ASpdb: an integrative knowledgebase of human protein isoforms from experimental and AI-predicted structures

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	Protein Summary
	AS Summary
	Protein Functional Features
	Gene Isoform Structures and Expression Levels
	Protein Structures
	pLDDT Score Distribution
	Ramachandran Plot of Protein Structures
	Potential Active Site Information
	Protein Structure and Feature Comparision
	Protein-Protein Interaction
	Related Drugs
	Related Diseases
	Clinically Important Variants

Protein:PAX3

Protein Summary

Gene summary

Gene name: PAX3
ASpdb.0 ID: 5077
	Gene
Gene symbol	PAX3
Gene ID	5077
Gene name	paired box 3
Synonyms	CDHS\|HUP2\|PAX-3\|WS1\|WS3
Cytomap	2q36.1
Type of gene	protein-coding
Description	paired box protein Pax-3paired box homeotic gene 3paired domain gene 3paired domain gene HuP2transcriptional factor PAX3
Modification date	20240310
UniProtAcc	P23760

Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Gene	PAX3	GO:0005654	nucleoplasm	-
Gene	PAX3	GO:0043565	sequence-specific DNA binding	11863357
Gene	PAX3	GO:0045893	positive regulation of DNA-templated transcription	11863357
Gene	PAX3	GO:0045944	positive regulation of transcription by RNA polymerase II	11863357
Gene	PAX3	GO:1990837	sequence-specific double-stranded DNA binding	28473536

AS Summary

Information of the canonical protein with experimentally identified structure from PDB (2023).

UniProt Acc	File name	PDB ID	Method	Resolution	Chain	Start	End
P23760-1	P23760-1_3cmy_A.pdb	3CMY	X-ray	1.95	A	219	277

ASpdb's canonical and alternatively spliced isoform information.

accession_id	gene_name	canonical_id	alternative_id	canonical_length	alternative_length	canonical_start	canonical_end	type	originalSEQ	variationSEQ	alternative_start	alternative_end
P23760	PAX3	P23760-1	P23760-2	479	215	196	215	Substitution	ASAPQSDEGSDIDSEPDLPL	GKRWRLGRRTCWVTWRASAS	196	215
P23760	PAX3	P23760-1	P23760-2	479	215	216	479	Deletion	none	none	215	215
P23760	PAX3	P23760-1	P23760-3	479	206	196	206	Substitution	ASAPQSDEGSD	GKALVSGVSSH	196	206
P23760	PAX3	P23760-1	P23760-3	479	206	207	479	Deletion	none	none	206	206
P23760	PAX3	P23760-1	P23760-4	479	403	393	479	Substitution	MGLLTNHGGVPHQPQTDYALSPLTGGLEPTTTVSASCSQRLDHMKSLDSLPTSQSYCPPTYSTTGYSMDPVTGYQYGQYGQSKPWTF	PFIISSQISRK	393	403
P23760	PAX3	P23760-1	P23760-5	479	407	393	479	Substitution	MGLLTNHGGVPHQPQTDYALSPLTGGLEPTTTVSASCSQRLDHMKSLDSLPTSQSYCPPTYSTTGYSMDPVTGYQYGQYGQSKPWTF	PFIISSQISLGFKSF	393	407
P23760	PAX3	P23760-1	P23760-6	479	483	108	108	Deletion	none	none	107	107
P23760	PAX3	P23760-1	P23760-6	479	483	475	479	Substitution	KPWTF	AFHYLKPDIA	474	483
P23760	PAX3	P23760-1	P23760-7	479	484	475	479	Substitution	KPWTF	AFHYLKPDIA	475	484
P23760	PAX3	P23760-1	P23760-8	479	505	475	479	Substitution	KPWTF	AFHYLKPDIAWFQILLNTFDKSSGEEEDLEQ	475	505

Multiple sequence alignment of our canonical and alternatively spliced PAX3

Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of PAX3

UniProt-id	ENSG	ENST	ENSP
P23760-1	ENSG00000135903.20	ENST00000350526.9	ENSP00000343052.4
P23760-2	ENSG00000135903.20	ENST00000409828.7	ENSP00000386817.3
P23760-3	ENSG00000135903.20	ENST00000258387.6	ENSP00000258387.5
P23760-4	ENSG00000135903.20	ENST00000344493.9	ENSP00000342092.4
P23760-5	ENSG00000135903.20	ENST00000336840.11	ENSP00000338767.5
P23760-6	ENSG00000135903.20	ENST00000409551.7	ENSP00000386750.3
P23760-7	ENSG00000135903.20	ENST00000392070.7	ENSP00000375922.3
P23760-8	ENSG00000135903.20	ENST00000392069.6	ENSP00000375921.2

UniProt-id	NM ID	NP ID
P23760-1	NM_181457.3	NP_852122.1
P23760-2	NM_000438.5	NP_000429.2
P23760-3	NM_013942.4	NP_039230.1
P23760-4	NM_181461.3	NP_852126.1
P23760-5	NM_181460.3	NP_852125.1
P23760-6	NM_001127366.2	NP_001120838.1
P23760-7	NM_181458.3	NP_852123.1
P23760-8	NM_181459.3	NP_852124.1

Amino acid sequences of our canonical and alternatively spliced PAX3

accession_id	Protein sequence
P23760-1	MTTLAGAVPRMMRPGPGQNYPRSGFPLEVSTPLGQGRVNQLGGVFINGRPLPNHIRHKIVEMAHHGIRPCVISRQLRVSHGCVSKILCRY QETGSIRPGAIGGSKPKQVTTPDVEKKIEEYKRENPGMFSWEIRDKLLKDAVCDRNTVPSVSSISRILRSKFGKGEEEEADLERKEAEES EKKAKHSIDGILSERASAPQSDEGSDIDSEPDLPLKRKQRRSRTTFTAEQLEELERAFERTHYPDIYTREELAQRAKLTEARVQVWFSNR RARWRKQAGANQLMAFNHLIPGGFPPTAMPTLPTYQLSETSYQPTSIPQAVSDPSSTVHRPQPLPPSTVHQSTIPSNPDSSSAYCLPSTR HGFSSYTDSFVPPSGPSNPMNPTIGNGLSPQVMGLLTNHGGVPHQPQTDYALSPLTGGLEPTTTVSASCSQRLDHMKSLDSLPTSQSYCP
P23760-2	MTTLAGAVPRMMRPGPGQNYPRSGFPLEVSTPLGQGRVNQLGGVFINGRPLPNHIRHKIVEMAHHGIRPCVISRQLRVSHGCVSKILCRY QETGSIRPGAIGGSKPKQVTTPDVEKKIEEYKRENPGMFSWEIRDKLLKDAVCDRNTVPSVSSISRILRSKFGKGEEEEADLERKEAEES
P23760-3	MTTLAGAVPRMMRPGPGQNYPRSGFPLEVSTPLGQGRVNQLGGVFINGRPLPNHIRHKIVEMAHHGIRPCVISRQLRVSHGCVSKILCRY QETGSIRPGAIGGSKPKQVTTPDVEKKIEEYKRENPGMFSWEIRDKLLKDAVCDRNTVPSVSSISRILRSKFGKGEEEEADLERKEAEES
P23760-4	MTTLAGAVPRMMRPGPGQNYPRSGFPLEVSTPLGQGRVNQLGGVFINGRPLPNHIRHKIVEMAHHGIRPCVISRQLRVSHGCVSKILCRY QETGSIRPGAIGGSKPKQVTTPDVEKKIEEYKRENPGMFSWEIRDKLLKDAVCDRNTVPSVSSISRILRSKFGKGEEEEADLERKEAEES EKKAKHSIDGILSERASAPQSDEGSDIDSEPDLPLKRKQRRSRTTFTAEQLEELERAFERTHYPDIYTREELAQRAKLTEARVQVWFSNR RARWRKQAGANQLMAFNHLIPGGFPPTAMPTLPTYQLSETSYQPTSIPQAVSDPSSTVHRPQPLPPSTVHQSTIPSNPDSSSAYCLPSTR
P23760-5	MTTLAGAVPRMMRPGPGQNYPRSGFPLEVSTPLGQGRVNQLGGVFINGRPLPNHIRHKIVEMAHHGIRPCVISRQLRVSHGCVSKILCRY QETGSIRPGAIGGSKPKQVTTPDVEKKIEEYKRENPGMFSWEIRDKLLKDAVCDRNTVPSVSSISRILRSKFGKGEEEEADLERKEAEES EKKAKHSIDGILSERASAPQSDEGSDIDSEPDLPLKRKQRRSRTTFTAEQLEELERAFERTHYPDIYTREELAQRAKLTEARVQVWFSNR RARWRKQAGANQLMAFNHLIPGGFPPTAMPTLPTYQLSETSYQPTSIPQAVSDPSSTVHRPQPLPPSTVHQSTIPSNPDSSSAYCLPSTR
P23760-6	MTTLAGAVPRMMRPGPGQNYPRSGFPLEVSTPLGQGRVNQLGGVFINGRPLPNHIRHKIVEMAHHGIRPCVISRQLRVSHGCVSKILCRY QETGSIRPGAIGGSKPKVTTPDVEKKIEEYKRENPGMFSWEIRDKLLKDAVCDRNTVPSVSSISRILRSKFGKGEEEEADLERKEAEESE KKAKHSIDGILSERASAPQSDEGSDIDSEPDLPLKRKQRRSRTTFTAEQLEELERAFERTHYPDIYTREELAQRAKLTEARVQVWFSNRR ARWRKQAGANQLMAFNHLIPGGFPPTAMPTLPTYQLSETSYQPTSIPQAVSDPSSTVHRPQPLPPSTVHQSTIPSNPDSSSAYCLPSTRH GFSSYTDSFVPPSGPSNPMNPTIGNGLSPQVMGLLTNHGGVPHQPQTDYALSPLTGGLEPTTTVSASCSQRLDHMKSLDSLPTSQSYCPP
P23760-7	MTTLAGAVPRMMRPGPGQNYPRSGFPLEVSTPLGQGRVNQLGGVFINGRPLPNHIRHKIVEMAHHGIRPCVISRQLRVSHGCVSKILCRY QETGSIRPGAIGGSKPKQVTTPDVEKKIEEYKRENPGMFSWEIRDKLLKDAVCDRNTVPSVSSISRILRSKFGKGEEEEADLERKEAEES EKKAKHSIDGILSERASAPQSDEGSDIDSEPDLPLKRKQRRSRTTFTAEQLEELERAFERTHYPDIYTREELAQRAKLTEARVQVWFSNR RARWRKQAGANQLMAFNHLIPGGFPPTAMPTLPTYQLSETSYQPTSIPQAVSDPSSTVHRPQPLPPSTVHQSTIPSNPDSSSAYCLPSTR HGFSSYTDSFVPPSGPSNPMNPTIGNGLSPQVMGLLTNHGGVPHQPQTDYALSPLTGGLEPTTTVSASCSQRLDHMKSLDSLPTSQSYCP
P23760-8	MTTLAGAVPRMMRPGPGQNYPRSGFPLEVSTPLGQGRVNQLGGVFINGRPLPNHIRHKIVEMAHHGIRPCVISRQLRVSHGCVSKILCRY QETGSIRPGAIGGSKPKQVTTPDVEKKIEEYKRENPGMFSWEIRDKLLKDAVCDRNTVPSVSSISRILRSKFGKGEEEEADLERKEAEES EKKAKHSIDGILSERASAPQSDEGSDIDSEPDLPLKRKQRRSRTTFTAEQLEELERAFERTHYPDIYTREELAQRAKLTEARVQVWFSNR RARWRKQAGANQLMAFNHLIPGGFPPTAMPTLPTYQLSETSYQPTSIPQAVSDPSSTVHRPQPLPPSTVHQSTIPSNPDSSSAYCLPSTR HGFSSYTDSFVPPSGPSNPMNPTIGNGLSPQVMGLLTNHGGVPHQPQTDYALSPLTGGLEPTTTVSASCSQRLDHMKSLDSLPTSQSYCP

Protein Functional Features

Main function of this protein. (from UniProt)

PAX3 (go to UniProt):P23760

Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at
download page
* Minus value of BPloci means that the break pointn is located before the CDS.

- Retained protein feature among the 13 regional features.

Accession_id	Subsection	Start	End	Funcitonal feature	Splicing information
P23760	DNA binding	34	161	Note=Paired;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00381	Type=Deletion;Start=108;End=108
P23760	DNA binding	219	278	Note=Homeobox;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00108	Type=Deletion;Start=216;End=479
P23760	DNA binding	219	278	Note=Homeobox;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00108	Type=Deletion;Start=207;End=479
P23760	Region	165	228	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=196;End=215
P23760	Region	165	228	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=216;End=479
P23760	Region	165	228	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=196;End=206
P23760	Region	165	228	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=207;End=479
P23760	Region	309	351	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=216;End=479
P23760	Region	309	351	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=207;End=479
P23760	Compositional bias	209	228	Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=196;End=215
P23760	Compositional bias	209	228	Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=216;End=479
P23760	Compositional bias	209	228	Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=207;End=479

Gene Isoform Structures and Expression Levels for PAX3

Gene structures of our canonical and alternative spliced genes of PAX3
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Expression levels of gene isoforms across GTEx.

Expression levels of gene isoforms across TCGA.

Protein Structures

PDB and CIF files of the predicted protein structures
* Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.

3D view using mol* of P23760-1

3D view using mol* of P23760-2

3D view using mol* of P23760-3

3D view using mol* of P23760-4

3D view using mol* of P23760-5

3D view using mol* of P23760-6

3D view using mol* of P23760-7

3D view using mol* of P23760-8

pLDDT Score Distribution

pLDDT score distribution of the predicted protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

pLDDT distribution across the protein length of P23760-1

pLDDT distribution across the protein length of P23760-2

pLDDT distribution across the protein length of P23760-3

pLDDT distribution across the protein length of P23760-4

pLDDT distribution across the protein length of P23760-5

pLDDT distribution across the protein length of P23760-6

pLDDT distribution across the protein length of P23760-7

pLDDT distribution across the protein length of P23760-8

Ramachandran Plot of Protein Structures

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide.

Ramachandran plot of P23760-1

Ramachandran plot of P23760-2

Ramachandran plot of P23760-3

Ramachandran plot of P23760-5

Ramachandran plot of P23760-6

Potential Active Site Information

The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.

UniProt-id	Site score	Size	D score	Volume	Exposure	Enclosure	Contact	Phobic	Philic	Balance	Don/Acc	Residues
P23760-1	0.973	232	1.016	742.938	0.682	0.62	0.771	0.391	0.908	0.431	0.814	27,28,29,31,39,43,44,45,46,47,48,49,50,51,52,53,55 ,56,75,76,77,78,79,82,85,86,88,89,90,92,93,94,95,9 6,97,98,99,101,210,211,212,213,214,215,216,217,218
P23760-2	0.856	75	0.869	234.612	0.737	0.598	0.729	0.262	0.932	0.281	0.501	39,43,44,45,46,47,48,49,50,51,52,55,56,76,77,78,79 ,82,86
P23760-3	0.966	108	0.949	312.13	0.631	0.647	0.859	0.356	1.164	0.306	0.405	33,39,43,44,45,46,47,48,49,50,51,52,55,56,76,77,78 ,79,82,85,86,89,98,99,101
P23760-4	0.986	115	0.948	366.667	0.61	0.677	0.914	0.418	1.222	0.342	0.598	39,43,44,45,46,47,48,49,50,51,52,55,56,76,77,78,79 ,82,85,86,89,98,99,101
P23760-5	0.98	106	0.948	331.681	0.671	0.668	0.893	0.518	1.205	0.43	0.475	27,29,31,32,35,39,43,44,45,46,47,48,49,50,51,52,55 ,56,78,79,82,85,86,88,89,92,93,98,99,101,220
P23760-6	0.996	121	1.026	359.807	0.657	0.671	0.894	0.597	0.971	0.615	0.748	26,27,28,29,31,39,43,44,45,46,49,50,51,52,53,54,55 ,56,58,75,76,77,78,79,82,86
P23760-7	1.005	107	1.047	295.323	0.628	0.663	0.883	0.704	0.892	0.789	1.315	26,27,28,29,31,32,39,42,43,44,45,46,49,50,51,52,54 ,55,58,75,76,77,78,79
P23760-8	1.088	116	1.154	544.341	0.517	0.726	0.964	1.448	0.681	2.127	1.396	60,63,64,66,67,68,69,70,72,80,84,87,88,90,91,92,21 8,482,483,484,485,486,489,490,493

Protein Structure and Feature Comparision

Protein Structure Comparision Using Template Modeling Scores (TM-score).

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)

3D view using mol* of P23760-1_P23760-1_3cmy_A.pdb

Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of P23760-1_3cmy_A_P23760-2.pdb

3D view using mol* of P23760-1_3cmy_A_P23760-3.pdb

3D view using mol* of P23760-1_3cmy_A_P23760-4.pdb

3D view using mol* of P23760-1_3cmy_A_P23760-5.pdb

3D view using mol* of P23760-1_3cmy_A_P23760-6.pdb

3D view using mol* of P23760-1_3cmy_A_P23760-7.pdb

3D view using mol* of P23760-1_3cmy_A_P23760-8.pdb

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of P23760-1_P23760-2.pdb

3D view using mol* of P23760-1_P23760-3.pdb

3D view using mol* of P23760-1_P23760-4.pdb

3D view using mol* of P23760-1_P23760-5.pdb

3D view using mol* of P23760-1_P23760-6.pdb

3D view using mol* of P23760-1_P23760-7.pdb

3D view using mol* of P23760-1_P23760-8.pdb

Protein Feature Comparison of the protein sequendary structures among the protiens.

./stats/secondary_structure/figure/P23760-1_vs_P23760-2.png

./stats/secondary_structure/figure/P23760-1_vs_P23760-3.png

./stats/secondary_structure/figure/P23760-1_vs_P23760-4.png

./stats/secondary_structure/figure/P23760-1_vs_P23760-5.png

./stats/secondary_structure/figure/P23760-1_vs_P23760-6.png

./stats/secondary_structure/figure/P23760-1_vs_P23760-7.png

./stats/secondary_structure/figure/P23760-1_vs_P23760-8.png

Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.

./stats/relative_asa/P23760-1_vs_P23760-2.png

./stats/relative_asa/P23760-1_vs_P23760-3.png

./stats/relative_asa/P23760-1_vs_P23760-4.png

./stats/relative_asa/P23760-1_vs_P23760-5.png

./stats/relative_asa/P23760-1_vs_P23760-6.png

./stats/relative_asa/P23760-1_vs_P23760-7.png

./stats/relative_asa/P23760-1_vs_P23760-8.png

Protein-Protein Interaction

Interactors from UniProt.

Accession_id

Subsection

Start

End

Funcitonal feature

Splicing information

Interactors from STRING.

Gene name

Interactors

Related Drugs to PAX3

Drugs targeting this gene/protein.
(DrugBank)

UniProt accession

Gene name

DrugBank ID

Drug name

Drug group

Actions

Related Diseases to PAX3

Previous studies relating to the alternative splicing of PAX3 and disease information from the MeSH term (PubMed)

Gene	PMID	Title	Abstract	MeSH ID	MeSH term
PAX3	7545913	Isolation of two isoforms of the PAX3 gene transcripts and their tissue-specific alternative expression in human adult tissues.	We have isolated two isoforms of cDNA clones from the human PAX3 gene, a candidate gene responsible for Waardenburg syndrome type I (WSI) as well as a gene associated with development of alveolar rhabdomyosarcoma. The gene product is considered to be one of transcription factors, and the two cDNA clones isolated, termed PAX3A and PAX3B, were generated by alternative splicing. The transcripts coded 215 and 206 amino acids, respectively, and shared 196 amino acids at the NH2 end. The amino acid sequence in the common region (residues 1-196) showed a 100% identity with that of exons 1-4 of the mouse Pax-3 gene. However, both of the PAX3 cDNAs lacked the DNA sequence corresponding to the paired-type homeodomain of the mouse Pax-3 gene. Analysis of gene expression in human adult tissues by reverse transcriptase polymerase chain reaction (RT-PCR) revealed tissue-specific expression of this gene. PAX3B was expressed in most of the tissues examined, but the PAX3A type of transcript was detected only in the cerebellum, esophagus, and skeletal muscle.	D014849	Waardenburg Syndrome
PAX3	15688409	Co-expression of alternatively spliced forms of PAX3, PAX7, PAX3-FKHR and PAX7-FKHR with distinct DNA binding and transactivation properties in rhabdomyosarcoma.	PAX3 and PAX7 encode transcription factors implicated in the pathogenesis of rhabdomyosarcoma (RMS), including alveolar RMS in which chromosomal translocations generate PAX3-FKHR and PAX7-FKHR fusions. Previous studies of wild-type PAX3 and PAX7 identified alternative splicing events that modify the paired box and generate 2 isoforms of PAX3 (Q+ and Q-) and 4 isoforms of PAX7 (Q+GL+, Q+GL-, Q-GL+, Q-GL-). In our study, we investigated alternative splicing of the wild-type and fusion forms of PAX3 and PAX7 in alveolar and embryonal RMS and assessed the functional implications. For PAX3 and PAX3-FKHR, the Q+ and Q- isoforms were consistently co-expressed in RMS tumors with slightly higher levels of the Q+ isoform. For PAX7 and PAX7-FKHR, there was a consistent pattern of co-expression of the 4 isoforms in RMS tumors: Q+GL- > Q+GL+ >/= Q-GL- > Q-GL+. DNA binding analysis demonstrated that PAX3 and PAX3-FKHR Q- isoforms exhibit higher affinity than corresponding Q+ isoforms for class I sites and no difference for class II sites. For PAX7 and PAX7-FKHR, the relative affinity was Q-GL- > Q+GL- > Q-GL+ >/= Q+GL+ for class I sites and Q-GL-, Q+GL- > Q-GL+, Q+GL+ for class II sites. Finally, the transcriptional activities of the PAX3-FKHR and PAX7-FKHR isoforms on reporter plasmids varied over a 5-fold and 50-fold range, respectively, in accord with the differences in DNA binding activity. In conclusion, these studies reveal that PAX3, PAX7 and their fusions with FKHR are each expressed in RMS tumors as a consistent mixture of functionally distinct isoforms.	D014178	Translocation, Genetic
PAX3	25880082	Mechanisms contributing to differential regulation of PAX3 downstream target genes in normal human epidermal melanocytes versus melanoma cells.	Melanoma is a highly aggressive and drug resistant form of skin cancer. It arises from melanocytes, the pigment producing cells of the skin. The formation of these melanocytes is driven by the transcription factor PAX3 early during embryonic development. As a result of alternative splicing, the PAX3 gene gives rise to eight different transcripts which encode isoforms that have different structures and activate different downstream target genes involved in pathways of cell proliferation, migration, differentiation and survival. Furthermore, post-translational modifications have also been shown to alter the functions of PAX3. We previously identified PAX3 downstream target genes in melanocytes and melanoma cells. Here we assessed the effects of PAX3 down-regulation on this panel of target genes in primary melanocytes versus melanoma cells. We show that PAX3 differentially regulates various downstream target genes involved in cell proliferation in melanoma cells compared to melanocytes. To determine mechanisms behind this differential downstream target gene regulation, we performed immunoprecipitation to assess post-translational modifications of the PAX3 protein as well as RNAseq to determine PAX3 transcript expression profiles in melanocytes compared to melanoma cells. Although PAX3 was found to be post-translationally modified, there was no qualitative difference in phosphorylation and ubiquitination between melanocytes and melanoma cells, while acetylation of PAX3 was reduced in melanoma cells. Additionally, there were differences in PAX3 transcript expression profiles between melanocytes and melanoma cells. In particular the PAX3E transcript, responsible for reducing melanocyte proliferation and increasing apoptosis, was found to be down-regulated in melanoma cells compared to melanocytes. These results suggest that alternate transcript expression profiles activate different downstream target genes leading to the melanoma phenotype.	D008545	Melanoma

Clinically important variants in PAX3

(ClinVar, 04/20/2024)

accession_id	uniprot_id	gene_name	Type	Variant	Clinical_significance
P23760	P23760-1	PAX3	single nucleotide variant	p.Gly81Ala	Pathogenic
P23760	P23760-1	PAX3	single nucleotide variant	p.Gly81Ala	Pathogenic