CD158k KIR3DL2 (killer cell immunoglobulin-like receptor 3 domains, long cytoplasmic tail, 2), NKAT4
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
NK Cell
T Cell
70 / 70
150 / 150

Expression
CD158k is expressed on subsets of NK cells, on subsets of cytotoxic cells and some T cells.  Expression on individual NK cells is complex and several members of the KIR family.  The repertoire of KIR molecules varies among NK cells and is not determined solely by the HLA hapotypes.

Structure
MOLECULAR FAMILY NAME: Belongs to the immunoglobulin gene superfamily.

CD158k  is a single-pass type-1 455 aa transmembrane glycoprotein.  It contains an a 21 aa signal peptide, an extracellular domain which contains 3 Ig-like C2-type domains (D0, D1 and D2) with 3 potential N-linked glycosylation sites, a 20 aa hydrophobic transmembrane domain and a 84-95 aa long cytoplasmic domain which contains 2 ITIM sequences.  It has been noted that a pair of cysteines at the N-terminal of the transmembrane portion could be involved in disulfide bridge formation.  CD158k maybe expressed as a disulfide-linked dimer and interacts with certain HLA-A molecules.  Using Western blot analysis, CD158k is expressed as a 150 kDa protein under nonreducing conditions or as a 70 kDa protein under reducing conditions.
 
MOLECULAR MASS
Cell type Unreduced Reduced
150 kDa 70 kDa




POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION: No information.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD158k

CD158k possibly binds certain HLA-A molecules.

Function
CD158k is involved in the suppression of NK cell mediated cytotoxicity.  CD158k forms disulfide-linked homidimers of 2 p70 subunits.  KIR with ITIM sequences in the cytoplasmic domain inhibit NK and CTL mediated lysis against certain target cells expressing an appropriate MHC class I ligand.  In addition, interactions between KIR on NK or T cells and MHC class I on antigen presenting cells can inhibit cytokine production.  In contrast, NK and T cells expressing KIR without an ITIM may enhance cytolysis against target cells expressing an appropriate MHC class I ligand.  However, inhibitory KIR can prevent stimulation by an activating KIR if the potential target or antigen presenting cell also expresses a ligand of the inhibitory KIR.  CD158k regulates the NK cell mediated cytolytic activity upon interaction with appropriate HLA-C alleles, recognizing these groups of HLA class 1 allotypes rather than individual MHC class I peptide complexes.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD158k IN INTACT ANIMAL

CD158k is a potential marker for Sezary syndrome and is being investigated as a potential therapeutic agent in the treatment of various cancers.

Comments

Killer cell immunoglobulin (Ig)-like receptors (KIR), also called killer cell inhibitory receptors, are glycoproteins expressed in natural killer (NK) cells and some T cells.  The KIR family is estimated to include about 11 genes.  Some members of the KIR family bind to certain HLA class I deficient cell lines.  Ligation of such KIR by HLA class I molecules on target cells results in inhibition of the NK or T cell cytotoxic activity.  The inhibition could be disrupted by antibodies against membrane glycoproteins on NK cells that recognized HLA- and HLA-C.  Inhibitory KIRs are found in 3 distinct isoforms.  KIRs that recognize HLA-C are usually monomeric glycoproteins of about 58 kDa with 2 Ig-like domains (KIR2D).  KIRs that are reactive with HLA-B are approximately 70 kDa monomeric glycoproteins with 3 Ig-like domains (KIR3D).  The KIR family is further subdivided into forms with short and long intracytoplasmic tails.  The 1st and 2nd Ig domains in KIR2D are closely related in aa sequence to the 2nd and 3rd Ig domains in KIR3D. These 2 related Ig domains are called D1 and D2, respectively.  D0 is the 1st Ig domain in KIR3D.  KIR members vary in the length of the cytoplasmic tails.  Most of the long cytoplasmic tails, KIR2DL and KIR3DL, deliver an inhibitory signal and carry 2 immunoreceptor tyrosine-based inhibition motifs (ITIM) which recruit and activate protein tyrosine phosphates, SHP-1 and or SHP-2.  Other receptors, of about 50 kDa, with short cytoplasmic regions (KIR2DS and KIR3DS) are truncated before the 1st ITIM causing them to have no ITIMs.  They are are connected to a transmembrane region which includes a lysine residue and can activate NK or T cell responses.  The short tail associates with a disulfide dimer of 14 kDa. phosphoproteins called DAP12 which is also known as killer activating protein (KARAP).

MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD158k: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD158k: No information.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3812P43630
Antibodies

Revised June 25, 2008


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