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FAIM (Fas apoptotic inhibitory molecule)

Written2009-12Miguel F Segura, Carme Sole, Rana S Moubarak, Victor J Yuste, Joan X Comella
Department of Pathology, New York University School of Medicine, New York, USA (MFS); Department of Ciencies Experimentals i de la Salut, University Pompeu Fabra, Barcelona, Spain (CS); Cell Signaling, Apoptosis Group, Institut de Neurociencies, Universitat Autonoma de Barcelona, Centro de Investigacion Biomedica en Red Enfermedades Neurodegenerativas (CIBERNED), Spain (RSM, JXC); Cell Death, Senescence, Survival Group, Institut de Neurociencies, Universitat Autonoma de Barcelona, Centro de Investigacion Biomedica en Red Enfermedades Neurodegenerativas (CIBERNED), Spain (VJY)

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Identity

Alias (NCBI)FAIM1
FLJ10582
HGNC (Hugo) FAIM
HGNC Alias symbFLJ10582
FAIM1
LocusID (NCBI) 55179
Atlas_Id 43251
Location 3q22.3  [Link to chromosome band 3q22]
Location_base_pair Starts at 138609049 and ends at 138633371 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping FAIM.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
FAIM (3q22.3)::SLAIN1 (13q22.3)

DNA/RNA

 
  Genomic organization and splice variants of FAIM gene. Schematic representation of the structure of FAIM gene, that contains 4 different transcripts and 6 alternative splice variants but only two resulting proteins have been characterized so far: FAIM-S and FAIM-L (adapted from Zhong et al., 2001).
Description The genomic structure of the FAIM locus gives two alternative splicing results, FAIM-S and FAIM-L, that share part of the 5_UTR (exon I). Part of the coding sequence in FAIM-L (diagonal bar of exon III) serves as part of the UTR of FAIM-S. The additional 22 amino acid sequence is indicated above the correlating exons (Zhong et al., 2001).
Transcription FAIM-S: mRNA size: 1104 nucleotides (nt); coding sequence: 539 nt;
FAIM-L: mRNA size: 1164 nt; coding sequence: 605 nt.

Protein

Note Signaling pathways controlling cell death and survival are crucial for the normal development and tissue homeostasis. In contrast to most cell types, differentiated cells such as neurons require a highly controlled mechanism that allows survival for the entire life of the organism and protecting it from multitude of stimuli that can affect cellular integrity. Among those stimuli, cell death induction and more precisely, apoptosis induced by the extrinsic pathway mediated by Death Receptors (DRs), has been widely reported in the pathological loss of neurons. Therefore, those proteins that are able to block the apoptotic pathway will play a key role in the protection from neuronal death. Among all the described anti-apoptotic proteins, FAIM, with no homology with a previously known protein, may constitute a new family of proteins that regulate the DR signaling pathway.
 
  Proposed mechanism of FAIM action in B-cells.
Description Fas apoptosis inhibitory molecule (FAIM) is a Fas antagonist that was initially characterized by differential display as a gene that is up-regulated in B cells resistant to Fas-mediated cell death and functions as an inhibitor of Fas-induced cell death (Schneider et al., 1999). Shortly after, a new alternative splice variant was described and named FAIM-L. FAIM-S is composed of 179 aminoacids (aa), with stable structure and rich in beta-sheets, and FAIM-L contains 22 additional aa in the N-terminus part of the protein. This extra sequence does not have any particular defined structure.
Expression FAIM-S mRNA has been detected in all tissues analyzed so far, whereas FAIM-L has a more restricted pattern of expression, being predominantly expressed in the nervous system and testis. Protein immunostaining confirmed restricted expression in different areas of the brain.
Localisation Both isoforms, FAIM-S and FAIM-L are cytosolic.
Function Fas apoptosis inhibitory molecule (FAIM) was first identified as a Fas antagonist in B-cells. The overexpression of FAIM-S, but not FAIM-L, enhances NGF-induced neurite outgrowth in different neuronal populations through activation of the NF-kB pathway. No anti-apoptotic function of FAIM-S has been described in the nervous system (Sole et al., 2004). However, FAIM-L is specifically expressed in neurons and its expression is regulated during development. FAIM-L does not affect neurite outgrowth, nor does it modulate NF-kB activation. However, cells overexpressing FAIM-L are resistant to apoptotic cell death induced by DRs such as Fas or TNFR1. Reduction of endogenous expression shows that endogenous FAIM-L protects primary neurons against DR-induced cell death. FAIM-L normally binds the Fas receptor and prevents its activation. Fas-L binding to Fas induces the release of FAIM-L from Fas, allows the binding of FADD and caspase-8 , and leads to apoptosis activation (Segura et al., 2007).
Homology FAIM is highly conserved in evolution from Caenorhabditis elegans to humans (Rothstein et al., 2000). However, FAIM-L is only conserved in superior vertebrates (Zhong et al., 2001; Segura et al., 2007). There is no homology with previously characterized families of proteins.

Bibliography

Fas apoptosis inhibitory molecule contains a novel beta-sandwich in contact with a partially ordered domain.
Hemond M, Rothstein TL, Wagner G.
J Mol Biol. 2009 Mar 6;386(4):1024-37. Epub 2009 Jan 13.
PMID 19168072
 
Genetic deletion of faim reveals its role in modulating c-FLIP expression during CD95-mediated apoptosis of lymphocytes and hepatocytes.
Huo J, Xu S, Guo K, Zeng Q, Lam KP.
Cell Death Differ. 2009 Jul;16(7):1062-70. Epub 2009 Mar 20.
PMID 19300454
 
Fas apoptosis inhibitory molecule expression in B cells is regulated through IRF4 in a feed-forward mechanism.
Kaku H, Rothstein TL.
J Immunol. 2009 Nov 1;183(9):5575-81.
PMID 19843941
 
Inducible resistance to Fas-mediated apoptosis in B cells.
Rothstein TL.
Cell Res. 2000 Dec;10(4):245-66.
PMID 11191348
 
A novel gene coding for a Fas apoptosis inhibitory molecule (FAIM) isolated from inducibly Fas-resistant B lymphocytes.
Schneider TJ, Fischer GM, Donohoe TJ, Colarusso TP, Rothstein TL.
J Exp Med. 1999 Mar 15;189(6):949-56.
PMID 10075978
 
The long form of Fas apoptotic inhibitory molecule is expressed specifically in neurons and protects them against death receptor-triggered apoptosis.
Segura MF, Sole C, Pascual M, Moubarak RS, Perez-Garcia MJ, Gozzelino R, Iglesias V, Badiola N, Bayascas JR, Llecha N, Rodriguez-Alvarez J, Soriano E, Yuste VJ, Comella JX.
J Neurosci. 2007 Oct 17;27(42):11228-41.
PMID 17942717
 
The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-kapp B signaling.
Sole C, Dolcet X, Segura MF, Gutierrez H, Diaz-Meco MT, Gozzelino R, Sanchis D, Bayascas JR, Gallego C, Moscat J, Davies AM, Comella JX.
J Cell Biol. 2004 Nov 8;167(3):479-92. Epub 2004 Nov 1.
PMID 15520226
 
Death receptors and caspases but not mitochondria are activated in the GDNF- or BDNF-deprived dopaminergic neurons.
Yu LY, Saarma M, Arumae U.
J Neurosci. 2008 Jul 23;28(30):7467-75.
PMID 18650325
 
An alternatively spliced long form of Fas apoptosis inhibitory molecule (FAIM) with tissue-specific expression in the brain.
Zhong X, Schneider TJ, Cabral DS, Donohoe TJ, Rothstein TL.
Mol Immunol. 2001 Jan;38(1):65-72.
PMID 11483211
 

Citation

This paper should be referenced as such :
Segura, MF ; Sole, C ; Moubarak, RS ; Yuste, VJ ; Comella, JX
FAIM (Fas apoptotic inhibitory molecule)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(9):878-880.
Free journal version : [ pdf ]   [ DOI ]


External links

 

Nomenclature
HGNC (Hugo)FAIM   18703
Cards
AtlasFAIMID43251ch3q22
Entrez_Gene (NCBI)FAIM    Fas apoptotic inhibitory molecule
AliasesFAIM1
GeneCards (Weizmann)FAIM
Ensembl hg19 (Hinxton)ENSG00000158234 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000158234 [Gene_View]  ENSG00000158234 [Sequence]  chr3:138609049-138633371 [Contig_View]  FAIM [Vega]
ICGC DataPortalENSG00000158234
TCGA cBioPortalFAIM
AceView (NCBI)FAIM
Genatlas (Paris)FAIM
SOURCE (Princeton)FAIM
Genetics Home Reference (NIH)FAIM
Genomic and cartography
GoldenPath hg38 (UCSC)FAIM  -     chr3:138609049-138633371 +  3q22.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)FAIM  -     3q22.3   [Description]    (hg19-Feb_2009)
GoldenPathFAIM - 3q22.3 [CytoView hg19]  FAIM - 3q22.3 [CytoView hg38]
ImmunoBaseENSG00000158234
Genome Data Viewer NCBIFAIM [Mapview hg19]  
OMIM617535   
Gene and transcription
Genbank (Entrez)AK001444 AK125477 BC012478 BM469375 BM738750
RefSeq transcript (Entrez)NM_001033030 NM_001033031 NM_001033032 NM_018147
Consensus coding sequences : CCDS (NCBI)FAIM
Gene ExpressionFAIM [ NCBI-GEO ]   FAIM [ EBI - ARRAY_EXPRESS ]   FAIM [ SEEK ]   FAIM [ MEM ]
Gene Expression Viewer (FireBrowse)FAIM [ Firebrowse - Broad ]
GenevisibleExpression of FAIM in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)55179
GTEX Portal (Tissue expression)FAIM
Human Protein AtlasENSG00000158234-FAIM [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9NVQ4   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9NVQ4  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9NVQ4
PhosPhoSitePlusQ9NVQ4
Domains : Interpro (EBI)FAIM1    FAIM1_dom_sf   
Domain families : Pfam (Sanger)FAIM1 (PF06905)   
Domain families : Pfam (NCBI)pfam06905   
Conserved Domain (NCBI)FAIM
PDB (RSDB)2KW1    3MX7   
PDB Europe2KW1    3MX7   
PDB (PDBSum)2KW1    3MX7   
PDB (IMB)2KW1    3MX7   
Structural Biology KnowledgeBase2KW1    3MX7   
SCOP (Structural Classification of Proteins)2KW1    3MX7   
CATH (Classification of proteins structures)2KW1    3MX7   
SuperfamilyQ9NVQ4
AlphaFold pdb e-kbQ9NVQ4   
Human Protein Atlas [tissue]ENSG00000158234-FAIM [tissue]
HPRD16874
Protein Interaction databases
DIP (DOE-UCLA)Q9NVQ4
IntAct (EBI)Q9NVQ4
BioGRIDFAIM
STRING (EMBL)FAIM
ZODIACFAIM
Ontologies - Pathways
QuickGOQ9NVQ4
Ontology : AmiGOprotein binding  cytoplasm  apoptotic process  I-kappaB kinase/NF-kappaB signaling  positive regulation of neurogenesis  negative regulation of extrinsic apoptotic signaling pathway via death domain receptors  
Ontology : EGO-EBIprotein binding  cytoplasm  apoptotic process  I-kappaB kinase/NF-kappaB signaling  positive regulation of neurogenesis  negative regulation of extrinsic apoptotic signaling pathway via death domain receptors  
NDEx NetworkFAIM
Atlas of Cancer Signalling NetworkFAIM
Wikipedia pathwaysFAIM
Orthology - Evolution
OrthoDB55179
GeneTree (enSembl)ENSG00000158234
Phylogenetic Trees/Animal Genes : TreeFamFAIM
Homologs : HomoloGeneFAIM
Homology/Alignments : Family Browser (UCSC)FAIM
Gene fusions - Rearrangements
Fusion : QuiverFAIM
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerFAIM [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)FAIM
dbVarFAIM
ClinVarFAIM
MonarchFAIM
1000_GenomesFAIM 
Exome Variant ServerFAIM
GNOMAD BrowserENSG00000158234
Varsome BrowserFAIM
ACMGFAIM variants
VarityQ9NVQ4
Genomic Variants (DGV)FAIM [DGVbeta]
DECIPHERFAIM [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisFAIM 
Mutations
ICGC Data PortalFAIM 
TCGA Data PortalFAIM 
Broad Tumor PortalFAIM
OASIS PortalFAIM [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICFAIM  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DFAIM
Mutations and Diseases : HGMDFAIM
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
BioMutaFAIM
DgiDB (Drug Gene Interaction Database)FAIM
DoCM (Curated mutations)FAIM
CIViC (Clinical Interpretations of Variants in Cancer)FAIM
NCG (London)FAIM
Cancer3DFAIM
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM617535   
Orphanet
DisGeNETFAIM
MedgenFAIM
Genetic Testing Registry FAIM
NextProtQ9NVQ4 [Medical]
GENETestsFAIM
Target ValidationFAIM
Huge Navigator FAIM [HugePedia]
ClinGenFAIM
Clinical trials, drugs, therapy
MyCancerGenomeFAIM
Protein Interactions : CTDFAIM
Pharm GKB GenePA38647
PharosQ9NVQ4
Clinical trialFAIM
Miscellaneous
canSAR (ICR)FAIM
HarmonizomeFAIM
DataMed IndexFAIM
Probes
Litterature
PubMed28 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
EVEXFAIM
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:17:40 CEST 2021

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