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Q9Y696 (CLIC4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Chloride intracellular channel protein 4
Alternative name(s):
Intracellular chloride ion channel protein p64H1
Gene names
Name:CLIC4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length253 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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). Ref.7 Ref.9 Ref.10 Ref.13 Ref.15 Ref.20

Subunit structure

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. Ref.6 Ref.8 Ref.13 Ref.20

Subcellular location

Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Cytoplasmic vesicle membrane; Single-pass membrane protein Probable. Nucleus matrix. Cell membrane; Single-pass membrane protein Probable. Mitochondrion. Cell junction. Note: Colocalized with AKAP9 at the centrosome and midbody. Exists both as soluble cytoplasmic protein and as membrane protein with probably a single transmembrane domain. Present in an intracellular vesicular compartment that likely represent trans-Golgi network vesicles. Ref.9 Ref.11 Ref.12 Ref.13 Ref.20

Tissue specificity

Detected in epithelial cells from colon, esophagus and kidney (at protein level). Expression is prominent in heart, kidney, placenta and skeletal muscle. Ref.6 Ref.11 Ref.12

Induction

Up-regulated by calcium ions in differentiating keratinocytes. Up-regulated in myofibroblasts. Ref.7 Ref.12

Domain

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. Ref.21

Sequence similarities

Belongs to the chloride channel CLIC family.

Contains 1 GST C-terminal domain.

Ontologies

Keywords
   Biological processIon transport
Transport
   Cellular componentCell junction
Cell membrane
Cytoplasm
Cytoplasmic vesicle
Cytoskeleton
Membrane
Mitochondrion
Nucleus
   DomainTransmembrane
Transmembrane helix
   LigandChloride
   Molecular functionChloride channel
Ion channel
Voltage-gated channel
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: Ensembl

branching morphogenesis of an epithelial tube

Inferred from electronic annotation. Source: Ensembl

cell differentiation

Traceable author statement Ref.7. Source: UniProtKB

cellular response to calcium ion

Inferred from mutant phenotype Ref.12. Source: UniProtKB

chloride transmembrane transport

Traceable author statement PubMed 9295337. Source: GOC

chloride transport

Non-traceable author statement Ref.6. Source: UniProtKB

endothelial cell morphogenesis

Inferred from electronic annotation. Source: Ensembl

establishment or maintenance of apical/basal cell polarity

Non-traceable author statement Ref.9. Source: UniProtKB

fertilization

Inferred from electronic annotation. Source: Ensembl

keratinocyte differentiation

Inferred from mutant phenotype Ref.12. Source: UniProtKB

multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell migration

Inferred from direct assay Ref.7. Source: UniProtKB

regulation of cytoskeleton organization

Non-traceable author statement Ref.9. Source: UniProtKB

retina vasculature morphogenesis in camera-type eye

Inferred from electronic annotation. Source: Ensembl

vacuolar acidification

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentactin cytoskeleton

Traceable author statement Ref.7. Source: UniProtKB

apical part of cell

Inferred from direct assay Ref.9. Source: UniProtKB

cell surface

Inferred from direct assay Ref.9. Source: UniProtKB

cell-cell junction

Inferred from direct assay Ref.9. Source: UniProtKB

centrosome

Inferred from direct assay Ref.9. Source: UniProtKB

chloride channel complex

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Inferred from direct assay Ref.6Ref.9. Source: UniProtKB

cytoplasmic vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from direct assay PubMed 10026142PubMed 19776349. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 20458337PubMed 23376485. Source: UniProt

intracellular

Inferred from direct assay. Source: LIFEdb

microvillus

Inferred from direct assay Ref.9. Source: UniProtKB

midbody

Inferred from direct assay Ref.9. Source: UniProtKB

mitochondrion

Inferred from direct assay Ref.9. Source: UniProtKB

nuclear matrix

Inferred from direct assay Ref.9. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay Ref.9. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 19776349. Source: UniProtKB

   Molecular_functionchloride channel activity

Traceable author statement PubMed 9295337. Source: ProtInc

protein binding

Inferred from physical interaction Ref.6Ref.8. Source: UniProtKB

voltage-gated chloride channel activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.5
Chain2 – 253252Chloride intracellular channel protein 4
PRO_0000144210

Regions

Transmembrane37 – 5721Helical; Note=After insertion into the membrane; Potential
Domain104 – 244141GST C-terminal
Region2 – 101100Required for insertion into the membrane Probable

Amino acid modifications

Modified residue21N-acetylalanine Ref.5 Ref.14 Ref.18
Modified residue41Phosphoserine Ref.18
Modified residue1301N6-acetyllysine Ref.16
Modified residue2361Phosphoserine By similarity

Experimental info

Sequence conflict141D → Y in AAD26136. Ref.2
Sequence conflict133 – 1342RP → SA in AAD38446. Ref.1
Sequence conflict133 – 1342RP → SA in AAD26136. Ref.2
Sequence conflict2251Y → S in AAD26136. Ref.2
Sequence conflict2331T → A in AAD26136. Ref.2

Secondary structure

..................................... 253
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9Y696 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 3DD21A33C66626A5

FASTA25328,772
        10         20         30         40         50         60 
MALSMPLNGL KEEDKEPLIE LFVKAGSDGE SIGNCPFSQR LFMILWLKGV VFSVTTVDLK 

        70         80         90        100        110        120 
RKPADLQNLA PGTHPPFITF NSEVKTDVNK IEEFLEEVLC PPKYLKLSPK HPESNTAGMD 

       130        140        150        160        170        180 
IFAKFSAYIK NSRPEANEAL ERGLLKTLQK LDEYLNSPLP DEIDENSMED IKFSTRKFLD 

       190        200        210        220        230        240 
GNEMTLADCN LLPKLHIVKV VAKKYRNFDI PKEMTGIWRY LTNAYSRDEF TNTCPSDKEV 

       250 
EIAYSDVAKR LTK 

« Hide

References

« Hide 'large scale' references
[1]"A novel p64-related Cl- channel: subcellular distribution and nephron segment-specific expression."
Edwards J.C.
Am. J. Physiol. 276:F398-F408(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"A 29 kDa intracellular chloride channel p64H1 is associated with large dense-core vesicles in rat hippocampal neurons."
Chuang J.Z., Milner T.A., Zhu M., Sung C.H.
J. Neurosci. 19:2919-2928(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Ovary.
[5]Bienvenut W.V., Claeys D.
Submitted (FEB-2006) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-24; 41-60; 62-85 AND 125-130, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Platelet.
[6]"Identification of a novel member of the chloride intracellular channel gene family (CLIC5) that associates with the actin cytoskeleton of placental microvilli."
Berryman M., Bretscher A.
Mol. Biol. Cell 11:1509-1521(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, TISSUE SPECIFICITY.
[7]"Differential expression of a chloride intracellular channel gene, CLIC4, in transforming growth factor-beta1-mediated conversion of fibroblasts to myofibroblasts."
Ronnov-Jessen L., Villadsen R., Edwards J.C., Petersen O.W.
Am. J. Pathol. 161:471-480(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, FUNCTION.
[8]"AKAP350 at the Golgi apparatus. II. Association of AKAP350 with a novel chloride intracellular channel (CLIC) family member."
Shanks R.A., Larocca M.C., Berryman M., Edwards J.C., Urushidani T., Navarre J., Goldenring J.R.
J. Biol. Chem. 277:40973-40980(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AKAP9.
[9]"CLIC4 is enriched at cell-cell junctions and colocalizes with AKAP350 at the centrosome and midbody of cultured mammalian cells."
Berryman M.A., Goldenring J.R.
Cell Motil. Cytoskeleton 56:159-172(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]"Proteomic analysis of vascular endothelial growth factor-induced endothelial cell differentiation reveals a role for chloride intracellular channel 4 (CLIC4) in tubular morphogenesis."
Bohman S., Matsumoto T., Suh K., Dimberg A., Jakobsson L., Yuspa S., Claesson-Welsh L.
J. Biol. Chem. 280:42397-42404(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Reciprocal modifications of CLIC4 in tumor epithelium and stroma mark malignant progression of multiple human cancers."
Suh K.S., Crutchley J.M., Koochek A., Ryscavage A., Bhat K., Tanaka T., Oshima A., Fitzgerald P., Yuspa S.H.
Clin. Cancer Res. 13:121-131(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[12]"CLIC4 mediates and is required for Ca2+-induced keratinocyte differentiation."
Suh K.S., Mutoh M., Mutoh T., Li L., Ryscavage A., Crutchley J.M., Dumont R.A., Cheng C., Yuspa S.H.
J. Cell Sci. 120:2631-2640(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INDUCTION, SUBCELLULAR LOCATION.
[13]"CLIC4 interacts with histamine H3 receptor and enhances the receptor cell surface expression."
Maeda K., Haraguchi M., Kuramasu A., Sato T., Ariake K., Sakagami H., Kondo H., Yanai K., Fukunaga K., Yanagisawa T., Sukegawa J.
Biochem. Biophys. Res. Commun. 369:603-608(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HRH3, FUNCTION, SUBCELLULAR LOCATION.
[14]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Chloride intracellular channel 4 is involved in endothelial proliferation and morphogenesis in vitro."
Tung J.J., Hobert O., Berryman M., Kitajewski J.
Angiogenesis 12:209-220(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-130, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"Crystal structure of the soluble form of the redox-regulated chloride ion channel protein CLIC4."
Littler D.R., Assaad N.N., Harrop S.J., Brown L.J., Pankhurst G.J., Luciani P., Aguilar M.-I., Mazzanti M., Berryman M.A., Breit S.N., Curmi P.M.G.
FEBS J. 272:4996-5007(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS), SUBUNIT, FUNCTION, SUBCELLULAR LOCATION.
[21]"Trimeric structure of the wild soluble chloride intracellular ion channel CLIC4 observed in crystals."
Li Y., Li D., Zeng Z., Wang D.
Biochem. Biophys. Res. Commun. 343:1272-1278(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), DOMAIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF097330 mRNA. Translation: AAD38446.1.
AF109196 mRNA. Translation: AAD26136.1.
AL117424 mRNA. Translation: CAB55916.1.
BC012444 mRNA. Translation: AAH12444.1.
CCDSCCDS256.1.
PIRT17226.
RefSeqNP_039234.1. NM_013943.2.
UniGeneHs.440544.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2AHEX-ray1.80A1-251[»]
2D2ZX-ray2.20A/B/C1-253[»]
3OQSX-ray2.00B198-207[»]
ProteinModelPortalQ9Y696.
SMRQ9Y696. Positions 6-253.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117431. 9 interactions.
IntActQ9Y696. 3 interactions.
MINTMINT-3087884.
STRING9606.ENSP00000363500.

Protein family/group databases

TCDB1.A.12.1.6. the intracellular chloride channel (clic) family.

PTM databases

PhosphoSiteQ9Y696.

Polymorphism databases

DMDM20141285.

2D gel databases

OGPQ9Y696.
REPRODUCTION-2DPAGEIPI00001960.

Proteomic databases

MaxQBQ9Y696.
PaxDbQ9Y696.
PeptideAtlasQ9Y696.
PRIDEQ9Y696.

Protocols and materials databases

DNASU25932.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000374379; ENSP00000363500; ENSG00000169504.
ENST00000488683; ENSP00000436538; ENSG00000169504.
GeneID25932.
KEGGhsa:25932.
UCSCuc001bjo.2. human.

Organism-specific databases

CTD25932.
GeneCardsGC01P025071.
HGNCHGNC:13518. CLIC4.
HPAHPA008019.
MIM606536. gene.
neXtProtNX_Q9Y696.
PharmGKBPA26591.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG282171.
HOGENOMHOG000231548.
HOVERGENHBG050994.
InParanoidQ9Y696.
KOK05024.
OMAIDHNSIE.
OrthoDBEOG7X3QR3.
PhylomeDBQ9Y696.
TreeFamTF315438.

Gene expression databases

ArrayExpressQ9Y696.
BgeeQ9Y696.
CleanExHS_CLIC4.
GenevestigatorQ9Y696.

Family and domain databases

Gene3D1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProIPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR002946. Int_Cl_channel.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PfamPF13417. GST_N_3. 1 hit.
[Graphical view]
PRINTSPR01263. INTCLCHANNEL.
SUPFAMSSF47616. SSF47616. 1 hit.
SSF52833. SSF52833. 1 hit.
TIGRFAMsTIGR00862. O-ClC. 1 hit.
PROSITEPS50405. GST_CTER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCLIC4. human.
EvolutionaryTraceQ9Y696.
GeneWikiCLIC4.
GenomeRNAi25932.
NextBio47480.
PROQ9Y696.
SOURCESearch...

Entry information

Entry nameCLIC4_HUMAN
AccessionPrimary (citable) accession number: Q9Y696
Secondary accession number(s): Q9UFW9, Q9UQJ6
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 137 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM