TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
8.A.40.1.1









CD81 (TAPA1, Tspan28) co-receptor of Hepatitis C Virus (HCV); 236 aas; it forms a heterodimer with SR-B1 (TC#9.B.39.1.3). Defects cause CVID6. It plays a role in hepatitis C entry via endocytosis (Farquhar et al., 2011), and also plays roles in immune and other physiological functions (Yeh and Klesius 2009).  Sperm-egg interaction and fusion would not happen in mammals without tetraspanin superfamily members including protein CD81 (Jankovicova et al. 2016). Abnormal levels occur in plasma neuron-derived extracellular vesicles of early schizophrenia and other neurodevelopmental diseases (Goetzl et al. 2022).  Tetraspanin CD81 serves as a functional entry factor for porcine circovirus type 2 infection (Li et al. 2025).

Eukaryota
Metazoa, Chordata
CD81 of Homo sapiens (P60033)
8.A.40.1.2









Tetraspanin-7 (Tspan-7; TALLA1; MXS1; TM4SF2) (Hemler, 2005). Defects in humans result in mental retardation, called x-linked type 58 (MRX58) (Hemler, 2005).  Contains sphingolipid binding motifs (Björkholm et al. 2014).  Tspan-7 is the target of autoantibodies and type I diabetes (McLaughlin et al. 2016). Tspan7 is an islet autoantigen involved in autoimmune type 1 diabetes and regulates beta-cell L-type Ca2+ channel activity (McLaughlin et al. 2022). It thereby regulates Ca2+-dependent exocytosis in beta-cells (McLaughlin et al. 2022).

Eukaryota
Metazoa, Chordata
Tspan-7 of Homo sapiens (P41732)
8.A.40.1.3









Peripherin-2 of 346 aas and 4 TMSs; Rod outer segment membrane protein; RDS; PRDH2. Causes retenal degeneration.  Links rhodopsin (TC# 9.A.14.1.2) to a cyclic nucleotide-dependent channel (TC# 1.A.1.5.3) in the outer segments of rod photoreceptors.  The G266D retinitis pigmentosa mutation in TMS4 of rhodopsin abolishes binding of peripherin-2 and prevents association with the CNGA1/CNGB1a subunits present in the complex (Becirovic et al. 2014).

Eukaryota
Metazoa, Chordata
Peripherin-2 of Homo sapiens (P23942)
8.A.40.1.4









Late bloomer; facilitates synapse and cell junction formation 

Eukaryota
Metazoa, Arthropoda
Late bloomer of Drosophila melanogaster (Q24188)
8.A.40.1.5









CD63 antigen-like tetraspanin.  Involved in trafficking and transport regulation (Pols and Klumperman 2009).

Eukaryota
Metazoa, Platyhelminthes
CD63-like protein of Schistosoma mansoni (G4VD44)
8.A.40.1.6









Tetraspannin, Tsp3A; involved in phagocytosis; engulfment.

Eukaryota
Metazoa, Arthropoda
Tsp3A of Drosophila melanogaster
8.A.40.1.7









 

Tetraspannin, Tsp42Fi

Eukaryota
Metazoa, Arthropoda
Tsp42Fi of Drosophila melanogaster
8.A.40.1.8









Tretraspanin-13.  TSPAN-13 (NET6, TM4F13, UNC260,PRO296) specifically modulates the efficiency of coupling between voltage sensor activation and pore opening of the CaV2.2 α-subunit channel and accelerates the voltage-dependent activation and inactivation of the Ba2+ current through CaV2.2.  TSPAN-13 may regulate CaV2.2 Ca2+ channel activity in defined synaptic membrane compartments and thereby influences transmitter release (Mallmann et al. 2013; Lacinova et al. 2020). The human ortholog is 96% identical to the mouse protein.

Eukaryota
Metazoa, Chordata
Tetraspanin-13 of Mus musculus
8.A.40.1.9









Tetraspanin 29 (TSPAN29; CD9 antigen; GIG2; leucocyte antigen MIC3) of 228 aas and 4 TMSs.  Plays a role in mast cell chemotaxis (Hálová et al. 2013).  Also required for egg-sperm interactions during cell-cell fusion (Sabetian et al. 2014). It is associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (Ikeyama et al. 1993, Higginbottom et al. 2003, Nakazawa et al. 2008). In myoblasts, it associates with CD81 and PTGFRN and inhibits myotube fusion during muscle regeneration. In macrophages, it associates with CD81 and beta-1 and beta-2 integrins, to prevent macrophage fusion into multinucleated giant cells specialized in ingesting complement-opsonized large particles (Takeda et al. 2003).

 

 

Eukaryota
Metazoa, Chordata
Tetraspanin 29 of Homo sapiens
8.A.40.1.10









Tetraspanin 10 (Haining et al., 2012).

Eukaryota
Metazoa, Chordata
Tetraspanin 10 of Homo sapiens
8.A.40.1.11









Tetraspanin 33; penumbra (Haining et al. 2012).

Eukaryota
Metazoa, Chordata
Penumbra of Homo sapiens
8.A.40.1.12









Catfish CD63 antigen tetraspanin of 237 aas (Yeh and Klesius 2010).  Involved in trafficking and transport regulation (Pols and Klumperman 2009).

Eukaryota
Metazoa, Chordata
CD63 of Ictalurus punctatus (Channel catfish) (Silurus punctatus)
8.A.40.1.13









Uncharacterized protein of 221 aas and 4 TMSs.

Eukaryota
Metazoa, Arthropoda
UP of Danaus plexippus
8.A.40.1.14









Uncharacterized protein of 219 aas and 4 TMSs.

Eukaryota
Rhodophyta
UP of Galdieria sulphuraria
8.A.40.1.15









The tetraspan 24 protein, TSPAN24 or CD151 of 254 aas and 4 TMSs in a 3 + 1 TM arrangement.  It is essential for the proper assembly of the glomerular and tubular basement membranes in kidney, and also functions in egg-sperm interactions, possibly in cell-cell fusion, where oocyte CD151 interacts with CD49 in the sperm (Sabetian et al. 2014).

Eukaryota
Metazoa, Chordata
CD151 of Homo sapiens
8.A.40.1.16









Tetraspanin-3 (TSPAN3) of 253 aas and 4 TMSs in a 3+ 1 arrangement.  Plays a role in myeloid leukemia and other cancers (Yang et al. 2016).

Eukaryota
Metazoa, Chordata
TSPAN3 of Homo sapiens
8.A.40.1.17









Tetraspannin 15, TSPAN15 of 294 aas and 4 TMSs.  Interacts with and regulates the targetting and activity of the sheddase, ADAM10 (TC# 8.A.77) (Prox et al. 2012).

Eukaryota
Metazoa, Chordata
TSPAN15 of Homo sapiens
8.A.40.1.18









Human Leukocyte surface antigen CD53 of 219 aas and 4 TMSs (Halova and Draber 2016). CD53 mediates dyslipidemia and integrates inflammatory and metabolic signaling in hepatocytes (Higgins et al. 2022).

Eukaryota
Metazoa, Chordata
CD53 of Homo sapiens
8.A.40.1.19









Antigen CD63 of 238 aas and 4 TMSs.  It functions as cell surface receptor, and plays a role in the activation of cellular signaling cascades.  It also plays a role in intracellular and extracellular vesicular transport processes, and is required for normal trafficking that is essential for the development and maturation of melanocytes (van Niel et al. 2011; Lee et al. 2014). CD63 is on natural exosomes (cell derived extracellular vesicles), and it is highly enriched on the external surfaces of these membranes (Curley et al. 2020). Distinct scaffolds based on engineering of CD63 enable flexible engineering of the exosome surface for applications in disease-targeted drug delivery and therapy. CD63 proximal interacting proteins comprise the network of partners required for endocytic trafficking and extracellular vesicle cargo sorting, formation, and secretion (Cheerathodi et al. 2021). Climbazole and heparin undermine membrane-bound tetraspanin CD63 expression, significantly disrupted ALIX protein, and alter human carcinoma lung cell-derived extracellular vesicle formation (Ipinmoroti et al. 2023). CD63 also participates in extracellular vesicle loading and delivery (Bui et al. 2023); see also TC Family 1.F.4.

 

Eukaryota
Metazoa, Chordata
CD63 of Homo sapiens
8.A.40.1.20









Tetraspanin-12, Tspan12, of 305 aas and 4 TMSs.  Regulator of cell surface receptor signal transduction. Plays a central role in retinal vascularization by regulating norrin (NDP) signal transduction. Acts in concert with norrin (NDP) to promote FZD4 multimerization and subsequent activation of FZD4, leading to accumulation of beta-catenin (CTNNB1) and stimulation of LEF/TCF-mediated transcriptional programs (Lafleur et al. 2009). It activates ADAM10-dependent cleavage activity of amyloid precursor protein (APP) (Xu et al. 2009).  The biology of tetraspanins and how they interact with APP processing pathways have been reviewed (Seipold and Saftig 2016).

Eukaryota
Metazoa, Chordata
Tspan12 of Homo sapiens
8.A.40.1.21









Tetraspanin14 (Tspan14) of 270 aas and 4 TMSs. Interacts with disintegrin and metalloprotease 10 (ADAM10), a ubiquitously expressed transmembranemetalloprotease that cleaves the extracellular regions from its transmembrane substrates (Noy et al. 2016). ADAM10 is essential for embryonic development and is implicated in cancer, Alzheimer's disease, and inflammatory diseases. The tetraspanins are a superfamily of 33 four-transmembrane proteins in mammals, of which the TspanC8 subgroup (Tspan5, 10, 14, 15, 17, and 33) promote ADAM10 intracellular trafficking and enzymatic maturation (Jouannet et al. 2016).

Eukaryota
Metazoa, Chordata
TspanC8 of Homo sapiens
8.A.40.1.22









Tetraspan-9, Tspan9, of 239 aas and 4 TMSs.  Plays a role in aggregation and secretion induced by the platelet collagen receptor, GPVI, despite normal surface GPVI expression levels. This is because Tspan9 plays a role in platelet activation by regulating GPVI membrane dynamics (Haining et al. 2017).

Eukaryota
Metazoa, Chordata
Tspan9 of Homo sapiens
8.A.40.1.23









Tetraspannin, Tspan18 of 248 aas and 4 TMSs in a 3 + 1 arrangement.  It is a regulator of Orai1, a store-operated Ca2+ channels in the plasma membrane which is critical to cell function. Orai1 loss causes severe immunodeficiency and developmental defects (Noy et al. 2018).

Eukaryota
Metazoa, Chordata
Tspan18 of Homo sapiens
8.A.40.1.24









Uncharacterized protein of 258 aas and 4 TMSs

Eukaryota
Metazoa, Mollusca
UP of Stentor coeruleus
8.A.40.2.1









Tetraspanin

Eukaryota
Fungi, Ascomycota
Tetraspanin of Neurospora crassa (Q8J0D3)
8.A.40.2.2









Tetraspanin 

Eukaryota
Fungi, Basidiomycota
Tetraspanin of Melampsora laricipopulina (F4S576)
8.A.40.2.3









Similar to tetraspanin

Eukaryota
Fungi, Ascomycota
Tetraspanin homologue of Leptosphaeria maculans
8.A.40.3.1









Tetraspanin family protein of 390 aas and 4 TMSs in a 3 + 1 TMS arrangemet.

Eukaryota
Ciliophora
Tetraspanin of Tetrahymena thermophila
8.A.40.3.2









Uncharacterized protein of 318 aas and 4 TMSs in a 3 + 1 TMS arrangement.

Eukaryota
Ciliophora
UP of Pseudocohnilembus persalinus
8.A.40.3.3









Uncharacterized protein of 316 aas and 4 TMSs in a 3 + 1 TMS arrangement.

Eukaryota
Ciliophora
UP of Stentor coeruleus
8.A.40.3.4









Uncharacterized protein showing sequence similarity with CD9, CD81, CD82 and CD151 of 332 aas and 4 TMSs in a 3 + 1 TMS arrangement.

Eukaryota
Ciliophora
UP of Stylonychia lemnae
8.A.40.3.5









Uncharacterized protein of 396 aas and 4 TMSs in a 3 + 1 TMS arrangement.

Eukaryota
Ciliophora
UP of Halteria grandinella
8.A.40.4.1









Putative senescence-associated protein of 285 aas and 4 TMSs in a 3 + 1 TMS arrangement.

Eukaryota
Viridiplantae, Streptophyta
Putative senescence-associated protein of Oryza sativa
8.A.40.4.2









Tetraspanin-10 of 284 aas and 4 TMSs (Boavida et al. 2013).

Eukaryota
Viridiplantae, Streptophyta
Tetraspanin-18 of Arabidopsis thaliana
8.A.40.4.3









Tetraspanin-16 of 248 aas and 4 TMSs (Boavida et al. 2013).

Eukaryota
Viridiplantae, Streptophyta
Tetraspanin-16 of Arabidopsis thaliana
8.A.40.4.4









Tetraspanin-8-like protein of 270 aas and 4 putative TMSs. TETRASPANIN 8-1 from Phaseolus vulgaris plays a key role during mutualistic interactions (Parra-Aguilar et al. 2023).

Eukaryota
Viridiplantae, Streptophyta
4 TMS protein of Camellia sinensis
8.A.40.5.1









Tetraspanin-20 of 281 aas and 4 TMSs (Boavida et al. 2013).

Eukaryota
Viridiplantae, Streptophyta
Tetraspanin-20 of Arabidopsis thaliana
8.A.40.5.2









Tetraspanin 18 of 270 aas and 4 TMSs (Boavida et al. 2013).

Eukaryota
Viridiplantae, Streptophyta
Tetraspanin-18 of Arabidopsis thaliana
8.A.40.6.1









Tetraspanin-14 of 260 aas and 4 TMSs (Boavida et al. 2013).

Eukaryota
Viridiplantae, Streptophyta
Tetraspanin-14 of Arabidopsis thaliana
8.A.40.6.2









Tetraspanin-15 of 317 aas and 4 TMSs (Boavida et al. 2013).

Eukaryota
Viridiplantae, Streptophyta
Tetraspanin-15 of Arabidopsis thaliana
8.A.40.7.1









Uroplakin 1a (UPK1A or TSPAN21) of 258 aas and 4 TMSs in a 3 + 1 arrangement.  Component of the asymmetric unit membrane (AUM), a highly specialized biomembrane elaborated by terminally differentiated urothelial cells. May play a role in normal bladder epithelial physiology, possibly in regulating membrane permeability of superficial umbrella cells (Chicote et al. 2017).

Eukaryota
Metazoa, Chordata
UPK1A of Homo sapiens
8.A.40.7.2









Uroplakin 1b, UPK1B of 260 aas and 4 TMSs in a 3 + 1 arrangement.  Like UPK1A, it may be a component of the asymmetric unit membrane (AUM), a highly specialized biomembrane elaborated by terminally differentiated urothelial cells. May play an important role in normal bladder epithelial physiology, possibly in regulating membrane permeability of superficial umbrella cells (Chicote et al. 2017). Proper formation of helical bundles consisting of the 4 tetraspanin TMSs seems to be a prerequisite for UPIb to exit from the ER into the plasma membrane (Tu et al. 2006).

Eukaryota
Metazoa, Chordata
UKB1B of Homo sapiens