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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_symbol (synonym)FLJ10582
FAIM1
Other alias
HGNC (Hugo) FAIM
LocusID (NCBI) 55179
Atlas_Id 43251
Location 3q22.3  [Link to chromosome band 3q22]
Location_base_pair Starts at 138327542 and ends at 138352213 bp from pter ( according to hg19-Feb_2009)  [Mapping FAIM.png]
Fusion genes
(updated 2016)
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 ]
On line version : http://AtlasGeneticsOncology.org/Genes/FAIMID43251ch3q22.html


External links

Nomenclature
HGNC (Hugo)FAIM   18703
Cards
AtlasFAIMID43251ch3q22
Entrez_Gene (NCBI)FAIM  55179  Fas apoptotic inhibitory molecule
AliasesFAIM1
GeneCards (Weizmann)FAIM
Ensembl hg19 (Hinxton)ENSG00000158234 [Gene_View]  chr3:138327542-138352213 [Contig_View]  FAIM [Vega]
Ensembl hg38 (Hinxton)ENSG00000158234 [Gene_View]  chr3:138327542-138352213 [Contig_View]  FAIM [Vega]
ICGC DataPortalENSG00000158234
TCGA cBioPortalFAIM
AceView (NCBI)FAIM
Genatlas (Paris)FAIM
WikiGenes55179
SOURCE (Princeton)FAIM
Genetics Home Reference (NIH)FAIM
Genomic and cartography
GoldenPath hg19 (UCSC)FAIM  -     chr3:138327542-138352213 +  3q23   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)FAIM  -     3q23   [Description]    (hg38-Dec_2013)
EnsemblFAIM - 3q23 [CytoView hg19]  FAIM - 3q23 [CytoView hg38]
Mapping of homologs : NCBIFAIM [Mapview hg19]  FAIM [Mapview hg38]
Gene and transcription
Genbank (Entrez)AK001444 AK125477 BC012478 BM469375 BM738750
RefSeq transcript (Entrez)NM_001033030 NM_001033031 NM_001033032 NM_018147
RefSeq genomic (Entrez)NC_000003 NC_018914 NG_029625 NT_005612 NW_004929311
Consensus coding sequences : CCDS (NCBI)FAIM
Cluster EST : UnigeneHs.173438 [ NCBI ]
CGAP (NCI)Hs.173438
Alternative Splicing GalleryENSG00000158234
Gene ExpressionFAIM [ NCBI-GEO ]   FAIM [ EBI - ARRAY_EXPRESS ]   FAIM [ SEEK ]   FAIM [ MEM ]
Gene Expression Viewer (FireBrowse)FAIM [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)55179
GTEX Portal (Tissue expression)FAIM
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
Splice isoforms : SwissVarQ9NVQ4
PhosPhoSitePlusQ9NVQ4
Domains : Interpro (EBI)FAIM1   
Domain families : Pfam (Sanger)FAIM1 (PF06905)   
Domain families : Pfam (NCBI)pfam06905   
Conserved Domain (NCBI)FAIM
DMDM Disease mutations55179
Blocks (Seattle)FAIM
PDB (SRS)2KW1    3MX7   
PDB (PDBSum)2KW1    3MX7   
PDB (IMB)2KW1    3MX7   
PDB (RSDB)2KW1    3MX7   
Structural Biology KnowledgeBase2KW1    3MX7   
SCOP (Structural Classification of Proteins)2KW1    3MX7   
CATH (Classification of proteins structures)2KW1    3MX7   
SuperfamilyQ9NVQ4
Human Protein AtlasENSG00000158234
Peptide AtlasQ9NVQ4
HPRD16874
IPIIPI00018733   IPI00394989   IPI00651712   IPI00943830   
Protein Interaction databases
DIP (DOE-UCLA)Q9NVQ4
IntAct (EBI)Q9NVQ4
FunCoupENSG00000158234
BioGRIDFAIM
STRING (EMBL)FAIM
ZODIACFAIM
Ontologies - Pathways
QuickGOQ9NVQ4
Ontology : AmiGOprotein binding  cytoplasm  apoptotic process  negative regulation of apoptotic process  
Ontology : EGO-EBIprotein binding  cytoplasm  apoptotic process  negative regulation of apoptotic process  
NDEx NetworkFAIM
Atlas of Cancer Signalling NetworkFAIM
Wikipedia pathwaysFAIM
Orthology - Evolution
OrthoDB55179
GeneTree (enSembl)ENSG00000158234
Phylogenetic Trees/Animal Genes : TreeFamFAIM
HOVERGENQ9NVQ4
HOGENOMQ9NVQ4
Homologs : HomoloGeneFAIM
Homology/Alignments : Family Browser (UCSC)FAIM
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerFAIM [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)FAIM
dbVarFAIM
ClinVarFAIM
1000_GenomesFAIM 
Exome Variant ServerFAIM
ExAC (Exome Aggregation Consortium)FAIM (select the gene name)
Genetic variants : HAPMAP55179
Genomic Variants (DGV)FAIM [DGVbeta]
DECIPHER (Syndromes)3:138327542-138352213  ENSG00000158234
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]  
Mutations and Diseases : HGMDFAIM
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch FAIM
DgiDB (Drug Gene Interaction Database)FAIM
DoCM (Curated mutations)FAIM (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)FAIM (select a term)
intoGenFAIM
NCG5 (London)FAIM
Cancer3DFAIM(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM
Orphanet
MedgenFAIM
Genetic Testing Registry FAIM
NextProtQ9NVQ4 [Medical]
TSGene55179
GENETestsFAIM
Huge Navigator FAIM [HugePedia]
snp3D : Map Gene to Disease55179
BioCentury BCIQFAIM
ClinGenFAIM
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD55179
Chemical/Pharm GKB GenePA38647
Clinical trialFAIM
Miscellaneous
canSAR (ICR)FAIM (select the gene name)
Probes
Litterature
PubMed16 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineFAIM
EVEXFAIM
GoPubMedFAIM
iHOPFAIM
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue Mar 14 13:40:32 CET 2017

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