IGSF8 (immunoglobulin superfamily, member 8)

2010-08-01   Yanhui 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

Identity

HGNC
LOCATION
1q23.2
IMAGE
Atlas Image
LOCUSID
ALIAS
CD316,CD81P3,EWI-2,EWI2,KCT-4,LIR-D1,PGRL
FUSION GENES

DNA/RNA

Atlas Image
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
IGSF8-001ENST000003144852343ENSP000003166646137
IGSF8-002ENST000004484171059ENSP000003974643014
IGSF8-003ENST000003680862366ENSP000003570656137
IGSF8-201ENST000003584752004ENSP000003512615268
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
aApr07235277.3667471.88.2
bApr07230487.6066470.48.3
cApr07199542.9231132.78.2
dApr07100545.5828330.56.7
eApr07-unspliced618416.1816618.16.7
fApr07 (partial mRNA)57144.7116517.97.3
variant gApr07-unspliced (partial mRNA)5811

0.58

Appear non coding

91

Appear non coding

9.6

Appear non coding

11.5

Appear non coding

Pseudogene

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

Proteins

Atlas Image
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 (

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.

Mutations

Note

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

Implicated in

Entity name
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 name
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 name
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 name
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 name
Type 2 diabetes mellitus
Note
CD316 is a candidate for human disorders on 1q22-q23, including type 2 diabetes mellitus (Murdoch et al., 2003).

Bibliography

Pubmed IDLast YearTitleAuthors
127089692003EWI-2 is a new component of the tetraspanin web in hepatocytes and lymphoid cells.Charrin S et al
197624652009The Ig domain protein CD9P-1 down-regulates CD81 ability to support Plasmodium yoelii infection.Charrin S et al
116735222001PGRL is a major CD81-associated protein on lymphocytes and distinguishes a new family of cell surface proteins.Clark KL et al
193281982009Mutation of juxtamembrane cysteines in the tetraspanin CD81 affects palmitoylation and alters interaction with other proteins at the cell surface.Delandre C et al
192109202009Immunoglobulin 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 et al
191078282009Loss of surface EWI-2 on CD9 null oocytes.He ZY et al
177854352007EWI-2/CD316 is an inducible receptor of HSPA8 on human dendritic cells.Kettner S et al
191072342009Glioblastoma inhibition by cell surface immunoglobulin protein EWI-2, in vitro and in vivo.Kolesnikova TV et al
150042272004Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association.Little KD et al
125952392003Genomic organization and embryonic expression of Igsf8, an immunoglobulin superfamily member implicated in development of the nervous system and organ epithelia.Murdoch JN et al
183826562008The CD81 partner EWI-2wint inhibits hepatitis C virus entry.Rocha-Perugini V et al
166906122006EWI-2 and EWI-F link the tetraspanin web to the actin cytoskeleton through their direct association with ezrin-radixin-moesin proteins.Sala-Valdés M et al
146627542003EWI-2 regulates alpha3beta1 integrin-dependent cell functions on laminin-5.Stipp CS et al
162030892006Neuronal 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 et al
165375452006Contrasting effects of EWI proteins, integrins, and protein palmitoylation on cell surface CD9 organization.Yang XH et al
127502952003EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells.Zhang XA et al

Other Information

Locus ID:

NCBI: 93185
MIM: 606644
HGNC: 17813
Ensembl: ENSG00000162729

Variants:

dbSNP: 93185
ClinVar: 93185
TCGA: ENSG00000162729
COSMIC: IGSF8

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000162729ENST00000314485Q969P0
ENSG00000162729ENST00000368086Q969P0
ENSG00000162729ENST00000448417C9J8Z4
ENSG00000162729ENST00000614243Q969P0

Expression (GTEx)

0
50
100
150
200
250
300

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
166906122006EWI-2 and EWI-F link the tetraspanin web to the actin cytoskeleton through their direct association with ezrin-radixin-moesin proteins.76
183826562008The CD81 partner EWI-2wint inhibits hepatitis C virus entry.48
127502952003EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells.31
213433092011Interacting regions of CD81 and two of its partners, EWI-2 and EWI-2wint, and their effect on hepatitis C virus infection.27
226898822012EWI-2 association with α-actinin regulates T cell immune synapses and HIV viral infection.23
150706782004EWI-2 modulates lymphocyte integrin alpha4beta1 functions.19
165375452006Contrasting effects of EWI proteins, integrins, and protein palmitoylation on cell surface CD9 organization.19
191072342009Glioblastoma inhibition by cell surface immunoglobulin protein EWI-2, in vitro and in vivo.19
223604202012Proteomic analysis identifies dysfunction in cellular transport, energy, and protein metabolism in different brain regions of atypical frontotemporal lobar degeneration.18
233511942013EWI-2wint promotes CD81 clustering that abrogates Hepatitis C Virus entry.18

Citation

Yanhui H Zhang ; Mekel M Richardson ; Xin A Zhang

IGSF8 (immunoglobulin superfamily, member 8)

Atlas Genet Cytogenet Oncol Haematol. 2010-08-01

Online version: http://atlasgeneticsoncology.org/gene/45820/igsf8