Q9H2S1 · KCNN2_HUMAN
- ProteinSmall conductance calcium-activated potassium channel protein 2
- GeneKCNN2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids579 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
The current is characterized by a voltage-independent activation, an intracellular calcium concentration increase-dependent activation and a single-channel conductance of about 3 picosiemens (PubMed:10991935).
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:10991935).
The inward rectification could be due to a blockade of the outward current by intracellular divalent cations such as calcium and magnesium and could also be due to an intrinsic property of the channel pore, independent of intracellular divalent ions. There are three positively charged amino acids in the S6 transmembrane domain, close to the pore, that collectively control the conductance and rectification through an electrostatic mechanism. Additionally, electrostatic contributions from these residues also play an important role in determining the intrinsic open probability of the channel in the absence of calcium, affecting the apparent calcium affinity for activation. Forms an heteromeric complex with calmodulin, which is constitutively associated in a calcium-independent manner. Channel opening is triggered when calcium binds the calmodulin resulting in a rotary movement leading to the formation of the dimeric complex to open the gate (By similarity).
Plays a role in the repolarization phase of cardiac action potential (PubMed:13679367).
Catalytic activity
- K+(in) = K+(out)
Activity regulation
Inhibited by UCL 1684 and tetraethylammonium (TEA) (By similarity).
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cell surface | |
Cellular Component | dendritic spine | |
Cellular Component | membrane | |
Cellular Component | neuronal cell body | |
Cellular Component | plasma membrane | |
Cellular Component | Z disc | |
Molecular Function | alpha-actinin binding | |
Molecular Function | calcium-activated potassium channel activity | |
Molecular Function | calmodulin binding | |
Molecular Function | inward rectifier potassium channel activity | |
Molecular Function | protein domain specific binding | |
Molecular Function | protein homodimerization activity | |
Molecular Function | small conductance calcium-activated potassium channel activity | |
Biological Process | membrane repolarization during atrial cardiac muscle cell action potential | |
Biological Process | potassium ion transmembrane transport | |
Biological Process | potassium ion transport | |
Biological Process | regulation of potassium ion transmembrane transport |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameSmall conductance calcium-activated potassium channel protein 2
- Short namesSK2; SKCa 2; SKCa2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9H2S1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Features
Showing features for transmembrane, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 138-158 | Helical; Name=Segment S1 | ||||
Sequence: ALIFGMFGIVVMVIETELSWG | ||||||
Transmembrane | 168-188 | Helical; Name=Segment S2 | ||||
Sequence: LALKCLISLSTIILLGLIIVY | ||||||
Transmembrane | 214-234 | Helical; Name=Segment S3 | ||||
Sequence: IFFICLEILVCAIHPIPGNYT | ||||||
Transmembrane | 256-276 | Helical; Name=Segment S4 | ||||
Sequence: IILSIPMFLRLYLIARVMLLH | ||||||
Transmembrane | 305-325 | Helical; Name=Segment S5 | ||||
Sequence: LMTICPGTVLLVFSISLWIIA | ||||||
Intramembrane | 345-365 | Pore-forming; Name=Segment H5 | ||||
Sequence: FLGAMWLISITFLSIGYGDMV | ||||||
Transmembrane | 374-394 | Helical; Name=Segment S6 | ||||
Sequence: VCLLTGIMGAGCTALVVAVVA |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Dystonia 34, myoclonic (DYT34)
- Note
- DescriptionA form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT34 is an autosomal dominant form characterized by childhood-onset dystonia predominantly affecting hands and neck, with a fast tremor with superimposed myoclonus and, in some individuals, subtle cerebellar signs.
- See alsoMIM:619724
Natural variants in DYT34
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_086749 | 371 | G>E | in DYT34; uncertain significance |
Neurodevelopmental disorder with or without variable movement or behavioral abnormalities (NEDMAB)
- Note
- DescriptionAn autosomal dominant disorder characterized by motor and language developmental delay, intellectual disability often associated with early-onset movement disorders comprising cerebellar ataxia and/or extrapyramidal symptoms. Other variable features include autism spectrum disorder or autistic features and epilepsy.
- See alsoMIM:619725
Natural variants in NEDMAB
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_086742 | 30 | E>Q | in NEDMAB; uncertain significance; no effect on channel function | |
VAR_086743 | 160-579 | missing | in NEDMAB | |
VAR_086744 | 288 | I>S | in NEDMAB; requires 2 nucleotide substitutions | |
VAR_086745 | 321 | missing | in NEDMAB; loss of function of homomeric channels | |
VAR_086746 | 359 | I>M | in NEDMAB; loss of function of homomeric channels | |
VAR_086747 | 361 | Y>C | in NEDMAB | |
VAR_086748 | 362 | G>S | in NEDMAB; loss of function of homomeric channels | |
VAR_086750 | 388 | L>V | in NEDMAB; loss of function of homomeric channels | |
VAR_086751 | 432 | L>P | in NEDMAB; loss of function of homomeric channels |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_086742 | 30 | in NEDMAB; uncertain significance; no effect on channel function | |||
Sequence: E → Q | ||||||
Natural variant | VAR_086743 | 160-579 | in NEDMAB | |||
Sequence: Missing | ||||||
Natural variant | VAR_086744 | 288 | in NEDMAB; requires 2 nucleotide substitutions | |||
Sequence: I → S | ||||||
Natural variant | VAR_086745 | 321 | in NEDMAB; loss of function of homomeric channels | |||
Sequence: Missing | ||||||
Natural variant | VAR_086746 | 359 | in NEDMAB; loss of function of homomeric channels | |||
Sequence: I → M | ||||||
Natural variant | VAR_086747 | 361 | in NEDMAB | |||
Sequence: Y → C | ||||||
Natural variant | VAR_086748 | 362 | in NEDMAB; loss of function of homomeric channels | |||
Sequence: G → S | ||||||
Natural variant | VAR_086749 | 371 | in DYT34; uncertain significance | |||
Sequence: G → E | ||||||
Natural variant | VAR_086750 | 388 | in NEDMAB; loss of function of homomeric channels | |||
Sequence: L → V | ||||||
Natural variant | VAR_086751 | 432 | in NEDMAB; loss of function of homomeric channels | |||
Sequence: L → P |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 10 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000155010 | 1-579 | UniProt | Small conductance calcium-activated potassium channel protein 2 | |||
Sequence: MSSCRYNGGVMRPLSNLSASRRNLHEMDSEAQPLQPPASVGGGGGASSPSAAAAAAAAVSSSAPEIVVSKPEHNNSNNLALYGTGGGGSTGGGGGGGGSGHGSSSGTKSSKKKNQNIGYKLGHRRALFEKRKRLSDYALIFGMFGIVVMVIETELSWGAYDKASLYSLALKCLISLSTIILLGLIIVYHAREIQLFMVDNGADDWRIAMTYERIFFICLEILVCAIHPIPGNYTFTWTARLAFSYAPSTTTADVDIILSIPMFLRLYLIARVMLLHSKLFTDASSRSIGALNKINFNTRFVMKTLMTICPGTVLLVFSISLWIIAAWTVRACERYHDQQDVTSNFLGAMWLISITFLSIGYGDMVPNTYCGKGVCLLTGIMGAGCTALVVAVVARKLELTKAEKHVHNFMMDTQLTKRVKNAAANVLRETWLIYKNTKLVKKIDHAKVRKHQRKFLQAIHQLRSVKMEQRKLNDQANTLVDLAKTQNIMYDMISDLNERSEDFEKRIVTLETKLETLIGSIHALPGLISQTIRQQQRDFIEAQMESYDKHVTYNAERSRSSSRRRRSSSTAPPTSSESS | |||||||
Modified residue | 160 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 567 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed
Gene expression databases
Organism-specific databases
Interaction
Subunit
Heteromultimer with KCNN1 and KCNN3 (PubMed:20689065, PubMed:9287325).
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 (via N-terminal domain) with MPP2 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9H2S1 | ACTN2 P35609 | 3 | EBI-6658875, EBI-77797 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-54 | Disordered | ||||
Sequence: MSSCRYNGGVMRPLSNLSASRRNLHEMDSEAQPLQPPASVGGGGGASSPSAAAA | ||||||
Region | 90-115 | Disordered | ||||
Sequence: TGGGGGGGGSGHGSSSGTKSSKKKNQ | ||||||
Compositional bias | 100-115 | Polar residues | ||||
Sequence: GHGSSSGTKSSKKKNQ | ||||||
Region | 412-488 | Calmodulin-binding | ||||
Sequence: DTQLTKRVKNAAANVLRETWLIYKNTKLVKKIDHAKVRKHQRKFLQAIHQLRSVKMEQRKLNDQANTLVDLAKTQNI | ||||||
Region | 551-579 | Disordered | ||||
Sequence: VTYNAERSRSSSRRRRSSSTAPPTSSESS | ||||||
Compositional bias | 565-579 | Polar residues | ||||
Sequence: RRSSSTAPPTSSESS |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q9H2S1-1
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.
- Name1
- Length579
- Mass (Da)63,760
- Last updated2008-10-14 v2
- Checksum2ED87FE13C106183
Q9H2S1-2
- Name2
- Differences from canonical
- 1-348: Missing
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A3F2YNY5 | A0A3F2YNY5_HUMAN | KCNN2 | 857 | ||
D6RGY7 | D6RGY7_HUMAN | KCNN2 | 95 | ||
A0A0J9YW81 | A0A0J9YW81_HUMAN | KCNN2 | 595 | ||
A0A9L9PY74 | A0A9L9PY74_HUMAN | KCNN2 | 86 | ||
A0A669KBH3 | A0A669KBH3_HUMAN | KCNN2 | 791 |
Features
Showing features for alternative sequence, sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_044584 | 1-348 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 50 | in Ref. 3; AAK84039 | ||||
Sequence: S → SA | ||||||
Sequence conflict | 52 | in Ref. 1; AAG16728 | ||||
Sequence: A → D | ||||||
Sequence conflict | 58 | in Ref. 2; AAP45946 | ||||
Sequence: A → AA | ||||||
Compositional bias | 100-115 | Polar residues | ||||
Sequence: GHGSSSGTKSSKKKNQ | ||||||
Sequence conflict | 323 | in Ref. 3; AAK84039 | ||||
Sequence: I → T | ||||||
Sequence conflict | 530 | in Ref. 2; AAP45946 and 3; AAK84039 | ||||
Sequence: Q → R | ||||||
Compositional bias | 565-579 | Polar residues | ||||
Sequence: RRSSSTAPPTSSESS |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF239613 EMBL· GenBank· DDBJ | AAG16728.1 EMBL· GenBank· DDBJ | mRNA | ||
AY258141 EMBL· GenBank· DDBJ | AAP45946.1 EMBL· GenBank· DDBJ | mRNA | ||
AF397175 EMBL· GenBank· DDBJ | AAK84039.1 EMBL· GenBank· DDBJ | mRNA | ||
AK289948 EMBL· GenBank· DDBJ | BAF82637.1 EMBL· GenBank· DDBJ | mRNA | ||
AC025761 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC109482 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471086 EMBL· GenBank· DDBJ | EAW48975.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471086 EMBL· GenBank· DDBJ | EAW48976.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC015371 EMBL· GenBank· DDBJ | AAH15371.1 EMBL· GenBank· DDBJ | mRNA | ||
BC117454 EMBL· GenBank· DDBJ | AAI17455.1 EMBL· GenBank· DDBJ | mRNA | ||
BC117456 EMBL· GenBank· DDBJ | AAI17457.1 EMBL· GenBank· DDBJ | mRNA |