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Q9UGI6

- KCNN3_HUMAN

UniProt

Q9UGI6 - KCNN3_HUMAN

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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

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
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: 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
Complete GO annotation...

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

BgeeiQ9UGI6.
CleanExiHS_KCNN3.
ExpressionAtlasiQ9UGI6. baseline and differential.
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 475-679.
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.
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. 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

        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:
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 475-679.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109983. 6 interactions.
STRINGi 9606.ENSP00000271915.

Chemistry

BindingDBi Q9UGI6.
ChEMBLi CHEMBL3381.
DrugBanki DB01110. Miconazole.
DB00721. Procaine.
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 GC01M154669.
H-InvDB HIX0023527.
HGNCi HGNC:6292. KCNN3.
HPAi HPA017990.
MIMi 602983. gene.
neXtProti NX_Q9UGI6.
PharmGKBi PA30072.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG320393.
GeneTreei ENSGT00500000044784.
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

Bgeei Q9UGI6.
CleanExi HS_KCNN3.
ExpressionAtlasi Q9UGI6. baseline and differential.
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

« 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: October 29, 2014
This is version 123 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