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Protein

Potassium voltage-gated channel subfamily C member 4

Gene

KCNC4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This protein mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.

GO - Molecular functioni

  • delayed rectifier potassium channel activity Source: GO_Central
  • potassium channel activity Source: ProtInc
  • voltage-gated potassium channel activity Source: ProtInc

GO - Biological processi

  • chemical synaptic transmission Source: ProtInc
  • potassium ion transport Source: ProtInc
  • protein homooligomerization Source: InterPro
  • regulation of neurotransmitter secretion Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Potassium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000116396-MONOMER.
ReactomeiR-HSA-1296072. Voltage gated Potassium channels.
SIGNORiQ03721.

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium voltage-gated channel subfamily C member 4
Alternative name(s):
KSHIIIC
Voltage-gated potassium channel subunit Kv3.4
Gene namesi
Name:KCNC4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:6236. KCNC4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 226CytoplasmicSequence analysisAdd BLAST226
Transmembranei227 – 247Helical; Name=Segment S1Sequence analysisAdd BLAST21
Transmembranei278 – 298Helical; Name=Segment S2Sequence analysisAdd BLAST21
Topological domaini299 – 312CytoplasmicSequence analysisAdd BLAST14
Transmembranei313 – 333Helical; Name=Segment S3Sequence analysisAdd BLAST21
Transmembranei345 – 364Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd BLAST20
Topological domaini365 – 380CytoplasmicSequence analysisAdd BLAST16
Transmembranei381 – 401Helical; Name=Segment S5Sequence analysisAdd BLAST21
Transmembranei452 – 472Helical; Name=Segment S6Sequence analysisAdd BLAST21
Topological domaini473 – 635CytoplasmicSequence analysisAdd BLAST163

GO - Cellular componenti

  • axon terminus Source: Ensembl
  • neuromuscular junction Source: Ensembl
  • plasma membrane Source: Reactome
  • voltage-gated potassium channel complex Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi8S → A: Decreased inhibition of channel closure by PKC. Inhibition of channel closure is nearly abolished; when associated with A-9. 1 Publication1
Mutagenesisi8S → D: Decreased rate of channel inactivation. Loss of channel inactivation; when associated with D-9; D-15 and D-21. 1 Publication1
Mutagenesisi9S → A: Strong decrease of inhibition of channel closure by PKC. Inhibition of channel closure is nearly abolished; when associated with A-8. 1 Publication1
Mutagenesisi9S → D: Decreased rate of channel inactivation. Loss of channel inactivation; when associated with D-8; D-15 and D-21. 1 Publication1
Mutagenesisi15S → A: Decreased inhibition of channel closure by PKC. 2 Publications1
Mutagenesisi15S → D: Slightly decreased rate of channel inactivation. Loss of channel inactivation; when associated with D-8; D-9 and D-21. 2 Publications1
Mutagenesisi21S → A: Decreased inhibition of channel closure by PKC. 2 Publications1
Mutagenesisi21S → D: Slightly decreased rate of channel inactivation. Loss of channel inactivation; when associated with D-8; D-9 and D-15. 2 Publications1

Organism-specific databases

DisGeNETi3749.
OpenTargetsiENSG00000116396.
PharmGKBiPA30028.

Chemistry databases

ChEMBLiCHEMBL2362996.

Polymorphism and mutation databases

BioMutaiKCNC4.
DMDMi66774206.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000540581 – 635Potassium voltage-gated channel subfamily C member 4Add BLAST635

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei8Phosphoserine1 Publication1
Modified residuei9Phosphoserine1 Publication1
Modified residuei15Phosphoserine1 Publication1
Modified residuei21Phosphoserine1 Publication1
Glycosylationi256N-linked (GlcNAc...)Sequence analysis1
Glycosylationi265N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Phosphorylation of serine residues in the inactivation gate inhibits rapid channel closure.2 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ03721.
PeptideAtlasiQ03721.
PRIDEiQ03721.
TopDownProteomicsiQ03721-3. [Q03721-3]

PTM databases

iPTMnetiQ03721.
PhosphoSitePlusiQ03721.

Expressioni

Gene expression databases

BgeeiENSG00000116396.
CleanExiHS_KCNC4.
ExpressionAtlasiQ03721. baseline and differential.
GenevisibleiQ03721. HS.

Organism-specific databases

HPAiHPA014740.

Interactioni

Subunit structurei

Homotetramer (Probable). Heterotetramer of potassium channel proteins (By similarity).By similarityCurated

Protein-protein interaction databases

BioGridi109951. 27 interactors.
IntActiQ03721. 1 interactor.
STRINGi9606.ENSP00000358802.

Structurei

Secondary structure

1635
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni3 – 5Combined sources3
Beta strandi14 – 16Combined sources3
Beta strandi19 – 21Combined sources3
Turni26 – 29Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B4GNMR-A1-30[»]
1B4INMR-A1-30[»]
1ZTNNMR-A1-30[»]
ProteinModelPortaliQ03721.
SMRiQ03721.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ03721.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 28Inactivation gateAdd BLAST28

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi436 – 441Selectivity filterBy similarity6

Domaini

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
The tail may be important in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3713. Eukaryota.
COG1226. LUCA.
GeneTreeiENSGT00760000118846.
HOGENOMiHOG000231012.
HOVERGENiHBG105862.
InParanoidiQ03721.
KOiK04890.
OMAiGCEFFFD.
OrthoDBiEOG091G0EJL.
PhylomeDBiQ03721.
TreeFamiTF352511.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR000210. BTB/POZ_dom.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR003968. K_chnl_volt-dep_Kv.
IPR003974. K_chnl_volt-dep_Kv3.
IPR005405. K_chnl_volt-dep_Kv3.4.
IPR021105. K_chnl_volt-dep_Kv3_ID.
IPR011333. SKP1/BTB/POZ.
IPR003131. T1-type_BTB.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 3 hits.
PfamiPF02214. BTB_2. 1 hit.
PF00520. Ion_trans. 1 hit.
PF11404. Potassium_chann. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01583. KV34CHANNEL.
PR01491. KVCHANNEL.
PR01498. SHAWCHANNEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q03721-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MISSVCVSSY RGRKSGNKPP SKTCLKEEMA KGEASEKIII NVGGTRHETY
60 70 80 90 100
RSTLRTLPGT RLAWLADPDG GGRPETDGGG VGSSGSSGGG GCEFFFDRHP
110 120 130 140 150
GVFAYVLNYY RTGKLHCPAD VCGPLFEEEL TFWGIDETDV EPCCWMTYRQ
160 170 180 190 200
HRDAEEALDI FESPDGGGSG AGPSDEAGDD ERELALQRLG PHEGGAGHGA
210 220 230 240 250
GSGGCRGWQP RMWALFEDPY SSRAARVVAF ASLFFILVSI TTFCLETHEA
260 270 280 290 300
FNIDRNVTEI LRVGNITSVH FRREVETEPI LTYIEGVCVL WFTLEFLVRI
310 320 330 340 350
VCCPDTLDFV KNLLNIIDFV AILPFYLEVG LSGLSSKAAR DVLGFLRVVR
360 370 380 390 400
FVRILRIFKL TRHFVGLRVL GHTLRASTNE FLLLIIFLAL GVLIFATMIY
410 420 430 440 450
YAERIGARPS DPRGNDHTDF KNIPIGFWWA VVTMTTLGYG DMYPKTWSGM
460 470 480 490 500
LVGALCALAG VLTIAMPVPV IVNNFGMYYS LAMAKQKLPK KRKKHVPRPA
510 520 530 540 550
QLESPMYCKS EETSPRDSTC SDTSPPAREE GMIERKRADS KQNGDANAVL
560 570 580 590 600
SDEEGAGLTQ PLASSPTPEE RRALRRSTTR DRNKKAAACF LLSTGDYACA
610 620 630
DGSVRKGTFV LRDLPLQHSP EAACPPTAGT LFLPH
Length:635
Mass (Da):69,767
Last modified:May 24, 2005 - v2
Checksum:i8A36F0A16AD17722
GO
Isoform 2 (identifier: Q03721-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     539-582: DSKQNGDANA...ALRRSTTRDR → GEIRGWEGKS...GFPKHKDVPL
     583-635: Missing.

Note: Could be a cloning artifact.
Show »
Length:582
Mass (Da):64,547
Checksum:i427587A53154E5E0
GO
Isoform 3 (identifier: Q03721-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     607-635: GTFVLRDLPLQHSPEAACPPTAGTLFLPH → ETCQDALSSNYAQAEVLTLS

Note: Gene prediction based on EST data.
Show »
Length:626
Mass (Da):68,824
Checksum:i25385AD738077B52
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti86S → T in AAA57263 (PubMed:1381835).Curated1
Sequence conflicti351F → I in AAA57263 (PubMed:1381835).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034051318D → Y.Corresponds to variant rs35167146dbSNPEnsembl.1
Natural variantiVAR_062185516R → Q.Corresponds to variant rs59123361dbSNPEnsembl.1
Natural variantiVAR_027505520C → Y.Corresponds to variant rs12411176dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_020581539 – 582DSKQN…TTRDR → GEIRGWEGKSLFPQWPREFP NGPQTLGFGMCFVWGFPKHK DVPL in isoform 2. 2 PublicationsAdd BLAST44
Alternative sequenceiVSP_020582583 – 635Missing in isoform 2. 2 PublicationsAdd BLAST53
Alternative sequenceiVSP_040033607 – 635GTFVL…LFLPH → ETCQDALSSNYAQAEVLTLS in isoform 3. CuratedAdd BLAST29

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64676 mRNA. Translation: AAA57263.1.
AL137790 Genomic DNA. Translation: CAI18831.1.
BC019010 mRNA. No translation available.
BC101769 mRNA. Translation: AAI01770.1.
CCDSiCCDS44193.1. [Q03721-3]
CCDS821.1. [Q03721-1]
RefSeqiNP_001034663.1. NM_001039574.2. [Q03721-3]
NP_004969.2. NM_004978.4. [Q03721-1]
UniGeneiHs.153521.

Genome annotation databases

EnsembliENST00000369787; ENSP00000358802; ENSG00000116396. [Q03721-1]
ENST00000438661; ENSP00000393655; ENSG00000116396. [Q03721-3]
ENST00000469655; ENSP00000436656; ENSG00000116396. [Q03721-1]
GeneIDi3749.
KEGGihsa:3749.
UCSCiuc001dzg.4. human. [Q03721-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64676 mRNA. Translation: AAA57263.1.
AL137790 Genomic DNA. Translation: CAI18831.1.
BC019010 mRNA. No translation available.
BC101769 mRNA. Translation: AAI01770.1.
CCDSiCCDS44193.1. [Q03721-3]
CCDS821.1. [Q03721-1]
RefSeqiNP_001034663.1. NM_001039574.2. [Q03721-3]
NP_004969.2. NM_004978.4. [Q03721-1]
UniGeneiHs.153521.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B4GNMR-A1-30[»]
1B4INMR-A1-30[»]
1ZTNNMR-A1-30[»]
ProteinModelPortaliQ03721.
SMRiQ03721.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109951. 27 interactors.
IntActiQ03721. 1 interactor.
STRINGi9606.ENSP00000358802.

Chemistry databases

ChEMBLiCHEMBL2362996.

PTM databases

iPTMnetiQ03721.
PhosphoSitePlusiQ03721.

Polymorphism and mutation databases

BioMutaiKCNC4.
DMDMi66774206.

Proteomic databases

PaxDbiQ03721.
PeptideAtlasiQ03721.
PRIDEiQ03721.
TopDownProteomicsiQ03721-3. [Q03721-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000369787; ENSP00000358802; ENSG00000116396. [Q03721-1]
ENST00000438661; ENSP00000393655; ENSG00000116396. [Q03721-3]
ENST00000469655; ENSP00000436656; ENSG00000116396. [Q03721-1]
GeneIDi3749.
KEGGihsa:3749.
UCSCiuc001dzg.4. human. [Q03721-1]

Organism-specific databases

CTDi3749.
DisGeNETi3749.
GeneCardsiKCNC4.
H-InvDBHIX0023584.
HGNCiHGNC:6236. KCNC4.
HPAiHPA014740.
MIMi176265. gene.
neXtProtiNX_Q03721.
OpenTargetsiENSG00000116396.
PharmGKBiPA30028.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3713. Eukaryota.
COG1226. LUCA.
GeneTreeiENSGT00760000118846.
HOGENOMiHOG000231012.
HOVERGENiHBG105862.
InParanoidiQ03721.
KOiK04890.
OMAiGCEFFFD.
OrthoDBiEOG091G0EJL.
PhylomeDBiQ03721.
TreeFamiTF352511.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000116396-MONOMER.
ReactomeiR-HSA-1296072. Voltage gated Potassium channels.
SIGNORiQ03721.

Miscellaneous databases

EvolutionaryTraceiQ03721.
GeneWikiiKCNC4.
GenomeRNAii3749.
PROiQ03721.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000116396.
CleanExiHS_KCNC4.
ExpressionAtlasiQ03721. baseline and differential.
GenevisibleiQ03721. HS.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR000210. BTB/POZ_dom.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR003968. K_chnl_volt-dep_Kv.
IPR003974. K_chnl_volt-dep_Kv3.
IPR005405. K_chnl_volt-dep_Kv3.4.
IPR021105. K_chnl_volt-dep_Kv3_ID.
IPR011333. SKP1/BTB/POZ.
IPR003131. T1-type_BTB.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 3 hits.
PfamiPF02214. BTB_2. 1 hit.
PF00520. Ion_trans. 1 hit.
PF11404. Potassium_chann. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01583. KV34CHANNEL.
PR01491. KVCHANNEL.
PR01498. SHAWCHANNEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiKCNC4_HUMAN
AccessioniPrimary (citable) accession number: Q03721
Secondary accession number(s): Q3MIM4, Q5TBI6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 24, 2005
Last modified: November 2, 2016
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.