The transmembrane cation channel superfamily was defined in InterPro and Pfam as the family of tetrameric ion channels. These include the sodium, potassium, calcium, ryanodine receptor, HCN, CNG, CatSper, and TRP channels. This large group of ion channels apparently includes families , , , and of the TCDB transporter classification.
They are described as minimally having two transmembrane helices flanking a loop which determines the ion selectivity of the channel pore. Many eukaryotic channels have four additional transmembrane helices (TM) (), related to or vestigial of voltage gating. The proteins with only two transmembrane helices () are most commonly found in bacteria. This also includes the 2-TM inward-rectifier potassium channels () found primarily in eukaryotes. There are commonly additional regulatory domains which serve to regulate ion conduction and channel gating. The pores may also be homotetramers or heterotetramers; where heterotetramers may be encoded as distinct genes or as multiple pore domains within a single polypeptide. The HVCN1 and Putative tyrosine-protein phosphatase proteins do not contain an expected ion conduction pore domain, but rather have homology only to the voltage sensor domain of voltage gated ion channels.
Human channels with 6 TM helices
Cation
Transient receptor potential
Canonical
TRPC1; TRPC3; TRPC4; TRPC5; TRPC6; TRPC7
Melastatin
TRPM1; TRPM2; TRPM3; TRPM4; TRPM5; TRPM6; TRPM7; TRPM8
Vanilloid
TRPV1; TRPV2; TRPV3; TRPV4; TRPV5; TRPV6
Mucolipin
MCOLN1; MCOLN2; MCOLN3;
Ankyrin
TRPA1
TRPP
PKD1L3;
Calcium
Voltage-dependent
CACNA1A; CACNA1B; CACNA1C; CACNA1D; CACNA1E; CACNA1F; CACNA1G; CACNA1H; CACNA1I; CACNA1S
Sperm
CATSPER1; CATSPER2; CATSPER3; CATSPER4
Ryanodine receptor
RYR1; RYR2; RYR3
Potassium
Voltage-gated potassium
Delayed rectifier
Kvα1.x - Shaker-related: Kv1.1 (KCNA1), Kv1.2 (KCNA2), Kv1.3 (KCNA3), Kv1.5 (KCNA5), Kv1.6 (KCNA6), Kv1.7 (KCNA7), Kv1.8 (KCNA10) Kvα2.x - Shab-related: Kv2.1 (KCNB1), Kv2.2 (KCNB2) Kvα3.x - Shaw-related: Kv3.1 (KCNC1), Kv3.2 (KCNC2) Kvα7.x: Kv7.1 (KCNQ1) - KvLQT1, Kv7.2 (KCNQ2), Kv7.3 (KCNQ3), Kv7.4 (KCNQ4), Kv7.5 (KCNQ5) Kvα10.x: Kv10.1 (KCNH1)
A-type potassium
Kvα1.x - Shaker-related: Kv1.4 (KCNA4) Kvα3.x - Shaw-related: Kv3.3 (KCNC3), Kv3.4 (KCNC4) Kvα4.x - Shal-related: Kv4.1 (KCND1), Kv4.2 (KCND2), Kv4.3 (KCND3)
Outward-rectifying
Kvα10.x: Kv10.2 (KCNH5)
Inwardly-rectifying
Kvα11.x - ether-a-go-go potassium channels: Kv11.1 (KCNH2) - hERG, Kv11.2 (KCNH6), Kv11.3 (KCNH7)
Slowly activating
Kvα12.x: Kv12.1 (KCNH8), Kv12.2 (KCNH3), Kv12.3 (KCNH4)
Modifier/silencer
Kvα5.x: Kv5.1 (KCNF1) Kvα6.x: Kv6.1 (KCNG1), Kv6.2 (KCNG2), Kv6.3 (KCNG3), Kv6.4 (KCNG4) Kvα8.x: Kv8.1 (KCNV1), Kv8.2 (KCNV2) Kvα9.x: Kv9.1 (KCNS1), Kv9.2 (KCNS2), Kv9.3 (KCNS3)
Calcium-activated
BK
KCa1.1 (BK, Slo1, Maxi-K, )
SK
KCa2.x: KCa2.1 (KCNN1) - SK1, KCa2.2 (KCNN2) - SK2, KCa2.3 (KCNN3) - SK3
KCa3.x: KCa3.1 (KCNN4) - SK4
KCa4.x: KCa4.1 (KCNT1) - SLACK, KCa4.2 (KCNT2) - SLICK
IK
KCa3.1 (IKCa1, SK4, )
Other subfamilies
KCa5.1 (Slo3, )
Inward-rectifier potassium
Sodium
NALCN
SCN1A; SCN2A; SCN2A2; SCN3A; SCN4A; SCN5A; SCN7A; SCN8A; SCN9A; SCN10A; SCN11A
SLC9A10; SLC9A11
Cyclic nucleotide-gated
CNGA1; CNGA2; CNGA3; CNGA4
CNGB1; CNGB3
HCN1; HCN2; HCN3; HCN4
ITPR1; ITPR2; ITPR3
Proton
HVCN1
Related proteins
TPTE, part of the larger Voltage sensitive phosphatase family
Human channels with 2 TM helices in each subunit
Potassium
Tandem pore domain potassium channel
KCNK1; KCNK2; KCNK3; KCNK4; KCNK5; KCNK6; KCNK7; KCNK9; KCNK10; KCNK12; KCNK13; KCNK15; KCNK16; KCNK17; KCNK18