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Protein

Chloride intracellular channel protein 4

Gene

CLIC4

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 poorly selective ion channels that may also transport chloride ions. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Promotes cell-surface expression of HRH3. Has alternate cellular functions like a potential role in angiogenesis or in maintaining apical-basolateral membrane polarity during mitosis and cytokinesis. Could also promote endothelial cell proliferation and regulate endothelial morphogenesis (tubulogenesis).6 Publications

GO - Molecular functioni

  • chloride channel activity Source: ProtInc
  • voltage-gated ion channel activity Source: UniProtKB-KW

GO - Biological processi

  • angiogenesis Source: GO_Central
  • apoptotic process Source: InterPro
  • branching morphogenesis of an epithelial tube Source: Ensembl
  • cell differentiation Source: UniProtKB
  • cellular response to calcium ion Source: UniProtKB
  • chloride transport Source: UniProtKB
  • endothelial cell morphogenesis Source: Ensembl
  • establishment or maintenance of apical/basal cell polarity Source: UniProtKB
  • fertilization Source: Ensembl
  • keratinocyte differentiation Source: UniProtKB
  • multicellular organism growth Source: Ensembl
  • negative regulation of cell migration Source: UniProtKB
  • regulation of cytoskeleton organization Source: UniProtKB
  • retina vasculature morphogenesis in camera-type eye Source: Ensembl
  • vacuolar acidification Source: Ensembl
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:ENSG00000169504-MONOMER.

Protein family/group databases

TCDBi1.A.12.1.6. the intracellular chloride channel (clic) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Chloride intracellular channel protein 4
Alternative name(s):
Intracellular chloride ion channel protein p64H1
Gene namesi
Name:CLIC4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:13518. CLIC4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei37 – 57Helical; Note=After insertion into the membraneSequence analysisAdd BLAST21

GO - Cellular componenti

  • actin cytoskeleton Source: UniProtKB
  • apical part of cell Source: UniProtKB
  • cell-cell junction Source: UniProtKB
  • cell surface Source: UniProtKB
  • centrosome Source: UniProtKB
  • chloride channel complex Source: UniProtKB-KW
  • cytoplasm Source: UniProtKB
  • cytoplasmic vesicle membrane Source: UniProtKB-SubCell
  • cytosol Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • intracellular Source: LIFEdb
  • microvillus Source: UniProtKB
  • midbody Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • nuclear matrix Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Membrane, Mitochondrion, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi25932.
OpenTargetsiENSG00000169504.
PharmGKBiPA26591.

Polymorphism and mutation databases

BioMutaiCLIC4.
DMDMi20141285.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001442102 – 253Chloride intracellular channel protein 4Add BLAST252

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei4PhosphoserineCombined sources1
Modified residuei130N6-acetyllysineCombined sources1
Modified residuei236PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9Y696.
MaxQBiQ9Y696.
PaxDbiQ9Y696.
PeptideAtlasiQ9Y696.
PRIDEiQ9Y696.
TopDownProteomicsiQ9Y696.

2D gel databases

OGPiQ9Y696.
REPRODUCTION-2DPAGEIPI00001960.

PTM databases

iPTMnetiQ9Y696.
PhosphoSitePlusiQ9Y696.
SwissPalmiQ9Y696.

Expressioni

Tissue specificityi

Detected in epithelial cells from colon, esophagus and kidney (at protein level). Expression is prominent in heart, kidney, placenta and skeletal muscle.3 Publications

Inductioni

Up-regulated by calcium ions in differentiating keratinocytes. Up-regulated in myofibroblasts.2 Publications

Gene expression databases

BgeeiENSG00000169504.
CleanExiHS_CLIC4.
ExpressionAtlasiQ9Y696. baseline and differential.
GenevisibleiQ9Y696. HS.

Organism-specific databases

HPAiHPA008019.
HPA060804.

Interactioni

Subunit structurei

Component of a multimeric complex consisting of several cytoskeletal proteins, including actin, ezrin, alpha-actinin, gelsolin, IQGAP1 and CLIC5A. Binds directly to brain dynamin I in a complex containing actin, tubulin and 14-3-3 isoforms. Monomer. Interacts with HRH3. Interacts with AKAP9.4 Publications

Protein-protein interaction databases

BioGridi117431. 47 interactors.
IntActiQ9Y696. 5 interactors.
MINTiMINT-3087884.
STRINGi9606.ENSP00000363500.

Structurei

Secondary structure

1253
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi19 – 25Combined sources7
Beta strandi29 – 32Combined sources4
Helixi36 – 48Combined sources13
Beta strandi53 – 57Combined sources5
Helixi64 – 69Combined sources6
Beta strandi77 – 80Combined sources4
Beta strandi83 – 85Combined sources3
Helixi88 – 98Combined sources11
Turni101 – 103Combined sources3
Helixi112 – 115Combined sources4
Turni116 – 120Combined sources5
Helixi121 – 130Combined sources10
Helixi134 – 136Combined sources3
Helixi137 – 156Combined sources20
Beta strandi181 – 183Combined sources3
Helixi186 – 206Combined sources21
Helixi215 – 225Combined sources11
Helixi228 – 231Combined sources4
Helixi237 – 243Combined sources7
Turni244 – 247Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AHEX-ray1.80A1-251[»]
2D2ZX-ray2.20A/B/C1-253[»]
3OQSX-ray2.00B198-207[»]
ProteinModelPortaliQ9Y696.
SMRiQ9Y696.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y696.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini104 – 244GST C-terminalAdd BLAST141

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 101Required for insertion into the membraneCuratedAdd BLAST100

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.1 Publication

Sequence similaritiesi

Belongs to the chloride channel CLIC family.Curated
Contains 1 GST C-terminal domain.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1422. Eukaryota.
ENOG410ZRK6. LUCA.
GeneTreeiENSGT00550000074477.
HOGENOMiHOG000231548.
HOVERGENiHBG050994.
InParanoidiQ9Y696.
KOiK05024.
OMAiIWKYLNN.
OrthoDBiEOG091G0IHT.
PhylomeDBiQ9Y696.
TreeFamiTF315438.

Family and domain databases

Gene3Di1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProiIPR002946. CLIC.
IPR030257. CLIC-4.
IPR010987. Glutathione-S-Trfase_C-like.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11260:SF185. PTHR11260:SF185. 2 hits.
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.

Q9Y696-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALSMPLNGL KEEDKEPLIE LFVKAGSDGE SIGNCPFSQR LFMILWLKGV
60 70 80 90 100
VFSVTTVDLK RKPADLQNLA PGTHPPFITF NSEVKTDVNK IEEFLEEVLC
110 120 130 140 150
PPKYLKLSPK HPESNTAGMD IFAKFSAYIK NSRPEANEAL ERGLLKTLQK
160 170 180 190 200
LDEYLNSPLP DEIDENSMED IKFSTRKFLD GNEMTLADCN LLPKLHIVKV
210 220 230 240 250
VAKKYRNFDI PKEMTGIWRY LTNAYSRDEF TNTCPSDKEV EIAYSDVAKR

LTK
Length:253
Mass (Da):28,772
Last modified:January 23, 2007 - v4
Checksum:i3DD21A33C66626A5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti14D → Y in AAD26136 (PubMed:10191309).Curated1
Sequence conflicti133 – 134RP → SA in AAD38446 (PubMed:10070163).Curated2
Sequence conflicti133 – 134RP → SA in AAD26136 (PubMed:10191309).Curated2
Sequence conflicti225Y → S in AAD26136 (PubMed:10191309).Curated1
Sequence conflicti233T → A in AAD26136 (PubMed:10191309).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF097330 mRNA. Translation: AAD38446.1.
AF109196 mRNA. Translation: AAD26136.1.
AL117424 mRNA. Translation: CAB55916.1.
BC012444 mRNA. Translation: AAH12444.1.
CCDSiCCDS256.1.
PIRiT17226.
RefSeqiNP_039234.1. NM_013943.2.
UniGeneiHs.440544.

Genome annotation databases

EnsembliENST00000374379; ENSP00000363500; ENSG00000169504.
ENST00000488683; ENSP00000436538; ENSG00000169504.
GeneIDi25932.
KEGGihsa:25932.
UCSCiuc001bjo.3. human.

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF097330 mRNA. Translation: AAD38446.1.
AF109196 mRNA. Translation: AAD26136.1.
AL117424 mRNA. Translation: CAB55916.1.
BC012444 mRNA. Translation: AAH12444.1.
CCDSiCCDS256.1.
PIRiT17226.
RefSeqiNP_039234.1. NM_013943.2.
UniGeneiHs.440544.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AHEX-ray1.80A1-251[»]
2D2ZX-ray2.20A/B/C1-253[»]
3OQSX-ray2.00B198-207[»]
ProteinModelPortaliQ9Y696.
SMRiQ9Y696.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117431. 47 interactors.
IntActiQ9Y696. 5 interactors.
MINTiMINT-3087884.
STRINGi9606.ENSP00000363500.

Protein family/group databases

TCDBi1.A.12.1.6. the intracellular chloride channel (clic) family.

PTM databases

iPTMnetiQ9Y696.
PhosphoSitePlusiQ9Y696.
SwissPalmiQ9Y696.

Polymorphism and mutation databases

BioMutaiCLIC4.
DMDMi20141285.

2D gel databases

OGPiQ9Y696.
REPRODUCTION-2DPAGEIPI00001960.

Proteomic databases

EPDiQ9Y696.
MaxQBiQ9Y696.
PaxDbiQ9Y696.
PeptideAtlasiQ9Y696.
PRIDEiQ9Y696.
TopDownProteomicsiQ9Y696.

Protocols and materials databases

DNASUi25932.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000374379; ENSP00000363500; ENSG00000169504.
ENST00000488683; ENSP00000436538; ENSG00000169504.
GeneIDi25932.
KEGGihsa:25932.
UCSCiuc001bjo.3. human.

Organism-specific databases

CTDi25932.
DisGeNETi25932.
GeneCardsiCLIC4.
HGNCiHGNC:13518. CLIC4.
HPAiHPA008019.
HPA060804.
MIMi606536. gene.
neXtProtiNX_Q9Y696.
OpenTargetsiENSG00000169504.
PharmGKBiPA26591.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1422. Eukaryota.
ENOG410ZRK6. LUCA.
GeneTreeiENSGT00550000074477.
HOGENOMiHOG000231548.
HOVERGENiHBG050994.
InParanoidiQ9Y696.
KOiK05024.
OMAiIWKYLNN.
OrthoDBiEOG091G0IHT.
PhylomeDBiQ9Y696.
TreeFamiTF315438.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000169504-MONOMER.

Miscellaneous databases

ChiTaRSiCLIC4. human.
EvolutionaryTraceiQ9Y696.
GeneWikiiCLIC4.
GenomeRNAii25932.
PROiQ9Y696.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169504.
CleanExiHS_CLIC4.
ExpressionAtlasiQ9Y696. baseline and differential.
GenevisibleiQ9Y696. HS.

Family and domain databases

Gene3Di1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProiIPR002946. CLIC.
IPR030257. CLIC-4.
IPR010987. Glutathione-S-Trfase_C-like.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11260:SF185. PTHR11260:SF185. 2 hits.
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 nameiCLIC4_HUMAN
AccessioniPrimary (citable) accession number: Q9Y696
Secondary accession number(s): Q9UFW9, Q9UQJ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 159 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

Keywords - Technical termi

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

Documents

  1. Human chromosome 1
    Human chromosome 1: 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.