TSPAN8 (tetraspanin 8)

2009-10-01   Uwe Matthias Galli  

Department of Tumour Cell Biology, University Hospital of Surgery, Heidelberg, Germany

Identity

HGNC
TSPAN8
LOCATION
12q21.1
LOCUSID
7103
ALIAS
CO-029,TM4SF3
FUSION GENES
Show Gene Fusions

DNA/RNA

Atlas Image
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

Atlas Image
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.

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.

Bibliography

Pubmed IDLast YearTitleAuthors
95315641998Association between the rat homologue of CO-029, a metastasis-associated tetraspanin molecule and consumption coagulopathy.Claas C et al
158377312005Colocalization of the tetraspanins, CO-029 and CD151, with integrins in human pancreatic adenocarcinoma: impact on cell motility.Gesierich S et al
145359892003Possible involvement of tetraspanin CO-029 in hematogenous intrahepatic metastasis of liver cancer cells.Kanetaka K et al
175791172007A complex of EpCAM, claudin-7, CD44 variant isoforms, and tetraspanins promotes colorectal cancer progression.Kuhn S et al
164671802006Profiling of the tetraspanin web of human colon cancer cells.Le Naour F et al
23958761990Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens.Szala S et al
183657562008TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression.Zhou Z et al
190789742009Tetraspanins: 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 IDTranscript IDUniprot
ENSG00000127324ENST00000247829P19075
ENSG00000127324ENST00000393330P19075
ENSG00000127324ENST00000546561P19075

Expression (GTEx)

0
50
100
150
200
250
300
350
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Protein levels (Protein atlas)

Not detected
Low
Medium
High
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

References

Pubmed IDYearTitleCitations
384300352024miR-378a-5p represses Barrett's esophagus cells proliferation, migration and invasion through targeting TSPAN8.0
388618382024Overexpression of TSPAN8 in consensus molecular subtype 3 colorectal cancer.0
384300352024miR-378a-5p represses Barrett's esophagus cells proliferation, migration and invasion through targeting TSPAN8.0
388618382024Overexpression of TSPAN8 in consensus molecular subtype 3 colorectal cancer.0
369513012023The Transmembrane Protein TM4SF3 Interacts With AR and AR-V7 and is Recruited to AR Target Genes.3
375352462023TSPAN8 regulates EGFR/AKT pathway to enhance metastasis in gastric cancer.4
369513012023The Transmembrane Protein TM4SF3 Interacts With AR and AR-V7 and is Recruited to AR Target Genes.3
375352462023TSPAN8 regulates EGFR/AKT pathway to enhance metastasis in gastric cancer.4
351976082022EGFR signaling promotes nuclear translocation of plasma membrane protein TSPAN8 to enhance tumor progression via STAT3-mediated transcription.16
359042322022TSPAN8 alleviates high glucose-induced apoptosis and autophagy via targeting mTORC2.2
360845472022Histone demethylase KDM2A suppresses EGF-TSPAN8 pathway to inhibit breast cancer cell migration and invasion in vitro.1
351976082022EGFR signaling promotes nuclear translocation of plasma membrane protein TSPAN8 to enhance tumor progression via STAT3-mediated transcription.16
359042322022TSPAN8 alleviates high glucose-induced apoptosis and autophagy via targeting mTORC2.2
360845472022Histone demethylase KDM2A suppresses EGF-TSPAN8 pathway to inhibit breast cancer cell migration and invasion in vitro.1
336746032021Identification 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/favicon/meetings/favicon/apple-touch-icon.png