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:FAS

Protein Summary

Gene summary

Gene name: FAS
ASpdb.0 ID: 355
	Gene
Gene symbol	FAS
Gene ID	355
Gene name	Fas cell surface death receptor
Synonyms	ALPS1A\|APO-1\|APT1\|CD95\|FAS1\|FASTM\|TNFRSF6
Cytomap	10q23.31
Type of gene	protein-coding
Description	tumor necrosis factor receptor superfamily member 6APO-1 cell surface antigenCD95 antigenFASLG receptorFas (TNF receptor superfamily, member 6)Fas AMATNF receptor superfamily member 6apoptosis antigen 1apoptosis signaling receptor FASapoptosis-me
Modification date	20240407
UniProtAcc	P25445

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

Partner	Gene	GO ID	GO term	PubMed ID
Gene	FAS	GO:0005516	calmodulin binding	24914971
Gene	FAS	GO:0005829	cytosol	-
Gene	FAS	GO:0005886	plasma membrane	-
Gene	FAS	GO:0006915	apoptotic process	9681877
Gene	FAS	GO:0009986	cell surface	22891283
Gene	FAS	GO:0016604	nuclear body	-
Gene	FAS	GO:0031264	death-inducing signaling complex	11101870\|21803845
Gene	FAS	GO:0031265	CD95 death-inducing signaling complex	20935634
Gene	FAS	GO:0043065	positive regulation of apoptotic process	21625644
Gene	FAS	GO:0045121	membrane raft	21382479

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
P25445-1	P25445-1_3ezq_A.pdb	3EZQ	X-ray	2.73	A	223	335

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
P25445	FAS	P25445-1	P25445-2	335	103	66	103	Substitution	GERKARDCTVNGDEPDCVPCQEGKEYTDKAHFSSKCRR	DVNMESSRNAHSPATPSAKRKDPDLTWGGFVFFFCQFH	66	103
P25445	FAS	P25445-1	P25445-2	335	103	104	335	Deletion	none	none	103	103
P25445	FAS	P25445-1	P25445-3	335	86	66	86	Substitution	GERKARDCTVNGDEPDCVPCQ	DVNMESSRNAHSPATPSAKRK	66	86
P25445	FAS	P25445-1	P25445-3	335	86	87	335	Deletion	none	none	86	86
P25445	FAS	P25445-1	P25445-4	335	149	112	149	Substitution	GLEVEINCTRTQNTKCRCKPNFFCNSTVCEHCDPCTKC	DVNMESSRNAHSPATPSAKRKDPDLTWGGFVFFFCQFH	112	149
P25445	FAS	P25445-1	P25445-4	335	149	150	335	Deletion	none	none	149	149
P25445	FAS	P25445-1	P25445-5	335	132	112	132	Substitution	GLEVEINCTRTQNTKCRCKPN	DVNMESSRNAHSPATPSAKRK	112	132
P25445	FAS	P25445-1	P25445-5	335	132	133	335	Deletion	none	none	132	132
P25445	FAS	P25445-1	P25445-6	335	314	169	189	Deletion	none	none	168	168
P25445	FAS	P25445-1	P25445-7	335	220	218	220	Substitution	ETV	MLT	218	220
P25445	FAS	P25445-1	P25445-7	335	220	221	335	Deletion	none	none	220	220

Multiple sequence alignment of our canonical and alternatively spliced FAS

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

UniProt-id	ENSG	ENST	ENSP
P25445-1	ENSG00000026103.25	ENST00000652046.1	ENSP00000498466.1
P25445-2	ENSG00000026103.25	ENST00000484444.6	ENSP00000420975.1
P25445-3	ENSG00000026103.25	ENST00000479522.6	ENSP00000424113.1
P25445-4	ENSG00000026103.25	ENST00000488877.6	ENSP00000425159.1
P25445-4	ENSG00000026103.25	ENST00000494410.5	ENSP00000423755.1
P25445-4	ENSG00000026103.25	ENST00000697036.1	ENSP00000513060.1
P25445-5	ENSG00000026103.25	ENST00000492756.7	ENSP00000422453.1
P25445-6	ENSG00000026103.25	ENST00000357339.7	ENSP00000349896.2
P25445-7	ENSG00000026103.25	ENST00000355279.2	ENSP00000347426.2

UniProt-id	NM ID	NP ID
P25445-1	NM_000043.5	NP_000034.1
P25445-6	NM_152871.3	NP_690610.1
P25445-7	NM_152872.3	NP_690611.1

Amino acid sequences of our canonical and alternatively spliced FAS

accession_id	Protein sequence
P25445-1	MLGIWTLLPLVLTSVARLSSKSVNAQVTDINSKGLELRKTVTTVETQNLEGLHHDGQFCHKPCPPGERKARDCTVNGDEPDCVPCQEGKE YTDKAHFSSKCRRCRLCDEGHGLEVEINCTRTQNTKCRCKPNFFCNSTVCEHCDPCTKCEHGIIKECTLTSNTKCKEEGSRSNLGWLCLL LLPIPLIVWVKRKEVQKTCRKHRKENQGSHESPTLNPETVAINLSDVDLSKYITTIAGVMTLSQVKGFVRKNGVNEAKIDEIKNDNVQDT
P25445-2	MLGIWTLLPLVLTSVARLSSKSVNAQVTDINSKGLELRKTVTTVETQNLEGLHHDGQFCHKPCPPDVNMESSRNAHSPATPSAKRKDPDL
P25445-3
P25445-4	MLGIWTLLPLVLTSVARLSSKSVNAQVTDINSKGLELRKTVTTVETQNLEGLHHDGQFCHKPCPPGERKARDCTVNGDEPDCVPCQEGKE
P25445-5	MLGIWTLLPLVLTSVARLSSKSVNAQVTDINSKGLELRKTVTTVETQNLEGLHHDGQFCHKPCPPGERKARDCTVNGDEPDCVPCQEGKE
P25445-6	MLGIWTLLPLVLTSVARLSSKSVNAQVTDINSKGLELRKTVTTVETQNLEGLHHDGQFCHKPCPPGERKARDCTVNGDEPDCVPCQEGKE YTDKAHFSSKCRRCRLCDEGHGLEVEINCTRTQNTKCRCKPNFFCNSTVCEHCDPCTKCEHGIIKECTLTSNTKCKEEVKRKEVQKTCRK HRKENQGSHESPTLNPETVAINLSDVDLSKYITTIAGVMTLSQVKGFVRKNGVNEAKIDEIKNDNVQDTAEQKVQLLRNWHQLHGKKEAY
P25445-7	MLGIWTLLPLVLTSVARLSSKSVNAQVTDINSKGLELRKTVTTVETQNLEGLHHDGQFCHKPCPPGERKARDCTVNGDEPDCVPCQEGKE YTDKAHFSSKCRRCRLCDEGHGLEVEINCTRTQNTKCRCKPNFFCNSTVCEHCDPCTKCEHGIIKECTLTSNTKCKEEGSRSNLGWLCLL

Protein Functional Features

Main function of this protein. (from UniProt)

FAS (go to UniProt):P25445

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
P25445	Topological domain	26	173	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Substitution;Start=66;End=103
P25445	Topological domain	26	173	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=104;End=335
P25445	Topological domain	26	173	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Substitution;Start=66;End=86
P25445	Topological domain	26	173	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=87;End=335
P25445	Topological domain	26	173	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Substitution;Start=112;End=149
P25445	Topological domain	26	173	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=150;End=335
P25445	Topological domain	26	173	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Substitution;Start=112;End=132
P25445	Topological domain	26	173	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=133;End=335
P25445	Topological domain	26	173	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=189
P25445	Transmembrane	174	190	Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=104;End=335
P25445	Transmembrane	174	190	Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=87;End=335
P25445	Transmembrane	174	190	Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=150;End=335
P25445	Transmembrane	174	190	Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=133;End=335
P25445	Transmembrane	174	190	Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=189
P25445	Topological domain	191	335	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=104;End=335
P25445	Topological domain	191	335	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=87;End=335
P25445	Topological domain	191	335	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=150;End=335
P25445	Topological domain	191	335	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=133;End=335
P25445	Topological domain	191	335	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Substitution;Start=218;End=220
P25445	Topological domain	191	335	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=221;End=335
P25445	Repeat	47	83	Note=TNFR-Cys 1	Type=Substitution;Start=66;End=103
P25445	Repeat	47	83	Note=TNFR-Cys 1	Type=Substitution;Start=66;End=86
P25445	Repeat	84	127	Note=TNFR-Cys 2	Type=Substitution;Start=66;End=103
P25445	Repeat	84	127	Note=TNFR-Cys 2	Type=Deletion;Start=104;End=335
P25445	Repeat	84	127	Note=TNFR-Cys 2	Type=Substitution;Start=66;End=86
P25445	Repeat	84	127	Note=TNFR-Cys 2	Type=Deletion;Start=87;End=335
P25445	Repeat	84	127	Note=TNFR-Cys 2	Type=Substitution;Start=112;End=149
P25445	Repeat	84	127	Note=TNFR-Cys 2	Type=Substitution;Start=112;End=132
P25445	Repeat	128	166	Note=TNFR-Cys 3	Type=Deletion;Start=104;End=335
P25445	Repeat	128	166	Note=TNFR-Cys 3	Type=Deletion;Start=87;End=335
P25445	Repeat	128	166	Note=TNFR-Cys 3	Type=Substitution;Start=112;End=149
P25445	Repeat	128	166	Note=TNFR-Cys 3	Type=Deletion;Start=150;End=335
P25445	Repeat	128	166	Note=TNFR-Cys 3	Type=Substitution;Start=112;End=132
P25445	Repeat	128	166	Note=TNFR-Cys 3	Type=Deletion;Start=133;End=335
P25445	Domain	230	314	Note=Death;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00064	Type=Deletion;Start=104;End=335
P25445	Domain	230	314	Note=Death;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00064	Type=Deletion;Start=87;End=335
P25445	Domain	230	314	Note=Death;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00064	Type=Deletion;Start=150;End=335
P25445	Domain	230	314	Note=Death;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00064	Type=Deletion;Start=133;End=335
P25445	Domain	230	314	Note=Death;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00064	Type=Deletion;Start=221;End=335
P25445	Region	212	317	Note=Interaction with HIPK3;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Deletion;Start=104;End=335
P25445	Region	212	317	Note=Interaction with HIPK3;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Deletion;Start=87;End=335
P25445	Region	212	317	Note=Interaction with HIPK3;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Deletion;Start=150;End=335
P25445	Region	212	317	Note=Interaction with HIPK3;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Deletion;Start=133;End=335
P25445	Region	212	317	Note=Interaction with HIPK3;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Substitution;Start=218;End=220
P25445	Region	212	317	Note=Interaction with HIPK3;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Deletion;Start=221;End=335
P25445	Region	230	254	Note=Interaction with CALM;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:24914971;Dbxref=PMID:24914971	Type=Deletion;Start=104;End=335
P25445	Region	230	254	Note=Interaction with CALM;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:24914971;Dbxref=PMID:24914971	Type=Deletion;Start=87;End=335
P25445	Region	230	254	Note=Interaction with CALM;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:24914971;Dbxref=PMID:24914971	Type=Deletion;Start=150;End=335
P25445	Region	230	254	Note=Interaction with CALM;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:24914971;Dbxref=PMID:24914971	Type=Deletion;Start=133;End=335
P25445	Region	230	254	Note=Interaction with CALM;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:24914971;Dbxref=PMID:24914971	Type=Deletion;Start=221;End=335

Gene Isoform Structures and Expression Levels for FAS

Gene structures of our canonical and alternative spliced genes of FAS
* 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 P25445-1

3D view using mol* of P25445-2

3D view using mol* of P25445-3

3D view using mol* of P25445-4

3D view using mol* of P25445-5

3D view using mol* of P25445-6

3D view using mol* of P25445-7

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 P25445-1

pLDDT distribution across the protein length of P25445-2

pLDDT distribution across the protein length of P25445-3

pLDDT distribution across the protein length of P25445-4

pLDDT distribution across the protein length of P25445-5

pLDDT distribution across the protein length of P25445-6

pLDDT distribution across the protein length of P25445-7

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 P25445-1

Ramachandran plot of P25445-3

Ramachandran plot of P25445-4

Ramachandran plot of P25445-5

Ramachandran plot of P25445-6

Ramachandran plot of P25445-7

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
P25445-1	0.673	33	0.477	120.736	0.68	0.675	0.955	0.203	1.435	0.142	0.854	105,125,126,127,128,129,135,136,137,138,139,140,15 9,160
P25445-2	0.684	14	0.71	22.981	0.588	0.631	1.034	2.397	0.064	37.342		8,9,12,13,16,98,102
P25445-3	0.513	14	0.457	38.416	0.77	0.56	0.782	0.713	0.707	1.008	0.862	59,60,61,62,63,76
P25445-4	0.972	224	1.019	568.694	0.66	0.611	0.841	0.495	0.884	0.56	0.914	65,66,88,89,91,92,93,94,96,98,100,101,102,103,104, 105,106,107,108,109,111,113,115,117,120,121,122,12 3,124,126,136,137,138,139,140,141,142,143,144,145, 146,147,148,149
P25445-5	1.026	105	1.089	188.307	0.516	0.65	0.9	0.864	0.737	1.172	1.81	65,66,67,84,85,86,87,88,90,91,92,93,104,121,122,12 3,124,125
P25445-6	0.987	93	1.043	282.632	0.711	0.632	0.668	0.401	0.744	0.54	1.069	170,171,172,173,174,175,178,179,181,182,183,185,18 6,271,274,275,278,281,282,283,284,287
P25445-7	0.734	54	0.668	133.084	0.686	0.592	0.777	0.12	1.158	0.103	1.157	105,124,125,126,127,128,129,135,137,138,139,140,15 9,160

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 P25445-1_P25445-1_3ezq_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 P25445-1_3ezq_A_P25445-2.pdb

3D view using mol* of P25445-1_3ezq_A_P25445-3.pdb

3D view using mol* of P25445-1_3ezq_A_P25445-4.pdb

3D view using mol* of P25445-1_3ezq_A_P25445-5.pdb

3D view using mol* of P25445-1_3ezq_A_P25445-6.pdb

3D view using mol* of P25445-1_3ezq_A_P25445-7.pdb

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

3D view using mol* of P25445-1_P25445-2.pdb

3D view using mol* of P25445-1_P25445-3.pdb

3D view using mol* of P25445-1_P25445-4.pdb

3D view using mol* of P25445-1_P25445-5.pdb

3D view using mol* of P25445-1_P25445-6.pdb

3D view using mol* of P25445-1_P25445-7.pdb

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

./stats/secondary_structure/figure/P25445-1_vs_P25445-2.png

./stats/secondary_structure/figure/P25445-1_vs_P25445-3.png

./stats/secondary_structure/figure/P25445-1_vs_P25445-4.png

./stats/secondary_structure/figure/P25445-1_vs_P25445-5.png

./stats/secondary_structure/figure/P25445-1_vs_P25445-6.png

./stats/secondary_structure/figure/P25445-1_vs_P25445-7.png

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

./stats/relative_asa/P25445-1_vs_P25445-2.png

./stats/relative_asa/P25445-1_vs_P25445-3.png

./stats/relative_asa/P25445-1_vs_P25445-4.png

./stats/relative_asa/P25445-1_vs_P25445-5.png

./stats/relative_asa/P25445-1_vs_P25445-6.png

./stats/relative_asa/P25445-1_vs_P25445-7.png

Protein-Protein Interaction

Interactors from UniProt.

Accession_id	Subsection	Start	End	Funcitonal feature	Splicing information
P25445	Region	212	317	Note=Interaction with HIPK3;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Deletion;Start=104;End=335
P25445	Region	212	317	Note=Interaction with HIPK3;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Deletion;Start=87;End=335
P25445	Region	212	317	Note=Interaction with HIPK3;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Deletion;Start=150;End=335
P25445	Region	212	317	Note=Interaction with HIPK3;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Deletion;Start=133;End=335
P25445	Region	212	317	Note=Interaction with HIPK3;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Substitution;Start=218;End=220
P25445	Region	212	317	Note=Interaction with HIPK3;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Deletion;Start=221;End=335
P25445	Region	230	254	Note=Interaction with CALM;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:24914971;Dbxref=PMID:24914971	Type=Deletion;Start=104;End=335
P25445	Region	230	254	Note=Interaction with CALM;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:24914971;Dbxref=PMID:24914971	Type=Deletion;Start=87;End=335
P25445	Region	230	254	Note=Interaction with CALM;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:24914971;Dbxref=PMID:24914971	Type=Deletion;Start=150;End=335
P25445	Region	230	254	Note=Interaction with CALM;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:24914971;Dbxref=PMID:24914971	Type=Deletion;Start=133;End=335
P25445	Region	230	254	Note=Interaction with CALM;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:24914971;Dbxref=PMID:24914971	Type=Deletion;Start=221;End=335

Interactors from STRING.

Gene name

Interactors

Related Drugs to FAS

Drugs targeting this gene/protein.
(DrugBank)

UniProt accession

Gene name

DrugBank ID

Drug name

Drug group

Actions

Related Diseases to FAS

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

Gene	PMID	Title	Abstract	MeSH ID	MeSH term
FAS	12855687	Oligomerization of soluble Fas antigen induces its cytotoxicity.	"Soluble Fas antigen can protect cells against Fas-mediated apoptosis. High level soluble Fas antigen characteristic for blood of patients with autoimmune disease or cancer is believed to prevent the elimination of autoimmune lymphocytes or tumor cells. Here we first report that human recombinant FasDeltaTM, i.e. soluble Fas generated by alternative splicing of the intact exon 6, is capable of inducing death of transformed cells by ""reverse"" apoptotic signaling via transmembrane Fas ligand. FasDeltaTM, as well as transmembrane Fas antigen, can be either monomeric or oligomeric, and both its forms are efficient in blocking Fas-mediated apoptosis, although the cytotoxic activity is exhibited solely by the latter. An in vivo analysis of soluble Fas antigen showed that unlike in healthy controls, nearly the total FasDeltaTM present in sera of rheumatoid arthritis patients was oligomeric. This resulted in suppression of cell proliferation in the experimental sera and in its promotion in controls. Thus, oligomerization/depolymerization of soluble Fas antigen can regulate its activity and contribute to the pathogenesis of autoimmune diseases and cancer."	D001172	Arthritis, Rheumatoid
FAS	12855687	Oligomerization of soluble Fas antigen induces its cytotoxicity.	"Soluble Fas antigen can protect cells against Fas-mediated apoptosis. High level soluble Fas antigen characteristic for blood of patients with autoimmune disease or cancer is believed to prevent the elimination of autoimmune lymphocytes or tumor cells. Here we first report that human recombinant FasDeltaTM, i.e. soluble Fas generated by alternative splicing of the intact exon 6, is capable of inducing death of transformed cells by ""reverse"" apoptotic signaling via transmembrane Fas ligand. FasDeltaTM, as well as transmembrane Fas antigen, can be either monomeric or oligomeric, and both its forms are efficient in blocking Fas-mediated apoptosis, although the cytotoxic activity is exhibited solely by the latter. An in vivo analysis of soluble Fas antigen showed that unlike in healthy controls, nearly the total FasDeltaTM present in sera of rheumatoid arthritis patients was oligomeric. This resulted in suppression of cell proliferation in the experimental sera and in its promotion in controls. Thus, oligomerization/depolymerization of soluble Fas antigen can regulate its activity and contribute to the pathogenesis of autoimmune diseases and cancer."	D009369	Neoplasms
FAS	19751723	Identification, characterisation and regulation by CD40 activation of novel CD95 splice variants in CD95-apoptosis-resistant, human, B-cell non-Hodgkin's lymphoma.	CD95 gene and splicing aberrations have been detected in B-cell non-Hodgkin lymphoma (B-NHL) where they are thought to contribute to CD95 apoptosis resistance. To further investigate this, we have performed extensive CD95 transcript sequencing and functional analysis in B-NHL with demonstrated resistance to CD95-induced apoptosis (B-NHLr). Strikingly, instead of showing CD95 mutations per se, B cells from B-NHLr co-expressed wild-type and multiple, normal (CD95nv) and novel alternatively spliced variant CD95 transcripts (CD95av). CD95av were predicted, by sequencing, to encode soluble, potentially apoptosis inhibitory proteins. However, their overexpression, by transfection, in Jurkat cells did not interfere with endogenous CD95 death signalling. Furthermore, CD95av-expressing B-NHLr did not show mutations in CD95 splice-regulatory elements and CD95av expression was 'reversible' by CD40 activation. This, in conjunction with treatment by the protein synthesis inhibitor, cycloheximide, could sensitise a subset of B-NHLr to CD95 apoptosis. In normal and lymphoma B cells, this correlated to increased CD95 membrane expression, enhanced DISC activity and engagement of the mitochondrial death pathway via Bid cleavage, although the latter occurred less efficiently in B-NHLr. Thus, immune modulation of CD95 transcription and alternative splicing combined with enhanced engagement of mitochondrial death signalling offer potential for restoration of CD95 apoptosis sensitivity in B-NHLr.	D016393	Lymphoma, B-Cell
FAS	25411246	Interleukin 7 up-regulates CD95 protein on CD4+ T cells by affecting mRNA alternative splicing: priming for a synergistic effect on HIV-1 reservoir maintenance.	Interleukin-7 (IL-7) has been used as an immunoregulatory and latency-reversing agent in human immunodeficiency virus type 1 (HIV-1) infection. Although IL-7 can restore circulating CD4(+) T cell counts in HIV-1-infected patients, the anti-apoptotic and proliferative effects of IL-7 appear to benefit survival and expansion of HIV-1-latently infected memory CD4(+) T lymphocytes. IL-7 has been shown to elevate CD95 on CD4(+) T cells in HIV-1-infected individuals and prime CD4(+) T lymphocytes to CD95-mediated proliferative or apoptotic signals. Here we observed that through increasing microRNA-124, IL-7 down-regulates the splicing regulator polypyrimidine tract binding protein (PTB), leading to inclusion of the transmembrane domain-encoding exon 6 of CD95 mRNA and, subsequently, elevation of CD95 on memory CD4(+) T cells. Moreover, IL-7 up-regulates cellular FLICE-like inhibitory protein (c-FLIP) and stimulates c-Jun N-terminal kinase (JNK) phosphorylation, which switches CD95 signaling to survival mode in memory CD4(+) T lymphocytes. As a result, co-stimulation through IL-7/IL-7R and FasL/CD95 signal pathways augments IL-7-mediated survival and expansion of HIV-1-latently infected memory CD4(+) T lymphocytes. Collectively, we have demonstrated a novel mechanism for IL-7-mediated maintenance of HIV-1 reservoir.	D015658	HIV Infections

Clinically important variants in FAS

(ClinVar, 04/20/2024)

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