CD151 (CD151 molecule (Raph blood group))
2009-07-01 Judith Weidenhofer , Leonie K Ashman AffiliationMedical Biochemistry, School of Biomedical Sciences, Pharmacy, University of Newcastle, NSW, Australia
Identity
HGNC
LOCATION
11p15.5
LOCUSID
ALIAS
GP27,MER2,PETA-3,RAPH,SFA1,TSPAN24
FUSION GENES
DNA/RNA
Note
Information sourced from UCSC Genome Database Mar 2006 Assembly (hg18) RefSeq genes and from analysis of mouse gene organisation (Fitter et al., 1998) and human gene structure (Whittock et al., 2001).
The red bars indicate utr and green bars indicate coding exons. The size of each intron is indicated at the top and each exon below. An alternate transcript may be generated from splicing out exon 2 in the 5utr as indicated with the blue lines.
Description
5884 bp, 9 exons (7 coding).
Transcription
mRNA 1574bp (length may vary for utr alternate splicing).
Pseudogene
None in humans.
Proteins
The red bars indicate transmembrane regions as predicted by TMHMM (Krogh et al., 2001), with the green circles palmitoylation sites (Berditchevski et al., 2002). The blue Y indicates an N-linked glycosylation site (Fitter et al., 1995) and the light blue lines indicate approximate sites of potential di-sulphide bridges (Seigneuret et al., 2001).
Description
Size: 253 aa, 28247 Da with a mature protein size of 32 kDa; pI: pH 7.44.
Post-translational modifications include disulphide bridges and an N-linked glycosylation site in the large extracellular loop and 6 palmitoylation sites.
Post-translational modifications include disulphide bridges and an N-linked glycosylation site in the large extracellular loop and 6 palmitoylation sites.
Expression
Widely expressed, particularly on epithelial cells, endothelial cells, Schwann cells, muscle cells, megakaryocytes and platelets. Tissues typically display expression restricted to these cell types with lung, kidney, spleen, tonsil and cardiac muscle all having high levels. Low expression detected on fibroblasts, erythrocytes and leukocytes (Sincock et al., 1997).
Highly expressed (mRNA) in: heart, uterus, lung, prostate, liver (adult), spleen, placenta, pancreas.
Low/no expression (mRNA) in: foetal liver, brain, testes, ovaries.
Highly expressed (mRNA) in: heart, uterus, lung, prostate, liver (adult), spleen, placenta, pancreas.
Low/no expression (mRNA) in: foetal liver, brain, testes, ovaries.
Localisation
Plasma membrane, endosomes, endothelial cell junctions and hemidesmosomes in basal epithelial cells (Sincock et al., 1999; Sterk et al., 2000).
Function
CD151 is a major component of tetraspanin enriched microdomains, which are platforms for assembly of membrane signalling complexes (Hemler et al., 2005; Charrin et al., 2009). CD151 functions in signal transduction through forming direct complexes with integrins particularly alpha3beta1, alpha6beta1, alpha6beta4 and alphaIIbbeta3, thereby influencing a variety of cell functions including motility and adhesion which are outlined further below. CD151 also affects matrix metalloproteinase activity, with overexpression of CD151 in human melanoma cells resulting in increased expression of MMP9 (Hong et al., 2006). CD151 has been shown to interact with pro-matrix metalloptroteinase 7 in osteoarthritic cartilage and regulate its activity (Fujita et al., 2006). In endothelial cells CD151 associates with the matrix metalloproteinase MT1-MMP and regulates its collagenolytic activity (Yañez-Mó et al., 2008).
Homology
Tetraspanin protein family. This protein family has 33 members in humans and is well conserved throughout vertebrates and also present in invertebrates. Key characteristics include the presence of 4 transmembrane domains with both N- and C-terminals in the cytoplasm, conserved cysteine-containing motifs and disulphide bonds in the large extra cellular loop and charged residues in the transmembrane domains.
Mutations
Note
Only 3 mutations have been identified in humans to date, two (G533A and C511T), are predicted not to significantly alter CD151 function and are not associated with disease (Karamatic Crew et al., 2004; Karamatic Crew et al., 2008).
Germinal
Homozygous 1bp insertion, G383, resulting in a frameshift at Lys127 and a truncated protein at codon 140.
Homozygous G533A substitution resulting in an Arg178His mutation.
Homozygous C511T substitution resulting in an Arg171His mutation.
Homozygous G533A substitution resulting in an Arg178His mutation.
Homozygous C511T substitution resulting in an Arg171His mutation.
Implicated in
Note
In vitro studies
In vitro assays on Cd151-null keratinocytes, showed lack of migration compared to wild-type keratinocytes (Geary et al., 2008). Over-expression and knock-down studies of CD151 in various cell lines generally show that CD151 promotes migration and adhesion, however these finding are influenced by cell type and extracellular matrix components and primarily appear to be modified by the expression of the integrin alpha3beta1 (Berditchevski et al., 2002; Winterwood et al., 2006; Liu et al., 2007; Yang et al., 2008). CD151 is down-regulated by HIF-1alpha in colon cancer cells and is re-expressed upon normal oxygenation. This is proposed to allow detachment from the primary tumour and re-attachment at sites of metastasis (Chien et al., 2008).
In vitro assays on Cd151-null keratinocytes, showed lack of migration compared to wild-type keratinocytes (Geary et al., 2008). Over-expression and knock-down studies of CD151 in various cell lines generally show that CD151 promotes migration and adhesion, however these finding are influenced by cell type and extracellular matrix components and primarily appear to be modified by the expression of the integrin alpha3beta1 (Berditchevski et al., 2002; Winterwood et al., 2006; Liu et al., 2007; Yang et al., 2008). CD151 is down-regulated by HIF-1alpha in colon cancer cells and is re-expressed upon normal oxygenation. This is proposed to allow detachment from the primary tumour and re-attachment at sites of metastasis (Chien et al., 2008).
Oncogenesis
Increased CD151 expression may lead to enhanced tumour progression and metastatic capacity based on enhanced motility, migration and adhesion of CD151 expressing cells. Antibodies to CD151 blocked in vivo metastasis in model systems (Testa et al., 1999; Zijlstra et al., 2008). Xenograft breast cancer models involving silencing of CD151 showed a delay in tumour formation (Yang et al., 2008). CD151 expression is increased in metastasis compared to primary tumour site in colon cancer (Chien et al. 2008).
Entity name
Prostate cancer
Note
Immunohistochemical detection of CD151 in a prostate cancer tissue specimens had greater prognostic value than Gleason grading (Ang et al., 2004).
Prognosis
High CD151 expression was indicative of poor outcome.
Oncogenesis
High CD151 expression indicated poor survival outcome, suggesting a role for CD151 in enhancing tumourigenesis or resistance to treatment. Also refer to In vitro studies.
Entity name
Gingival squamous cell carcinoma
Note
Real-time PCR analysis of CD151 gene expression compared to GAPDH was analysed (Hirano et al., 2009). Assessment of protein expression by immunohistochemistry correlated with gene expression however no statistical analyses were performed on protein expression.
Prognosis
High CD151 expression was indicative of poor outcome.
Oncogenesis
High CD151 expression indicated poor survival outcome, suggesting a role for CD151 in enhancing tumourigenesis or resistance to treatment. Also refer to In vitro studies.
Entity name
Colon cancer
Note
Real-time PCR analysis of CD151 gene expression compared to beta-actin was analysed (Hashida et al., 2003). Assessment of protein expression by immunohistochemistry correlated with gene expression however no statistical analyses were performed on protein expression.
Prognosis
High CD151 expression was indicative of poor outcome.
Oncogenesis
High CD151 expression indicated poor survival outcome, suggesting a role for CD151 in enhancing tumourigenesis or resistance to treatment. Also refer to In vitro studies.
Entity name
Hepatocellular carcinoma
Note
Real-time PCR analysis of CD151 gene expression compared to GAPDH was analysed. Assessment of protein expression by immunohistochemistry and immunoblotting generally correlated with gene expression. CD151 expression was increased in hepatocellular carcinomas compared to normal liver tissues (Ke et al., 2009).
Immunohistochemical analysis of tissue microarrays identified a positive correlation between CD151 expression and aggressive histopathological factors such as vascular invasion and poor tumour differentiation. CD151 expression was also indicative of poor outcome (Ke et al., 2009).
Immunohistochemical analysis of tissue microarrays identified a positive correlation between CD151 expression and aggressive histopathological factors such as vascular invasion and poor tumour differentiation. CD151 expression was also indicative of poor outcome (Ke et al., 2009).
Prognosis
High CD151 expression was indicative of poor outcome.
Oncogenesis
High CD151 expression indicated poor survival outcome, suggesting a role for CD151 in enhancing tumourigenesis or resistance to treatment. Also refer to In vitro studies.
Entity name
Non-small cell lung carcinoma
Note
Real-time PCR analysis of CD151 gene expression compared to beta-actin was analysed (Tokuhara et al., 2001). Assessment of protein expression by immunohistochemistry correlated with gene expression however no statistical analyses were performed on protein expression.
Prognosis
High CD151 expression was indicative of poor outcome.
Oncogenesis
High CD151 expression indicated poor survival outcome, suggesting a role for CD151 in enhancing tumourigenesis or resistance to treatment. Also refer to In vitro studies.
Entity name
Breast cancer
Note
Immunohistochemical analysis of CD151 expression in a cohort of invasive ductal carcinoma identified a significantly higher risk of death from breast cancer in CD151 positive tumours compared to CD151 negative tumours. CD151 expression was also positively associated with the involvement of regional lymph nodes. No associations between CD151 expression and other clinical factors including estrogen receptor status were found (Sadej et al.,2009).
Immunohistochemical analysis of CD151 in breast tissue Microarrays identified positive correlations between CD151 expression and high tumour grade as well as negativity for the estrogen receptor. No other associations were identified between CD151 expression and clinical factors (Yang et al., 2008). Associations between CD151 expression and outcome were not able to be made due to unavailability of data.
Immunohistochemical analysis of CD151 in breast tissue Microarrays identified positive correlations between CD151 expression and high tumour grade as well as negativity for the estrogen receptor. No other associations were identified between CD151 expression and clinical factors (Yang et al., 2008). Associations between CD151 expression and outcome were not able to be made due to unavailability of data.
Prognosis
High CD151 expression was indicative of poor outcome.
Oncogenesis
High CD151 expression indicated poor survival outcome, suggesting a role for CD151 in enhancing tumourigenesis or resistance to treatment. Also refer to In vitro studies.
Entity name
Pancreatic cancer
Note
Immunohistochemical analysis of pancreatic cancer cell lines and pancreatic tumours identified high CD151 expression associated with tumours/cell lines compared to normal tissue. Tumour stroma also expressed CD151 (Geiserich et al., 2005).
Oncogenesis
Refer to In vitro studies.
Entity name
Neovascularisation/Pathologic Angiogenesis
Note
Determined from in vivo studies in Cd151-null mice and in vitro studies of Cd151-null mouse lung endothelial cells (Takeda et al., 2007). Analysis of a rat myocardial ischaemia model also showed that viral delivery of CD151 can promote neovascularisation (Zheng and Liu, 2006).
Disease
Cancer, ischaemia
Oncogenesis
Lack of Cd151 expression resulted in impaired tumour angiogenesis, suggesting that Cd151 may be involved in promoting tumour angiogenesis.
Entity name
Nephropathy
Note
CD151 is expressed normally in the kidney particularly in the glomerular basement membrane (Sincock et al., 1997).
Disease
Nephropathy in humans (Karamatic Crew et al., 2004).
Cd151-null mice develop progressive renal failure on the FVB/N strain but not the C57BL/6 strain (Sachs et al., 2006; Baleato et al., 2008).
Cd151-null mice develop progressive renal failure on the FVB/N strain but not the C57BL/6 strain (Sachs et al., 2006; Baleato et al., 2008).
Prognosis
Loss of CD151 activity leads to chronic renal failure.
Cytogenetics
Homozygous frameshift mutation causing a premature stop codon (codon 140) due to the insertion of 1bp in exon 5 of CD151 (G383).
Hybrid gene
Resultant protein lacks the integrin binding domain and causes null expression of the CD151/MER2 antigen (Karamatic Crew et al., 2004).
Entity name
Pretibial epidermolysis bullosa
Note
The Nephropathy described above is attributed to the same mutation in CD151 and occurs in conjunction with pretibial epidermolysis bullosa and deafness (Karamatic Crew et al., 2004).
Wound repair in wild-type mice is associated with an up-regulation of Cd151 in the migrating epidermis at the wound edge (Cowin et al. 2006).
Wound repair in wild-type mice is associated with an up-regulation of Cd151 in the migrating epidermis at the wound edge (Cowin et al. 2006).
Disease
Pretibial epidermolysis bullosa in humans.
Defective wound repair in Cd151-null mice (Cowin et al. 2006; Geary et al 2008).
Defective wound repair in Cd151-null mice (Cowin et al. 2006; Geary et al 2008).
Cytogenetics
Homozygous frameshift mutation causing a premature stop codon (codon 140) due to the insertion of 1bp in exon 5 of CD151 (G383).
Hybrid gene
Resultant protein lacks the integrin binding domain and causes null expression of the CD151/MER2 antigen.
Entity name
Deafness
Note
This loss of function of CD151 is attributed to the same mutation in CD151 as that described above for nephropathy and pretibial epidermolysis bullosa, with all 3 disorders occurring in the same patients (Karamatic Crew et al., 2004).
Prognosis
Progressive deafness occurring by early adulthood.
Cytogenetics
Homozygous frameshift mutation causing a premature stop codon (codon 140) due to the insertion of 1bp in exon 5 of CD151 (G383).
Hybrid gene
Resultant protein lacks the integrin binding domain and causes null expression of the CD151/MER2 antigen.
Entity name
Hemostasis
Note
As assessed in Cd151-null mice, loss of Cd151 caused increased bleeding time and decreased clotting ability, suggesting endothelial and/or platelet cell functional defects. Cd151-null mice did not show any overt physiological differences unless challenged (Wright et al., 2004). Further in vitro analysis of Cd151-null platelets showed impaired functions relating to aggregation, spreading and clot retraction (Lau et al., 2004).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 15533898 | 2004 | CD151 protein expression predicts the clinical outcome of low-grade primary prostate cancer better than histologic grading: a new prognostic indicator? | Ang J et al |
| 18787104 | 2008 | Deletion of CD151 results in a strain-dependent glomerular disease due to severe alterations of the glomerular basement membrane. | Baleato RM et al |
| 12110679 | 2002 | Expression of the palmitoylation-deficient CD151 weakens the association of alpha 3 beta 1 integrin with the tetraspanin-enriched microdomains and affects integrin-dependent signaling. | Berditchevski F et al |
| 19426143 | 2009 | Lateral organization of membrane proteins: tetraspanins spin their web. | Charrin S et al |
| 19073968 | 2008 | Regulation of CD151 by hypoxia controls cell adhesion and metastasis in colorectal cancer. | Chien CW et al |
| 16410781 | 2006 | Wound healing is defective in mice lacking tetraspanin CD151. | Cowin AJ et al |
| 9602068 | 1998 | Characterisation of the mouse homologue of CD151 (PETA-3/SFA-1); genomic structure, chromosomal localisation and identification of 2 novel splice forms. | Fitter S et al |
| 7632941 | 1995 | Molecular cloning of cDNA encoding a novel platelet-endothelial cell tetra-span antigen, PETA-3. | Fitter S et al |
| 17009258 | 2006 | Tetraspanin CD151 is expressed in osteoarthritic cartilage and is involved in pericellular activation of pro-matrix metalloproteinase 7 in osteoarthritic chondrocytes. | Fujita Y et al |
| 18534576 | 2008 | The role of the tetraspanin CD151 in primary keratinocyte and fibroblast functions: implications for wound healing. | Geary SM et al |
| 15837731 | 2005 | Colocalization of the tetraspanins, CO-029 and CD151, with integrins in human pancreatic adenocarcinoma: impact on cell motility. | Gesierich S et al |
| 12838318 | 2003 | Clinical significance of transmembrane 4 superfamily in colon cancer. | Hashida H et al |
| 16314869 | 2005 | Tetraspanin functions and associated microdomains. | Hemler ME et al |
| 19330835 | 2009 | Tetraspanin gene expression levels as potential biomarkers for malignancy of gingival squamous cell carcinoma. | Hirano C et al |
| 16798740 | 2006 | Homophilic interactions of Tetraspanin CD151 up-regulate motility and matrix metalloproteinase-9 expression of human melanoma cells through adhesion-dependent c-Jun activation signaling pathways. | Hong IK et al |
| 18522704 | 2008 | Two MER2-negative individuals with the same novel CD151 mutation and evidence for clinical significance of anti-MER2. | Karamatic Crew V et al |
| 19065669 | 2009 | Role of overexpression of CD151 and/or c-Met in predicting prognosis of hepatocellular carcinoma. | Ke AW et al |
| 11152613 | 2001 | Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. | Krogh A et al |
| 15226180 | 2004 | The tetraspanin superfamily member CD151 regulates outside-in integrin alphaIIbbeta3 signaling and platelet function. | Lau LM et al |
| 17716972 | 2007 | Tetraspanin CD151 promotes cell migration by regulating integrin trafficking. | Liu L et al |
| 17015618 | 2006 | Kidney failure in mice lacking the tetraspanin CD151. | Sachs N et al |
| 19531562 | 2009 | CD151 regulates tumorigenesis by modulating the communication between tumor cells and endothelium. | Sadej R et al |
| 11483611 | 2001 | Structure of the tetraspanin main extracellular domain. A partially conserved fold with a structurally variable domain insertion. | Seigneuret M et al |
| 10036233 | 1999 | PETA-3/CD151, a member of the transmembrane 4 superfamily, is localised to the plasma membrane and endocytic system of endothelial cells, associates with multiple integrins and modulates cell function. | Sincock PM et al |
| 10811835 | 2000 | The tetraspan molecule CD151, a novel constituent of hemidesmosomes, associates with the integrin alpha6beta4 and may regulate the spatial organization of hemidesmosomes. | Sterk LM et al |
| 17023588 | 2007 | Deletion of tetraspanin Cd151 results in decreased pathologic angiogenesis in vivo and in vitro. | Takeda Y et al |
| 10447000 | 1999 | Eukaryotic expression cloning with an antimetastatic monoclonal antibody identifies a tetraspanin (PETA-3/CD151) as an effector of human tumor cell migration and metastasis. | Testa JE et al |
| 11751509 | 2001 | Clinical significance of CD151 gene expression in non-small cell lung cancer. | Tokuhara T et al |
| 11181065 | 2001 | Genomic organization, amplification, fine mapping, and intragenic polymorphisms of the human hemidesmosomal tetraspanin CD151 gene. | Whittock NV et al |
| 16571677 | 2006 | A critical role for tetraspanin CD151 in alpha3beta1 and alpha6beta4 integrin-dependent tumor cell functions on laminin-5. | Winterwood NE et al |
| 15199151 | 2004 | Characterization of mice lacking the tetraspanin superfamily member CD151. | Wright MD et al |
| 18663148 | 2008 | MT1-MMP collagenolytic activity is regulated through association with tetraspanin CD151 in primary endothelial cells. | Yañez-Mó M et al |
| 18451146 | 2008 | CD151 accelerates breast cancer by regulating alpha 6 integrin function, signaling, and molecular organization. | Yang XH et al |
| 17225869 | 2006 | CD151 gene delivery activates PI3K/Akt pathway and promotes neovascularization after myocardial infarction in rats. | Zheng Z et al |
| 18328426 | 2008 | The inhibition of tumor cell intravasation and subsequent metastasis via regulation of in vivo tumor cell motility by the tetraspanin CD151. | Zijlstra A et al |
Other Information
Locus ID:
NCBI: 977
MIM: 602243
HGNC: 1630
Ensembl: ENSG00000177697
Variants:
dbSNP: 977
ClinVar: 977
TCGA: ENSG00000177697
COSMIC: CD151
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38418926 | 2024 | CD151 expression marks atrial- and ventricular- differentiation from human induced pluripotent stem cells. | 0 |
| 38557119 | 2024 | CD151 Maintains Endolysosomal Protein Quality to Inhibit Vascular Inflammation. | 0 |
| 38418926 | 2024 | CD151 expression marks atrial- and ventricular- differentiation from human induced pluripotent stem cells. | 0 |
| 38557119 | 2024 | CD151 Maintains Endolysosomal Protein Quality to Inhibit Vascular Inflammation. | 0 |
| 36448565 | 2023 | CD151 and prostate cancer progression: A review of current literature. | 3 |
| 37094754 | 2023 | Exploring the role of CD151 in the tumor immune microenvironment: Therapeutic and clinical perspectives. | 1 |
| 36448565 | 2023 | CD151 and prostate cancer progression: A review of current literature. | 3 |
| 37094754 | 2023 | Exploring the role of CD151 in the tumor immune microenvironment: Therapeutic and clinical perspectives. | 1 |
| 33450381 | 2021 | Downregulation of CD151 induces oxidative stress and apoptosis in trophoblast cells via inhibiting ERK/Nrf2 signaling pathway in preeclampsia. | 7 |
| 33767593 | 2021 | CD151 promotes Colorectal Cancer progression by a crosstalk involving CEACAM6, LGR5 and Wnt signaling via TGFβ1. | 7 |
| 34108040 | 2021 | CD151 drives cancer progression depending on integrin α3β1 through EGFR signaling in non-small cell lung cancer. | 17 |
| 34157361 | 2021 | CD151 enrichment in exosomes of luminal androgen receptor breast cancer cell line contributes to cell invasion. | 3 |
| 34265469 | 2021 | Proteomic Landscape of Exosomes Reveals the Functional Contributions of CD151 in Triple-Negative Breast Cancer. | 27 |
| 34368867 | 2021 | circCD151 promotes GLI2 expression by regulating miR‑30d‑5p and enhancing proliferation, invasion and stemness of lung cancer. | 2 |
| 33450381 | 2021 | Downregulation of CD151 induces oxidative stress and apoptosis in trophoblast cells via inhibiting ERK/Nrf2 signaling pathway in preeclampsia. | 7 |
Citation
Judith Weidenhofer ; Leonie K Ashman
CD151 (CD151 molecule (Raph blood group))
Atlas Genet Cytogenet Oncol Haematol. 2009-07-01
Online version: http://atlasgeneticsoncology.org/gene/967/cd151
