Affinage

KIR2DL3

Killer cell immunoglobulin-like receptor 2DL3 · UniProt P43628

Length
341 aa
Mass
37.9 kDa
Annotated
2026-04-28
100 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KIR2DL3 is an inhibitory natural killer cell receptor of the immunoglobulin superfamily that recognizes HLA-C group 1 (C1) allotypes in a peptide-sequence-dependent manner to suppress NK cell cytotoxicity (PMID:8340759, PMID:9126935). Ligand specificity is determined by position 44 in the first Ig-like domain, while positions 70, 71, and 131 govern binding avidity and cross-reactivity, and allosteric residues distal to the binding interface (positions 11, 16, 35, 148) modulate affinity by altering the interdomain hinge angle revealed by crystallography (PMID:9126959, PMID:22772445, PMID:10196125, PMID:18322206, PMID:23686481). KIR2DL3 delivers weaker inhibitory signals than the closely related KIR2DL2 and exhibits greater sensitivity to peptide content of HLA-C, a property exploited by viral sequence variants in HIV-1 and HCV that enhance KIR2DL3 engagement to evade NK cell responses (PMID:25359276, PMID:26575988, PMID:27057987). Inhibitory signaling is transmitted through the long cytoplasmic tail via association with CD3ζ chains and p56lck, and is context-dependent, as strong T cell activation can override KIR2DL3-mediated inhibition (PMID:7523145, PMID:10498612).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1993 High

    The fundamental question of whether p58/GL183 molecules function as NK inhibitory receptors recognizing HLA-C was answered: masking p58 restored lysis of HLA-C-protected targets, establishing KIR2DL3 as an HLA-C-specific inhibitory receptor.

    Evidence Antibody blocking/reconstitution cytotoxicity assays with HLA-C transfectants and multiple NK clones

    PMID:8340759

    Open questions at the time
    • Molecular identity and sequence of the receptor not yet determined
    • Signaling pathway downstream of receptor engagement unknown
    • Precise HLA-C allotype specificity not defined
  2. 1994 High

    How KIR2DL3 signals intracellularly was partially resolved: p58 associates with CD3ζ chains and p56lck, yet inhibition does not require downregulation of CD16-associated ζ-chain phosphorylation, revealing a signaling mechanism distinct from simple signal blockade.

    Evidence Co-immunoprecipitation, 2D diagonal gel electrophoresis, anti-phosphotyrosine immunoblotting

    PMID:7523145

    Open questions at the time
    • Role of ITIM-recruited phosphatases (SHP-1/SHP-2) not yet identified
    • Stoichiometry and dynamics of ζ-chain association unclear
    • Whether ζ-chain association is required for inhibitory function untested
  3. 1995 High

    Molecular cloning established KIR2DL3 as a member of the immunoglobulin superfamily with two extracellular Ig domains and a long cytoplasmic tail, and showed that inhibitory (p58) and activating (p50) KIR forms differ in cytoplasmic domain composition rather than glycosylation.

    Evidence cDNA cloning/sequencing, biochemical deglycosylation, 2D peptide mapping, calcium flux and cytotoxicity assays

    PMID:7650491 PMID:7749980

    Open questions at the time
    • Three-dimensional structure not yet determined
    • Structural basis for activating vs inhibitory signaling unknown
  4. 1995 High

    Coexpression of KIR2DL3 (GL183) and KIR2DL1 (EB6) on individual NK clones was shown to confer independent, additive inhibition against distinct HLA-C allotypes, and p70 (KIR3DL1) was demonstrated to be physically and functionally independent of p58, establishing that KIR receptors operate as non-redundant, independent modules.

    Evidence Co-immunoprecipitation, antibody blocking, cytotoxicity assays with HLA-C allele-specific transfectants

    PMID:7724594 PMID:8643653

    Open questions at the time
    • Whether KIR co-expression affects signaling thresholds quantitatively unknown
    • Integration of signals from multiple KIR at the synapse not addressed
  5. 1997 High

    The molecular determinants of HLA-C allotype specificity and binding affinity were identified: position 44 switches C1 vs C2 specificity, position 70 is critical for binding affinity, and KIR2DL3 binding to HLA-C is peptide-dependent with selectivity at peptide positions 7 and 8.

    Evidence Site-directed mutagenesis of KIR-Ig fusion proteins, direct binding assays to HLA-C transfectants and peptide-loaded TAP-deficient cells

    PMID:9126935 PMID:9126959 PMID:9464792

    Open questions at the time
    • Structural basis for peptide selectivity at positions 7-8 not resolved
    • Full spectrum of permissive vs non-permissive peptides unknown
  6. 1998 High

    Kinetic analysis showed KIR2DL3 (p58) binds HLA-Cw7 with rapid on/off rates while the activating p50 counterpart binds weakly or not at all, localizing the binding difference to extracellular domain features rather than solely cytoplasmic regions.

    Evidence Quantitative binding assays comparing p58 and p50 receptor variants with HLA-Cw7

    PMID:9826699

    Open questions at the time
    • Exact structural difference between p58 and p50 extracellular domains responsible for binding difference not pinpointed
  7. 1999 High

    The crystal structure of KIR2DL3 revealed an unusually acute 23° interdomain hinge angle distinct from KIR2DL1, with the HLA-C binding site spanning both domains at the elbow, providing a structural framework for how domain orientation tunes ligand recognition.

    Evidence X-ray crystallography of KIR2DL3 extracellular region

    PMID:10196125

    Open questions at the time
    • No co-crystal with HLA-C yet obtained
    • Dynamic hinge movements not characterized
    • How hinge angle relates to signaling strength not addressed
  8. 1999 Medium

    Transgenic expression in T cells showed KIR2DL3 inhibitory signaling is context-dependent: it inhibits MLR and anti-CD3-redirected killing but cannot override strong antigen-driven CTL activation.

    Evidence KIR2DL3 transgenic mouse model with functional cytotoxicity and MLR assays

    PMID:10498612

    Open questions at the time
    • Threshold of activation signal required to override KIR2DL3 inhibition not quantified
    • Relevance of mouse transgenic system to human NK cell biology uncertain
    • Signaling intermediates that are overridden not identified
  9. 2008 High

    The lower avidity of KIR2DL3 compared to KIR2DL2 was mapped to allosteric positions 16 and 148, distal to the ligand-binding interface, that synergistically modulate hinge angle and domain orientation rather than direct contact residues.

    Evidence Binding assays across 93 HLA isoforms combined with site-directed mutagenesis of recombinant KIR

    PMID:18322206

    Open questions at the time
    • Exact hinge angle changes induced by positions 16 and 148 not measured structurally
    • Whether these positions affect signaling dynamics beyond avidity unknown
  10. 2012 High

    Systematic mutagenesis comprehensively mapped functional residue contributions: position 70 dominates avidity, position 44 governs C1/C2 specificity, and positions 71/131 control cross-reactivity with HLA-A*11:02, establishing KIR2DL3 as a lower-avidity but broader-specificity receptor than KIR2DL1.

    Evidence Systematic point mutagenesis at six positions with binding to 95 HLA allotypes

    PMID:22772445

    Open questions at the time
    • Functional significance of HLA-A cross-reactivity in vivo unknown
    • Whether avidity/specificity tradeoff is physiologically adaptive not tested
  11. 2013 High

    The KIR2DL3*005 allele achieves KIR2DL2-like binding affinity through allosteric residues Arg11 and Glu35 that alter the hinge angle, demonstrating that natural polymorphism uses the same allosteric mechanism to tune inhibitory strength.

    Evidence Surface plasmon resonance, mutagenesis, molecular modeling, primary NK cell functional assays

    PMID:23686481

    Open questions at the time
    • Crystal structure of KIR2DL3*005 not obtained
    • Population-level functional consequences of this allele not established
  12. 2015 High

    Viral exploitation of peptide-dependent KIR2DL3 recognition was demonstrated: an HIV-1 Gag variant (T303V) selected in KIR2DL3+/HLA-C*03:04+ individuals enhances KIR2DL3 binding and suppresses NK activation, establishing peptide-mediated immune evasion.

    Evidence KIR2DL3-IgG fusion binding, primary NK cell functional assays, SPR, structural modeling, patient cohort data

    PMID:26575988

    Open questions at the time
    • Whether this escape mechanism operates during acute vs chronic infection unclear
    • Breadth of viral peptide variants exploiting this pathway not fully catalogued
  13. 2016 High

    HCV similarly exploits peptide-dependent KIR2DL3 modulation: an HCV core peptide bound to HLA-C*03:04 enhances KIR2DL3 binding and suppresses NK function, while genotype-specific sequence variation reduces inhibition, revealing convergent viral immune evasion across pathogens.

    Evidence KIR2DL3-IgG binding, HLA stabilization assay, primary NK cell functional assays

    PMID:27057987

    Open questions at the time
    • Structural basis for peptide-dependent enhancement at the co-crystal level not determined for HCV peptides
    • In vivo validation in HCV-infected patients not performed
  14. 2021 High

    Co-crystal structures of KIR2DL2 and KIR2DL3 with HLA-C*07:02 revealed distinct docking modalities between the two receptors, providing the structural basis for their differential recognition of C1 allotypes and explaining why KIR2DS2 influences KIR2DL2 vs KIR2DL3 functional outcomes.

    Evidence X-ray crystallography of KIR/HLA-C complexes with mutagenesis and primary NK cell assays

    PMID:33846289

    Open questions at the time
    • Structures with diverse peptides not obtained
    • How docking modality differences translate to signaling kinetics at the immune synapse not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how KIR2DL3 integrates inhibitory signaling at the immune synapse (role of ITIM-recruited phosphatases, signaling dynamics), the full repertoire of self and viral peptides that tune KIR2DL3 engagement, and how hinge-angle dynamics measured in solution relate to signaling strength in living NK cells.
  • ITIM/SHP-1/SHP-2 signaling mechanism not directly characterized for KIR2DL3
  • No comprehensive peptide-KIR2DL3-HLA-C structural survey exists
  • Biophysical measurements of hinge dynamics in membrane-embedded KIR lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 2
Partners
CD3ZHLA-CLCK

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 p58 (KIR2DL3/GL183) molecules function as NK cell receptors for HLA-C alleles; masking p58 with F(ab')2 antibody fragments restores lysis of HLA-C-protected target cells, demonstrating that p58 delivers an inhibitory signal upon HLA-C recognition. Antibody blocking/reconstitution assay, functional cytotoxicity assay with HLA-C transfectants The Journal of experimental medicine High 8340759
1995 KIR2DL3 (p58/GL183) and related p58 molecules are members of the immunoglobulin superfamily with diversity in both extracellular Ig-like domains and intracellular cytoplasmic domains; at least five distinct p58 receptors exist in a single individual with three types of transmembrane/cytoplasmic domains. Molecular cloning, cDNA sequence analysis Immunity High 7749980
1995 EB6 (KIR2DL1-related) molecules exist in both inhibitory p58 (~58 kD) and activatory p50 (~50 kD) forms; the molecular weight difference is not due to differential glycosylation but reflects distinct peptide compositions as shown by two-dimensional peptide mapping; cross-linking of p50 triggers cytolytic activity and Ca2+ flux, while p58 cross-linking inhibits lysis without Ca2+ increase. Biochemical deglycosylation, proteolytic peptide mapping, 2D peptide mapping, calcium flux assay, cytotoxicity assay The Journal of experimental medicine High 7650491
1994 p58 molecules associate in vivo with CD3 zeta chains (preferentially as zeta-zeta homodimers or zeta-gamma heterodimers) and with the p56lck kinase; mAb-mediated signaling via p58 enhances p58/p56lck association; however, p58-mediated inhibition of NK triggering is not accompanied by down-regulation of tyrosine phosphorylation of CD16-associated CD3 zeta chains. Co-immunoprecipitation, 2D diagonal gel electrophoresis, anti-phosphotyrosine immunoblotting, surface modulation experiments European journal of immunology High 7523145
1997 A single amino acid at position 44 of the first Ig domain of KIR2DL3 (lysine 44) determines specificity for HLA-Cw3-related alleles; swapping methionine 44 (in Cw4-specific KIR) with lysine 44 (in Cw3-specific KIR) is sufficient to switch HLA-C allotype specificity. Site-directed mutagenesis of KIR-Ig fusion proteins, direct binding assay to HLA-C transfectants Journal of immunology High 9126959
1997 Direct binding of soluble KIR2DL3 (cl42) to HLA-Cw4 on TAP-deficient RMA-S cells requires exogenous peptide loading and exhibits peptide selectivity; substitutions at positions 7 and 8 of the nonamer peptide QYDDAVYKL abolish KIR binding despite similar HLA-C surface expression. Direct binding assay of soluble KIR-Ig fusion protein to peptide-loaded TAP-deficient cells, NK cell inhibition assay The Journal of experimental medicine High 9126935
1997 Position 70 in the p58.1 (KIR2DL3-related) inhibitory receptor is a critical determinant of binding affinity for HLA-Cw4; substitution of threonine 70 by lysine in p58.1 almost abolishes HLA-C binding, while the reverse substitution in the activatory p50.1 (lysine→threonine) dramatically increases affinity. Soluble receptor-Fc fusion proteins, site-directed mutagenesis, binding assay to HLA-C transfectants European journal of immunology High 9464792
1998 Inhibitory p58 (NKAT2/KIR2DL3) binds HLA-Cw7 with rapid association and dissociation rates, while the highly homologous activating p50 receptors bind HLA-C only very weakly or not at all; the difference in HLA-C recognition capacity resides in the transmembrane/cytoplasmic tail differences between p58 and p50. Direct binding assay comparing p58 and p50 receptors to HLA-Cw7, kinetic analysis Proceedings of the National Academy of Sciences of the United States of America High 9826699
1999 Crystal structure of the extracellular region of KIR2DL3 reveals two tandem immunoglobulin-like domains with an unusually acute interdomain elbow angle of 23° different from the related receptor KIR2DL1; the putative HLA class I binding site spans both domains at the outer surface of the elbow, suggesting domain orientation modulates ligand binding. X-ray crystallography Structure High 10196125
1995 Coexpression of two functionally independent p58 inhibitory receptors (GL183 for Cw3-related alleles and EB6 for Cw4-related alleles) in individual NK clones results in inability to kill all normal allogeneic HLA-C+ targets; the two receptors function independently and can be co-immunoprecipitated from GL183+/EB6+ clones in digitonin. Co-immunoprecipitation, antibody blocking, cytotoxicity assay with HLA-C allele-specific transfectants Proceedings of the National Academy of Sciences of the United States of America High 7724594
2008 KIR2DL2 is a stronger receptor for HLA-C than KIR2DL3; the avidity difference maps to the Ig-like domains, specifically a synergistic combination of arginine for proline 16 in D1 and cysteine for arginine 148 in D2 (neither near the ligand-binding site); these substitutions likely alter the hinge angle between domains and change relative domain orientation. Binding assays to 93 HLA isoforms, site-directed mutagenesis of recombinant KIR, functional analysis Journal of immunology High 18322206
2012 Position 70 dominates avidity modulation of KIR2DL3 for HLA-C; position 44 modulates specificity for HLA-C allotype groups (C1 vs C2); positions 71 and 131 control cross-reactivity with HLA-A*11:02. KIR2DL3 has lower avidity and broader specificity than KIR2DL1 and can be mutated to increase avidity, while KIR2DL1 specificity is resistant to mutation. Systematic point mutagenesis at six positions, binding to 95 HLA allotypes Journal of immunology High 22772445
2013 KIR2DL3*005, a KIR2DL3 allele, has increased binding affinity and avidity for HLA-C comparable to KIR2DL2; site-directed mutagenesis showed that the combination of arginine at residue 11 and glutamic acid at residue 35 (distal to the KIR/HLA-C interface) is critical, likely by altering the interdomain hinge angle. Surface plasmon resonance, KIR binding to HLA allotype panel, site-directed mutagenesis, molecular modeling, NK cell functional assay Journal of immunology High 23686481
2021 Crystal structures of KIR2DL2 and KIR2DL3 in complex with HLA-C*07:02 reveal that KIR2DL2 and KIR2DL3 differ in docking modality over HLA-C*07:02; mutagenesis assays demonstrated differences in the mechanism of HLA-C1 allotype recognition by KIR2DL2 vs KIR2DL3; KIR2DS2 influences functional differences between KIR2DL2 and KIR2DL3 recognition. X-ray crystallography of KIR/HLA-C complexes, mutagenesis, primary NK cell functional assay Nature communications High 33846289
1999 Engagement of KIR2DL3 (transgenic) in T cells can inhibit mixed lymphocyte reaction and anti-CD3-redirected cytotoxicity; however, antigen- and anti-CD3-induced cytotoxicity by alloreactive CTLs cannot be inhibited by KIR2DL3 engagement, demonstrating that KIR2DL3 inhibitory signaling is context-dependent and varies with the activation state of T cells. KIR2DL3 transgenic mouse model, functional cytotoxicity assays, MLR assay Blood Medium 10498612
2015 A p24 Gag sequence variant (T303V) selected in HIV-1-infected individuals with KIR2DL3 and HLA-C*03:04 significantly enhances KIR2DL3 binding to HLA-C*03:04-expressing cells, resulting in reduced activation of primary KIR2DL3+ NK cells; structural modeling and surface plasmon resonance confirmed peptide-dependent modulation of KIR2DL3/HLA-C interaction as a viral immune escape mechanism. KIR2DL3-IgG fusion binding assay, primary NK cell functional assay, surface plasmon resonance, structural modeling PLoS medicine High 26575988
2016 A specific HCV core-derived peptide (YIPLVGAPL) bound to HLA-C*03:04 significantly enhances KIR2DL3 binding and suppresses primary KIR2DL3+ NK cell function; genotype-specific sequence variations in this peptide reduce KIR2DL3 binding and NK cell inhibition, demonstrating peptide-sequence-dependent regulation of KIR2DL3 inhibitory signaling. KIR2DL3-IgG fusion protein binding assay, HLA stabilization assay, primary NK cell functional assay Journal of hepatology High 27057987
2017 HLA-B*46:01, formed by mini-conversion introducing the C1 epitope from HLA-C*01:02 into HLA-B, has a low-diversity peptidome; 21% of its peptides (with common C-terminal characteristics) form ligands for KIR2DL3, establishing that peptide C-terminal features determine which HLA-B*46:01-peptide complexes engage KIR2DL3. High-resolution mass spectrometry peptidome analysis, KIR2DL3 binding assays Cell reports Medium 28514659
2014 KIR2DL3-positive NK cells are more sensitive to changes in peptide content of MHC class I than KIR2DL2-positive NK cells; weakly inhibitory peptide VAPWNSRAL discriminates KIR2DL3 from KIR2DL2 NK cell responses, suggesting KIR2DL3 has a finer peptide discrimination threshold than KIR2DL2. NK cell functional assay with defined peptides, mathematical modeling European journal of immunology Medium 25359276
2010 KIR2DL3 alleles KIR2DL3*005 and KIR2DL3*015 are not recognized by the anti-KIR2DL3-specific ECM41 mAb; site-directed mutagenesis demonstrated that glutamine at position 35 is required for ECM41 staining, and glutamic acid 35 and arginine 50 are relevant for EB6B/11PB6 mAb staining; KIR2DL3*005 HLA-C specificity is not different from other KIR2DL2/L3 alleles. Genotype/phenotype analysis, site-directed mutagenesis, functional HLA-C specificity testing Journal of immunology Medium 20525888
1996 p70 (Bw4-specific) and p58 (HLA-C-specific, including KIR2DL3-related) NK receptors are physically and functionally independent; co-immunoprecipitation and cross-modulation experiments demonstrate no physical association between p70 and p58, and antibody-mediated cross-linking of one does not affect the other. Co-immunoprecipitation, antibody cross-modulation, functional cytotoxicity assay Proceedings of the National Academy of Sciences of the United States of America Medium 8643653

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Molecular clones of the p58 NK cell receptor reveal immunoglobulin-related molecules with diversity in both the extra- and intracellular domains. Immunity 543 7749980
1993 P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities. The Journal of experimental medicine 514 8340759
1995 Existence of both inhibitory (p58) and activatory (p50) receptors for HLA-C molecules in human natural killer cells. The Journal of experimental medicine 423 7650491
2008 Synergistic polymorphism at two positions distal to the ligand-binding site makes KIR2DL2 a stronger receptor for HLA-C than KIR2DL3. Journal of immunology (Baltimore, Md. : 1950) 324 18322206
1996 The natural killer cell receptor specific for HLA-A allotypes: a novel member of the p58/p70 family of inhibitory receptors that is characterized by three immunoglobulin-like domains and is expressed as a 140-kD disulphide-linked dimer. The Journal of experimental medicine 314 8760804
1999 The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor are components of CNS synapses. The Journal of neuroscience : the official journal of the Society for Neuroscience 242 10460236
1995 Cytolytic T lymphocytes displaying natural killer (NK)-like activity: expression of NK-related functional receptors for HLA class I molecules (p58 and CD94) and inhibitory effect on the TCR-mediated target cell lysis or lymphokine production. International immunology 206 7547697
1992 Morphological analysis of protein transport from the ER to Golgi membranes in digitonin-permeabilized cells: role of the P58 containing compartment. The Journal of cell biology 205 1447290
1997 Role of amino acid position 70 in the binding affinity of p50.1 and p58.1 receptors for HLA-Cw4 molecules. European journal of immunology 186 9464792
1997 A single amino acid in the p58 killer cell inhibitory receptor controls the ability of natural killer cells to discriminate between the two groups of HLA-C allotypes. Journal of immunology (Baltimore, Md. : 1950) 175 9126959
1997 The direct binding of a p58 killer cell inhibitory receptor to human histocompatibility leukocyte antigen (HLA)-Cw4 exhibits peptide selectivity. The Journal of experimental medicine 165 9126935
1998 Differential binding to HLA-C of p50-activating and p58-inhibitory natural killer cell receptors. Proceedings of the National Academy of Sciences of the United States of America 147 9826699
1994 T cell clones expressing the natural killer cell-related p58 receptor molecule display heterogeneity in phenotypic properties and p58 function. European journal of immunology 135 7925558
2013 p58(IPK)-mediated attenuation of the proapoptotic PERK-CHOP pathway allows malignant progression upon low glucose. Molecular cell 126 23395000
2008 Regulated association of misfolded endoplasmic reticulum lumenal proteins with P58/DNAJc3. The EMBO journal 121 18923430
1996 A novel surface molecule homologous to the p58/p50 family of receptors is selectively expressed on a subset of human natural killer cells and induces both triggering of cell functions and proliferation. European journal of immunology 117 8765026
1999 The cellular inhibitor of the PKR protein kinase, P58(IPK), is an influenza virus-activated co-chaperone that modulates heat shock protein 70 activity. The Journal of biological chemistry 109 9920933
2007 An iron-sulfur cluster in the C-terminal domain of the p58 subunit of human DNA primase. The Journal of biological chemistry 106 17893144
1996 Physical and functional independency of p70 and p58 natural killer (NK) cell receptors for HLA class I: their role in the definition of different groups of alloreactive NK cell clones. Proceedings of the National Academy of Sciences of the United States of America 101 8643653
2009 Co-evolution of KIR2DL3 with HLA-C in a human population retaining minimal essential diversity of KIR and HLA class I ligands. Proceedings of the National Academy of Sciences of the United States of America 100 19837691
1997 Yeast counterparts of subunits S5a and p58 (S3) of the human 26S proteasome are encoded by two multicopy suppressors of nin1-1. Molecular biology of the cell 93 9017604
1995 cDNA cloning and baculovirus expression of the human liver endoplasmic reticulum P58: characterization as a protein disulfide isomerase isoform, but not as a protease or a carnitine acyltransferase. Archives of biochemistry and biophysics 93 7487104
2012 Diverse functionality among human NK cell receptors for the C1 epitope of HLA-C: KIR2DS2, KIR2DL2, and KIR2DL3. Frontiers in immunology 92 23189078
1992 The inner nuclear membrane protein p58 associates in vivo with a p58 kinase and the nuclear lamins. The EMBO journal 87 1327755
2013 Large spectrum of HLA-C recognition by killer Ig-like receptor (KIR)2DL2 and KIR2DL3 and restricted C1 SPECIFICITY of KIR2DS2: dominant impact of KIR2DL2/KIR2DS2 on KIR2D NK cell repertoire formation. Journal of immunology (Baltimore, Md. : 1950) 85 24078689
1999 The unstable F-box protein p58-Ctf13 forms the structural core of the CBF3 kinetochore complex. The Journal of cell biology 84 10352012
1994 Type B lamins remain associated with the integral nuclear envelope protein p58 during mitosis: implications for nuclear reassembly. The EMBO journal 84 8168487
1999 Crystal structure of the human p58 killer cell inhibitory receptor (KIR2DL3) specific for HLA-Cw3-related MHC class I. Structure (London, England : 1993) 81 10196125
2002 The p58 subunit of human DNA primase is important for primer initiation, elongation, and counting. Biochemistry 79 11939784
1995 Coexpression of two functionally independent p58 inhibitory receptors in human natural killer cell clones results in the inability to kill all normal allogeneic target cells. Proceedings of the National Academy of Sciences of the United States of America 77 7724594
2004 Failure to proliferate and mitotic arrest of CDK11(p110/p58)-null mutant mice at the blastocyst stage of embryonic cell development. Molecular and cellular biology 75 15060143
2012 Mutation at positively selected positions in the binding site for HLA-C shows that KIR2DL1 is a more refined but less adaptable NK cell receptor than KIR2DL3. Journal of immunology (Baltimore, Md. : 1950) 73 22772445
2002 Interaction of p58(PITSLRE), a G2/M-specific protein kinase, with cyclin D3. The Journal of biological chemistry 72 12082095
2015 Selection of an HLA-C*03:04-Restricted HIV-1 p24 Gag Sequence Variant Is Associated with Viral Escape from KIR2DL3+ Natural Killer Cells: Data from an Observational Cohort in South Africa. PLoS medicine 70 26575988
2007 CDK11(p58) is required for the maintenance of sister chromatid cohesion. Journal of cell science 70 17606997
2002 Crystal structure of the carbohydrate recognition domain of p58/ERGIC-53, a protein involved in glycoprotein export from the endoplasmic reticulum. The Journal of biological chemistry 70 11850423
1996 The P58 cellular inhibitor complexes with the interferon-induced, double-stranded RNA-dependent protein kinase, PKR, to regulate its autophosphorylation and activity. The Journal of biological chemistry 70 8576172
2003 P58(IPK), a plant ortholog of double-stranded RNA-dependent protein kinase PKR inhibitor, functions in viral pathogenesis. Developmental cell 69 12737801
2002 Efficient chemoselective carboxylation of aromatics to arylcarboxylic acids with a superelectrophilically activated carbon dioxide-Al(2)Cl(6)/Al system. Journal of the American Chemical Society 68 12236753
1994 The human natural killer cell receptor for major histocompatibility complex class I molecules. Surface modulation of p58 molecules and their linkage to CD3 zeta chain, Fc epsilon RI gamma chain and the p56lck kinase. European journal of immunology 61 7523145
2013 Allelic variation in KIR2DL3 generates a KIR2DL2-like receptor with increased binding to its HLA-C ligand. Journal of immunology (Baltimore, Md. : 1950) 60 23686481
2007 Natural killer cells in perinatally HIV-1-infected children exhibit less degranulation compared to HIV-1-exposed uninfected children and their expression of KIR2DL3, NKG2C, and NKp46 correlates with disease severity. Journal of immunology (Baltimore, Md. : 1950) 58 17709553
2012 Significant association of KIR2DL3-HLA-C1 combination with cerebral malaria and implications for co-evolution of KIR and HLA. PLoS pathogens 52 22412373
1997 Cloning, human chromosomal assignment, and adipose and hepatic expression of the CL-6/INSIG1 gene. Genomics 52 9268630
1991 Localization of the expressed human p58 protein kinase chromosomal gene to chromosome 1p36 and a highly related sequence to chromosome 15. Genomics 52 1774066
2001 TCR gamma delta cytotoxic T lymphocytes expressing the killer cell-inhibitory receptor p58.2 (CD158b) selectively lyse acute myeloid leukemia cells. Bone marrow transplantation 49 11438826
2021 Structural plasticity of KIR2DL2 and KIR2DL3 enables altered docking geometries atop HLA-C. Nature communications 45 33846289
2003 The crystal structure of the carbohydrate-recognition domain of the glycoprotein sorting receptor p58/ERGIC-53 reveals an unpredicted metal-binding site and conformational changes associated with calcium ion binding. Journal of molecular biology 44 14643651
2000 Protein-protein interactions of the primase subunits p58 and p48 with simian virus 40 T antigen are required for efficient primer synthesis in a cell-free system. The Journal of biological chemistry 43 10747950
1999 Interactions of DNA with human DNA primase monitored with photoactivatable cross-linking agents: implications for the role of the p58 subunit. Biochemistry 43 10504261
1997 Molecular basis of HLA-C recognition by p58 natural killer cell inhibitory receptors. Journal of immunology (Baltimore, Md. : 1950) 42 9378975
1990 Transient expression of a p58 protein kinase cDNA enhances mammalian glycosyltransferase activity. Biochemical and biophysical research communications 41 2118342
2017 The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands. Cell reports 39 28514659
2016 Sequence variations in HCV core-derived epitopes alter binding of KIR2DL3 to HLA-C∗03:04 and modulate NK cell function. Journal of hepatology 39 27057987
2009 P58(IPK): a novel "CIHD" member of the host innate defense response against pathogenic virus infection. PLoS pathogens 38 19461876
1999 Inhibition of double-stranded RNA- and tumor necrosis factor alpha-mediated apoptosis by tetratricopeptide repeat protein and cochaperone P58(IPK). Molecular and cellular biology 38 10373525
1992 Isolation, sequence and differential expression of the p58 gene family of Babesia bigemina. Molecular and biochemical parasitology 35 1501634
1991 Immunogenicity and sequence analysis of recombinant p58: a neutralization-sensitive, antigenically conserved Babesia bigemina merozoite surface protein. Molecular and biochemical parasitology 34 1944417
2016 p58(IPK) suppresses NLRP3 inflammasome activation and IL-1β production via inhibition of PKR in macrophages. Scientific reports 33 27113095
2014 KIR2DL3⁺NKG2A⁻ natural killer cells are associated with protection from productive hepatitis C virus infection in people who inject drugs. Journal of hepatology 32 24780303
2011 CDK11(p58) is required for centriole duplication and Plk4 recruitment to mitotic centrosomes. PloS one 30 21297952
1999 Modulation of T-cell functions in KIR2DL3 (CD158b) transgenic mice. Blood 30 10498612
2011 P58-A and P58-B: novel proteins that mediate skeletogenesis in the sea urchin embryo. Developmental biology 29 21362416
2010 Combined genotypic and phenotypic killer cell Ig-like receptor analyses reveal KIR2DL3 alleles displaying unexpected monoclonal antibody reactivity: identification of the amino acid residues critical for staining. Journal of immunology (Baltimore, Md. : 1950) 29 20525888
1990 Mammalian drug resistant mutants with multiple gene amplifications: genes encoding the M1 component of ribonucleotide reductase, the M2 component of ribonucleotide reductase, ornithine decarboxylase, p5-8, the H-subunit of ferritin and the L-subunit of ferritin. Biochimica et biophysica acta 29 2223878
2019 A novel curcumin derivative CL-6 exerts antitumor effect in human gastric cancer cells by inducing apoptosis through Hippo-YAP signaling pathway. OncoTargets and therapy 28 30988630
2014 Peptide selectivity discriminates NK cells from KIR2DL2- and KIR2DL3-positive individuals. European journal of immunology 28 25359276
2003 Functional supertype of HLA-A2 in the presentation of Flu matrix p58-66 to induce CD8+ T-cell response in a Northern Chinese population. Tissue antigens 27 12974795
2002 Inactivation of the PKR protein kinase and stimulation of mRNA translation by the cellular co-chaperone P58(IPK) does not require J domain function. Biochemistry 27 11939789
1999 Subcellular distribution of the Xenopus p58/lamin B receptor in oocytes and eggs. Journal of cell science 27 10393814
2011 25-OCH3-PPD induces the apoptosis of activated t-HSC/Cl-6 cells via c-FLIP-mediated NF-κB activation. Chemico-biological interactions 26 21924252
2009 Inhibition of G(1) to S phase progression by a novel zinc finger protein P58(TFL) at P-bodies. Molecular cancer research : MCR 26 19531561
2000 The p58-positive pre-golgi intermediates consist of distinct subpopulations of particles that show differential binding of COPI and COPII coats and contain vacuolar H(+)-ATPase. Journal of cell science 26 11017878
2015 KIR2DL3 and KIR2DL1 show similar impact on licensing of human NK cells. European journal of immunology 25 26467237
2009 XRCC1 interacts with the p58 subunit of DNA Pol alpha-primase and may coordinate DNA repair and replication during S phase. Nucleic acids research 24 19305001
2005 Downregulation of beta1,4-galactosyltransferase 1 inhibits CDK11(p58)-mediated apoptosis induced by cycloheximide. Biochemical and biophysical research communications 24 15629159
2017 KIR2DL3 and the KIR ligand groups HLA-A-Bw4 and HLA-C2 predict the outcome of hepatitis B virus infection. Journal of viral hepatitis 23 28211154
1999 Mapping of structural determinants for the oligomerization of p58, a lectin-like protein of the intermediate compartment and cis-Golgi. European journal of biochemistry 23 10095773
2023 Two-Dimensional Cs2 AgInx Bi1- x Cl6 Alloyed Double Perovskite Nanoplatelets for Solution-Processed Light-Emitting Diodes. Advanced materials (Deerfield Beach, Fla.) 22 36906925
2011 Polypyrimidine tract-binding protein regulates the cell cycle through IRES-dependent translation of CDK11(p58) in mouse embryonic stem cells. Cell cycle (Georgetown, Tex.) 22 22037210
2010 Crystal structure of P58(IPK) TPR fragment reveals the mechanism for its molecular chaperone activity in UPR. Journal of molecular biology 22 20184891
2008 P58(IPK) inhibition of endoplasmic reticulum stress in human retinal capillary endothelial cells in vitro. Molecular vision 21 18568130
2002 Novel isoform of insulin receptor substrate p53/p58 is generated by alternative splicing in the CRIB/SH3-binding region. The Journal of biological chemistry 21 12006592
2019 Killer Immunoglobulin-Like Receptor 2DS2 (KIR2DS2), KIR2DL2-HLA-C1, and KIR2DL3 as Genetic Markers for Stratifying the Risk of Cytomegalovirus Infection in Kidney Transplant Recipients. International journal of molecular sciences 20 30696053
2011 Cytotoxic activity of artemisinin derivatives against cholangiocarcinoma (CL-6) and hepatocarcinoma (Hep-G2) cell lines. Asian Pacific journal of cancer prevention : APJCP 20 21517231
2014 Deletion of P58(IPK), the Cellular Inhibitor of the Protein Kinases PKR and PERK, Causes Bone Changes and Joint Degeneration in Mice. Frontiers in endocrinology 19 25368604
2005 Cyclin-dependent kinase 11(p58) interacts with HBO1 and enhances its histone acetyltransferase activity. FEBS letters 19 15963510
1997 Insulin induction of pip 92, CL-6, and novel mRNAs in rat hepatoma cells. Endocrine 19 9549046
1996 Tyrosine phosphorylation at the membrane-microfilament interface: a p185neu-associated signal transduction particle containing Src, Abl and phosphorylated p58, a membrane- and microfilament-associated retroviral gag-like protein. Oncogene 19 8649794
2011 The crystal structure of the human co-chaperone P58(IPK). PloS one 18 21799829
2005 Aloe emodin-induced apoptosis in t-HSC/Cl-6 cells involves a mitochondria-mediated pathway. Basic & clinical pharmacology & toxicology 18 15910415
1996 Metal Binding of Polyalcohols. 4. Structure and Magnetism of the Hexanuclear, &mgr;(6)-Oxo-Centered [OFe(6)(H(-)(3)thme)(3)(OCH(3))(3)Cl(6)](2)(-) (thme = 1,1,1-Tris(hydroxymethyl)ethane). Inorganic chemistry 18 11666660
1996 Characterization of the p68/p58 heterodimer of human immunodeficiency virus type 2 reverse transcriptase. Biochemistry 18 8639674
2011 Virus infection rapidly activates the P58(IPK) pathway, delaying peak kinase activation to enhance viral replication. Virology 17 21612809
2010 Thr-370 is responsible for CDK11(p58) autophosphorylation, dimerization, and kinase activity. The Journal of biological chemistry 17 21078675
2004 Investigation of killer cell immunoglobulin-like receptor gene diversity III. KIR2DL3. Tissue antigens 17 15245374
2014 The bean pod mottle virus RNA2-encoded 58-kilodalton protein P58 is required in cis for RNA2 accumulation. Journal of virology 16 24390330
2014 CDK11(p58) kinase activity is required to protect sister chromatid cohesion at centromeres in mitosis. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 16 24436071
1991 Phosphorylation of numatrin and other nuclear proteins by cdc2 containing CTD kinase cdc2/p58. The Journal of biological chemistry 16 1874752
1991 Physical mapping of the genes for three components of the mouse DNA replication complex: polymerase alpha to the X chromosome, primase p49 subunit to chromosome 10, and primase p58 subunit to chromosome 1. Genomics 16 2037291