KCNN2_HUMAN
ID KCNN2_HUMAN Reviewed; 579 AA.
AC Q9H2S1; A6NF94; Q0VFZ4; Q6PJI0; Q6X2Y2;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Small conductance calcium-activated potassium channel protein 2;
DE Short=SK2;
DE Short=SKCa 2;
DE Short=SKCa2;
DE AltName: Full=KCa2.2;
GN Name=KCNN2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=10991935; DOI=10.1074/jbc.m001562200;
RA Desai R., Peretz A., Idelson H., Lazarovici P., Attali B.;
RT "Ca2+-activated K+ channels in human leukemic Jurkat T cells. Molecular
RT cloning, biochemical and functional characterization.";
RL J. Biol. Chem. 275:39954-39963(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Heart;
RX PubMed=13679367; DOI=10.1074/jbc.m307508200;
RA Xu Y., Tuteja D., Zhang Z., Xu D., Zhang Y., Rodriguez J., Nie L.,
RA Tuxson H.R., Young J.N., Glatter K.A., Vazquez A.E., Yamoah E.N.,
RA Chiamvimonvat N.;
RT "Molecular identification and functional roles of a Ca(2+)-activated K+
RT channel in human and mouse hearts.";
RL J. Biol. Chem. 278:49085-49094(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Myometrium;
RA Mazzone J.N., Kaiser R.A., Buxton I.L.O.;
RT "Characterization of calcium-activated potassium channels in human
RT myometrium.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=9287325; DOI=10.1074/jbc.272.37.23195;
RA Ishii T.M., Maylie J., Adelman J.P.;
RT "Determinants of apamin and d-tubocurarine block in SK potassium
RT channels.";
RL J. Biol. Chem. 272:23195-23200(1997).
CC -!- FUNCTION: Forms a voltage-independent potassium channel activated by
CC intracellular calcium (PubMed:10991935, PubMed:9287325). Activation is
CC followed by membrane hyperpolarization. Thought to regulate neuronal
CC excitability by contributing to the slow component of synaptic
CC afterhyperpolarization. {ECO:0000269|PubMed:10991935,
CC ECO:0000269|PubMed:9287325}.
CC -!- ACTIVITY REGULATION: Inhibited by bee venom neurotoxin apamin
CC (PubMed:10991935, PubMed:9287325). Inhibited by UCL 1684 and
CC tetraethylammonium (TEA) (By similarity).
CC {ECO:0000250|UniProtKB:P70604, ECO:0000269|PubMed:10991935,
CC ECO:0000269|PubMed:9287325}.
CC -!- SUBUNIT: Heterooligomer. The complex is composed of 4 channel subunits
CC each of which binds to a calmodulin subunit which regulates the channel
CC activity through calcium-binding (By similarity).
CC {ECO:0000250|UniProtKB:P70604}.
CC -!- INTERACTION:
CC Q9H2S1; P35609: ACTN2; NbExp=3; IntAct=EBI-6658875, EBI-77797;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H2S1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H2S1-2; Sequence=VSP_044584;
CC -!- TISSUE SPECIFICITY: Expressed in atrial myocytes (at protein level).
CC Widely expressed. {ECO:0000269|PubMed:13679367}.
CC -!- SIMILARITY: Belongs to the potassium channel KCNN family. KCa2.2/KCNN2
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF239613; AAG16728.1; -; mRNA.
DR EMBL; AY258141; AAP45946.1; -; mRNA.
DR EMBL; AF397175; AAK84039.1; -; mRNA.
DR EMBL; AK289948; BAF82637.1; -; mRNA.
DR EMBL; AC025761; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC109482; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471086; EAW48975.1; -; Genomic_DNA.
DR EMBL; CH471086; EAW48976.1; -; Genomic_DNA.
DR EMBL; BC015371; AAH15371.1; -; mRNA.
DR EMBL; BC117454; AAI17455.1; -; mRNA.
DR EMBL; BC117456; AAI17457.1; -; mRNA.
DR CCDS; CCDS43352.1; -. [Q9H2S1-2]
DR RefSeq; NP_001265133.1; NM_001278204.1. [Q9H2S1-2]
DR RefSeq; NP_067627.2; NM_021614.3.
DR RefSeq; NP_740721.1; NM_170775.2. [Q9H2S1-2]
DR PDB; 5V02; X-ray; 1.78 A; B=395-486.
DR PDB; 5WBX; X-ray; 1.90 A; B=395-486.
DR PDB; 5WC5; X-ray; 2.30 A; B=395-486.
DR PDB; 6ALE; X-ray; 2.50 A; B=394-486.
DR PDBsum; 5V02; -.
DR PDBsum; 5WBX; -.
DR PDBsum; 5WC5; -.
DR PDBsum; 6ALE; -.
DR AlphaFoldDB; Q9H2S1; -.
DR BMRB; Q9H2S1; -.
DR SMR; Q9H2S1; -.
DR BioGRID; 109982; 6.
DR DIP; DIP-48997N; -.
DR IntAct; Q9H2S1; 4.
DR STRING; 9606.ENSP00000427120; -.
DR BindingDB; Q9H2S1; -.
DR ChEMBL; CHEMBL4469; -.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB00721; Procaine.
DR DrugBank; DB16733; Rimtuzalcap.
DR DrugBank; DB09089; Trimebutine.
DR DrugCentral; Q9H2S1; -.
DR GuidetoPHARMACOLOGY; 382; -.
DR TCDB; 1.A.1.16.1; the voltage-gated ion channel (vic) superfamily.
DR iPTMnet; Q9H2S1; -.
DR PhosphoSitePlus; Q9H2S1; -.
DR BioMuta; KCNN2; -.
DR DMDM; 209572638; -.
DR EPD; Q9H2S1; -.
DR jPOST; Q9H2S1; -.
DR MassIVE; Q9H2S1; -.
DR MaxQB; Q9H2S1; -.
DR PaxDb; Q9H2S1; -.
DR PeptideAtlas; Q9H2S1; -.
DR PRIDE; Q9H2S1; -.
DR ProteomicsDB; 67208; -.
DR ProteomicsDB; 80583; -. [Q9H2S1-1]
DR ABCD; Q9H2S1; 1 sequenced antibody.
DR Antibodypedia; 13591; 127 antibodies from 30 providers.
DR DNASU; 3781; -.
DR Ensembl; ENST00000264773.7; ENSP00000264773.2; ENSG00000080709.16. [Q9H2S1-1]
DR Ensembl; ENST00000503706.5; ENSP00000421439.1; ENSG00000080709.16. [Q9H2S1-2]
DR Ensembl; ENST00000610748.4; ENSP00000483124.1; ENSG00000080709.16. [Q9H2S1-2]
DR GeneID; 3781; -.
DR KEGG; hsa:3781; -.
DR UCSC; uc003kqo.4; human. [Q9H2S1-1]
DR CTD; 3781; -.
DR DisGeNET; 3781; -.
DR GeneCards; KCNN2; -.
DR HGNC; HGNC:6291; KCNN2.
DR HPA; ENSG00000080709; Tissue enhanced (adrenal gland, brain, liver).
DR MalaCards; KCNN2; -.
DR MIM; 605879; gene.
DR neXtProt; NX_Q9H2S1; -.
DR OpenTargets; ENSG00000080709; -.
DR PharmGKB; PA30071; -.
DR VEuPathDB; HostDB:ENSG00000080709; -.
DR eggNOG; KOG3684; Eukaryota.
DR GeneTree; ENSGT00950000182904; -.
DR HOGENOM; CLU_014617_0_1_1; -.
DR InParanoid; Q9H2S1; -.
DR OrthoDB; 907751at2759; -.
DR PhylomeDB; Q9H2S1; -.
DR TreeFam; TF315015; -.
DR PathwayCommons; Q9H2S1; -.
DR Reactome; R-HSA-1296052; Ca2+ activated K+ channels.
DR Reactome; R-HSA-9667769; Acetylcholine inhibits contraction of outer hair cells.
DR SignaLink; Q9H2S1; -.
DR SIGNOR; Q9H2S1; -.
DR BioGRID-ORCS; 3781; 10 hits in 1072 CRISPR screens.
DR ChiTaRS; KCNN2; human.
DR GeneWiki; KCNN2; -.
DR GenomeRNAi; 3781; -.
DR Pharos; Q9H2S1; Tchem.
DR PRO; PR:Q9H2S1; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9H2S1; protein.
DR Bgee; ENSG00000080709; Expressed in secondary oocyte and 148 other tissues.
DR ExpressionAtlas; Q9H2S1; baseline and differential.
DR Genevisible; Q9H2S1; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0030018; C:Z disc; ISS:BHF-UCL.
DR GO; GO:0051393; F:alpha-actinin binding; IPI:BHF-UCL.
DR GO; GO:0015269; F:calcium-activated potassium channel activity; IDA:BHF-UCL.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0005242; F:inward rectifier potassium channel activity; IDA:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0016286; F:small conductance calcium-activated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0006811; P:ion transport; IBA:GO_Central.
DR GO; GO:0098914; P:membrane repolarization during atrial cardiac muscle cell action potential; ISS:BHF-UCL.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; NAS:UniProtKB.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; IDA:BHF-UCL.
DR InterPro; IPR004178; CaM-bd_dom.
DR InterPro; IPR036122; CaM-bd_dom_sf.
DR InterPro; IPR015449; K_chnl_Ca-activ_SK.
DR InterPro; IPR013099; K_chnl_dom.
DR PANTHER; PTHR10153; PTHR10153; 1.
DR Pfam; PF02888; CaMBD; 1.
DR Pfam; PF07885; Ion_trans_2; 1.
DR Pfam; PF03530; SK_channel; 1.
DR PRINTS; PR01451; SKCHANNEL.
DR SMART; SM01053; CaMBD; 1.
DR SUPFAM; SSF81327; SSF81327; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calmodulin-binding; Ion channel;
KW Ion transport; Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..579
FT /note="Small conductance calcium-activated potassium
FT channel protein 2"
FT /id="PRO_0000155010"
FT TRANSMEM 138..158
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TRANSMEM 214..234
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TRANSMEM 256..276
FT /note="Helical; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TRANSMEM 305..325
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT INTRAMEM 345..365
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TRANSMEM 374..394
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT REGION 1..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 90..115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 412..488
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250"
FT REGION 551..579
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 100..115
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 565..579
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 160
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P70604"
FT VAR_SEQ 1..348
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044584"
FT CONFLICT 50
FT /note="S -> SA (in Ref. 3; AAK84039)"
FT /evidence="ECO:0000305"
FT CONFLICT 52
FT /note="A -> D (in Ref. 1; AAG16728)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="A -> AA (in Ref. 2; AAP45946)"
FT /evidence="ECO:0000305"
FT CONFLICT 323
FT /note="I -> T (in Ref. 3; AAK84039)"
FT /evidence="ECO:0000305"
FT CONFLICT 530
FT /note="Q -> R (in Ref. 2; AAP45946 and 3; AAK84039)"
FT /evidence="ECO:0000305"
FT STRAND 405..409
FT /evidence="ECO:0007829|PDB:6ALE"
FT HELIX 410..412
FT /evidence="ECO:0007829|PDB:5WBX"
FT HELIX 413..438
FT /evidence="ECO:0007829|PDB:5V02"
FT STRAND 439..442
FT /evidence="ECO:0007829|PDB:5WBX"
FT HELIX 445..484
FT /evidence="ECO:0007829|PDB:5V02"
SQ SEQUENCE 579 AA; 63760 MW; 2ED87FE13C106183 CRC64;
MSSCRYNGGV MRPLSNLSAS RRNLHEMDSE AQPLQPPASV GGGGGASSPS AAAAAAAAVS
SSAPEIVVSK PEHNNSNNLA LYGTGGGGST GGGGGGGGSG HGSSSGTKSS KKKNQNIGYK
LGHRRALFEK RKRLSDYALI FGMFGIVVMV IETELSWGAY DKASLYSLAL KCLISLSTII
LLGLIIVYHA REIQLFMVDN GADDWRIAMT YERIFFICLE ILVCAIHPIP GNYTFTWTAR
LAFSYAPSTT TADVDIILSI PMFLRLYLIA RVMLLHSKLF TDASSRSIGA LNKINFNTRF
VMKTLMTICP GTVLLVFSIS LWIIAAWTVR ACERYHDQQD VTSNFLGAMW LISITFLSIG
YGDMVPNTYC GKGVCLLTGI MGAGCTALVV AVVARKLELT KAEKHVHNFM MDTQLTKRVK
NAAANVLRET WLIYKNTKLV KKIDHAKVRK HQRKFLQAIH QLRSVKMEQR KLNDQANTLV
DLAKTQNIMY DMISDLNERS EDFEKRIVTL ETKLETLIGS IHALPGLISQ TIRQQQRDFI
EAQMESYDKH VTYNAERSRS SSRRRRSSST APPTSSESS
