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Q9UGI6 (KCNN3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:KCNN3
Synonyms:K3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length736 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Subunit structure

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.

Subcellular location

Membrane; Multi-pass membrane protein.

Polymorphism

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

Sequence similarities

Belongs to the potassium channel KCNN family. KCa2.3/KCNN3 subfamily.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UGI6-1)

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.
Isoform 2 (identifier: Q9UGI6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-310: Missing.
     311-315: WGLYS → MERPI
Isoform 3 (identifier: Q9UGI6-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 736736Small conductance calcium-activated potassium channel protein 3
PRO_0000155013

Regions

Transmembrane293 – 31321Helical; Name=Segment S1; Potential
Transmembrane320 – 34021Helical; Name=Segment S2; Potential
Transmembrane371 – 39121Helical; Name=Segment S3; Potential
Transmembrane410 – 43021Helical; Name=Segment S4; Potential
Transmembrane459 – 47921Helical; Name=Segment S5; Potential
Intramembrane499 – 51921Pore-forming; Name=Segment H5; Potential
Transmembrane528 – 54821Helical; Name=Segment S6; Potential
Region566 – 64277Calmodulin-binding By similarity
Compositional bias30 – 9970Gln-rich
Compositional bias42 – 6423Pro-rich
Compositional bias688 – 6925Poly-Gln
Compositional bias732 – 7354Poly-Ser

Natural variations

Alternative sequence1 – 318318Missing in isoform 3.
VSP_047641
Alternative sequence1 – 310310Missing in isoform 2.
VSP_039461
Alternative sequence311 – 3155WGLYS → MERPI in isoform 2.
VSP_039462
Natural variant81 – 855Missing.
VAR_012204

Experimental info

Sequence conflict2541T → A in AAC26099. Ref.1
Sequence conflict2811L → P in AAC26099. Ref.1
Sequence conflict3471V → A in AAC26099. Ref.1
Sequence conflict4851V → A in AAC26099. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: CCD0CC1621FFAE9C

FASTA73682,026
        10         20         30         40         50         60 
MDTSGHFHDS GVGDLDEDPK CPCPSSGDEQ QQQQQQQQQQ QPPPPAPPAA PQQPLGPSLQ 

        70         80         90        100        110        120 
PQPPQLQQQQ QQQQQQQQQQ QQQQQPPHPL SQLAQLQSQP VHPGLLHSSP TAFRAPPSSN 

       130        140        150        160        170        180 
STAILHPSSR QGSQLNLNDH LLGHSPSSTA TSGPGGGSRH RQASPLVHRR DSNPFTEIAM 

       190        200        210        220        230        240 
SSCKYSGGVM KPLSRLSASR RNLIEAETEG QPLQLFSPSN PPEIVISSRE DNHAHQTLLH 

       250        260        270        280        290        300 
HPNATHNHQH AGTTASSTTF PKANKRKNQN IGYKLGHRRA LFEKRKRLSD YALIFGMFGI 

       310        320        330        340        350        360 
VVMVIETELS WGLYSKDSMF SLALKCLISL STIILLGLII AYHTREVQLF VIDNGADDWR 

       370        380        390        400        410        420 
IAMTYERILY ISLEMLVCAI HPIPGEYKFF WTARLAFSYT PSRAEADVDI ILSIPMFLRL 

       430        440        450        460        470        480 
YLIARVMLLH SKLFTDASSR SIGALNKINF NTRFVMKTLM TICPGTVLLV FSISLWIIAA 

       490        500        510        520        530        540 
WTVRVCERYH DQQDVTSNFL GAMWLISITF LSIGYGDMVP HTYCGKGVCL LTGIMGAGCT 

       550        560        570        580        590        600 
ALVVAVVARK LELTKAEKHV HNFMMDTQLT KRIKNAAANV LRETWLIYKH TKLLKKIDHA 

       610        620        630        640        650        660 
KVRKHQRKFL QAIHQLRSVK MEQRKLSDQA NTLVDLSKMQ NVMYDLITEL NDRSEDLEKQ 

       670        680        690        700        710        720 
IGSLESKLEH LTASFNSLPL LIADTLRQQQ QQLLSAIIEA RGVSVAVGTT HTPISDSPIG 

       730 
VSSTSFPTPY TSSSSC 

« Hide

Isoform 2 [UniParc].

Checksum: 1EBE12900FA7719D
Show »

FASTA42648,050
Isoform 3 (SK3-1B) [UniParc].

Checksum: B4CD0E43E758BDC8
Show »

FASTA41847,093

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS1072.1. [Q9UGI6-2]
RefSeqNP_001191016.1. NM_001204087.1.
NP_002240.3. NM_002249.5.
NP_740752.1. NM_170782.2. [Q9UGI6-2]
UniGeneHs.490765.

3D structure databases

ProteinModelPortalQ9UGI6.
SMRQ9UGI6. Positions 480-679.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109983. 6 interactions.
STRING9606.ENSP00000271915.

Chemistry

BindingDBQ9UGI6.
ChEMBLCHEMBL3381.
GuidetoPHARMACOLOGY383.

PTM databases

PhosphoSiteQ9UGI6.

Polymorphism databases

DMDM17367120.

Proteomic databases

MaxQBQ9UGI6.
PaxDbQ9UGI6.
PRIDEQ9UGI6.

Protocols and materials databases

DNASU3782.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000358505; ENSP00000351295; ENSG00000143603. [Q9UGI6-3]
ENST00000361147; ENSP00000354764; ENSG00000143603. [Q9UGI6-2]
GeneID3782.
KEGGhsa:3782.
UCSCuc001ffo.3. human. [Q9UGI6-2]
uc031ppq.1. human. [Q9UGI6-1]

Organism-specific databases

CTD3782.
GeneCardsGC01M154680.
H-InvDBHIX0023527.
HGNCHGNC:6292. KCNN3.
HPAHPA017990.
MIM602983. gene.
neXtProtNX_Q9UGI6.
PharmGKBPA30072.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG320393.
HOGENOMHOG000276908.
HOVERGENHBG052241.
InParanoidQ9UGI6.
KOK04944.
OrthoDBEOG73FQMC.
PhylomeDBQ9UGI6.
TreeFamTF315015.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

ArrayExpressQ9UGI6.
BgeeQ9UGI6.
CleanExHS_KCNN3.
GenevestigatorQ9UGI6.

Family and domain databases

InterProIPR013099. 2pore_dom_K_chnl_dom.
IPR004178. CaM-bd_dom.
IPR015449. K_chnl_Ca-activ_SK.
[Graphical view]
PANTHERPTHR10153. PTHR10153. 1 hit.
PfamPF02888. CaMBD. 1 hit.
PF07885. Ion_trans_2. 1 hit.
PF03530. SK_channel. 1 hit.
[Graphical view]
PRINTSPR01451. SKCHANNEL.
SMARTSM01053. CaMBD. 1 hit.
[Graphical view]
SUPFAMSSF81327. SSF81327. 1 hit.
ProtoNetSearch...

Other

GeneWikiSK3.
GenomeRNAi3782.
NextBio14843.
PROQ9UGI6.
SOURCESearch...

Entry information

Entry nameKCNN3_HUMAN
AccessionPrimary (citable) accession number: Q9UGI6
Secondary accession number(s): B1ANX0 expand/collapse secondary AC list , O43517, Q86VF9, Q8WXG7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: May 1, 2000
Last modified: July 9, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM