KCNN3

Protein identityUniProt · HPA

UniProt accession

Q9UGI6

Gene

KCNN3

Ensembl

ENSG00000143603

Chromosome

1

Canonical length

731 aa

Protein class

Disease related genes, FDA approved drug targets, Human disease related genes, Predicted membrane proteins, Transporters, Voltage-gated ion channels

Subcellular location

Plasma membrane,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. This gene belongs to the KCNN family of potassium channels. It encodes an integral membrane protein that forms a voltage-independent calcium-activated channel, which is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene contains two CAG repeat regions in the coding sequence. It was thought that expansion of one or both of these repeats could lead to an increased susceptibility to schizophrenia or bipolar disorder, but studies indicate that this is probably not the case. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

Canonical amino-acid sequenceUniProt

731 residues, UniProt reviewed canonical sequence.

>Q9UGI6|KCNN3
     1  MDTSGHFHDS GVGDLDEDPK CPCPSSGDEQ QQQQQQQQQQ QPPPPAPPAA PQQPLGPSLQ
    61  PQPPQLQQQQ QQQQQQQQQQ PPHPLSQLAQ LQSQPVHPGL LHSSPTAFRA PPSSNSTAIL
   121  HPSSRQGSQL NLNDHLLGHS PSSTATSGPG GGSRHRQASP LVHRRDSNPF TEIAMSSCKY
   181  SGGVMKPLSR LSASRRNLIE AETEGQPLQL FSPSNPPEIV ISSREDNHAH QTLLHHPNAT
   241  HNHQHAGTTA SSTTFPKANK RKNQNIGYKL GHRRALFEKR KRLSDYALIF GMFGIVVMVI
   301  ETELSWGLYS KDSMFSLALK CLISLSTIIL LGLIIAYHTR EVQLFVIDNG ADDWRIAMTY
   361  ERILYISLEM LVCAIHPIPG EYKFFWTARL AFSYTPSRAE ADVDIILSIP MFLRLYLIAR
   421  VMLLHSKLFT DASSRSIGAL NKINFNTRFV MKTLMTICPG TVLLVFSISL WIIAAWTVRV
   481  CERYHDQQDV TSNFLGAMWL ISITFLSIGY GDMVPHTYCG KGVCLLTGIM GAGCTALVVA
   541  VVARKLELTK AEKHVHNFMM DTQLTKRIKN AAANVLRETW LIYKHTKLLK KIDHAKVRKH
   601  QRKFLQAIHQ LRSVKMEQRK LSDQANTLVD LSKMQNVMYD LITELNDRSE DLEKQIGSLE
   661  SKLEHLTASF NSLPLLIADT LRQQQQQLLS AIIEARGVSV AVGTTHTPIS DSPIGVSSTS
   721  FPTPYTSSSS C

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against KCNN3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

6

Mean surface accessibility (rSASA)

0.51

Highest tissue expression

14 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about KCNN3.

Disease | AllUniProt

Conditions KCNN3 is implicated in, by any mechanism.

• Zimmermann-Laband syndrome 3 (ZLS3) MIM:618658

Disease | GeneticClinVar

7 pathogenic / likely-pathogenic of 166 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Zimmermann-Laband syndrome 3
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.32

gnomAD pLI

0.97

gnomAD missense Z

3.33

DepMap mean gene effect

0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• potassium ion transmembrane transport

Molecular functions

• calmodulin binding
• inward rectifier potassium channel activity
• small conductance calcium-activated potassium channel activity

Cellular components

• neuron projection
• neuronal cell body
• plasma membrane
• Z disc

Protein domainsUniProt · Pfam · InterPro

• Calmodulin-binding domain
• Potassium channel domain
• Potassium channel, calcium-activated, SK
• SK, calmodulin-binding domain superfamily
• Calmodulin binding domain
• Calcium-activated SK potassium channel
• Ion channel

KeywordsUniProt

• Calmodulin-binding
• Cell membrane
• Coiled coil
• Cytoplasm
• Ion channel
• Ion transport
• Membrane
• Phosphoprotein
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of KCNN3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CALM1