Potassium channel tetramerisation domain

K+ channel tetramerisation domain is the N-terminal, cytoplasmic tetramerisation domain (T1) of voltage-gated K+ channels. It defines molecular determinants for subfamily-specific assembly of alpha-subunits into functional tetrameric channels. It is distantly related to the BTB/POZ domain .

Potassium channels

Potassium channels are the most diverse group of the ion channel family

Ion channel family

Transmembrane ion channel family was defined in InterPro and Pfam as the family of tetrameric sodium, potassium, and calcium ion channels, in which two C-terminal transmembrane helices flank a loop which determines ion selectivity of the channel pore...

. They are important in shaping the action potential, and in neuronal excitability and plasticity. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.

These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K⁺ channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers. In eukaryotic cells, K⁺ channels are involved in neural signalling and generation of
the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs)
and may have a role in target cell lysis by cytotoxic T-lymphocytes. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis.

Alpha subunits of the channels

All K⁺ channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has
been termed the K⁺ selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K⁺ across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K⁺ channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K⁺ channels; and three types of calcium (Ca)-activated K⁺ channels (BK, IK and SK). The 2TM domain family comprises inward-rectifying K⁺ channels. In addition, there are K⁺ channel alpha-subunits that possess two P-domains. These are usually highly regulated K⁺ selective leak channels.

The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential. More recently, 4 new electrically-silent alpha subunits have been
cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.

Tetramerization domain

The N-terminal, cytoplasmic tetramerization domain (T1) of voltage-gated potassium channels encodes molecular determinants for subfamily-specific assembly of alpha-subunits into functional tetrameric channels. This domain is found in a subset of a larger group of proteins that contain the BTB/POZ domain.

Human proteins containing this domain

BTBD10; KCNA1

KCNA1

Potassium voltage-gated channel subfamily A member 1 also known as Kv1.1 is a shaker related voltage-gated potassium channel that in humans is encoded by the KCNA1 gene. The Isaacs syndrome is a result of an autoimmune reaction against the Kv1.1 ion channel.- Genomics :The gene is located on the...

; KCNA10

KCNA10

Potassium voltage-gated channel subfamily A member 10 also known as Kv1.8 is a protein that in humans is encoded by the KCNA10 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit....

; KCNA2

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.-Interactions:KCNA2 has been shown to interact with KCNA4, DLG4, PTPRA, KCNAB2, RHOA and Cortactin....

; KCNA3

KCNA3

Potassium voltage-gated channel, shaker-related subfamily, member 3, also known as KCNA3 or Kv1.3, is a protein which in humans is encoded by the KCNA3 gene....

; KCNA4

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 , the main contributing current to the repolarizing phase 1 of the cardiac action...

; KCNA5

KCNA5

Potassium voltage-gated channel, shaker-related subfamily, member 5, also known as KCNA5 or Kv1.5, is a protein that in humans is encoded by the KCNA5 gene.-Function:...

; KCNA6

KCNA6

Potassium voltage-gated channel subfamily A member 6 also known as Kv1.6 is a protein that in humans is encoded by the KCNA6 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit....

;
KCNA7

KCNA7

Potassium voltage-gated channel subfamily A member 7 also known as Kv1.7 is a protein that in humans is encoded by the KCNA7 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit. It may contribute to the cardiac transient outward potassium current , the main...

; KCNB1

KCNB1

Potassium voltage-gated channel, Shab-related subfamily, member 1, also known as KCNB1 or Kv2.1, is a protein which in humans is encoded by the KCNB1 gene.-Species and tissue distribution:...

; KCNB2

KCNB2

Potassium voltage-gated channel subfamily B member 2 is a protein that in humans is encoded by the KCNB2 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit....

; KCNC1

KCNC1

Potassium voltage-gated channel subfamily C member 1 is a protein that in humans is encoded by the KCNC1 gene.The Shaker gene family of Drosophila encodes components of voltage-gated potassium channels and comprises four subfamilies. Based on sequence similarity, this gene is similar to one of...

; KCNC2

KCNC2

Potassium voltage-gated channel subfamily C member 2 is a protein that in humans is encoded by the KCNC2 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit.-Expression pattern:...

; KCNC3

KCNC3

Potassium voltage-gated channel, Shaw-related subfamily, member 3 also known as KCNC3 or Kv3.3 is a protein which in humans is encoded by the KCNC3.- Function :...

; KCNC4

KCNC4

Potassium voltage-gated channel, Shaw-related subfamily, member 4 , also known as Kv3.4, is a human gene.-Further reading:...

; KCND1

KCND1

Potassium voltage-gated channel, Shal-related subfamily, member 1 , also known as Kv4.1, is a human gene.-Further reading:...

;
KCND2

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 , the main contributing current to the repolarizing phase 1 of the cardiac action...

; KCND3

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 , the main contributing current to the repolarizing phase 1 of the cardiac action potential.- Function...

; KCNF1

KCNF1

Potassium voltage-gated channel subfamily F member 1 is a protein that in humans is encoded by the KCNF1 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit....

; KCNG1

KCNG1

Potassium voltage-gated channel subfamily G member 1 is a protein that in humans is encoded by the KCNG1 gene....

; KCNG2

KCNG2

Potassium voltage-gated channel subfamily G member 2 is a protein that in humans is encoded by the KCNG2 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit....

; KCNG3

KCNG3

Potassium voltage-gated channel subfamily G member 3 is a protein that in humans is encoded by the KCNG3 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit....

; KCNG4

KCNG4

Potassium voltage-gated channel subfamily G member 4 is a protein that in humans is encoded by the KCNG4 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit....

; KCNRG

KCNRG

Potassium channel regulator, also known as KCNRG, is a protein which in humans is encoded by theKCNRG gene.- Function :KCNRG is a soluble protein with characteristics suggesting it forms hetero-tetramers with voltage-gated K+ channels and inhibits their function.- Clinical significance :KCNRG has...

;
KCNS1

KCNS1

Potassium voltage-gated channel subfamily S member 1 is a protein that in humans is encoded by the KCNS1 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit....

; KCNS2

KCNS2

Potassium voltage-gated channel subfamily S member 2 is a protein that in humans is encoded by the KCNS2 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit....

; KCNS3

KCNS3

Potassium voltage-gated channel subfamily S member 3 is a protein that in humans is encoded by the KCNS3 gene.-Further reading:...

; KCNV1

KCNV1

Potassium voltage-gated channel subfamily V member 1 is a protein that in humans is encoded by the KCNV1 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit....

; KCNV2

KCNV2

Potassium voltage-gated channel subfamily V member 2 is a protein that in humans is encoded by the KCNV2 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit....

; KCTD1; KCTD10; KCTD11;
KCTD12

KCTD12

BTB/POZ domain-containing protein KCTD12 is a protein that in humans is encoded by the KCTD12 gene.-Further reading:...

; KCTD13

KCTD13

BTB/POZ domain-containing protein KCTD13 is a protein that in humans is encoded by the KCTD13 gene.-Further reading:...

; KCTD14; KCTD15

KCTD15

Potassium channel tetramerisation domain containing 15 also known as BTB/POZ domain-containing protein KCTD15 is protein that in humans is encoded by the KCTD15 gene....

; KCTD16; KCTD17; KCTD18; KCTD19;
KCTD2; KCTD20; KCTD21; KCTD3; KCTD4; KCTD5; KCTD6; KCTD7;
KCTD8; KCTD9; SHKBP1; TNFAIP1

TNFAIP1

BTB/POZ domain-containing protein TNFAIP1 is a protein that in humans is encoded by the TNFAIP1 gene.-Further reading:...

;