Alternative titles; symbols
HGNC Approved Gene Symbol: CD151
Cytogenetic location: 11p15.5 Genomic coordinates (GRCh38): 11:832,952-838,831 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 11p15.5 | [Blood group, Raph] | 179620 | 3 | |
| Epidermolysis bullosa simplex 7, with nephropathy and deafness | 609057 | Autosomal recessive | 3 |
Transmembrane 4 (4TM) superfamily proteins are membrane proteins with 4 conserved transmembrane domains. Fitter et al. (1995) showed that the platelet surface glycoprotein gp27 identified by Ashman et al. (1991) is a member of this group. Fitter et al. (1995) cloned the gp27 gene, designated PETA3 by them, by sequencing purified protein and using the resulting probes in RT-PCR to obtain a cDNA from megakaryoblastic cells. Fitter et al. (1995) assigned this 253-amino acid protein to the 4TM group because it has 4 predicted hydrophobic regions and 30% homology to other members of the group. Northern blot analysis showed that PETA3 is expressed in most tissues, but not in brain. Hasegawa et al. (1996) cloned the same gene, which they named SFA1, during a screen for genes induced by HTLV-1 transformation in T cells. The 62-bp difference between the 5-prime untranslated regions of the PETA3 and SFA1 cDNAs was ascribed to alternative splicing in an erratum to Hasegawa et al. (1996).
Bill et al. (1987) cloned the MER2 (179620) gene using a strategy that involved cotransfection of resistance to an antibiotic.
Hemidesmosomes are specialized junctional complexes that function as cell-attachment sites for binding to basement membranes. They appear as electron-dense structures, resembling half a desmosome. Alpha-6 (ITGA6; 147556)/beta-4 (ITGB4; 147557) integrin is a major component of hemidesmosomes. In addition to ITGA6/ITGB4, classic type I hemidesmosomes contain BP180 (COL17A1; 113811) and BP230 (BPAG1; 113810), while type II hemidesmosomes, which are found in cylindrical epithelia, contain plectin (601282). Using immunohistochemistry and immunoelectron microscopy, Sterk et al. (2000) identified CD151, but not the tetraspanins CD9 (143030) or CD81 (186845), codistributed with ITGA6/ITGB4 in hemidesmosomes but not desmosomes at the basolateral surfaces of basal keratinocytes. Immunoprecipitation and immunoblot analysis showed that CD151 associates with ITGA6/ITGB4 and with ITGA3 (605025)/ITGB1 (135630), but not with ITGA5 (135620)/ITGB1. In pyloric atresia-junctional epidermolysis bullosa (PA-JEB; see 226730) cells lacking ITGB4 (thus lacking hemidesmosomes), CD151 colocalized with ITGA3/ITGB1. Expression of ITGB4 in PA-JEB cells induced surface expression of ITGA6/ITGB4 in hemidesmosomes together with CD151 and the apparent replacement of ITGA3/ITGB1. Fluorescent microscopy showed that CD151 is a component of both type I and type II hemidesmosomes. The authors demonstrated that recruitment of CD151 requires the heterodimerization of ITGB4 with ITGA6, with which CD151 is associated.
The 4-transmembrane domain superfamily (the tetraspanins) are integral cell membrane proteins comprising at least 28 members in mammals. Tetraspanins are widely distributed on animal cells, and several are known to be expressed on human hematopoietic cells, including CD151. Tetraspanin CD151 forms very stable laminin-binding complexes with integrins alpha-3-beta-1 (605025; 135630) and alpha-6-beta-1 (147556; 135630) in kidney and alpha-3-beta-1 and alpha-6-beta-4 (147558; 147557) in skin. Karamatic Crew et al. (2004) demonstrated that CD151 expresses the MER2 blood group antigen and is located on erythrocytes.
CD151 is highly expressed in megakaryocytes and, to a lesser extent, in platelets. Using Cd151-deficient mice, Lau et al. (2004) provided the first direct evidence that CD151 is essential for normal platelet function and that disruption of CD151 induces a moderate outside-in integrin alpha-IIb-beta-3 (see 607759, 173470) signaling defect.
Using immunoprecipitation analysis, Sharma et al. (2008) showed that ZDHHC2 (618621) expression specifically and selectively promoted palmitoylation of the tetraspanins CD9 and CD151 and thereby enhanced CD9-CD151 association. Knockdown of ZDHHC2 in HEK293 cells resulted in loss of CD9 and CD151 palmitoylation, enhanced lysosomal proteolysis and degradation and CD9 and CD151, and cell dispersion.
By PCR and genomic sequence analyses, Whittock and McLean (2001) determined that the CD151 gene contains 8 exons spanning 4.3 kb, with exons 2 to 8 encoding the CD151 protein. They also described a PCR-based mutation-detection strategy to facilitate identification of pathogenic mutations in patients with fragile skin and mucous membranes.
Karamatic Crew et al. (2004) studied the CD151 gene in 3 patients (EBS7; 609057) who were negative for the blood group antigen MER2 (179620), which is expressed by the CD151 tetraspanin. The patients were of Indian Jewish origin and had end-stage kidney disease. In addition to hereditary nephritis, the sibs had sensorineural deafness, pretibial epidermolysis bullosa, and beta-thalassemia minor. All 3 patients were homozygous for a single-nucleotide insertion in exon 5 of CD151, causing a frameshift and premature stop signal at codon 140 (602243.0001). The resultant truncated protein would lack its integrin-binding domain. Karamatic Crew et al. (2004) concluded that CD151 is essential for the proper assembly of the glomerular and tubular basement membrane in kidney, has functional significance in the skin, is probably a component of the inner ear, and could play a role in erythropoiesis, as suggested by the presence of beta-thalassemia minor.
Hasegawa et al. (1997) mapped the PETA3 gene to 11p15.5 by fluorescence in situ hybridization. Whittock and McLean (2001) confirmed that the CD151 gene maps to 11p15.5 by radiation hybrid analysis.
Daniels et al. (1987) assigned the MER2 locus to 11p15 by study of somatic cell hybrids.
Wright et al. (2004) generated mice with a homozygous deletion of all 6 coding exons of the Cd151 gene. The Cd151 -/- mice were viable, fertile, and healthy, with normal blood and marrow cell counts and normal tissue morphology and integrin expression in skin. However, the mice had a minor abnormality in hemostasis, with longer bleeding times, greater blood loss, and increased incidence of spontaneous tail vein rebleeding. Cd151 -/- keratinocytes migrated poorly in skin explant cultures, and mutant lymphocytes were hyperproliferative after mitogen stimulation in vitro. Wright et al. (2004) noted that other tetraspanin deletion mutants produce mild phenotypes and suggested that this may be due to complementation by other tetraspanins or that these proteins function as modifiers rather than as essential components of the molecular complexes in which they participate.
In 3 MER2-negative patients of Indian Jewish origin with epidermolysis bullosa simplex and end-stage kidney disease (EBS7; 609057), Karamatic Crew et al. (2004) found homozygosity for a single-nucleotide insertion (383_384insG) in exon 5 of the CD151 gene, causing a frameshift and premature stop signal in codon 140. The resultant truncated protein would lack its integrin-binding domain. The findings suggested that CD151 is essential for the proper assembly of the glomerular and tubular basement membrane in kidney, as well as having functional significance in skin and probably the inner ear.
Ashman, L. K., Aylett, G. W., Mehrabani, P. A., Bendall, L. J., Niutta, S., Cambareri, A. C., Cole, S. R., Berndt, M. C. The murine monoclonal antibody, 14A2.H1, identifies a novel platelet surface antigen. Brit. J. Haemat. 79: 263-270, 1991. [PubMed: 1958484] [Full Text: https://doi.org/10.1111/j.1365-2141.1991.tb04531.x]
Bill, J., Palmer, E., Jones, C. Molecular cloning of MER-2, a human chromosome-11-encoded red blood cell antigen, using linkage of cotransfected markers. Somat. Cell Molec. Genet. 13: 553-561, 1987. [PubMed: 2821633] [Full Text: https://doi.org/10.1007/BF01534496]
Daniels, G. L., Tippett, P., Palmer, D. K., Miller, Y. E., Geyer, D., Jones, C. MER2: a red cell polymorphism defined by monoclonal antibodies. Vox Sang. 52: 107-110, 1987. [PubMed: 3604155] [Full Text: https://doi.org/10.1111/j.1423-0410.1987.tb03002.x]
Fitter, S., Tetaz, T. J., Berndt, M. C., Ashman, L. K. Molecular cloning of cDNA encoding a novel platelet-endothelial cell tetra-span antigen, PETA-3. Blood 86: 1348-1355, 1995. [PubMed: 7632941]
Hasegawa, H., Kishimoto, K., Yanagisawa, K., Terasaki, H., Shimadzu, M., Fujita, S. Assignment of SFA-1 (PETA-3), a member of the transmembrane 4 superfamily, to human chromosome 11p15.5 by fluorescence in situ hybridization. Genomics 40: 193-196, 1997. [PubMed: 9070943] [Full Text: https://doi.org/10.1006/geno.1996.4563]
Hasegawa, H., Utsunomiya, Y., Kishimoto, K., Yanagisawa, K., Fujita, S. SFA-1, a novel cellular gene induced by human T-cell leukemia virus type 1, is a member of the transmembrane 4 superfamily. J. Virol. 70: 3258-3263, 1996. Note: Erratum: J. Virol. 71: 1737, 1997. [PubMed: 8627808] [Full Text: https://doi.org/10.1128/JVI.70.5.3258-3263.1996]
Karamatic Crew, V., Burton, N., Kagan, A., Green, C. A., Levene, C., Flinter, F., Brady, R. L., Daniels, G., Anstee, D. J. CD151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin. Blood 104: 2217-2223, 2004. [PubMed: 15265795] [Full Text: https://doi.org/10.1182/blood-2004-04-1512]
Lau, L.-M., Wee, J. L., Wright, M. D., Moseley, G. W., Hogarth, P. M., Ashman, L. K., Jackson, D. E. The tetraspanin superfamily member CD151 regulates outside-in integrin alpha(IIb)-beta(3) signaling and platelet function. Blood 104: 2368-2375, 2004. Note: Erratum: Blood 105: 1395 only, 2005. [PubMed: 15226180] [Full Text: https://doi.org/10.1182/blood-2003-12-4430]
Sharma, C., Yang, X. H., Hemler, M. E. DHHC2 affects palmitoylation, stability, and functions of tetraspanins CD9 and CD151. Molec. Biol. Cell 19: 3415-3425, 2008. [PubMed: 18508921] [Full Text: https://doi.org/10.1091/mbc.e07-11-1164]
Sterk, L. M. Th., Geuijen, C. A. W., Oomen, L. C. J. M., Calafat, J., Janssen, H., Sonnenberg, A. The tetraspan molecule CD151, a novel constituent of hemidesmosomes, associates with the integrin alpha-6/beta-4 and may regulate the spatial organization of hemidesmosomes. J. Cell Biol. 149: 969-982, 2000. [PubMed: 10811835] [Full Text: https://doi.org/10.1083/jcb.149.4.969]
Whittock, N. V., McLean, W. H. I. Genomic organization, amplification, fine mapping, and intragenic polymorphisms of the human hemidesmosomal tetraspanin CD151 gene. Biochem. Biophys. Res. Commun. 281: 425-430, 2001. [PubMed: 11181065] [Full Text: https://doi.org/10.1006/bbrc.2001.4384]
Wright, M. D., Geary, S. M., Fitter, S., Moseley, G. W., Lau, L.-M., Sheng, K.-C., Apostolopoulos, V., Stanley, E. G., Jackson, D. E., Ashman, L. K. Characterization of mice lacking the tetraspanin superfamily member CD151. Molec. Cell. Biol. 24: 5978-5988, 2004. [PubMed: 15199151] [Full Text: https://doi.org/10.1128/MCB.24.13.5978-5988.2004]