O43526 (KCNQ2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Potassium voltage-gated channel subfamily KQT member 2

Alternative name(s):
KQT-like 2
Neuroblastoma-specific potassium channel subunit alpha KvLQT2
Voltage-gated potassium channel subunit Kv7.2

Gene names

Name:

KCNQ2

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	872 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. KCNQ2/KCNQ3 current is blocked by linopirdine and XE991, and activated by the anticonvulsant retigabine. Muscarinic agonist oxotremorine-M strongly suppress KCNQ2/KCNQ3 current in cells in which cloned KCNQ2/KCNQ3 channels were coexpressed with M1 muscarinic receptors.
Subunit structure	Heteromultimer with KCNQ3. May associate with KCNE2.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	In adult and fetal brain. Highly expressed in areas containing neuronal cell bodies, low in spinal chord and corpus callosum. Isoform 2 is preferentially expressed in differentiated neurons. Isoform 6 is prominent in fetal brain, undifferentiated neuroblastoma cells and brain tumors. Ref.19
Domain	The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position By similarity.
Post-translational modification	In Xenopus oocytes KCNQ2/KCNQ3 heteromeric current can be increased by intracellular cyclic AMP, an effect that depends on phosphorylation of Ser-52 in the N-terminus region.
Involvement in disease	Seizures, benign familial neonatal 1 (BFNS1) [MIM:121200]: A disorder characterized by clusters of seizures occurring in the first days of life. Most patients have spontaneous remission by 12 months of age and show normal psychomotor development. Some rare cases manifest an atypical severe phenotype associated with epileptic encephalopathy and psychomotor retardation. The disorder is distinguished from benign familial infantile seizures by an earlier age at onset. In some patients, neonatal convulsions are followed later in life by myokymia, a benign condition characterized by spontaneous involuntary contractions of skeletal muscles fiber groups that can be observed as vermiform movement of the overlying skin. Electromyography typically shows continuous motor unit activity with spontaneous oligo- and multiplet-discharges of high intraburst frequency (myokymic discharges). Some patients may have isolated myokymia. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.23 Ref.24 Ref.25 Ref.27 Epileptic encephalopathy, early infantile, 7 (EIEE7) [MIM:613720]: An autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26 Ref.27
Miscellaneous	Inclusion of isoform 6 in heteromultimers results in attenuation of potassium current. Prominent expression of isoform 6 in the developing brain may alter firing repertoires of immature neurons excitability to provide cues for proliferation rather than differentiation. Mutagenesis experiments were carried out in Xenopus oocytes by coexpression of either KCNQ2(mut) and KCNQ3 at the ratio of 1:1, or of KCNQ2(mut), KCNQ2(wt) and KCNQ3 at the ratio of 1:1:2, to mimic the situation in a heterozygous patient with BFNC1 disease.
Sequence similarities	Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.2/KCNQ2 sub-subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Epilepsy Mental retardation
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
Molecular function	Ion channel Potassium channel Voltage-gated channel
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon guidance Traceable author statement. Source: Reactome nervous system development Traceable author statement Ref.2. Source: ProtInc potassium ion transport Traceable author statement Ref.6. Source: ProtInc synaptic transmission Traceable author statement. Source: Reactome transmission of nerve impulse Inferred from electronic annotation. Source: Ensembl
Cellular_component	axon initial segment Inferred from sequence or structural similarity PubMed 16525039. Source: BHF-UCL node of Ranvier Inferred from sequence or structural similarity PubMed 16525039. Source: BHF-UCL plasma membrane Inferred from sequence or structural similarity PubMed 16525039. Source: BHF-UCL voltage-gated potassium channel complex Traceable author statement Ref.6. Source: ProtInc
Molecular_function	ankyrin binding Inferred from physical interaction PubMed 16525039. Source: BHF-UCL delayed rectifier potassium channel activity Inferred from Biological aspect of Ancestor. Source: RefGenome potassium channel activity Traceable author statement Ref.3. Source: ProtInc voltage-gated potassium channel activity Traceable author statement Ref.6. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: O43526-1)

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: O43526-2)

The sequence of this isoform differs from the canonical sequence as follows:
     417-434: Missing.

Isoform 3 (identifier: O43526-3)

The sequence of this isoform differs from the canonical sequence as follows:
     373-382: Missing.
     417-434: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 4 (identifier: O43526-4)

The sequence of this isoform differs from the canonical sequence as follows:
     417-446: Missing.
     509-509: Missing.

Isoform 5 (identifier: O43526-5)

The sequence of this isoform differs from the canonical sequence as follows:
     310-320: Missing.
     417-434: Missing.

Isoform 6 (identifier: O43526-6)

Also known as: HNSPC;

The sequence of this isoform differs from the canonical sequence as follows:
     373-393: SSQTQTYGASRLIPPLNQLEL → RYRRRAPATKQLFHFLFSICS
     394-872: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 872	872	Potassium voltage-gated channel subfamily KQT member 2		PRO_0000054030
Regions
	Transmembrane	92 – 112	21	Helical; Name=Segment S1; Potential
	Topological domain	113 – 122	10	Extracellular Potential
	Transmembrane	123 – 143	21	Helical; Name=Segment S2; Potential
	Topological domain	144 – 166	23	Cytoplasmic Potential
	Transmembrane	167 – 187	21	Helical; Name=Segment S3; Potential
	Topological domain	188 – 195	8	Extracellular Potential
	Transmembrane	196 – 218	23	Helical; Voltage-sensor; Name=Segment S4; Potential
	Topological domain	219 – 231	13	Cytoplasmic Potential
	Transmembrane	232 – 252	21	Helical; Name=Segment S5; Potential
	Topological domain	253 – 264	12	Extracellular Potential
	Intramembrane	265 – 285	21	Pore-forming; Name=Segment H5; Potential
	Topological domain	286 – 291	6	Extracellular Potential
	Transmembrane	292 – 312	21	Helical; Name=Segment S6; Potential
	Topological domain	313 – 872	560	Cytoplasmic Potential
	Motif	277 – 282	6	Selectivity filter By similarity
Amino acid modifications
	Modified residue	52	1	Phosphoserine; by PKA Ref.10
	Modified residue	217	1	Phosphothreonine Ref.21
Natural variations
	Alternative sequence	310 – 320	11	Missing in isoform 5.		VSP_000984
	Alternative sequence	373 – 393	21	SSQTQ…NQLEL → RYRRRAPATKQLFHFLFSIC S in isoform 6.		VSP_000986
	Alternative sequence	373 – 382	10	Missing in isoform 3.		VSP_000985
	Alternative sequence	394 – 872	479	Missing in isoform 6.		VSP_000987
	Alternative sequence	417 – 446	30	Missing in isoform 4.		VSP_000989
	Alternative sequence	417 – 434	18	Missing in isoform 2, isoform 3 and isoform 5.		VSP_000988
	Alternative sequence	509	1	Missing in isoform 4.		VSP_000990
	Natural variant	207	1	R → Q in a patient with isolated myokymia and no history of neonatal seizures; leads to a shift of voltage-dependent activation. Ref.28		VAR_043819
	Natural variant	207	1	R → W in BFNS1; phenotype manifestations include myokymia in some patients; leads to a shift of voltage-dependent activation of the channel and a dramatic slowing of activation upon depolarization. Ref.24		VAR_026987
	Natural variant	208	1	M → V in BFNS1; minor effect on maximal current but clearly exhibits a faster rate of deactivation. Ref.25		VAR_026988
	Natural variant	214	1	R → W in BFNS1. Ref.23 Corresponds to variant rs28939684 [ dbSNP | Ensembl ].		VAR_010929
	Natural variant	228	1	H → Q in BFNS1. Ref.25		VAR_026989
	Natural variant	243	1	L → F in BFNS1. Ref.25		VAR_026990
	Natural variant	247	1	S → W in EIEE7; reduces channel currents by more than 50% in homomeric channels. Ref.26		VAR_026991
	Natural variant	284	1	Y → C in BFNS1; 30%-60% reduction of wt heteromeric current. Ratio 1:1 or 20%-30%; ratio of 1:1:2. Ref.2 Ref.10 Ref.25 Corresponds to variant rs28939683 [ dbSNP | Ensembl ].		VAR_010930
	Natural variant	306	1	A → T in BFNS1; 20%-40% reduction of wt heteromeric current. Ratio of 1:1:2. Ref.2 Ref.10 Ref.25		VAR_010931
	Natural variant	333	1	R → Q in BFNS1; moderate effect; less than 50% reduction in current compared with wt heteromeric channels. Ref.25		VAR_026992
	Natural variant	554	1	K → N in BFNS1 and EIEE7; decreases the voltage-dependence of the channel. Ref.27		VAR_026993
	Natural variant	780	1	N → T. Ref.22 Corresponds to variant rs1801475 [ dbSNP | Ensembl ].		VAR_010932
Experimental info
	Mutagenesis	52	1	S → E: 40% increase in potassium current amplitude. Ratio of 1:1. Ref.10
	Mutagenesis	52	1	S → Q: Decrease of PKA stimulation. Ratio of 1:1. Ref.10
	Mutagenesis	217	1	T → A: No effect on current or expression. Ref.21
	Mutagenesis	217	1	T → D: Abolishes currents without reducing channel protein expression. Ref.21
	Mutagenesis	279	1	G → S: More than 50% reduction of wt heteromeric current. Ratio of 1:1 and 1:1:2. Ref.10
	Sequence conflict	699	1	K → E in AAD16988. Ref.4
	Sequence conflict	854	1	R → C in AAD16988. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 2. Checksum: 22E8A0880A27B58C	FASTA	872	95,848
	10 20 30 40 50 60 MVQKSRNGGV YPGPSGEKKL KVGFVGLDPG APDSTRDGAL LIAGSEAPKR GSILSKPRAG 70 80 90 100 110 120 GAGAGKPPKR NAFYRKLQNF LYNVLERPRG WAFIYHAYVF LLVFSCLVLS VFSTIKEYEK 130 140 150 160 170 180 SSEGALYILE IVTIVVFGVE YFVRIWAAGC CCRYRGWRGR LKFARKPFCV IDIMVLIASI 190 200 210 220 230 240 AVLAAGSQGN VFATSALRSL RFLQILRMIR MDRRGGTWKL LGSVVYAHSK ELVTAWYIGF 250 260 270 280 290 300 LCLILASFLV YLAEKGENDH FDTYADALWW GLITLTTIGY GDKYPQTWNG RLLAATFTLI 310 320 330 340 350 360 GVSFFALPAG ILGSGFALKV QEQHRQKHFE KRRNPAAGLI QSAWRFYATN LSRTDLHSTW 370 380 390 400 410 420 QYYERTVTVP MYSSQTQTYG ASRLIPPLNQ LELLRNLKSK SGLAFRKDPP PEPSPSKGSP 430 440 450 460 470 480 CRGPLCGCCP GRSSQKVSLK DRVFSSPRGV AAKGKGSPQA QTVRRSPSAD QSLEDSPSKV 490 500 510 520 530 540 PKSWSFGDRS RARQAFRIKG AASRQNSEEA SLPGEDIVDD KSCPCEFVTE DLTPGLKVSI 550 560 570 580 590 600 RAVCVMRFLV SKRKFKESLR PYDVMDVIEQ YSAGHLDMLS RIKSLQSRVD QIVGRGPAIT 610 620 630 640 650 660 DKDRTKGPAE AELPEDPSMM GRLGKVEKQV LSMEKKLDFL VNIYMQRMGI PPTETEAYFG 670 680 690 700 710 720 AKEPEPAPPY HSPEDSREHV DRHGCIVKIV RSSSSTGQKN FSAPPAAPPV QCPPSTSWQP 730 740 750 760 770 780 QSHPRQGHGT SPVGDHGSLV RIPPPPAHER SLSAYGGGNR ASMEFLRQED TPGCRPPEGN 790 800 810 820 830 840 LRDSDTSISI PSVDHEELER SFSGFSISQS KENLDALNSC YAAVAPCAKV RPYIAEGESD 850 860 870 TDSDLCTPCG PPPRSATGEG PFGDVGWAGP RK
	Isoform 2 [UniParc]. Checksum: CF3F5EC2E23E21FC	FASTA	854	94,100
	10 20 30 40 50 60 MVQKSRNGGV YPGPSGEKKL KVGFVGLDPG APDSTRDGAL LIAGSEAPKR GSILSKPRAG 70 80 90 100 110 120 GAGAGKPPKR NAFYRKLQNF LYNVLERPRG WAFIYHAYVF LLVFSCLVLS VFSTIKEYEK 130 140 150 160 170 180 SSEGALYILE IVTIVVFGVE YFVRIWAAGC CCRYRGWRGR LKFARKPFCV IDIMVLIASI 190 200 210 220 230 240 AVLAAGSQGN VFATSALRSL RFLQILRMIR MDRRGGTWKL LGSVVYAHSK ELVTAWYIGF 250 260 270 280 290 300 LCLILASFLV YLAEKGENDH FDTYADALWW GLITLTTIGY GDKYPQTWNG RLLAATFTLI 310 320 330 340 350 360 GVSFFALPAG ILGSGFALKV QEQHRQKHFE KRRNPAAGLI QSAWRFYATN LSRTDLHSTW 370 380 390 400 410 420 QYYERTVTVP MYSSQTQTYG ASRLIPPLNQ LELLRNLKSK SGLAFRKDPP PEPSPSQKVS 430 440 450 460 470 480 LKDRVFSSPR GVAAKGKGSP QAQTVRRSPS ADQSLEDSPS KVPKSWSFGD RSRARQAFRI 490 500 510 520 530 540 KGAASRQNSE EASLPGEDIV DDKSCPCEFV TEDLTPGLKV SIRAVCVMRF LVSKRKFKES 550 560 570 580 590 600 LRPYDVMDVI EQYSAGHLDM LSRIKSLQSR VDQIVGRGPA ITDKDRTKGP AEAELPEDPS 610 620 630 640 650 660 MMGRLGKVEK QVLSMEKKLD FLVNIYMQRM GIPPTETEAY FGAKEPEPAP PYHSPEDSRE 670 680 690 700 710 720 HVDRHGCIVK IVRSSSSTGQ KNFSAPPAAP PVQCPPSTSW QPQSHPRQGH GTSPVGDHGS 730 740 750 760 770 780 LVRIPPPPAH ERSLSAYGGG NRASMEFLRQ EDTPGCRPPE GNLRDSDTSI SIPSVDHEEL 790 800 810 820 830 840 ERSFSGFSIS QSKENLDALN SCYAAVAPCA KVRPYIAEGE SDTDSDLCTP CGPPPRSATG 850 EGPFGDVGWA GPRK
	Isoform 3 [UniParc]. Checksum: 5228E1B8C3D8C17F	FASTA	844	93,089
	10 20 30 40 50 60 MVQKSRNGGV YPGPSGEKKL KVGFVGLDPG APDSTRDGAL LIAGSEAPKR GSILSKPRAG 70 80 90 100 110 120 GAGAGKPPKR NAFYRKLQNF LYNVLERPRG WAFIYHAYVF LLVFSCLVLS VFSTIKEYEK 130 140 150 160 170 180 SSEGALYILE IVTIVVFGVE YFVRIWAAGC CCRYRGWRGR LKFARKPFCV IDIMVLIASI 190 200 210 220 230 240 AVLAAGSQGN VFATSALRSL RFLQILRMIR MDRRGGTWKL LGSVVYAHSK ELVTAWYIGF 250 260 270 280 290 300 LCLILASFLV YLAEKGENDH FDTYADALWW GLITLTTIGY GDKYPQTWNG RLLAATFTLI 310 320 330 340 350 360 GVSFFALPAG ILGSGFALKV QEQHRQKHFE KRRNPAAGLI QSAWRFYATN LSRTDLHSTW 370 380 390 400 410 420 QYYERTVTVP MYRLIPPLNQ LELLRNLKSK SGLAFRKDPP PEPSPSQKVS LKDRVFSSPR 430 440 450 460 470 480 GVAAKGKGSP QAQTVRRSPS ADQSLEDSPS KVPKSWSFGD RSRARQAFRI KGAASRQNSE 490 500 510 520 530 540 EASLPGEDIV DDKSCPCEFV TEDLTPGLKV SIRAVCVMRF LVSKRKFKES LRPYDVMDVI 550 560 570 580 590 600 EQYSAGHLDM LSRIKSLQSR VDQIVGRGPA ITDKDRTKGP AEAELPEDPS MMGRLGKVEK 610 620 630 640 650 660 QVLSMEKKLD FLVNIYMQRM GIPPTETEAY FGAKEPEPAP PYHSPEDSRE HVDRHGCIVK 670 680 690 700 710 720 IVRSSSSTGQ KNFSAPPAAP PVQCPPSTSW QPQSHPRQGH GTSPVGDHGS LVRIPPPPAH 730 740 750 760 770 780 ERSLSAYGGG NRASMEFLRQ EDTPGCRPPE GNLRDSDTSI SIPSVDHEEL ERSFSGFSIS 790 800 810 820 830 840 QSKENLDALN SCYAAVAPCA KVRPYIAEGE SDTDSDLCTP CGPPPRSATG EGPFGDVGWA GPRK
	Isoform 4 [UniParc]. Checksum: 065E37AF63726B10	FASTA	841	92,596
	10 20 30 40 50 60 MVQKSRNGGV YPGPSGEKKL KVGFVGLDPG APDSTRDGAL LIAGSEAPKR GSILSKPRAG 70 80 90 100 110 120 GAGAGKPPKR NAFYRKLQNF LYNVLERPRG WAFIYHAYVF LLVFSCLVLS VFSTIKEYEK 130 140 150 160 170 180 SSEGALYILE IVTIVVFGVE YFVRIWAAGC CCRYRGWRGR LKFARKPFCV IDIMVLIASI 190 200 210 220 230 240 AVLAAGSQGN VFATSALRSL RFLQILRMIR MDRRGGTWKL LGSVVYAHSK ELVTAWYIGF 250 260 270 280 290 300 LCLILASFLV YLAEKGENDH FDTYADALWW GLITLTTIGY GDKYPQTWNG RLLAATFTLI 310 320 330 340 350 360 GVSFFALPAG ILGSGFALKV QEQHRQKHFE KRRNPAAGLI QSAWRFYATN LSRTDLHSTW 370 380 390 400 410 420 QYYERTVTVP MYSSQTQTYG ASRLIPPLNQ LELLRNLKSK SGLAFRKDPP PEPSPSPRGV 430 440 450 460 470 480 AAKGKGSPQA QTVRRSPSAD QSLEDSPSKV PKSWSFGDRS RARQAFRIKG AASRQNSEAS 490 500 510 520 530 540 LPGEDIVDDK SCPCEFVTED LTPGLKVSIR AVCVMRFLVS KRKFKESLRP YDVMDVIEQY 550 560 570 580 590 600 SAGHLDMLSR IKSLQSRVDQ IVGRGPAITD KDRTKGPAEA ELPEDPSMMG RLGKVEKQVL 610 620 630 640 650 660 SMEKKLDFLV NIYMQRMGIP PTETEAYFGA KEPEPAPPYH SPEDSREHVD RHGCIVKIVR 670 680 690 700 710 720 SSSSTGQKNF SAPPAAPPVQ CPPSTSWQPQ SHPRQGHGTS PVGDHGSLVR IPPPPAHERS 730 740 750 760 770 780 LSAYGGGNRA SMEFLRQEDT PGCRPPEGNL RDSDTSISIP SVDHEELERS FSGFSISQSK 790 800 810 820 830 840 ENLDALNSCY AAVAPCAKVR PYIAEGESDT DSDLCTPCGP PPRSATGEGP FGDVGWAGPR K
	Isoform 5 [UniParc]. Checksum: AF6F5146789F4167	FASTA	843	93,057
	10 20 30 40 50 60 MVQKSRNGGV YPGPSGEKKL KVGFVGLDPG APDSTRDGAL LIAGSEAPKR GSILSKPRAG 70 80 90 100 110 120 GAGAGKPPKR NAFYRKLQNF LYNVLERPRG WAFIYHAYVF LLVFSCLVLS VFSTIKEYEK 130 140 150 160 170 180 SSEGALYILE IVTIVVFGVE YFVRIWAAGC CCRYRGWRGR LKFARKPFCV IDIMVLIASI 190 200 210 220 230 240 AVLAAGSQGN VFATSALRSL RFLQILRMIR MDRRGGTWKL LGSVVYAHSK ELVTAWYIGF 250 260 270 280 290 300 LCLILASFLV YLAEKGENDH FDTYADALWW GLITLTTIGY GDKYPQTWNG RLLAATFTLI 310 320 330 340 350 360 GVSFFALPAQ EQHRQKHFEK RRNPAAGLIQ SAWRFYATNL SRTDLHSTWQ YYERTVTVPM 370 380 390 400 410 420 YSSQTQTYGA SRLIPPLNQL ELLRNLKSKS GLAFRKDPPP EPSPSQKVSL KDRVFSSPRG 430 440 450 460 470 480 VAAKGKGSPQ AQTVRRSPSA DQSLEDSPSK VPKSWSFGDR SRARQAFRIK GAASRQNSEE 490 500 510 520 530 540 ASLPGEDIVD DKSCPCEFVT EDLTPGLKVS IRAVCVMRFL VSKRKFKESL RPYDVMDVIE 550 560 570 580 590 600 QYSAGHLDML SRIKSLQSRV DQIVGRGPAI TDKDRTKGPA EAELPEDPSM MGRLGKVEKQ 610 620 630 640 650 660 VLSMEKKLDF LVNIYMQRMG IPPTETEAYF GAKEPEPAPP YHSPEDSREH VDRHGCIVKI 670 680 690 700 710 720 VRSSSSTGQK NFSAPPAAPP VQCPPSTSWQ PQSHPRQGHG TSPVGDHGSL VRIPPPPAHE 730 740 750 760 770 780 RSLSAYGGGN RASMEFLRQE DTPGCRPPEG NLRDSDTSIS IPSVDHEELE RSFSGFSISQ 790 800 810 820 830 840 SKENLDALNS CYAAVAPCAK VRPYIAEGES DTDSDLCTPC GPPPRSATGE GPFGDVGWAG PRK
	Isoform 6 (HNSPC) [UniParc]. Checksum: 9415BC4FC2F84675	FASTA	393	44,261
	10 20 30 40 50 60 MVQKSRNGGV YPGPSGEKKL KVGFVGLDPG APDSTRDGAL LIAGSEAPKR GSILSKPRAG 70 80 90 100 110 120 GAGAGKPPKR NAFYRKLQNF LYNVLERPRG WAFIYHAYVF LLVFSCLVLS VFSTIKEYEK 130 140 150 160 170 180 SSEGALYILE IVTIVVFGVE YFVRIWAAGC CCRYRGWRGR LKFARKPFCV IDIMVLIASI 190 200 210 220 230 240 AVLAAGSQGN VFATSALRSL RFLQILRMIR MDRRGGTWKL LGSVVYAHSK ELVTAWYIGF 250 260 270 280 290 300 LCLILASFLV YLAEKGENDH FDTYADALWW GLITLTTIGY GDKYPQTWNG RLLAATFTLI 310 320 330 340 350 360 GVSFFALPAG ILGSGFALKV QEQHRQKHFE KRRNPAAGLI QSAWRFYATN LSRTDLHSTW 370 380 390 QYYERTVTVP MYRYRRRAPA TKQLFHFLFS ICS

References

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[1]	"Identification and cloning of neuroblastoma-specific and nerve tissue-specific genes through compiled expression profiles." Yokoyama M., Nishi Y., Yoshii J., Okubo K., Matsubara K. DNA Res. 3:311-320(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6). Tissue: Neuroblastoma.
[2]	"A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns." Singh N.A., Charlier C., Stauffer D., DuPont B.R., Leach R.J., Melis R., Ronen G.M., Bjerre I., Quattlebaum T., Murphy J.V., McHarg M.L., Gagnon D., Rosales T.O., Peiffer A., Anderson V.E., Leppert M. Nat. Genet. 18:25-29(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS BFNS1 CYS-284 AND THR-306. Tissue: Brain, Fetal brain and Temporal cortex.
[3]	"A potassium channel mutation in neonatal human epilepsy." Biervert C., Schroeder B.C., Kubisch C., Berkovic S.F., Propping P., Jentsch T.J., Steinlein O.K. Science 279:403-406(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3). Tissue: Fetal brain.
[4]	"KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel." Wang H.-S., Pan Z., Shi W., Brown B.S., Wymore R.S., Cohen I.S., Dixon J.E., McKinnon D. Science 282:1890-1893(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
[5]	"The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3." Tinel N., Lauritzen I., Chouabe C., Lazdunski M., Borsotto M. FEBS Lett. 438:171-176(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 5).
[6]	"Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy." Yang W.-P., Levesque P.C., Little W.A., Conder M.L., Ramakrishnan P., Neubauer M.G., Blanar M.A. J. Biol. Chem. 273:19419-19423(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION. Tissue: Brain and Fetal brain.
[7]	"Differential expression of KCNQ2 splice variants: implications to M current function during neuronal development." Smith J.S., Iannotti C.A., Dargis P.G., Christian E.P., Aiyar J. J. Neurosci. 21:1096-1103(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Brain.
[8]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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 6). Tissue: Eye.
[10]	"Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy." Schroeder B.C., Kubisch C., Stein V., Jentsch T.J. Nature 396:687-690(1998) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF SER-52 AND GLY-279, PHOSPHORYLATION AT SER-52, CHARACTERIZATION OF VARIANTS CYS-284 AND THR-306.
[11]	"Two types of K(+) channel subunit, Erg1 and KCNQ2/3, contribute to the M-like current in a mammalian neuronal cell." Selyanko A.A., Hadley J.K., Wood I.C., Abogadie F.C., Delmas P., Buckley N.J., London B., Brown D.A. J. Neurosci. 19:7742-7756(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN M-LIKE CURRENT.
[12]	"M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 subunit." Tinel N., Diochot S., Lauritzen I., Barhanin J., Lazdunski M., Borsotto M. FEBS Lett. 480:137-141(2000) [PubMed] [Europe PMC] [Abstract] Cited for: ASSOCIATION WITH KCNE2.
[13]	"Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy." Schwake M., Pusch M., Kharkovets T., Jentsch T.J. J. Biol. Chem. 275:13343-13348(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SURFACE EXPRESSION OF HETEROMERS.
[14]	"Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels that underlie the neuronal M current." Shapiro M.S., Roche J.P., Kaftan E.J., Cruzblanca H., Mackie K., Hille B. J. Neurosci. 20:1710-1721(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INHIBITION BY M1 MUSCARINIC RECEPTORS.
[15]	"Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors." Selyanko A.A., Hadley J.K., Wood I.C., Abogadie F.C., Jentsch T.J., Brown D.A. J. Physiol. (Lond.) 522:349-355(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INHIBITION BY M1 MUSCARINIC RECEPTORS.
[16]	"Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine." Main M.J., Cryan J.E., Dupere J.R., Cox B., Clare J.J., Burbidge S.A. Mol. Pharmacol. 58:253-262(2000) [PubMed] [Europe PMC] [Abstract] Cited for: ACTIVATION BY RETICABINE.
[17]	"Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels." Wickenden A.D., Yu W., Zou A., Jegla T., Wagoner P.K. Mol. Pharmacol. 58:591-600(2000) [PubMed] [Europe PMC] [Abstract] Cited for: ACTIVATION BY RETICABINE.
[18]	"The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells transfected with human KCNQ2/3 subunits." Rundfeldt C., Netzer R. Neurosci. Lett. 282:73-76(2000) [PubMed] [Europe PMC] [Abstract] Cited for: ACTIVATION BY RETICABINE.
[19]	"Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy." Cooper E.C., Aldape K.D., Abosch A., Barbaro N.M., Berger M.S., Peacock W.S., Jan Y.N., Jan L.Y. Proc. Natl. Acad. Sci. U.S.A. 97:4914-4919(2000) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, BIOCHEMICAL CHARACTERIZATION.
[20]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[21]	"Identification by mass spectrometry and functional characterization of two phosphorylation sites of KCNQ2/KCNQ3 channels." Surti T.S., Huang L., Jan Y.N., Jan L.Y., Cooper E.C. Proc. Natl. Acad. Sci. U.S.A. 102:17828-17833(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-217, MUTAGENESIS OF THR-217.
[22]	"Structural and mutational analysis of KCNQ2, the major gene locus for benign familial neonatal convulsions." Biervert C., Steinlein O.K. Hum. Genet. 104:234-240(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT THR-780.
[23]	"Benign familial neonatal convulsions (BFNC) resulting from mutation of the KCNQ2 voltage sensor." Miraglia del Giudice E., Coppola G., Scuccimarra G., Cirillo G., Bellini G., Pascotto A. Eur. J. Hum. Genet. 8:994-997(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BFNS1 TRP-214.
[24]	"Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K+ channel." Dedek K., Kunath B., Kananura C., Reuner U., Jentsch T.J., Steinlein O.K. Proc. Natl. Acad. Sci. U.S.A. 98:12272-12277(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BFNS1 TRP-207, CHARACTERIZATION OF VARIANT BFNS1 TRP-207.
[25]	"KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum." The BFNC physician consortium Singh N.A., Westenskow P., Charlier C., Pappas C., Leslie J., Dillon J., Anderson V.E., Sanguinetti M.C., Leppert M.F. Brain 126:2726-2737(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BFNS1 VAL-208; GLN-228; PHE-243; CYS-284; THR-306 AND GLN-333, CHARACTERIZATION OF VARIANTS BFNS1 VAL-208 AND GLN-333.
[26]	"Neonatal convulsions and epileptic encephalopathy in an Italian family with a missense mutation in the fifth transmembrane region of KCNQ2." Dedek K., Fusco L., Teloy N., Steinlein O.K. Epilepsy Res. 54:21-27(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EIEE7 TRP-247, CHARACTERIZATION OF VARIANT EIEE7 TRP-247.
[27]	"A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation." Borgatti R., Zucca C., Cavallini A., Ferrario M., Panzeri C., Castaldo P., Soldovieri M.V., Baschirotto C., Bresolin N., Dalla Bernardina B., Taglialatela M., Bassi M.T. Neurology 63:57-65(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BFNS1 ASN-554, VARIANT EIEE7 ASN-554, CHARACTERIZATION OF VARIANT BFNS1 ASN-554.
[28]	"Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations." Wuttke T.V., Jurkat-Rott K., Paulus W., Garncarek M., Lehmann-Horn F., Lerche H. Neurology 69:2045-2053(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLN-207, CHARACTERIZATION OF VARIANT GLN-207.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	D82346 mRNA. Translation: BAA11557.1. AF033348 mRNA. Translation: AAB97315.1. Y15065 mRNA. Translation: CAA75348.1. AF110020 mRNA. Translation: AAD16988.1. AF074247 mRNA. Translation: AAC25921.1. AL353658, AL121827, AL121829 Genomic DNA. Translation: CAH72958.1. AL353658, AL121827, AL121829 Genomic DNA. Translation: CAH72959.1. AL121827, AL121829, AL353658 Genomic DNA. Translation: CAI95054.1. AL121829, AL121827, AL353658 Genomic DNA. Translation: CAI95740.1. AL121829, AL121827, AL353658 Genomic DNA. Translation: CAI95744.1. BC000699 mRNA. Translation: AAH00699.1.
PIR	JC5275.
RefSeq	NP_004509.2. NM_004518.4. NP_742104.1. NM_172106.1. NP_742105.1. NM_172107.2. NP_742106.1. NM_172108.3. NP_742107.1. NM_172109.1.
UniGene	Hs.161851. Hs.652468.
3D structure databases
ProteinModelPortal	O43526.
SMR	O43526. Positions 65-316, 530-555, 615-644.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	109986. 5 interactions.
IntAct	O43526. 1 interaction.
MINT	MINT-8402812.
STRING	9606.ENSP00000352035.
Chemistry
BindingDB	O43526.
ChEMBL	CHEMBL2363063.
DrugBank	DB00321. Amitriptyline.
GuidetoPHARMACOLOGY	561.
Protein family/group databases
TCDB	1.A.1.15.2. the voltage-gated ion channel (vic) superfamily.
PTM databases
PhosphoSite	O43526.
Proteomic databases
PaxDb	O43526.
PRIDE	O43526.
Protocols and materials databases
DNASU	3785.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000344425; ENSP00000345523; ENSG00000075043. [O43526-6] ENST00000344462; ENSP00000339611; ENSG00000075043. [O43526-4] ENST00000357249; ENSP00000349789; ENSG00000075043. [O43526-2] ENST00000359125; ENSP00000352035; ENSG00000075043. [O43526-1] ENST00000360480; ENSP00000353668; ENSG00000075043. [O43526-3]
GeneID	3785.
KEGG	hsa:3785.
UCSC	uc002yey.1. human. [O43526-1] uc002yez.1. human. [O43526-4] uc002yfa.1. human. [O43526-2] uc002yfb.1. human. [O43526-3]
Organism-specific databases
CTD	3785.
GeneCards	GC20M062038.
HGNC	HGNC:6296. KCNQ2.
HPA	HPA016642.
MIM	121200. phenotype. 602235. gene. 613720. phenotype.
neXtProt	NX_O43526.
Orphanet	306. Benign familial infantile seizures. 1949. Benign familial neonatal seizures. 140927. Benign familial neonatal-infantile seizures. 1934. Early infantile epileptic encephalopathy.
PharmGKB	PA30074.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1226.
HOVERGEN	HBG059014.
KO	K04927.
OrthoDB	EOG73804Z.
PhylomeDB	O43526.
TreeFam	TF315186.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	O43526.
Bgee	O43526.
CleanEx	HS_KCNQ2.
Genevestigator	O43526.
Family and domain databases
InterPro	IPR020969. Ankyrin-G_BS. IPR005821. Ion_trans_dom. IPR003091. K_chnl. IPR003937. K_chnl_volt-dep_KCNQ. IPR003947. K_chnl_volt-dep_KCNQ2. IPR013821. K_chnl_volt-dep_KCNQ_C. IPR028325. VG_K_chnl. [Graphical view]
PANTHER	PTHR11537. PTHR11537. 1 hit.
Pfam	PF00520. Ion_trans. 1 hit. PF03520. KCNQ_channel. 1 hit. PF11956. KCNQC3-Ank-G_bd. 1 hit. [Graphical view]
PRINTS	PR00169. KCHANNEL. PR01461. KCNQ2CHANNEL. PR01459. KCNQCHANNEL.
ProtoNet	Search...
Other
ChiTaRS	KCNQ2. human.
GeneWiki	KvLQT2.
GenomeRNAi	3785.
NextBio	14859.
PRO	O43526.
SOURCE	Search...

Entry information

Entry name

KCNQ2_HUMAN

Accession

Primary (citable) accession number: O43526
Secondary accession number(s): O43796 , O75580, O95845, Q4VXP4, Q4VXR6, Q5VYT8, Q96J59, Q99454

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 2001
Last sequence update:	June 1, 2001
Last modified:	April 16, 2014
This is version 152 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.