The transmembrane cation channel superfamily was defined in
InterPro and
Pfam
Pfam is a database of protein families that includes their annotations and multiple sequence alignments generated using hidden Markov models. The latest version of Pfam, 37.0, was released in June 2024 and contains 21,979 families. It is cur ...
as the family of
tetrameric ion channels
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ...
. These include the
sodium
Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...
,
potassium
Potassium is a chemical element; it has Symbol (chemistry), symbol K (from Neo-Latin ) and atomic number19. It is a silvery white metal that is soft enough to easily cut with a knife. Potassium metal reacts rapidly with atmospheric oxygen to ...
,
calcium
Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...
,
ryanodine receptor
Ryanodine receptors (RyR) make up a class of high-conductance, intracellular calcium channels present in various forms, such as animal muscles and neurons. There are three major isoforms of the ryanodine receptor, which are found in different tissu ...
,
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
Vestigiality is the retention, during the process of evolution, of genetically determined structures or attributes that have lost some or all of the ancestral function in a given species. Assessment of the vestigiality must generally rely on co ...
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 channel
Inward-rectifier potassium channels (Kir, IRK) are a specific Lipid-gated_ion_channels, lipid-gated subset of potassium channels. To date, seven subfamilies have been identified in various mammalian cell types, plants, and bacteria. They are acti ...
s () 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
Transient receptor potential canonical 1 (TRPC1) is a protein that in humans is encoded by the ''TRPC1'' gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of n ...
;
TRPC3;
TRPC4
The short transient receptor potential channel 4 (TrpC4), also known as Trp-related protein 4, is a protein that in humans is encoded by the ''TRPC4'' gene.
Function
TrpC4 is a member of the transient receptor potential cation channels. This ...
;
TRPC5
Short transient receptor potential channel 5 (TrpC5) also known as transient receptor protein 5 (TRP-5) is a protein that in humans is encoded by the ''TRPC5'' gene. TrpC5 is subtype of the TRPC family of mammalian transient receptor potential io ...
;
TRPC6
Transient receptor potential cation channel, subfamily C, member 6 or Transient receptor potential canonical 6, also known as TRPC6, is a protein encoded in the human by the ''TRPC6'' gene. TRPC6 is a transient receptor potential channel of the c ...
;
TRPC7
= Melastatin
=
*
TRPM1
Transient receptor potential cation channel subfamily M member 1 is a protein that in humans is encoded by the ''TRPM1'' gene.
Function
The protein encoded by this gene is a member of the transient receptor potential (TRP) family of non-select ...
;
TRPM2
Transient receptor potential cation channel, subfamily M, member 2, also known as TRPM2, is a protein that in humans is encoded by the ''TRPM2'' gene.
Structure
The protein encoded by this gene is a non-selective calcium-permeable cation channe ...
;
TRPM3
Transient receptor potential cation channel subfamily M member 3 is a protein that in humans is encoded by the ''TRPM3'' gene.
Function
The product of this gene belongs to the family of Transient receptor potential channel, transient receptor ...
;
TRPM4;
TRPM5;
TRPM6;
TRPM7;
TRPM8
Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the ''TRPM8'' gene. The TRPM8 channel is the primary molecular ...
= Vanilloid
=
*
TRPV1
The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the ''TRPV1'' gene. It was the first isolated member of ...
;
TRPV2;
TRPV3;
TRPV4
Transient receptor potential cation channel subfamily V member 4 is an ion channel protein that in humans is encoded by the ''TRPV4'' gene.
The ''TRPV4'' gene encodes TRPV4, initially named "vanilloid-receptor related osmotically activated chann ...
;
TRPV5
Transient receptor potential cation channel subfamily V member 5 is a calcium channel protein that in humans is encoded by the ''TRPV5'' gene.
Function
The ''TRPV5'' gene is a member of the transient receptor family and the TRPV subfamily. Th ...
;
TRPV6
TRPV6 is a membrane calcium (Ca2+) channel protein which is particularly involved in the first step in Ca2+absorption in the intestine.
Classification
Transient Receptor Potential Vanilloid subfamily member 6 (TRPV6) is an epithelial Ca2+ ...
= Mucolipin
=
*
MCOLN1;
MCOLN2;
MCOLN3;
= Ankyrin
=
*
TRPA1
Transient receptor potential cation channel, subfamily A, member 1, also known as transient receptor potential ankyrin 1, TRPA1, or The Mustard and Wasabi Receptor, is a protein that in humans is encoded by the ''TRPA1'' (and in mice and rats by ...
= TRPP
=
*
PKD1L3;
Calcium
Voltage-dependent
*
CACNA1A;
CACNA1B
The voltage-dependent N-type calcium channel subunit alpha-1B is a protein that in humans is encoded by the CACNA1B gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a s ...
;
CACNA1C;
CACNA1D;
CACNA1E;
CACNA1F;
CACNA1G;
CACNA1H;
CACNA1I;
CACNA1S
Sperm
*
CATSPER1;
CATSPER2;
CATSPER3;
CATSPER4
Ryanodine receptor
*
RYR1
Ryanodine receptor 1 (RYR-1) also known as skeletal muscle calcium release channel or skeletal muscle-type ryanodine receptor is one of a class of ryanodine receptors and a protein found primarily in skeletal muscle. In humans, it is encoded by th ...
;
RYR2
Ryanodine receptor 2 (RYR2) is one of a class of ryanodine receptors and a protein found primarily in cardiac muscle. In humans, it is encoded by the ''RYR2'' gene. In the process of cardiac calcium-induced calcium release, RYR2 is the major med ...
;
RYR3
Ryanodine receptor 3 is one of a class of ryanodine receptors and a protein that in humans is encoded by the ''RYR3'' gene. The protein encoded by this gene is both a calcium channel and a receptor for the plant alkaloid ryanodine. RYR3 and ...
Potassium
Voltage-gated potassium
= Delayed rectifier
=
*K
vα1.x -
Shaker-related: K
v1.1 (
KCNA1), K
v1.2 (
KCNA2
Potassium voltage-gated channel subfamily A member 2 also known as Kv1.2 is a protein that in humans is encoded by the ''KCNA2'' gene.
Function
Potassium channels represent the most complex class of voltage-gated ion channels from both functio ...
), K
v1.3 (
KCNA3
Potassium voltage-gated channel, shaker-related subfamily, member 3, also known as KCNA3 or Kv1.3, is a protein that in humans is encoded by the ''KCNA3'' gene.
Potassium channels represent the most complex class of voltage-gated ion channels f ...
), 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
Kv7.1 (KvLQT1) is a potassium channel protein whose primary subunit in humans is encoded by the ''KCNQ1'' gene. Its mutation causes Long QT syndrome, Kv7.1 is a voltage and lipid-gated potassium channel present in the cell membranes of cardi ...
) -
KvLQT1
Kv7.1 (KvLQT1) is a potassium ion channel, channel protein whose primary subunit in humans is encoded by the ''KCNQ1'' gene. Its mutation causes Long QT syndrome, Kv7.1 is a voltage and Lipid-gated ion channels, lipid-gated potassium channel pr ...
, K
v7.2 (
KCNQ2), K
v7.3 (
KCNQ3), K
v7.4 (
KCNQ4
Potassium voltage-gated channel subfamily KQT member 4, also known as voltage-gated potassium channel subunit Kv7.4, is a protein that in humans is encoded by the ''KCNQ4'' gene.
Function
The protein encoded by this gene forms a potassium chan ...
), K
v7.5 (
KCNQ5
Potassium voltage-gated channel subfamily KQT member 5 is a protein that in humans is encoded by the ''KCNQ5'' gene.
This gene is a member of the KCNQ potassium channel gene family that is differentially expressed in subregions of the brain and i ...
)
*K
vα10.x: K
v10.1 (
KCNH1
Potassium voltage-gated channel subfamily H member 1 (KV10.1, EAG1) is a protein that in humans is encoded by the ''KCNH1'' gene. Mutations in ''KCNH1'' cause genetic epilepsy and developmental encephalopathies, and aberant expression is associat ...
)
= A-type potassium
=
*K
vα1.x - Shaker-related: K
v1.4 (
KCNA4
Potassium voltage-gated channel subfamily A member 4 also known as Kv1.4 is a protein that in humans is encoded by the ''KCNA4'' gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the ...
)
*K
vα3.x - Shaw-related: K
v3.3 (
KCNC3), K
v3.4 (
KCNC4)
*K
vα4.x - Shal-related: K
v4.1 (
KCND1
Potassium voltage-gated channel, Shal-related subfamily, member 1 (KCND1), also known as Kv4.1, is a human gene.
Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structu ...
), K
v4.2 (
KCND2
Potassium voltage-gated channel subfamily D member 2 is a protein that in humans is encoded by the ''KCND2'' gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase ...
), K
v4.3 (
KCND3
Potassium voltage-gated channel subfamily D member 3 also known as Kv4.3 is a protein that in humans is encoded by the ''KCND3'' gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the ...
)
= Outward-rectifying
=
*K
vα10.x: K
v10.2 (
KCNH5
Potassium voltage-gated channel, subfamily H (eag-related), member 5, also known as KCNH5, is a human gene encoding the Kv10.2 protein.
Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both ...
)
= Inwardly-rectifying
=
*K
vα11.x -
ether-a-go-go potassium channels: K
v11.1 (
KCNH2
hERG (the human '' Ether-à-go-go''-Related Gene) is a gene () that codes for a protein known as Kv11.1, the alpha subunit of a potassium ion channel. This ion channel (sometimes simply denoted as 'hERG') is best known for its contribution t ...
) -
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
=
*
KCa1.1 (BK, Slo1, Maxi-K, )
= SK
=
* K
Ca2.x: K
Ca2.1 (
KCNN1
Potassium intermediate/small conductance calcium-activated channel, subfamily N, member 1 , also known as KCNN1 is a human gene encoding the KCa2.1 protein.
Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) t ...
) - 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
=
*
KCa3.1 (IKCa1, SK4, )
= Other subfamilies
=
*
KCa5.1 (Slo3, )
Inward-rectifier potassium
Sodium
*
NALCN
*
SCN1A
Sodium channel protein type 1 subunit alpha (SCN1A), is a protein which in humans is encoded by the ''SCN1A'' gene.
Gene location
The ''SCN1A'' gene is located on chromosome 2 of humans, and is made up of 26 exons spanning a total length of 6 ...
;
SCN2A;
SCN2A2;
SCN3A
Sodium channel, voltage-gated, type III, alpha subunit (SCN3A) is a protein that in humans is encoded by the ''SCN3A'' gene.
Function
Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit wi ...
;
SCN4A;
SCN5A;
SCN7A;
SCN8A;
SCN9A;
SCN10A;
SCN11A
Sodium channel, voltage-gated, type XI, alpha subunit also known as SCN11A or Nav1.9 is a voltage-gated ion channel, voltage-gated sodium ion channel protein which is encoded by the ''SCN11A'' gene on Chromosome 3 (human), chromosome 3 in human ...
*
SLC9A10;
SLC9A11
Cyclic nucleotide-gated
*
CNGA1;
CNGA2;
CNGA3;
CNGA4
*
CNGB1;
CNGB3
*
HCN1;
HCN2;
HCN3;
HCN4
*
ITPR1
Inositol 1,4,5-trisphosphate receptor type 1 is a protein that in humans is encoded by the ''ITPR1'' gene.
Interactions
ITPR1 has been shown to interact with:
* AHCYL1,
* CA8,
* EPB41L1
* FKBP1A,
* MRVI1,
* PRKG1,
* RHOA
Tran ...
;
ITPR2
Inositol 1,4,5-trisphosphate receptor, type 2, also known as ITPR2, is a protein which in humans is encoded by the ''ITPR2'' gene. The protein encoded by this gene is both a receptor for inositol triphosphate and a calcium channel
A calcium ...
;
ITPR3
Inositol 1,4,5-trisphosphate receptor, type 3, also known as ITPR3, is a protein which in humans is encoded by the ''ITPR3'' gene. The protein encoded by this gene is both a receptor for inositol triphosphate and a calcium channel.
Function
...
Proton
*
HVCN1
Related proteins
*
TPTE, part of the larger
Voltage sensitive phosphatase
Voltage sensitive phosphatases or voltage sensor-containing phosphatases, commonly abbreviated VSPs, are a protein family found in many species, including humans, mice, zebrafish, frogs, and sea squirt.
Discovery
The first voltage sensitive phos ...
family
Human channels with 2 TM helices in each subunit
Potassium
Tandem pore domain potassium channel
*
KCNK1;
KCNK2
Potassium channel subfamily K member 2, also known as TREK-1, is a protein that in humans is encoded by the ''KCNK2'' gene.
This gene encodes K2P2.1, a lipid-gated ion channel belonging to the two-pore-domain background potassium channel protei ...
;
KCNK3;
KCNK4;
KCNK5;
KCNK6;
KCNK7;
KCNK9;
KCNK10;
KCNK12;
KCNK13;
KCNK15;
KCNK16;
KCNK17;
KCNK18
Non-human channels
Two-pore
*
TPCN1
*
TPCN2
Pore-only potassium
*
KcsA
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
*
{{InterPro content, IPR005821
Protein domains
Protein families
Transmembrane proteins
Ion channels