KCNK4
entrez
50801
canonical
uniprot
Q9NYG8
canonical
ensembl
ENSG00000182450
resolver
ensp
ENSP00000378033
resolver
ensp
ENSP00000402797
resolver
genesymbol
KCNK4
resolver
genesymbol_syn
TRAAK
resolver
hgnc
HGNC:6279
resolver
uniprot
B5TJL1
resolver
uniprot
Q2YDA1
resolver
uniprot
Q96T94
resolver
uniprot_entry
KCNK4_HUMAN
resolver
uniprot_entry
Q2YDA1_HUMAN
resolver
uniprot_sec
B5TJL1
resolver
uniprot_sec
Q96T94
resolver
activity_regulation
ACTIVITY REGULATION: Activated by mechanical stretch and arachidonic acid. {ECO:0000269|PubMed:22282805, ECO:0000269|PubMed:25500157, ECO:0000269|PubMed:30290154, ECO:0000269|PubMed:38605031}.
uniprot
proteins
amino_acid_sequence
MRSTTLLALLALVLLYLVSGALVFRALEQPHEQQAQRELGEVREKFLRAHPCVSDQELGLLIKEVADALGGGADPETNSTSNSSHSAWDLGSAFFFSGTIITTIGYGNVALRTDAGRLFCIFYALVGIPLFGILLAGVGDRLGSSLRHGIGHIEAIFLKWHVPPELVRVLSAMLFLLIGCLLFVLTPTFVFCYMEDWSKLEAIYFVIVTLTTVGFGDYVAGADPRQDSPAYQPLVWFWILLGLAYFASVLTTIGNWLRVVSRRTRAEMGGLTAQAASWTGTVTARVTQRAGPAAPPPEKEQPLLPPPPCPAQPLGRPRSPSPPEKAQPPSPPTASALDYPSENLAFIDESSDTQSERGCPLPRAPRGRRRPNPPRKPVRPRGPGRPRDKGVPV
uniprot
proteins
disease_involvement
DISEASE: Facial dysmorphism, hypertrichosis, epilepsy, intellectual and developmental delay, and gingival overgrowth syndrome (FHEIG) [MIM:618381]: An autosomal dominant syndrome characterized by delayed motor and intellectual development, poor speech, seizures, generalized hypertrichosis and facial dysmorphic features, including hypotonic facies, bitemporal narrowing, micrognathia, deep-set eyes, bushy eyebrows and long eyelashes, low-set ears, short deep philtrum, gingival overgrowth, prominent upper and lower vermilion, and everted upper lip. {ECO:0000269|PubMed:30290154}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where outward but not inward ion flow opens the gate. Converts to voltage-independent 'leak' conductance mode upon stimulation by various stimuli including mechanical membrane stretch, basic pH, heat and lipids (PubMed:22282805, PubMed:25471887, PubMed:25500157, PubMed:26919430, PubMed:30290154, PubMed:38605031). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties (PubMed:26919430). At trigeminal A-beta afferent nerves, the heterodimer of KCNK2/TREK-1 and KCNK4/TRAAK is mostly coexpressed at nodes of Ranvier where it conducts voltage-independent mechanosensitive and thermosensitive currents, allowing rapid action potential repolarization, high speed and high frequence saltatory conduction on myelinated nerves to ensure prompt sensory responses (By similarity). Permeable to other monovalent cations such as Rb(+) and Cs(+) (PubMed:26919430). {ECO:0000250|UniProtKB:G3V8V5, ECO:0000269|PubMed:22282805, ECO:0000269|PubMed:25471887, ECO:0000269|PubMed:25500157, ECO:0000269|PubMed:26919430, ECO:0000269|PubMed:30290154, ECO:0000269|PubMed:38605031}.
uniprot
proteins
mass_dalton
42704
uniprot
proteins
mutagenesis
MUTAGEN 98; /note="G->I: Strongly increases basal level of channel activity, decreases further activation by pressure and abolishes further activation by arachidonic acid."; /evidence="ECO:0000269|PubMed:25500157"; MUTAGEN 103; /note="T->C: Loss of voltage-dependent channel gating. Displays linear current-voltage relationship."; /evidence="ECO:0000269|PubMed:26919430"; MUTAGEN 212; /note="T->C: Loss of voltage-dependent channel gating. Abolishes activation by arachidonic acid and PIP2."; /evidence="ECO:0000269|PubMed:26919430"; MUTAGEN 232; /note="Q->K: Gain of a cryptic cation-pi interaction that activates channel gating."; /evidence="ECO:0000269|PubMed:28693035"; MUTAGEN 236; /note="W->S: Increases basal level of channel activity and decreases further activation by pressure, but has little effect on further activation by arachidonic acid."; /evidence="ECO:0000269|PubMed:25500157
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000269|PubMed:22282805}.
uniprot
proteins
protein_family
Two pore domain potassium channel (TC 1.A.1.8) family
uniprot
proteins
pubmed
10767409
uniprot
proteins
pubmed
11042359
uniprot
proteins
pubmed
12191490
uniprot
proteins
pubmed
14759258
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
22282805
uniprot
proteins
pubmed
23341632
uniprot
proteins
pubmed
25471887
uniprot
proteins
pubmed
25500157
uniprot
proteins
pubmed
26919430
uniprot
proteins
pubmed
28693035
uniprot
proteins
pubmed
30290154
uniprot
proteins
pubmed
34390650
uniprot
proteins
pubmed
38605031
uniprot
proteins
sequence_length
393
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22282805, ECO:0000269|PubMed:23341632, ECO:0000269|PubMed:25471887, ECO:0000269|PubMed:25500157}; Multi-pass membrane protein {ECO:0000269|PubMed:22282805, ECO:0000269|PubMed:23341632, ECO:0000269|PubMed:25471887, ECO:0000269|PubMed:25500157}. Cell projection, axon {ECO:0000250|UniProtKB:G3V8V5}. Note=Localizes at the Ranvier nodes of myelinated afferent nerves. {ECO:0000250|UniProtKB:G3V8V5}.
uniprot
proteins
transmembrane_region
TRANSMEM 4..24; /note="Helical; Name=M1"; /evidence="ECO:0000269|PubMed:22282805, ECO:0000269|PubMed:23341632, ECO:0000269|PubMed:25471887, ECO:0000269|PubMed:25500157, ECO:0007744|PDB:3UM7, ECO:0007744|PDB:4I9W, ECO:0007744|PDB:4RUE, ECO:0007744|PDB:4WFE"; TRANSMEM 118..150; /note="Helical; Name=M2"; /evidence="ECO:0000269|PubMed:22282805, ECO:0000269|PubMed:23341632, ECO:0000269|PubMed:25471887, ECO:0000269|PubMed:25500157, ECO:0007744|PDB:3UM7, ECO:0007744|PDB:4I9W, ECO:0007744|PDB:4RUE, ECO:0007744|PDB:4WFE"; TRANSMEM 173..194; /note="Helical; Name=M3"; /evidence="ECO:0000269|PubMed:22282805, ECO:0000269|PubMed:23341632, ECO:0000269|PubMed:25471887, ECO:0000269|PubMed:25500157, ECO:0007744|PDB:3UM7, ECO:0007744|PDB:4I9W, ECO:0007744|PDB:4RUE, ECO:0007744|PDB:4WFE"; TRANSMEM 234..260; /note="Helical; Name=M4"; /evidence="ECO:0000269|PubMed:22282805, ECO:0000269|PubMed:23341632, ECO:0000269|PubMed:25471887, ECO:0000269|PubMed:25500157, ECO:0007744|PDB:3UM7, ECO:0007744|PDB:4I9W, ECO:0007744|PDB:4RUE, ECO:0007744|PDB:4WFE
uniprot
proteins