TSPAN8 (tetraspanin 8)
2009-10-01 Uwe Matthias Galli AffiliationDepartment of Tumour Cell Biology, University Hospital of Surgery, Heidelberg, Germany
Identity
HGNC
LOCATION
12q21.1
LOCUSID
ALIAS
CO-029,TM4SF3
FUSION GENES
DNA/RNA
The human Tspan8 gene contains 9 exons and 8 introns and was predicted to span over 32,9 kb appoximately of the genomic DNA. Transcript length: 1130 bps, translation length: 237 residues.
Proteins
Tetraspanin 8 has a short amino- and carboxy-terminal tail, a small intracellular loop between transmembrane region 2 (TM2) and TM3, a small extracellular loop (ECL1) between TM1 and TM2 and a large extracellular loop (ECL2) between TM3 and TM4. Extracellular loop 2 contains six conserved cysteine residues (red) including the CCG motif; disulphide bonds are indicated. The transmembrane regions 1 and 4 have polar amino acids (green), the cytoplasmic domains contain palmitoylation sites (pink) and the carboxy-terminal domain contains a sorting motif (blue).
Description
Tspan8 is a member of the transmembrane 4 superfamily, also known as the tetraspanin family.
Expression
Tetraspanin 8 is expressed in squamous epithelial cells (not epidermis), capillary endothelial cells, nerves, smooth and striated muscle cells, and subpopulations of hematopoietic progenitor cells.
Function
Like other tetraspanins, Tspan8 act as a "molecular facilitator" by forming a web in glycolipid-enriched membrane microdomains, called TEM (tetraspanin enriched membrane domains). Tspan8 associates with additional tetraspanins, integrins, preferentially CD49c, CD104, but also CD49d. It is directly associated with EWI-F, CD13 and intersectin 2. Via its associated molecules Tspan8 becomes involved in cell adhesion and motility as well as signal transduction. Motility promotion mostly proceeds via its association with CD104 and is in line with pronounced metastatic spread of Tspan8 overexpressing tumors as described for hepatocellular cancer. Similar to other tetraspanins, Tspan8 is abundantly present in exosomes, where it accounts via its association with CD49d for endothelial cell and endothelial cell progenitor targeting with the consequence of endothelial cell activation and endothelial cell progenitor maturation.
Regulates cell motility and survival and is involved in the promotion of angiogenesis.
Regulates cell motility and survival and is involved in the promotion of angiogenesis.
Mutations
Note
Not known in Homo sapiens.
Implicated in
Entity name
Tumors of the gastrointestinal tract
Note
CO-029 is associated with tumor progression and is supposed to promote metastasis formation. It has been described as a marker of several types of carcinomas and sarcomas. In gastrointestinal tumors the expression of CO-029 has been associated with a poor pognosis.
Disease
Gastric tumors, colorectal tumors, pancreatic tumors and liver tumors.
Entity name
Hepatocellular carcinoma (HCC)
Note
Tetraspanin CO-029 was found to be frequently and significantly overexpressed in HCC. CO-029 was overexpressed in poorly differentiated HCCs compared with well to moderately differentiated tumors, and in HCCs showing intrahepatic spreading compared with those without spreading.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 9531564 | 1998 | Association between the rat homologue of CO-029, a metastasis-associated tetraspanin molecule and consumption coagulopathy. | Claas C 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 |
| 14535989 | 2003 | Possible involvement of tetraspanin CO-029 in hematogenous intrahepatic metastasis of liver cancer cells. | Kanetaka K et al |
| 17579117 | 2007 | A complex of EpCAM, claudin-7, CD44 variant isoforms, and tetraspanins promotes colorectal cancer progression. | Kuhn S et al |
| 16467180 | 2006 | Profiling of the tetraspanin web of human colon cancer cells. | Le Naour F et al |
| 2395876 | 1990 | Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens. | Szala S et al |
| 18365756 | 2008 | TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression. | Zhou Z et al |
| 19078974 | 2009 | Tetraspanins: push and pull in suppressing and promoting metastasis. | Zöller M et al |
Other Information
Locus ID:
NCBI: 7103
MIM: 600769
HGNC: 11855
Ensembl: ENSG00000127324
Variants:
dbSNP: 7103
ClinVar: 7103
TCGA: ENSG00000127324
COSMIC: TSPAN8
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000127324 | ENST00000247829 | P19075 |
| ENSG00000127324 | ENST00000393330 | P19075 |
| ENSG00000127324 | ENST00000546561 | P19075 |
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38430035 | 2024 | miR-378a-5p represses Barrett's esophagus cells proliferation, migration and invasion through targeting TSPAN8. | 0 |
| 38861838 | 2024 | Overexpression of TSPAN8 in consensus molecular subtype 3 colorectal cancer. | 0 |
| 38430035 | 2024 | miR-378a-5p represses Barrett's esophagus cells proliferation, migration and invasion through targeting TSPAN8. | 0 |
| 38861838 | 2024 | Overexpression of TSPAN8 in consensus molecular subtype 3 colorectal cancer. | 0 |
| 36951301 | 2023 | The Transmembrane Protein TM4SF3 Interacts With AR and AR-V7 and is Recruited to AR Target Genes. | 3 |
| 37535246 | 2023 | TSPAN8 regulates EGFR/AKT pathway to enhance metastasis in gastric cancer. | 4 |
| 36951301 | 2023 | The Transmembrane Protein TM4SF3 Interacts With AR and AR-V7 and is Recruited to AR Target Genes. | 3 |
| 37535246 | 2023 | TSPAN8 regulates EGFR/AKT pathway to enhance metastasis in gastric cancer. | 4 |
| 35197608 | 2022 | EGFR signaling promotes nuclear translocation of plasma membrane protein TSPAN8 to enhance tumor progression via STAT3-mediated transcription. | 16 |
| 35904232 | 2022 | TSPAN8 alleviates high glucose-induced apoptosis and autophagy via targeting mTORC2. | 2 |
| 36084547 | 2022 | Histone demethylase KDM2A suppresses EGF-TSPAN8 pathway to inhibit breast cancer cell migration and invasion in vitro. | 1 |
| 35197608 | 2022 | EGFR signaling promotes nuclear translocation of plasma membrane protein TSPAN8 to enhance tumor progression via STAT3-mediated transcription. | 16 |
| 35904232 | 2022 | TSPAN8 alleviates high glucose-induced apoptosis and autophagy via targeting mTORC2. | 2 |
| 36084547 | 2022 | Histone demethylase KDM2A suppresses EGF-TSPAN8 pathway to inhibit breast cancer cell migration and invasion in vitro. | 1 |
| 33674603 | 2021 | Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma. | 33 |
Citation
Uwe Matthias Galli
TSPAN8 (tetraspanin 8)
Atlas Genet Cytogenet Oncol Haematol. 2009-10-01
Online version: http://atlasgeneticsoncology.org/gene/42585/tspan8
