The PXN gene is 55.314 kb and consists of 12 exons. This gene is a member of the Human CCDS set: CCDS44996, CCDS44997, CCDS44998.

The transcript is 3788 base pairs long. 4 isoforms have been identified.

Not known.

4 isoforms have been identified by alternative splicing. The 1st isoform is the normal variant and is comprised of 591 AA and weighs 68 kDa. The amino terminus region contains 5 LD-motifs, while the carboxy terminus contains 4 LIM-zinc binding domains. The protein also contains a proline rich region and several potential phosphorylation sites.

Epithelium.

Found in the cytoplasm closely apposed to the plasma membrane at sites of focal adhesion to the extracellular matrix.

Focal adhesion protein: This protein is a cytoskeletal component involved in focal actin-membrane attachments to the extracellular matrix. PXN can interact with multiple structural molecules and regulatory proteins to modulate adhesion, motility and survival of the cell by changing actin dynamics. Some PXN binding proteins have oncogenic equivalents, allowing cells to bypass normal adhesion and GF signaling cascades.
Regulation: PXN activity is regulated by various kinases. Adhesion and GFs stimulate these kinases to phosphorylate LD motifs or LIM domains. Molecules such as Vinculin, FAK and SRC phosphorylate tyrosine residues of the N-terminal LD motifs. This results in recruitment of downstream effectors (like CRK) to mediate changes in cell motility or in modulation of gene expression via MAPK pathways. N-terminal serine phosphorylation has also been identified. Phosphorylation of serine and threonine residues of C-terminal LIM domains results in recruitment to focal adhesions. Identification of the C-terminal kinases is currently under investigation.

Abbreviations: CRK (CT10 sarcoma oncogene cellular homolog ); FAK (focal adhesion kinase); GF (growth factor); MAPK (mitogen activated protein kinase); SRC (Rous sarcoma oncogene cellular homolog).

Member of the paxillin family, containing the 4 LIM-zinc binding domains.

Not known.

Several single nucleotide polymorphisms have been identified. Point mutations between the LD1 and LD2 motifs have been associated with lung cancer, the A127T mutation being the most frequent mutation (Jagadeeswaran, et al., 2008).