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TSPAN8 (tetraspanin 8)

Written2009-10Uwe Matthias Galli
Department of Tumour Cell Biology, University Hospital of Surgery, Heidelberg, Germany

(Note : for Links provided by Atlas : click)


Alias (NCBI)CO-029
HGNC Alias symbCO-029
HGNC Previous nameTM4SF3
HGNC Previous nametransmembrane 4 superfamily member 3
LocusID (NCBI) 7103
Atlas_Id 42585
Location 12q21.1  [Link to chromosome band 12q21]
Location_base_pair Starts at 71125096 and ends at 71157999 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping TSPAN8.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CNTN1 (12q12)::TSPAN8 (12q21.1)FRS2 (12q15)::TSPAN8 (12q21.1)KIF21A (12q12)::TSPAN8 (12q21.1)
OSBPL8 (12q21.2)::TSPAN8 (12q21.1)SPATS2 (12q13.12)::TSPAN8 (12q21.1)TMEM19 (12q21.1)::TSPAN8 (12q21.1)
TSPAN8 (12q21.1)::HDAC9 (7p21.1)TSPAN8 (12q21.1)::TSPAN8 (12q21.1)WNT11 (11q13.5)::TSPAN8 (12q21.1)


  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.


  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.


Note Not known in Homo sapiens.

Implicated in

Entity 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 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.


Association between the rat homologue of CO-029, a metastasis-associated tetraspanin molecule and consumption coagulopathy.
Claas C, Seiter S, Claas A, Savelyeva L, Schwab M, Zoller M.
J Cell Biol. 1998 Apr 6;141(1):267-80.
PMID 9531564
Colocalization of the tetraspanins, CO-029 and CD151, with integrins in human pancreatic adenocarcinoma: impact on cell motility.
Gesierich S, Paret C, Hildebrand D, Weitz J, Zgraggen K, Schmitz-Winnenthal FH, Horejsi V, Yoshie O, Herlyn D, Ashman LK, Zoller M.
Clin Cancer Res. 2005 Apr 15;11(8):2840-52.
PMID 15837731
Possible involvement of tetraspanin CO-029 in hematogenous intrahepatic metastasis of liver cancer cells.
Kanetaka K, Sakamoto M, Yamamoto Y, Takamura M, Kanematsu T, Hirohashi S.
J Gastroenterol Hepatol. 2003 Nov;18(11):1309-14.
PMID 14535989
A complex of EpCAM, claudin-7, CD4 variant isoforms, and tetraspanins promotes colorectal cancer progression.
Kuhn S, Koch M, Nubel T, Ladwein M, Antolovic D, Klingbeil P, Hildebrand D, Moldenhauer G, Langbein L, Franke WW, Weitz J, Zoller M.
Mol Cancer Res. 2007 Jun;5(6):553-67.
PMID 17579117
Profiling of the tetraspanin web of human colon cancer cells.
Le Naour F, Andre M, Greco C, Billard M, Sordat B, Emile JF, Lanza F, Boucheix C, Rubinstein E.
Mol Cell Proteomics. 2006 May;5(5):845-57. Epub 2006 Feb 7.
PMID 16467180
Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens.
Szala S, Kasai Y, Steplewski Z, Rodeck U, Koprowski H, Linnenbach AJ.
Proc Natl Acad Sci U S A. 1990 Sep;87(17):6833-7.
PMID 2395876
TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression.
Zhou Z, Ran YL, Hu H, Pan J, Li ZF, Chen LZ, Sun LC, Peng L, Zhao XL, Yu L, Sun LX, Yang ZH.
Clin Exp Metastasis. 2008;25(5):537-48. Epub 2008 Mar 26.
PMID 18365756
A Tetraspanins: push and pull in suppressing and promoting metastasis.
Zoller M.
Nat Rev Cancer. 2009 Jan;9(1):40-55. Epub 2008 Dec 11. (REVIEW)
PMID 19078974


This paper should be referenced as such :
Galli, UM
TSPAN8 (tetraspanin 8)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(8):788-789.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)TSPAN8   11855
Entrez_Gene (NCBI)TSPAN8    tetraspanin 8
AliasesCO-029; TM4SF3
GeneCards (Weizmann)TSPAN8
Ensembl hg19 (Hinxton)ENSG00000127324 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000127324 [Gene_View]  ENSG00000127324 [Sequence]  chr12:71125096-71157999 [Contig_View]  TSPAN8 [Vega]
ICGC DataPortalENSG00000127324
Genatlas (Paris)TSPAN8
SOURCE (Princeton)TSPAN8
Genetics Home Reference (NIH)TSPAN8
Genomic and cartography
GoldenPath hg38 (UCSC)TSPAN8  -     chr12:71125096-71157999 -  12q21.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)TSPAN8  -     12q21.1   [Description]    (hg19-Feb_2009)
GoldenPathTSPAN8 - 12q21.1 [CytoView hg19]  TSPAN8 - 12q21.1 [CytoView hg38]
Genome Data Viewer NCBITSPAN8 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AK223022 AK313112 BC005246 BC070168 M35252
RefSeq transcript (Entrez)NM_001369760 NM_004616
Consensus coding sequences : CCDS (NCBI)TSPAN8
Gene ExpressionTSPAN8 [ NCBI-GEO ]   TSPAN8 [ EBI - ARRAY_EXPRESS ]   TSPAN8 [ SEEK ]   TSPAN8 [ MEM ]
Gene Expression Viewer (FireBrowse)TSPAN8 [ Firebrowse - Broad ]
GenevisibleExpression of TSPAN8 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7103
GTEX Portal (Tissue expression)TSPAN8
Human Protein AtlasENSG00000127324-TSPAN8 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP19075   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP19075  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP19075
Domaine pattern : Prosite (Expaxy)TM4_1 (PS00421)   
Domains : Interpro (EBI)Tetraspanin    Tetraspanin/Peripherin    Tetraspanin_CS    Tetraspanin_EC2_sf   
Domain families : Pfam (Sanger)Tetraspanin (PF00335)   
Domain families : Pfam (NCBI)pfam00335   
Conserved Domain (NCBI)TSPAN8
AlphaFold pdb e-kbP19075   
Human Protein Atlas [tissue]ENSG00000127324-TSPAN8 [tissue]
Protein Interaction databases
IntAct (EBI)P19075
Ontologies - Pathways
Ontology : AmiGOintegrin binding  protein binding  integral component of plasma membrane  spermatogenesis  cell surface  regulation of gene expression  negative regulation of blood coagulation  extracellular exosome  
Ontology : EGO-EBIintegrin binding  protein binding  integral component of plasma membrane  spermatogenesis  cell surface  regulation of gene expression  negative regulation of blood coagulation  extracellular exosome  
NDEx NetworkTSPAN8
Atlas of Cancer Signalling NetworkTSPAN8
Wikipedia pathwaysTSPAN8
Orthology - Evolution
GeneTree (enSembl)ENSG00000127324
Phylogenetic Trees/Animal Genes : TreeFamTSPAN8
Homologs : HomoloGeneTSPAN8
Homology/Alignments : Family Browser (UCSC)TSPAN8
Gene fusions - Rearrangements
Fusion : MitelmanCNTN1::TSPAN8 [12q12/12q21.1]  
Fusion : MitelmanFRS2::TSPAN8 [12q15/12q21.1]  
Fusion : MitelmanKIF21A::TSPAN8 [12q12/12q21.1]  
Fusion : MitelmanOSBPL8::TSPAN8 [12q21.2/12q21.1]  
Fusion : MitelmanTMEM19::TSPAN8 [12q21.1/12q21.1]  
Fusion : MitelmanWNT11::TSPAN8 [11q13.5/12q21.1]  
Fusion : QuiverTSPAN8
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTSPAN8 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TSPAN8
Exome Variant ServerTSPAN8
GNOMAD BrowserENSG00000127324
Varsome BrowserTSPAN8
ACMGTSPAN8 variants
Genomic Variants (DGV)TSPAN8 [DGVbeta]
DECIPHERTSPAN8 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTSPAN8 
ICGC Data PortalTSPAN8 
TCGA Data PortalTSPAN8 
Broad Tumor PortalTSPAN8
OASIS PortalTSPAN8 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTSPAN8  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DTSPAN8
Mutations and Diseases : HGMDTSPAN8
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)TSPAN8
DoCM (Curated mutations)TSPAN8
CIViC (Clinical Interpretations of Variants in Cancer)TSPAN8
NCG (London)TSPAN8
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry TSPAN8
NextProtP19075 [Medical]
Target ValidationTSPAN8
Huge Navigator TSPAN8 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDTSPAN8
Pharm GKB GenePA36556
Clinical trialTSPAN8
DataMed IndexTSPAN8
PubMed76 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:30:15 CEST 2021

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