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Cation channel superfamily

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
Melastatin
Vanilloid
Mucolipin
Ankyrin
TRPP

Calcium

Voltage-dependent

Sperm

Ryanodine receptor

Potassium

Voltage-gated potassium

Delayed rectifier
  • K<sub>v</sub>α1.x - Shaker-related: K<sub>v</sub>1.1 (KCNA1), K<sub>v</sub>1.2 (KCNA2), K<sub>v</sub>1.3 (KCNA3), K<sub>v</sub>1.5 (KCNA5), K<sub>v</sub>1.6 (KCNA6), K<sub>v</sub>1.7 (KCNA7), K<sub>v</sub>1.8 (KCNA10)
  • K<sub>v</sub>α2.x - Shab-related: K<sub>v</sub>2.1 (KCNB1), K<sub>v</sub>2.2 (KCNB2)
  • K<sub>v</sub>α3.x - Shaw-related: K<sub>v</sub>3.1 (KCNC1), K<sub>v</sub>3.2 (KCNC2)
  • K<sub>v</sub>α7.x: K<sub>v</sub>7.1 (KCNQ1) - KvLQT1, K<sub>v</sub>7.2 (KCNQ2), K<sub>v</sub>7.3 (KCNQ3), K<sub>v</sub>7.4 (KCNQ4), K<sub>v</sub>7.5 (KCNQ5)
  • K<sub>v</sub>α10.x: K<sub>v</sub>10.1 (KCNH1)
A-type potassium
  • K<sub>v</sub>α1.x - Shaker-related: K<sub>v</sub>1.4 (KCNA4)
  • K<sub>v</sub>α3.x - Shaw-related: K<sub>v</sub>3.3 (KCNC3), K<sub>v</sub>3.4 (KCNC4)
  • K<sub>v</sub>α4.x - Shal-related: K<sub>v</sub>4.1 (KCND1), K<sub>v</sub>4.2 (KCND2), K<sub>v</sub>4.3 (KCND3)
Outward-rectifying
  • K<sub>v</sub>α10.x: K<sub>v</sub>10.2 (KCNH5)
Inwardly-rectifying
Slowly activating
  • K<sub>v</sub>α12.x: K<sub>v</sub>12.1 (KCNH8), K<sub>v</sub>12.2 (KCNH3), K<sub>v</sub>12.3 (KCNH4)
Modifier/silencer
  • K<sub>v</sub>α5.x: K<sub>v</sub>5.1 (KCNF1)
  • K<sub>v</sub>α6.x: K<sub>v</sub>6.1 (KCNG1), K<sub>v</sub>6.2 (KCNG2), K<sub>v</sub>6.3 (KCNG3), K<sub>v</sub>6.4 (KCNG4)
  • K<sub>v</sub>α8.x: K<sub>v</sub>8.1 (KCNV1), K<sub>v</sub>8.2 (KCNV2)
  • K<sub>v</sub>α9.x: K<sub>v</sub>9.1 (KCNS1), K<sub>v</sub>9.2 (KCNS2), K<sub>v</sub>9.3 (KCNS3)

Calcium-activated

BK
SK
  • K<sub>Ca</sub>2.x: K<sub>Ca</sub>2.1 (KCNN1) - SK1, K<sub>Ca</sub>2.2 (KCNN2) - SK2, K<sub>Ca</sub>2.3 (KCNN3) - SK3
  • K<sub>Ca</sub>3.x: K<sub>Ca</sub>3.1 (KCNN4) - SK4
  • K<sub>Ca</sub>4.x: K<sub>Ca</sub>4.1 (KCNT1) - SLACK, K<sub>Ca</sub>4.2 (KCNT2) - SLICK
IK
Other subfamilies

Inward-rectifier potassium

Sodium

Cyclic nucleotide-gated

Proton

Related proteins

Human channels with 2 TM helices in each subunit

Potassium

Tandem pore domain potassium channel

Non-human channels

Two-pore

Pore-only potassium

Ligand-gated potassium

  • GluR0

Voltage-gated potassium

  • KvAP

Prokaryotic KCa

  • Kch
  • MthK
  • TrkA/TrkH
  • KtrAB
  • GsuK
  • TM1088

Voltage and cyclic nucleotide gated potassium

  • MlotiK1

Sodium

  • NaChBac
  • NaVAb
  • NaVAe1
  • NaVAp
  • NaVMm

Non-selective

  • NaK

Prokaryotic inward-rectifier potassium

  • KirBac

Engineered

  • NaK2CNG
  • NaK2K

References

External links