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CD81 (Cluster of Differentiation 81)

Written2019-09Sylwia Hasterok, Barnabas Nyesiga, Anette Gjörloff-Wingren
Faculty of Biology and Environmental Protection, University of Silesia, Katowice, Poland hasterok.sylwia@gmail.com (HS); Biomedical science, Health and society, Malmö University, Malmö, Sweden nyesigabarnabas@gmail.com; anette.gjorloff-wingren@mau.se (BN; GWA)

Abstract Cluster of differentiation (CD81) is a type of protein, which is encoded by CD81 gene. Beside that CD81 is also known under other names such as Target of the Antiproliferative Antibody 1 (TAPA-1) and Tetraspanin-28 (TSPAN28). Location of CD81 is known to be on chromosome 11 (11p15.5), where it contains 15-20 bases in length. It is expressed mostly in cells of testis, ovary, endometrium, placenta, bone marrow, smooth muscles and others. The main function of the CD81 protein is to mediate signal transduction events, which are important for cells' development, activation, growth and motility. The CD81 gene is also known as a candidate for many malignancies because of its location. The characteristic feature of CD81 is that it is highly hydrophobic and contains a short N- and C-terminal cytoplasmic domains together with cytoplasmic cysteines, potential sites of palmitoylation as well as four transmembrane domains where they together hold the protein in a cell membrane. There are two CD81 isoforms, isoform 1 and isoform 2. Isoforms of CD81 are usually found in a tumor-suppressor region where they have a great impact on tumor development. There has always been a high interest in research on CD81 function in viral disease development. In fact, it is known that CD81 contributes in the development of diseases such as hepatitis C, malaria and various types of cancer. Since the complete effect of CD81 is unknown, further research and scientific methodology could potentially discover all possible functions and mechanisms regulated by the CD81 protein in human body.

Keywords CD81, TAPA-1, Tetraspanin-28, malignancies, isoforms, viral disease.

(Note : for Links provided by Atlas : click)

Identity

Alias_namesTAPA1
CD81 antigen (target of antiproliferative antibody 1)
Alias_symbol (synonym)TAPA-1
TSPAN28
Other aliasTAPA-1; TAPA1; TAPA (Target of the Antiproliferative Antibody 1)
CD 81 antigen; CD81 molecule
TSPAN28; TSPAN-28 (Tetraspanin-28)
S5.7
CVID6
HGNC (Hugo) CD81
LocusID (NCBI) 975
Atlas_Id 991
Location 11p15.5  [Link to chromosome band 11p15]
Location_base_pair Starts at 2377317 and ends at 2397419 bp from pter ( according to hg19-Feb_2009)  [Mapping CD81.png]
 
  Figure 1. Mapping of CD81 gene on chromosome 11p15.5 (from Ensembl CD81 gene). Source: Ensembl data base (https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000110651;r=11:2376177-2397419
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

Note The highest level of CD81 gene expression is in endometrium (RPKM 241.8), fat (RPKM 237.1), lung (RPKM 191.2) and 24 other tissues in the human body. Proteins encoded by the CD81 gene are important for transduction of signals, cell development, growth and motility (RefSeq NCBI et al., 2019).
 
  Figure 2. Homo sapiens CD81 molecule RefSeqGene (LRG_142) on chromosome 11. (RefSeq NCBI et al., 2019).
Description Cluster of Differentiation 81 (CD81) is a type of protein, which belongs to tetraspanin family of proteins (Thomas and Mohler, 2011). According to the study, it is an important molecule for the biological system of living organisms that regulates several types of mechanisms in the body (Thomas and Mohler, 2011). The molecule was previously known as TAPA-1 but changed its name to CD81, after the Fifth International Workshop on Human Leukocyte Differentiation Antigens' (IUIS/WHO Subcommittee on CD Nomenclature, 1994).
CD81 gene constitutes a protein coding gene which is located in the chromosomal region 11p15.5 of human genome. Using 5A6 (immunoglobulin- γ1), a monoclonal antiproliferative antibody, Oren et al. (1990) performed the first isolation of cDNAs encoding CD81. The chromosomal localization of CD81 gene in the short arm of chromosome 11 was determined by Andria et al. (1991) in Southern blot experiments in which DNA isolated from somatic cell hybrids was used. In order to assign CD81 gene to a specific region on the chromosome 11, Virtaneva et al. (1994) performed experiments by hybridizing CD81 gene to derivative somatic cell hybrid DNAs of human chromosome 11. The exact location of CD81 gene is shown in the figure 1. To date, 17 transcript variants have been found for this gene.
As indicated by Andria et al. (1991), the 5' untranslated region of the CD81 gene is abundant in CpG islands, which is a common feature observed in many housekeeping genes (Andria et al.,1991; Levy et al., 1998). High content of G + C nucleotides in this region correlates with a high susceptibility to methylation events, which can affect the expression of the receptor (Houldsworth et al., 2013). It also contains a TATA box at -25 position and presumably, binding sites for SP1 transcription factor (Maecker et al., 1997). Additionally, it has been reported that the region in which CD81 gene is located constitutes a tumor-suppressor region, which makes a CD81 gene an important candidate for various malignancies.
Transcription There are several ongoing studies regarding the CD81 gene due to its transcriptional activity (Hong et al., 2014; Tardif et al., 2005). In an experiment in which promoter analysis was performed, it has been shown that there is an essential role of the SP1 transcription factor in CD81-induced MT1-MMP transcription (Hong et al., 2014). Having CD81 with high MT1-MMP expression levels is of a great importance since it is associated with malignant melanoma development (Hong et al., 2014). The antigen itself is very much vital for the malignancies, primarily due to the location of the CD81 gene in a tumour-suppressor region (Levy et al., 2014). Mature transcript of CD81 is made of eight exons, all of which code information for protein synthesis. The transcript itself is 1,714 bp long.

Protein

 
  Figure 3. CD81 structure (Levy, 2014).
Description CD81 antigen, previously known as TAPA1, constitues a membrane protein of 26-kDa molecular weight, which is expressed in many cell types, including hemopoietic, endothelial as well as epithelial cells. It is a founding member of a highly conserved tetraspan family of transmembrane 4 superfamily, also known as tetraspanin family. Members of this family are expressed not only in mammals, but also in all other multicellular organisms, including insects such as Drosophila, plants as well as fungi.
CD81 is a highly hydrophobic protein which contains a short N- and C-terminal cytoplasmic domains with cytoplasmic cysteins, potential sites of palmitoylation as well as four transmembrane domains (TM 1-4) that hold the protein in a cell membrane. The protein folds itself creating a large extracellular loop (LEL) with CCG motif and two disulfide bridges, small extracellular loop (SEL) and even a smaller loop of intracellular location (Levy, 2014). Unlike many other members of the family, CD81 does not undergo glycosylation. The protein exibits a strong homology with two antigens - CD37 (65% identical) as well as ME491 melanoma-associated antigen (98% identical) also known as CD63 molecule. Originally, CD81 protein was characterized as a target of an antiproliferative antibody that leads to the inhibition of B cell proliferation (Levy, 2014).
C According to the Zimmerman et al. (2016), transmembrane parts of CD81 contain two largely disconnected couples of spirals, covered with a bulky extracellular loop at the exterior membrane leaflet. These two sets of coils converge at the position of internal leaflet to generate an intramembrane abridged with supplementary electron concentration corresponding to a cholesterol molecule in a cavity. Molecular subtleties simulation recognizes a supplementary conformation in which extracellular loop splits considerably from the transmembrane domain. Cholesterol binding appears to modulate CD81 activity in cells, signifying a probable mechanism for regulation of tetraspanin occupation.
 
  Figure 4. Model of CD81 protein (Source: SWISS-MODEL https://swissmodel.expasy.org/interactive)
Expression On a protein level the expression of CD81 occurs on B-cells, hepatocytes, monocytes/macrophages and on both naive and memory CD4-positive T cells (Takeda et al., 2003; Silvie et al., 2003; van Zelm et al., 2010; Sagi et al., 2012)
 
  Figure 5. Structure of CD81 protein (Source: UNIPORT https://www.uniprot.org/uniprot/P60033)
Localisation CD81 gene can be localised in the tumor-suppressor region where two different isoforms can be found.
 
  Figure 6. CD81 isoform 1. Location 10-228 (RefSeq NCBI et al., 2019)
Function CD 81 plays a significant role in several physiological functions such as regulation of cell activation, development, motility and growth (Fagerberg et al., 2014). It is also involved in signal transduction. CD81 encoded glycoprotein associated with the cell surface is known to create a complex with integrins, which helps to promote fusion of muscle cells as well as maintenance of myotubes.
According to Thomas and Mohler (2011), CD81 is expressed on the surface of oocytes and absence of this molecule is associated with a reduced fertility in the mice system due to egg-sperm fusion defects. On the other hand, Kaji et al. (2002) proved that CD81 and CD9 have corresponding utilities in the egg-sperm fusion. The activity of CD9 is reduced by the absence of the CD81 which was observed in the mice model system. There are several reports available in which it has been proven that CD81 actively prevents development of some viral diseases like hepatitis C virus (Nalesnik and Kanto, 2010). Geisert et al. (2002) showed that CD81 is involved in the development of the central nervous system. According to the experiment, in comparison to normal mice, CD81 mutation in the cells of central nervous system results in the development of 30% larger brains.
When CD81 is increased in the body, it may be promoting breast cancer. Scientific study designed by Zhang et al. (2018) on MDA-MB-435S and MDA-MB-231 human breast cancer cell lines showed that when CD81 expression increases as an effect it can promote breast cancer. Malaria parasite Plasmodium uses CD81 membrane protein to attack liver cells in a human body (Bruening et al., 2018). It is also known that CD81 has an ability to bind to cholesterol where the amount of cholesterol controls the expression of CD81 (van Zelm et al., 2010; Vences-Catalán et al., 2015).
 
  Figure 7. CD81 isoform 2. Location 42-131 (RefSeq NCBI et al., 2019).
Homology Highest homology level of CD81 protein can be found between humans and mice (Boismenu et al., 1996). By analysing the homology between human and mouse variants, it has been shown that the transmembrane domain residues are mostly sequentially conserved. Beside that it has been also proven that extracellular domains significantly differ from each other as presented in a figure 9 (Frolikova et al., 2018). The protein exhibits a strong homology with two antigens - CD37 (65% identical) as well as ME491, melanoma-associated antigen (98% identical) also known as CD63 molecule (Levy et al., 2014).
 
  Figure 8. CD81-cholesterol interactions (Zimmerman et al., 2016).
 
  Figure 9. CD81 in human and mouse (Frolikova et al., 2018). Figure 9 presents the transmembrane domain residues and differences between extracellular domains. The whole protein consists of non-identical acids between human and mouse CD81 and CD9 projected onto the model of CD9/CD81 complex. The difference is the amount of amino acids where CD81 contains 17 different amino acids in the extracellular domain while CD9 differs in 25 amino acids on same location (Frolikova et al.,2018).

Mutations

Note Mutations associated with CD81 are often caused by viral infections such as hepatitis C. According to the study where the hepatitis C virus envelope protein (E)2 interacts with cellular receptor CD81 it was possible to obtain the modulation of B and T cell function. Despite positive results, the importance of the mutation is unknown even though the mutation was caused by the modulation of these two proteins as well as the effect and the correlation between CD81 and binding regions of HCV Geno/subtypes (Kronenberger B et al., 2004).
Mutations associated with CD81 are often caused by viral infections such as hepatitis C. According to the study where the hepatitis C virus envelope protein (E)2 interacts with cellular receptor CD81 it was possible to obtain the modulation of B and T cell function. Despite positive It is known that CD19 and CD81 depend on each other regardless if the mutation occurs or not. Dependence was described on a group of patients with an increased susceptibility to infection, hypogammaglobulinemia, and normal numbers of mature B cells in blood, but all the patients had a mutation in CD19 in common (van Zelm et al., 2006). Usually, CD81 is expressed on blood cells such as blood lymphocytes, monocytes, basophilic granulocytes, and eosinophils. The absence of CD81 in membrane has never been found in humans before. However, a study performed on B cells from 611 neonatal cord blood samples showed that the absence can occur (Duijts et al., 2009).
Mutations associated with CD81 are often caused by viral infections such as hepatitis C. According to the study where the hepatitis C virus envelope protein (E)2 interacts with cellular receptor CD81 it was possible to obtain the modulation of B and T cell function. Despite positive In a study where a patient had severe nephropathy and profound hypogammaglobulinemia as well as immunodeficiency with decreased memory B cell numbers, with help of DNA sequencing of all 8 exons in which homozygous G>A substitution was found, splice sites were directly identified downstream of exon 6: c.561+1G>A. This kind of exons cause frameshift before the fourth transmembrane domain as well as premature stop (p. Glu188MetfsX13). Because of the mutation, the splice donor site was disrupted and sixth intron in cryptic splice site was used (van Zelm et al., 2010).
 
  Figure 10. Presentation of the CD81 gene with 8 exons. Patient who participated in the study was homozygous for a splice site mutation downstream of exon 6 (exon6+1 G>A). This is resulting in the usage of a cryptic splice site 13 nucleotides downstream of exon 6. Premature stop codon upstream of the fourth transmembrane domain of the CD81 protein, TM transmembrane domain; SEL, short extracellular loop; LEL, large extracellular loop as well as frameshift are caused by the insertion of the 13-nucleotide region (van Zelm et al., 2010).
Epigenetics Cluster analysis have found 25 types of genes that were hypermethylated and hypomethylated, respectively, in 20% in all of the studies. One of the most frequently hypermethylated genes was CD81. CD81 has been found in larger amounts as target of polycomb repressive complex 2 in embryonic stem cells in a medical condition called Glioblastoma multiforme, a devastating brain tumor in adults. CD81 is a member of membranal-embedded tetraspanin superfamily and it is usually observed in multiple myelomas. Tetraspanin genes associated with signalling proteins modulate fundamental biological functions and can potentially be involved in CD81 gene as a metastasis suppressor (Martinez et al., 2009).
Somatic CD81 also has an ability to regulate CD19 in B-lymphocytes, which can trigger the progression of hepatitis C virus infection in human cells. Scientific research in which human cells underwent a procedure of immunohistological staining proved that normal hematopoietic tissue resulted in a strong staining for CD81 in a normal germinal centre B cell. Another analytical method called high-dimensional flow cytometry confirmed that among B and T cell subsets, germinal centre B cells had the highest level of CD81 expression (Luo et al., 2010). Moreover, scientific study performed on mice showed that there is a correlation between the amount of CD81 and CD9 presented in somatic cells with successful fertilisation of spices. It is proven that the lack of CD81 and CD9 leads to a lower chance of successful fertilisation. In somatic cells, CD81 and CD9 associate with each other together with other, non-tetraspanin molecules, creating proteolipid complexes. Artificial removal of CD81 gene in mice leads to 40% reduction of female fertility (Rubinstein et al., 2006).

Implicated in

Note The CD81 protein is a highly involved in the development of several diseases including hepatitis C, malaria, several types of cancer, HIV, fungal diseases, parasites etc. The main mechanism involves CD81 acting as a signalling molecule with a pathogen attached to the extracellular loop of CD81. This means that it acts as a getaway for the infection. It has also been proven that CD81 is important for the immune system due to its close association with CD19 in B cells. Simultaneously, it plays an important role in T cells by acting as a costimulatory agent for CD3 (Vences-Catalán et al., 2015). Presumably, further research on CD81 may provide information on all other possible functions and mechanisms of action of this molecule (Monk and Partridge, 2012).
  
Entity Hepatitis C
Note Research on hepatitis C virus and CD81 has always been of a high interest.
  
  
Entity Malaria
Note Malaria parasites such as Plasmodium yoelii and Plasmodium falciparum sporozoites are involved in the CD81 expression. In a study where correlation of CD81 and malaria infection has been analysed, direct link between CD81 and cholesterol during the infection of malaria parasites has been shown. Additionally, it has been proven that the loops of these tetraspanins contain a new type of microdomains that potentially could be used by pathogens for infection (Silvie et al., 2006).
  
  
Entity Breast cancer
Note The role of CD81 protein in breast cancer is unknown (Zhang et al., 2018). According to the scientific study the expression of CD81 during breast cancer state is significantly increased compared to the normal breast tissue. The increase of CD81 is associated with lymph node metastasis. (Zhang et al., 2018). It has been concluded that CD81 may be used as a prognostic biomarker associated with poor patient prognosis in breast cancer (Zhang et al., 2018).
  
  
Entity Hepatocellular carcinoma
Note CD81 is known to be a receptor for hepatitis C. This kind of characteristic is a major cause of hepatocellular carcinoma (Charrin et al., 2001).
  
  
Entity Acute myeloid leukaemia (AML)
Note The medical condition AML is known to be heterogeneous disease and lately, novel prognostic factors have been of a great importance in order to propose appropriate therapy. CD81 does have negative impact on survival outcome in AML patients. It is known that CD81 could be used in therapeutic approaches in stating proper AML treatment. Further studies are needed in order to confirm prognostic impact of CD81 and AML (Boyer et al., 2016).
  
  
Entity HIV infection
Note Some reports have indicated that CD81 is associated with CD4, which provides a costimulatory signal that increases HIV-1 gene expression (Gordón-Alonso et al., 2006) CD81 has the ability to deliver a co-signal for T cells. This action triggers cytokine production, which leads to the cellular proliferation. Signalling processes are initiated through the T-cell receptor (TCR)/CD3 complex where coactivator CD28 affects immunodeficiency virus type 1 (HIV-1) gene expression. According to Tardig et al. (2005) no study has investigated the putative costimulatory activity of CD81 on HIV-1 transcriptional activity.
  

Bibliography

CD81 molecule [Homo sapiens (human)]
RefSeq National Center for Biotechnology Information, U.S. 2019. National Library of Medicine 86000 Rockville Pike, Bethesda MD, 20894 USA
 
Genomic organization and chromosomal localization of the TAPA-1 gene
Andria ML, Hsieh CL, Oren R, Francke U, Levy S
J Immunol 1991 Aug 1;147(3):1030-6
PMID 1650385
 
A role for CD81 in early T cell development
Boismenu R, Rhein M, Fischer WH, Havran WL
Science 1996 Jan 12;271(5246):198-200
PMID 8539618
 
Tetraspanin CD81 is an adverse prognostic marker in acute myeloid leukemia
Boyer T, Guihard S, Roumier C, Peyrouze P, Gonzales F, Berthon C, Quesnel B, Preudhomme C, Behal H, Duhamel A, Roche-Lestienne C, Cheok M
Oncotarget 2016 Sep 20;7(38):62377-62385
PMID 27566555
 
Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB
Bruening J, Lasswitz L, Banse P, Kahl S, Marinach C, Vondran FW, Kaderali L, Silvie O, Pietschmann T, Meissner F, Gerold G
PLoS Pathog 2018 Jul 19;14(7):e1007111
PMID 30024968
 
IUIS/WHO Subcommittee on CD Nomenclature
CD antigens 1993: an updated nomenclature for clusters of differentiation on human cells
Bull World Health Organ 1994;72(5):807-8
PMID 7955032
 
The major CD9 and CD81 molecular partner
Charrin S, Le Naour F, Oualid M, Billard M, Faure G, Hanash SM, Boucheix C, Rubinstein E
Identification and characterization of the complexes J Biol Chem
PMID 11278880
 
CD81 is an entry coreceptor for hepatitis C virus
Cormier EG, Tsamis F, Kajumo F, Durso RJ, Gardner JP, Dragic T
Proc Natl Acad Sci U S A 2004 May 11;101(19):7270-4
PMID 15123813
 
Fetal growth influences lymphocyte subset counts at birth: the Generation R Study
Duijts L, Bakker-Jonges LE, Labout JA, Jaddoe VW, Hofman A, Steegers EA, van Dongen JJ, Hooijkaas H, Moll HA
Neonatology 2009;95(2):149-56
PMID 18776729
 
CD81 and hepatitis C virus (HCV) infection
Fénéant L, Levy S, Cocquerel L
Viruses 2014 Feb 6;6(2):535-72
PMID 24509809
 
Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, Habuka M, Tahmasebpoor S, Danielsson A, Edlund K, Asplund A, Sjöstedt E, Lundberg E, Szigyarto CA, Skogs M, Takanen JO, Berling H, Tegel H, Mulder J, Nilsson P, Schwenk JM, Lindskog C, Danielsson F, Mardinoglu A, Sivertsson A, von Feilitzen K, Forsberg M, Zwahlen M, Olsson I, Navani S, Huss M, Nielsen J, Ponten F, Uhlén M
Mol Cell Proteomics 2014 Feb;13(2):397-406
PMID 24309898
 
CD9 and CD81 Interactions and Their Structural Modelling in Sperm Prior to Fertilization
Frolikova M, Manaskova-Postlerova P, Cerny J, Jankovicova J, Simonik O, Pohlova A, Secova P, Antalikova J, Dvorakova-Hortova K
Int J Mol Sci 2018 Apr 19;19(4)
PMID 29671763
 
Increased brain size and glial cell number in CD81-null mice
Geisert EE Jr, Williams RW, Geisert GR, Fan L, Asbury AM, Maecker HT, Deng J, Levy S
J Comp Neurol 2002 Nov 4;453(1):22-32
PMID 12357429
 
Tetraspanins CD9 and CD81 modulate HIV-1-induced membrane fusion
Gordón-Alonso M, Yañez-Mó M, Barreiro O, Alvarez S, Muñoz-Fernández MA, Valenzuela-Fernández A, Sánchez-Madrid F
J Immunol 2006 Oct 15;177(8):5129-37
PMID 17015697
 
The tetraspanin CD81 protein increases melanoma cell motility by up-regulating metalloproteinase MT1-MMP expression through the pro-oncogenic Akt-dependent Sp1 activation signaling pathways
Hong IK, Byun HJ, Lee J, Jin YJ, Wang SJ, Jeoung DI, Kim YM, Lee H
J Biol Chem 2014 May 30;289(22):15691-704
PMID 24733393
 
CD81 sequence and susceptibility to hepatitis C infection
Houldsworth A, Metzner MM, Demaine A, Hodgkinson A, Kaminski E, Cramp M
J Med Virol 2014 Jan;86(1):162-8
PMID 24122777
 
Infertility of CD9-deficient mouse eggs is reversed by mouse CD9, human CD9, or mouse CD81; polyadenylated mRNA injection developed for molecular analysis of sperm-egg fusion
Kaji K, Oda S, Miyazaki S, Kudo A
Dev Biol 2002 Jul 15;247(2):327-34
PMID 12086470
 
Mutations in the putative HCV-E2 CD81 binding regions and correlation with cell surface CD81 expression
Kronenberger B, Sarrazin C, Hofmann WP, von Wagner M, Herrmann E, Welsch C, Elez R, Rüster B, Piiper A, Zeuzem S
J Viral Hepat 2004 Jul;11(4):310-8
PMID 15230853
 
Function of the tetraspanin molecule CD81 in B and T cells
Levy S
Immunol Res 2014 May;58(2-3):179-85
PMID 24522698
 
Structure and membrane topology of TAPA-1
Levy S, Nguyen VQ, Andria ML, Takahashi S
J Biol Chem 1991 Aug 5;266(22):14597-602
PMID 1860863
 
CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system
Levy S, Todd SC, Maecker HT
Annu Rev Immunol 1998;16:89-109
PMID 9597125
 
CD81 protein is expressed at high levels in normal germinal center B cells and in subtypes of human lymphomas
Luo RF, Zhao S, Tibshirani R, Myklebust JH, Sanyal M, Fernandez R, Gratzinger D, Marinelli RJ, Lu ZS, Wong A, Levy R, Levy S, Natkunam Y
Hum Pathol 2010 Feb;41(2):271-80
PMID 20004001
 
The tetraspanin superfamily: molecular facilitators
Maecker HT, Todd SC, Levy S
FASEB J 1997 May;11(6):428-42
PMID 9194523
 
A microarray-based DNA methylation study of glioblastoma multiforme
Martinez R, Martin-Subero JI, Rohde V, Kirsch M, Alaminos M, Fernandez AF, Ropero S, Schackert G, Esteller M
Epigenetics 2009 May 16;4(4):255-64
PMID 19550145
 
Tetraspanins: gateways for infection
Monk PN, Partridge LJ
Infect Disord Drug Targets 2012 Feb;12(1):4-17
PMID 22034932
 
Chapter Forty-Four - Natural killer cells and hepatitis C virus infection.
Nalesnik MA, Kanto T.
Natural Killer Cells. B Sci. Clini Appl.; 5; 571-587.
 
TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins
Oren R, Takahashi S, Doss C, Levy R, Levy S
Mol Cell Biol 1990 Aug;10(8):4007-15
PMID 1695320
 
Binding of hepatitis C virus to CD81
Pileri P, Uematsu Y, Campagnoli S, Galli G, Falugi F, Petracca R, Weiner AJ, Houghton M, Rosa D, Grandi G, Abrignani S
Science 1998 Oct 30;282(5390):938-41
PMID 9794763
 
Reduced fertility of female mice lacking CD81
Rubinstein E, Ziyyat A, Prenant M, Wrobel E, Wolf JP, Levy S, Le Naour F, Boucheix C
Dev Biol 2006 Feb 15;290(2):351-8
PMID 16380109
 
Complementary costimulation of human T-cell subpopulations by cluster of differentiation 28 (CD28) and CD81
Sagi Y, Landrigan A, Levy R, Levy S
Proc Natl Acad Sci U S A 2012 Jan 31;109(5):1613-8
PMID 22307619
 
New insights into the mechanisms and roles of cell-cell fusion
Shinn-Thomas JH, Mohler WA
Int Rev Cell Mol Biol 2011;289:149-209
PMID 21749901
 
Cholesterol contributes to the organization of tetraspanin-enriched microdomains and to CD81-dependent infection by malaria sporozoites
Silvie O, Charrin S, Billard M, Franetich JF, Clark KL, van Gemert GJ, Sauerwein RW, Dautry F, Boucheix C, Mazier D, Rubinstein E
J Cell Sci 2006 May 15;119(Pt 10):1992-2002
PMID 16687736
 
Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity
Silvie O, Rubinstein E, Franetich JF, Prenant M, Belnoue E, Rénia L, Hannoun L, Eling W, Levy S, Boucheix C, Mazier D
Nat Med 2003 Jan;9(1):93-6
PMID 12483205
 
Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear phagocytes
Takeda Y, Tachibana I, Miyado K, Kobayashi M, Miyazaki T, Funakoshi T, Kimura H, Yamane H, Saito Y, Goto H, Yoneda T, Yoshida M, Kumagai T, Osaki T, Hayashi S, Kawase I, Mekada E
J Cell Biol 2003 Jun 9;161(5):945-56
PMID 12796480
 
Tetraspanin CD81 provides a costimulatory signal resulting in increased human immunodeficiency virus type 1 gene expression in primary CD4+ T lymphocytes through NF-kappaB, NFAT, and AP-1 transduction pathways
Tardif MR, Tremblay MJ
J Virol 2005 Apr;79(7):4316-28
PMID 15767432
 
Immune Targeting of Tetraspanins Involved in Cell Invasion and Metastasis
Vences-Catalán F, Levy S
Front Immunol 2018 Jun 12;9:1277
PMID 29946318
 
Chromosomal localization of three human genes coding for A15, L6, and S5
Virtaneva KI, Emi N, Marken JS, Aruffo A, Jones C, Spurr NK, Schröder JP
7 (TAPA1): all members of the transmembrane 4 superfamily of proteins Immunogenetics
PMID 8168850
 
Increased Expression of CD81 in Breast Cancer Tissue is Associated with Reduced Patient Prognosis and Increased Cell Migration and Proliferation in MDA-MB-231 and MDA-MB-435S Human Breast Cancer Cell Lines In Vitro
Zhang N, Zuo L, Zheng H, Li G, Hu X
Med Sci Monit 2018 Aug 17;24:5739-5747
PMID 30117494
 
Crystal Structure of a Full-Length Human Tetraspanin Reveals a Cholesterol-Binding Pocket
Zimmerman B, Kelly B, McMillan BJ, Seegar TCM, Dror RO, Kruse AC, Blacklow SC
Cell 2016 Nov 3;167(4):1041-1051
PMID 27881302
 
CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency
van Zelm MC, Smet J, Adams B, Mascart F, Schandené L, Janssen F, Ferster A, Kuo CC, Levy S, van Dongen JJ, van der Burg M
J Clin Invest 2010 Apr;120(4):1265-74
PMID 20237408
 

Citation

This paper should be referenced as such :
Hastero S, Nyesiga B, Gjörloff-Wingren A
CD81 (Cluster of Differentiation 81);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/CD81ID991ch11p15.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(9;11)(q34;p15) CD81/SURF4


External links

Nomenclature
HGNC (Hugo)CD81   1701
LRG (Locus Reference Genomic)LRG_142
Cards
AtlasCD81ID991ch11p15
Entrez_Gene (NCBI)CD81  975  CD81 molecule
AliasesCVID6; S5.7; TAPA1; TSPAN28
GeneCards (Weizmann)CD81
Ensembl hg19 (Hinxton)ENSG00000110651 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000110651 [Gene_View]  ENSG00000110651 [Sequence]  chr11:2377317-2397419 [Contig_View]  CD81 [Vega]
ICGC DataPortalENSG00000110651
TCGA cBioPortalCD81
AceView (NCBI)CD81
Genatlas (Paris)CD81
WikiGenes975
SOURCE (Princeton)CD81
Genetics Home Reference (NIH)CD81
Genomic and cartography
GoldenPath hg38 (UCSC)CD81  -     chr11:2377317-2397419 +  11p15.5   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CD81  -     11p15.5   [Description]    (hg19-Feb_2009)
GoldenPathCD81 - 11p15.5 [CytoView hg19]  CD81 - 11p15.5 [CytoView hg38]
ImmunoBaseENSG00000110651
Mapping of homologs : NCBICD81 [Mapview hg19]  CD81 [Mapview hg38]
OMIM186845   613496   
Gene and transcription
Genbank (Entrez)AB209380 AI334163 BC002978 BC093047 BG397506
RefSeq transcript (Entrez)NM_001297649 NM_004356
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CD81
Cluster EST : UnigeneHs.54457 [ NCBI ]
CGAP (NCI)Hs.54457
Alternative Splicing GalleryENSG00000110651
Gene ExpressionCD81 [ NCBI-GEO ]   CD81 [ EBI - ARRAY_EXPRESS ]   CD81 [ SEEK ]   CD81 [ MEM ]
Gene Expression Viewer (FireBrowse)CD81 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)975
GTEX Portal (Tissue expression)CD81
Human Protein AtlasENSG00000110651-CD81 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP60033   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP60033  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP60033
Splice isoforms : SwissVarP60033
PhosPhoSitePlusP60033
Domaine pattern : Prosite (Expaxy)TM4_1 (PS00421)   
Domains : Interpro (EBI)Tetraspanin    Tetraspanin/Peripherin    Tetraspanin_CS    Tetraspanin_EC2_sf   
Domain families : Pfam (Sanger)Tetraspannin (PF00335)   
Domain families : Pfam (NCBI)pfam00335   
Conserved Domain (NCBI)CD81
DMDM Disease mutations975
Blocks (Seattle)CD81
PDB (RSDB)1G8Q    1IV5    2AVZ    3X0E    5DFV    5DFW    5M2C    5M33    5M3D    5M3T    5M4R    5TCX   
PDB Europe1G8Q    1IV5    2AVZ    3X0E    5DFV    5DFW    5M2C    5M33    5M3D    5M3T    5M4R    5TCX   
PDB (PDBSum)1G8Q    1IV5    2AVZ    3X0E    5DFV    5DFW    5M2C    5M33    5M3D    5M3T    5M4R    5TCX   
PDB (IMB)1G8Q    1IV5    2AVZ    3X0E    5DFV    5DFW    5M2C    5M33    5M3D    5M3T    5M4R    5TCX   
Structural Biology KnowledgeBase1G8Q    1IV5    2AVZ    3X0E    5DFV    5DFW    5M2C    5M33    5M3D    5M3T    5M4R    5TCX   
SCOP (Structural Classification of Proteins)1G8Q    1IV5    2AVZ    3X0E    5DFV    5DFW    5M2C    5M33    5M3D    5M3T    5M4R    5TCX   
CATH (Classification of proteins structures)1G8Q    1IV5    2AVZ    3X0E    5DFV    5DFW    5M2C    5M33    5M3D    5M3T    5M4R    5TCX   
SuperfamilyP60033
Human Protein Atlas [tissue]ENSG00000110651-CD81 [tissue]
Peptide AtlasP60033
HPRD08924
IPIIPI00000190   IPI00555750   IPI00657752   IPI00975882   IPI00980190   IPI00977561   IPI00983214   IPI00979139   IPI00979839   IPI00982190   IPI00981672   IPI00978459   
Protein Interaction databases
DIP (DOE-UCLA)P60033
IntAct (EBI)P60033
FunCoupENSG00000110651
BioGRIDCD81
STRING (EMBL)CD81
ZODIACCD81
Ontologies - Pathways
QuickGOP60033
Ontology : AmiGOactivation of MAPK activity  virus receptor activity  immunological synapse formation  immunological synapse  humoral immune response mediated by circulating immunoglobulin  positive regulation of inflammatory response to antigenic stimulus  integrin binding  protein binding  plasma membrane  plasma membrane  integral component of plasma membrane  integral component of plasma membrane  focal adhesion  protein localization  positive regulation of cell proliferation  myoblast fusion involved in skeletal muscle regeneration  cholesterol binding  membrane  integral component of membrane  basolateral plasma membrane  MHC class II protein complex binding  regulation of complement activation  positive regulation of B cell proliferation  receptor internalization  regulation of protein stability  vesicle  macrophage fusion  CD4-positive, alpha-beta T cell costimulation  MHC class II protein binding  positive regulation of 1-phosphatidylinositol 4-kinase activity  positive regulation of transcription by RNA polymerase II  viral entry into host cell  receptor-mediated virion attachment to host cell  positive regulation of peptidyl-tyrosine phosphorylation  regulation of immune response  positive regulation of B cell receptor signaling pathway  positive regulation of B cell receptor signaling pathway  positive regulation of T cell receptor signaling pathway  protein localization to lysosome  extracellular exosome  extracellular exosome  positive regulation of protein exit from endoplasmic reticulum  cellular response to low-density lipoprotein particle stimulus  protein localization to plasma membrane  protein localization to plasma membrane  osteoclast fusion  tetraspanin-enriched microdomain  positive regulation of receptor clustering  positive regulation of protein catabolic process in the vacuole  regulation of macrophage migration  positive regulation of adaptive immune memory response  transferrin receptor binding  positive regulation of T-helper 2 cell cytokine production  positive regulation of CD4-positive, alpha-beta T cell proliferation  positive regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell  
Ontology : EGO-EBIactivation of MAPK activity  virus receptor activity  immunological synapse formation  immunological synapse  humoral immune response mediated by circulating immunoglobulin  positive regulation of inflammatory response to antigenic stimulus  integrin binding  protein binding  plasma membrane  plasma membrane  integral component of plasma membrane  integral component of plasma membrane  focal adhesion  protein localization  positive regulation of cell proliferation  myoblast fusion involved in skeletal muscle regeneration  cholesterol binding  membrane  integral component of membrane  basolateral plasma membrane  MHC class II protein complex binding  regulation of complement activation  positive regulation of B cell proliferation  receptor internalization  regulation of protein stability  vesicle  macrophage fusion  CD4-positive, alpha-beta T cell costimulation  MHC class II protein binding  positive regulation of 1-phosphatidylinositol 4-kinase activity  positive regulation of transcription by RNA polymerase II  viral entry into host cell  receptor-mediated virion attachment to host cell  positive regulation of peptidyl-tyrosine phosphorylation  regulation of immune response  positive regulation of B cell receptor signaling pathway  positive regulation of B cell receptor signaling pathway  positive regulation of T cell receptor signaling pathway  protein localization to lysosome  extracellular exosome  extracellular exosome  positive regulation of protein exit from endoplasmic reticulum  cellular response to low-density lipoprotein particle stimulus  protein localization to plasma membrane  protein localization to plasma membrane  osteoclast fusion  tetraspanin-enriched microdomain  positive regulation of receptor clustering  positive regulation of protein catabolic process in the vacuole  regulation of macrophage migration  positive regulation of adaptive immune memory response  transferrin receptor binding  positive regulation of T-helper 2 cell cytokine production  positive regulation of CD4-positive, alpha-beta T cell proliferation  positive regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell  
Pathways : KEGGB cell receptor signaling pathway    Malaria    Hepatitis C   
REACTOMEP60033 [protein]
REACTOME PathwaysR-HSA-977606 [pathway]   
NDEx NetworkCD81
Atlas of Cancer Signalling NetworkCD81
Wikipedia pathwaysCD81
Orthology - Evolution
OrthoDB975
GeneTree (enSembl)ENSG00000110651
Phylogenetic Trees/Animal Genes : TreeFamCD81
HOGENOMP60033
Homologs : HomoloGeneCD81
Homology/Alignments : Family Browser (UCSC)CD81
Gene fusions - Rearrangements
Fusion : MitelmanCD81/SURF4 [11p15.5/9q34.2]  
Fusion PortalCD81 11p15.5 SURF4 9q34.2 PRAD
Fusion : FusionGDB23003    6270    6271    6272    6273    6274    6275    6276    6277    6278    6279    6280   
Fusion : Fusion_HubAP2A2--CD81    ARF1--CD81    ARNTL--CD81    CD81--ARMC3    CD81--ATPIF1    CD81--ATXN2L    CD81--AUTS2    CD81--B2M    CD81--C17ORF62    CD81--CYHR1    CD81--DNM1L    CD81--FLNA    CD81--GPC1    CD81--IGH@    CD81--IGHG1   
CD81--KIAA2013    CD81--NDUFV1    CD81--NOTCH1    CD81--PAXBP1    CD81--PRSS2    CD81--SEPT9    CD81--SPAG6    CD81--SUPT16H    CD81--SURF4    CD81--TOB1    CD81--TPTE2P1    CD81--TRA@    CD81--TSSC4    CD81--TYK2    CD81--UBE2E3   
CD81--YKT6    CD81--ZNF664    CD81-AS1--CD81    COL3A1--CD81    COL6A2--CD81    CPSF6--CD81    CST3--CD81    DENND1A--CD81    GALNS--CD81    MYH9--CD81    PAK4--CD81    TPM1--CD81   
Fusion : QuiverCD81
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCD81 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CD81
dbVarCD81
ClinVarCD81
1000_GenomesCD81 
Exome Variant ServerCD81
ExAC (Exome Aggregation Consortium)ENSG00000110651
GNOMAD BrowserENSG00000110651
Varsome BrowserCD81
Genetic variants : HAPMAP975
Genomic Variants (DGV)CD81 [DGVbeta]
DECIPHERCD81 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCD81 
Mutations
ICGC Data PortalCD81 
TCGA Data PortalCD81 
Broad Tumor PortalCD81
OASIS PortalCD81 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCD81  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DCD81
Mutations and Diseases : HGMDCD81
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)**PUBLIC** CCHMC Molecular Genetics Laboratory Mutation Database
BioMutasearch CD81
DgiDB (Drug Gene Interaction Database)CD81
DoCM (Curated mutations)CD81 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CD81 (select a term)
intoGenCD81
NCG5 (London)CD81
Cancer3DCD81(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM186845    613496   
Orphanet3469   
DisGeNETCD81
MedgenCD81
Genetic Testing Registry CD81
NextProtP60033 [Medical]
TSGene975
GENETestsCD81
Target ValidationCD81
Huge Navigator CD81 [HugePedia]
snp3D : Map Gene to Disease975
BioCentury BCIQCD81
ClinGenCD81
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD975
Chemical/Pharm GKB GenePA26240
Clinical trialCD81
Miscellaneous
canSAR (ICR)CD81 (select the gene name)
DataMed IndexCD81
Probes
Litterature
PubMed275 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCD81
EVEXCD81
GoPubMedCD81
iHOPCD81
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Nov 13 21:08:17 CET 2019

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