KCNN2_RAT
ID KCNN2_RAT Reviewed; 580 AA.
AC P70604;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 169.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND ACTIVITY REGULATION.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=8781233; DOI=10.1126/science.273.5282.1709;
RA Koehler M., Hirschberg B., Bond C.T., Kinzie J.M., Marrion N.V., Maylie J.,
RA Adelman J.P.;
RT "Small-conductance, calcium-activated potassium channels from mammalian
RT brain.";
RL Science 273:1709-1714(1996).
RN [2]
RP INTERACTION WITH CALMODULIN.
RX PubMed=9774106; DOI=10.1038/26758;
RA Xia X.M., Fakler B., Rivard A.F., Wayman G., Johnson-Pais T., Keen J.E.,
RA Ishii T., Hirschberg B., Bond C.T., Lutsenko S., Maylie J., Adelman J.P.;
RT "Mechanism of calcium gating in small-conductance calcium-activated
RT potassium channels.";
RL Nature 395:503-507(1998).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-161, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [4]
RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF HIS-337; ASN-345 AND
RP ASN-368.
RX PubMed=20562108; DOI=10.1074/jbc.m110.110072;
RA Lamy C., Goodchild S.J., Weatherall K.L., Jane D.E., Liegeois J.F.,
RA Seutin V., Marrion N.V.;
RT "Allosteric block of KCa2 channels by apamin.";
RL J. Biol. Chem. 285:27067-27077(2010).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 395-490 WITH CALMODULIN.
RX PubMed=11323678; DOI=10.1038/35074145;
RA Schumacher M.A., Rivard A.F., Bachinger H.P., Adelman J.P.;
RT "Structure of the gating domain of a Ca2+-activated K+ channel complexed
RT with Ca2+/calmodulin.";
RL Nature 410:1120-1124(2001).
CC -!- FUNCTION: Forms a voltage-independent potassium channel activated by
CC intracellular calcium (PubMed:8781233, PubMed:20562108). 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:20562108,
CC ECO:0000269|PubMed:8781233}.
CC -!- ACTIVITY REGULATION: Inhibited by bee venom neurotoxin apamin
CC (PubMed:8781233, PubMed:20562108). Inhibited by UCL 1684 and
CC tetraethylammonium (TEA) (PubMed:20562108).
CC {ECO:0000269|PubMed:20562108, ECO:0000269|PubMed:8781233}.
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. {ECO:0000269|PubMed:11323678,
CC ECO:0000269|PubMed:9774106}.
CC -!- INTERACTION:
CC P70604; P62161: Calm3; NbExp=6; IntAct=EBI-1031103, EBI-397530;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Brain.
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; U69882; AAB09563.1; -; mRNA.
DR RefSeq; NP_062187.1; NM_019314.2.
DR PDB; 1G4Y; X-ray; 1.60 A; B=396-487.
DR PDB; 1KKD; NMR; -; A=396-487.
DR PDB; 1QX7; X-ray; 3.09 A; D=411-487.
DR PDB; 2PNV; X-ray; 2.10 A; A/B=488-526.
DR PDB; 3SJQ; X-ray; 1.90 A; C/D=412-487.
DR PDB; 4G27; X-ray; 1.65 A; B=396-487.
DR PDB; 4G28; X-ray; 1.63 A; B=396-487.
DR PDB; 4J9Y; X-ray; 1.51 A; B=396-487.
DR PDB; 4J9Z; X-ray; 1.66 A; B=396-487.
DR PDB; 4QNH; X-ray; 2.02 A; B=396-487.
DR PDB; 6CZQ; X-ray; 2.20 A; B=395-487.
DR PDBsum; 1G4Y; -.
DR PDBsum; 1KKD; -.
DR PDBsum; 1QX7; -.
DR PDBsum; 2PNV; -.
DR PDBsum; 3SJQ; -.
DR PDBsum; 4G27; -.
DR PDBsum; 4G28; -.
DR PDBsum; 4J9Y; -.
DR PDBsum; 4J9Z; -.
DR PDBsum; 4QNH; -.
DR PDBsum; 6CZQ; -.
DR AlphaFoldDB; P70604; -.
DR BMRB; P70604; -.
DR SMR; P70604; -.
DR DIP; DIP-35337N; -.
DR IntAct; P70604; 1.
DR MINT; P70604; -.
DR STRING; 10116.ENSRNOP00000060708; -.
DR BindingDB; P70604; -.
DR ChEMBL; CHEMBL2547; -.
DR DrugCentral; P70604; -.
DR GuidetoPHARMACOLOGY; 382; -.
DR iPTMnet; P70604; -.
DR PhosphoSitePlus; P70604; -.
DR jPOST; P70604; -.
DR PaxDb; P70604; -.
DR PRIDE; P70604; -.
DR ABCD; P70604; 1 sequenced antibody.
DR GeneID; 54262; -.
DR KEGG; rno:54262; -.
DR UCSC; RGD:2963; rat.
DR CTD; 3781; -.
DR RGD; 2963; Kcnn2.
DR VEuPathDB; HostDB:ENSRNOG00000016675; -.
DR eggNOG; KOG3684; Eukaryota.
DR HOGENOM; CLU_014617_0_1_1; -.
DR InParanoid; P70604; -.
DR OrthoDB; 907751at2759; -.
DR PhylomeDB; P70604; -.
DR TreeFam; TF315015; -.
DR Reactome; R-RNO-1296052; Ca2+ activated K+ channels.
DR EvolutionaryTrace; P70604; -.
DR PRO; PR:P70604; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Bgee; ENSRNOG00000016675; Expressed in frontal cortex and 15 other tissues.
DR ExpressionAtlas; P70604; baseline and differential.
DR Genevisible; P70604; RN.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; ISO:RGD.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; ISO:RGD.
DR GO; GO:0030315; C:T-tubule; ISO:RGD.
DR GO; GO:0030018; C:Z disc; ISO:RGD.
DR GO; GO:0051393; F:alpha-actinin binding; ISO:RGD.
DR GO; GO:0015269; F:calcium-activated potassium channel activity; ISO:RGD.
DR GO; GO:0005516; F:calmodulin binding; IMP:RGD.
DR GO; GO:0005242; F:inward rectifier potassium channel activity; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0043268; P:positive regulation of potassium ion transport; IMP:RGD.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISO:RGD.
DR GO; GO:0006813; P:potassium ion transport; IDA:UniProtKB.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IMP:RGD.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; ISO:RGD.
DR DisProt; DP01141; -.
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; Calmodulin-binding; Ion channel; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..580
FT /note="Small conductance calcium-activated potassium
FT channel protein 2"
FT /id="PRO_0000155012"
FT TRANSMEM 140..160
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TRANSMEM 169..189
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TRANSMEM 215..235
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TRANSMEM 257..277
FT /note="Helical; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TRANSMEM 306..326
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT INTRAMEM 346..366
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TRANSMEM 375..395
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT REGION 1..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 88..116
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 413..489
FT /note="Calmodulin-binding"
FT REGION 551..580
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 101..116
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 566..580
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 161
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MUTAGEN 337
FT /note="H->N: Loss of inhibition by apamin and the organic
FT molecule blockers UCL 1684 and d-tubocurarine. No effect on
FT inhibition by tetraethylammonium (TEA)."
FT /evidence="ECO:0000269|PubMed:20562108"
FT MUTAGEN 345
FT /note="N->G: Reduced inhibition by apamin but binding to
FT apamin is unaffected."
FT /evidence="ECO:0000269|PubMed:20562108"
FT MUTAGEN 368
FT /note="N->H: Reduced inhibition by apamin but binding to
FT apamin is unaffected."
FT /evidence="ECO:0000269|PubMed:20562108"
FT STRAND 398..401
FT /evidence="ECO:0007829|PDB:1KKD"
FT HELIX 414..439
FT /evidence="ECO:0007829|PDB:4J9Y"
FT STRAND 440..443
FT /evidence="ECO:0007829|PDB:6CZQ"
FT HELIX 446..485
FT /evidence="ECO:0007829|PDB:4J9Y"
FT HELIX 489..523
FT /evidence="ECO:0007829|PDB:2PNV"
SQ SEQUENCE 580 AA; 63848 MW; F71E0DAF7EEFA8D4 CRC64;
MSSCRYNGGV MRPLSNLSSS RRNLHEMDSE AQPLQPPASV VGGGGGASSP SAAAAASSSA
PEIVVSKPEH NNSNNLALYG TGGGGSTGGG GGGGGGGGGS GHGSSSGTKS SKKKNQNIGY
KLGHRRALFE KRKRLSDYAL IFGMFGIVVM VIETELSWGA YDKASLYSLA LKCLISLSTI
ILLGLIIVYH AREIQLFMVD NGADDWRIAM TYERIFFICL EILVCAIHPI PGNYTFTWTA
RLAFSYAPST TTADVDIILS IPMFLRLYLI ARVMLLHSKL FTDASSRSIG ALNKINFNTR
FVMKTLMTIC PGTVLLVFSI SLWIIAAWTV RACERYHDQQ DVTSNFLGAM WLISITFLSI
GYGDMVPNTY CGKGVCLLTG IMGAGCTALV VAVVARKLEL TKAEKHVHNF MMDTQLTKRV
KNAAANVLRE TWLIYKNTKL VKKIDHAKVR KHQRKFLQAI HQLRSVKMEQ RKLNDQANTL
VDLAKTQNIM YDMISDLNER SEDFEKRIVT LETKLETLIG SIHALPGLIS QTIRQQQRDF
IETQMENYDK HVTYNAERSR SSSRRRRSSS TAPPTSSESS
