Q03721 (KCNC4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Potassium voltage-gated channel subfamily C member 4

Alternative name(s):
KSHIIIC
Voltage-gated potassium channel subunit Kv3.4

Gene names

Name:

KCNC4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	635 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subunit structure	Homotetramer Probable. Heterotetramer of potassium channel proteins By similarity.
Subcellular location	Membrane; Multi-pass membrane protein.
Domain	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.
Post-translational modification	Phosphorylation of serine residues in the inactivation gate inhibits rapid channel closure.
Sequence similarities	Belongs to the potassium channel family. C (Shaw) (TC 1.A.1.2) subfamily. Kv3.4/KCNC4 sub-subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
Molecular function	Ion channel Potassium channel Voltage-gated channel
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein homooligomerization Inferred from electronic annotation. Source: InterPro regulation of neurotransmitter secretion Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	axon terminus Inferred from electronic annotation. Source: Compara neuromuscular junction Inferred from electronic annotation. Source: Compara voltage-gated potassium channel complex Traceable author statement PubMed 1920536. Source: ProtInc
Molecular_function	delayed rectifier potassium channel activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q03721-1)

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.

Isoform 2 (identifier: Q03721-2)

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.

Isoform 3 (identifier: Q03721-3)

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

Note: Gene prediction based on EST data.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 635

635

Potassium voltage-gated channel subfamily C member 4

PRO_0000054058

Regions

Topological domain

1 – 226

226

Cytoplasmic Potential

Transmembrane

227 – 247

21

Helical; Name=Segment S1; Potential

Transmembrane

278 – 298

21

Helical; Name=Segment S2; Potential

Topological domain

299 – 312

14

Cytoplasmic Potential

Transmembrane

313 – 333

21

Helical; Name=Segment S3; Potential

Transmembrane

345 – 364

20

Helical; Voltage-sensor; Name=Segment S4; Potential

Topological domain

365 – 380

16

Cytoplasmic Potential

Transmembrane

381 – 401

21

Helical; Name=Segment S5; Potential

Transmembrane

452 – 472

21

Helical; Name=Segment S6; Potential

Topological domain

473 – 635

163

Cytoplasmic Potential

Region

1 – 28

28

Inactivation gate

Motif

436 – 441

6

Selectivity filter By similarity

Amino acid modifications

Modified residue

8

1

Phosphoserine Ref.5

Modified residue

9

1

Phosphoserine Ref.5

Modified residue

15

1

Phosphoserine Ref.4

Modified residue

21

1

Phosphoserine Ref.4

Glycosylation

256

1

N-linked (GlcNAc...) Potential

Glycosylation

265

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

539 – 582

44

DSKQN…TTRDR → GEIRGWEGKSLFPQWPREFP NGPQTLGFGMCFVWGFPKHK DVPL in isoform 2.

VSP_020581

Alternative sequence

583 – 635

53

Missing in isoform 2.

VSP_020582

Alternative sequence

607 – 635

29

GTFVL…LFLPH → ETCQDALSSNYAQAEVLTLS in isoform 3.

VSP_040033

Natural variant

318

1

D → Y.
Corresponds to variant rs35167146 [ dbSNP | Ensembl ].

VAR_034051

Natural variant

516

1

R → Q.
Corresponds to variant rs59123361 [ dbSNP | Ensembl ].

VAR_062185

Natural variant

520

1

C → Y.
Corresponds to variant rs12411176 [ dbSNP | Ensembl ].

VAR_027505

Experimental info

Mutagenesis

8

1

S → A: Decreased inhibition of channel closure by PKC. Inhibition of channel closure is nearly abolished; when associated with A-9. Ref.5

Mutagenesis

8

1

S → D: Decreased rate of channel inactivation. Loss of channel inactivation; when associated with D-9; D-15 and D-21. Ref.5

Mutagenesis

9

1

S → A: Strong decrease of inhibition of channel closure by PKC. Inhibition of channel closure is nearly abolished; when associated with A-8. Ref.5

Mutagenesis

9

1

S → D: Decreased rate of channel inactivation. Loss of channel inactivation; when associated with D-8; D-15 and D-21. Ref.5

Mutagenesis

15

1

S → A: Decreased inhibition of channel closure by PKC. Ref.4 Ref.5

Mutagenesis

15

1

S → D: Slightly decreased rate of channel inactivation. Loss of channel inactivation; when associated with D-8; D-9 and D-21. Ref.4 Ref.5

Mutagenesis

21

1

S → A: Decreased inhibition of channel closure by PKC. Ref.4 Ref.5

Mutagenesis

21

1

S → D: Slightly decreased rate of channel inactivation. Loss of channel inactivation; when associated with D-8; D-9 and D-15. Ref.4 Ref.5

Sequence conflict

86

1

S → T in AAA57263. Ref.1

Sequence conflict

351

1

F → I in AAA57263. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

635

Helix Strand Turn

Details...

Turn

3 – 5

3

Beta strand

14 – 16

3

Beta strand

19 – 21

3

Turn

26 – 29

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 24, 2005. Version 2. Checksum: 8A36F0A16AD17722	FASTA	635	69,767
	10 20 30 40 50 60 MISSVCVSSY RGRKSGNKPP SKTCLKEEMA KGEASEKIII NVGGTRHETY RSTLRTLPGT 70 80 90 100 110 120 RLAWLADPDG GGRPETDGGG VGSSGSSGGG GCEFFFDRHP GVFAYVLNYY RTGKLHCPAD 130 140 150 160 170 180 VCGPLFEEEL TFWGIDETDV EPCCWMTYRQ HRDAEEALDI FESPDGGGSG AGPSDEAGDD 190 200 210 220 230 240 ERELALQRLG PHEGGAGHGA GSGGCRGWQP RMWALFEDPY SSRAARVVAF ASLFFILVSI 250 260 270 280 290 300 TTFCLETHEA FNIDRNVTEI LRVGNITSVH FRREVETEPI LTYIEGVCVL WFTLEFLVRI 310 320 330 340 350 360 VCCPDTLDFV KNLLNIIDFV AILPFYLEVG LSGLSSKAAR DVLGFLRVVR FVRILRIFKL 370 380 390 400 410 420 TRHFVGLRVL GHTLRASTNE FLLLIIFLAL GVLIFATMIY YAERIGARPS DPRGNDHTDF 430 440 450 460 470 480 KNIPIGFWWA VVTMTTLGYG DMYPKTWSGM LVGALCALAG VLTIAMPVPV IVNNFGMYYS 490 500 510 520 530 540 LAMAKQKLPK KRKKHVPRPA QLESPMYCKS EETSPRDSTC SDTSPPAREE GMIERKRADS 550 560 570 580 590 600 KQNGDANAVL SDEEGAGLTQ PLASSPTPEE RRALRRSTTR DRNKKAAACF LLSTGDYACA 610 620 630 DGSVRKGTFV LRDLPLQHSP EAACPPTAGT LFLPH
	Isoform 2 [UniParc]. Checksum: 427587A53154E5E0	FASTA	582	64,547
	10 20 30 40 50 60 MISSVCVSSY RGRKSGNKPP SKTCLKEEMA KGEASEKIII NVGGTRHETY RSTLRTLPGT 70 80 90 100 110 120 RLAWLADPDG GGRPETDGGG VGSSGSSGGG GCEFFFDRHP GVFAYVLNYY RTGKLHCPAD 130 140 150 160 170 180 VCGPLFEEEL TFWGIDETDV EPCCWMTYRQ HRDAEEALDI FESPDGGGSG AGPSDEAGDD 190 200 210 220 230 240 ERELALQRLG PHEGGAGHGA GSGGCRGWQP RMWALFEDPY SSRAARVVAF ASLFFILVSI 250 260 270 280 290 300 TTFCLETHEA FNIDRNVTEI LRVGNITSVH FRREVETEPI LTYIEGVCVL WFTLEFLVRI 310 320 330 340 350 360 VCCPDTLDFV KNLLNIIDFV AILPFYLEVG LSGLSSKAAR DVLGFLRVVR FVRILRIFKL 370 380 390 400 410 420 TRHFVGLRVL GHTLRASTNE FLLLIIFLAL GVLIFATMIY YAERIGARPS DPRGNDHTDF 430 440 450 460 470 480 KNIPIGFWWA VVTMTTLGYG DMYPKTWSGM LVGALCALAG VLTIAMPVPV IVNNFGMYYS 490 500 510 520 530 540 LAMAKQKLPK KRKKHVPRPA QLESPMYCKS EETSPRDSTC SDTSPPAREE GMIERKRAGE 550 560 570 580 IRGWEGKSLF PQWPREFPNG PQTLGFGMCF VWGFPKHKDV PL
	Isoform 3 [UniParc]. Checksum: 25385AD738077B52	FASTA	626	68,824
	10 20 30 40 50 60 MISSVCVSSY RGRKSGNKPP SKTCLKEEMA KGEASEKIII NVGGTRHETY RSTLRTLPGT 70 80 90 100 110 120 RLAWLADPDG GGRPETDGGG VGSSGSSGGG GCEFFFDRHP GVFAYVLNYY RTGKLHCPAD 130 140 150 160 170 180 VCGPLFEEEL TFWGIDETDV EPCCWMTYRQ HRDAEEALDI FESPDGGGSG AGPSDEAGDD 190 200 210 220 230 240 ERELALQRLG PHEGGAGHGA GSGGCRGWQP RMWALFEDPY SSRAARVVAF ASLFFILVSI 250 260 270 280 290 300 TTFCLETHEA FNIDRNVTEI LRVGNITSVH FRREVETEPI LTYIEGVCVL WFTLEFLVRI 310 320 330 340 350 360 VCCPDTLDFV KNLLNIIDFV AILPFYLEVG LSGLSSKAAR DVLGFLRVVR FVRILRIFKL 370 380 390 400 410 420 TRHFVGLRVL GHTLRASTNE FLLLIIFLAL GVLIFATMIY YAERIGARPS DPRGNDHTDF 430 440 450 460 470 480 KNIPIGFWWA VVTMTTLGYG DMYPKTWSGM LVGALCALAG VLTIAMPVPV IVNNFGMYYS 490 500 510 520 530 540 LAMAKQKLPK KRKKHVPRPA QLESPMYCKS EETSPRDSTC SDTSPPAREE GMIERKRADS 550 560 570 580 590 600 KQNGDANAVL SDEEGAGLTQ PLASSPTPEE RRALRRSTTR DRNKKAAACF LLSTGDYACA 610 620 DGSVRKETCQ DALSSNYAQA EVLTLS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of ShIII (Shaw-like) cDNAs encoding a novel high-voltage-activating, TEA-sensitive, type-A K+ channel." de Miera E.V.-S., Moreno H., Fruhling D., Kentros C., Rudy B. Proc. R. Soc. B 248:9-18(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Brain.
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 166-635 (ISOFORM 1). Tissue: Brain.
[4]	"Elimination of rapid potassium channel inactivation by phosphorylation of the inactivation gate." Covarrubias M., Wei A., Salkoff L., Vyas T.B. Neuron 13:1403-1412(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-15 AND SER-21, MUTAGENESIS OF SER-15 AND SER-21.
[5]	"Interactions between multiple phosphorylation sites in the inactivation particle of a K+ channel. Insights into the molecular mechanism of protein kinase C action." Beck E.J., Sorensen R.G., Slater S.J., Covarrubias M. J. Gen. Physiol. 112:71-84(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-8 AND SER-9, MUTAGENESIS OF SER-8; SER-9; SER-15 AND SER-21.
[6]	"NMR structure of inactivation gates from mammalian voltage-dependent potassium channels." Antz C., Geyer M., Fakler B., Schott M.K., Guy H.R., Frank R., Ruppersberg J.P., Kalbitzer H.R. Nature 385:272-275(1997) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-30.
[7]	"Control of K+ channel gating by protein phosphorylation: structural switches of the inactivation gate." Antz C., Bauer T., Kalbacher H., Frank R., Covarrubias M., Kalbitzer H.R., Ruppersberg J.P., Baukrowitz T., Fakler B. Nat. Struct. Biol. 6:146-150(1999) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-30.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M64676 mRNA. Translation: AAA57263.1.
AL137790 Genomic DNA. Translation: CAI18831.1.
BC019010 mRNA. No translation available.
BC101769 mRNA. Translation: AAI01770.1.

IPI

IPI00306756.
IPI00604682.
IPI00736536.

RefSeq

NP_001034663.1. NM_001039574.2.
NP_004969.2. NM_004978.4.

UniGene

Hs.153521.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B4G	NMR	-	A	1-30	[»]
1B4I	NMR	-	A	1-30	[»]
1ZTN	NMR	-	A	1-30	[»]

ProteinModelPortal

Q03721.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000358802.

PTM databases

PhosphoSite

Q03721.

Polymorphism databases

DMDM

66774206.

Proteomic databases

PaxDb

Q03721.

PRIDE

Q03721.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000369787; ENSP00000358802; ENSG00000116396.
ENST00000438661; ENSP00000393655; ENSG00000116396.
ENST00000469655; ENSP00000436656; ENSG00000116396.

GeneID

3749.

KEGG

hsa:3749.

UCSC

uc001dzf.3. human.
uc001dzg.3. human.
uc001dzh.3. human.

Organism-specific databases

CTD

3749.

GeneCards

GC01P110753.

H-InvDB

HIX0023584.

HGNC

HGNC:6236. KCNC4.

HPA

HPA014740.

MIM

176265. gene.

neXtProt

NX_Q03721.

PharmGKB

PA30028.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1226.

HOGENOM

HOG000231012.

HOVERGEN

HBG105862.

InParanoid

Q03721.

KO

K04890.

OMA

HFRREVE.

OrthoDB

EOG4HMJ92.

PhylomeDB

Q03721.

Enzyme and pathway databases

Reactome

REACT_13685. Neuronal System.

Gene expression databases

ArrayExpress

Q03721.

Bgee

Q03721.

CleanEx

HS_KCNC4.

Genevestigator

Q03721.

GermOnline

ENSG00000116396. Homo sapiens.

Family and domain databases

Gene3D

3.30.710.10. 1 hit.

InterPro

IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR005821. Ion_trans_dom.
IPR003091. K_chnl.
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.
IPR003131. T1-type_BTB.
[Graphical view]

PANTHER

PTHR11537. PTHR11537. 1 hit.

Pfam

PF00520. Ion_trans. 1 hit.
PF02214. K_tetra. 1 hit.
PF11404. Potassium_chann. 1 hit.
[Graphical view]

PRINTS

PR00169. KCHANNEL.
PR01583. KV34CHANNEL.
PR01491. KVCHANNEL.
PR01498. SHAWCHANNEL.

SMART

SM00225. BTB. 1 hit.
[Graphical view]

SUPFAM

SSF54695. BTB/POZ_fold. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

Q03721.

GenomeRNAi

3749.

NextBio

14675.

SOURCE

Search...

Entry information

Entry name

KCNC4_HUMAN

Accession

Primary (citable) accession number: Q03721
Secondary accession number(s): Q3MIM4, Q5TBI6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	May 24, 2005
Last modified:	May 1, 2013
This is version 120 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.