TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*1.H.1.1.1









Claudin 16 (CLDN16; Paracellin) (defects in CLDN16 are the cause of familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) (primary hypomagnesemia) (Hou et al., 2007; Ikari et al., 2008).  Forms a Mg2+/Ca2+-selective pore together with Claudin-3 and Claudin-19 (Brandao et al. 2012; Milatz et al. 2017).  The tight junction archetecture and constituent proteins have been reviewed (Van Itallie and Anderson 2014). Claudin-16 and -19 form a stable dimer through cis-association of transmembrane domains 3 and 4, and mutations disrupting the claudin-16/19 cis-interaction increase tight junction ultrastructural complexity but reduce tight junction permeability (Gong et al. 2015).

Eukaryota
Metazoa
Cldn 16 of Homo sapiens
(Q9Y5I7)
*1.H.1.1.2









Claudin 7 (anion selective; Angelow et al., 2008).  25% identity with Cldn 16; down regulated in breast cancer. 

Eukaryota
Metazoa
Cldn 7 of Homo sapiens
(O95471)
*1.H.1.1.3









Claudin 22 (function unknown; distantly related to most claudins)
Eukaryota
Metazoa
Cldn 22 of Homo sapiens
(Q8N7P3)
*1.H.1.1.4









Claudin 23 (function unknown; distantly related to most claudins including Cldn 22). Related to cancer invasion/metastasis; it may regulate these phenomena through activation of the MEK signalling pathway in pancreatic cancer (Wang et al., 2010). Shows reduced levels in atopic dermatitis (De Benedetto et al., 2011).

Eukaryota
Metazoa
Cldn 23 of Homo sapiens
(Q96B33)
*1.H.1.1.5









Claudin-19 (Cldn19) (interacts with Cldn3 and Cldn16 to form divalent cation (Mg2+ and Ca2+)-selective tight junctions; mutations in both proteins can give rise to hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), an inherited disorder (Hou et al., 2008). Claudins 16 and 19 belong to the PMP22-Claudin subfamily.  The structure of Claudin 19 with Clostridium perfringens enterotoxin bound (3.7Å resolution) revelaed interactions with the two extracellular loops of the claudin giving rise to helix displacement as the mechanism of tight junction disruption (Saitoh et al. 2015).  Claudin-16 and -19 form a stable dimer through cis-association of transmembrane domains 3 and 4, and mutations disrupting the claudin-16/19 cis-interaction increase tight junction ultrastructural complexity but reduce its permeability (Gong et al. 2015).

Eukaryota
Metazoa
Cldn19 of Homo sapiens (Q8N6F1)
*1.H.1.1.6









Claudin 4 (209aas) forms paracellular chloride channels in the kidney collecting duct and requires Claudin 8 for tight junctions localization (Hou et al., 2010).

Eukaryota
Metazoa
Cldn4 of Homo sapiens (O14493)
*1.H.1.1.7









Claudin 8 (225aas) is required for localization of Claudin 4 (TC# 1.H.1.1.6) to the kidney tight junctions (Hou et al., 2010). Bartter's syndrome patients have a single nucleotide substitution of C for T at position 451 of the claudin-8 gene sequence that changes the amino acid residue from serine to proline at position 151 in the second extracellular domain of the claudin-8 gene (Chen et al., 2009).

Eukaryota
Metazoa
Cldn8 of Homo sapiens (P56748)
*1.H.1.1.8









PM22_Claudin family (CLDN_18A2.1; CRA_C; 264 aas)
Eukaryota
Metazoa
Claudin-18A2.1 of Mus musculus (P56857)
*1.H.1.1.9









Claudin 15 (cation selective; Angelow et al., 2008)
Eukaryota
Metazoa
Cldn15 of Homo sapiens (P56746)
*1.H.1.1.10









Claudin 10a (Claudin-10a; isoform 1) has an anion-selective paracellular channel (Angelow et al., 2008) while Claudin 10b (Claudin-10b; isoform 2) has a cation-selective paracellular channel (Milatz and Breiderhoff 2017).

Eukaryota
Metazoa
Cldn10a of Mus musculus (Q9Z0S6)
*1.H.1.1.11









Claudin 2 (Claudin-2) (forms narrow, fluid filled, water-permeable cation-selective paracellular pores) (Angelow et al., 2008; Yu et al., 2009).  It is a dimer in a high molecular weight protein complex (Van Itallie et al. 2011; Krug et al. 2014). Transports Na+, K+ and water through the paracellular channel (Fromm et al. 2017).

Eukaryota
Metazoa
Cldn2 of Mus musculus (O88552)
*1.H.1.1.12









Claudin-15 of 227 aas and 4 TMSs, Cldn15.  Suzuki et al. 2013 reported the crystal structure of mouse claudin-15 at a resolution of 2.4 angstroms. The structure revealed a characteristic β-sheet fold consisting of two extracellular segments anchored to a transmembrane four-helix bundle by a consensus motif. Potential paracellular pathways with distinctive charges on the extracellular surface provided insight into the molecular basis of ion homeostasis across tight junctions.

Eukaryota
Metazoa
Cldn15 of Mus musculus
*1.H.1.1.13









Claudin 17 (Cluadin-17; CLDN17) of 224 aas and 4 TMSs.  Selectively permeable to anions (Krug et al. 2014).

Eukaryota
Metazoa
CLDN17 of Homo sapiens
*1.H.1.1.14









Claudin-1 (CLDN1) of 211 aas.  Forms homoligomers as well as heterooligomers with Claudin-3 (Milatz et al. 2015).

Eukaryota
Metazoa
Claudin-1 of Homo sapiens
*1.H.1.1.15









Claudin-3 (CLDN3) of 220 aas.  Forms homooligomers as well as heterooligomers with CLNVN1 (Milatz et al. 2015). Also forms hetero-oligomers with Claudin-16 and Claudin-19 which are divalent cation (Ca2+ and Mg2+)-selective (Milatz et al. 2017).

Eukaryota
Metazoa
CLDN3 of Homo sapiens
*1.H.1.1.16









Claudin 5 of 218 aas and 4 TMSs.  Plays an important role in the tight junctions that comprise the blood-brain barrier (Irudayanathan et al. 2015). Polyinosinic-polycytidylic acid [Poly(I:C)], a synthetic analog of viral double-stranded RNA (dsRNA) commonly used to simulate viral infections, decreases the expression of claudin-5, and gives rise to increased endothelial permeability (Huang et al. 2016).

Eukaryota
Metazoa
Claudin-5 of Homo sapiens
*1.H.1.1.17









Claudin 10b of 233 aas and 4 TMSs with a monovalent cation-selective paracellular channel (Milatz and Breiderhoff 2017).

Eukaryota
Metazoa
Claudin 10b of Danio rerio (Zebrafish) (Brachydanio rerio)
*1.H.1.2.1









Epithelial membrane protein2 EMP2. This protein interconnects the Claudin superfamily with the LACC (SUR7) family (1.A.81) of mating-dependent 4TMS Ca2+ channels in fungi and the 4TMS Ca2+ channel auxiliary subunit γ1-γ8 (CCAγ) family of animals (8.A.16).

Eukaryota
Metazoa
EMP2 of Mus musculus (Q8CGC1)
*1.H.1.2.2









Peripheral myelin protein 22, PMP22 of 160 aas and 4 TMSs.  May be involved in growth regulation and myelinization in the peripheral nervous system (Magyar et al. 1997).

Eukaryota
Metazoa
PMP22 of Homo sapiens
*1.H.1.3.1









Claudin family protein (related to Sur7; TC# 1.A.81)

Eukaryota
Fungi
Sur7 family protein of Cryptococcus formans
*1.H.1.4.1









Putative 5 TMS Claudin family member, distantly related to Sur7 in family 1.A.81.

Eukaryota
Fungi
Claudin-like protein of Neurospora crassa
*1.H.1.4.2









Protein up-regulated during nitrogen stress 1, PUN1 (YLR414c).  Colocalizes with Sur7 in punctate patches of the plasma membrane.

Eukaryota
Fungi
PUN1 of Saccharomyces cerevisiae
*1.H.1.4.3









Uncharacterized protein

Eukaryota
Fungi
UP of Aspergillus niger
*1.H.1.4.4









4 TMS uncharacterized protein

Eukaryota
Fungi
UP of Saccharomyces cerevisiae
*1.H.1.4.5









Uncharacterized protein

Eukaryota
Fungi
UP of Aspergillus oryzae
*1.H.1.4.6









Ecm7, (448aas; 4 TMS), is a member of the PMP-22/EMP/MP20 Claudin superfamily of transmembrane proteins that includes gamma-subunits of voltage-gated calcium channels.  It appears to interact with Mid1 and regulate the activity of the Cch1/Mid1 channel (TC# 1.A.1.11.10; Martin et al., 2011). Ecm7p is related to members of TC families 1.H.1, 1.H.2 and 1.A.81.

Eukaryota
Fungi
Ecm7 of Saccharomyces cerevisiae
*1.H.1.5.1









β-type IP39 protein of 264 aas and 4 TMSs in a 1 3 TMS arrangement.  Euglenoid flagellates have striped surface structures comprising pellicles, which allow the cell shape to vary from rigid to flexible during the characteristic movement of the flagellates. In Euglena gracilis, the pellicular strip membranes are covered with paracrystalline arrays of a major integral membrane protein, IP39, a four TMS protein with the conserved sequence motif of the PMP-22/EMP/MP20/Claudin superfamily. Suzuki et al. 2013 reported the three-dimensional structure of Euglena IP39 determined by electron crystallography. Two-dimensional crystals of IP39 formed a striated pattern of antiparallel double-rows in which trimeric IP39 units are longitudinally polymerised, resulting in continuously extending zigzag-shaped lines. Structural analysis revealed an asymmetric molecular arrangement in the trimer, suggesting that at least four different interactions between neighbouring protomers are involved. A combination of such multiple interactions would be important for linear strand formation of membrane proteins in a lipid bilayer (Suzuki et al. 2013).

Eukaryota
Euglenida
IP39 of Euglena gracilis
*1.H.1.5.2









α-type IP39 protein of 263 aas.  Nearly identical to 1.H.1.5.1. The low resolution 3-d structure is available (Suzuki et al. 2013).

Eukaryota
Euglenida
IP39 of Euglena gracilis
*1.H.1.6.1









Claudin-like protein (shows similarity to members of both 1.H.1 and 1.H.2). 

Eukaryota
Metazoa
Claudin-like protein of Ciona intestinalis (sea squirt) (F6YNZ8)
*1.H.1.7.1









Sur7p Ca2+ channel (4TMSs); affects sphingolipid metabolism and is involved in sporulation (Young et al., 2002). Related proteins contribute to secretion, biofilm formation and macrophage killing (see 1.A.81.3.2; Bernardo and Lee, 2010).

Eukaryota
Fungi
Sur7p of Saccharomyces cerevisiae (P54003)
*1.H.1.7.2









4TMS Sur7 family cortical patch protein. Contributes to secretion, biofilm formation and macrophage killing (Bernardo and Lee, 2010).  

Eukaryota
Fungi
Sur7p of Candida albicans (Q5A4M8)