{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9UGI6","secondaryAccessions":["B1ANX0","O43517","Q86VF9","Q8WXG7"],"uniProtkbId":"KCNN3_HUMAN","entryAudit":{"firstPublicDate":"2001-11-16","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2018-12-05","entryVersion":195,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Small conductance calcium-activated potassium channel protein 3"},"shortNames":[{"value":"SK3"},{"value":"SKCa 3"},{"value":"SKCa3"}]},"alternativeNames":[{"fullName":{"value":"KCa2.3"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:6292"}],"value":"KCNN3"},"synonyms":[{"value":"K3"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P70605"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12808432"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20562108"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31155282"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36502918"}],"value":"Small conductance calcium-activated potassium channel that mediates the voltage-independent transmembrane transfer of potassium across the cell membrane through a constitutive interaction with calmodulin which binds the intracellular calcium allowing its opening (PubMed:12808432, PubMed:20562108, PubMed:31155282, PubMed:36502918). The current is characterized by a voltage-independent activation, an intracellular calcium concentration increase-dependent activation and a single-channel conductance of 10 picosiemens (PubMed:12808432, PubMed:20562108, PubMed:31155282, PubMed:36502918). Also presents an inwardly rectifying current, thus reducing its already small outward conductance of potassium ions, which is particularly the case when the membrane potential displays positive values, above + 20 mV (PubMed:12808432). Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12808432"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"12808432"}],"value":"Does not function as a small conductance calcium-activated potassium channel (Probable). Selectively suppresses endogenous KCNN3 currents, in a dominant-negative fashion by decreasing the abundance of functional channels in the plasma membrane, possibly by selectively coassembling with and sequestering native KCNN3 protein in intracellular compartments (PubMed:12808432). This dominant inhibitory effect extends to other members of the SK subfamily (PubMed:12808432)"}],"commentType":"FUNCTION","molecule":"Isoform 3"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"K(+)(in) = K(+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:29463"},{"database":"ChEBI","id":"CHEBI:29103"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12808432"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20562108"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31155282"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36502918"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20562108"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31155282"}],"value":"Inhibited by bee venom neurotoxin apamin"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P70604"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20689065"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31155282"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36502918"}],"value":"Homodimer (PubMed:20689065). Heteromultimer with KCNN2 or KCNN1; this modulates plasma membrane expression and consequently the small conductance calcium-activated potassium channel activity (PubMed:20689065, PubMed:36502918). 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). Interacts with CALM1 (PubMed:31155282)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9UGI6-2","intActId":"EBI-17888181"},"interactantTwo":{"uniProtKBAccession":"P51798","geneName":"CLCN7","intActId":"EBI-4402346"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UGI6-2","intActId":"EBI-17888181"},"interactantTwo":{"uniProtKBAccession":"P50402","geneName":"EMD","intActId":"EBI-489887"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UGI6-2","intActId":"EBI-17888181"},"interactantTwo":{"uniProtKBAccession":"Q7Z2K6","geneName":"ERMP1","intActId":"EBI-10976398"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UGI6-2","intActId":"EBI-17888181"},"interactantTwo":{"uniProtKBAccession":"Q9H115","geneName":"NAPB","intActId":"EBI-3921185"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12808432"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36502918"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P58391"}],"value":"Cytoplasm, myofibril, sarcomere, Z line","id":"SL-0314"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q9UGI6-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q9UGI6-2"],"sequenceIds":["VSP_039461","VSP_039462"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"synonyms":[{"value":"SK3-1B"}],"isoformIds":["Q9UGI6-3"],"sequenceIds":["VSP_047641"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12808432"}],"value":"Widely distributed in human tissues and is present at 20-60% of KCNN3 in the brain"}],"commentType":"TISSUE SPECIFICITY","molecule":"Isoform 3"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20689065"}],"value":"The coiled-coil domaim mediates heteromeic assembly"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9491810"}],"value":"The second poly-Gln region of KCNN3 is highly polymorphic and the number of Gln varies from 12 to 28 in the population"}],"commentType":"POLYMORPHISM"},{"commentType":"DISEASE","disease":{"diseaseId":"Zimmermann-Laband syndrome 3","diseaseAccession":"DI-05702","acronym":"ZLS3","description":"A form of Zimmermann-Laband syndrome, a rare developmental disorder characterized by facial dysmorphism with bulbous nose and thick floppy ears, gingival enlargement, hypoplasia or aplasia of terminal phalanges and nails, hypertrichosis, joint hyperextensibility, and hepatosplenomegaly. 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