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PXN (paxillin)

Written2011-08Tiffany Pierson, Brendan C Stack Jr
Department of Otolaryngology-Head, Neck Surgery, University of Arkansas for Medical Sciences, AR 72205, USA

(Note : for Links provided by Atlas : click)

Identity

Other aliasFLJ16691
HGNC (Hugo) PXN
LocusID (NCBI) 5829
Atlas_Id 41953
Location 12q24.23  [Link to chromosome band 12q24]
Location_base_pair Starts at 120210439 and ends at 120265771 bp from pter ( according to hg19-Feb_2009)  [Mapping PXN.png]
Local_order Information about the local order of PXN can be found at ensembl.org.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
C11orf58 (11p15.1) / PXN (12q24.23)GAB2 (11q14.1) / PXN (12q24.23)LLGL2 (17q25.1) / PXN (12q24.23)
MGRN1 (16p13.3) / PXN (12q24.23)MYBPC1 (12q23.2) / PXN (12q24.23)PXN (12q24.23) / MSI1 (12q24.31)
PXN (12q24.23) / MYBPC1 (12q23.2)PXN (12q24.23) / PLA2G1B (12q24.31)PXN (12q24.23) / RPL38 (17q25.1)
UQCR10 (22q12.2) / PXN (12q24.23)ZMYND19 (9q34.3) / PXN (12q24.23)

DNA/RNA

Description 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.
Transcription The transcript is 3788 base pairs long. 4 isoforms have been identified.
Pseudogene Not known.

Protein

Description 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.
Expression Epithelium.
Localisation Found in the cytoplasm closely apposed to the plasma membrane at sites of focal adhesion to the extracellular matrix.
 
Function 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 GF's 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).

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

Mutations

Germinal Not known.
Somatic 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

Note
  
Entity Head and neck cancers
Note 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 Lung cancer
Note 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 Breast cancer
Note 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 Prostate cancer
Note PXN up regulation was found to promote adhesion and motility of prostate cancer cells (Bokobza et al., 2010).
  

To be noted

The link between PXN mutations and increased growth rate and invasion of cancer cells is controversial. On the contrary, amplification and/or overexpression of PXN has been consistently reported in the literature.

Bibliography

Growth 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, Ye L, Kynaston HG, Jiang WG.
Oncol Rep. 2010 Dec;24(6):1653-9.
PMID 21042764
 
Paxillin: adapting to change.
Brown MC, Turner CE.
Physiol Rev. 2004 Oct;84(4):1315-39. (REVIEW)
PMID 15383653
 
Expression of paxillin in breast cancer cell with high and low metastatic potentiality.
Cai H, Zhang T, Tang WX, Li SL.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2010 Jan;41(1):91-4.
PMID 20369478
 
Paxillin modulates squamous cancer cell adhesion and is important in pressure-augmented adhesion.
Conway WC, Van der Voort van Zyp J, Thamilselvan V, Walsh MF, Crowe DL, Basson MD.
J Cell Biochem. 2006 Aug 15;98(6):1507-16.
PMID 16552730
 
Calpain-mediated proteolysis of paxillin negatively regulates focal adhesion dynamics and cell migration.
Cortesio CL, Boateng LR, Piazza TM, Bennin DA, Huttenlocher A.
J Biol Chem. 2011 Mar 25;286(12):9998-10006. Epub 2011 Jan 26.
PMID 21270128
 
Extraribosomal function of metallopanstimulin-1: reducing paxillin in head and neck squamous cell carcinoma and inhibiting tumor growth.
Dai Y, Pierson SE, Dudney WC, Stack BC Jr.
Int J Cancer. 2010 Feb 1;126(3):611-9.
PMID 19642098
 
Paxillin comes of age.
Deakin NO, Turner CE.
J Cell Sci. 2008 Aug 1;121(Pt 15):2435-44. (REVIEW)
PMID 18650496
 
Paxillin is a target for somatic mutations in lung cancer: implications for cell growth and invasion.
Jagadeeswaran R, Surawska H, Krishnaswamy S, Janamanchi V, Mackinnon AC, Seiwert TY, Loganathan S, Kanteti R, Reichman T, Nallasura V, Schwartz S, Faoro L, Wang YC, Girard L, Tretiakova MS, Ahmed S, Zumba O, Soulii L, Bindokas VP, Szeto LL, Gordon GJ, Bueno R, Sugarbaker D, Lingen MW, Sattler M, Krausz T, Vigneswaran W, Natarajan V, Minna J, Vokes EE, Ferguson MK, Husain AN, Salgia R.
Cancer Res. 2008 Jan 1;68(1):132-42.
PMID 18172305
 
Absence of paxillin gene mutation in lung cancer and other common solid cancers.
Kim MS, Yoo NJ, Lee SH.
Tumori. 2011 Mar-Apr;97(2):211-3. doi: 10.1700/667.7785.
PMID 21617717
 
Increased expression of paxillin is found in human oesophageal squamous cell carcinoma: a tissue microarray study.
Li BZ, Lei W, Zhang CY, Zhou F, Li N, Shi SS, Feng XL, Chen ZL, Hang J, Qiu B, Wan JT, Shao K, Xing XZ, Tan XG, Wang Z, Xiong MH, He J.
J Int Med Res. 2008 Mar-Apr;36(2):273-8.
PMID 18380937
 
Paxillin expression and amplification in early lung lesions of high-risk patients, lung adenocarcinoma and metastatic disease.
Mackinnon AC, Tretiakova M, Henderson L, Mehta RG, Yan BC, Joseph L, Krausz T, Husain AN, Reid ME, Salgia R.
J Clin Pathol. 2011 Jan;64(1):16-24. Epub 2010 Nov 2.
PMID 21045234
 
No somatic genetic change in the paxillin gene in nonsmall-cell lung cancer.
Pallier K, Houllier AM, Le Corre D, Cazes A, Laurent-Puig P, Blons H.
Mol Carcinog. 2009 Jul;48(7):581-5.
PMID 19353596
 
The value of TOP2A, EZH2 and paxillin expression as markers of aggressive breast cancer: relationship with other prognostic factors.
Panousis D, Patsouris E, Lagoudianakis E, Pappas A, Kyriakidou V, Voulgaris Z, Xepapadakis G, Manouras A, Athanassiadou AM, Athanassiadou P.
Eur J Gynaecol Oncol. 2011;32(2):156-9.
PMID 21614903
 
Role of the cytoskeletal protein paxillin in oncogenesis.
Sattler M, Pisick E, Morrison PT, Salgia R.
Crit Rev Oncog. 2000;11(1):63-76. (REVIEW)
PMID 10795627
 
Paxillin's LD4 motif interacts with bcl-2.
Sheibani N, Tang Y, Sorenson CM.
J Cell Physiol. 2008 Mar;214(3):655-61.
PMID 17786945
 
Paxillin expression levels are correlated with clinical stage and metastasis in salivary adenoid cystic carcinoma.
Shi J, Wang S, Zhao E, Shi L, Xu X, Fang M.
J Oral Pathol Med. 2010 Aug 1;39(7):548-51. Epub 2010 Jan 28.
PMID 20136697
 
The 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, Yoder BJ, Tarr SM, Prescott NL, Laniauskas S, Coleman KA, Downs-Kelly E, Pettay JD, Choueiri TK, Crowe JP, Tubbs RR, Budd TG, Hicks DG.
Breast J. 2007 Mar-Apr;13(2):130-9.
PMID 17319853
 
Paxillin predicts survival and relapse in non-small cell lung cancer by microRNA-218 targeting.
Wu DW, Cheng YW, Wang J, Chen CY, Lee H.
Cancer Res. 2010 Dec 15;70(24):10392-401.
PMID 21159652
 
Identification and functional characterization of paxillin as a target of protein tyrosine phosphatase receptor T.
Zhao Y, Zhang X, Guda K, Lawrence E, Sun Q, Watanabe T, Iwakura Y, Asano M, Wei L, Yang Z, Zheng W, Dawson D, Willis J, Markowitz SD, Satake M, Wang Z.
Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2592-7. Epub 2010 Jan 21.
PMID 20133777
 

Citation

This paper should be referenced as such :
Pierson, T ; Stack, BCJr
PXN (paxillin)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(2):100-102.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PXNID41953ch12q24.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  Chronic myelogenous leukaemia (CML)
t(11;21)(q21;q22) RUNX1/LPXN


External links

Nomenclature
HGNC (Hugo)PXN   9718
Cards
AtlasPXNID41953ch12q24
Entrez_Gene (NCBI)PXN  5829  paxillin
Aliases
GeneCards (Weizmann)PXN
Ensembl hg19 (Hinxton)ENSG00000089159 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000089159 [Gene_View]  chr12:120210439-120265771 [Contig_View]  PXN [Vega]
ICGC DataPortalENSG00000089159
TCGA cBioPortalPXN
AceView (NCBI)PXN
Genatlas (Paris)PXN
WikiGenes5829
SOURCE (Princeton)PXN
Genetics Home Reference (NIH)PXN
Genomic and cartography
GoldenPath hg38 (UCSC)PXN  -     chr12:120210439-120265771 -  12q24.23   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PXN  -     12q24.23   [Description]    (hg19-Feb_2009)
EnsemblPXN - 12q24.23 [CytoView hg19]  PXN - 12q24.23 [CytoView hg38]
Mapping of homologs : NCBIPXN [Mapview hg19]  PXN [Mapview hg38]
OMIM602505   
Gene and transcription
Genbank (Entrez)AA922640 AB209034 AK026695 AK122964 AK128712
RefSeq transcript (Entrez)NM_001080855 NM_001243756 NM_002859 NM_025157
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PXN
Cluster EST : UnigeneHs.446336 [ NCBI ]
CGAP (NCI)Hs.446336
Alternative Splicing GalleryENSG00000089159
Gene ExpressionPXN [ NCBI-GEO ]   PXN [ EBI - ARRAY_EXPRESS ]   PXN [ SEEK ]   PXN [ MEM ]
Gene Expression Viewer (FireBrowse)PXN [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5829
GTEX Portal (Tissue expression)PXN
Human Protein AtlasENSG00000089159-PXN [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP49023   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP49023  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP49023
Splice isoforms : SwissVarP49023
PhosPhoSitePlusP49023
Domaine pattern : Prosite (Expaxy)LIM_DOMAIN_1 (PS00478)    LIM_DOMAIN_2 (PS50023)   
Domains : Interpro (EBI)Paxillin    Znf_LIM   
Domain families : Pfam (Sanger)LIM (PF00412)   
Domain families : Pfam (NCBI)pfam00412   
Domain families : Smart (EMBL)LIM (SM00132)  
Conserved Domain (NCBI)PXN
DMDM Disease mutations5829
Blocks (Seattle)PXN
PDB (SRS)1KKY    1KL0    1OW6    1OW7    1OW8    2K2R    2O9V    2VZD    2VZG    2VZI    3GM1    3PY7    3RQE    3RQF    3RQG    3U3F    4EDN    4R32    4XGZ    4XH2   
PDB (PDBSum)1KKY    1KL0    1OW6    1OW7    1OW8    2K2R    2O9V    2VZD    2VZG    2VZI    3GM1    3PY7    3RQE    3RQF    3RQG    3U3F    4EDN    4R32    4XGZ    4XH2   
PDB (IMB)1KKY    1KL0    1OW6    1OW7    1OW8    2K2R    2O9V    2VZD    2VZG    2VZI    3GM1    3PY7    3RQE    3RQF    3RQG    3U3F    4EDN    4R32    4XGZ    4XH2   
PDB (RSDB)1KKY    1KL0    1OW6    1OW7    1OW8    2K2R    2O9V    2VZD    2VZG    2VZI    3GM1    3PY7    3RQE    3RQF    3RQG    3U3F    4EDN    4R32    4XGZ    4XH2   
Structural Biology KnowledgeBase1KKY    1KL0    1OW6    1OW7    1OW8    2K2R    2O9V    2VZD    2VZG    2VZI    3GM1    3PY7    3RQE    3RQF    3RQG    3U3F    4EDN    4R32    4XGZ    4XH2   
SCOP (Structural Classification of Proteins)1KKY    1KL0    1OW6    1OW7    1OW8    2K2R    2O9V    2VZD    2VZG    2VZI    3GM1    3PY7    3RQE    3RQF    3RQG    3U3F    4EDN    4R32    4XGZ    4XH2   
CATH (Classification of proteins structures)1KKY    1KL0    1OW6    1OW7    1OW8    2K2R    2O9V    2VZD    2VZG    2VZI    3GM1    3PY7    3RQE    3RQF    3RQG    3U3F    4EDN    4R32    4XGZ    4XH2   
SuperfamilyP49023
Human Protein Atlas [tissue]ENSG00000089159-PXN [tissue]
Peptide AtlasP49023
IPIIPI00335634   IPI00220030   IPI00220031   IPI00890738   IPI00915404   IPI00941515   IPI00335727   IPI01013237   IPI00555917   IPI01022943   IPI01022776   IPI01020807   IPI01022360   IPI01015055   IPI01015504   
Protein Interaction databases
DIP (DOE-UCLA)P49023
IntAct (EBI)P49023
FunCoupENSG00000089159
BioGRIDPXN
STRING (EMBL)PXN
ZODIACPXN
Ontologies - Pathways
QuickGOP49023
Ontology : AmiGOstress fiber  integrin binding  protein binding  cytosol  cytosol  microtubule associated complex  plasma membrane  plasma membrane  focal adhesion  cell cortex  muscle contraction  cell adhesion  cell-matrix adhesion  signal transduction  signal complex assembly  epidermal growth factor receptor signaling pathway  transforming growth factor beta receptor signaling pathway  beta-catenin binding  zinc ion binding  vinculin binding  protein kinase binding  lamellipodium  ubiquitin protein ligase binding  cellular response to reactive oxygen species  vascular endothelial growth factor receptor signaling pathway  growth hormone receptor signaling pathway  
Ontology : EGO-EBIstress fiber  integrin binding  protein binding  cytosol  cytosol  microtubule associated complex  plasma membrane  plasma membrane  focal adhesion  cell cortex  muscle contraction  cell adhesion  cell-matrix adhesion  signal transduction  signal complex assembly  epidermal growth factor receptor signaling pathway  transforming growth factor beta receptor signaling pathway  beta-catenin binding  zinc ion binding  vinculin binding  protein kinase binding  lamellipodium  ubiquitin protein ligase binding  cellular response to reactive oxygen species  vascular endothelial growth factor receptor signaling pathway  growth hormone receptor signaling pathway  
Pathways : KEGG   
REACTOMEP49023 [protein]
REACTOME PathwaysR-HSA-8849471 [pathway]   
NDEx NetworkPXN
Atlas of Cancer Signalling NetworkPXN
Wikipedia pathwaysPXN
Orthology - Evolution
OrthoDB5829
GeneTree (enSembl)ENSG00000089159
Phylogenetic Trees/Animal Genes : TreeFamPXN
HOVERGENP49023
HOGENOMP49023
Homologs : HomoloGenePXN
Homology/Alignments : Family Browser (UCSC)PXN
Gene fusions - Rearrangements
Fusion : MitelmanMYBPC1/PXN [12q23.2/12q24.23]  [t(12;12)(q23;q24)]  
Fusion : MitelmanPXN/MSI1 [12q24.23/12q24.31]  [t(12;12)(q24;q24)]  
Fusion : MitelmanPXN/MYBPC1 [12q24.23/12q23.2]  [t(12;12)(q23;q24)]  
Fusion: TCGAMYBPC1 12q23.2 PXN 12q24.23 LGG
Fusion: TCGAPXN 12q24.23 MSI1 12q24.31 HNSC LUAD
Fusion: TCGAPXN 12q24.23 MYBPC1 12q23.2 LGG
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPXN [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PXN
dbVarPXN
ClinVarPXN
1000_GenomesPXN 
Exome Variant ServerPXN
ExAC (Exome Aggregation Consortium)ENSG00000089159
GNOMAD BrowserENSG00000089159
Genetic variants : HAPMAP5829
Genomic Variants (DGV)PXN [DGVbeta]
DECIPHERPXN [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPXN 
Mutations
ICGC Data PortalPXN 
TCGA Data PortalPXN 
Broad Tumor PortalPXN
OASIS PortalPXN [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPXN  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPXN
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PXN
DgiDB (Drug Gene Interaction Database)PXN
DoCM (Curated mutations)PXN (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PXN (select a term)
intoGenPXN
NCG5 (London)PXN
Cancer3DPXN(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602505   
Orphanet
MedgenPXN
Genetic Testing Registry PXN
NextProtP49023 [Medical]
TSGene5829
GENETestsPXN
Target ValidationPXN
Huge Navigator PXN [HugePedia]
snp3D : Map Gene to Disease5829
BioCentury BCIQPXN
ClinGenPXN
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5829
Chemical/Pharm GKB GenePA34062
Clinical trialPXN
Miscellaneous
canSAR (ICR)PXN (select the gene name)
Probes
Litterature
PubMed285 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePXN
EVEXPXN
GoPubMedPXN
iHOPPXN
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 12 16:31:44 CEST 2017

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