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Protein

Chloride intracellular channel protein 1

Gene

CLIC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Sites

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

GO - Molecular functioni

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

GO - Biological processi

  • chloride transport Source: MGI
  • platelet aggregation Source: UniProtKB
  • positive regulation of osteoblast differentiation Source: Ensembl
  • regulation of cell cycle Source: InterPro
  • regulation of mitochondrial membrane potential Source: Ensembl
  • signal transduction Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Chloride channel, Ion channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Transport

Keywords - Ligandi

Chloride

Enzyme and pathway databases

BioCyciZFISH:ENSG00000096238-MONOMER.
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

HGNCiHGNC:2062. CLIC1.

Subcellular locationi

Topology

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

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • brush border Source: UniProtKB
  • cell-cell adherens junction Source: BHF-UCL
  • chloride channel complex Source: UniProtKB-KW
  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular space Source: UniProtKB
  • membrane Source: UniProtKB
  • mitochondrion Source: Ensembl
  • nuclear envelope Source: MGI
  • nuclear membrane Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: BHF-UCL
  • plasma membrane Source: UniProtKB-SubCell
  • vesicle Source: UniProtKB
Complete GO annotation...

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.
OpenTargetsiENSG00000206394.
ENSG00000213719.
ENSG00000223639.
ENSG00000226248.
ENSG00000226417.
ENSG00000226651.
ENSG00000230685.
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.
TopDownProteomicsiO00299.

2D gel databases

OGPiO00299.
SWISS-2DPAGEO00299.

PTM databases

iPTMnetiO00299.
PhosphoSitePlusiO00299.
SwissPalmiO00299.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000206394.
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

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL

Protein-protein interaction databases

BioGridi107604. 56 interactors.
IntActiO00299. 42 interactors.
MINTiMINT-1033423.
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K0MX-ray1.40A/B1-241[»]
1K0NX-ray1.80A/B1-241[»]
1K0OX-ray1.75A/B1-241[»]
1RK4X-ray1.79A/B1-241[»]
3O3TX-ray1.70A1-241[»]
3P8WX-ray2.00A1-241[»]
3P90X-ray2.30A1-241[»]
3QR6X-ray1.78A1-241[»]
3SWLX-ray2.35A6-241[»]
3TGZX-ray2.30A/B1-241[»]
3UVHX-ray1.84A/B1-241[»]
4IQAX-ray2.49A/B6-241[»]
4JZQX-ray1.35A/B1-241[»]
4K0GX-ray1.40A2-241[»]
4K0NX-ray1.25A1-241[»]
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
Contains 1 GST C-terminal domain.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProiIPR002946. CLIC.
IPR030259. CLIC-1.
IPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11260:SF210. PTHR11260:SF210. 2 hits.
PfamiPF13409. GST_N_2. 1 hit.
[Graphical view]
PRINTSiPR01263. INTCLCHANNEL.
SUPFAMiSSF47616. SSF47616. 1 hit.
SSF52833. SSF52833. 1 hit.
TIGRFAMsiTIGR00862. O-ClC. 1 hit.
PROSITEiPS50405. GST_CTER. 1 hit.
[Graphical view]

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. Translation: CAI18417.1.
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.

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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. Translation: CAI18417.1.
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K0MX-ray1.40A/B1-241[»]
1K0NX-ray1.80A/B1-241[»]
1K0OX-ray1.75A/B1-241[»]
1RK4X-ray1.79A/B1-241[»]
3O3TX-ray1.70A1-241[»]
3P8WX-ray2.00A1-241[»]
3P90X-ray2.30A1-241[»]
3QR6X-ray1.78A1-241[»]
3SWLX-ray2.35A6-241[»]
3TGZX-ray2.30A/B1-241[»]
3UVHX-ray1.84A/B1-241[»]
4IQAX-ray2.49A/B6-241[»]
4JZQX-ray1.35A/B1-241[»]
4K0GX-ray1.40A2-241[»]
4K0NX-ray1.25A1-241[»]
ProteinModelPortaliO00299.
SMRiO00299.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107604. 56 interactors.
IntActiO00299. 42 interactors.
MINTiMINT-1033423.
STRINGi9606.ENSP00000364934.

Protein family/group databases

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

PTM databases

iPTMnetiO00299.
PhosphoSitePlusiO00299.
SwissPalmiO00299.

Polymorphism and mutation databases

BioMutaiCLIC1.

2D gel databases

OGPiO00299.
SWISS-2DPAGEO00299.

Proteomic databases

EPDiO00299.
PaxDbiO00299.
PeptideAtlasiO00299.
PRIDEiO00299.
TopDownProteomicsiO00299.

Protocols and materials databases

DNASUi1192.
Structural Biology KnowledgebaseSearch...

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.

Organism-specific databases

CTDi1192.
DisGeNETi1192.
GeneCardsiCLIC1.
HGNCiHGNC:2062. CLIC1.
HPAiCAB020825.
CAB040557.
MIMi602872. gene.
neXtProtiNX_O00299.
OpenTargetsiENSG00000206394.
ENSG00000213719.
ENSG00000223639.
ENSG00000226248.
ENSG00000226417.
ENSG00000226651.
ENSG00000230685.
PharmGKBiPA26588.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000096238-MONOMER.
SignaLinkiO00299.

Miscellaneous databases

ChiTaRSiCLIC1. human.
EvolutionaryTraceiO00299.
GeneWikiiCLIC1.
GenomeRNAii1192.
PROiO00299.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000206394.
CleanExiHS_CLIC1.
ExpressionAtlasiO00299. baseline and differential.
GenevisibleiO00299. HS.

Family and domain databases

Gene3Di1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProiIPR002946. CLIC.
IPR030259. CLIC-1.
IPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11260:SF210. PTHR11260:SF210. 2 hits.
PfamiPF13409. GST_N_2. 1 hit.
[Graphical view]
PRINTSiPR01263. INTCLCHANNEL.
SUPFAMiSSF47616. SSF47616. 1 hit.
SSF52833. SSF52833. 1 hit.
TIGRFAMsiTIGR00862. O-ClC. 1 hit.
PROSITEiPS50405. GST_CTER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCLIC1_HUMAN
AccessioniPrimary (citable) accession number: O00299
Secondary accession number(s): Q15089, Q502X1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 181 of the entry and version 4 of the sequence. [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

Miscellaneous

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

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.