Kcnn4 potassium calcium-activated channel subfamily N member 4 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Kcnn4provided by RGD
Official Full Name: potassium calcium-activated channel subfamily N member 4provided by RGD
Primary source: RGD:621476
See related: EnsemblRapid:ENSRNOG00000019440 AllianceGenome:RGD:621476
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: SMIK; rIK1; rSK4; KCa3.1; rKCNN4c
Summary: Enables intermediate conductance calcium-activated potassium channel activity and inward rectifier potassium channel activity. Involved in several processes, including hepatocyte apoptotic process; regulation of cytokine production; and regulation of systemic arterial blood pressure. Located in apical plasma membrane; basolateral plasma membrane; and neuronal cell body. Used to study hypertension; middle cerebral artery infarction; and temporal lobe epilepsy. Biomarker of type 2 diabetes mellitus. Human ortholog(s) of this gene implicated in angiosarcoma; cerebral infarction; dehydrated hereditary stomatocytosis 2; and myocardial infarction. Orthologous to human KCNN4 (potassium calcium-activated channel subfamily N member 4). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in Thymus (RPKM 103.3), Spleen (RPKM 70.8) and 1 other tissue See more
Orthologs: human mouse all
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Genomic context

Location:: 1q21

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	1	NC_086019.1 (89084306..89102279)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	1	NC_051336.1 (79956380..79974354)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	1	NC_005100.4 (81227855..81245986)

Chromosome 1 - NC_086019.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Corticotropin Releasing Factor Mediates KCa3.1 Inhibition, Hyperexcitability, and Seizures in Acquired Epilepsy.
Title: Corticotropin Releasing Factor Mediates K(Ca)3.1 Inhibition, Hyperexcitability, and Seizures in Acquired Epilepsy.
The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to alkalinization-induced vascular calcification in vitro.
Title: The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to alkalinization-induced vascular calcification in vitro.
KCNN4 Expression Is Elevated in Inflammatory Bowel Disease: This Might Be a Novel Marker and Therapeutic Option Targeting Potassium Channels.
Title: KCNN4 Expression Is Elevated in Inflammatory Bowel Disease: This Might Be a Novel Marker and Therapeutic Option Targeting Potassium Channels.
A critical role of the KCa 3.1 channel in mechanical stretch-induced proliferation of rat bone marrow-derived mesenchymal stem cells.
Title: A critical role of the K(Ca) 3.1 channel in mechanical stretch-induced proliferation of rat bone marrow-derived mesenchymal stem cells.
Ca(2+)-activated KCa3.1 potassium channels contribute to the slow afterhyperpolarization in L5 neocortical pyramidal neurons.
Title: Ca(2+)-activated KCa3.1 potassium channels contribute to the slow afterhyperpolarization in L5 neocortical pyramidal neurons.
adiposederived stem cells transduced with SK4 may be used to generate biological pacemakers in ex vivo rat hearts.
Title: Adipose‑derived stem cells overexpressing SK4 calcium‑activated potassium channel generate biological pacemakers.
The present study provided evidence that SK4 and HCN2 combined could construct an ectopic pacemaker, laying the groundwork for the development of improved biological pacing mechanisms in the future.
Title: Overexpression of the medium‑conductance calcium‑activated potassium channel (SK4) and the HCN2 channel to generate a biological pacemaker.
KC a3.1 channels facilitate myocardial inflammation and the differentiation of bone marrow-derived monocytes into myofibroblasts in cardiac fibrosis caused by angiotensin II infusion.
Title: K(Ca)3.1 Channels Promote Cardiac Fibrosis Through Mediating Inflammation and Differentiation of Monocytes Into Myofibroblasts in Angiotensin II -Treated Rats.
expression significantly decreased in the penile corpus cavernosum of castrated groups, and expression positively correlated with level of androgen
Title: Effect of low androgen levels on IKca and SKca3 channels in rat penile corpus cavernosum.
T-cell dependency on Kv1.3 or KCa3.1 might be irreversibly modulated by antigen exposure.
Title: Potassium channels Kv1.3 and KCa3.1 cooperatively and compensatorily regulate antigen-specific memory T cell functions.

Submit: New GeneRIF Correction See all GeneRIFs (46)

General gene information

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Markers

RH131024 (e-PCR)
- UniSTS:214307

Kcnn4 (e-PCR), detects polymorphism
- UniSTS:507006

D1Got82 (e-PCR)
- UniSTS:111588

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables calcium-activated potassium channel activity	ISO Inferred from Sequence Orthology more info
enables calmodulin binding	IBA Inferred from Biological aspect of Ancestor more info
enables calmodulin binding	IEA Inferred from Electronic Annotation more info
enables calmodulin binding	ISO Inferred from Sequence Orthology more info
enables intermediate conductance calcium-activated potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables intermediate conductance calcium-activated potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables intermediate conductance calcium-activated potassium channel activity	IEA Inferred from Electronic Annotation more info
enables intermediate conductance calcium-activated potassium channel activity	ISO Inferred from Sequence Orthology more info
enables inward rectifier potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables potassium channel activity	ISO Inferred from Sequence Orthology more info
enables protein homodimerization activity	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein phosphatase binding	IEA Inferred from Electronic Annotation more info
enables protein phosphatase binding	ISO Inferred from Sequence Orthology more info
enables small conductance calcium-activated potassium channel activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in calcium ion transport	IEA Inferred from Electronic Annotation more info
involved_in calcium ion transport	ISO Inferred from Sequence Orthology more info
involved_in cardiac muscle hypertrophy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell volume homeostasis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cell volume homeostasis	ISO Inferred from Sequence Orthology more info
involved_in cellular response to hypoxia	IEP Inferred from Expression Pattern more info	PubMed
involved_in establishment of localization in cell	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within establishment of localization in cell	ISO Inferred from Sequence Orthology more info
involved_in hepatocyte apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in macropinocytosis	IEA Inferred from Electronic Annotation more info
involved_in macropinocytosis	ISO Inferred from Sequence Orthology more info
involved_in monoatomic anion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in mononuclear cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cardiac muscle hypertrophy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell volume	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of hepatic stellate cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phospholipid translocation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within phospholipid translocation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of G0 to G1 transition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of T cell receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of T cell receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of microglial cell activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of p38MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein secretion	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of protein secretion	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of smooth muscle cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in potassium ion export across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in potassium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in potassium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in potassium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in protein homotetramerization	IEA Inferred from Electronic Annotation more info
involved_in protein homotetramerization	ISO Inferred from Sequence Orthology more info
involved_in regulation of angiotensin levels in blood	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of calcium ion import across plasma membrane	IEA Inferred from Electronic Annotation more info
involved_in regulation of calcium ion import across plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in regulation of monocyte chemotactic protein-1 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of renin secretion into blood stream	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of smooth muscle cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to hypoxia	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to insulin	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to tetrachloromethane	IEP Inferred from Expression Pattern more info	PubMed
involved_in saliva secretion	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within saliva secretion	ISO Inferred from Sequence Orthology more info
involved_in stabilization of membrane potential	IEA Inferred from Electronic Annotation more info
involved_in stabilization of membrane potential	ISO Inferred from Sequence Orthology more info
involved_in vascular associated smooth muscle cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vascular associated smooth muscle cell proliferation	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor more info
is_active_in neuronal cell body	IBA Inferred from Biological aspect of Ancestor more info
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in ruffle membrane	IEA Inferred from Electronic Annotation more info
located_in ruffle membrane	ISO Inferred from Sequence Orthology more info
located_in vesicle	IEA Inferred from Electronic Annotation more info
located_in vesicle	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: intermediate conductance calcium-activated potassium channel protein 4

Names: IK1; KCa4; SK4; SKCa 4; SKCa4; intermediate conductance K channel; intermediate-conductance Ca-activated K channel; potassium channel, calcium activated intermediate/small conductance subfamily N alpha, member 4; potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4; smooth muscle intermediate-conductance KCa channel

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001270701.1 → NP_001257630.1 intermediate conductance calcium-activated potassium channel protein 4 isoform a

See identical proteins and their annotated locations for NP_001257630.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 3' UTR compared to variant 1. Variants 1 and 2 both encode the same isoform (a).

Source sequence(s)

BC128736, JAXUCZ010000001

UniProtKB/Swiss-Prot

Q9QYW1, Q9R198, Q9WVA5

UniProtKB/TrEMBL

A1A5N3, A6J8Y4, C6ZGH2, C6ZGH3, F1M7L2

Related

ENSRNOP00000084392.2, ENSRNOT00000107668.2

Conserved Domains (3) summary

pfam02888
Location:302 → 371

CaMBD; Calmodulin binding domain

pfam03530
Location:15 → 121

SK_channel; Calcium-activated SK potassium channel

pfam07885
Location:235 → 288

Ion_trans_2; Ion channel
NM_001270702.1 → NP_001257631.1 intermediate conductance calcium-activated potassium channel protein 4 isoform b

See identical proteins and their annotated locations for NP_001257631.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site at the 5' end of an exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.

Source sequence(s)

BC128736, JAXUCZ010000001

UniProtKB/TrEMBL

A0A8I5ZZ67, C6ZGH4

Conserved Domains (3) summary

smart01053
Location:273 → 345

CaMBD; Calmodulin binding domain

pfam03530
Location:15 → 92

SK_channel; Calcium-activated SK potassium channel

pfam07885
Location:206 → 259

Ion_trans_2; Ion channel
NM_001270703.1 → NP_001257632.1 intermediate conductance calcium-activated potassium channel protein 4 isoform c

Status: VALIDATED

Description

Transcript Variant: This variant (4) lacks an alternate segment in the 3' end of the coding sequence compared to variant 1, that causes a frameshift. The resulting isoform (c) has a shorter and distinct C-terminus compared to isoform a.

Source sequence(s)

BC128736, JAXUCZ010000001

UniProtKB/TrEMBL

A9CP48

Conserved Domains (3) summary

pfam03530
Location:15 → 121

SK_channel; Calcium-activated SK potassium channel

pfam07885
Location:235 → 288

Ion_trans_2; Ion channel

cl03763
Location:302 → 351

CaMBD; Calmodulin binding domain
NM_023021.2 → NP_075410.2 intermediate conductance calcium-activated potassium channel protein 4 isoform a

See identical proteins and their annotated locations for NP_075410.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a). Variants 1 and 2 both encode the same isoform (a).

Source sequence(s)

BC128736, JAXUCZ010000001

UniProtKB/Swiss-Prot

Q9QYW1, Q9R198, Q9WVA5

UniProtKB/TrEMBL

A1A5N3, A6J8Y4, C6ZGH2, C6ZGH3, F1M7L2

Conserved Domains (3) summary

pfam02888
Location:302 → 371

CaMBD; Calmodulin binding domain

pfam03530
Location:15 → 121

SK_channel; Calcium-activated SK potassium channel

pfam07885
Location:235 → 288

Ion_trans_2; Ion channel

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCr8

Genomic

NC_086019.1 Reference GRCr8

Range

89084306..89102279

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_063272991.1 → XP_063129061.1 intermediate conductance calcium-activated potassium channel protein 4 isoform X2

UniProtKB/TrEMBL

A0A8I6A0D8

Related

ENSRNOP00000083641.1, ENSRNOT00000098055.2
XM_006228471.3 → XP_006228533.1 intermediate conductance calcium-activated potassium channel protein 4 isoform X7

UniProtKB/TrEMBL

A0A0G2K4V7, A9CP48

Related

ENSRNOP00000073190.2, ENSRNOT00000077952.3

Conserved Domains (3) summary

pfam03530
Location:15 → 121

SK_channel; Calcium-activated SK potassium channel

pfam07885
Location:235 → 288

Ion_trans_2; Ion channel

cl03763
Location:302 → 351

CaMBD; Calmodulin binding domain
XM_063272995.1 → XP_063129065.1 intermediate conductance calcium-activated potassium channel protein 4 isoform X3

UniProtKB/TrEMBL

A0A8I5ZZ67

Related

ENSRNOP00000026489.7, ENSRNOT00000026489.9
XM_063273007.1 → XP_063129077.1 intermediate conductance calcium-activated potassium channel protein 4 isoform X5

UniProtKB/TrEMBL

A6J8Y3
XM_017589696.3 → XP_017445185.1 intermediate conductance calcium-activated potassium channel protein 4 isoform X1

UniProtKB/TrEMBL

A0A8I6A0D8

Conserved Domains (3) summary

pfam02888
Location:307 → 376

CaMBD; Calmodulin binding domain

pfam03530
Location:61 → 126

SK_channel; Calcium-activated SK potassium channel

pfam07885
Location:240 → 293

Ion_trans_2; Ion channel
XM_006228469.3 → XP_006228531.1 intermediate conductance calcium-activated potassium channel protein 4 isoform X1

UniProtKB/TrEMBL

A0A8I6A0D8

Conserved Domains (3) summary

pfam02888
Location:307 → 376

CaMBD; Calmodulin binding domain

pfam03530
Location:61 → 126

SK_channel; Calcium-activated SK potassium channel

pfam07885
Location:240 → 293

Ion_trans_2; Ion channel
XM_063273000.1 → XP_063129070.1 intermediate conductance calcium-activated potassium channel protein 4 isoform X4
XM_039090032.2 → XP_038945960.1 intermediate conductance calcium-activated potassium channel protein 4 isoform X6

Conserved Domains (1) summary

pfam03530
Location:61 → 126

SK_channel; Calcium-activated SK potassium channel