P51788 (CLCN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Chloride channel protein 2
Short name=ClC-2

Gene names

Name:

CLCN2

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	898 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport. Ref.7 Ref.11
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Ubiquitously expressed. Moderately expressed in aortic and coronary vascular smooth muscle cells and expressed at a low level in aortic endothelial cells. Ref.6
Involvement in disease	Epilepsy, idiopathic generalized 11 (EIG11) [MIM:607628]: A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Juvenile absence epilepsy 2 (JAE2) [MIM:607628]: A subtype of idiopathic generalized epilepsy characterized by onset occurring around puberty, absence seizures, generalized tonic-clonic seizures (GTCS), GTCS on awakening, and myoclonic seizures. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Juvenile myoclonic epilepsy 8 (EJM8) [MIM:607628]: A subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
Miscellaneous	The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The absence of conserved gating glutamate residues is typical for family members that function as channels By similarity.
Sequence similarities	Belongs to the chloride channel (TC 2.A.49) family. ClC-2/CLCN2 subfamily. [View classification] Contains 2 CBS domains.
Sequence caution	The sequence AAH21578.1 differs from that shown. Reason: Erroneous translation. Wrong choice of frame.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Epilepsy
Domain	CBS domain Repeat Transmembrane Transmembrane helix
Ligand	Chloride
Molecular function	Chloride channel Ion channel Voltage-gated channel
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation involved in salivary gland development Inferred from electronic annotation. Source: Compara retina development in camera-type eye Inferred from electronic annotation. Source: Compara
Cellular_component	chloride channel complex Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	voltage-gated chloride channel activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P51788-1)

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: P51788-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-359: Missing.
     443-485: FWMSALATTI...SMAAWFPDGI → HLGVWWVKAW...WSGQLRWQER
     486-898: 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 3 (identifier: P51788-3)

The sequence of this isoform differs from the canonical sequence as follows:
     466-482: Missing.

Isoform 4 (identifier: P51788-4)

The sequence of this isoform differs from the canonical sequence as follows:
     74-117: Missing.

Note: No experimental confirmation available.

Isoform 5 (identifier: P51788-5)

The sequence of this isoform differs from the canonical sequence as follows:
     806-834: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 898	898	Chloride channel protein 2		PRO_0000094433
Regions
	Topological domain	1 – 87	87	Cytoplasmic By similarity
	Transmembrane	88 – 121	34	Helical; By similarity
	Transmembrane	130 – 155	26	Helical; By similarity
	Intramembrane	164 – 171	8	Helical; Potential
	Transmembrane	180 – 198	19	Helical; By similarity
	Transmembrane	205 – 223	19	Helical; By similarity
	Intramembrane	239 – 251	13	Helical; By similarity
	Intramembrane	255 – 263	9	Helical; By similarity
	Transmembrane	275 – 295	21	Helical; By similarity
	Transmembrane	321 – 349	29	Helical; By similarity
	Transmembrane	358 – 377	20	Helical; By similarity
	Transmembrane	429 – 449	21	Helical; By similarity
	Transmembrane	457 – 480	24	Helical; By similarity
	Intramembrane	497 – 511	15	Helical; By similarity
	Intramembrane	512 – 513	2	Note=Loop between two helices; By similarity
	Intramembrane	514 – 525	12	Helical; By similarity
	Intramembrane	526 – 530	5	Note=Loop between two helices; By similarity
	Transmembrane	531 – 548	18	Helical; By similarity
	Topological domain	549 – 898	350	Cytoplasmic By similarity
	Domain	584 – 642	59	CBS 1
	Domain	790 – 850	61	CBS 2
	Motif	161 – 165	5	Selectivity filter part_1 By similarity
	Motif	203 – 207	5	Selectivity filter part_2 By similarity
	Motif	457 – 461	5	Selectivity filter part_3 By similarity
	Compositional bias	2 – 6	5	Poly-Ala
Sites
	Binding site	162	1	Chloride By similarity
	Binding site	459	1	Chloride; via amide nitrogen By similarity
	Binding site	553	1	Chloride By similarity
Natural variations
	Alternative sequence	1 – 359	359	Missing in isoform 2.		VSP_007831
	Alternative sequence	74 – 117	44	Missing in isoform 4.		VSP_045457
	Alternative sequence	443 – 485	43	FWMSA…FPDGI → HLGVWWVKAWLPGSQMEFIR TAAPTGLCLGATLWSGQLRW QER in isoform 2.		VSP_007832
	Alternative sequence	466 – 482	17	Missing in isoform 3.		VSP_036456
	Alternative sequence	486 – 898	413	Missing in isoform 2.		VSP_036455
	Alternative sequence	806 – 834	29	Missing in isoform 5.		VSP_045458
	Natural variant	48	1	P → R Reduces channel activity. Ref.9		VAR_057886
	Natural variant	68	1	R → H Reduces channel activity. Ref.9		VAR_057887
	Natural variant	199	1	G → A No effect. Ref.9		VAR_057888
	Natural variant	235	1	R → Q Confers susceptibility to juvenile myoclonic epilepsy type 8; the mutant channel has accelerated deactivation rates compared to wild-type, but normal activation and peak current. Ref.11		VAR_057889
	Natural variant	577	1	R → Q Confers susceptibility to idiopathic generalized epilepsy type 11; the mutant channel has accelerated deactivation rates compared to wild-type, but normal activation and peak current. Ref.11		VAR_057890
	Natural variant	644	1	R → C No effect. Ref.11		VAR_057891
	Natural variant	646	1	R → Q Reduces channel activity. Ref.9		VAR_057892
	Natural variant	668	1	T → S. Ref.1 Ref.3 Ref.9 Corresponds to variant rs9820367 [ dbSNP | Ensembl ].		VAR_054550
	Natural variant	715	1	G → E May confer susceptibility to juvenile absence epilepsy type 2. Ref.8 Corresponds to variant rs28938470 [ dbSNP | Ensembl ].		VAR_015989
	Natural variant	718	1	E → D. Corresponds to variant rs2228292 [ dbSNP | Ensembl ].		VAR_054551
	Natural variant	719	1	S → L in a patient with childhood absence epilepsy. Ref.10		VAR_058426
	Natural variant	725	1	R → W Slightly faster channel activation. Ref.9		VAR_057893
	Natural variant	747	1	R → H Slightly faster channel activation. Ref.9		VAR_057894
Experimental info
	Sequence conflict	17	1	Y → H in AAB34722. Ref.1
	Sequence conflict	537	1	A → V in AAH21578. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 9, 2010. Version 2. Checksum: 5F20FA8713C0C74E	FASTA	898	98,535
	10 20 30 40 50 60 MAAAAAEEGM EPRALQYEQT LMYGRYTQDL GAFAKEEAAR IRLGGPEPWK GPPSSRAAPE 70 80 90 100 110 120 LLEYGRSRCA RCRVCSVRCH KFLVSRVGED WIFLVLLGLL MALVSWVMDY AIAACLQAQQ 130 140 150 160 170 180 WMSRGLNTSI LLQYLAWVTY PVVLITFSAG FTQILAPQAV GSGIPEMKTI LRGVVLKEYL 190 200 210 220 230 240 TLKTFIAKVI GLTCALGSGM PLGKEGPFVH IASMCAALLS KFLSLFGGIY ENESRNTEML 250 260 270 280 290 300 AAACAVGVGC CFAAPIGGVL FSIEVTSTFF AVRNYWRGFF AATFSAFIFR VLAVWNRDEE 310 320 330 340 350 360 TITALFKTRF RLDFPFDLQE LPAFAVIGIA SGFGGALFVY LNRKIVQVMR KQKTINRFLM 370 380 390 400 410 420 RKRLLFPALV TLLISTLTFP PGFGQFMAGQ LSQKETLVTL FDNRTWVRQG LVEELEPPST 430 440 450 460 470 480 SQAWNPPRAN VFLTLVIFIL MKFWMSALAT TIPVPCGAFM PVFVIGAAFG RLVGESMAAW 490 500 510 520 530 540 FPDGIHTDSS TYRIVPGGYA VVGAAALAGA VTHTVSTAVI VFELTGQIAH ILPVMIAVIL 550 560 570 580 590 600 ANAVAQSLQP SLYDSIIRIK KLPYLPELGW GRHQQYRVRV EDIMVRDVPH VALSCTFRDL 610 620 630 640 650 660 RLALHRTKGR MLALVESPES MILLGSIERS QVVALLGAQL SPARRRQHMQ ERRATQTSPL 670 680 690 700 710 720 SDQEGPPTPE ASVCFQVNTE DSAFPAARGE THKPLKPALK RGPSVTRNLG ESPTGSAESA 730 740 750 760 770 780 GIALRSLFCG SPPPEAASEK LESCEKRKLK RVRISLASDA DLEGEMSPEE ILEWEEQQLD 790 800 810 820 830 840 EPVNFSDCKI DPAPFQLVER TSLHKTHTIF SLLGVDHAYV TSIGRLIGIV TLKELRKAIE 850 860 870 880 890 GSVTAQGVKV RPPLASFRDS ATSSSDTETT EVHALWGPHS RHGLPREGSP SDSDDKCQ
	Isoform 2 [UniParc]. Checksum: 69843C961A8FC3DF	FASTA	126	14,383
	10 20 30 40 50 60 MRKRLLFPAL VTLLISTLTF PPGFGQFMAG QLSQKETLVT LFDNRTWVRQ GLVEELEPPS 70 80 90 100 110 120 TSQAWNPPRA NVFLTLVIFI LMKHLGVWWV KAWLPGSQME FIRTAAPTGL CLGATLWSGQ LRWQER
	Isoform 3 [UniParc]. Checksum: F44E1264FC92758F	FASTA	881	96,786
	10 20 30 40 50 60 MAAAAAEEGM EPRALQYEQT LMYGRYTQDL GAFAKEEAAR IRLGGPEPWK GPPSSRAAPE 70 80 90 100 110 120 LLEYGRSRCA RCRVCSVRCH KFLVSRVGED WIFLVLLGLL MALVSWVMDY AIAACLQAQQ 130 140 150 160 170 180 WMSRGLNTSI LLQYLAWVTY PVVLITFSAG FTQILAPQAV GSGIPEMKTI LRGVVLKEYL 190 200 210 220 230 240 TLKTFIAKVI GLTCALGSGM PLGKEGPFVH IASMCAALLS KFLSLFGGIY ENESRNTEML 250 260 270 280 290 300 AAACAVGVGC CFAAPIGGVL FSIEVTSTFF AVRNYWRGFF AATFSAFIFR VLAVWNRDEE 310 320 330 340 350 360 TITALFKTRF RLDFPFDLQE LPAFAVIGIA SGFGGALFVY LNRKIVQVMR KQKTINRFLM 370 380 390 400 410 420 RKRLLFPALV TLLISTLTFP PGFGQFMAGQ LSQKETLVTL FDNRTWVRQG LVEELEPPST 430 440 450 460 470 480 SQAWNPPRAN VFLTLVIFIL MKFWMSALAT TIPVPCGAFM PVFVIDGIHT DSSTYRIVPG 490 500 510 520 530 540 GYAVVGAAAL AGAVTHTVST AVIVFELTGQ IAHILPVMIA VILANAVAQS LQPSLYDSII 550 560 570 580 590 600 RIKKLPYLPE LGWGRHQQYR VRVEDIMVRD VPHVALSCTF RDLRLALHRT KGRMLALVES 610 620 630 640 650 660 PESMILLGSI ERSQVVALLG AQLSPARRRQ HMQERRATQT SPLSDQEGPP TPEASVCFQV 670 680 690 700 710 720 NTEDSAFPAA RGETHKPLKP ALKRGPSVTR NLGESPTGSA ESAGIALRSL FCGSPPPEAA 730 740 750 760 770 780 SEKLESCEKR KLKRVRISLA SDADLEGEMS PEEILEWEEQ QLDEPVNFSD CKIDPAPFQL 790 800 810 820 830 840 VERTSLHKTH TIFSLLGVDH AYVTSIGRLI GIVTLKELRK AIEGSVTAQG VKVRPPLASF 850 860 870 880 RDSATSSSDT ETTEVHALWG PHSRHGLPRE GSPSDSDDKC Q
	Isoform 4 [UniParc]. Checksum: EA949779A2E7B686	FASTA	854	93,583
	10 20 30 40 50 60 MAAAAAEEGM EPRALQYEQT LMYGRYTQDL GAFAKEEAAR IRLGGPEPWK GPPSSRAAPE 70 80 90 100 110 120 LLEYGRSRCA RCRAQQWMSR GLNTSILLQY LAWVTYPVVL ITFSAGFTQI LAPQAVGSGI 130 140 150 160 170 180 PEMKTILRGV VLKEYLTLKT FIAKVIGLTC ALGSGMPLGK EGPFVHIASM CAALLSKFLS 190 200 210 220 230 240 LFGGIYENES RNTEMLAAAC AVGVGCCFAA PIGGVLFSIE VTSTFFAVRN YWRGFFAATF 250 260 270 280 290 300 SAFIFRVLAV WNRDEETITA LFKTRFRLDF PFDLQELPAF AVIGIASGFG GALFVYLNRK 310 320 330 340 350 360 IVQVMRKQKT INRFLMRKRL LFPALVTLLI STLTFPPGFG QFMAGQLSQK ETLVTLFDNR 370 380 390 400 410 420 TWVRQGLVEE LEPPSTSQAW NPPRANVFLT LVIFILMKFW MSALATTIPV PCGAFMPVFV 430 440 450 460 470 480 IGAAFGRLVG ESMAAWFPDG IHTDSSTYRI VPGGYAVVGA AALAGAVTHT VSTAVIVFEL 490 500 510 520 530 540 TGQIAHILPV MIAVILANAV AQSLQPSLYD SIIRIKKLPY LPELGWGRHQ QYRVRVEDIM 550 560 570 580 590 600 VRDVPHVALS CTFRDLRLAL HRTKGRMLAL VESPESMILL GSIERSQVVA LLGAQLSPAR 610 620 630 640 650 660 RRQHMQERRA TQTSPLSDQE GPPTPEASVC FQVNTEDSAF PAARGETHKP LKPALKRGPS 670 680 690 700 710 720 VTRNLGESPT GSAESAGIAL RSLFCGSPPP EAASEKLESC EKRKLKRVRI SLASDADLEG 730 740 750 760 770 780 EMSPEEILEW EEQQLDEPVN FSDCKIDPAP FQLVERTSLH KTHTIFSLLG VDHAYVTSIG 790 800 810 820 830 840 RLIGIVTLKE LRKAIEGSVT AQGVKVRPPL ASFRDSATSS SDTETTEVHA LWGPHSRHGL 850 PREGSPSDSD DKCQ
	Isoform 5 [UniParc]. Checksum: E0D9292146DD1AA5	FASTA	869	95,399
	10 20 30 40 50 60 MAAAAAEEGM EPRALQYEQT LMYGRYTQDL GAFAKEEAAR IRLGGPEPWK GPPSSRAAPE 70 80 90 100 110 120 LLEYGRSRCA RCRVCSVRCH KFLVSRVGED WIFLVLLGLL MALVSWVMDY AIAACLQAQQ 130 140 150 160 170 180 WMSRGLNTSI LLQYLAWVTY PVVLITFSAG FTQILAPQAV GSGIPEMKTI LRGVVLKEYL 190 200 210 220 230 240 TLKTFIAKVI GLTCALGSGM PLGKEGPFVH IASMCAALLS KFLSLFGGIY ENESRNTEML 250 260 270 280 290 300 AAACAVGVGC CFAAPIGGVL FSIEVTSTFF AVRNYWRGFF AATFSAFIFR VLAVWNRDEE 310 320 330 340 350 360 TITALFKTRF RLDFPFDLQE LPAFAVIGIA SGFGGALFVY LNRKIVQVMR KQKTINRFLM 370 380 390 400 410 420 RKRLLFPALV TLLISTLTFP PGFGQFMAGQ LSQKETLVTL FDNRTWVRQG LVEELEPPST 430 440 450 460 470 480 SQAWNPPRAN VFLTLVIFIL MKFWMSALAT TIPVPCGAFM PVFVIGAAFG RLVGESMAAW 490 500 510 520 530 540 FPDGIHTDSS TYRIVPGGYA VVGAAALAGA VTHTVSTAVI VFELTGQIAH ILPVMIAVIL 550 560 570 580 590 600 ANAVAQSLQP SLYDSIIRIK KLPYLPELGW GRHQQYRVRV EDIMVRDVPH VALSCTFRDL 610 620 630 640 650 660 RLALHRTKGR MLALVESPES MILLGSIERS QVVALLGAQL SPARRRQHMQ ERRATQTSPL 670 680 690 700 710 720 SDQEGPPTPE ASVCFQVNTE DSAFPAARGE THKPLKPALK RGPSVTRNLG ESPTGSAESA 730 740 750 760 770 780 GIALRSLFCG SPPPEAASEK LESCEKRKLK RVRISLASDA DLEGEMSPEE ILEWEEQQLD 790 800 810 820 830 840 EPVNFSDCKI DPAPFQLVER TSLHKLRKAI EGSVTAQGVK VRPPLASFRD SATSSSDTET 850 860 TEVHALWGPH SRHGLPREGS PSDSDDKCQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a putative human voltage-gated chloride channel (ClC-2) cDNA widely expressed in human tissues." Cid L.P., Montrose-Rafizadeh C., Smith D.I., Guggino W.B., Cutting G.R. Hum. Mol. Genet. 4:407-413(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-668. Tissue: Placenta.
[2]	Rae J.L., Shepard A.R. Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Lens epithelium.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5), VARIANT SER-668. Tissue: Testis.
[4]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORMS 2 AND 3). Tissue: Lung and Uterus.
[6]	"Expression of CLCN voltage-gated chloride channel genes in human blood vessels." Lamb F.S., Clayton G.H., Liu B.-X., Smith R.L., Barna T.J., Schutte B.C. J. Mol. Cell. Cardiol. 31:657-666(1999) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY. Tissue: Aortic endothelium and Vascular smooth muscle.
[7]	"Voltage-dependent and -independent titration of specific residues accounts for complex gating of a ClC chloride channel by extracellular protons." Niemeyer M.I., Cid L.P., Yusef Y.R., Briones R., Sepulveda F.V. J. Physiol. (Lond.) 587:1387-1400(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies." Haug K., Warnstedt M., Alekov A.K., Sander T., Ramirez A., Poser B., Maljevic S., Hebeisen S., Kubisch C., Rebstock J., Horvath S., Hallmann K., Dullinger J.S., Rau B., Haverkamp F., Beyenburg S., Schulz H., Janz D. , Giese B., Mueller-Newen G., Propping P., Elger C.E., Fahlke C., Lerche H., Heils A. Nat. Genet. 33:527-532(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLU-715.
[9]	"Alterations in the cytoplasmic domain of CLCN2 result in altered gating kinetics." Paul J., Jeyaraj S., Huber S.M., Seebohm G., Boehmer C., Lang F., Kremsner P.G., Kun J.F.J. Cell. Physiol. Biochem. 20:441-454(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARG-48; HIS-68; ALA-199; GLN-646; SER-668; TRP-725 AND HIS-747, CHARACTERIZATION OF VARIANTS ARG-48; HIS-68; ALA-199; GLN-646; TRP-725 AND HIS-747.
[10]	"Clinical and genetic familial study of a large cohort of Italian children with idiopathic epilepsy." Combi R., Grioni D., Contri M., Redaelli S., Redaelli F., Bassi M.T., Barisani D., Lavitrano M.L., Tredici G., Tenchini M.L., Bertolini M., Dalpra L. Brain Res. Bull. 79:89-96(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-719.
[11]	"Two novel CLCN2 mutations accelerating chloride channel deactivation are associated with idiopathic generalized epilepsy." Saint-Martin C., Gauvain G., Teodorescu G., Gourfinkel-An I., Fedirko E., Weber Y.G., Maljevic S., Ernst J.-P., Garcia-Olivares J., Fahlke C., Nabbout R., LeGuern E., Lerche H., Christophe Poncer J., Depienne C. Hum. Mutat. 30:397-405(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GLN-235; GLN-577 AND CYS-644, CHARACTERIZATION OF VARIANTS GLN-235; GLN-577 AND CYS-644, FUNCTION.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	S77770 mRNA. Translation: AAB34722.2. AF026004 mRNA. Translation: AAB88807.1. AK298952 mRNA. Translation: BAG61051.1. AK302759 mRNA. Translation: BAG63970.1. AC078797 Genomic DNA. No translation available. BC021578 mRNA. Translation: AAH21578.1. Sequence problems. BC072004 mRNA. Translation: AAH72004.1.
IPI	IPI00020504. IPI00290972. IPI00922766. IPI00925821. IPI00926166.
RefSeq	NP_001164558.1. NM_001171087.2. NP_001164559.1. NM_001171088.2. NP_001164560.1. NM_001171089.2. NP_004357.3. NM_004366.5.
UniGene	Hs.436847.
3D structure databases
ProteinModelPortal	P51788.
SMR	P51788. Positions 93-651, 766-841.
ModBase	Search...
Protein-protein interaction databases
IntAct	P51788. 2 interactions.
STRING	9606.ENSP00000265593.
PTM databases
PhosphoSite	P51788.
Polymorphism databases
DMDM	288558807.
Proteomic databases
PaxDb	P51788.
PRIDE	P51788.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265593; ENSP00000265593; ENSG00000114859. ENST00000344937; ENSP00000345056; ENSG00000114859. ENST00000423355; ENSP00000412226; ENSG00000114859. ENST00000434054; ENSP00000400425; ENSG00000114859. ENST00000457512; ENSP00000391928; ENSG00000114859.
GeneID	1181.
KEGG	hsa:1181.
UCSC	uc003foi.3. human. uc010hya.2. human.
Organism-specific databases
CTD	1181.
GeneCards	GC03M184063.
HGNC	HGNC:2020. CLCN2.
HPA	CAB009397. HPA014545. HPA024108.
MIM	600570. gene. 607628. phenotype.
neXtProt	NX_P51788.
Orphanet	307. Juvenile myoclonic epilepsy.
PharmGKB	PA26547.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0038.
HOGENOM	HOG000231297.
HOVERGEN	HBG005332.
InParanoid	P51788.
KO	K05011.
OMA	ETHKPLK.
OrthoDB	EOG4G7BXQ.
PhylomeDB	P51788.
Gene expression databases
ArrayExpress	P51788.
Bgee	P51788.
CleanEx	HS_CLCN2.
Genevestigator	P51788.
GermOnline	ENSG00000114859. Homo sapiens.
Family and domain databases
Gene3D	1.10.3080.10. 1 hit.
InterPro	IPR002244. Cl-channel-2. IPR014743. Cl-channel_core. IPR001807. Cl-channel_volt-gated. IPR000644. Cysta_beta_synth_core. [Graphical view]
Pfam	PF00571. CBS. 1 hit. PF00654. Voltage_CLC. 1 hit. [Graphical view]
PRINTS	PR00762. CLCHANNEL. PR01113. CLCHANNEL2.
SMART	SM00116. CBS. 1 hit. [Graphical view]
SUPFAM	SSF81340. Cl-channel_core. 1 hit.
PROSITE	PS51371. CBS. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1628478.
ChiTaRS	CLCN2. human.
DrugBank	DB01046. Lubiprostone.
GenomeRNAi	1181.
NextBio	4880.
SOURCE	Search...

Entry information

Entry name

CLCN2_HUMAN

Accession

Primary (citable) accession number: P51788
Secondary accession number(s): B4DQT9 , B4DZ58, E9PBD9, E9PCD2, O14864, Q6IPA9, Q8WU13

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	February 9, 2010
Last modified:	May 1, 2013
This is version 124 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.