IGSF8 (immunoglobulin superfamily, member 8)
2010-08-01 Yanhui H Zhang  , Mekel M Richardson  , Xin A Zhang   AffiliationVascular Biology, Cancer Centers, Departments of Medicine, Molecular Science, University of Tennessee Health Science Center, Memphis, USA
Identity

DNA/RNA

Description
Gene size: 7604 bp, 7 exons.
Transcription
There are 5 transcripts (Ensembl).
| Name | Transcript ID | Length (bp) | Protein ID | Length (aa) | Exon |
| IGSF8-001 | ENST00000314485 | 2343 | ENSP00000316664 | 613 | 7 |
| IGSF8-002 | ENST00000448417 | 1059 | ENSP00000397464 | 301 | 4 |
| IGSF8-003 | ENST00000368086 | 2366 | ENSP00000357065 | 613 | 7 |
| IGSF8-201 | ENST00000358475 | 2004 | ENSP00000351261 | 526 | 8 |
| IGSF8-004 | ENST00000460351 | 876 | No protein product | - | 2 |
There are 7 putative alternative splicing forms (AceView).
| IGSF8 alternative variant | mRNA size (bp) | Exons | NCBI 36, March 2006 genome (kb) | Aa | Protein size (kDa) | pI |
| aApr07 | 2352 | 7 | 7.36 | 674 | 71.8 | 8.2 |
| bApr07 | 2304 | 8 | 7.60 | 664 | 70.4 | 8.3 |
| cApr07 | 1995 | 4 | 2.92 | 311 | 32.7 | 8.2 |
| dApr07 | 1005 | 4 | 5.58 | 283 | 30.5 | 6.7 |
| eApr07-unspliced | 6184 | 1 | 6.18 | 166 | 18.1 | 6.7 |
| fApr07 (partial mRNA) | 571 | 4 | 4.71 | 165 | 17.9 | 7.3 |
| variant gApr07-unspliced (partial mRNA) | 581 | 1 | 0.58 Appear non coding | 91 Appear non coding | 9.6 Appear non coding | 11.5 Appear non coding |
Pseudogene
Proteins

Description
Basal isoelectric point: 8.23 (
Expression
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
Function
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
Mutations
Note
Implicated in
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 12708969 | 2003 | EWI-2 is a new component of the tetraspanin web in hepatocytes and lymphoid cells. | Charrin S et al |
| 19762465 | 2009 | The Ig domain protein CD9P-1 down-regulates CD81 ability to support Plasmodium yoelii infection. | Charrin S et al |
| 11673522 | 2001 | PGRL is a major CD81-associated protein on lymphocytes and distinguishes a new family of cell surface proteins. | Clark KL et al |
| 19328198 | 2009 | Mutation of juxtamembrane cysteines in the tetraspanin CD81 affects palmitoylation and alters interaction with other proteins at the cell surface. | Delandre C et al |
| 19210920 | 2009 | 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 et al |
| 19107828 | 2009 | Loss of surface EWI-2 on CD9 null oocytes. | He ZY et al |
| 17785435 | 2007 | EWI-2/CD316 is an inducible receptor of HSPA8 on human dendritic cells. | Kettner S et al |
| 19107234 | 2009 | Glioblastoma inhibition by cell surface immunoglobulin protein EWI-2, in vitro and in vivo. | Kolesnikova TV et al |
| 15004227 | 2004 | 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 et al |
| 12595239 | 2003 | Genomic organization and embryonic expression of Igsf8, an immunoglobulin superfamily member implicated in development of the nervous system and organ epithelia. | Murdoch JN et al |
| 18382656 | 2008 | The CD81 partner EWI-2wint inhibits hepatitis C virus entry. | Rocha-Perugini V et al |
| 16690612 | 2006 | EWI-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 |
| 14662754 | 2003 | EWI-2 regulates alpha3beta1 integrin-dependent cell functions on laminin-5. | Stipp CS et al |
| 16203089 | 2006 | 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 et al |
| 16537545 | 2006 | Contrasting effects of EWI proteins, integrins, and protein palmitoylation on cell surface CD9 organization. | Yang XH et al |
| 12750295 | 2003 | EWI2/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 ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000162729 | ENST00000314485 | Q969P0 |
| ENSG00000162729 | ENST00000368086 | Q969P0 |
| ENSG00000162729 | ENST00000448417 | C9J8Z4 |
| ENSG00000162729 | ENST00000614243 | Q969P0 |
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38657602 | 2024 | IGSF8 is an innate immune checkpoint and cancer immunotherapy target. | 2 |
| 38657602 | 2024 | IGSF8 is an innate immune checkpoint and cancer immunotherapy target. | 2 |
| 36788350 | 2023 | EWI2 and its relatives in Tetraspanin-enriched membrane domains regulate malignancy. | 2 |
| 36788350 | 2023 | EWI2 and its relatives in Tetraspanin-enriched membrane domains regulate malignancy. | 2 |
| 35339615 | 2022 | EWI2 promotes endolysosome-mediated turnover of growth factor receptors and integrins to suppress lung cancer. | 2 |
| 35773608 | 2022 | EWI2 prevents EGFR from clustering and endocytosis to reduce tumor cell movement and proliferation. | 0 |
| 35339615 | 2022 | EWI2 promotes endolysosome-mediated turnover of growth factor receptors and integrins to suppress lung cancer. | 2 |
| 35773608 | 2022 | EWI2 prevents EGFR from clustering and endocytosis to reduce tumor cell movement and proliferation. | 0 |
| 33605506 | 2021 | EWI-2 controls nucleocytoplasmic shuttling of EGFR signaling molecules and miRNA sorting in exosomes to inhibit prostate cancer cell metastasis. | 11 |
| 33605506 | 2021 | EWI-2 controls nucleocytoplasmic shuttling of EGFR signaling molecules and miRNA sorting in exosomes to inhibit prostate cancer cell metastasis. | 11 |
| 31757023 | 2019 | EWI-2 Inhibits Cell-Cell Fusion at the HIV-1 Virological Presynapse. | 7 |
| 31757023 | 2019 | EWI-2 Inhibits Cell-Cell Fusion at the HIV-1 Virological Presynapse. | 7 |
| 25656846 | 2015 | EWI-2 negatively regulates TGF-β signaling leading to altered melanoma growth and metastasis. | 28 |
| 25656846 | 2015 | EWI-2 negatively regulates TGF-β signaling leading to altered melanoma growth and metastasis. | 28 |
| 23351194 | 2013 | EWI-2wint promotes CD81 clustering that abrogates Hepatitis C Virus entry. | 22 |
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
