CLCN2

Functionⁱ

Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume, membrane potential stabilization, signal transduction and transepithelial transport. Involved in the regulation of aldosterone production. The opening of CLCN2 channels at hyperpolarized membrane potentials in the glomerulosa causes cell membrane depolarization, activation of voltage-gated Ca2+ channels and increased expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis (PubMed:29403011, PubMed:29403012).4 Publications

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).By similarity

Sites

Feature key	Position(s)	DescriptionActions	Length
Binding siteⁱ	162	ChlorideBy similarity	1
Binding siteⁱ	459	Chloride; via amide nitrogenBy similarity	1
Binding siteⁱ	553	ChlorideBy similarity	1

GO - Molecular functionⁱ

voltage-gated chloride channel activity
Source: UniProtKB
Inferred from direct assayⁱ
- Ref.12
  "CLCN2 chloride channel mutations in familial hyperaldosteronism type II."
  Scholl U.I., Stoelting G., Schewe J., Thiel A., Tan H., Nelson-Williams C., Vichot A.A., Jin S.C., Loring E., Untiet V., Yoo T., Choi J., Xu S., Wu A., Kirchner M., Mertins P., Rump L.C., Onder A.M.
  Lifton R.P.
  Nat. Genet. 50:349-354(2018) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INVOLVEMENT IN HALD2, VARIANTS HALD2 LYS-22; ASN-26; GLN-172; LYS-362 DEL AND ARG-865, CHARACTERIZATION OF VARIANTS HALD2 LYS-22; ASN-26; GLN-172; LYS-362 DEL AND ARG-865.

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Chloride channel, Ion channel, Voltage-gated channel
Biological process	Ion transport, Transport
Ligand	Chloride

Enzyme and pathway databases

Reactomeⁱ	R-HSA-2672351 Stimuli-sensing channels

Reactomeⁱ

R-HSA-2672351 Stimuli-sensing channels

Protein family/group databases

TCDBⁱ	2.A.49.2.12 the chloride carrier/channel (clc) family

TCDBⁱ

2.A.49.2.12 the chloride carrier/channel (clc) family

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Chloride channel protein 2 Short name: ClC-2
Gene namesⁱ	Name:CLCN2
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	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
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 3

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000114859.14
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:2020 CLCN2
MIMⁱ	600570 gene
neXtProtⁱ	NX_P51788

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	2 – 87	CytoplasmicBy similarityAdd BLAST	86
Transmembraneⁱ	88 – 121	HelicalBy similarityAdd BLAST	34
Transmembraneⁱ	130 – 155	HelicalBy similarityAdd BLAST	26
Intramembraneⁱ	164 – 171	HelicalSequence analysis	8
Transmembraneⁱ	180 – 198	HelicalBy similarityAdd BLAST	19
Transmembraneⁱ	205 – 223	HelicalBy similarityAdd BLAST	19
Intramembraneⁱ	239 – 251	HelicalBy similarityAdd BLAST	13
Intramembraneⁱ	255 – 263	HelicalBy similarity	9
Transmembraneⁱ	275 – 295	HelicalBy similarityAdd BLAST	21
Transmembraneⁱ	321 – 349	HelicalBy similarityAdd BLAST	29
Transmembraneⁱ	358 – 377	HelicalBy similarityAdd BLAST	20
Transmembraneⁱ	429 – 449	HelicalBy similarityAdd BLAST	21
Transmembraneⁱ	457 – 480	HelicalBy similarityAdd BLAST	24
Intramembraneⁱ	497 – 511	HelicalBy similarityAdd BLAST	15
Intramembraneⁱ	512 – 513	Note=Loop between two helicesBy similarity	2
Intramembraneⁱ	514 – 525	HelicalBy similarityAdd BLAST	12
Intramembraneⁱ	526 – 530	Note=Loop between two helicesBy similarity	5
Transmembraneⁱ	531 – 548	HelicalBy similarityAdd BLAST	18
Topological domainⁱ	549 – 898	CytoplasmicBy similarityAdd BLAST	350

Keywords - Cellular componentⁱ

Cell membrane, Membrane

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Epilepsy, idiopathic generalized 11 (EIG11)1 Publication

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionA 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.

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_057890	577	R → Q in EIG11; associated with disease susceptibility; the mutant channel has accelerated deactivation rates compared to wild-type, but normal activation and peak current. 1 PublicationCorresponds to variant dbSNP:rs137852682EnsemblClinVar.		1

Juvenile absence epilepsy 2 (JAE2)1 Publication

Disease susceptibility may be associated with variations affecting the gene represented in this entry.

Disease descriptionA subtype of idiopathic generalized epilepsy characterized by onset occurring around puberty, absence seizures, generalized tonic-clonic seizures (GTCS), GTCS on awakening, and myoclonic seizures.

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_015989	715	G → E in JAE2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs137852681EnsemblClinVar.		1

Juvenile myoclonic epilepsy 8 (EJM8)1 Publication

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionA 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.

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_057889	235	R → Q in EJM8; associated with disease susceptibility; the mutant channel has accelerated deactivation rates compared to wild-type, but normal activation and peak current. 1 PublicationCorresponds to variant dbSNP:rs71318369EnsemblClinVar.		1

Leukoencephalopathy with ataxia (LKPAT)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn autosomal recessive neurologic disorder with a characteristic pattern of white matter abnormalities on brain MRI. Affected individuals have prominent signal abnormalities and decreased apparent diffusion coefficient values in the posterior limbs of the internal capsules, middle cerebral peduncles, pyramidal tracts in the pons, and middle cerebellar peduncles, suggesting myelin microvacuolation. Clinical features include ataxia and unstable gait. More variable abnormalities may include visual field defects, headaches, and learning disabilities.

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_070976	144 – 145	Missing in LKPAT; loss of function mutation; the mutant protein is restricted to the endoplasmic reticulum and hardly reached the plasma membrane; lower amounts of the mutant protein compared to wild-type. 1 Publication		2
Natural variantⁱVAR_070977	500	A → V in LKPAT; loss of function mutation; the mutant protein is restricted to the endoplasmic reticulum and hardly reaches the plasma membrane; lower amounts of the mutant protein compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs587777111EnsemblClinVar.		1

Hyperaldosteronism, familial, 2 (HALD2)2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn autosomal dominant disorder characterized by elevated plasma aldosterone level and hypertension of varying severity even within members of the same family. Hypokalemia is observed in some patients. In HALD2, hypertension does not improve with glucocorticoid treatment.

Keywords - Diseaseⁱ

Disease mutation, Epilepsy

Organism-specific databases

DisGeNET More...DisGeNETⁱ	1181
GeneReviewsⁱ	CLCN2
MalaCards human disease database More...MalaCardsⁱ	CLCN2
MIMⁱ	605635 phenotype 607628 phenotype 615651 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000114859
Orphanetⁱ	307 Juvenile myoclonic epilepsy 363540 Leukoencephalopathy with mild cerebellar ataxia and white matter edema
PharmGKBⁱ	PA26547

Chemistry databases

ChEMBLⁱ	CHEMBL1628478
Drug and drug target database More...DrugBankⁱ	DB01046 Lubiprostone
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	699

Polymorphism and mutation databases

BioMutaⁱ	CLCN2
DMDMⁱ	288558807

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Initiator methionineⁱ		RemovedCombined sources
ChainⁱPRO_0000094433	2 – 898	Chloride channel protein 2Add BLAST		897

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	2	N-acetylalanineCombined sources	1
Modified residueⁱ	20	PhosphothreonineBy similarity	1
Modified residueⁱ	712	PhosphoserineCombined sources	1
Modified residueⁱ	758	PhosphoserineBy similarity	1

Post-translational modificationⁱ

Phosphorylated. Activated by dephosphorylation.By similarity

Keywords - PTMⁱ

Acetylation, Phosphoprotein

Proteomic databases

EPDⁱ	P51788
jPOSTⁱ	P51788
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P51788
PaxDbⁱ	P51788
PeptideAtlas More...PeptideAtlasⁱ	P51788
PRIDEⁱ	P51788
ProteomicsDBⁱ	56385 56386 [P51788-2] 56387 [P51788-3]

PTM databases

iPTMnetⁱ	P51788
PhosphoSitePlusⁱ	P51788

Expressionⁱ

Tissue specificityⁱ

Ubiquitously expressed. Moderately expressed in aortic and coronary vascular smooth muscle cells and expressed at a low level in aortic endothelial cells. Expressed in the adrenal gland, predominantly in the zona glomerulosa (PubMed:29403011).2 Publications

Gene expression databases

Bgeeⁱ	ENSG00000114859 Expressed in 114 organ(s), highest expression level in right testis
ExpressionAtlasⁱ	P51788 baseline and differential
Genevisibleⁱ	P51788 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB009397 HPA014545 HPA024108

HPAⁱ

CAB009397
HPA014545
HPA024108

Interactionⁱ

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
UBQLN1	Q9UMX0-2	3	EBI-16431116,EBI-10173939

With

Entry

#Exp.

IntAct

Notes

UBQLN1

Q9UMX0-2

3

EBI-16431116,EBI-10173939

Protein-protein interaction databases

BioGridⁱ	107595, 21 interactors
IntActⁱ	P51788, 33 interactors
STRINGⁱ	9606.ENSP00000265593

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	P51788
SMRⁱ	P51788
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	584 – 642	CBS 1PROSITE-ProRule annotationAdd BLAST		59
Domainⁱ	790 – 850	CBS 2PROSITE-ProRule annotationAdd BLAST		61

Motif

Feature key	Position(s)	DescriptionActions	Length
Motifⁱ	161 – 165	Selectivity filter part_1By similarity	5
Motifⁱ	203 – 207	Selectivity filter part_2By similarity	5
Motifⁱ	457 – 461	Selectivity filter part_3By similarity	5

Compositional bias

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Compositional biasⁱ	2 – 6	Poly-Ala		5

Sequence similaritiesⁱ

Belongs to the chloride channel (TC 2.A.49) family. ClC-2/CLCN2 subfamily. [View classification]Curated

Keywords - Domainⁱ

CBS domain, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	KOG0476 Eukaryota COG0038 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00940000155439
HOGENOMⁱ	HOG000231297
HOVERGENⁱ	HBG005332
InParanoidⁱ	P51788
KEGG Orthology (KO) More...KOⁱ	K05011
OMAⁱ	SGMYNIY
Database of Orthologous Groups More...OrthoDBⁱ	1131873at2759
PhylomeDBⁱ	P51788
TreeFamⁱ	TF300522

Family and domain databases

Gene3Dⁱ	1.10.3080.10, 1 hit
InterProⁱ	View protein in InterPro IPR000644 CBS_dom IPR002244 Cl-channel-2 IPR014743 Cl-channel_core IPR001807 Cl-channel_volt-gated
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00654 Voltage_CLC, 1 hit
PRINTSⁱ	PR00762 CLCHANNEL PR01113 CLCHANNEL2
SUPFAMⁱ	SSF81340 SSF81340, 1 hit
PROSITEⁱ	View protein in PROSITE PS51371 CBS, 2 hits

Sequences (5+)ⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 5 described isoforms and 10 potential isoforms that are computationally mapped.Show all Align All

Isoform 1 (identifier: P51788-1) [UniParc]FASTA Add 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
MAAAAAEEGM EPRALQYEQT LMYGRYTQDL GAFAKEEAAR IRLGGPEPWK 
        60         70         80         90        100
GPPSSRAAPE LLEYGRSRCA RCRVCSVRCH KFLVSRVGED WIFLVLLGLL 
       110        120        130        140        150
MALVSWVMDY AIAACLQAQQ WMSRGLNTSI LLQYLAWVTY PVVLITFSAG 
       160        170        180        190        200
FTQILAPQAV GSGIPEMKTI LRGVVLKEYL TLKTFIAKVI GLTCALGSGM 
       210        220        230        240        250
PLGKEGPFVH IASMCAALLS KFLSLFGGIY ENESRNTEML AAACAVGVGC 
       260        270        280        290        300
CFAAPIGGVL FSIEVTSTFF AVRNYWRGFF AATFSAFIFR VLAVWNRDEE 
       310        320        330        340        350
TITALFKTRF RLDFPFDLQE LPAFAVIGIA SGFGGALFVY LNRKIVQVMR 
       360        370        380        390        400
KQKTINRFLM RKRLLFPALV TLLISTLTFP PGFGQFMAGQ LSQKETLVTL 
       410        420        430        440        450
FDNRTWVRQG LVEELEPPST SQAWNPPRAN VFLTLVIFIL MKFWMSALAT 
       460        470        480        490        500
TIPVPCGAFM PVFVIGAAFG RLVGESMAAW FPDGIHTDSS TYRIVPGGYA 
       510        520        530        540        550
VVGAAALAGA VTHTVSTAVI VFELTGQIAH ILPVMIAVIL ANAVAQSLQP 
       560        570        580        590        600
SLYDSIIRIK KLPYLPELGW GRHQQYRVRV EDIMVRDVPH VALSCTFRDL 
       610        620        630        640        650
RLALHRTKGR MLALVESPES MILLGSIERS QVVALLGAQL SPARRRQHMQ 
       660        670        680        690        700
ERRATQTSPL SDQEGPPTPE ASVCFQVNTE DSAFPAARGE THKPLKPALK 
       710        720        730        740        750
RGPSVTRNLG ESPTGSAESA GIALRSLFCG SPPPEAASEK LESCEKRKLK 
       760        770        780        790        800
RVRISLASDA DLEGEMSPEE ILEWEEQQLD EPVNFSDCKI DPAPFQLVER 
       810        820        830        840        850
TSLHKTHTIF SLLGVDHAYV TSIGRLIGIV TLKELRKAIE GSVTAQGVKV 
       860        870        880        890 
RPPLASFRDS ATSSSDTETT EVHALWGPHS RHGLPREGSP SDSDDKCQ

Length:898

Mass (Da):98,535

Last modified:February 9, 2010 - v2

Checksum:ⁱ5F20FA8713C0C74E

GO

Isoform 2 (identifier: P51788-2) [UniParc]FASTA Add to basket

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

« Hide

        10         20         30         40         50
MRKRLLFPAL VTLLISTLTF PPGFGQFMAG QLSQKETLVT LFDNRTWVRQ 
        60         70         80         90        100
GLVEELEPPS TSQAWNPPRA NVFLTLVIFI LMKHLGVWWV KAWLPGSQME 
       110        120 
FIRTAAPTGL CLGATLWSGQ LRWQER

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

Show »

Length:126

Mass (Da):14,383

Checksum:ⁱ69843C961A8FC3DF

GO

Isoform 3 (identifier: P51788-3) [UniParc]FASTA Add to basket

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

« Hide

        10         20         30         40         50
MAAAAAEEGM EPRALQYEQT LMYGRYTQDL GAFAKEEAAR IRLGGPEPWK 
        60         70         80         90        100
GPPSSRAAPE LLEYGRSRCA RCRVCSVRCH KFLVSRVGED WIFLVLLGLL 
       110        120        130        140        150
MALVSWVMDY AIAACLQAQQ WMSRGLNTSI LLQYLAWVTY PVVLITFSAG 
       160        170        180        190        200
FTQILAPQAV GSGIPEMKTI LRGVVLKEYL TLKTFIAKVI GLTCALGSGM 
       210        220        230        240        250
PLGKEGPFVH IASMCAALLS KFLSLFGGIY ENESRNTEML AAACAVGVGC 
       260        270        280        290        300
CFAAPIGGVL FSIEVTSTFF AVRNYWRGFF AATFSAFIFR VLAVWNRDEE 
       310        320        330        340        350
TITALFKTRF RLDFPFDLQE LPAFAVIGIA SGFGGALFVY LNRKIVQVMR 
       360        370        380        390        400
KQKTINRFLM RKRLLFPALV TLLISTLTFP PGFGQFMAGQ LSQKETLVTL 
       410        420        430        440        450
FDNRTWVRQG LVEELEPPST SQAWNPPRAN VFLTLVIFIL MKFWMSALAT 
       460        470        480        490        500
TIPVPCGAFM PVFVIDGIHT DSSTYRIVPG GYAVVGAAAL AGAVTHTVST 
       510        520        530        540        550
AVIVFELTGQ IAHILPVMIA VILANAVAQS LQPSLYDSII RIKKLPYLPE 
       560        570        580        590        600
LGWGRHQQYR VRVEDIMVRD VPHVALSCTF RDLRLALHRT KGRMLALVES 
       610        620        630        640        650
PESMILLGSI ERSQVVALLG AQLSPARRRQ HMQERRATQT SPLSDQEGPP 
       660        670        680        690        700
TPEASVCFQV NTEDSAFPAA RGETHKPLKP ALKRGPSVTR NLGESPTGSA 
       710        720        730        740        750
ESAGIALRSL FCGSPPPEAA SEKLESCEKR KLKRVRISLA SDADLEGEMS 
       760        770        780        790        800
PEEILEWEEQ QLDEPVNFSD CKIDPAPFQL VERTSLHKTH TIFSLLGVDH 
       810        820        830        840        850
AYVTSIGRLI GIVTLKELRK AIEGSVTAQG VKVRPPLASF RDSATSSSDT 
       860        870        880 
ETTEVHALWG PHSRHGLPRE GSPSDSDDKC Q

Show »

Length:881

Mass (Da):96,786

Checksum:ⁱF44E1264FC92758F

GO

Isoform 4 (identifier: P51788-4) [UniParc]FASTA Add to basket

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

« Hide

        10         20         30         40         50
MAAAAAEEGM EPRALQYEQT LMYGRYTQDL GAFAKEEAAR IRLGGPEPWK 
        60         70         80         90        100
GPPSSRAAPE LLEYGRSRCA RCRAQQWMSR GLNTSILLQY LAWVTYPVVL 
       110        120        130        140        150
ITFSAGFTQI LAPQAVGSGI PEMKTILRGV VLKEYLTLKT FIAKVIGLTC 
       160        170        180        190        200
ALGSGMPLGK EGPFVHIASM CAALLSKFLS LFGGIYENES RNTEMLAAAC 
       210        220        230        240        250
AVGVGCCFAA PIGGVLFSIE VTSTFFAVRN YWRGFFAATF SAFIFRVLAV 
       260        270        280        290        300
WNRDEETITA LFKTRFRLDF PFDLQELPAF AVIGIASGFG GALFVYLNRK 
       310        320        330        340        350
IVQVMRKQKT INRFLMRKRL LFPALVTLLI STLTFPPGFG QFMAGQLSQK 
       360        370        380        390        400
ETLVTLFDNR TWVRQGLVEE LEPPSTSQAW NPPRANVFLT LVIFILMKFW 
       410        420        430        440        450
MSALATTIPV PCGAFMPVFV IGAAFGRLVG ESMAAWFPDG IHTDSSTYRI 
       460        470        480        490        500
VPGGYAVVGA AALAGAVTHT VSTAVIVFEL TGQIAHILPV MIAVILANAV 
       510        520        530        540        550
AQSLQPSLYD SIIRIKKLPY LPELGWGRHQ QYRVRVEDIM VRDVPHVALS 
       560        570        580        590        600
CTFRDLRLAL HRTKGRMLAL VESPESMILL GSIERSQVVA LLGAQLSPAR 
       610        620        630        640        650
RRQHMQERRA TQTSPLSDQE GPPTPEASVC FQVNTEDSAF PAARGETHKP 
       660        670        680        690        700
LKPALKRGPS VTRNLGESPT GSAESAGIAL RSLFCGSPPP EAASEKLESC 
       710        720        730        740        750
EKRKLKRVRI SLASDADLEG EMSPEEILEW EEQQLDEPVN FSDCKIDPAP 
       760        770        780        790        800
FQLVERTSLH KTHTIFSLLG VDHAYVTSIG RLIGIVTLKE LRKAIEGSVT 
       810        820        830        840        850
AQGVKVRPPL ASFRDSATSS SDTETTEVHA LWGPHSRHGL PREGSPSDSD 

DKCQ

Note: No experimental confirmation available.

Show »

Length:854

Mass (Da):93,583

Checksum:ⁱEA949779A2E7B686

GO

Isoform 5 (identifier: P51788-5) [UniParc]FASTA Add to basket

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

« Hide

        10         20         30         40         50
MAAAAAEEGM EPRALQYEQT LMYGRYTQDL GAFAKEEAAR IRLGGPEPWK 
        60         70         80         90        100
GPPSSRAAPE LLEYGRSRCA RCRVCSVRCH KFLVSRVGED WIFLVLLGLL 
       110        120        130        140        150
MALVSWVMDY AIAACLQAQQ WMSRGLNTSI LLQYLAWVTY PVVLITFSAG 
       160        170        180        190        200
FTQILAPQAV GSGIPEMKTI LRGVVLKEYL TLKTFIAKVI GLTCALGSGM 
       210        220        230        240        250
PLGKEGPFVH IASMCAALLS KFLSLFGGIY ENESRNTEML AAACAVGVGC 
       260        270        280        290        300
CFAAPIGGVL FSIEVTSTFF AVRNYWRGFF AATFSAFIFR VLAVWNRDEE 
       310        320        330        340        350
TITALFKTRF RLDFPFDLQE LPAFAVIGIA SGFGGALFVY LNRKIVQVMR 
       360        370        380        390        400
KQKTINRFLM RKRLLFPALV TLLISTLTFP PGFGQFMAGQ LSQKETLVTL 
       410        420        430        440        450
FDNRTWVRQG LVEELEPPST SQAWNPPRAN VFLTLVIFIL MKFWMSALAT 
       460        470        480        490        500
TIPVPCGAFM PVFVIGAAFG RLVGESMAAW FPDGIHTDSS TYRIVPGGYA 
       510        520        530        540        550
VVGAAALAGA VTHTVSTAVI VFELTGQIAH ILPVMIAVIL ANAVAQSLQP 
       560        570        580        590        600
SLYDSIIRIK KLPYLPELGW GRHQQYRVRV EDIMVRDVPH VALSCTFRDL 
       610        620        630        640        650
RLALHRTKGR MLALVESPES MILLGSIERS QVVALLGAQL SPARRRQHMQ 
       660        670        680        690        700
ERRATQTSPL SDQEGPPTPE ASVCFQVNTE DSAFPAARGE THKPLKPALK 
       710        720        730        740        750
RGPSVTRNLG ESPTGSAESA GIALRSLFCG SPPPEAASEK LESCEKRKLK 
       760        770        780        790        800
RVRISLASDA DLEGEMSPEE ILEWEEQQLD EPVNFSDCKI DPAPFQLVER 
       810        820        830        840        850
TSLHKLRKAI EGSVTAQGVK VRPPLASFRD SATSSSDTET TEVHALWGPH 
       860 
SRHGLPREGS PSDSDDKCQ

Note: No experimental confirmation available.

Show »

Length:869

Mass (Da):95,399

Checksum:ⁱE0D9292146DD1AA5

GO

Computationally mapped potential isoform sequencesⁱ

There are 10 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

A0A1B0GVL9	A0A1B0GVL9_HUMAN	Chloride channel protein 2 Chloride channel protein 2	CLCN2	305	Annotation score:
A0A1B0GVU4	A0A1B0GVU4_HUMAN	Chloride channel protein 2 Chloride channel protein 2	CLCN2	277	Annotation score:
A0A1B0GUY6	A0A1B0GUY6_HUMAN	Chloride channel protein 2 Chloride channel protein 2	CLCN2	449	Annotation score:
A0A1B0GUZ8	A0A1B0GUZ8_HUMAN	Chloride channel protein 2 Chloride channel protein 2	CLCN2	465	Annotation score:
A0A1B0GV52	A0A1B0GV52_HUMAN	Chloride channel protein 2 Chloride channel protein 2	CLCN2	288	Annotation score:
A0A1B0GTJ3	A0A1B0GTJ3_HUMAN	Chloride channel protein 2 Chloride channel protein 2	CLCN2	96	Annotation score:
A0A1B0GVW7	A0A1B0GVW7_HUMAN	Chloride channel protein 2 Chloride channel protein 2	CLCN2	256	Annotation score:
A0A1B0GWC8	A0A1B0GWC8_HUMAN	Chloride channel protein 2 Chloride channel protein 2	CLCN2	155	Annotation score:
H7C0Q8	H7C0Q8_HUMAN	Chloride channel protein 2 Chloride channel protein 2	CLCN2	133	Annotation score:
A0A1B0GTY0	A0A1B0GTY0_HUMAN	Chloride channel protein 2 Chloride channel protein 2	CLCN2	113	Annotation score:

Sequence cautionⁱ

The sequence AAH21578 differs from that shown. Reason: Erroneous translation. Wrong choice of frame.Curated

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	17	Y → H in AAB34722 (PubMed:7795595).Curated		1
Sequence conflictⁱ	537	A → V in AAH21578 (PubMed:15489334).Curated		1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_081154	22	M → K in HALD2; increased voltage-gated chloride currents due to higher channel open probabilities at physiological cell membrane potentials. 1 Publication	1
Natural variantⁱVAR_081155	24	G → D in HALD2; increased voltage-gated chloride currents; increased aldosterone synthase expression. 1 PublicationCorresponds to variant dbSNP:rs1085307938EnsemblClinVar.	1
Natural variantⁱVAR_081156	26	Y → N in HALD2; increased voltage-gated chloride currents due to higher channel open probabilitiesat at physiological cell membrane potentials. 1 Publication	1
Natural variantⁱVAR_057886	48	P → R Polymorphism; reduces channel activity. 1 PublicationCorresponds to variant dbSNP:rs115661422EnsemblClinVar.	1
Natural variantⁱVAR_057887	68	R → H Polymorphism; reduces channel activity. 1 PublicationCorresponds to variant dbSNP:rs61729156EnsemblClinVar.	1
Natural variantⁱVAR_070976	144 – 145	Missing in LKPAT; loss of function mutation; the mutant protein is restricted to the endoplasmic reticulum and hardly reached the plasma membrane; lower amounts of the mutant protein compared to wild-type. 1 Publication	2
Natural variantⁱVAR_081157	172	R → Q in HALD2; increased voltage-gated chloride currents due to higher channel open probabilities at physiological cell membrane potentials; increased aldosterone synthase expression. 1 PublicationCorresponds to variant dbSNP:rs1293789661EnsemblClinVar.	1
Natural variantⁱVAR_057888	199	G → A Polymorphism; no effect. 1 PublicationCorresponds to variant dbSNP:rs863225248EnsemblClinVar.	1
Natural variantⁱVAR_057889	235	R → Q in EJM8; associated with disease susceptibility; the mutant channel has accelerated deactivation rates compared to wild-type, but normal activation and peak current. 1 PublicationCorresponds to variant dbSNP:rs71318369EnsemblClinVar.	1
Natural variantⁱVAR_081158	362	Missing in HALD2; increased voltage-gated chloride currents due to higher channel open probabilities at physiological cell membrane potentials. 1 Publication	1
Natural variantⁱVAR_070977	500	A → V in LKPAT; loss of function mutation; the mutant protein is restricted to the endoplasmic reticulum and hardly reaches the plasma membrane; lower amounts of the mutant protein compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs587777111EnsemblClinVar.	1
Natural variantⁱVAR_057890	577	R → Q in EIG11; associated with disease susceptibility; the mutant channel has accelerated deactivation rates compared to wild-type, but normal activation and peak current. 1 PublicationCorresponds to variant dbSNP:rs137852682EnsemblClinVar.	1
Natural variantⁱVAR_057891	644	R → C Polymorphism; no effect. 1 PublicationCorresponds to variant dbSNP:rs148545588EnsemblClinVar.	1
Natural variantⁱVAR_057892	646	R → Q Polymorphism; reduces channel activity. 1 PublicationCorresponds to variant dbSNP:rs115961753EnsemblClinVar.	1
Natural variantⁱVAR_054550	668	T → S3 PublicationsCorresponds to variant dbSNP:rs9820367EnsemblClinVar.	1
Natural variantⁱVAR_015989	715	G → E in JAE2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs137852681EnsemblClinVar.	1
Natural variantⁱVAR_054551	718	E → D. Corresponds to variant dbSNP:rs2228292EnsemblClinVar.	1
Natural variantⁱVAR_058426	719	S → L Found in a patient with childhood absence epilepsy; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs138573287Ensembl.	1
Natural variantⁱVAR_057893	725	R → W Polymorphism; slightly faster channel activation. 1 PublicationCorresponds to variant dbSNP:rs114702742EnsemblClinVar.	1
Natural variantⁱVAR_057894	747	R → H Polymorphism; slightly faster channel activation. 1 PublicationCorresponds to variant dbSNP:rs144164281EnsemblClinVar.	1
Natural variantⁱVAR_081159	865	S → R in HALD2; increased voltage-gated chloride currents due to higher channel open probabilities at physiological cell membrane potentials. 1 Publication	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_007831	1 – 359	Missing in isoform 2. 1 PublicationAdd BLAST	359
Alternative sequenceⁱVSP_045457	74 – 117	Missing in isoform 4. 1 PublicationAdd BLAST	44
Alternative sequenceⁱVSP_007832	443 – 485	FWMSA…FPDGI → HLGVWWVKAWLPGSQMEFIR TAAPTGLCLGATLWSGQLRW QER in isoform 2. 1 PublicationAdd BLAST	43
Alternative sequenceⁱVSP_036456	466 – 482	Missing in isoform 3. 1 PublicationAdd BLAST	17
Alternative sequenceⁱVSP_036455	486 – 898	Missing in isoform 2. 1 PublicationAdd BLAST	413
Alternative sequenceⁱVSP_045458	806 – 834	Missing in isoform 5. 1 PublicationAdd BLAST	29

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS3263.1 [P51788-1] CCDS54690.1 [P51788-4] CCDS54691.1 [P51788-3] CCDS54692.1 [P51788-5]
NCBI Reference Sequences More...RefSeqⁱ	NP_001164558.1, NM_001171087.2 [P51788-3] NP_001164559.1, NM_001171088.2 [P51788-4] NP_001164560.1, NM_001171089.2 [P51788-5] NP_004357.3, NM_004366.5 [P51788-1]
UniGeneⁱ	Hs.436847

Genome annotation databases

Ensemblⁱ	ENST00000265593; ENSP00000265593; ENSG00000114859 [P51788-1] ENST00000344937; ENSP00000345056; ENSG00000114859 [P51788-3] ENST00000434054; ENSP00000400425; ENSG00000114859 [P51788-4] ENST00000457512; ENSP00000391928; ENSG00000114859 [P51788-5]
GeneIDⁱ	1181
KEGGⁱ	hsa:1181
UCSC genome browser More...UCSCⁱ	uc003foi.4 human [P51788-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P51788	Chloride channel protein (Fragment)		HUMAN		422	UniRef100_P51788
UPI0003EAEAF2		HUMAN		512
P51788-2	Chloride channel protein 2 (Fragment)		HUMAN		449	UniRef100_P51788-2
CLCN2 isoform 6 (Fragment)		PANTR		132

Protein	Similar proteins		Species	Score	Length	Source
P51788	Chloride channel protein (Fragment)		HUMAN		422	UniRef90_P51788
Chloride voltage-gated channel 2		HORSE		980
Chloride channel protein		SHEEP		910
Chloride channel protein 2		MOUSE		908
chloride channel protein 2 isoform X1		DELLE		908
+110
P51788-2	Chloride channel protein 2 (Fragment)		HUMAN		449	UniRef90_P51788-2
CLCN2 isoform 6 (Fragment)		PANTR		132
CLCN2 isoform 14 (Fragment)		PONAB		448
CLCN2 isoform 6 (Fragment)		PONAB		132
CLCN2 isoform 15 (Fragment)		PANTR		448
P51788-4	Chloride channel protein		TARSY		975	UniRef90_P51788-4
Uncharacterized protein		PROCO		873
CLCN2 isoform 11		PANTR		869
Uncharacterized protein		COLAP		869
Chloride channel protein		MACMU		854
+32
P51788-5	Chloride channel protein		SAIBB		974	UniRef90_P51788-5
chloride channel protein 2 isoform X2		CALUR		883
Uncharacterized protein		Cebus capucinus imitator		870
Uncharacterized protein		AOTNA		870
Chloride voltage-gated channel 2		CALJA		870
+19

Protein	Similar proteins		Species	Score	Length	Source
P51788	Chloride channel protein (Fragment)		HUMAN		422	UniRef50_P51788
Chloride voltage-gated channel 2		HORSE		980
Chloride channel protein		SHEEP		910
chloride channel protein 2 isoform X1		DELLE		908
Chloride channel protein 2		MOUSE		908
+877
P51788-2	Chloride channel protein 2 (Fragment)		HUMAN		449	UniRef50_P51788-2
CLCN2 isoform 6 (Fragment)		PANTR		132
CLCN2 isoform 14 (Fragment)		PONAB		448
UPI0005291CD8		brown roatelo		440
CLCN2 isoform 6 (Fragment)		PONAB		132
+1

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	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
CCDSⁱ	CCDS3263.1 [P51788-1] CCDS54690.1 [P51788-4] CCDS54691.1 [P51788-3] CCDS54692.1 [P51788-5]
RefSeqⁱ	NP_001164558.1, NM_001171087.2 [P51788-3] NP_001164559.1, NM_001171088.2 [P51788-4] NP_001164560.1, NM_001171089.2 [P51788-5] NP_004357.3, NM_004366.5 [P51788-1]
UniGeneⁱ	Hs.436847

3D structure databases

ProteinModelPortalⁱ	P51788
SMRⁱ	P51788
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	107595, 21 interactors
IntActⁱ	P51788, 33 interactors
STRINGⁱ	9606.ENSP00000265593

Chemistry databases

ChEMBLⁱ	CHEMBL1628478
DrugBankⁱ	DB01046 Lubiprostone
GuidetoPHARMACOLOGYⁱ	699

Protein family/group databases

TCDBⁱ	2.A.49.2.12 the chloride carrier/channel (clc) family

TCDBⁱ

2.A.49.2.12 the chloride carrier/channel (clc) family

PTM databases

iPTMnetⁱ	P51788
PhosphoSitePlusⁱ	P51788

Polymorphism and mutation databases

BioMutaⁱ	CLCN2
DMDMⁱ	288558807

Proteomic databases

EPDⁱ	P51788
jPOSTⁱ	P51788
MaxQBⁱ	P51788
PaxDbⁱ	P51788
PeptideAtlasⁱ	P51788
PRIDEⁱ	P51788
ProteomicsDBⁱ	56385 56386 [P51788-2] 56387 [P51788-3]

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENST00000265593; ENSP00000265593; ENSG00000114859 [P51788-1] ENST00000344937; ENSP00000345056; ENSG00000114859 [P51788-3] ENST00000434054; ENSP00000400425; ENSG00000114859 [P51788-4] ENST00000457512; ENSP00000391928; ENSG00000114859 [P51788-5]
GeneIDⁱ	1181
KEGGⁱ	hsa:1181
UCSCⁱ	uc003foi.4 human [P51788-1]

Organism-specific databases

CTDⁱ	1181
DisGeNETⁱ	1181
EuPathDBⁱ	HostDB:ENSG00000114859.14
GeneCardsⁱ	CLCN2
GeneReviewsⁱ	CLCN2
HGNCⁱ	HGNC:2020 CLCN2
HPAⁱ	CAB009397 HPA014545 HPA024108
MalaCardsⁱ	CLCN2
MIMⁱ	600570 gene 605635 phenotype 607628 phenotype 615651 phenotype
neXtProtⁱ	NX_P51788
OpenTargetsⁱ	ENSG00000114859
Orphanetⁱ	307 Juvenile myoclonic epilepsy 363540 Leukoencephalopathy with mild cerebellar ataxia and white matter edema
PharmGKBⁱ	PA26547
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG0476 Eukaryota COG0038 LUCA
GeneTreeⁱ	ENSGT00940000155439
HOGENOMⁱ	HOG000231297
HOVERGENⁱ	HBG005332
InParanoidⁱ	P51788
KOⁱ	K05011
OMAⁱ	SGMYNIY
OrthoDBⁱ	1131873at2759
PhylomeDBⁱ	P51788
TreeFamⁱ	TF300522

Enzyme and pathway databases

Reactomeⁱ

R-HSA-2672351 Stimuli-sensing channels

Miscellaneous databases

ChiTaRSⁱ	CLCN2 human
GeneWikiⁱ	CLCN2
GenomeRNAiⁱ	1181
Protein Ontology More...PROⁱ	PR:P51788
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000114859 Expressed in 114 organ(s), highest expression level in right testis
ExpressionAtlasⁱ	P51788 baseline and differential
Genevisibleⁱ	P51788 HS

Family and domain databases

Gene3Dⁱ	1.10.3080.10, 1 hit
InterProⁱ	View protein in InterPro IPR000644 CBS_dom IPR002244 Cl-channel-2 IPR014743 Cl-channel_core IPR001807 Cl-channel_volt-gated
Pfamⁱ	View protein in Pfam PF00654 Voltage_CLC, 1 hit
PRINTSⁱ	PR00762 CLCHANNEL PR01113 CLCHANNEL2
SUPFAMⁱ	SSF81340 SSF81340, 1 hit
PROSITEⁱ	View protein in PROSITE PS51371 CBS, 2 hits
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	CLCN2_HUMAN
Accessionⁱ	P51788Primary (citable) accession number: P51788 Secondary accession number(s): B4DQT9 Q8WU13
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
	Last sequence update:	February 9, 2010
	Last modified:	February 13, 2019
	This is version 178 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	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.

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations

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UniProtKB - P51788 (CLCN2_HUMAN)

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Chloride channel protein 2

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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GO - Biological processi

Enzyme and pathway databases

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<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

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Plasma Membrane

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Topology

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Keywords - Diseasei

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<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

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Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

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<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

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<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

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<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

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Chemistry databases

Protein family/group databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

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Organism-specific databases

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Gene expression databases

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<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Sequence cautionⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ