STRINGSTRING
GZMH GZMH GZMB GZMB NKG7 NKG7 CLEC2B CLEC2B KLRB1 KLRB1 ULBP1 ULBP1 KLRK1 KLRK1 LILRB3 LILRB3 HCST HCST MICB MICB TRIM45 TRIM45 HLA-F HLA-F FGFBP2 FGFBP2 CLEC2D CLEC2D GZMM GZMM STAC STAC GZMA GZMA KIR3DL3 KIR3DL3 NCR1 NCR1 KLRC4 KLRC4 CTSW CTSW KMT2E KMT2E LILRB1 LILRB1 KIR3DL2 KIR3DL2 KIR2DL1 KIR2DL1 KLRD1 KLRD1 KIR2DL4 KIR2DL4 NCR3LG1 NCR3LG1 NCR3 NCR3 KIR2DL3 KIR2DL3 RAET1E RAET1E ULBP3 ULBP3 RAET1L RAET1L ULBP2 ULBP2 RAET1G RAET1G FCRL6 FCRL6 SORBS1 SORBS1 NCR2 NCR2 HLA-C HLA-C HLA-E HLA-E HLA-G HLA-G KLRC2 KLRC2 KLRC3 KLRC3 KIR3DL1 KIR3DL1 LILRB2 LILRB2 LILRA6 LILRA6 HLA-A HLA-A FCHSD2 FCHSD2 ZNF683 ZNF683 DCLK3 DCLK3 CLEC2A CLEC2A PRF1 PRF1 HLA-B HLA-B SAMD3 SAMD3 MICA MICA SPART SPART CST7 CST7 IL32 IL32 GNLY GNLY KLRC3-2 KLRC3-2 KLRC1 KLRC1 KLRF2 KLRF2 KLRF1 KLRF1
Nodes:
Network nodes represent proteins
splice isoforms or post-translational modifications are collapsed, i.e. each node represents all the proteins produced by a single, protein-coding gene locus.
Node Color
colored nodes:
query proteins and first shell of interactors
white nodes:
second shell of interactors
Node Content
empty nodes:
proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
Edges:
Edges represent protein-protein associations
associations are meant to be specific and meaningful, i.e. proteins jointly contribute to a shared function; this does not necessarily mean they are physically binding to each other.
Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
Others
textmining
co-expression
protein homology
Your Input:
GZMHGranzyme H; Cytotoxic chymotrypsin-like serine protease with preference for bulky and aromatic residues at the P1 position and acidic residues at the P3' and P4' sites. Probably necessary for target cell lysis in cell-mediated immune responses. Participates in the antiviral response via direct cleavage of several proteins essential for viral replication. (246 aa)
GZMBGranzyme B; This enzyme is necessary for target cell lysis in cell- mediated immune responses. It cleaves after Asp. Seems to be linked to an activation cascade of caspases (aspartate-specific cysteine proteases) responsible for apoptosis execution. Cleaves caspase-3, -7, -9 and 10 to give rise to active enzymes mediating apoptosis; Belongs to the peptidase S1 family. Granzyme subfamily. (247 aa)
NKG7Protein NKG7; Natural killer cell granule protein 7; Belongs to the PMP-22/EMP/MP20 family. (165 aa)
CLEC2BC-type lectin domain family 2 member B. (149 aa)
KLRB1Killer cell lectin-like receptor subfamily B member 1; Plays an inhibitory role on natural killer (NK) cells cytotoxicity. Activation results in specific acid sphingomyelinase/SMPD1 stimulation with subsequent marked elevation of intracellular ceramide. Activation also leads to AKT1/PKB and RPS6KA1/RSK1 kinases stimulation as well as markedly enhanced T-cell proliferation induced by anti-CD3. Acts as a lectin that binds to the terminal carbohydrate Gal-alpha(1,3)Gal epitope as well as to the N- acetyllactosamine epitope. Binds also to CLEC2D/LLT1 as a ligand and inhibits NK cell-mediat [...] (225 aa)
ULBP1UL16-binding protein 1; Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity. (244 aa)
KLRK1NKG2-D type II integral membrane protein; 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-exp [...] (216 aa)
LILRB3Leukocyte immunoglobulin-like receptor subfamily B member 3; May act as receptor for class I MHC antigens. Becomes activated upon coligation of LILRB3 and immune receptors, such as FCGR2B and the B-cell receptor. Down-regulates antigen-induced B-cell activation by recruiting phosphatases to its immunoreceptor tyrosine- based inhibitor motifs (ITIM). (632 aa)
HCSTHematopoietic cell signal transducer; Transmembrane adapter protein which associates with KLRK1 to form an activation receptor KLRK1-HCST in lymphoid and myeloid cells; this receptor plays a major role in triggering cytotoxicity against target cells expressing cell surface ligands such as MHC class I chain- related MICA and MICB, and UL16-binding proteins (ULBPs); these ligands are up-regulated by stress conditions and pathological state such as viral infection and tumor transformation. Functions as docking site for PI3-kinase PIK3R1 and GRB2. Interaction of ULBPs with KLRK1-HCST trigg [...] (93 aa)
MICBMHC class I polypeptide-related sequence B; Seems to have no role in antigen presentation. Acts as a stress-induced self-antigen that is recognized by gamma delta T cells. Ligand for the KLRK1/NKG2D receptor. Binding to KLRK1 leads to cell lysis; Belongs to the MHC class I family. MIC subfamily. (383 aa)
TRIM45Tripartite motif-containing protein 45; May act as a transcriptional repressor in mitogen-activated protein kinase signaling pathway. (580 aa)
HLA-FHLA class I histocompatibility antigen, alpha chain F; Non-classical major histocompatibility class Ib molecule postulated to play a role in immune surveillance, immune tolerance and inflammation. Functions in two forms, as a heterotrimeric complex with B2M/beta-2 microglobulin and a peptide (peptide-bound HLA-F-B2M) and as an open conformer (OC) devoid of peptide and B2M (peptide-free OC). In complex with B2M, presents non-canonical self-peptides carrying post- translational modifications, particularly phosphorylated self-peptides. Peptide-bound HLA-F-B2M acts as a ligand for LILRB1 i [...] (442 aa)
FGFBP2Fibroblast growth factor binding protein 2. (223 aa)
CLEC2DC-type lectin domain family 2 member D; Receptor for KLRB1 that protects target cells against natural killer cell-mediated lysis. Inhibits osteoclast formation. Inhibits bone resorption. Modulates the release of interferon-gamma. Binds high molecular weight sulfated glycosaminoglycans. (194 aa)
GZMMGranzyme M; Cleaves peptide substrates after methionine, leucine, and norleucine. Physiological substrates include EZR, alpha-tubulins and the apoptosis inhibitor BIRC5/Survivin. Promotes caspase activation and subsequent apoptosis of target cells. (257 aa)
STACSH3 and cysteine-rich domain-containing protein; Promotes expression of the ion channel CACNA1H at the cell membrane, and thereby contributes to the regulation of channel activity. Plays a minor and redundant role in promoting the expression of calcium channel CACNA1S at the cell membrane, and thereby contributes to increased channel activity. Slows down the inactivation rate of the calcium channel CACNA1C. (402 aa)
GZMAGranzyme A; Abundant protease in the cytosolic granules of cytotoxic T- cells and NK-cells which activates caspase-independent cell death with morphological features of apoptosis when delivered into the target cell through the immunological synapse. It cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity. Cleaves the nucleosome assembly protein SET after 'Lys-189', which disrupts its nucleosome assembly activity and allows the SET complex to translocate into the nucleus to nick and degrade the DNA. Belongs to the peptidase S1 family. Granzym [...] (262 aa)
KIR3DL3Killer cell immunoglobulin-like receptor 3DL3; Receptor on natural killer cells. May inhibit the activity of NK cells thus preventing cell lysis. (410 aa)
NCR1Natural cytotoxicity triggering receptor 1; Cytotoxicity-activating receptor that may contribute to the increased efficiency of activated natural killer (NK) cells to mediate tumor cell lysis. (304 aa)
KLRC4NKG2-F type II integral membrane protein; May play a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells. (158 aa)
CTSWCathepsin W; May have a specific function in the mechanism or regulation of T-cell cytolytic activity; Belongs to the peptidase C1 family. (376 aa)
KMT2EInactive histone-lysine N-methyltransferase 2E; Associates with chromatin regions downstream of transcriptional start sites of active genes and thus regulates gene transcription. Chromatin interaction is mediated via the binding to tri-methylated histone H3 at 'Lys-4' (H3K4me3). Key regulator of hematopoiesis involved in terminal myeloid differentiation and in the regulation of hematopoietic stem cell (HSCs) self-renewal by a mechanism that involves DNA methylation (By similarity). Also acts as an important cell cycle regulator, participating in cell cycle regulatory network machinery [...] (1858 aa)
LILRB1Leukocyte immunoglobulin-like receptor subfamily B member 1; Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C, HLA-G and HLA-F alleles. Receptor for H301/UL18, a human cytomegalovirus class I MHC homolog. Ligand binding results in inhibitory signals and down-regulation of the immune response. Engagement of LILRB1 present on natural killer cells or T-cells by class I MHC molecules protects the target cells from lysis. Interaction with HLA-B or HLA-E leads to inhibition of FCER1A signaling and serotonin release. Inhibits FCGR1A-mediated phosphorylatio [...] (652 aa)
KIR3DL2Killer cell immunoglobulin-like receptor 3DL2; Receptor on natural killer (NK) cells and T cells for MHC class I molecules. Upon binding of peptide-free HLA-F open conformer, negatively regulates NK and T cell effector functions. Acts as a receptor on astrocytes for HLA-F. Through interaction with HLA-F, may protect motor neurons from astrocyte-induced toxicity. Belongs to the immunoglobulin superfamily. (455 aa)
KIR2DL1Killer cell immunoglobulin-like receptor 2DL1; Receptor on natural killer (NK) cells for some HLA-C alleles such as w4 and w6. Inhibits the activity of NK cells thus preventing cell lysis; Belongs to the immunoglobulin superfamily. (348 aa)
KLRD1Natural killer cells antigen CD94; Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. (179 aa)
KIR2DL4Killer cell immunoglobulin-like receptor 2DL4; Receptor for non-classical major histocompatibility class Ib HLA-G molecules. Recognizes HLA-G in complex with B2M/beta-2 microglobulin and a nonamer self-peptide (peptide-bound HLA-G-B2M). In decidual NK cells, binds peptide-bound HLA-G-B2M complex and triggers NK cell senescence-associated secretory phenotype as a molecular switch to promote vascular remodeling and fetal growth in early pregnancy. May play a role in balancing tolerance and antiviral-immunity at maternal-fetal interface by keeping in check the effector functions of NK, CD [...] (342 aa)
NCR3LG1Natural cytotoxicity triggering receptor 3 ligand 1; Triggers NCR3-dependent natural killer cell activation. (454 aa)
NCR3Natural cytotoxicity triggering receptor 3; Cell membrane receptor of natural killer/NK cells that is activated by binding of extracellular ligands including BAG6 and NCR3LG1. Stimulates NK cells cytotoxicity toward neighboring cells producing these ligands. It controls, for instance, NK cells cytotoxicity against tumor cells. Engagement of NCR3 by BAG6 also promotes myeloid dendritic cells (DC) maturation, both through killing DCs that did not acquire a mature phenotype, and inducing the release by NK cells of TNFA and IFNG which promote DC maturation. (201 aa)
KIR2DL3Killer cell immunoglobulin-like receptor 2DL3; Receptor on natural killer (NK) cells for HLA-C alleles (HLA- Cw1, HLA-Cw3 and HLA-Cw7). Inhibits the activity of NK cells thus preventing cell lysis. (341 aa)
RAET1ERetinoic acid early transcript 1E; Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity; Belongs to the MHC class I family. (263 aa)
ULBP3UL16-binding protein 3; Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity; Belongs to the MHC class I family. (244 aa)
RAET1LUL16-binding protein 6; Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity; Belongs to the MHC class I family. (246 aa)
ULBP2UL16-binding protein 2; Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity. (246 aa)
RAET1GUL-16 binding protein 5; [Isoform 1]: Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity. [Isoform 2]: Stimulates natural killer cells to secrete IFNG. Belongs to the MHC class I family. (334 aa)
FCRL6Fc receptor-like protein 6; Acts as a MHC class II receptor. When stimulated on its own, does not play a role in cytokine production or the release of cytotoxic granules by NK cells and cytotoxic CD8(+) T cells. Does not act as an Fc receptor. (434 aa)
SORBS1Sorbin and SH3 domain-containing protein 1; Plays a role in tyrosine phosphorylation of CBL by linking CBL to the insulin receptor. Required for insulin-stimulated glucose transport. Involved in formation of actin stress fibers and focal adhesions (By similarity). (1292 aa)
NCR2Natural cytotoxicity triggering receptor 2; Cytotoxicity-activating receptor that may contribute to the increased efficiency of activated natural killer (NK) cells to mediate tumor cell lysis. (276 aa)
HLA-CHLA class I histocompatibility antigen, C alpha chain; Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity. In complex with B2M/beta 2 microglobulin displays a restricted repertoire of self and viral peptides and acts as a dominant ligand for inhibitory and activating killer immunoglobulin receptors (KIRs) expressed on NK cells. In an allogeneic setting, such as during pregnancy, mediates interaction of extravillous trophoblasts with KIR on uterine NK cells and regulate trophoblast invasion necessary [...] (366 aa)
HLA-ESoluble HLA class I histocompatibility antigen, alpha chain E; Non-classical major histocompatibility class Ib molecule involved in immune self-nonself discrimination. In complex with B2M/beta-2-microglobulin binds nonamer self-peptides derived from the signal sequence of classical MHC class Ia molecules (VL9 peptides). Peptide-bound HLA- E-B2M heterotrimeric complex primarily functions as a ligand for natural killer (NK) cell inhibitory receptor KLRD1-KLRC1, enabling NK cells to monitor the expression of other MHC class I molecules in healthy cells and to tolerate self. Upon cellular [...] (358 aa)
HLA-GSoluble HLA class I histocompatibility antigen, alpha chain G; [Isoform 1]: Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface. In complex with B2M/beta-2 microglobulin binds a limited repertoire of nonamer self-peptides derived from intracellular proteins including histones and ribosomal proteins. Peptide-bound HLA-G-B2M complex acts as a ligand for inhibitory/activating KIR2DL4, LILRB1 and LILRB2 receptors on uterine immune cells to promote fetal development while maintaining maternal- fetal tolerance. Upon [...] (343 aa)
KLRC2NKG2-C type II integral membrane protein; Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. (231 aa)
KLRC3Killer cell lectin like receptor C3. (257 aa)
KIR3DL1Killer cell immunoglobulin-like receptor 3DL1; Receptor on natural killer (NK) cells for HLA Bw4 allele. Inhibits the activity of NK cells thus preventing cell lysis. (444 aa)
LILRB2Leukocyte immunoglobulin-like receptor subfamily B member 2; Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C, HLA-G and HLA-F alleles. Involved in the down-regulation of the immune response and the development of tolerance. Recognizes HLA-G in complex with B2M/beta-2 microglobulin and a nonamer self-peptide (peptide-bound HLA-G-B2M) triggering differentiation of type 1 regulatory T cells and myeloid-derived suppressor cells, both of which actively maintain maternal-fetal tolerance. Competes with CD8A for binding to class I MHC antigens. Inhibits FC [...] (598 aa)
LILRA6Leukocyte immunoglobulin-like receptor subfamily A member 6; May act as receptor for class I MHC antigens. (481 aa)
HLA-AHLA class I histocompatibility antigen, A alpha chain; Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-A-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells. May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usuall [...] (365 aa)
FCHSD2F-BAR and double SH3 domains protein 2; Adapter protein that plays a role in endocytosis via clathrin-coated pits. Contributes to the internalization of cell surface receptors, such as integrin ITGB1 and transferrin receptor. Promotes endocytosis of EGFR in cancer cells, and thereby contributes to the down-regulation of EGFR signaling. Recruited to clathrin-coated pits during a mid-to- late stage of assembly, where it is required for normal progress from U-shaped intermediate stage pits to terminal, omega-shaped pits. Binds to membranes enriched in phosphatidylinositol 3,4-bisphosphate [...] (740 aa)
ZNF683Tissue-resident T-cell transcription regulator protein ZNF683; Transcription factor that mediates a transcriptional program in various innate and adaptive immune tissue-resident lymphocyte T-cell types such as tissue-resident memory T (Trm), natural killer (trNK) and natural killer T (NKT) cells and negatively regulates gene expression of proteins that promote the egress of tissue-resident T-cell populations from non-lymphoid organs. Plays a role in the development, retention and long-term establishment of adaptive and innate tissue- resident lymphocyte T cell types in non-lymphoid org [...] (524 aa)
DCLK3Serine/threonine-protein kinase DCLK3; Doublecortin like kinase 3. (648 aa)
CLEC2AC-type lectin domain family 2 member A; Plays a role in modulating the extent of T-cell expansion. Enhances the expansion of TCR-stimulated T-cells by increasing their survival through enhanced expression of anti-apoptotic proteins. May modulate the capacity of T-cells to home to lymph nodes through SELL. Facilitates dedicated immune recognition of keratinocytes via interaction with its receptor KLRF2 by stimulating natural killer cell mediated cytotoxicity. (174 aa)
PRF1Perforin-1; Plays a key role in secretory granule-dependent cell death, and in defense against virus-infected or neoplastic cells. Plays an important role in killing other cells that are recognized as non-self by the immune system, e.g. in transplant rejection or some forms of autoimmune disease. Can insert into the membrane of target cells in its calcium-bound form, oligomerize and form large pores. Promotes cytolysis and apoptosis of target cells by facilitating the uptake of cytotoxic granzymes. Belongs to the complement C6/C7/C8/C9 family. (555 aa)
HLA-BHLA class I histocompatibility antigen, B alpha chain; Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-B-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells. May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usuall [...] (362 aa)
SAMD3Sterile alpha motif domain containing 3. (544 aa)
MICAMHC class I polypeptide-related sequence A; Seems to have no role in antigen presentation. Acts as a stress-induced self-antigen that is recognized by gamma delta T-cells. Ligand for the KLRK1/NKG2D receptor. Binding to KLRK1 leads to cell lysis. Belongs to the MHC class I family. MIC subfamily. (332 aa)
SPARTSpartin; May be implicated in endosomal trafficking, or microtubule dynamics, or both. Participates in cytokinesis. (666 aa)
CST7Cystatin-F; Inhibits papain and cathepsin L but with affinities lower than other cystatins. May play a role in immune regulation through inhibition of a unique target in the hematopoietic system. (145 aa)
IL32Interleukin-32; Cytokine that may play a role in innate and adaptive immune responses. It induces various cytokines such as TNFA/TNF-alpha and IL8. It activates typical cytokine signal pathways of NF-kappa-B and p38 MAPK. (234 aa)
GNLYGranulysin; Antimicrobial protein that kills intracellular pathogens. Active against a broad range of microbes, including Gram-positive and Gram-negative bacteria, fungi, and parasites. Kills Mycobacterium tuberculosis. (172 aa)
KLRC3-2NKG2-E type II integral membrane protein; Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. (240 aa)
KLRC1NKG2-A/NKG2-B type II integral membrane protein; Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. (233 aa)
KLRF2Killer cell lectin-like receptor subfamily F member 2; C-type lectin-like receptor involved in natural killer cell mediated cytotoxicity and cytokine secretion in keratinocytes via its interaction with CLEC2A. (207 aa)
KLRF1Killer cell lectin-like receptor subfamily F member 1; Involved in the natural killer (NK)-mediated cytolysis of PHA-induced lymphoblasts. (231 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
Server load: low (36%) [HD]
STRING is a Core Data Resource as designated by Global Biodata Coalition and ELIXIR.