Details of the Target

General Information of Target

Target ID LDTP03372
Target Name NKG2-D type II integral membrane protein (KLRK1)
Gene Name KLRK1
Gene ID 100528032
Synonyms
D12S2489E; NKG2D; NKG2-D type II integral membrane protein; Killer cell lectin-like receptor subfamily K member 1; NK cell receptor D; NKG2-D-activating NK receptor; CD antigen CD314
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGWIRGRRSRHSWEMSEFHNYNLDLKKSDFSTRWQKQRCPVVKSKCRENASPFFFCCFIA
VAMGIRFIIMVTIWSAVFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNW
YESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLT
IIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV
Target Type
Clinical trial
Target Bioclass
Transporter and channel
Subcellular location
Cell membrane
Function
Functions as an activating and costimulatory receptor involved in immunosurveillance upon binding to various cellular stress-inducible ligands displayed at the surface of autologous tumor cells and virus-infected cells. Provides both stimulatory and costimulatory innate immune responses on activated killer (NK) cells, leading to cytotoxic activity. Acts as a costimulatory receptor for T-cell receptor (TCR) in CD8(+) T-cell-mediated adaptive immune responses by amplifying T-cell activation. Stimulates perforin-mediated elimination of ligand-expressing tumor cells. Signaling involves calcium influx, culminating in the expression of TNF-alpha. Participates in NK cell-mediated bone marrow graft rejection. May play a regulatory role in differentiation and survival of NK cells. Binds to ligands belonging to various subfamilies of MHC class I-related glycoproteins including MICA, MICB, RAET1E, RAET1G, RAET1L/ULBP6, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4.
TTD ID
T35289
Uniprot ID
P26718
DrugMap ID
TTLRN4A
Ensemble ID
ENST00000240618.11
HGNC ID
HGNC:18788

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
22RV1 SNV: p.Y95F .
CCK81 SNV: p.W34Ter .
HCT15 SNV: p.V158E .
IGROV1 SNV: p.P206L .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
IA-alkyne
 Probe Info  		C39(9.14)  LDD1703  [1]
IPIAA_H
 Probe Info  		N.A.  LDD0030  [2]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 T cell C39(9.14)  LDD1703  [1]
 LDCM0024  KB05 T cell C39(12.27)  LDD1705  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Immunoglobulin
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
MHC class I polypeptide-related sequence A (MICA) MHC class I family Q29983
Other
Click To Hide/Show 6 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Retinoic acid early transcript 1E (RAET1E) MHC class I family Q8TD07
UL-16 binding protein 5 (RAET1G) MHC class I family Q6H3X3
UL16-binding protein 1 (ULBP1) MHC class I family Q9BZM6
UL16-binding protein 2 (ULBP2) MHC class I family Q9BZM5
UL16-binding protein 3 (ULBP3) MHC class I family Q9BZM4
UL16-binding protein 6 (RAET1L) MHC class I family Q5VY80

The Drug(s) Related To This Target

Phase 2
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Nn8555 . D06JUE
Phase 1
Click To Hide/Show 4 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Cm-cs1 T-cell CAR T Cell Therapy D0NC9M
Cyad-101 CAR T Cell Therapy D0FB4W
Nkr-2 Car-t Cells CAR T Cell Therapy D08YHE
Nkr-2 Cells CAR T Cell Therapy D0QR2K

References

1 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.
2 SP3-Enabled Rapid and High Coverage Chemoproteomic Identification of Cell-State-Dependent Redox-Sensitive Cysteines. Mol Cell Proteomics. 2022 Apr;21(4):100218. doi: 10.1016/j.mcpro.2022.100218. Epub 2022 Feb 25.
Mass spectrometry data entry: PXD029500 , PXD031647