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Protein

Chloride intracellular channel protein 1

Gene

CLIC1

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

Functioni

Can insert into membranes and form chloride ion channels. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Involved in regulation of the cell cycle.7 Publications

Miscellaneous

The protein seems to have very low affinity for glutathione, even though glutathione binding was observed in protein crystals.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei64Glutathione; via carbonyl oxygen1 Publication1
Binding sitei77Glutathione1 Publication1

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • chloride channel activity Source: MGI
  • voltage-gated ion channel activity Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionChloride channel, Ion channel, Voltage-gated channel
Biological processIon transport, Transport
LigandChloride

Enzyme and pathway databases

SignaLinkiO00299

Protein family/group databases

TCDBi1.A.12.1.2 the intracellular chloride channel (clic) family

Names & Taxonomyi

Protein namesi
Recommended name:
Chloride intracellular channel protein 1
Alternative name(s):
Chloride channel ABP
Nuclear chloride ion channel 27
Short name:
NCC27
Regulatory nuclear chloride ion channel protein
Short name:
hRNCC
Gene namesi
Name:CLIC1
Synonyms:G6, NCC27
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000213719.8
HGNCiHGNC:2062 CLIC1
MIMi602872 gene
neXtProtiNX_O00299

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei26 – 46Helical; Note=After insertion into the membraneSequence analysisAdd BLAST21

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi24C → S: Loss of dimerization and of ion transport activity. 1 Publication1
Mutagenesisi59C → S: Loss of dimerization and of ion transport activity. 1 Publication1

Organism-specific databases

DisGeNETi1192
OpenTargetsiENSG00000213719
PharmGKBiPA26588

Polymorphism and mutation databases

BioMutaiCLIC1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001442012 – 241Chloride intracellular channel protein 1Add BLAST240

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei13N6-acetyllysineCombined sources1
Disulfide bondi24 ↔ 59Alternate1 Publication
Modified residuei24S-glutathionyl cysteine; alternate1 Publication1
Modified residuei119N6-acetyllysineCombined sources1
Modified residuei121PhosphoserineCombined sources1
Modified residuei131N6-acetyllysineCombined sources1
Modified residuei156PhosphoserineCombined sources1
Modified residuei211PhosphoserineCombined sources1
Modified residuei233PhosphotyrosineBy similarity1

Post-translational modificationi

Hydrogen peroxide treatment causes a conformation change, leading to dimerization and formation of an intramolecular disulfide bond between Cys-24 and Cys-59.

Keywords - PTMi

Acetylation, Disulfide bond, Glutathionylation, Phosphoprotein

Proteomic databases

EPDiO00299
PaxDbiO00299
PeptideAtlasiO00299
PRIDEiO00299
ProteomicsDBi47828
TopDownProteomicsiO00299

2D gel databases

OGPiO00299
SWISS-2DPAGEiO00299

PTM databases

iPTMnetiO00299
PhosphoSitePlusiO00299
SwissPalmiO00299

Expressioni

Tissue specificityi

Expression is prominent in heart, placenta, liver, kidney and pancreas.1 Publication

Gene expression databases

BgeeiENSG00000213719
CleanExiHS_CLIC1
ExpressionAtlasiO00299 baseline and differential
GenevisibleiO00299 HS

Organism-specific databases

HPAiCAB020825
CAB040557

Interactioni

Subunit structurei

Monomer. Homodimer (in vitro). Interacts with TRAPPC2. Dimerization requires a conformation change that leads to the exposure of a large hydrophobic surface. In vivo, this may lead to membrane insertion. Interacts with AKAP9.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PSMD10O758329EBI-347404,EBI-752185

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107604, 61 interactors
IntActiO00299, 50 interactors
MINTiO00299
STRINGi9606.ENSP00000364934

Structurei

Secondary structure

1241
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi8 – 14Combined sources7
Beta strandi18 – 21Combined sources4
Helixi25 – 37Combined sources13
Beta strandi42 – 46Combined sources5
Beta strandi48 – 50Combined sources3
Helixi53 – 58Combined sources6
Beta strandi64 – 69Combined sources6
Beta strandi72 – 76Combined sources5
Helixi77 – 87Combined sources11
Turni90 – 92Combined sources3
Helixi101 – 104Combined sources4
Turni105 – 109Combined sources5
Helixi110 – 119Combined sources10
Helixi123 – 125Combined sources3
Helixi126 – 145Combined sources20
Helixi149 – 151Combined sources3
Helixi157 – 159Combined sources3
Beta strandi166 – 172Combined sources7
Helixi175 – 195Combined sources21
Helixi204 – 214Combined sources11
Helixi217 – 220Combined sources4
Helixi226 – 232Combined sources7
Helixi234 – 237Combined sources4

3D structure databases

ProteinModelPortaliO00299
SMRiO00299
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00299

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini93 – 233GST C-terminalAdd BLAST141

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 90Required for insertion into the membraneAdd BLAST89

Domaini

Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion.2 Publications

Sequence similaritiesi

Belongs to the chloride channel CLIC family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410INGZ Eukaryota
ENOG410ZZZX LUCA
GeneTreeiENSGT00550000074477
HOGENOMiHOG000231548
HOVERGENiHBG050994
InParanoidiO00299
KOiK05021
OMAiLWRYLNA
OrthoDBiEOG091G0IHT
PhylomeDBiO00299
TreeFamiTF315438

Family and domain databases

InterProiView protein in InterPro
IPR002946 CLIC
IPR030259 CLIC-1
IPR010987 Glutathione-S-Trfase_C-like
IPR036282 Glutathione-S-Trfase_C_sf
IPR004045 Glutathione_S-Trfase_N
IPR036249 Thioredoxin-like_sf
PANTHERiPTHR43920:SF2 PTHR43920:SF2, 1 hit
PfamiView protein in Pfam
PF13409 GST_N_2, 1 hit
PRINTSiPR01263 INTCLCHANNEL
SUPFAMiSSF47616 SSF47616, 1 hit
SSF52833 SSF52833, 1 hit
TIGRFAMsiTIGR00862 O-ClC, 1 hit
PROSITEiView protein in PROSITE
PS50405 GST_CTER, 1 hit

Sequencei

Sequence statusi: Complete.

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

O00299-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEEQPQVEL FVKAGSDGAK IGNCPFSQRL FMVLWLKGVT FNVTTVDTKR
60 70 80 90 100
RTETVQKLCP GGQLPFLLYG TEVHTDTNKI EEFLEAVLCP PRYPKLAALN
110 120 130 140 150
PESNTAGLDI FAKFSAYIKN SNPALNDNLE KGLLKALKVL DNYLTSPLPE
160 170 180 190 200
EVDETSAEDE GVSQRKFLDG NELTLADCNL LPKLHIVQVV CKKYRGFTIP
210 220 230 240
EAFRGVHRYL SNAYAREEFA STCPDDEEIE LAYEQVAKAL K
Length:241
Mass (Da):26,923
Last modified:January 23, 2007 - v4
Checksum:i163EEB7481826A0A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti63Q → E in AAC25675 (PubMed:9139710).Curated1
Sequence conflicti63Q → E in AAD26137 (PubMed:10191309).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U93205 mRNA Translation: AAC25675.1
AF034607 mRNA Translation: AAD20437.1
AF109197 mRNA Translation: AAD26137.1
AJ012008 Genomic DNA Translation: CAB46078.1
CR542071 mRNA Translation: CAG46868.1
AF129756 Genomic DNA Translation: AAD18073.1
BA000025 Genomic DNA Translation: BAB63376.1
AL662899 Genomic DNA No translation available.
BC064527 mRNA Translation: AAH64527.1
BC095469 mRNA Translation: AAH95469.1
X87689 mRNA Translation: CAA61020.1
CCDSiCCDS4719.1
RefSeqiNP_001274522.1, NM_001287593.1
NP_001274523.1, NM_001287594.1
NP_001279.2, NM_001288.4
UniGeneiHs.414565

Genome annotation databases

EnsembliENST00000375779; ENSP00000364934; ENSG00000213719
ENST00000375780; ENSP00000364935; ENSG00000213719
ENST00000375784; ENSP00000364940; ENSG00000213719
ENST00000383404; ENSP00000372896; ENSG00000206394
ENST00000383405; ENSP00000372897; ENSG00000206394
ENST00000395892; ENSP00000379229; ENSG00000213719
ENST00000400052; ENSP00000382926; ENSG00000206394
ENST00000400058; ENSP00000382931; ENSG00000206394
ENST00000415179; ENSP00000409247; ENSG00000226248
ENST00000418285; ENSP00000407791; ENSG00000226417
ENST00000420458; ENSP00000410965; ENSG00000226651
ENST00000422167; ENSP00000407429; ENSG00000226248
ENST00000423055; ENSP00000406968; ENSG00000226417
ENST00000423143; ENSP00000404589; ENSG00000223639
ENST00000423804; ENSP00000409979; ENSG00000230685
ENST00000425464; ENSP00000401292; ENSG00000223639
ENST00000431921; ENSP00000408357; ENSG00000226248
ENST00000433916; ENSP00000391395; ENSG00000226651
ENST00000434202; ENSP00000400532; ENSG00000226651
ENST00000435242; ENSP00000412217; ENSG00000226417
ENST00000438708; ENSP00000406088; ENSG00000226248
ENST00000438750; ENSP00000404037; ENSG00000223639
ENST00000442045; ENSP00000400280; ENSG00000226417
ENST00000447338; ENSP00000413330; ENSG00000230685
ENST00000447369; ENSP00000408094; ENSG00000230685
ENST00000451546; ENSP00000416211; ENSG00000223639
ENST00000456863; ENSP00000406335; ENSG00000226651
ENST00000457485; ENSP00000398056; ENSG00000230685
ENST00000614673; ENSP00000480256; ENSG00000230685
ENST00000614982; ENSP00000477623; ENSG00000206394
ENST00000616760; ENSP00000479808; ENSG00000213719
ENST00000618288; ENSP00000479501; ENSG00000226417
ENST00000619727; ENSP00000482255; ENSG00000226651
ENST00000621055; ENSP00000478930; ENSG00000226248
ENST00000622613; ENSP00000484581; ENSG00000223639
GeneIDi1192
KEGGihsa:1192

Similar proteinsi

Entry informationi

Entry nameiCLIC1_HUMAN
AccessioniPrimary (citable) accession number: O00299
Secondary accession number(s): Q15089, Q502X1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 23, 2007
Last modified: July 18, 2018
This is version 198 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

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

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