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Protein

Small conductance calcium-activated potassium channel protein 3

Gene

KCNN3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

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: GO_Central
  2. small conductance calcium-activated potassium channel activity Source: GO_Central

GO - Biological processi

  1. positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
  2. potassium ion transmembrane transport Source: GO_Central
  3. synaptic transmission Source: Reactome
Complete GO annotation...

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 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:6292. KCNN3.

Subcellular locationi

Topology

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
Intramembranei499 – 51921Pore-forming; Name=Segment H5Sequence AnalysisAdd
BLAST
Transmembranei528 – 54821Helical; Name=Segment S6Sequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. neuronal cell body Source: GO_Central
  3. plasma membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30072.

Chemistry

DrugBankiDB01110. Miconazole.
DB00721. Procaine.

Polymorphism and mutation databases

BioMutaiKCNN3.
DMDMi17367120.

PTM / Processingi

Molecule processing

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

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei314 – 3141PhosphotyrosineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9UGI6.
PaxDbiQ9UGI6.
PRIDEiQ9UGI6.

PTM databases

PhosphoSiteiQ9UGI6.

Expressioni

Gene expression databases

BgeeiQ9UGI6.
CleanExiHS_KCNN3.
ExpressionAtlasiQ9UGI6. baseline and differential.
GenevestigatoriQ9UGI6.

Organism-specific databases

HPAiHPA017990.
HPA057127.

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 549-679.
ModBaseiSearch...
MobiDBiSearch...

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.
GeneTreeiENSGT00500000044784.
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. AlignAdd to basket

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

        10         20         30         40         50
MDTSGHFHDS GVGDLDEDPK CPCPSSGDEQ QQQQQQQQQQ QPPPPAPPAA
60 70 80 90 100
PQQPLGPSLQ PQPPQLQQQQ QQQQQQQQQQ QQQQQPPHPL SQLAQLQSQP
110 120 130 140 150
VHPGLLHSSP TAFRAPPSSN STAILHPSSR QGSQLNLNDH LLGHSPSSTA
160 170 180 190 200
TSGPGGGSRH RQASPLVHRR DSNPFTEIAM SSCKYSGGVM KPLSRLSASR
210 220 230 240 250
RNLIEAETEG QPLQLFSPSN PPEIVISSRE DNHAHQTLLH HPNATHNHQH
260 270 280 290 300
AGTTASSTTF PKANKRKNQN IGYKLGHRRA LFEKRKRLSD YALIFGMFGI
310 320 330 340 350
VVMVIETELS WGLYSKDSMF SLALKCLISL STIILLGLII AYHTREVQLF
360 370 380 390 400
VIDNGADDWR IAMTYERILY ISLEMLVCAI HPIPGEYKFF WTARLAFSYT
410 420 430 440 450
PSRAEADVDI ILSIPMFLRL YLIARVMLLH SKLFTDASSR SIGALNKINF
460 470 480 490 500
NTRFVMKTLM TICPGTVLLV FSISLWIIAA WTVRVCERYH DQQDVTSNFL
510 520 530 540 550
GAMWLISITF LSIGYGDMVP HTYCGKGVCL LTGIMGAGCT ALVVAVVARK
560 570 580 590 600
LELTKAEKHV HNFMMDTQLT KRIKNAAANV LRETWLIYKH TKLLKKIDHA
610 620 630 640 650
KVRKHQRKFL QAIHQLRSVK MEQRKLSDQA NTLVDLSKMQ NVMYDLITEL
660 670 680 690 700
NDRSEDLEKQ IGSLESKLEH LTASFNSLPL LIADTLRQQQ QQLLSAIIEA
710 720 730
RGVSVAVGTT HTPISDSPIG VSSTSFPTPY TSSSSC
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:
EMBLi
GenBanki
DDBJi
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 and mutation databases

BioMutaiKCNN3.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliQ9UGI6.
SMRiQ9UGI6. Positions 549-679.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109983. 6 interactions.
STRINGi9606.ENSP00000271915.

Chemistry

BindingDBiQ9UGI6.
ChEMBLiCHEMBL3381.
DrugBankiDB01110. Miconazole.
DB00721. Procaine.
GuidetoPHARMACOLOGYi383.

PTM databases

PhosphoSiteiQ9UGI6.

Polymorphism and mutation databases

BioMutaiKCNN3.
DMDMi17367120.

Proteomic databases

MaxQBiQ9UGI6.
PaxDbiQ9UGI6.
PRIDEiQ9UGI6.

Protocols and materials databases

DNASUi3782.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi3782.
GeneCardsiGC01M154669.
H-InvDBHIX0023527.
HGNCiHGNC:6292. KCNN3.
HPAiHPA017990.
HPA057127.
MIMi602983. gene.
neXtProtiNX_Q9UGI6.
PharmGKBiPA30072.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG320393.
GeneTreeiENSGT00500000044784.
HOGENOMiHOG000276908.
HOVERGENiHBG052241.
InParanoidiQ9UGI6.
KOiK04944.
OrthoDBiEOG73FQMC.
PhylomeDBiQ9UGI6.
TreeFamiTF315015.

Enzyme and pathway databases

ReactomeiREACT_75896. Ca2+ activated K+ channels.

Miscellaneous databases

ChiTaRSiKCNN3. human.
GeneWikiiSK3.
GenomeRNAii3782.
NextBioi14843.
PROiQ9UGI6.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UGI6.
CleanExiHS_KCNN3.
ExpressionAtlasiQ9UGI6. baseline and differential.
GenevestigatoriQ9UGI6.

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.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: April 29, 2015
This is version 128 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.