General Information of Target

Target ID LDTP04678
Target Name Nck-associated protein 1-like (NCKAP1L)
Gene Name NCKAP1L
Gene ID 3071
Synonyms
HEM1; Nck-associated protein 1-like; Hematopoietic protein 1; Membrane-associated protein HEM-1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSLTSAYQHKLAEKLTILNDRGQGVLIRMYNIKKTCSDPKSKPPFLLEKSMEPSLKYINK
KFPNIDVRNSTQHLGPVHREKAEIIRFLTNYYQSFVDVMEFRDHVYELLNTIDACQCHFD
INLNFDFTRSYLDLIVTYTSVILLLSRIEDRRILIGMYNCAHEMLHGHGDPSFARLGQMV
LEYDHPLKKLTEEFGPHTKAVSGALLSLHFLFVRRNQGAEQWRSAQLLSLISNPPAMINP
ANSDTMACEYLSVEVMERWIIIGFLLCHGCLNSNSQCQKLWKLCLQGSLYITLIREDVLQ
VHKVTEDLFSSLKGYGKRVADIKESKEHVIANSGQFHCQRRQFLRMAVKELETVLADEPG
LLGPKALFAFMALSFIRDEVTWLVRHTENVTKTKTPEDYADSSIAELLFLLEGIRSLVRR
HIKVIQQYHLQYLARFDALVLSDIIQNLSVCPEEESIIMSSFVSILSSLNLKQVDNGEKF
EFSGLRLDWFRLQAYTSVAKAPLHLHENPDLAKVMNLIVFHSRMLDSVEKLLVETSDLST
FCFHLRIFEKMFAMTLEESAMLRYAIAFPLICAHFVHCTHEMCPEEYPHLKNHGLHHCNS
FLEELAKQTSNCVLEICAEQRNLSEQLLPKHCATTISKAKNKKTRKQRQTPRKGEPERDK
PGAESHRKNRSIVTNMDKLHLNLTELALTMNHVYSFSVFEHTIFPSEYLSSHLEARLNRA
IVWLAGYNATTQEIVRPSELLAGVKAYIGFIQSLAQFLGADASRVIRNALLQQTQPLDSC
GEQTITTLYTNWYLESLLRQASSGTIILSPAMQAFVSLPREGEQNFSAEEFSDISEMRAL
AELLGPYGMKFLSENLMWHVTSQIVELKKLVVENMDILVQIRSNFSKPDLMASLLPQLTG
AENVLKRMTIIGVILSFRAMAQEGLREVFSSHCPFLMGPIECLKEFVTPDTDIKVTLSIF
ELASAAGVGCDIDPALVAAIANLKADTSSPEEEYKVACLLLIFLAVSLPLLATDPSSFYS
IEKDGYNNNIHCLTKAIIQVSAALFTLYNKNIETHLKEFLVVASVSLLQLGQETDKLKTR
NRESISLLMRLVVEESSFLTLDMLESCFPYVLLRNAYREVSRAFHLN
Target Bioclass
Other
Family
HEM-1/HEM-2 family
Subcellular location
Cell membrane
Function
Essential hematopoietic-specific regulator of the actin cytoskeleton (Probable). Controls lymphocyte development, activation, proliferation and homeostasis, erythrocyte membrane stability, as well as phagocytosis and migration by neutrophils and macrophages. Component of the WAVE2 complex which signals downstream of RAC to stimulate F-actin polymerization. Required for stabilization and/or translation of the WAVE2 complex proteins in hematopoietic cells. Within the WAVE2 complex, enables the cortical actin network to restrain excessive degranulation and granule release by T-cells. Required for efficient T-lymphocyte and neutrophil migration. Exhibits complex cycles of activation and inhibition to generate waves of propagating the assembly with actin. Also involved in mechanisms WAVE-independent to regulate myosin and actin polymerization during neutrophil chemotaxis. In T-cells, required for proper mechanistic target of rapamycin complex 2 (mTORC2)-dependent AKT phosphorylation, cell proliferation and cytokine secretion, including that of IL2 and TNF.
Uniprot ID
P55160
Ensemble ID
ENST00000293373.11
HGNC ID
HGNC:4862

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
A549 SNV: p.E961Ter .
COLO792 SNV: p.L1077F .
CORL88 SNV: p.F490I .
HCC15 SNV: p.V816L .
HT115 SNV: p.R907H; p.K1078T .
MCC13 SNV: p.S697F .
MDAMB468 SNV: p.R377H .
MELJUSO SNV: p.P63S .
MEWO Substitution: p.R28C .
NCIH196 SNV: p.H680Q .
OCIAML2 SNV: p.R214Q DBIA    Probe Info 
RKO SNV: p.R21H .
SKMEL28 SNV: p.R214Q; p.H337Y .
WM793 SNV: p.R621Q .

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
DBIA
 Probe Info 
C982(6.43); C338(3.52)  LDD3333  [1]
4-Iodoacetamidophenylacetylene
 Probe Info 
C338(0.00); C632(0.00); C780(0.00); C160(0.00)  LDD0038  [2]
IA-alkyne
 Probe Info 
C338(0.00); C160(0.00); C542(0.00); C598(0.00)  LDD0036  [2]
Lodoacetamide azide
 Probe Info 
C1032(0.00); C780(0.00); C970(0.00); C338(0.00)  LDD0037  [2]
Compound 10
 Probe Info 
N.A.  LDD2216  [3]
Compound 11
 Probe Info 
N.A.  LDD2213  [3]
PAL-AfBPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
VE-P
 Probe Info 
N.A.  LDD0396  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0625  F8 Ramos C338(2.44)  LDD2187  [5]
 LDCM0572  Fragment10 Ramos C338(1.22)  LDD2189  [5]
 LDCM0573  Fragment11 Ramos C338(0.33)  LDD2190  [5]
 LDCM0574  Fragment12 Ramos C338(0.74)  LDD2191  [5]
 LDCM0575  Fragment13 Ramos C338(1.02)  LDD2192  [5]
 LDCM0576  Fragment14 Ramos C338(0.89)  LDD2193  [5]
 LDCM0579  Fragment20 Ramos C338(0.75)  LDD2194  [5]
 LDCM0580  Fragment21 Ramos C338(0.73)  LDD2195  [5]
 LDCM0582  Fragment23 Ramos C338(1.24)  LDD2196  [5]
 LDCM0578  Fragment27 Ramos C338(1.94)  LDD2197  [5]
 LDCM0586  Fragment28 Ramos C338(0.74)  LDD2198  [5]
 LDCM0588  Fragment30 Ramos C338(1.21)  LDD2199  [5]
 LDCM0589  Fragment31 Ramos C338(0.90)  LDD2200  [5]
 LDCM0590  Fragment32 Ramos C338(1.25)  LDD2201  [5]
 LDCM0468  Fragment33 Ramos C338(1.42)  LDD2202  [5]
 LDCM0596  Fragment38 Ramos C338(2.17)  LDD2203  [5]
 LDCM0566  Fragment4 Ramos C338(0.92)  LDD2184  [5]
 LDCM0610  Fragment52 Ramos C338(1.43)  LDD2204  [5]
 LDCM0614  Fragment56 Ramos C338(1.02)  LDD2205  [5]
 LDCM0569  Fragment7 Ramos C338(5.42)  LDD2186  [5]
 LDCM0571  Fragment9 Ramos C338(0.54)  LDD2188  [5]
 LDCM0022  KB02 Ramos C338(3.83)  LDD2182  [5]
 LDCM0023  KB03 Ramos C338(0.94)  LDD2183  [5]
 LDCM0024  KB05 MOLM-13 C982(6.43); C338(3.52)  LDD3333  [1]
 LDCM0131  RA190 MM1.R C942(1.09)  LDD0304  [6]

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 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 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
4 Pharmacological Targeting of Vacuolar H(+)-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer. Cell Chem Biol. 2020 Nov 19;27(11):1359-1370.e8. doi: 10.1016/j.chembiol.2020.06.011. Epub 2020 Jul 9.
5 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
6 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.