Details of the Target

General Information of Target

Target ID LDTP07527
Target Name DENN domain-containing protein 1B (DENND1B)
Gene Name DENND1B
Gene ID 163486
Synonyms
C1orf218; FAM31B; DENN domain-containing protein 1B; Connecdenn 2; Protein FAM31B
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MDCRTKANPDRTFDLVLKVKCHASENEDPVVLWKFPEDFGDQEILQSVPKFCFPFDVERV
SQNQVGQHFTFVLTDIESKQRFGFCRLTSGGTICLCILSYLPWFEVYYKLLNTLADYLAK
ELENDLNETLRSLYNHPVPKANTPVNLSVNQEIFIACEQVLKDQPALVPHSYFIAPDVTG
LPTIPESRNLTEYFVAVDVNNMLQLYASMLHERRIVIISSKLSTLTACIHGSAALLYPMY
WQHIYIPVLPPHLLDYCCAPMPYLIGIHSSLIERVKNKSLEDVVMLNVDTNTLESPFSDL
NNLPSDVVSALKNKLKKQSTATGDGVARAFLRAQAALFGSYRDALRYKPGEPITFCEESF
VKHRSSVMKQFLETAINLQLFKQFIDGRLAKLNAGRGFSDVFEEEITSGGFCGGNPRSYQ
QWVHTVKKGGALFNTAMTKATPAVRTAYKFAKNHAKLGLKEVKSKLKHKENEEDYGTCSS
SVQYTPVYKLHNEKGGNSEKRKLAQARLKRPLKSLDGALYDDEDDDDIERASKLSSEDGE
EASAYLYESDDSVETRVKTPYSGEMDLLGEILDTLSTHSSDQGKLAAAKSLDFFRSMDDI
DYKPTNKSNAPSENNLAFLCGGSGDQAEWNLGQDDSALHGKHLPPSPRKRVSSSGLTDSL
FILKEENSNKHLGADNVSDPTSGLDFQLTSPEVSQTDKGKTEKRETLSQISDDLLIPGLG
RHSSTFVPWEKEGKEAKETSEDIGLLHEVVSLCHMTSDFQQSLNISDKNTNGNQT
Target Bioclass
Other
Subcellular location
Cytoplasm, cytosol
Function
Guanine nucleotide exchange factor (GEF) for RAB35 that acts as a regulator of T-cell receptor (TCR) internalization in TH2 cells. Acts by promoting the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form. Plays a role in clathrin-mediated endocytosis. Controls cytokine production in TH2 lymphocytes by controlling the rate of TCR internalization and routing to endosomes: acts by mediating clathrin-mediated endocytosis of TCR via its interaction with the adapter protein complex 2 (AP-2) and GEF activity. Dysregulation leads to impaired TCR down-modulation and recycling, affecting cytokine production in TH2 cells.
Uniprot ID
Q6P3S1
Ensemble ID
ENST00000235453.8
HGNC ID
HGNC:28404

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
COLO678 SNV: p.E404D .
HEC1 SNV: p.F71S; p.A227T .
HEC1B SNV: p.A227T .
HGC27 SNV: p.H491Q .
HT115 SNV: p.R214H .
LNCaP clone FGC SNV: p.L45I .
MCC13 SNV: p.P728L .
MDAMB231 SNV: p.N201S .
MFE319 SNV: p.D306E .
NB1 SNV: p.E294G .
OVISE SNV: p.H642Q .
OVK18 Insertion: p.S590EfsTer6 .
SKMEL2 SNV: p.V60A .
SUPT1 SNV: p.N287S .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C412(30.01); C52(45.20)  LDD0209  [1]
4-Iodoacetamidophenylacetylene
 Probe Info  		N.A.  LDD0038  [2]
IA-alkyne
 Probe Info  		N.A.  LDD0165  [3]
IPM
 Probe Info  		N.A.  LDD0005  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0215  AC10 HEK-293T C412(1.38); C356(1.05)  LDD1508  [5]
 LDCM0277  AC18 HEK-293T C412(0.80); C356(0.90)  LDD1516  [5]
 LDCM0279  AC2 HEK-293T C412(1.03); C356(1.01)  LDD1518  [5]
 LDCM0286  AC26 HEK-293T C412(1.12); C356(0.87)  LDD1525  [5]
 LDCM0295  AC34 HEK-293T C412(1.38); C356(1.17)  LDD1534  [5]
 LDCM0304  AC42 HEK-293T C412(0.83); C356(0.87)  LDD1543  [5]
 LDCM0313  AC50 HEK-293T C412(0.77); C356(1.09)  LDD1552  [5]
 LDCM0321  AC58 HEK-293T C412(1.05); C356(0.96)  LDD1560  [5]
 LDCM0367  CL1 HEK-293T C412(1.11)  LDD1571  [5]
 LDCM0370  CL101 HEK-293T C412(1.37)  LDD1574  [5]
 LDCM0371  CL102 HEK-293T C412(0.96); C356(1.01)  LDD1575  [5]
 LDCM0374  CL105 HEK-293T C412(1.14)  LDD1578  [5]
 LDCM0375  CL106 HEK-293T C412(1.01); C356(0.96)  LDD1579  [5]
 LDCM0378  CL109 HEK-293T C412(1.58)  LDD1582  [5]
 LDCM0380  CL110 HEK-293T C412(0.80); C356(1.03)  LDD1584  [5]
 LDCM0383  CL113 HEK-293T C412(1.28)  LDD1587  [5]
 LDCM0384  CL114 HEK-293T C412(1.03); C356(0.98)  LDD1588  [5]
 LDCM0387  CL117 HEK-293T C412(0.95)  LDD1591  [5]
 LDCM0388  CL118 HEK-293T C412(0.94); C356(1.04)  LDD1592  [5]
 LDCM0392  CL121 HEK-293T C412(1.96)  LDD1596  [5]
 LDCM0393  CL122 HEK-293T C412(0.85); C356(1.02)  LDD1597  [5]
 LDCM0396  CL125 HEK-293T C412(2.01)  LDD1600  [5]
 LDCM0397  CL126 HEK-293T C412(1.05); C356(1.03)  LDD1601  [5]
 LDCM0400  CL13 HEK-293T C412(1.60)  LDD1604  [5]
 LDCM0401  CL14 HEK-293T C412(1.06); C356(1.00)  LDD1605  [5]
 LDCM0405  CL18 HEK-293T C412(0.90); C356(1.01)  LDD1609  [5]
 LDCM0407  CL2 HEK-293T C412(1.07); C356(1.05)  LDD1611  [5]
 LDCM0413  CL25 HEK-293T C412(1.75)  LDD1617  [5]
 LDCM0414  CL26 HEK-293T C412(0.99); C356(1.08)  LDD1618  [5]
 LDCM0419  CL30 HEK-293T C412(0.96); C356(0.89)  LDD1623  [5]
 LDCM0426  CL37 HEK-293T C412(1.10)  LDD1630  [5]
 LDCM0432  CL42 HEK-293T C412(0.81); C356(1.00)  LDD1636  [5]
 LDCM0439  CL49 HEK-293T C412(1.10)  LDD1643  [5]
 LDCM0441  CL50 HEK-293T C412(1.12); C356(1.02)  LDD1645  [5]
 LDCM0445  CL54 HEK-293T C412(0.82); C356(1.04)  LDD1648  [5]
 LDCM0451  CL6 HEK-293T C412(0.88); C356(1.28)  LDD1654  [5]
 LDCM0453  CL61 HEK-293T C412(0.85)  LDD1656  [5]
 LDCM0454  CL62 HEK-293T C412(0.69); C356(1.08)  LDD1657  [5]
 LDCM0458  CL66 HEK-293T C412(0.74); C356(1.38)  LDD1661  [5]
 LDCM0466  CL73 HEK-293T C412(1.06)  LDD1669  [5]
 LDCM0467  CL74 HEK-293T C412(0.85); C356(0.94)  LDD1670  [5]
 LDCM0471  CL78 HEK-293T C412(1.00); C356(1.09)  LDD1674  [5]
 LDCM0479  CL85 HEK-293T C412(1.74)  LDD1682  [5]
 LDCM0480  CL86 HEK-293T C412(1.62); C356(0.95)  LDD1683  [5]
 LDCM0485  CL90 HEK-293T C412(0.90); C356(0.87)  LDD1688  [5]
 LDCM0492  CL97 HEK-293T C412(1.63)  LDD1695  [5]
 LDCM0493  CL98 HEK-293T C412(0.81); C356(0.97)  LDD1696  [5]
 LDCM0427  Fragment51 HEK-293T C412(0.92); C356(0.86)  LDD1631  [5]
 LDCM0022  KB02 T cell C356(5.20)  LDD1703  [6]
 LDCM0023  KB03 Jurkat C412(30.01); C52(45.20)  LDD0209  [1]
 LDCM0024  KB05 HMCB C65(1.35)  LDD3312  [7]
 LDCM0131  RA190 MM1.R C356(1.14)  LDD0304  [8]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
E3 ubiquitin-protein ligase LNX (LNX1) . Q8TBB1

References

1 Covalent Inhibition by a Natural Product-Inspired Latent Electrophile. J Am Chem Soc. 2023 May 24;145(20):11097-11109. doi: 10.1021/jacs.3c00598. Epub 2023 May 15.
2 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
3 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
4 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
5 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
6 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.
7 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
8 Physical and Functional Analysis of the Putative Rpn13 Inhibitor RA190. Cell Chem Biol. 2020 Nov 19;27(11):1371-1382.e6. doi: 10.1016/j.chembiol.2020.08.007. Epub 2020 Aug 27.