CD112 PRR2(poliovirus receptor-related 2protein), Nectin-2, HVEB(herpesvirus entry protein B)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Stem Cell
Pancreas
Endothelial Cell
Myelomonocytic cell
Epithelial Cell
Megakaryocyte
Placenta
Prostate
Liver
Kidney
Lung
Hematopoietic Progenitor Cell
Thyroid
Fibroblast
64 / 64
72 / 72

Expression
CD112, an intercellular adhesion molecule, is expressed on multiple tissues including prostate, placenta, kidney, lung, pancreas, thyroid and liver.  CD112 is expressed on cell lines of different lineages, including myelomonocytic and megakaryocytic hematopoietic lineages, neuronal, endothelial and epithelial cells.  CD112 is expressed on CD33+, CD14+ and CD41+ cells.  It is also expressed on CD34 + hematopoietic progenitor cells, stem cells, fibroblastic cells, epithelial cells and endothelial cells.


Structure
MOLECULAR FAMILY NAME:  Belongs to the immunoglobulin family.

CD112 is a single-pass type-1 glycoprotein.  It contains an extracellular domain which contains 2 Ig-like C2-type domains, 1 Ig-like V-type domain and 2 potential N-glycosylation sites, a transmembrane domain and cytoplasmic domain.  CD112 was originally identified in rodents as an orthologue of the human poliovirus receptor (PVR).  CD112 belongs to a new nectin family of immunoglobulin-like molecules that includes 4 members, CD111, CD112, CD113 and CD155.  CD112 show approximately 30% homology with CD11 and CD113.  The 2 corresponding transcripts of 4.4 kb and 3.0 kb were detected in several tissues.  The apparent Mr of the corresponding CD112 protein isoforms is 72 kDa and 64 kDa.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
various 72 kDa 72 kDa Long isoform
various 64 kDa 64 kDa Short isoform

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms, 1617 bp and 1437 bp long, that splice at the position 1042 in the ectodomain.  The two isoforms have been identified as nectin-2α and δ.  Transmembrane and cytoplasmic sequences are unrelated but both carry the A/ExYV ending sequence.  Homophilic adhesion correlates with the tyrosine phosphorylation of the long form.

POST-TRANSLATIONAL MODIFICATION

CD112 has 2 potential N-glycoslation sites.
 

Ligands
The extracellular region binds the related nectins-1 (CD111) and nectins-3 (CD113) and the poliovirus receptor CD155.  It can also interact with nectin-2 (CD112) on the same or on other cells.  It can also interact with CD112 on the same and on other cells (i.e. cis- and trans-homo-interaction.  CD112 is a receptor for the α herpes viruses HSV-1 and pseudoraboes virus (PRV).

LIGANDS AND MOLECULES ASSOCIATED WITH CD112
Molecule Comment
CD112 Ligand
PRR3 Ligand
afadin CD112 specifically localizes at adherens junctions through its cytoplasmic interaction with the scaffold F-actin binding protein afadin


Function
CD112 is an adhesion molecule involved in the formation of adherens junctions between cells.  The intracellular portion of nectins binds to actin cytoskeleton through afadin.  CD112 is specifically localized at adherens junctions through its cytoplasmic interaction with the scaffold F-actin binding protein afadin.  CD112 is expressed on hematopoietic cells but the function in hematopoietis is unknown but it has herpesvirus entry activity and may function as a co-receptor for HSV-1, HSV-2 and pseudorabies virus.  This interaction is mediated by a sequence located to the C terminal ends of both isoforms of CD112, A/ExYV, and the PDZ domain of afadin.  This sequence is also found in other members of the nectin family.  Disruption of the murine CD112 gene leads to infertility of male mice with morphologically aberrant spermatozoa.  CD112 mediates entry of some a herpesvirus mutants, also named HveB, via its V domain.  CD112 is also involved in cell to cell spreading of the virus.  CD112 also acts as an intercellular adhesion molecule and pseudorabies virus receptor and could be involved in the epithelial and endothelial cell physiology.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD112 IN INTACT ANIMAL 

CD112 functions as a receptor for some herpes viruses.  CD112 is one of the plasma membrane components of adherens junctions that serves as entry for certain mutant strains of herpes simplex virus and pseudorabies virus.  CD112 Fc fusion has been shown to block infection by HSV in vitro.  The R2.525 and BC-1 monoclonal antibodies recognize the V-type domain of the molecule and blocks virus entry and cell to cell spreading.  Mutations of CD112 have been associated with differences in the severity of multiple sclerosis.



Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD112: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD112: No information.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 5819Q92692
Antibodies

Revised June 25, 2008


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