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| | 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. |
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| Description | 613 amino acids, molecular weight is 65034 Da.
Basal isoelectric point: 8.23 (PhosphoSitePlus).
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| 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. |
| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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