Cation channel superfamily explained

See also: Voltage-gated ion channel.

The transmembrane cation channel superfamily was defined in InterPro and Pfam as the family of tetrameric ion channels. These include the sodium, potassium,^[1] 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

See main article: Transient receptor potential channel.

Canonical

See main article: Canonical TRP channels.

• TRPC1; TRPC3; TRPC4; TRPC5; TRPC6; TRPC7

Melastatin

See main article: Melastatin TRP channels.

• TRPM1; TRPM2; TRPM3; TRPM4; TRPM5; TRPM6; TRPM7; TRPM8

Vanilloid

See main article: Vanilloid TRP channels.

• TRPV1; TRPV2; TRPV3; TRPV4; TRPV5; TRPV6

Mucolipin

See main article: Mucolipin TRP channels.

• MCOLN1; MCOLN2; MCOLN3;

Ankyrin

See main article: Ankyrin TRP channels.

• TRPA1

TRPP

See main article: Transient Receptor Potential Polycystic.

• PKD1L3;

Calcium

Voltage-dependent

See main article: Voltage-dependent calcium channels.

• CACNA1A; CACNA1B; CACNA1C; CACNA1D; CACNA1E; CACNA1F; CACNA1G; CACNA1H; CACNA1I; CACNA1S

Sperm

See main article: Cation channels of sperm.

• CATSPER1; CATSPER2; CATSPER3; CATSPER4

Ryanodine receptor

See main article: Ryanodine receptor.

• RYR1; RYR2; RYR3

Potassium

Voltage-gated potassium

See main article: Voltage-gated potassium channels.

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

See main article: Calcium-activated potassium channels.

BK

See main article: BK channels.

• K_Ca1.1 (BK, Slo1, Maxi-K,)

SK

See main article: SK channels.

• 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

See main article: IK channels.

• K_Ca3.1 (IKCa1, SK4,)

Other subfamilies

• K_Ca5.1 (Slo3,)

Inward-rectifier potassium

See main article: Inward-rectifier potassium ion channel.

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

See main article: Tandem pore domain potassium channel.

• KCNK1; KCNK2; KCNK3; KCNK4; KCNK5; KCNK6; KCNK7; KCNK9; KCNK10; KCNK12; KCNK13; KCNK15; KCNK16; KCNK17; KCNK18

Non-human channels

Two-pore

See main article: Two-pore channels.

• TPCN1
• TPCN2

Pore-only potassium

See main article: Pore-only potassium channels.

• KcsA

Ligand-gated potassium

• GluR0^[2]

Voltage-gated potassium

See main article: Voltage-gated potassium channels.

• KvAP^[3]

Prokaryotic KCa

• Kch^{[4] [5]}
• MthK^{[6] [7] [8] [9] [10]}
• TrkA/TrkH^{[11] [12]}
• KtrAB^[13]
• GsuK^[14]
• TM1088^[15]

Voltage and cyclic nucleotide gated potassium

• MlotiK1^[16]

Sodium

• NaChBac^[17]
• NaVAb^[18]
• NaVAe1^[19]
• NaVAp^[20]
• NaVMm^[21]

Non-selective

• NaK^[22]

Prokaryotic inward-rectifier potassium

See main article: Inward-rectifier potassium channels.

• KirBac^[23]

Engineered

• NaK2CNG ^[24]
• NaK2K ^[25]

External links

• Web site: Voltage-gated Ion Channels . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2008-12-16 . 2021-04-17 . https://web.archive.org/web/20210417093732/https://www.iuphar-db.org/IC/ReceptorFamiliesForward . dead .

Notes and References

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4. Milkman R . An Escherichia coli homologue of eukaryotic potassium channel proteins . Proceedings of the National Academy of Sciences of the United States of America . 91 . 9 . 3510–4 . April 1994 . 8170937 . 43609 . 10.1073/pnas.91.9.3510 . 1994PNAS...91.3510M . free .
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7. Smith FJ, Pau VP, Cingolani G, Rothberg BS . Structural basis of allosteric interactions among Ca2+-binding sites in a K+ channel RCK domain . Nature Communications . 4 . 2621 . 2013 . 24126388 . 10.1038/ncomms3621 . 2013NatCo...4.2621S . free .
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13. Vieira-Pires RS, Szollosi A, Morais-Cabral JH . The structure of the KtrAB potassium transporter . Nature . 496 . 7445 . 323–8 . April 2013 . 23598340 . 10.1038/nature12055 . 2013Natur.496..323V . 10216/110345 . 205233489 . free .
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