CD158f KIR2DL5A (killer cell immunoglobulin-like receptor, 2 domains, long cytoplasmic tail, 5A)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
NK Cell
T Cell

Expression
CD158f 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.

CD158f is a single-pass type-1 375 aa glycoprotein.  It contains an extracellular domain containing 2 Ig domains (D1 and D2), a transmembrane domain with no charged residue and a 76-114 aa long cytoplasmic domain with 2 ITIMs.  CD158f shares a 79% sequence identity with CD158d. 

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Analysis shows that most CD158f clones do not contain all 8 exons suggesting alternative splicing.  It is shown that 2 nonexpressed splice variants have an identical substiution in a putative AML1-bind site.

POST-TRANSLATIONAL MODIFICATION: No information.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD158f

CD158f binds HLA-B.

Function
CD158f is involved in the suppression of NK mediated cytotoxicity.  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.  CD158f 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.

Studies of the human NK-like cell line determined CD158f is an inhibitory receptor that can recruit both HP1 and SHP2.  Its inhibitory capacity was more similar to that of the cytoplasmic domain of CD158d than to that of CD158e1/e2.  The differentces in KIR capacities are probably due to alterations in the ITIM sequences.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD158f IN INTACT ANIMAL

In murine models, inhibitory NK cell receptors that are functional homologs of human KIR (eg. the LY49 receptors) regulate rejection of bone marrow grafts from semi-allogeneic or allogeneic donors.  Expression of a human KIR transgene controls NK mediated rejection of allogeneic bone marrow grafts.  There is also evidence that KIR may be expressed on melanoma specific CTL and regulate their ability to kill these tumors.

Preeclampsia occurs due to failure of trophoblast invasion.  Only polymorphic histocompatibility antigens on the trophoblast surface are HLA-C molecules, including the paternal allele, which are recognized by members of the higly polymorphic KIR family of NK cell receptors.  Preecalampsia is more likely in a fetus with HLA-C2 while it is less likely with haplotype B, CD158f.  


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 CD158f: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD158f: No information.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene57292Q8N109
Antibodies

Revised June 25, 2008


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