Slo3

Description: potassium large conductance pH-sensitive channel, subfamily M, alpha member 3
Gene: Kcnu1
Alias: Slo3, kcnu1, Kcnma3, KCa5, Kcnma3, KCa5.1

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Introduction

The mouse Slo3 gene (KCNMA3) encodes a K+ channel that is regulated by changes in cytosolic pH. Like Slo1 subunits responsible for the Ca2+ and voltage-activated BK-type channel, the Slo3 α subunit contains a pore module with homology to voltage-gated K+ channels and also an extensive cytosolic C terminus thought to be responsible for ligand dependence. For the Slo3 K+ channel, increases in cytosolic pH promote channel activation, but very little is known about many fundamental properties of Slo3 currents. (Zhang [165])

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Gene

Slo3 shares the most extensive sequence homology with Slo1 (Schreiber 1998 [1160]).

Species	NCBI gene ID	Chromosome	Position
Human	157855	8	151751
Mouse	16532	8	89315
Rat	680912	16	87797

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Transcript

Species	NCBI accession	Length (nt)
Human	NM_001031836.3	3692
Mouse	NM_008432.3	3548

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Protein Isoforms

Species	Uniprot ID	Length (aa)
Human	A8MYU2	1149
Mouse	O54982	1121
Rat	D4A6Z8	1113

Isoforms

Transcript

Length (nt)

Protein

Length (aa)

Variant

Isoform

Known

NR_134267.2

3754

transcript variant 2

NM_001031836.3

3692

NP_001027006.2

1149

transcript variant 1

Predicted

XR_001745486.3

2274

transcript variant X6

XM_011544426.3

3579

XP_011542728.1

985

transcript variant X3

isoform X3

XM_017013144.3

3608

XP_016868633.1

1121

transcript variant X2

isoform X2

XM_011544424.3

3620

XP_011542726.1

1125

transcript variant X1

isoform X1

XM_024447080.2

2854

XP_024302848.1

933

transcript variant X4

isoform X4

XM_011544427.3

2533

XP_011542729.1

801

transcript variant X5

isoform X5

XR_008487815.1

2274

transcript variant X6

XM_054359859.1

3579

XP_054215834.1

985

transcript variant X3

isoform X3

XM_054359858.1

3608

XP_054215833.1

1121

transcript variant X2

isoform X2

XM_054359857.1

3620

XP_054215832.1

1125

transcript variant X1

isoform X1

XM_054359860.1

2854

XP_054215835.1

933

transcript variant X4

isoform X4

XM_054359861.1

2533

XP_054215836.1

801

transcript variant X5

isoform X5

Known

NM_008432.3

3548

NP_032458.3

1121

Predicted

XR_003947237.1

3854

transcript variant X6

XR_003947236.1

3795

transcript variant X5

XM_017312583.2

3358

XP_017168072.1

1039

transcript variant X4

isoform X4

XM_006509024.2

3569

XP_006509087.1

1131

transcript variant X1

isoform X1

XM_017312582.1

3374

XP_017168071.1

1066

transcript variant X3

isoform X3

XM_017312581.1

3479

XP_017168070.1

1101

transcript variant X2

isoform X2

Predicted

XR_005494752.1

3086

transcript variant X6

XR_005494753.1

2219

transcript variant X9

XR_005494755.1

1911

transcript variant X11

XR_005494754.1

1914

transcript variant X10

XM_039094932.1

3647

XP_038950860.1

1100

transcript variant X3

isoform X3

XM_039094933.1

3601

XP_038950861.1

1074

transcript variant X4

isoform X4

XM_017600381.2

3713

XP_017455870.1

1123

transcript variant X1

isoform X1

XM_039094934.1

3589

XP_038950862.1

1031

transcript variant X5

isoform X5

XM_006253336.4

3678

XP_006253398.1

1113

transcript variant X2

isoform X2

XM_039094936.1

2462

XP_038950864.1

683

transcript variant X8

isoform X7

XM_039094935.1

3362

XP_038950863.1

924

transcript variant X7

isoform X6

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Post-Translational Modifications

PTM

Position

Type

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Structure

K+ channels formed from α subunits encoded by the Slo gene family (Adelman et al., 1992 [1156]; Butler et al., 1993 [1157]) are characterized by a large cytosolic C-terminal structure that is thought to be involved in ligand-dependent regulation of the channels (Wei et al., 1994 [1158]; Schreiber and Salkoff [1159], 1997; Schreiber et al. , 1998 [1160]; Bhattacharjee et al., 2002 [1161]; Jiang et al., 2002 [625]; Shi et al., 2002 [1131]; Xia et al., 2002 [1136]; Bhattacharjee et al., 2003 [1141]; Yuan et al., 2003 [1139]; Xia et al., 2004 [164]). In fact, the hallmark for each member of the Slo family appears to be regulation by a specific cytosolic ligand: pH for Slo3 (Schreiber et al., 1998 [1160]; Xia et al., 2004 [164]).

Slo3 predicted AlphaFold size

Species	Area (Å²)	Reference
Human	8048.59	source
Mouse	7861.39	source
Rat	7379.14	source

Methodology for AlphaFold size prediction and disclaimer are available here

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Kinetics

Slo1 and Slo3 differ in two primary ways: first, the intrinsic voltage dependence of the Slo3 closed–open equilibrium is weaker, and, second, voltage sensor movement in Slo3 is much more weakly coupled to channel opening. Both activation and deactivation are best described by two exponential components, both of which are only weakly voltage dependent. Qualitatively, the properties of the two kinetic components in the activation time course suggest that increases in pH increase the fraction of more rapidly opening channels. (Zhang [165])

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Expression and Distribution

In contrast to the wide distribution of channels arising from either Slo1 and Slo2.x subunits, Slo3 has a much more limited pattern of expression than the other family members, being found predominantly in mouse testis (Schreiber et al., 1998 [1160]).

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Interaction

In contrast to Slo1, Slo3 is insensitive to cytosolic Ca2+ and appears sensitive to cytosolic pH (Schreiber et al., 1998 [1160]; Xia et al., 2004 [164]).

References

163

Santi CM et al. Bovine and mouse SLO3 K+ channels: evolutionary divergence points to an RCK1 region of critical function.
J. Biol. Chem., 2009 Aug 7 , 284 (21589-98).

164

Xia XM et al. Ligand-dependent activation of Slo family channels is defined by interchangeable cytosolic domains.
J. Neurosci., 2004 Jun 16 , 24 (5585-91).

165

Zhang X et al. Slo3 K+ channels: voltage and pH dependence of macroscopic currents.
J. Gen. Physiol., 2006 Sep , 128 (317-36).

625

Jiang Y et al. Crystal structure and mechanism of a calcium-gated potassium channel.
Nature, 2002 May 30 , 417 (515-22).

1132

Shi J et al. Mechanism of magnesium activation of calcium-activated potassium channels.
Nature, 2002 Aug 22 , 418 (876-80).

1136

Xia XM et al. Multiple regulatory sites in large-conductance calcium-activated potassium channels.
Nature, 2002 Aug 22 , 418 (880-4).

1139

Yuan A et al. The sodium-activated potassium channel is encoded by a member of the Slo gene family.
Neuron, 2003 Mar 6 , 37 (765-73).

1141

Bhattacharjee A et al. Slick (Slo2.1), a rapidly-gating sodium-activated potassium channel inhibited by ATP.
J. Neurosci., 2003 Dec 17 , 23 (11681-91).

1156

Adelman JP et al. Calcium-activated potassium channels expressed from cloned complementary DNAs.
Neuron, 1992 Aug , 9 (209-16).

1157

Butler A et al. mSlo, a complex mouse gene encoding "maxi" calcium-activated potassium channels.
Science, 1993 Jul 9 , 261 (221-4).

1158

Wei A et al. Calcium sensitivity of BK-type KCa channels determined by a separable domain.
Neuron, 1994 Sep , 13 (671-81).

1159

Schreiber M et al. Transplantable sites confer calcium sensitivity to BK channels.
Nat. Neurosci., 1999 May , 2 (416-21).

1160

Schreiber M et al. Slo3, a novel pH-sensitive K+ channel from mammalian spermatocytes.
J. Biol. Chem., 1998 Feb 6 , 273 (3509-16).

1161

Bhattacharjee A et al. Localization of the Slack potassium channel in the rat central nervous system.
J. Comp. Neurol., 2002 Dec 16 , 454 (241-54).

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Credits

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/71/ , accessed on 2024 Dec 21

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