CD340 ERBB2 (erythroblastic leukemia viral oncogene homolog 2), HER-2/neu
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Epithelial Cell
Mesenchymal Cell
Ovary
Stomach
Carcinoma Cell
Colon
Lung
Bone Marrow
Thymocyte
Leukemia cell
Neuroblastoma cell
Breast
Ovarian cancer
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Expression

CD340 is expressed by bone marrow CD271+ mesenchymal stem cells, subsets of C-ALL blasts and B lymphoblastis leukemia.  Several types of epithelial cells express CD340 and many cancers including neuroblastomas and carcinomas of the breast, stomach, lung, ovary, colon, cervix and ovarian tumors. 



Structure
MOLECULAR FAMILY NAME:  Belongs to the tyrosine kinase protein family.

CD340 is a single-pass type-1 1233 aa glycoprotein.  It contains a 630 aa extracellular domain which contains 4 domains (I-IV) and domain II and IV are cysteine-rich and 7 potential N-linked glycosylation sites, 23 aa transmembrane domain and a 580 aa intracellular cytoplasmic domain which contains a protein tyrosine kinase domain.  CD340 encodes a member of the tyrosine kinase family of the epidermal growth factor (EGF) receptor subfamily.  CD340 has 1 protein kinase domain has no ligand binding domain of its own and therefore cannot bind growth factors.  However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signaling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase.

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields several isoforms but all of which have not been characterized.

POST-TRANSLATIONAL MODIFICATION

CD340 has 7 potential N-linked glycosylation sites.



Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD340

Ligand binding increases phosphorylation of tyrosine kinases.



Function
Although no direct ligand has been observed for CD340, it forms heterodimers with ligand-bound ERBB family members and plexin-1.  Heterodimerization stabilizes ligand binding and contributes to kinase-mediated activation of MAPK, phospholipase-Cγ and PI-3K signaling pathways.  ERBB-heterodimers play a role in a wide range of cellular responses that vary depending on the ligand and the cell type.  CD340 forms a stable complex with plexin-B1 bound to its ligand CD100 (Sema4D).  CD340-mediated phosphorylation of plexin-B1 is involved in RhoA activation and ultimately in axonal growth cone collapse. 

BIOCHEMICALACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD340 IN INTACT ANIMAL

Homodimerization and receptor activation occurs when CD340 is overexpressed as occurs in several cancers.  In most cases overexpression is the result of gene amplification and increased promoter activity rather than mutations.  CD340 is a therapeutic target in the treatment of HER2-positive breast cancer with Trastuzumab (Herceptin).  Overexpression by carcinoma cells correlates with aggressive disease and a poor prognosis.  CD340 is a marker for bone marrow-MSC.



Comments
MOLECULAR INTERACTION-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD340: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD340: No information.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 2064P04626
Antibodies

Revised June 25, 2008


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