CD146 MCAM (melanoma cell adhesion molecule), MUC18, Mel-CAM, s-edo 
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Trophoblast
Mycoepithelium
Muscle, Smooth
Melanoma Cell
T Cell
Endothelial Cell
Dendritic Cell, Follicular
Schwann Cell
Fibroblast
Bone Marrow
Epithelium
Mycofibroblast
118 / 118
130 / 130

Expression
CD146 is expressed endothelial cells, smooth muscle, melanoma cells, Schwann cells, on Schwann cells, ganglion cells, myofibroblasts, bone marrow fibroblasts, cerebellar cortex, external root sheath of hair follicles, mammary ductal and lobular epithelium mycoepithelium, subcapsular epithelium of thymus, follicular dendritic reticulum cells and extravillous trophoblasts.  CD146 is variably expressed in parathyroid glands and basal cells of bronchial epithelium.  CD146 has been detected on a subpopulation of activated T cells from delayed-type hypersensitivity lesions of  the skin and in sinovial fluid of rheumatoid arthritis patients.  There is expression in endothelial cells in vascular tissue throughout the body and appears to be associated with tumor progression of metastasis in human malignant melanomas. There is expression in endothelial cells in vascular tissue throughout the body and appears to be associated with tumor progression of metastasis in human malignant melanomas.  Almost all melanomas, angiosarcomas, Kaposi's sarcomas, leimyosarcomas, placental trophoblastic tumors, choriocarcinomas and prostate carcinomas express CD146.  Focal and variable CD146 expression is detectable in some squamous cell and small cell lung carcinomasm some breast carcinomas, mucoepidermoid carsinomas of the salivary gland and between 15% and 43% of leukemias.




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

CD146 is a single-pass type-1 603 aa glycoprotein.  It contains a signal peptide, an extracellular domain which contains 3 Ig-like C2-type domains and 2 Ig-like V-type domain and is heavily glycosylated, a transmembrane domain and a 63 residue cytoplasmic domain and has potential recognition sites for protein kinases.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Endothelium
Melanoma 118 kDa 130 kDa
Glioma 118 kDa 130 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms.

POST-TRANSLATIONAL MODIFICATION

CD146 has N-linked glycosylation which accounts for about 50% of the apparent molecular weight.  In some cells, the molecule carries sulfate 3-glucuronyl moiety defined by anti-CD57 mAbs.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD146

Evidence suggests CD146 mediates heterotypic binding to an as yet unknown ligand.


Function
CD146 is an endothelial progenitor cell and is a circulating endothelial cell marker.  CD146 is a potential cell adhesion molecule as it is localized at the cell-cell junction and is in cohesion of the endothelial monolayer at intracellular junctions in vascular tissues.  The expression may allow melanoma cells to interact with cellular elements of the vascular system, thereby enhancing hematogeneous tumor spread.  It could be active in neural cells during embryonic development.  CD146 acts as a surface receptor that triggers tyrosine phosphorylaion of FYN and PTK2 and a transient increase in the intracellular calcium concentration.  Cross-linking of CD146  with anti-CD146 antibody results in the phosphorylation of several intracellular proteins.  Activated CD146 complexes with Stc family kinase p59fyn, which in turn phosphorylates p125FAK which associates with the cytoskeletal protein paxillin, and this complex is though to promote focal adhesion assembly.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD146 IN INTACT ANIMAL

CD146, a melanoma cell adhesion molecule, may be a marker of melanoma progression in man and may be a neural crest cell adhesion molecule during embryogesis.  CD146 plays an important role tumorigenesis and metastasis of melanoma and and malignant progression of human prostate cancer through interaction with vascular endothelium and CD146 is a prognostic marker of these diseases.  Expression confers increased tumorigenicity in nude mice.  CD146 is a disgnostic and prognostic marker of endothelial cell activation and injury related to coronary artery disease, chronic renal failure and peritoneally dialysed patients.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD146: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD146: No information.

ADDITIONAL INSIGHTS ON CD146

Subcellular localization occurs at the cell-cell junction.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 4162P43121
Antibodies

Revised June 25, 2008


Contact us: Webmaster |  509-335-9515 | Accessibility | Copyright | Policies
College of Veterinary Medicine Washington State University, Pullman, WA, 99164-7010 USA
Copyright 1995-2003 Washington State University