Q9UGI6 (KCNN3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	KCNN3
Synonyms:	K3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	736 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Calmodulin-binding
Molecular function	Ion channel
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	small conductance calcium-activated potassium channel activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 736	736	Small conductance calcium-activated potassium channel protein 3		PRO_0000155013
Regions
	Transmembrane	293 – 313	21	Helical; Name=Segment S1; Potential
	Transmembrane	320 – 340	21	Helical; Name=Segment S2; Potential
	Transmembrane	371 – 391	21	Helical; Name=Segment S3; Potential
	Transmembrane	410 – 430	21	Helical; Name=Segment S4; Potential
	Transmembrane	459 – 479	21	Helical; Name=Segment S5; Potential
	Intramembrane	499 – 519	21	Pore-forming; Name=Segment H5; Potential
	Transmembrane	528 – 548	21	Helical; Name=Segment S6; Potential
	Region	566 – 642	77	Calmodulin-binding By similarity
	Compositional bias	30 – 41	12	Poly-Gln
	Compositional bias	42 – 48	7	Poly-Pro
	Compositional bias	65 – 85	21	Poly-Gln
	Compositional bias	688 – 692	5	Poly-Gln
	Compositional bias	732 – 735	4	Poly-Ser
Natural variations
	Alternative sequence	1 – 310	310	Missing in isoform 2.		VSP_039461
	Alternative sequence	311 – 315	5	WGLYS → MERPI in isoform 2.		VSP_039462
	Natural variant	81 – 85	5	Missing.		VAR_012204
Experimental info
	Sequence conflict	254	1	T → A in AAC26099. Ref.1
	Sequence conflict	281	1	L → P in AAC26099. Ref.1
	Sequence conflict	347	1	V → A in AAC26099. Ref.1
	Sequence conflict	485	1	V → A in AAC26099. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: CCD0CC1621FFAE9C	FASTA	736	82,026
	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
	Isoform 2 [UniParc]. Checksum: 1EBE12900FA7719D	FASTA	426	48,050
	10 20 30 40 50 60 MERPIKDSMF SLALKCLISL STIILLGLII AYHTREVQLF VIDNGADDWR IAMTYERILY 70 80 90 100 110 120 ISLEMLVCAI HPIPGEYKFF WTARLAFSYT PSRAEADVDI ILSIPMFLRL YLIARVMLLH 130 140 150 160 170 180 SKLFTDASSR SIGALNKINF NTRFVMKTLM TICPGTVLLV FSISLWIIAA WTVRVCERYH 190 200 210 220 230 240 DQQDVTSNFL GAMWLISITF LSIGYGDMVP HTYCGKGVCL LTGIMGAGCT ALVVAVVARK 250 260 270 280 290 300 LELTKAEKHV HNFMMDTQLT KRIKNAAANV LRETWLIYKH TKLLKKIDHA KVRKHQRKFL 310 320 330 340 350 360 QAIHQLRSVK MEQRKLSDQA NTLVDLSKMQ NVMYDLITEL NDRSEDLEKQ IGSLESKLEH 370 380 390 400 410 420 LTASFNSLPL LIADTLRQQQ QQLLSAIIEA RGVSVAVGTT HTPISDSPIG VSSTSFPTPY TSSSSC

References

	« Hide 'large scale' referencesShow '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]	"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].
[6]	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. , 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].
[7]	"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. 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: EAW53182.1. BC042147 mRNA. Translation: AAH42147.1.
IPI	IPI00032465. IPI00395734.
RefSeq	NP_001191016.1. NM_001204087.1. NP_002240.3. NM_002249.5. NP_740752.1. NM_170782.2.
UniGene	Hs.490765.
3D structure databases
ProteinModelPortal	Q9UGI6.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000271915.
PTM databases
PhosphoSite	Q9UGI6.
Polymorphism databases
DMDM	17367120.
Proteomic databases
PaxDb	Q9UGI6.
PRIDE	Q9UGI6.
Protocols and materials databases
DNASU	3782.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000271915; ENSP00000271915; ENSG00000143603. ENST00000361147; ENSP00000354764; ENSG00000143603.
GeneID	3782.
KEGG	hsa:3782.
UCSC	uc001ffo.3. human.
Organism-specific databases
CTD	3782.
GeneCards	GC01M154680.
H-InvDB	HIX0023527.
HGNC	HGNC:6292. KCNN3.
HPA	HPA017990.
MIM	602983. gene.
neXtProt	NX_Q9UGI6.
PharmGKB	PA30072.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG320393.
HOGENOM	HOG000276908.
HOVERGEN	HBG052241.
InParanoid	Q9UGI6.
KO	K04944.
OrthoDB	EOG49CQ7G.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	Q9UGI6.
Bgee	Q9UGI6.
CleanEx	HS_KCNN3.
Genevestigator	Q9UGI6.
GermOnline	ENSG00000143603. Homo sapiens.
Family and domain databases
InterPro	IPR004178. CaM-bd_dom. IPR013099. Ion_trans_2. IPR015449. K_chnl_Ca-activ_SK. [Graphical view]
PANTHER	PTHR10153. PTHR10153. 1 hit.
Pfam	PF02888. CaMBD. 1 hit. PF07885. Ion_trans_2. 1 hit. PF03530. SK_channel. 1 hit. [Graphical view]
PRINTS	PR01451. SKCHANNEL.
SMART	SM01053. CaMBD. 1 hit. [Graphical view]
SUPFAM	SSF81327. CaM_bd. 1 hit.
ProtoNet	Search...
Other
BindingDB	Q9UGI6.
ChEMBL	CHEMBL3381.
GenomeRNAi	3782.
NextBio	14843.
SOURCE	Search...

Entry information

Entry name

KCNN3_HUMAN

Accession

Primary (citable) accession number: Q9UGI6
Secondary accession number(s): B1ANX0, O43517, Q8WXG7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 16, 2001
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.