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Protein

Chloride intracellular channel protein 4

Gene

CLIC4

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

GO - Biological processi

  • angiogenesis Source: GO_Central
  • branching morphogenesis of an epithelial tube Source: Ensembl
  • cell differentiation Source: UniProtKB
  • cellular response to calcium ion Source: UniProtKB
  • chloride transmembrane transport Source: GO_Central
  • 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
  • regulation of ion transmembrane transport Source: UniProtKB-KW
  • retina vasculature morphogenesis in camera-type eye Source: Ensembl
  • vacuolar acidification Source: Ensembl

Keywordsi

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

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

EuPathDBiHostDB:ENSG00000169504.14
HGNCiHGNC:13518 CLIC4
MIMi606536 gene
neXtProtiNX_Q9Y696

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
Transmembranei37 – 57Helical; Note=After insertion into the membraneSequence analysisAdd BLAST21

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 residuei24N6-acetyllysineBy similarity1
Modified residuei130N6-acetyllysineCombined sources1
Modified residuei132PhosphoserineBy similarity1
Modified residuei167PhosphoserineBy similarity1
Modified residuei236PhosphoserineBy similarity1
Modified residuei244PhosphotyrosineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9Y696
MaxQBiQ9Y696
PaxDbiQ9Y696
PeptideAtlasiQ9Y696
PRIDEiQ9Y696
TopDownProteomicsiQ9Y696

2D gel databases

OGPiQ9Y696
REPRODUCTION-2DPAGEiIPI00001960

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

BioGridi11743149 interactors.
IntActiQ9Y696 6 interactors.
MINTiQ9Y696
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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR002946 CLIC
IPR030257 CLIC-4
IPR010987 Glutathione-S-Trfase_C-like
IPR036282 Glutathione-S-Trfase_C_sf
IPR036249 Thioredoxin-like_sf
PANTHERiPTHR43920:SF7 PTHR43920:SF7, 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.

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

Similar proteinsi

Entry informationi

Entry nameiCLIC4_HUMAN
AccessioniPrimary (citable) accession number: Q9Y696
Secondary accession number(s): Q9UFW9, Q9UQJ6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: March 28, 2018
This is version 169 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