PXN (paxillin)

2011-08-01   Tiffany Pierson , Brendan C Stack Jr 

Department of Otolaryngology-Head, Neck Surgery, University of Arkansas for Medical Sciences, AR 72205, USA





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.




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


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).

Implicated in

Entity name
Head and neck cancers
PXN overexpression has been reported in various head and neck cancers (Li et al., 2008; Dai et al., 2010; Shi et al., 2010). Metallopanstimulin-1 expression has been associated with reduced PXN levels and tumor growth rate (Dai et al., 2010).
Entity name
Lung cancer
A significant correlation was found between the presence of the A127T mutation between the LD1 and LD2 regions of PXN with non small cell lung cancer (Jagadeeswaran et al., 2008). A possible mechanism is that mutations between the LD1 and 2 regions confer resistance to calpain mediated proteolysis of PXN (Cortesio et al., 2011). However, two later studies did not find this mutation to exist in lung cancer or any other solid tumor (Pallier et al., 2009; Kim et al., 2011).
Overexpression of PXN in non small cell lung cancer has been reported with less controversy (Jagadeeswaran et al., 2008; Zhao et al., 2010; Mackinnon et al., 2011). The overexpression could possibly be due to rearrangements on chromosome 12 (Wu et al., 2010).
Entity name
Breast cancer
Metastatic potential was found to be directly related to PXN levels (Cai et al., 2010). The relationship between PXN and Her-2 expression is controversial. A study in 2007 found a direct relationship between the 2 markers (Short et al., 2007) while a 2011 study found no such link (Panousis et al., 2011).
Entity name
Prostate cancer
PXN up regulation was found to promote adhesion and motility of prostate cancer cells (Bokobza et al., 2010).


Pubmed IDLast YearTitleAuthors
210427642010Growth and differentiation factor-9 promotes adhesive and motile capacity of prostate cancer cells by up-regulating FAK and Paxillin via Smad dependent pathway.Bokobza SM et al
153836532004Paxillin: adapting to change.Brown MC et al
203694782010[Expression of paxillin in breast cancer cell with high and low metastatic potentiality].Cai H et al
165527302006Paxillin modulates squamous cancer cell adhesion and is important in pressure-augmented adhesion.Conway WC et al
212701282011Calpain-mediated proteolysis of paxillin negatively regulates focal adhesion dynamics and cell migration.Cortesio CL et al
196420982010Extraribosomal function of metallopanstimulin-1: reducing paxillin in head and neck squamous cell carcinoma and inhibiting tumor growth.Dai Y et al
186504962008Paxillin comes of age.Deakin NO et al
181723052008Paxillin is a target for somatic mutations in lung cancer: implications for cell growth and invasion.Jagadeeswaran R et al
216177172011Absence of paxillin gene mutation in lung cancer and other common solid cancers.Kim MS et al
183809372008Increased expression of paxillin is found in human oesophageal squamous cell carcinoma: a tissue microarray study.Li BZ et al
210452342011Paxillin expression and amplification in early lung lesions of high-risk patients, lung adenocarcinoma and metastatic disease.Mackinnon AC et al
193535962009No somatic genetic change in the paxillin gene in nonsmall-cell lung cancer.Pallier K et al
216149032011The value of TOP2A, EZH2 and paxillin expression as markers of aggressive breast cancer: relationship with other prognostic factors.Panousis D et al
107956272000Role of the cytoskeletal protein paxillin in oncogenesis.Sattler M et al
177869452008Paxillin's LD4 motif interacts with bcl-2.Sheibani N et al
201366972010Paxillin expression levels are correlated with clinical stage and metastasis in salivary adenoid cystic carcinoma.Shi J et al
173198532007The expression of the cytoskeletal focal adhesion protein paxillin in breast cancer correlates with HER2 overexpression and may help predict response to chemotherapy: a retrospective immunohistochemical study.Short SM et al
211596522010Paxillin predicts survival and relapse in non-small cell lung cancer by microRNA-218 targeting.Wu DW et al
201337772010Identification and functional characterization of paxillin as a target of protein tyrosine phosphatase receptor T.Zhao Y et al

Other Information

Locus ID:

NCBI: 5829
MIM: 602505
HGNC: 9718
Ensembl: ENSG00000089159


dbSNP: 5829
ClinVar: 5829
TCGA: ENSG00000089159


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
VEGF signaling pathwayKEGGko04370
Focal adhesionKEGGko04510
Leukocyte transendothelial migrationKEGGko04670
Regulation of actin cytoskeletonKEGGko04810
VEGF signaling pathwayKEGGhsa04370
Focal adhesionKEGGhsa04510
Leukocyte transendothelial migrationKEGGhsa04670
Regulation of actin cytoskeletonKEGGhsa04810
Chemokine signaling pathwayKEGGko04062
Chemokine signaling pathwayKEGGhsa04062
Bacterial invasion of epithelial cellsKEGGko05100
Bacterial invasion of epithelial cellsKEGGhsa05100
Viral carcinogenesisKEGGhsa05203
Viral carcinogenesisKEGGko05203
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GAB1 signalosomeREACTOMER-HSA-180292
Signaling by VEGFREACTOMER-HSA-194138
Muscle contractionREACTOMER-HSA-397014
Smooth Muscle ContractionREACTOMER-HSA-445355
Cell-Cell communicationREACTOMER-HSA-1500931
Cell junction organizationREACTOMER-HSA-446728
Cell-extracellular matrix interactionsREACTOMER-HSA-446353
Localization of the PINCH-ILK-PARVIN complex to focal adhesionsREACTOMER-HSA-446343
Regulation of cytoskeletal remodeling and cell spreading by IPP complex componentsREACTOMER-HSA-446388
Signaling by PTK6REACTOMER-HSA-8848021
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinasesREACTOMER-HSA-8849471

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
128539632003JNK phosphorylates paxillin and regulates cell migration.178
211482922011Distinct roles for paxillin and Hic-5 in regulating breast cancer cell morphology, invasion, and metastasis.86
214869522011Actomyosin-generated tension controls the molecular kinetics of focal adhesions.76
285539382017The MBNL3 splicing factor promotes hepatocellular carcinoma by increasing PXN expression through the alternative splicing of lncRNA-PXN-AS1.66
181723052008Paxillin is a target for somatic mutations in lung cancer: implications for cell growth and invasion.55
175134572007Paxillin-beta-catenin interactions are involved in Rac/Cdc42-mediated endothelial barrier-protective response to oxidized phospholipids.52
117797092002Tyrosine phosphorylation of paxillin, FAK, and p130CAS: effects on cell spreading and migration.48
232751532013Overexpression of paxillin induced by miR-137 suppression promotes tumor progression and metastasis in colorectal cancer.46
180459962008Paxillin phosphorylation controls invadopodia/podosomes spatiotemporal organization.45
212701282011Calpain-mediated proteolysis of paxillin negatively regulates focal adhesion dynamics and cell migration.44


Tiffany Pierson ; Brendan C Stack Jr

PXN (paxillin)

Atlas Genet Cytogenet Oncol Haematol. 2011-08-01

Online version: http://atlasgeneticsoncology.org/gene/41953/pxn-(paxillin)