KIR2DL4

Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several "framework" genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response. This gene is one of the "framework" loci that is present on all haplotypes. Alternate alleles of this gene are represented on multiple alternate reference loci (ALT_REF_LOCs). Alternative splicing results in multiple transcript variants, some of which may not be annotated on the primary reference assembly. [provided by RefSeq, Jul 2016]

Killer Cell Immunoglobulin Like Receptor, Two Ig Domains And Long Cytoplasmic Tail 4

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 (PubMed:23184984, PubMed:29262349, PubMed:16366734).
May play a role in balancing tolerance and antiviral-immunity at maternal-fetal interface by keeping in check the effector functions of NK, CD8+ T cells and B cells (PubMed:10190900, PubMed:16366734).
Upon interaction with peptide-bound HLA-G-B2M, initiates signaling from the endosomal compartment leading to downstream activation of PRKDC-XRCC5 and AKT1, and ultimately triggering NF-kappa-B-dependent proinflammatory response (PubMed:20179272).

Cellular defense responseManual Assertion Based On ExperimentTAS:ProtInc
Negative regulation of natural killer cell mediated cytotoxicityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cellular senescenceManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of natural killer cell cytokine productionManual Assertion Based On ExperimentIDA:UniProtKB
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc

Cell membrane; Early endosome membrane

Extracellular: 22-242
Helical: 243-263
Cytoplasmic: 264-377