Details of the Target

General Information of Target

Target ID LDTP09509
Target Name Rap guanine nucleotide exchange factor 6 (RAPGEF6)
Gene Name RAPGEF6
Gene ID 51735
Synonyms
PDZGEF2; Rap guanine nucleotide exchange factor 6; PDZ domain-containing guanine nucleotide exchange factor 2; PDZ-GEF2; RA-GEF-2
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MNSPVDPGARQALRKKPPERTPEDLNTIYSYLHGMEILSNLREHQLRLMSARARYERYSG
NQVLFCSETIARCWYILLSGSVLVKGSMVLPPCSFGKQFGGKRGCDCLVLEPSEMIVVEN
AKDNEDSILQREIPARQSRRRFRKINYKGERQTITDDVEVNSYLSLPADLTKMHLTENPH
PQVTHVSSSQSGCSIASDSGSSSLSDIYQATESEVGDVDLTRLPEGPVDSEDDEEEDEEI
DRTDPLQGRDLVRECLEKEPADKTDDDIEQLLEFMHQLPAFANMTMSVRRELCSVMIFEV
VEQAGAIILEDGQELDSWYVILNGTVEISHPDGKVENLFMGNSFGITPTLDKQYMHGIVR
TKVDDCQFVCIAQQDYWRILNHVEKNTHKVEEEGEIVMVHEHRELDRSGTRKGHIVIKAT
PERLIMHLIEEHSIVDPTYIEDFLLTYRTFLESPLDVGIKLLEWFKIDSLRDKVTRIVLL
WVNNHFNDFEGDPAMTRFLEEFEKNLEDTKMNGHLRLLNIACAAKAKWRQVVLQKASRES
PLQFSLNGGSEKGFGIFVEGVEPGSKAADSGLKRGDQIMEVNGQNFENITFMKAVEILRN
NTHLALTVKTNIFVFKELLFRTEQEKSGVPHIPKIAEKKSNRHSIQHVPGDIEQTSQEKG
SKKVKANTVSGGRNKIRKILDKTRFSILPPKLFSDGGLSQSQDDSIVGTRHCRHSLAIMP
IPGTLSSSSPDLLQPTTSMLDFSNPSDIPDQVIRVFKVDQQSCYIIISKDTTAKEVVFHA
VHEFGLTGASDTYSLCEVSVTPEGVIKQRRLPDQFSKLADRIQLNGRYYLKNNMETETLC
SDEDAQELVKESQLSMLQLSTIEVATQLSMRDFDLFRNIEPTEYIDDLFKLNSKTGNTHL
KRFEDIVNQETFWVASEILTEANQLKRMKIIKHFIKIALHCRECKNFNSMFAIISGLNLA
SVARLRGTWEKLPSKYEKHLQDLQDIFDPSRNMAKYRNILSSQSMQPPIIPLFPVVKKDM
TFLHEGNDSKVDGLVNFEKLRMISKEIRQVVRMTSANMDPAMMFRQRSLSQGSTNSNMLD
VQGGAHKKRARRSSLLNAKKLYEDAQMARKVKQYLSSLDVETDEEKFQMMSLQWEPAYGT
LTKNLSEKRSAKSSEMSPVPMRSAGQTTKAHLHQPHRVSQVLQVPAVNLHPIRKKGQTKD
PALNTSLPQKVLGTTEEISGKKHTEDTISVASSLHSSPPASPQGSPHKGYTLIPSAKSDN
LSDSSHSEISSRSSIVSNCSVDSMSAALQDERCSSQALAVPESTGALEKTEHASGIGDHS
QHGPGWTLLKPSLIKCLAVSSSVSNEEISQEHIIIEAADSGRGSWTSCSSSSHDNFQSLP
NPKSWDFLNSYRHTHLDDPIAEVEPTDSEPYSCSKSCSRTCGQCKGSLERKSWTSSSSLS
DTYEPNYGTVKQRVLESTPAESSEGLDPKDATDPVYKTVTSSTEKGLIVYCVTSPKKDDR
YREPPPTPPGYLGISLADLKEGPHTHLKPPDYSVAVQRSKMMHNSLSRLPPASLSSNLVA
CVPSKIVTQPQRHNLQPFHPKLGDVTDADSEADENEQVSAV
Target Bioclass
Other
Subcellular location
Cytoplasm
Function Guanine nucleotide exchange factor (GEF) for Rap1A, Rap2A and M-Ras GTPases. Does not interact with cAMP.
Uniprot ID
Q8TEU7
Ensemble ID
ENST00000296859.10
HGNC ID
HGNC:20655

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CHL1 SNV: p.Y439F .
EFO27 SNV: p.R538H .
HT115 SNV: p.V805A .
IGR37 SNV: p.V707L DBIA    Probe Info 
IGR39 SNV: p.V707L DBIA    Probe Info 
IM95 SNV: p.H714Y DBIA    Probe Info 
MCC13 SNV: p.A717T .
NALM6 SNV: p.A282V .
NCIH1993 SNV: p.G1486C .
NCIH2286 SNV: p.S1267I .
NCIH2291 SNV: p.Y1138C DBIA    Probe Info 
OVCAR8 SNV: p.T1205A .
RL SNV: p.D820A .
YSCCC SNV: p.Q1071P .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 18 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info  		15.00  LDD0402  [1]
STPyne
 Probe Info  		K682(0.94)  LDD0277  [2]
BTD
 Probe Info  		C941(2.60)  LDD2093  [3]
AHL-Pu-1
 Probe Info  		C1293(17.21)  LDD0169  [4]
EA-probe
 Probe Info  		N.A.  LDD0440  [5]
DBIA
 Probe Info  		C93(4.05)  LDD0209  [6]
IPM
 Probe Info  		C522(2.72); C941(0.74)  LDD1702  [3]
IA-alkyne
 Probe Info  		C522(0.00); C255(0.00)  LDD0036  [7]
Lodoacetamide azide
 Probe Info  		C1293(0.00); C255(0.00); C522(0.00); C93(0.00)  LDD0037  [7]
NAIA_4
 Probe Info  		C1293(0.00); C1368(0.00); C1413(0.00)  LDD2226  [8]
NAIA_5
 Probe Info  		N.A.  LDD2224  [8]
TFBX
 Probe Info  		N.A.  LDD0027  [9]
Compound 10
 Probe Info  		N.A.  LDD2216  [10]
Compound 11
 Probe Info  		N.A.  LDD2213  [10]
VSF
 Probe Info  		N.A.  LDD0007  [11]
Phosphinate-6
 Probe Info  		N.A.  LDD0018  [12]
Methacrolein
 Probe Info  		N.A.  LDD0218  [13]
AOyne
 Probe Info  		15.00  LDD0443  [14]
PAL-AfBPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C046
 Probe Info  		12.13  LDD1745  [15]
C064
 Probe Info  		8.57  LDD1761  [15]
C347
 Probe Info  		8.75  LDD2008  [15]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0026  4SU-RNA+native RNA HEK-293T C1293(17.21)  LDD0169  [4]
 LDCM0156  Aniline NCI-H1299 11.48  LDD0403  [1]
 LDCM0632  CL-Sc Hep-G2 C522(20.00); C1491(0.46)  LDD2227  [8]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C522(2.72); C941(0.74)  LDD1702  [3]
 LDCM0175  Ethacrynic acid HeLa N.A.  LDD0440  [5]
 LDCM0625  F8 Ramos C1561(1.01); C93(1.35); C1293(1.50)  LDD2187  [16]
 LDCM0572  Fragment10 Ramos C1561(0.92); C1293(1.17); C1368(1.54)  LDD2189  [16]
 LDCM0573  Fragment11 Ramos C1561(4.47); C93(0.39); C1293(0.99); C1368(20.00)  LDD2190  [16]
 LDCM0574  Fragment12 Ramos C1561(1.07); C93(0.79); C1293(0.94); C1368(3.14)  LDD2191  [16]
 LDCM0575  Fragment13 Ramos C1561(0.88); C93(1.09); C1293(1.25); C1368(0.89)  LDD2192  [16]
 LDCM0576  Fragment14 Ramos C1561(0.85); C1491(1.04); C93(0.52); C1293(0.94)  LDD2193  [16]
 LDCM0579  Fragment20 Ramos C1561(0.90); C93(1.61); C1293(0.64); C1368(3.68)  LDD2194  [16]
 LDCM0580  Fragment21 Ramos C1561(0.81); C1491(0.83); C93(0.60); C1293(1.11)  LDD2195  [16]
 LDCM0582  Fragment23 Ramos C1561(1.31); C93(0.66); C1293(1.61); C1368(3.28)  LDD2196  [16]
 LDCM0578  Fragment27 Ramos C1561(0.91); C1491(0.94); C93(0.78); C1293(1.28)  LDD2197  [16]
 LDCM0586  Fragment28 Ramos C1561(0.97); C93(0.44); C1293(0.65); C1368(1.02)  LDD2198  [16]
 LDCM0588  Fragment30 Ramos C1561(0.88); C1491(0.61); C93(1.22); C1293(0.82)  LDD2199  [16]
 LDCM0589  Fragment31 Ramos C1561(1.00); C1491(0.90); C93(0.82); C1293(0.75)  LDD2200  [16]
 LDCM0590  Fragment32 Ramos C1561(0.60); C93(3.00); C1293(0.98)  LDD2201  [16]
 LDCM0468  Fragment33 Ramos C1561(0.80); C1491(0.52); C93(0.76); C1293(0.85)  LDD2202  [16]
 LDCM0596  Fragment38 Ramos C1561(0.86); C93(0.54); C1293(0.71); C1368(1.02)  LDD2203  [16]
 LDCM0566  Fragment4 Ramos C1561(1.73); C93(1.11); C1293(1.11)  LDD2184  [16]
 LDCM0610  Fragment52 Ramos C1561(1.05); C93(1.46); C1293(1.35); C1368(1.06)  LDD2204  [16]
 LDCM0614  Fragment56 Ramos C1561(1.24); C93(1.77); C1293(1.92); C1368(1.19)  LDD2205  [16]
 LDCM0569  Fragment7 Ramos C1561(1.30); C93(1.40); C1293(0.80); C1368(1.03)  LDD2186  [16]
 LDCM0571  Fragment9 Ramos C1561(1.14); C1293(1.04); C1368(1.29)  LDD2188  [16]
 LDCM0022  KB02 HEK-293T C1413(0.94); C93(0.83); C522(0.97); C1561(1.01)  LDD1492  [17]
 LDCM0023  KB03 Jurkat C93(4.05)  LDD0209  [6]
 LDCM0024  KB05 HMCB C522(5.99)  LDD3312  [18]
 LDCM0500  Nucleophilic fragment 13a MDA-MB-231 C941(2.60)  LDD2093  [3]

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
Tyrosine-protein phosphatase non-receptor type 13 (PTPN13) Protein-tyrosine phosphatase family Q12923
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Transcriptional coactivator YAP1 (YAP1) YAP1 family P46937

References

1 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
2 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
3 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
4 Chemoproteomic capture of RNA binding activity in living cells. Nat Commun. 2023 Oct 7;14(1):6282. doi: 10.1038/s41467-023-41844-z.
Mass spectrometry data entry: PXD044625
5 Chemoproteomic Profiling Reveals Ethacrynic Acid Targets Adenine Nucleotide Translocases to Impair Mitochondrial Function. Mol Pharm. 2018 Jun 4;15(6):2413-2422. doi: 10.1021/acs.molpharmaceut.8b00250. Epub 2018 May 15.
6 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.
7 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
8 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
9 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
10 Multiplexed CuAAC Suzuki-Miyaura Labeling for Tandem Activity-Based Chemoproteomic Profiling. Anal Chem. 2021 Feb 2;93(4):2610-2618. doi: 10.1021/acs.analchem.0c04726. Epub 2021 Jan 20.
Mass spectrometry data entry: PXD022279
11 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
12 DFT-Guided Discovery of Ethynyl-Triazolyl-Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling. Angew Chem Int Ed Engl. 2022 Oct 10;61(41):e202205348. doi: 10.1002/anie.202205348. Epub 2022 Aug 22.
Mass spectrometry data entry: PXD033004
13 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
14 Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.
15 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
16 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
17 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
18 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