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IGSF8 (immunoglobulin superfamily, member 8)

Written2010-08Yanhui H Zhang, Mekel M Richardson, Xin A Zhang
Vascular Biology, Cancer Centers, Departments of Medicine, Molecular Science, University of Tennessee Health Science Center, Memphis, USA

(Note : for Links provided by Atlas : click)


Alias (NCBI)CD316
HGNC Alias symbCD81P3
HGNC Previous nameimmunoglobulin superfamily, member 8
LocusID (NCBI) 93185
Atlas_Id 45820
Location 1q23.2  [Link to chromosome band 1q23]
Location_base_pair Starts at 160091346 and ends at 160098619 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping IGSF8.png]
Local_order Centromere -- PIGM - KCNJ10 - LOC100287448 - KCNJ9 - CD316/IGSF8 - ATP1A2 - ATP1A4 - CASQ1 - PEA15 -- Telomere (NCBI Map Viewer).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
SLC5A2 (16p11.2)::IGSF8 (1q23.2)USPL1 (13q12.3)::IGSF8 (1q23.2)


  CD316/IGSF8 gene typically contains 7 exons. The green bars represent the non-coding exons while the blue bars represent the coding ones. The length of each intron is indicated above and the size of each exon is indicated below (information sourced from Ensembl (ENSG00000162729)).
Description Gene type: protein coding.
Gene size: 7604 bp, 7 exons.
Transcription mRNA 2366 bp (length may vary for alternative splicing forms).
There are 5 transcripts (Ensembl).
NameTranscript IDLength (bp)Protein IDLength (aa)Exon
IGSF8-004ENST00000460351876No protein product-2

There are 7 putative alternative splicing forms (AceView).

IGSF8 alternative variantmRNA size (bp)ExonsNCBI 36, March 2006 genome (kb)AaProtein size (kDa)pI
fApr07 (partial mRNA)57144.7116517.97.3
variant gApr07-unspliced (partial mRNA)5811


Appear non coding


Appear non coding


Appear non coding


Appear non coding

Pseudogene IGSF8-004, an alternative splicing form of IGSF8/CD316, is predicted to have no protein product (Ensembl).


  Type I transmembrane protein CD316 contains an ectodomain that consists largely of four immunoglobulin domains, a transmembrane region, and a positively charged, 10-amino acid residue cytoplasmic tail. Glycosylation sites are found in the ectodomain and palmitoylation sites in the cytoplasmic domain. CD316 is constitutively palmitoylated and linked to actin cytoskeleton through direct association of its cytoplasmic domain with ezrin-radixin-moesin proteins. CD316 associates with tetraspanins such as CD9, CD81, and CD82.
Description 613 amino acids, molecular weight is 65034 Da.
Basal isoelectric point: 8.23 (PhosphoSitePlus).
Expression CD316 mRNA is ubiquitously expressed in human tissues, with high expression in brain, kidney, testis, liver and placenta, with low expression in peripheral blood cells, lung, and skeletal muscle.
CD316 protein is highly expressed in human brain (cortex, white matter, hippocampus and cerebellum), astrocytes, hepatocytes and lymphoid cells (majority of B-cells, T-cells and natural killer cells, but not on monocytes, polynuclear cells and platelets). CD316 is constitutively expressed on plasmacytoid dendritic cells and on cord blood-derived Langerhans-like cells. Upon stimulation, CD316 is expressed on monocytes, monocytes derived dendritic cells and myeloid dendritic cells.
Localisation Plasma membrane, cell-cell contacts, microvilli.
Function 1. Suppresses cell movement and cell aggregation.
2. Regulates integrin alpha3beta1- and alpha4beta1-dependent cell morphology and cell spreading.
3. May participate in the regulation of neurite outgrowth and maintenance of the neural network in the adult brain.
4. Interacts with its ligand, HSPA8, and may influence the behavior of dendritic cells and control adaptive immune response.
5. Links tetraspanin web to the actin cytoskeleton through direct associations with ezrin-radixin-moesin proteins.
6. Inhibits glioblastoma growth in vitro and in vivo.
7. EWI-2 wint inhibits hepatitis C virus entry.
8. May play a role in fertilization. Lack of CD316 present at the cell surface of CD9-null oocytes may contribute to the loss of ability of CD9-null oocytes to fuse with sperms.

CD316 typically inhibits cell migration and negatively regulates cell proliferation. It associates with tetraspanins CD9, CD81, and CD82 and likely contributes to various functions of these associated tetraspanins. It also regulates the functions of alpha3beta1 and alpha4beta1 integrins, probably through its associated tetraspanins (Clark et al., 2001; Stipp et al., 2001; Stipp et al., 2003; Zhang et al., 2003; Kolesnikova et al., 2004; Kolesnikova et al., 2009; Sala-Valdés et al., 2006).

Homology CD316 protein is conserved in chimpanzee, cow, mouse, rat, and zebrafish and belongs to the EWI subfamily of Ig superfamily. Other human EWI subfamily proteins include FPRP/CD9P-1, IGSF3, and CD101.


Note Currently there is no known disease-related or biologically significant mutation (see HGMD).

Implicated in

Entity Glioma or glioblastoma
Note CD316 inhibits glioblastoma growth in vitro and in vivo. Loss of CD316 expression correlates with a shorter survival time in human glioma patients (Kolesnikova et al., 2009).
Entity Hepatitis and liver cancer
Note Hepatitis C virus (HCV)-infected population has higher risk of developing liver cancer. Ectopic expression of EWI-2wint, i.e., EWI-2 without its N-terminus, can inhibit HCV entry and reduce HCV infection (Rocha-Perugini et al., 2008).
Entity Autoimmune diseases
Note It was reported that CD316 is an inducible receptor of HSPA8 on human dendritic cells, it may control the adaptive immune response through its influence on the behavior of dendritic cells. Therefore it maybe utilized in the treatment of antoimmune diseases such as rheumatoid arthritis (Kettner et al., 2007).
Entity Infertility
Note CD316 plays a role in fertilization. Oocytes from CD9 null mice cannot fuse with sperm. The level of CD316 proteins on the CD9-null oocyte surface is less than 10% of that on the wild-type one. The loss of CD316 on the CD9-null oocyte surface may be responsible for the loss of fusion ability (He et al., 2009; Glazar et al., 2009).
Entity Type 2 diabetes mellitus
Note CD316 is a candidate for human disorders on 1q22-q23, including type 2 diabetes mellitus (Murdoch et al., 2003).

To be noted

EWI-2wint, a cleavage product of EWI-2 in which the first Ig-domain of the 4 extracellular Ig-domains is cleaved off.


EWI-2 is a new component of the tetraspanin web in hepatocytes and lymphoid cells.
Charrin S, Le Naour F, Labas V, Billard M, Le Caer JP, Emile JF, Petit MA, Boucheix C, Rubinstein E.
Biochem J. 2003 Jul 15;373(Pt 2):409-21.
PMID 12708969
The Ig domain protein CD9P-1 down-regulates CD81 ability to support Plasmodium yoelii infection.
Charrin S, Yalaoui S, Bartosch B, Cocquerel L, Franetich JF, Boucheix C, Mazier D, Rubinstein E, Silvie O.
J Biol Chem. 2009 Nov 13;284(46):31572-8. Epub 2009 Sep 17.
PMID 19762465
PGRL is a major CD81-associated protein on lymphocytes and distinguishes a new family of cell surface proteins.
Clark KL, Zeng Z, Langford AL, Bowen SM, Todd SC.
J Immunol. 2001 Nov 1;167(9):5115-21.
PMID 11673522
Mutation of juxtamembrane cysteines in the tetraspanin CD81 affects palmitoylation and alters interaction with other proteins at the cell surface.
Delandre C, Penabaz TR, Passarelli AL, Chapes SK, Clem RJ.
Exp Cell Res. 2009 Jul 1;315(11):1953-63. Epub 2009 Mar 25.
PMID 19328198
Immunoglobulin superfamily member IgSF8 (EWI-2) and CD9 in fertilisation: evidence of distinct functions for CD9 and a CD9-associated protein in mammalian sperm-egg interaction.
Glazar AI, Evans JP.
Reprod Fertil Dev. 2009;21(2):293-303.
PMID 19210920
Loss of surface EWI-2 on CD9 null oocytes.
He ZY, Gupta S, Myles D, Primakoff P.
Mol Reprod Dev. 2009 Jul;76(7):629-36.
PMID 19107828
EWI-2/CD316 is an inducible receptor of HSPA8 on human dendritic cells.
Kettner S, Kalthoff F, Graf P, Priller E, Kricek F, Lindley I, Schweighoffer T.
Mol Cell Biol. 2007 Nov;27(21):7718-26. Epub 2007 Sep 4.
PMID 17785435
Glioblastoma inhibition by cell surface immunoglobulin protein EWI-2, in vitro and in vivo.
Kolesnikova TV, Kazarov AR, Lemieux ME, Lafleur MA, Kesari S, Kung AL, Hemler ME.
Neoplasia. 2009 Jan;11(1):77-86, 4p following 86.
PMID 19107234
Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association.
Little KD, Hemler ME, Stipp CS.
Mol Biol Cell. 2004 May;15(5):2375-87. Epub 2004 Mar 5.
PMID 15004227
Genomic organization and embryonic expression of Igsf8, an immunoglobulin superfamily member implicated in development of the nervous system and organ epithelia.
Murdoch JN, Doudney K, Gerrelli D, Wortham N, Paternotte C, Stanier P, Copp AJ.
Mol Cell Neurosci. 2003 Jan;22(1):62-74.
PMID 12595239
The CD81 partner EWI-2wint inhibits hepatitis C virus entry.
Rocha-Perugini V, Montpellier C, Delgrange D, Wychowski C, Helle F, Pillez A, Drobecq H, Le Naour F, Charrin S, Levy S, Rubinstein E, Dubuisson J, Cocquerel L.
PLoS One. 2008 Apr 2;3(4):e1866.
PMID 18382656
EWI-2 and EWI-F link the tetraspanin web to the actin cytoskeleton through their direct association with ezrin-radixin-moesin proteins.
Sala-Valdes M, Ursa A, Charrin S, Rubinstein E, Hemler ME, Sanchez-Madrid F, Yanez-Mo M.
J Biol Chem. 2006 Jul 14;281(28):19665-75. Epub 2006 May 10.
PMID 16690612
EWI-2 regulates alpha3beta1 integrin-dependent cell functions on laminin-5.
Stipp CS, Kolesnikova TV, Hemler ME.
J Cell Biol. 2003 Dec 8;163(5):1167-77.
PMID 14662754
Neuronal expression of keratinocyte-associated transmembrane protein-4, KCT-4, in mouse brain and its up-regulation by neurite outgrowth of Neuro-2a cells.
Yamada O, Tamura K, Yagihara H, Isotani M, Washizu T, Bonkobara M.
Neurosci Lett. 2006 Jan 16;392(3):226-30. Epub 2005 Oct 3.
PMID 16203089
Contrasting effects of EWI proteins, integrins, and protein palmitoylation on cell surface CD9 organization.
Yang XH, Kovalenko OV, Kolesnikova TV, Andzelm MM, Rubinstein E, Strominger JL, Hemler ME.
J Biol Chem. 2006 May 5;281(18):12976-85. Epub 2006 Mar 13.
PMID 16537545
EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells.
Zhang XA, Lane WS, Charrin S, Rubinstein E, Liu L.
Cancer Res. 2003 May 15;63(10):2665-74.
PMID 12750295


This paper should be referenced as such :
Zhang, YH ; Richardson, MM ; Zhang, XA
IGSF8 (immunoglobulin superfamily, member 8)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(5):415-418.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)IGSF8   17813
Entrez_Gene (NCBI)IGSF8    immunoglobulin superfamily member 8
AliasesCD316; CD81P3; EWI-2; EWI2; 
GeneCards (Weizmann)IGSF8
Ensembl hg19 (Hinxton)ENSG00000162729 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000162729 [Gene_View]  ENSG00000162729 [Sequence]  chr1:160091346-160098619 [Contig_View]  IGSF8 [Vega]
ICGC DataPortalENSG00000162729
TCGA cBioPortalIGSF8
Genatlas (Paris)IGSF8
SOURCE (Princeton)IGSF8
Genetics Home Reference (NIH)IGSF8
Genomic and cartography
GoldenPath hg38 (UCSC)IGSF8  -     chr1:160091346-160098619 -  1q23.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)IGSF8  -     1q23.2   [Description]    (hg19-Feb_2009)
GoldenPathIGSF8 - 1q23.2 [CytoView hg19]  IGSF8 - 1q23.2 [CytoView hg38]
Genome Data Viewer NCBIIGSF8 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AF311906 AF407274 AK055843 AK090396 AK308115
RefSeq transcript (Entrez)NM_001206665 NM_001320247 NM_052868
Consensus coding sequences : CCDS (NCBI)IGSF8
Gene ExpressionIGSF8 [ NCBI-GEO ]   IGSF8 [ EBI - ARRAY_EXPRESS ]   IGSF8 [ SEEK ]   IGSF8 [ MEM ]
Gene Expression Viewer (FireBrowse)IGSF8 [ Firebrowse - Broad ]
GenevisibleExpression of IGSF8 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)93185
GTEX Portal (Tissue expression)IGSF8
Human Protein AtlasENSG00000162729-IGSF8 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ969P0   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ969P0  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ969P0
Domaine pattern : Prosite (Expaxy)IG_LIKE (PS50835)   
Domains : Interpro (EBI)Ig-like_dom    Ig-like_dom_sf    Ig-like_fold    Ig_sub    Ig_V-set   
Domain families : Pfam (Sanger)V-set (PF07686)   
Domain families : Pfam (NCBI)pfam07686   
Domain families : Smart (EMBL)IG (SM00409)  
Conserved Domain (NCBI)IGSF8
AlphaFold pdb e-kbQ969P0   
Human Protein Atlas [tissue]ENSG00000162729-IGSF8 [tissue]
Protein Interaction databases
IntAct (EBI)Q969P0
Ontologies - Pathways
Ontology : AmiGOprotein binding  plasma membrane  single fertilization  nervous system development  skeletal muscle tissue development  membrane  integral component of membrane  integral component of membrane  intracellular membrane-bounded organelle  cell motility  extracellular exosome  
Ontology : EGO-EBIprotein binding  plasma membrane  single fertilization  nervous system development  skeletal muscle tissue development  membrane  integral component of membrane  integral component of membrane  intracellular membrane-bounded organelle  cell motility  extracellular exosome  
NDEx NetworkIGSF8
Atlas of Cancer Signalling NetworkIGSF8
Wikipedia pathwaysIGSF8
Orthology - Evolution
GeneTree (enSembl)ENSG00000162729
Phylogenetic Trees/Animal Genes : TreeFamIGSF8
Homologs : HomoloGeneIGSF8
Homology/Alignments : Family Browser (UCSC)IGSF8
Gene fusions - Rearrangements
Fusion : MitelmanUSPL1::IGSF8 [13q12.3/1q23.2]  
Fusion : QuiverIGSF8
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerIGSF8 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)IGSF8
Exome Variant ServerIGSF8
GNOMAD BrowserENSG00000162729
Varsome BrowserIGSF8
ACMGIGSF8 variants
Genomic Variants (DGV)IGSF8 [DGVbeta]
DECIPHERIGSF8 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisIGSF8 
ICGC Data PortalIGSF8 
TCGA Data PortalIGSF8 
Broad Tumor PortalIGSF8
OASIS PortalIGSF8 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICIGSF8  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DIGSF8
Mutations and Diseases : HGMDIGSF8
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)IGSF8
DoCM (Curated mutations)IGSF8
CIViC (Clinical Interpretations of Variants in Cancer)IGSF8
NCG (London)IGSF8
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry IGSF8
NextProtQ969P0 [Medical]
Target ValidationIGSF8
Huge Navigator IGSF8 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDIGSF8
Pharm GKB GenePA29767
Clinical trialIGSF8
DataMed IndexIGSF8
PubMed40 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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