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Q9UGI6

- KCNN3_HUMAN

UniProt

Q9UGI6 - KCNN3_HUMAN

Protein

Small conductance calcium-activated potassium channel protein 3

Gene

KCNN3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
    • BLAST
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 1 (01 May 2000)
      Previous versions | rss
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    Functioni

    Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.

    GO - Molecular functioni

    1. calmodulin binding Source: RefGenome
    2. small conductance calcium-activated potassium channel activity Source: RefGenome

    GO - Biological processi

    1. potassium ion transmembrane transport Source: RefGenome
    2. synaptic transmission Source: Reactome

    Keywords - Molecular functioni

    Ion channel

    Keywords - Biological processi

    Ion transport, Transport

    Keywords - Ligandi

    Calmodulin-binding

    Enzyme and pathway databases

    ReactomeiREACT_75896. Ca2+ activated K+ channels.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Small conductance calcium-activated potassium channel protein 3
    Short name:
    SK3
    Short name:
    SKCa 3
    Short name:
    SKCa3
    Alternative name(s):
    KCa2.3
    Gene namesi
    Name:KCNN3
    Synonyms:K3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:6292. KCNN3.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW
    2. neuronal cell body Source: RefGenome
    3. plasma membrane Source: RefGenome

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA30072.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 736736Small conductance calcium-activated potassium channel protein 3PRO_0000155013Add
    BLAST

    Proteomic databases

    MaxQBiQ9UGI6.
    PaxDbiQ9UGI6.
    PRIDEiQ9UGI6.

    PTM databases

    PhosphoSiteiQ9UGI6.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9UGI6.
    BgeeiQ9UGI6.
    CleanExiHS_KCNN3.
    GenevestigatoriQ9UGI6.

    Organism-specific databases

    HPAiHPA017990.

    Interactioni

    Subunit structurei

    Heterooligomer. The complex is composed of 4 channel subunits each of which binds to a calmodulin subunit which regulates the channel activity through calcium-binding By similarity.By similarity

    Protein-protein interaction databases

    BioGridi109983. 6 interactions.
    STRINGi9606.ENSP00000271915.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9UGI6.
    SMRiQ9UGI6. Positions 480-679.
    ModBaseiSearch...
    MobiDBiSearch...

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei499 – 51921Pore-forming; Name=Segment H5Sequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei293 – 31321Helical; Name=Segment S1Sequence AnalysisAdd
    BLAST
    Transmembranei320 – 34021Helical; Name=Segment S2Sequence AnalysisAdd
    BLAST
    Transmembranei371 – 39121Helical; Name=Segment S3Sequence AnalysisAdd
    BLAST
    Transmembranei410 – 43021Helical; Name=Segment S4Sequence AnalysisAdd
    BLAST
    Transmembranei459 – 47921Helical; Name=Segment S5Sequence AnalysisAdd
    BLAST
    Transmembranei528 – 54821Helical; Name=Segment S6Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni566 – 64277Calmodulin-bindingBy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi30 – 9970Gln-richAdd
    BLAST
    Compositional biasi42 – 6423Pro-richAdd
    BLAST
    Compositional biasi688 – 6925Poly-Gln
    Compositional biasi732 – 7354Poly-Ser

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG320393.
    HOGENOMiHOG000276908.
    HOVERGENiHBG052241.
    InParanoidiQ9UGI6.
    KOiK04944.
    OrthoDBiEOG73FQMC.
    PhylomeDBiQ9UGI6.
    TreeFamiTF315015.

    Family and domain databases

    InterProiIPR013099. 2pore_dom_K_chnl_dom.
    IPR004178. CaM-bd_dom.
    IPR015449. K_chnl_Ca-activ_SK.
    [Graphical view]
    PANTHERiPTHR10153. PTHR10153. 1 hit.
    PfamiPF02888. CaMBD. 1 hit.
    PF07885. Ion_trans_2. 1 hit.
    PF03530. SK_channel. 1 hit.
    [Graphical view]
    PRINTSiPR01451. SKCHANNEL.
    SMARTiSM01053. CaMBD. 1 hit.
    [Graphical view]
    SUPFAMiSSF81327. SSF81327. 1 hit.

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9UGI6-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MDTSGHFHDS GVGDLDEDPK CPCPSSGDEQ QQQQQQQQQQ QPPPPAPPAA    50
    PQQPLGPSLQ PQPPQLQQQQ QQQQQQQQQQ QQQQQPPHPL SQLAQLQSQP 100
    VHPGLLHSSP TAFRAPPSSN STAILHPSSR QGSQLNLNDH LLGHSPSSTA 150
    TSGPGGGSRH RQASPLVHRR DSNPFTEIAM SSCKYSGGVM KPLSRLSASR 200
    RNLIEAETEG QPLQLFSPSN PPEIVISSRE DNHAHQTLLH HPNATHNHQH 250
    AGTTASSTTF PKANKRKNQN IGYKLGHRRA LFEKRKRLSD YALIFGMFGI 300
    VVMVIETELS WGLYSKDSMF SLALKCLISL STIILLGLII AYHTREVQLF 350
    VIDNGADDWR IAMTYERILY ISLEMLVCAI HPIPGEYKFF WTARLAFSYT 400
    PSRAEADVDI ILSIPMFLRL YLIARVMLLH SKLFTDASSR SIGALNKINF 450
    NTRFVMKTLM TICPGTVLLV FSISLWIIAA WTVRVCERYH DQQDVTSNFL 500
    GAMWLISITF LSIGYGDMVP HTYCGKGVCL LTGIMGAGCT ALVVAVVARK 550
    LELTKAEKHV HNFMMDTQLT KRIKNAAANV LRETWLIYKH TKLLKKIDHA 600
    KVRKHQRKFL QAIHQLRSVK MEQRKLSDQA NTLVDLSKMQ NVMYDLITEL 650
    NDRSEDLEKQ IGSLESKLEH LTASFNSLPL LIADTLRQQQ QQLLSAIIEA 700
    RGVSVAVGTT HTPISDSPIG VSSTSFPTPY TSSSSC 736
    Length:736
    Mass (Da):82,026
    Last modified:May 1, 2000 - v1
    Checksum:iCCD0CC1621FFAE9C
    GO
    Isoform 2 (identifier: Q9UGI6-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-310: Missing.
         311-315: WGLYS → MERPI

    Show »
    Length:426
    Mass (Da):48,050
    Checksum:i1EBE12900FA7719D
    GO
    Isoform 3 (identifier: Q9UGI6-3) [UniParc]FASTAAdd to Basket

    Also known as: SK3-1B

    The sequence of this isoform differs from the canonical sequence as follows:
         1-318: Missing.

    Note: Do not produce functional channels, but selectively suppresses endogenous SK3 currents, in a dominant-negative fashion. This dominant inhibitory effect extends to other members of the SK subfamily. Widely distributed in human tissues and is present at 20-60% of SK3 in the brain.

    Show »
    Length:418
    Mass (Da):47,093
    Checksum:iB4CD0E43E758BDC8
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti254 – 2541T → A in AAC26099. (PubMed:9491810)Curated
    Sequence conflicti281 – 2811L → P in AAC26099. (PubMed:9491810)Curated
    Sequence conflicti347 – 3471V → A in AAC26099. (PubMed:9491810)Curated
    Sequence conflicti485 – 4851V → A in AAC26099. (PubMed:9491810)Curated

    Polymorphismi

    The second poly-Gln region of KCNN3 is highly polymorphic and the number of Gln varies from 12 to 28 in the population.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti81 – 855Missing.
    VAR_012204

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 318318Missing in isoform 3. 1 PublicationVSP_047641Add
    BLAST
    Alternative sequencei1 – 310310Missing in isoform 2. 2 PublicationsVSP_039461Add
    BLAST
    Alternative sequencei311 – 3155WGLYS → MERPI in isoform 2. 2 PublicationsVSP_039462

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF031815 mRNA. Translation: AAC26099.1.
    AJ251016 mRNA. Translation: CAB61331.1.
    AF438203 mRNA. Translation: AAL40801.1.
    AF336797 Genomic DNA. Translation: AAK15345.1.
    AY138900 mRNA. Translation: AAN46636.1.
    AL390204, AL606500, AL954342 Genomic DNA. Translation: CAH71150.1.
    AL390204, AL606500, AL954342 Genomic DNA. Translation: CAH71151.1.
    AL606500, AL390204, AL954342 Genomic DNA. Translation: CAH71910.1.
    AL606500, AL390204, AL954342 Genomic DNA. Translation: CAH71911.1.
    AL954342, AL390204, AL606500 Genomic DNA. Translation: CAH72738.1.
    AL954342, AL390204, AL606500 Genomic DNA. Translation: CAH72739.1.
    CH471121 Genomic DNA. Translation: EAW53180.1.
    CH471121 Genomic DNA. Translation: EAW53182.1.
    BC042147 mRNA. Translation: AAH42147.1.
    CCDSiCCDS1072.1. [Q9UGI6-2]
    RefSeqiNP_001191016.1. NM_001204087.1.
    NP_002240.3. NM_002249.5.
    NP_740752.1. NM_170782.2. [Q9UGI6-2]
    UniGeneiHs.490765.

    Genome annotation databases

    EnsembliENST00000358505; ENSP00000351295; ENSG00000143603. [Q9UGI6-3]
    ENST00000361147; ENSP00000354764; ENSG00000143603. [Q9UGI6-2]
    GeneIDi3782.
    KEGGihsa:3782.
    UCSCiuc001ffo.3. human. [Q9UGI6-2]
    uc031ppq.1. human. [Q9UGI6-1]

    Polymorphism databases

    DMDMi17367120.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF031815 mRNA. Translation: AAC26099.1 .
    AJ251016 mRNA. Translation: CAB61331.1 .
    AF438203 mRNA. Translation: AAL40801.1 .
    AF336797 Genomic DNA. Translation: AAK15345.1 .
    AY138900 mRNA. Translation: AAN46636.1 .
    AL390204 , AL606500 , AL954342 Genomic DNA. Translation: CAH71150.1 .
    AL390204 , AL606500 , AL954342 Genomic DNA. Translation: CAH71151.1 .
    AL606500 , AL390204 , AL954342 Genomic DNA. Translation: CAH71910.1 .
    AL606500 , AL390204 , AL954342 Genomic DNA. Translation: CAH71911.1 .
    AL954342 , AL390204 , AL606500 Genomic DNA. Translation: CAH72738.1 .
    AL954342 , AL390204 , AL606500 Genomic DNA. Translation: CAH72739.1 .
    CH471121 Genomic DNA. Translation: EAW53180.1 .
    CH471121 Genomic DNA. Translation: EAW53182.1 .
    BC042147 mRNA. Translation: AAH42147.1 .
    CCDSi CCDS1072.1. [Q9UGI6-2 ]
    RefSeqi NP_001191016.1. NM_001204087.1.
    NP_002240.3. NM_002249.5.
    NP_740752.1. NM_170782.2. [Q9UGI6-2 ]
    UniGenei Hs.490765.

    3D structure databases

    ProteinModelPortali Q9UGI6.
    SMRi Q9UGI6. Positions 480-679.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109983. 6 interactions.
    STRINGi 9606.ENSP00000271915.

    Chemistry

    BindingDBi Q9UGI6.
    ChEMBLi CHEMBL3381.
    GuidetoPHARMACOLOGYi 383.

    PTM databases

    PhosphoSitei Q9UGI6.

    Polymorphism databases

    DMDMi 17367120.

    Proteomic databases

    MaxQBi Q9UGI6.
    PaxDbi Q9UGI6.
    PRIDEi Q9UGI6.

    Protocols and materials databases

    DNASUi 3782.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000358505 ; ENSP00000351295 ; ENSG00000143603 . [Q9UGI6-3 ]
    ENST00000361147 ; ENSP00000354764 ; ENSG00000143603 . [Q9UGI6-2 ]
    GeneIDi 3782.
    KEGGi hsa:3782.
    UCSCi uc001ffo.3. human. [Q9UGI6-2 ]
    uc031ppq.1. human. [Q9UGI6-1 ]

    Organism-specific databases

    CTDi 3782.
    GeneCardsi GC01M154680.
    H-InvDB HIX0023527.
    HGNCi HGNC:6292. KCNN3.
    HPAi HPA017990.
    MIMi 602983. gene.
    neXtProti NX_Q9UGI6.
    PharmGKBi PA30072.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG320393.
    HOGENOMi HOG000276908.
    HOVERGENi HBG052241.
    InParanoidi Q9UGI6.
    KOi K04944.
    OrthoDBi EOG73FQMC.
    PhylomeDBi Q9UGI6.
    TreeFami TF315015.

    Enzyme and pathway databases

    Reactomei REACT_75896. Ca2+ activated K+ channels.

    Miscellaneous databases

    GeneWikii SK3.
    GenomeRNAii 3782.
    NextBioi 14843.
    PROi Q9UGI6.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9UGI6.
    Bgeei Q9UGI6.
    CleanExi HS_KCNN3.
    Genevestigatori Q9UGI6.

    Family and domain databases

    InterProi IPR013099. 2pore_dom_K_chnl_dom.
    IPR004178. CaM-bd_dom.
    IPR015449. K_chnl_Ca-activ_SK.
    [Graphical view ]
    PANTHERi PTHR10153. PTHR10153. 1 hit.
    Pfami PF02888. CaMBD. 1 hit.
    PF07885. Ion_trans_2. 1 hit.
    PF03530. SK_channel. 1 hit.
    [Graphical view ]
    PRINTSi PR01451. SKCHANNEL.
    SMARTi SM01053. CaMBD. 1 hit.
    [Graphical view ]
    SUPFAMi SSF81327. SSF81327. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder?"
      Chandy K.G., Fantino E., Wittekindt O., Kalman K., Tong L.-L., Ho T.-H., Gutman G.A., Crocq M.-A., Ganguli R., Nimgaonkar V., Morris-Rosendahl D.J., Gargus J.J.
      Mol. Psychiatry 3:32-37(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), POLYMORPHISM OF POLY-GLN REGION.
    2. Terstappen G.C., Pula G., Chen M.X., Roncarati R.
      Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "Splice variants of small conductance calcium-activated potassium channel gene, KCNN3/ SKCa3 cause dominant-negative suppression of SKCa currents."
      Tomita H., Shakkottai V., Wulff H., Sun G., Potkin S.G., Bunney W.E., Chandy G.K., Gargus J.J.
      Am. J. Hum. Genet. 69S:569-569(2001)
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    4. "Genomic organization and promoter analysis of human KCNN3 gene."
      Sun G., Tomita H., Shakkottai V.G., Gargus J.J.
      J. Hum. Genet. 46:463-470(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
    5. "Novel truncated isoform of SK3 potassium channel is a potent dominant-negative regulator of SK currents: implications in schizophrenia."
      Tomita H., Shakkottai V.G., Gutman G.A., Sun G., Bunney W.E., Cahalan M.D., Chandy K.G., Gargus J.J.
      Mol. Psychiatry 8:524-535(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
    6. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Lymph.

    Entry informationi

    Entry nameiKCNN3_HUMAN
    AccessioniPrimary (citable) accession number: Q9UGI6
    Secondary accession number(s): B1ANX0
    , O43517, Q86VF9, Q8WXG7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 16, 2001
    Last sequence update: May 1, 2000
    Last modified: October 1, 2014
    This is version 122 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3