Cation channel superfamily

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) (Pfam PF00520), related to or vestigial of voltage gating. The proteins with only two transmembrane helices (Pfam PF07885) are most commonly found in bacteria. This also includes the 2-TM inward-rectifier potassium channels (Pfam PF01007) 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

• K_vα1.x - Shaker-related: K_v1.1 (KCNA1), K_v1.2 (KCNA2), K_v1.3 (KCNA3), K_v1.5 (KCNA5), K_v1.6 (KCNA6), K_v1.7 (KCNA7), K_v1.8 (KCNA10)
• K_vα2.x - Shab-related: K_v2.1 (KCNB1), K_v2.2 (KCNB2)
• K_vα3.x - Shaw-related: K_v3.1 (KCNC1), K_v3.2 (KCNC2)
• K_vα7.x: K_v7.1 (KCNQ1) - KvLQT1, K_v7.2 (KCNQ2), K_v7.3 (KCNQ3), K_v7.4 (KCNQ4), K_v7.5 (KCNQ5)
• K_vα10.x: K_v10.1 (KCNH1)

A-type potassium

• K_vα1.x - Shaker-related: K_v1.4 (KCNA4)
• K_vα3.x - Shaw-related: K_v3.3 (KCNC3), K_v3.4 (KCNC4)
• K_vα4.x - Shal-related: K_v4.1 (KCND1), K_v4.2 (KCND2), K_v4.3 (KCND3)

Outward-rectifying

• K_vα10.x: K_v10.2 (KCNH5)

Inwardly-rectifying

• K_vα11.x - ether-a-go-go potassium channels: K_v11.1 (KCNH2) - hERG, K_v11.2 (KCNH6), K_v11.3 (KCNH7)

Slowly activating

• K_vα12.x: K_v12.1 (KCNH8), K_v12.2 (KCNH3), K_v12.3 (KCNH4)

Modifier/silencer

• K_vα5.x: K_v5.1 (KCNF1)
• K_vα6.x: K_v6.1 (KCNG1), K_v6.2 (KCNG2), K_v6.3 (KCNG3), K_v6.4 (KCNG4)
• K_vα8.x: K_v8.1 (KCNV1), K_v8.2 (KCNV2)
• K_vα9.x: K_v9.1 (KCNS1), K_v9.2 (KCNS2), K_v9.3 (KCNS3)

Calcium-activated

BK

• K_Ca1.1 (BK, Slo1, Maxi-K, KCNMA1)

SK

• K_Ca2.x: K_Ca2.1 (KCNN1) - SK1, K_Ca2.2 (KCNN2) - SK2, K_Ca2.3 (KCNN3) - SK3
• K_Ca3.x: K_Ca3.1 (KCNN4) - SK4
• K_Ca4.x: K_Ca4.1 (KCNT1) - SLACK, K_Ca4.2 (KCNT2) - SLICK

IK

• K_Ca3.1 (IKCa1, SK4, KCNN4)

Other subfamilies

• K_Ca5.1 (Slo3, KCNU1)

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