PXN

Summary

PXN (paxillin, HGNC:9718) is a protein-coding gene on chromosome 12q24.23, encoding Paxillin (P49023). Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion).

This gene encodes a cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Alternatively spliced transcript variants encoding different isoforms have been described for this gene. These isoforms exhibit different expression pattern, and have different biochemical, as well as physiological properties (PMID:9054445).

Source: NCBI Gene 5829 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 121 total
• Druggable target: yes
• MANE Select transcript: NM_001385981

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9718
Approved symbol	PXN
Name	paxillin
Location	12q24.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000089159
Ensembl biotype	protein_coding
OMIM	602505
Entrez	5829

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 35 protein_coding, 8 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000228307, ENST00000267257, ENST00000323871, ENST00000424649, ENST00000440827, ENST00000458477, ENST00000536957, ENST00000538144, ENST00000540221, ENST00000543331, ENST00000546532, ENST00000547746, ENST00000547772, ENST00000547983, ENST00000548912, ENST00000550205, ENST00000550795, ENST00000551327, ENST00000552550, ENST00000637386, ENST00000637617, ENST00000637624, ENST00000884789, ENST00000884790, ENST00000884791, ENST00000884792, ENST00000884793, ENST00000884794, ENST00000884795, ENST00000884796, ENST00000884797, ENST00000884798, ENST00000884799, ENST00000884800, ENST00000884801, ENST00000884802, ENST00000884803, ENST00000884804, ENST00000916171, ENST00000916172, ENST00000916173, ENST00000916174, ENST00000916175, ENST00000967074, ENST00000967075, ENST00000967076

RefSeq mRNA: 15 — MANE Select: NM_001385981 NM_001080855, NM_001243756, NM_001385981, NM_001385982, NM_001385983, NM_001385984, NM_001385985, NM_001385986, NM_001385987, NM_001385988, NM_001385989, NM_001385990, NM_001410986, NM_002859, NM_025157

CCDS: CCDS44996, CCDS44997, CCDS44998, CCDS58281, CCDS91758, CCDS91759

Canonical transcript exons

ENST00000637617 — 15 exons

Exon	Start	End
ENSE00001226595	120219207	120220091
ENSE00003480572	120214825	120214998
ENSE00003518203	120221623	120221758
ENSE00003524226	120214136	120214217
ENSE00003563867	120215560	120215661
ENSE00003593674	120215103	120215273
ENSE00003642718	120223718	120223833
ENSE00003643051	120213842	120213990
ENSE00003659864	120222549	120222750
ENSE00003663030	120224151	120224377
ENSE00003673877	120222863	120222999
ENSE00003794604	120265617	120265730
ENSE00003797090	120216273	120216581
ENSE00003799898	120216841	120217116
ENSE00003928961	120210447	120212580

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 98.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 78.5854 / max 1439.0609, expressed in 1821 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133616	59.4369	1808
133615	9.2096	1592
133603	4.6393	521
133600	1.3315	892
133607	0.8998	235
133601	0.8056	473
133614	0.5294	220
133612	0.3944	179
133598	0.2765	88
133613	0.2333	133

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.27	gold quality
tibial nerve	UBERON:0001323	97.88	gold quality
left uterine tube	UBERON:0001303	97.75	gold quality
apex of heart	UBERON:0002098	97.36	gold quality
gastrocnemius	UBERON:0001388	97.33	gold quality
endocervix	UBERON:0000458	97.24	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.08	gold quality
upper lobe of left lung	UBERON:0008952	97.03	gold quality
body of uterus	UBERON:0009853	97.02	gold quality
transverse colon	UBERON:0001157	96.88	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.85	gold quality
lower esophagus	UBERON:0013473	96.82	gold quality
omental fat pad	UBERON:0010414	96.68	gold quality
mucosa of stomach	UBERON:0001199	96.67	gold quality
peritoneum	UBERON:0002358	96.63	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.55	gold quality
muscle of leg	UBERON:0001383	96.47	gold quality
right atrium auricular region	UBERON:0006631	96.40	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.38	gold quality
right lobe of thyroid gland	UBERON:0001119	96.36	gold quality
sural nerve	UBERON:0015488	96.35	gold quality
right uterine tube	UBERON:0001302	96.29	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.22	gold quality
right lung	UBERON:0002167	96.20	gold quality
left lobe of thyroid gland	UBERON:0001120	96.18	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.15	gold quality
blood	UBERON:0000178	96.09	gold quality
upper lobe of lung	UBERON:0008948	96.01	gold quality
metanephros cortex	UBERON:0010533	95.92	gold quality
ectocervix	UBERON:0012249	95.88	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	20.77
E-MTAB-6678	yes	11.20
E-CURD-10	no	238.02
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

88 targeting PXN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-6797-5P	99.61	66.55	2084

Literature-anchored findings (GeneRIF, showing 40)

• Binding of Paxillin to the alpha 9 Integrin Cytoplasmic Domain Inhibits Cell Spreading. (PMID:11477105)
• expression in conventional renal cell carcinomas (RCCs), papillary RCCs, chromophobe RCCs, collecting duct carcinomas, oncocytomas; role in signal transductions as a focal adhesion between tumor cells and the ECM in tumors with collecting duct phenotypes (PMID:11759057)
• Tyrosine phosphorylation of PXN regulates localization and downstream signaling with profound effects on cell movement. (PMID:11779709)
• Binding of cytoskeletal paxillin to the C-terminal of Pyk2 in cultured human umbilical vein endothelial cells is phosphorylation-independent and is not affected by acute exposure to thrombin. (PMID:11820787)
• Amino acid substitutions at relevant serine residues in urokinase prevents paxillin redistribution in MCF-7 cells. (PMID:11928806)
• Paxillin binding to the alpha 4 integrin tail is required for both efficient communication between integrins alpha 4 beta 1 and alpha L beta 2 and for direct integrin alpha 4 beta 1-dependent T cell migration. (PMID:12794117)
• Integrin alpha 4 beta 1-dependent T cell migration requires both phosphorylation and dephosphorylation of the alpha 4 cytoplasmic domain to regulate the reversible binding of this protein. (PMID:12837751)
• phosphorylation of paxillin by JNK seems essential for maintaining the labile adhesions required for rapid cell migration (PMID:12853963)
• interaction of bcl-2 with paxillin plays an important role during nephrogenesis (PMID:14699151)
• Data show that phosphorylation of paxillin is involved in NGF-induced neurite extension of PC-12 cells, probably through regulating focal adhesion organization. (PMID:14970194)
• RhoA/Rho-kinase pathway followed by tyrosine phosphorylation of FAK and paxillin leads to ATP release and actin reorganization in vascular endothelium (PMID:15155793)
• Lysophosphatidic acid induces Rho activation and consequent tyrosine phosphorylation of paxillin in human corneal epithelial cellss. Likely contributes to promotion of corneal epithelial migration by this agent. (PMID:15175910)
• early spreading responses to HGF may partly relate to increased paxillin availability for incorporation into, and turnover within, dynamic cytoskeletal/membrane complexes whose rapid and transient adhesion to the matrix drives migration. (PMID:15191880)
• chemoattractant stimulation induces paxillin association with alpha4 integrins, particularly in leukocytes (PMID:15242880)
• paxillin tyrosine 31 and 118 phosphorylation controls polarization and motility of lymphoid cells and is PMA-sensitive (PMID:15252114)
• Myocilin impaired focal adhesion formation and specifically blocked the incorporation of paxillin, but not vinculin, into focal adhesions. (PMID:15652337)
• Angiotensin II mediates an increase in focal adhesion kinase and paxillin phosphorylation and induces human umbilical vein endothelial cells migration through signal transduction pathways (PMID:15652490)
• Expression of paxillin and syndecan-1 in hepatocellular carcinoma(HCC) may affect its invasive and metastatic ability. May be converse correlation between expression of paxillin and syndecan-1 protein in HCC. (PMID:15770719)
• Caco-2 migration on collagen IV is regulated by both p130cas and paxillin but Src phosphorylation of p130cas is more important for this process (PMID:15817476)
• overexpression of paxillin synergistically contribute to the high metastatic potential of human osteosarcoma through the hyperphosphorylation of paxillin (PMID:15870699)
• p130Cas and paxillin function as effectors of GD3-mediated signaling, leading to such malignant properties as rapid cell growth and invasion in melanoma cells (PMID:16040804)
• proteomic analysis of paxillin post-translational modifications and interacting proteins by mass spectrometry (PMID:16212439)
• Alpha4beta1-dependent adhesion strengthening under mechanical strain is regulated by paxillin association with the alpha4-cytoplasmic domain (PMID:16365170)
• Metastasizing squamous cancer cell adhesiveness may be increased by paxillin-overexpression or by paxillin activation by extracellular pressure during surgical manipulation or growth within a constraining compartment. (PMID:16552730)
• Our results indicate that Src maintains fibronectin matrix at the cell surface through its effect on integrin activity and paxillin phosphorylation. (PMID:17187346)
• Hic-5 and paxillin function as negative feedback regulators of Src family kinases in aggregated platelets (PMID:17233630)
• study reports paxillin is phosphorylated in response to fibronectin-bound group A Streptococcus that express either M1 or PrtF1/SfbI protein; integrin-linked kinase activity is indispensable for M1-induced paxillin recruitment and phosphorylation (PMID:17298394)
• analysis of paxillin and ponsin interaction in nascent costameres of muscle cells (PMID:17462669)
• OxPAPC promoted novel interactions between focal adhesion and adherens junction complexes via paxillin and beta-catenin association, which was critically dependent on Rac and Cdc42 activities. (PMID:17513457)
• These findings support a novel role for RACK1 as a key regulator of cell migration and adhesion dynamics through the regulation of Src activity, and the modulation of paxillin phosphorylation at early adhesions. (PMID:17574549)
• Invadopodia ring expansion is controlled by paxillin phosphorylations on tyrosine 31 and 118, which allows invadopodia disassembly. (PMID:18045996)
• Focal adhesion kinase as well as p130Cas and paxillin should be a crucial molecule undergoing stronger tyrosine phosphorylation in GD3-expressing melanoma cells. (PMID:18078823)
• These results establish an important role for paxillin in lung cancer. (PMID:18172305)
• Tissue factor pathway inhibitor prevented paxillin/focal adhesion kinase phosphorylation in endothelial cells to influence angiogenesis. (PMID:18327407)
• No correlation occurs with clinocopathological parameters of esophageal squamous cell carcinoma,nor is paxilcillin an effective prognositic marker in these patients. (PMID:18380937)
• Data show that genetic upregulation of matriptase-2 reduces the aggressiveness of prostate cancer cells in vitro and in vivo and affects FAK and paxillin localisation. (PMID:18449907)
• the alpha-parvin CH2-paxillin LD1 complex has a role in for focal adhesion assembly (PMID:18508764)
• analysis of PAFR activation and pleiotropic effects on tyrosine phospho-EGFR/Src/FAK/paxillin in ovarian cancer (PMID:18632638)
• These data show a dual role of paxillin in the HGF- and VEGF-mediated endothelial barrier regulation and suggest essential paxillin role in the modulation of Rac-Rho crosstalk. (PMID:18664639)
• PAK1-specific paxillin phosphorylation at Ser(273) is critically involved in the positive-feedback regulation of the Rac-PAK1 pathway. (PMID:18676874)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	pxnb	ENSDARG00000060766
danio_rerio	pxna	ENSDARG00000088590
mus_musculus	Pxn	ENSMUSG00000029528
rattus_norvegicus	Pxn	ENSRNOG00000001149
drosophila_melanogaster	Pax	FBGN0041789
drosophila_melanogaster	CG30178	FBGN0050178
drosophila_melanogaster	CG31624	FBGN0051624
drosophila_melanogaster	CG31988	FBGN0051988
drosophila_melanogaster	CG34325	FBGN0085354
caenorhabditis_elegans		WBGENE00016197
caenorhabditis_elegans	C34B2.4	WBGENE00016389
caenorhabditis_elegans	F33D11.1	WBGENE00018000

Paralogs (2): LPXN (ENSG00000110031), TGFB1I1 (ENSG00000140682)

Protein

Protein identifiers

Paxillin — P49023 (reviewed: P49023)

All UniProt accessions (12): P49023, A0A140VJQ8, A0A1B0GTU4, A0A1B0GU60, A0A1B0GV30, A0A1B0GWE7, F5GZ78, F5H836, F8VZ39, F8W0G0, F8W0K8, F8W1E0

UniProt curated annotations — full annotation on UniProt →

Function. Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Recruits other proteins such as TRIM15 to focal adhesion.

Subunit / interactions. Interacts in vitro with VCL/vinculin as well as to the SH3 domain of SRC and, when tyrosine phosphorylated, to the SH2 domain of CRK. Interacts with GIT1. Interacts with NUDT16L1/SDOS. Interacts with PTK2/FAK1. Interacts with PTK2B/PYK2. Interacts with ASAP2. Interacts with unphosphorylated ITGA4. Interacts with RNF5. Interacts with PDCD10. Interacts with NEK3, the interaction is prolactin-dependent. Interacts with PTK6. Interacts with TGFB1I1. Interacts with SORBS1. Interacts with PARVB. Interacts (via LD motif 4) with PARVA/PARVIN. Interacts (via LD motif 4) with ILK. Interacts (via cytoplasmic domain) with CEACAM1; the interaction is phosphotyrosyl-dependent. Interacts with LIMA1; this complex stabilizes actin dynamics. Interacts with CD36 (via C-terminus). Interacts with TRIM15. Interacts with PAK4; PAK4 acts as a scaffold to support PAXI phosphorylation at Ser-272. Interacts strongly with PTK2/FAK1 and weakly with VCL/vinculin. Interacts strongly with VCL/vinculin but only weakly with PTK2/FAK1.

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Focal adhesion. Cell cortex.

Post-translational modifications. Phosphorylated by MAPK1/ERK2. Phosphorylated on tyrosine residues during integrin-mediated cell adhesion, embryonic development, fibroblast transformation and following stimulation of cells by mitogens. Phosphorylation at Ser-244 by CDK5 reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation. Phosphorylation at Tyr-31 and Tyr-118 by PTK6 promote the activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion. Phosphorylation at Ser-250 by SLK is required for PXN redistribution and cell motility. Phosphorylation at Ser-272 promotes focal adhesion disassembly during cell migration.

Similarity. Belongs to the paxillin family.

Isoforms (4)

UniProt ID	Names	Canonical?
P49023-1	Beta	yes
P49023-2	Alpha
P49023-3	Gamma
P49023-4	4

RefSeq proteins (15): NP_001074324, NP_001230685, NP_001372910, NP_001372911, NP_001372912, NP_001372913, NP_001372914, NP_001372915, NP_001372916, NP_001372917, NP_001372918, NP_001372919, NP_001397915, NP_002850, NP_079433 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain
IPR001904	Paxillin_Lim_dom4	Domain
IPR047072	Paxillin_Lim_dom2	Domain
IPR047075	Paxillin_TGFB1I1_LIM_dom1	Domain

Pfam: PF00412, PF03535

UniProt features (81 total): modified residue 27, strand 15, helix 7, short sequence motif 5, turn 5, domain 4, compositionally biased region 4, region of interest 4, splice variant 3, sequence conflict 3, chain 1, sequence variant 1, mutagenesis site 1, initiator methionine 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
2O9V	X-RAY DIFFRACTION	1.63
2VZG	X-RAY DIFFRACTION	1.8
6PW8	X-RAY DIFFRACTION	1.95
4XH2	X-RAY DIFFRACTION	2
2VZD	X-RAY DIFFRACTION	2.1
2VZI	X-RAY DIFFRACTION	2.2
5UWH	X-RAY DIFFRACTION	2.26
3PY7	X-RAY DIFFRACTION	2.29
1OW6	X-RAY DIFFRACTION	2.35
3RQG	X-RAY DIFFRACTION	2.5
4XGZ	X-RAY DIFFRACTION	2.5
9QWO	X-RAY DIFFRACTION	2.54
1OW7	X-RAY DIFFRACTION	2.6
6IUI	X-RAY DIFFRACTION	2.6
3RQF	X-RAY DIFFRACTION	2.7
3RQE	X-RAY DIFFRACTION	2.8
1OW8	X-RAY DIFFRACTION	2.85
4EDN	X-RAY DIFFRACTION	2.9
3GM1	X-RAY DIFFRACTION	2.95
3U3F	X-RAY DIFFRACTION	3.1
4R32	X-RAY DIFFRACTION	3.5
2K2R	SOLUTION NMR
6U4M	SOLUTION NMR
6U4N	SOLUTION NMR
7QB0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49023-F1	66.18	0.36

Antibody-complex structures (SAbDab): 2 — 4XGZ, 4XH2

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (27): 1, 31, 83, 85, 88, 106, 118, 119, 126, 130, 132, 137, 140, 143, 181, 230, 244, 250, 258, 261 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
7–8	loss of interaction with pdcd10.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-180292	GAB1 signalosome
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-445355	Smooth Muscle Contraction
R-HSA-446343	Localization of the PINCH-ILK-PARVIN complex to focal adhesions
R-HSA-446388	Regulation of cytoskeletal remodeling and cell spreading by IPP complex components
R-HSA-8849471	PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-HSA-9926550	Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition

MSigDB gene sets: 363 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, REACTOME_GAB1_SIGNALOSOME, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, AREB6_01, MODULE_16, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, PID_INTEGRIN_A9B1_PATHWAY, RODRIGUES_NTN1_TARGETS_DN, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, PID_MTOR_4PATHWAY

GO Biological Process (10): cell adhesion (GO:0007155), signal transduction (GO:0007165), signal complex assembly (GO:0007172), transforming growth factor beta receptor signaling pathway (GO:0007179), cell migration (GO:0016477), substrate adhesion-dependent cell spreading (GO:0034446), cellular response to reactive oxygen species (GO:0034614), endothelial cell migration (GO:0043542), positive regulation of stress fiber assembly (GO:0051496), growth hormone receptor signaling pathway (GO:0060396)

GO Molecular Function (6): beta-catenin binding (GO:0008013), vinculin binding (GO:0017166), protein phosphatase binding (GO:0019903), neuropilin binding (GO:0038191), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (11): stress fiber (GO:0001725), cytosol (GO:0005829), microtubule associated complex (GO:0005875), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), focal adhesion (GO:0005925), cell cortex (GO:0005938), lamellipodium (GO:0030027), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Cell-extracellular matrix interactions	2
Signaling by EGFR	1
Signaling by VEGF	1
Muscle contraction	1
Signaling by PTK6	1
MITF-M-dependent gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
cytoplasm	2
cellular anatomical structure	2
cell periphery	2
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of signal transduction	1
protein-containing complex assembly	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell motility	1
cell-substrate adhesion	1
response to reactive oxygen species	1
cellular response to oxidative stress	1
cellular response to oxygen-containing compound	1
cell migration	1
positive regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to growth hormone stimulus	1
protein binding	1
cytoskeletal protein binding	1
phosphatase binding	1
signaling receptor binding	1
cation binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1
microtubule cytoskeleton	1
protein-containing complex	1
membrane	1
anchoring junction	1
cell-substrate junction	1
cell leading edge	1
plasma membrane bounded cell projection	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

3212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PXN	VCL	P18206	999
PXN	PTK2	Q05397	999
PXN	TLN1	Q9Y490	999
PXN	TLN2	Q9Y4G6	999
PXN	SRC	P12931	998
PXN	BCAR1	P56945	998
PXN	ILK	P57043	997
PXN	PTK2B	Q14289	997
PXN	GIT1	Q9Y2X7	997
PXN	GIT2	Q14161	996
PXN	CRK	P46108	995
PXN	PARVA	Q9NVD7	995
PXN	HCLS1	P14317	994
PXN	CTTN	Q14247	994
PXN	ZYX	Q15942	990

IntAct

177 interactions, top by confidence:

A	B	Type	Score
HRAS	RAF1	psi-mi:“MI:0914”(association)	0.980
PTK2	PXN	psi-mi:“MI:0915”(physical association)	0.940
PXN	PTK2	psi-mi:“MI:0915”(physical association)	0.940
PXN	PTK2	psi-mi:“MI:0403”(colocalization)	0.940
NRAS	RAF1	psi-mi:“MI:0914”(association)	0.930
PTPN12	SHC1	psi-mi:“MI:0914”(association)	0.860
PXN	PTPN12	psi-mi:“MI:0915”(physical association)	0.760
FN1	ITGB1	psi-mi:“MI:0914”(association)	0.750
EGFR	CTNND1	psi-mi:“MI:0914”(association)	0.750
E6	PXN	psi-mi:“MI:0407”(direct interaction)	0.740
E6	PXN	psi-mi:“MI:0915”(physical association)	0.740
RABGGTB	YKT6	psi-mi:“MI:0914”(association)	0.740
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
PXN	E6	psi-mi:“MI:0915”(physical association)	0.740
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730

BioGRID (498): PXN (Affinity Capture-RNA), PXN (Affinity Capture-RNA), PXN (Affinity Capture-RNA), PXN (Affinity Capture-Western), HDAC6 (Co-localization), HDAC6 (FRET), HDAC6 (Affinity Capture-Western), PXN (Affinity Capture-MS), PXN (Affinity Capture-MS), PXN (Affinity Capture-MS), PXN (Affinity Capture-MS), PXN (Affinity Capture-Western), TRIM15 (Affinity Capture-Western), PXN (Reconstituted Complex), CAP1 (Co-fractionation)

ESM2 similar proteins: A5D7K1, A5H447, B5DEH0, D3ZEN0, D3ZIE4, D3ZQL6, E1B7L7, E1BBG2, G5E5X0, O15117, O35601, O75112, P49023, Q03173, Q04584, Q0VA45, Q15942, Q3TN34, Q3ULZ2, Q4G0F8, Q5F464, Q5HYK7, Q5R7I1, Q5T0Z8, Q5XI07, Q62523, Q64GL0, Q68CZ2, Q6NZJ6, Q6ZU65, Q80WC1, Q80XI3, Q8BFW7, Q8BGT6, Q8CC35, Q8CI51, Q8IY33, Q8N3F8, Q8VI36, Q8WX93

Diamond homologs: A0A1L8F1M4, A0M8R4, A0M8S5, A0M8U6, A1Z6W3, A8WH69, O42565, O43900, O54785, O70209, P47226, P49023, P49024, P50464, P53666, P53667, P53668, P53669, P53670, P53671, Q00PK1, Q07DW1, Q07DX3, Q07DY3, Q07DZ4, Q07E27, Q07E40, Q07E51, Q09YI0, Q09YJ2, Q09YK3, Q09YL5, Q09YN8, Q108U9, Q14192, Q174I2, Q17QE2, Q28FG2, Q292U2, Q292U5

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
PXN	up-regulates	ILK	binding
MAPK14	unknown	PXN	phosphorylation
PAK1	unknown	PXN	phosphorylation
PAK4	unknown	PXN	phosphorylation
PTPRR	“down-regulates activity”	PXN	dephosphorylation
PTK2	“up-regulates activity”	PXN	binding
PXN	up-regulates	Cell_migration
SRC	“up-regulates activity”	PXN	phosphorylation
PTPRT	“down-regulates activity”	PXN	dephosphorylation
PXN	“up-regulates activity”	BCAR1
RNF5	“down-regulates quantity”	PXN	ubiquitination
CDK5	“up-regulates activity”	PXN	phosphorylation
MAP3K2	“down-regulates quantity”	PXN	phosphorylation
PTK2B	“down-regulates quantity by destabilization”	PXN	phosphorylation
PTK6	“up-regulates activity”	PXN	phosphorylation
PTK2	“up-regulates activity”	PXN	phosphorylation
MAPK8	“up-regulates activity”	PXN	phosphorylation
PTPRG	“up-regulates activity”	PXN	dephosphorylation
PXN	“up-regulates activity”	“IPP complex”	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 123 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Constitutive Signaling by EGFRvIII	6	46.0×	2e-07
Signaling by ERBB2 ECD mutants	6	43.3×	2e-07
GAB1 signalosome	6	40.9×	3e-07
Erythropoietin activates RAS	5	40.9×	4e-06
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	6	36.8×	6e-07
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	6	33.5×	1e-06
Downstream signal transduction	8	32.8×	6e-08
Tie2 Signaling	5	32.3×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine dephosphorylation	5	41.1×	1e-05
ephrin receptor signaling pathway	9	28.7×	1e-08
epidermal growth factor receptor signaling pathway	12	27.5×	2e-11
heterotypic cell-cell adhesion	5	26.9×	8e-05
insulin receptor signaling pathway	11	22.6×	1e-09
substrate adhesion-dependent cell spreading	7	22.3×	5e-06
positive regulation of substrate adhesion-dependent cell spreading	6	20.8×	4e-05
lamellipodium assembly	5	20.5×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

121 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	98
Likely benign	6
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

7013 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:120212335:G:C	C585W	1.000
12:120212336:C:A	C585F	1.000
12:120212336:C:G	C585S	1.000
12:120212336:C:T	C585Y	1.000
12:120212337:A:G	C585R	1.000
12:120212337:A:T	C585S	1.000
12:120212344:A:C	C582W	1.000
12:120212345:C:A	C582F	1.000
12:120212345:C:G	C582S	1.000
12:120212345:C:T	C582Y	1.000
12:120212346:A:G	C582R	1.000
12:120212346:A:T	C582S	1.000
12:120212349:A:C	Y581D	1.000
12:120212351:G:T	P580H	1.000
12:120212371:G:C	F573L	1.000
12:120212371:G:T	F573L	1.000
12:120212372:A:C	F573C	1.000
12:120212372:A:G	F573S	1.000
12:120212373:A:G	F573L	1.000
12:120212378:C:T	G571D	1.000
12:120212379:C:G	G571R	1.000
12:120212387:A:G	L568P	1.000
12:120212387:A:T	L568H	1.000
12:120212396:A:G	L565P	1.000
12:120212398:G:C	C564W	1.000
12:120212399:C:A	C564F	1.000
12:120212399:C:G	C564S	1.000
12:120212399:C:T	C564Y	1.000
12:120212400:A:G	C564R	1.000
12:120212400:A:T	C564S	1.000

dbSNP variants (sampled 300 via entrez): RS1000015133 (12:120230028 C>A,T), RS1000050487 (12:120265497 G>A), RS1000080809 (12:120215237 G>A,C,T), RS1000085904 (12:120223093 G>A,C,T), RS1000146458 (12:120256933 C>T), RS1000212568 (12:120211930 A>G), RS1000217169 (12:120229906 G>C), RS1000296673 (12:120227102 C>A), RS1000327725 (12:120242383 C>G), RS1000592044 (12:120221279 C>A,T), RS1000612463 (12:120239884 T>A), RS1000634217 (12:120255635 A>C,T), RS1000653226 (12:120218611 G>A), RS1000810580 (12:120252947 C>G,T), RS1000814255 (12:120213317 T>G)

Disease associations

OMIM: gene MIM:602505 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005991_20	Platelet count	3.000000e-09
GCST008103_87	Bipolar disorder	1.000000e-06
GCST011198_9	Left ventricular end-systolic volume	7.000000e-06
GCST011208_3	Left ventricular mass to end-diastolic volume ratio	3.000000e-10
GCST011214_4	Left ventricle wall thickness	2.000000e-06
GCST90002397_217	Mean spheric corpuscular volume	4.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0008206	left ventricular systolic function measurement
EFO:0010556	Left ventricular mass to end-diastolic volume ratio
EFO:0008205	left ventricular structural measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5715 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

89 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	4
Estradiol	increases expression, increases phosphorylation, decreases expression, decreases reaction, affects expression (+1 more)	4
Tretinoin	affects cotreatment, increases expression, increases reaction, decreases reaction	4
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases expression	3
Endosulfan	decreases expression	3
Valproic Acid	decreases expression, increases expression, affects expression	3
oxophenylarsine	affects cotreatment, decreases reaction, increases phosphorylation, affects localization	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Acetaminophen	increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Cadmium	decreases expression, increases abundance, increases expression	2
Formaldehyde	increases phosphorylation, increases activity, decreases expression	2
Methotrexate	increases expression	2
Ozone	affects expression, affects cotreatment, increases oxidation, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
diethyl maleate	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases abundance, increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases phosphorylation	1
dictamnine	decreases phosphorylation	1
coumarin	affects phosphorylation	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4411701	Binding	Effect on paxillin phosphorylation in human A549 cells up to 50 uM after 24 hrs by Western blot analysis	Ulleungdin, a Lasso Peptide with Cancer Cell Migration Inhibitory Activity Discovered by the Genome Mining Approach. — J Nat Prod

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1CM	Abcam A-431 PXN KO	Cancer cell line	Female
CVCL_B2CX	Abcam HeLa PXN KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.