Cation channel superfamily

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 1.A.1, 1.A.2, 1.A.3, and 1.A.4 of the TCDB transporter classification.

Ion channel (eukaryotic)
Potassium channel Kv1.2 (with beta2 auxiliary subunits), structure in a membrane-like environment. Calculated hydrocarbon boundaries of the lipid bilayer are indicated by red and blue dots.
Identifiers
Symbol	Ion_trans
Pfam	PF00520
InterPro	IPR005821
SCOP2	1bl8 / SCOPe / SUPFAM
TCDB	1.A.1
OPM superfamily	8
OPM protein	2a79
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary PDB 1qg9A:157-176 2a79B:225-409 1ho7A:378-397 1ho2A:378-397 1ujlA:570-611

Ion channel (bacterial)
Potassium channel KcsA. Calculated hydrocarbon boundaries of the lipid bilayer are indicated by red and blue dots.
Identifiers
Symbol	Ion_trans_2
Pfam	PF07885
InterPro	IPR013099
SCOP2	1bl8 / SCOPe / SUPFAM
OPM protein	1r3j
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary PDB 1lnqE:25-100 2a0lB:169-250 1orqC:169-250 1k4cC:34-116 1r3iC:34-116 2bocC:34-116 1j95C:34-116 1r3lC:34-116 1jvmB:34-116 1bl8C:34-116 2a9hD:34-116 1k4dC:34-116 1r3jC:34-116 1r3kC:34-116 2bobC:34-116 1p7bB:77-151

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

Main article: Transient receptor potential channel

Canonical

Main article: Canonical TRP channels

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

Melastatin

Main article: Melastatin TRP channels

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

Vanilloid

Main article: Vanilloid TRP channels

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

Mucolipin

Main article: Mucolipin TRP channels

• MCOLN1; MCOLN2; MCOLN3;

Ankyrin

Main article: Ankyrin TRP channels

• TRPA1

TRPP

Main article: Transient Receptor Potential Polycystic

• PKD1L3;

Calcium

Voltage-dependent

Main article: Voltage-dependent calcium channels

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

Sperm

Main article: Cation channels of sperm

• CATSPER1; CATSPER2; CATSPER3; CATSPER4

Ryanodine receptor

Main article: Ryanodine receptor

• RYR1; RYR2; RYR3

Potassium

Voltage-gated potassium

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

Main article: Calcium-activated potassium channels

BK

Main article: BK channels

• K_Ca1.1 (BK, Slo1, Maxi-K, KCNMA1)

SK

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

Main article: IK channels

• K_Ca3.1 (IKCa1, SK4, KCNN4)

Other subfamilies

• K_Ca5.1 (Slo3, KCNU1)

Inward-rectifier potassium

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

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

Main article: Two-pore channels

• TPCN1
• TPCN2

Pore-only potassium

Main article: Pore-only potassium channels

• KcsA

Ligand-gated potassium

• GluR0^[2]

Voltage-gated potassium

Main article: Voltage-gated potassium channels

• KvAP^[3]

Prokaryotic KCa

Main article: Prokaryotic KCa channels

• 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

Main article: Inward-rectifier potassium channels

• KirBac^[23]

Engineered

• NaK2CNG ^[24]
• NaK2K ^[25]