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    KCNN1 potassium calcium-activated channel subfamily N member 1 [ Homo sapiens (human) ]

    Gene ID: 3780, updated on 3-Apr-2024

    Summary

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    Official Symbol
    KCNN1provided by HGNC
    Official Full Name
    potassium calcium-activated channel subfamily N member 1provided by HGNC
    Primary source
    HGNC:HGNC:6290
    See related
    Ensembl:ENSG00000105642 MIM:602982; AllianceGenome:HGNC:6290
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SK1; hSK1; SKCA1; KCa2.1
    Summary
    Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. The protein encoded by this gene is activated before membrane hyperpolarization and is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. The encoded protein is an integral membrane protein that forms a voltage-independent calcium-activated channel with three other calmodulin-binding subunits. This gene is a member of the KCNN family of potassium channel genes. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in brain (RPKM 5.8), testis (RPKM 0.7) and 1 other tissue See more
    Orthologs
    mouse all
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    Genomic context

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    See KCNN1 in Genome Data Viewer
    Location:
    19p13.11
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (17951290..18000085)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (18085382..18134163)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (18062099..18110894)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:17984524-17985296 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:17988651-17989150 Neighboring gene solute carrier family 5 member 5 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14288 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:18029877-18030622 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:18030623-18031368 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:18033123-18033624 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14289 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14290 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:18042902-18043440 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14291 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14292 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10363 Neighboring gene coiled-coil domain containing 124 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10364 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18062016-18062634 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18062635-18063252 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18063253-18063870 Neighboring gene MPRA-validated peak3398 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18073163-18073735 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18076903-18077620 Neighboring gene MPRA-validated peak3399 silencer Neighboring gene RNA, 5S ribosomal pseudogene 468 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18095189-18095870 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18098837-18099338 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18099339-18099838 Neighboring gene Sharpr-MPRA regulatory region 11250 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18107595-18108096 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10367 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14293 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18124072-18124572 Neighboring gene arrestin domain containing 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14294 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:18132997-18133546 Neighboring gene CS pseudogene 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Differential regulation of K(Ca) 2.1 (KCNN1) K(+) channel expression by histone deacetylases in atrial fibrillation with concomitant heart failure. Rahm AK, et al. Physiol Rep, 2021 Jun. PMID 34111326, Free PMC Article
    2. Targeting K(ca)3.1 Channels in Cancer. Todesca LM, et al. Cell Physiol Biochem, 2021 May 28. PMID 34043300
    3. Calcium-activated potassium channel SK1- and IK1-like immunoreactivity in injured human sensory neurones and its regulation by neurotrophic factors. Boettger MK, et al. Brain, 2002 Feb. PMID 11844726
    4. Calmodulin binding to the C-terminus of the small-conductance Ca2+-activated K+ channel hSK1 is affected by alternative splicing. Zhang BM, et al. Biochemistry, 2001 Mar 13. PMID 11258935
    5. The pharmacology of hSK1 Ca2+-activated K+ channels expressed in mammalian cell lines. Shah M, et al. Br J Pharmacol, 2000 Feb. PMID 10683185, Free PMC Article

    See all (24) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. KCNN1 promotes proliferation and metastasis of breast cancer via ERLIN2-mediated stabilization and K63-dependent ubiquitination of Cyclin B1.
      Title: KCNN1 promotes proliferation and metastasis of breast cancer via ERLIN2-mediated stabilization and K63-dependent ubiquitination of Cyclin B1.
    2. A single coiled-coil domain mutation in hIKCa channel subunits disrupts preferential formation of heteromeric hSK1:hIKCa channels.
      Title: A single coiled-coil domain mutation in hIKCa channel subunits disrupts preferential formation of heteromeric hSK1:hIKCa channels.
    3. Differential regulation of KCa 2.1 (KCNN1) K(+) channel expression by histone deacetylases in atrial fibrillation with concomitant heart failure.
      Title: Differential regulation of K(Ca) 2.1 (KCNN1) K(+) channel expression by histone deacetylases in atrial fibrillation with concomitant heart failure.
    4. Targeting Kca3.1 Channels in Cancer.
      Title: Targeting K(ca)3.1 Channels in Cancer.
    5. Data demonstrate that IKCa and SK1 subunits prefer to form heteromeric channels when coexpressed in a heterologous system that will alter their responsiveness to pharmacological tools typically used to define their expression pattern.
      Title: Preferred Formation of Heteromeric Channels between Coexpressed SK1 and IKCa Channel Subunits Provides a Unique Pharmacological Profile of Ca(2+)-Activated Potassium Channels.
    6. SK current is increased via the enhanced activation of CaMKII in patients with atrial fibrillation.
      Title: Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII) Increases Small-Conductance Ca2+-Activated K+ Current in Patients with Chronic Atrial Fibrillation.
    7. Differentiated dopaminergic neurons expressed low levels of SK2 channels and high levels of SK1 and SK3 channels.
      Title: Subcellular expression and neuroprotective effects of SK channels in human dopaminergic neurons.
    8. Decreased expression of small-conductance Ca2+-activated K+ channels SK1 and SK2 in human chronic atrial fibrillation.
      Title: Decreased expression of small-conductance Ca2+-activated K+ channels SK1 and SK2 in human chronic atrial fibrillation.
    9. IK1-like immunoreactivity is observed in enteric neurons of human colon, with a significant decrease of IK1-positive cells in inflamed colon from patients with Crohn's disease and ulcerative colitis.
      Title: Decreased potassium channel IK1 and its regulator neurotrophin-3 (NT-3) in inflamed human bowel.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of potassium intermediate/small conductance calcium-activated channel, subfamily N, member 1 (KCNN1) by siRNA enhances the early stages of HIV-1 replication in HeLa-CD4 cells infected with viral pseudotypes HIV89.6R and HIV8.2N PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 from both CCR5- and CXCR4-tropic HIV-1 strains opens calcium-activated potassium (K(Ca)), chloride, and calcium-permeant nonselective cation channels in macrophages; these signals are mediated by CCR5 and CXCR4 PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium-activated potassium channel activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables calmodulin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables inward rectifier potassium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables small conductance calcium-activated potassium channel activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables small conductance calcium-activated potassium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in chemical synaptic transmission TAS
    Traceable Author Statement
    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 transport TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    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
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of voltage-gated potassium channel complex TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    small conductance calcium-activated potassium channel protein 1
    Names
    potassium channel, calcium activated intermediate/small conductance subfamily N alpha, member 1
    potassium intermediate/small conductance calcium-activated channel, subfamily N, member 1
    small conductance calcium-activated potassium channel 1

    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.

    Genomic

    1. NG_029893.1 RefSeqGene

      Range
      20806..53784
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001386974.1 → NP_001373903.1  small conductance calcium-activated potassium channel protein 1 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC020904
      Consensus CDS
      CCDS67611.1
      UniProtKB/Swiss-Prot
      Q5KR10, Q6DJU4, Q92952
      UniProtKB/TrEMBL
      A0A087X2E7
      Related
      ENSP00000507021.1, ENST00000684775.1
      Conserved Domains (3) summary
      smart01053
      Location:384 → 461
      CaMBD; Calmodulin binding domain
      pfam03530
      Location:96 → 203
      SK_channel; Calcium-activated SK potassium channel
      pfam07885
      Location:291 → 370
      Ion_trans_2; Ion channel

    2. NM_001386975.1 → NP_001373904.1  small conductance calcium-activated potassium channel protein 1 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC020904
      Consensus CDS
      CCDS92562.1
      UniProtKB/TrEMBL
      A0A087X2E7, A0A804HIW7
      Related
      ENSP00000507977.1, ENST00000683588.1
      Conserved Domains (3) summary
      smart01053
      Location:387 → 464
      CaMBD; Calmodulin binding domain
      pfam03530
      Location:96 → 203
      SK_channel; Calcium-activated SK potassium channel
      pfam07885
      Location:291 → 373
      Ion_trans_2; Ion channel

    3. NM_001386976.1 → NP_001373905.1  small conductance calcium-activated potassium channel protein 1 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC005602, AC020904
      Consensus CDS
      CCDS92562.1
      UniProtKB/TrEMBL
      A0A087X2E7, A0A804HIW7
      Related
      ENSP00000507255.1, ENST00000682733.1
      Conserved Domains (3) summary
      smart01053
      Location:387 → 464
      CaMBD; Calmodulin binding domain
      pfam03530
      Location:96 → 203
      SK_channel; Calcium-activated SK potassium channel
      pfam07885
      Location:291 → 373
      Ion_trans_2; Ion channel

    4. NM_001386977.1 → NP_001373906.1  small conductance calcium-activated potassium channel protein 1 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC020904
      Consensus CDS
      CCDS92563.1
      UniProtKB/TrEMBL
      A0A087X2E7, A0A804HIF9
      Related
      ENSP00000507047.1, ENST00000682421.1
      Conserved Domains (3) summary
      smart01053
      Location:384 → 458
      CaMBD; Calmodulin binding domain
      pfam03530
      Location:96 → 203
      SK_channel; Calcium-activated SK potassium channel
      pfam07885
      Location:291 → 370
      Ion_trans_2; Ion channel

    5. NM_002248.5 → NP_002239.2  small conductance calcium-activated potassium channel protein 1 isoform 1

      See identical proteins and their annotated locations for NP_002239.2

      Status: REVIEWED

      Source sequence(s)
      AC005602, AC020904
      Consensus CDS
      CCDS67611.1
      UniProtKB/Swiss-Prot
      Q5KR10, Q6DJU4, Q92952
      UniProtKB/TrEMBL
      A0A087X2E7
      Related
      ENSP00000476519.1, ENST00000222249.13
      Conserved Domains (3) summary
      smart01053
      Location:384 → 461
      CaMBD; Calmodulin binding domain
      pfam03530
      Location:96 → 203
      SK_channel; Calcium-activated SK potassium channel
      pfam07885
      Location:291 → 370
      Ion_trans_2; Ion channel

    RNA

    1. NR_170373.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC020904
      Related
      ENST00000683930.1

    2. NR_170374.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC020904
      Related
      ENST00000682726.1

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      17951290..18000085
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011528004.2 → XP_011526306.1  small conductance calcium-activated potassium channel protein 1 isoform X1

      UniProtKB/TrEMBL
      A0A087X2E7
      Related
      ENSP00000484926.2, ENST00000615435.2
      Conserved Domains (4) summary
      pfam02888
      Location:470 → 542
      CaMBD; Calmodulin binding domain
      pfam03530
      Location:179 → 286
      SK_channel; Calcium-activated SK potassium channel
      pfam07885
      Location:374 → 456
      Ion_trans_2; Ion channel
      pfam15240
      Location:35 → 146
      Pro-rich; Proline-rich

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      18085382..18134163
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054320942.1 → XP_054176917.1  small conductance calcium-activated potassium channel protein 1 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q92952.2 GenPept UniProtKB/Swiss-Prot:Q92952

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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