM0414  CL26 HEK-293T C1202(0.90)  LDD1618  [7]
 LDCM0419  CL30 HEK-293T C1202(0.96)  LDD1623  [7]
 LDCM0426  CL37 HEK-293T C1202(0.96)  LDD1630  [7]
 LDCM0432  CL42 HEK-293T C1202(1.04)  LDD1636  [7]
 LDCM0439  CL49 HEK-293T C1202(1.02)  LDD1643  [7]
 LDCM0441  CL50 HEK-293T C1202(0.96)  LDD1645  [7]
 LDCM0445  CL54 HEK-293T C1202(1.29)  LDD1648  [7]
 LDCM0451  CL6 HEK-293T C1202(1.23)  LDD1654  [7]
 LDCM0453  CL61 HEK-293T C1202(1.18)  LDD1656  [7]
 LDCM0454  CL62 HEK-293T C1202(0.94)  LDD1657  [7]
 LDCM0458  CL66 HEK-293T C1202(1.05)  LDD1661  [7]
 LDCM0466  CL73 HEK-293T C1202(0.96)  LDD1669  [7]
 LDCM0467  CL74 HEK-293T C1202(0.95)  LDD1670  [7]
 LDCM0471  CL78 HEK-293T C1202(1.05)  LDD1674  [7]
 LDCM0479  CL85 HEK-293T C1202(0.94)  LDD1682  [7]
 LDCM0480  CL86 HEK-293T C1202(1.07)  LDD1683  [7]
 LDCM0485  CL90 HEK-293T C1202(1.34)  LDD1688  [7]
 LDCM0492  CL97 HEK-293T C1202(1.00)  LDD1695  [7]
 LDCM0493  CL98 HEK-293T C1202(1.01)  LDD1696  [7]
 LDCM0634  CY-0357 Hep-G2 C197(0.25)  LDD2228  [6]
 LDCM0625  F8 Ramos C932(0.52); C2091(1.35); C685(0.96); C939(0.80)  LDD2187  [8]
 LDCM0572  Fragment10 Ramos C932(1.14); C2091(2.16); C685(0.44); C939(2.02)  LDD2189  [8]
 LDCM0573  Fragment11 Ramos C932(5.15); C2091(5.85); C685(3.97); C939(2.53)  LDD2190  [8]
 LDCM0574  Fragment12 Ramos C932(0.73); C2091(0.82); C685(0.47); C939(1.26)  LDD2191  [8]
 LDCM0575  Fragment13 Ramos C932(0.66); C2091(0.83); C685(1.13); C939(1.16)  LDD2192  [8]
 LDCM0576  Fragment14 Ramos C932(1.06); C2091(1.50); C685(0.84); C939(0.41)  LDD2193  [8]
 LDCM0579  Fragment20 Ramos C932(0.89); C2091(0.85); C685(0.35); C939(1.06)  LDD2194  [8]
 LDCM0580  Fragment21 Ramos C932(0.78); C2091(0.88); C685(0.84); C939(0.93)  LDD2195  [8]
 LDCM0582  Fragment23 Ramos C932(0.69); C2091(0.86); C685(0.83); C939(1.43)  LDD2196  [8]
 LDCM0578  Fragment27 Ramos C932(0.84); C2091(0.82); C685(1.13); C939(1.13)  LDD2197  [8]
 LDCM0586  Fragment28 Ramos C932(0.71); C2091(0.95); C685(0.86); C939(0.80)  LDD2198  [8]
 LDCM0588  Fragment30 Ramos C932(1.05); C2091(1.26); C685(0.90); C939(1.80)  LDD2199  [8]
 LDCM0589  Fragment31 Ramos C932(0.79); C2091(0.90); C685(1.03); C939(1.24)  LDD2200  [8]
 LDCM0590  Fragment32 Ramos C932(1.39); C2091(1.44); C685(0.45); C939(1.54)  LDD2201  [8]
 LDCM0468  Fragment33 Ramos C932(1.00); C2091(1.10); C685(0.75); C939(1.80)  LDD2202  [8]
 LDCM0596  Fragment38 Ramos C932(0.80); C2091(0.92); C685(0.68); C939(1.46)  LDD2203  [8]
 LDCM0566  Fragment4 Ramos C932(0.54); C2091(0.96); C685(0.63); C939(0.98)  LDD2184  [8]
 LDCM0427  Fragment51 HEK-293T C1202(0.94)  LDD1631  [7]
 LDCM0610  Fragment52 Ramos C932(1.02); C2091(1.12); C685(1.37); C939(1.99)  LDD2204  [8]
 LDCM0614  Fragment56 Ramos C932(1.40); C2091(1.65); C685(1.45); C939(1.85)  LDD2205  [8]
 LDCM0569  Fragment7 Ramos C932(0.46); C2091(1.37); C685(0.47); C939(1.38)  LDD2186  [8]
 LDCM0571  Fragment9 Ramos C932(0.83); C2091(1.31); C685(0.40); C939(1.73)  LDD2188  [8]
 LDCM0022  KB02 T cell C143(5.07)  LDD1703  [9]
 LDCM0023  KB03 Ramos C932(0.43); C2091(0.90); C685(0.58); C939(1.19)  LDD2183  [8]
 LDCM0024  KB05 MEWO C197(1.41); C685(1.27)  LDD3319  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Exosome complex component RRP46 (EXOSC5) RNase PH family Q9NQT4
E3 ubiquitin-protein ligase FANCL (FANCL) . Q9NW38
F-box/LRR-repeat protein 12 (FBXL12) . Q9NXK8
Transcription factor
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Homeobox protein MOX-2 (MEOX2) . P50222
Zinc finger protein 581 (ZNF581) . Q9P0T4
Other
Click To Hide/Show 17 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Bystin (BYSL) Bystin family Q13895
Conserved oligomeric Golgi complex subunit 6 (COG6) COG6 family Q9Y2V7
Protein FAM124A (FAM124A) FAM124 family Q86V42
Protein FAM161A (FAM161A) FAM161 family Q3B820
Hemoglobin subunit zeta (HBZ) Globin family P02008
Keratin, type I cytoskeletal 40 (KRT40) Intermediate filament family Q6A162
Mediator of RNA polymerase II transcription subunit 30 (MED30) Mediator complex subunit 30 family Q96HR3
Charged multivesicular body protein 2a (CHMP2A) SNF7 family O43633
Calcium-regulated heat-stable protein 1 (CARHSP1) . Q9Y2V2
DISP complex protein LRCH3 (LRCH3) . Q96II8
Heat shock factor 2-binding protein (HSF2BP) . O75031
Leucine-rich repeat and calponin homology domain-containing protein 1 (LRCH1) . Q9Y2L9
Leucine-rich repeat and calponin homology domain-containing protein 2 (LRCH2) . Q5VUJ6
Leucine-rich repeat and calponin homology domain-containing protein 4 (LRCH4) . O75427
Myeloid differentiation primary response protein MyD88 (MYD88) . Q99836
Protein PIMREG (PIMREG) . Q9BSJ6
Receptor-transporting protein 5 (RTP5) . Q14D33

References

1 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
2 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
3 Cyclopropenone, Cyclopropeniminium Ion, and Cyclopropenethione as Novel Electrophilic Warheads for Potential Target Discovery of Triple-Negative Breast Cancer. J Med Chem. 2023 Feb 23;66(4):2851-2864. doi: 10.1021/acs.jmedchem.2c01889. Epub 2023 Feb 10.
4 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
5 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
6 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
7 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
8 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578
9 An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell. 2020 Aug 20;182(4):1009-1026.e29. doi: 10.1016/j.cell.2020.07.001. Epub 2020 Jul 29.