Hmdb loader
Identification
HMDB Protein ID HMDBP08193
Secondary Accession Numbers
  • 13904
Name Chloride intracellular channel protein 4
Synonyms
  1. Intracellular chloride ion channel protein p64H1
Gene Name CLIC4
Protein Type Unknown
Biological Properties
General Function Involved in voltage-gated chloride channel activity
Specific 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)
Pathways Not Available
Reactions Not Available
GO Classification
Component
membrane
cell part
Function
voltage-gated chloride channel activity
anion channel activity
chloride channel activity
transmembrane transporter activity
substrate-specific transmembrane transporter activity
ion transmembrane transporter activity
transporter activity
ion channel activity
Process
establishment of localization
transport
chloride transport
anion transport
inorganic anion transport
ion transport
Cellular Location
  1. Cell membrane
  2. Cytoplasm
  3. Mitochondrion
  4. cytoskeleton
  5. centrosome
  6. Cell junction
  7. Nucleus matrix
  8. Cytoplasmic vesicle membrane
  9. Single-pass membrane protein (Probable)
  10. Single-pass membrane protein (Probable)
Gene Properties
Chromosome Location Chromosome:1
Locus 1p36.11
SNPs CLIC4
Gene Sequence
>762 bp
ATGGCGTTGTCGATGCCGCTGAATGGGCTGAAGGAGGAGGACAAAGAGCCCCTCATCGAG
CTCTTCGTCAAGGCTGGCAGTGATGGTGAAAGCATAGGAAACTGCCCCTTTTCCCAGAGG
CTCTTCATGATTCTTTGGCTCAAAGGAGTTGTATTTAGTGTGACGACTGTTGACCTGAAA
AGGAAGCCAGCAGACCTGCAGAACTTGGCTCCCGGGACCCACCCACCATTTATAACTTTC
AACAGTGAAGTCAAAACGGATGTAAATAAGATTGAGGAATTTCTTGAAGAAGTCTTATGC
CCTCCCAAGTACTTAAAGCTTTCACCAAAACACCCAGAATCAAATACTGCTGGAATGGAC
ATCTTTGCCAAATTCTCTGCATATATCAAGAATTCAAGCGCAGAGGCTAATGAAGCACTG
GAGAGGGGTCTCCTGAAAACCCTGCAGAAACTGGATGAATATCTGAATTCTCCTCTCCCT
GATGAAATTGATGAAAATAGTATGGAGGACATAAAGTTTTCTACACGTAAATTTCTGGAT
GGCAATGAAATGACATTAGCTGATTGCAACCTGCTGCCCAAACTGCATATTGTCAAGGTG
GTGGCCAAAAAATATCGCAACTTTGATATTCCAAAAGAAATGACTGGCATCTGGAGATAC
CTAACTAATGCATACAGTAGGGACGAGTTCACCAATACCTGTCCCAGTGATAAGGAGGTT
GAAATAGCATATAGTGATGTAGCCAAAAGACTCACCAAGTAA
Protein Properties
Number of Residues 253
Molecular Weight 28771.8
Theoretical pI 5.26
Pfam Domain Function Not Available
Signals
  • None
Transmembrane Regions
  • 37-57
Protein Sequence
>Chloride intracellular channel protein 4
MALSMPLNGLKEEDKEPLIELFVKAGSDGESIGNCPFSQRLFMILWLKGVVFSVTTVDLK
RKPADLQNLAPGTHPPFITFNSEVKTDVNKIEEFLEEVLCPPKYLKLSPKHPESNTAGMD
IFAKFSAYIKNSRPEANEALERGLLKTLQKLDEYLNSPLPDEIDENSMEDIKFSTRKFLD
GNEMTLADCNLLPKLHIVKVVAKKYRNFDIPKEMTGIWRYLTNAYSRDEFTNTCPSDKEV
EIAYSDVAKRLTK
GenBank ID Protein 5052202
UniProtKB/Swiss-Prot ID Q9Y696
UniProtKB/Swiss-Prot Entry Name CLIC4_HUMAN
PDB IDs Not Available
GenBank Gene ID AF097330
GeneCard ID CLIC4
GenAtlas ID CLIC4
HGNC ID HGNC:13518
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  4. Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Bocher M, Blocker H, Bauersachs S, Blum H, Lauber J, Dusterhoft A, Beyer A, Kohrer K, Strack N, Mewes HW, Ottenwalder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A: Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome Res. 2001 Mar;11(3):422-35. [PubMed:11230166 ]
  5. Shanks RA, Larocca MC, Berryman M, Edwards JC, Urushidani T, Navarre J, Goldenring JR: AKAP350 at the Golgi apparatus. II. Association of AKAP350 with a novel chloride intracellular channel (CLIC) family member. J Biol Chem. 2002 Oct 25;277(43):40973-80. Epub 2002 Aug 5. [PubMed:12163479 ]
  6. Chuang JZ, Milner TA, Zhu M, Sung CH: A 29 kDa intracellular chloride channel p64H1 is associated with large dense-core vesicles in rat hippocampal neurons. J Neurosci. 1999 Apr 15;19(8):2919-28. [PubMed:10191309 ]
  7. Berryman M, Bretscher A: Identification of a novel member of the chloride intracellular channel gene family (CLIC5) that associates with the actin cytoskeleton of placental microvilli. Mol Biol Cell. 2000 May;11(5):1509-21. [PubMed:10793131 ]
  8. Edwards JC: A novel p64-related Cl- channel: subcellular distribution and nephron segment-specific expression. Am J Physiol. 1999 Mar;276(3 Pt 2):F398-408. [PubMed:10070163 ]
  9. Ronnov-Jessen L, Villadsen R, Edwards JC, Petersen OW: Differential expression of a chloride intracellular channel gene, CLIC4, in transforming growth factor-beta1-mediated conversion of fibroblasts to myofibroblasts. Am J Pathol. 2002 Aug;161(2):471-80. [PubMed:12163372 ]
  10. Berryman MA, Goldenring JR: CLIC4 is enriched at cell-cell junctions and colocalizes with AKAP350 at the centrosome and midbody of cultured mammalian cells. Cell Motil Cytoskeleton. 2003 Nov;56(3):159-72. [PubMed:14569596 ]
  11. Bohman S, Matsumoto T, Suh K, Dimberg A, Jakobsson L, Yuspa S, Claesson-Welsh L: Proteomic analysis of vascular endothelial growth factor-induced endothelial cell differentiation reveals a role for chloride intracellular channel 4 (CLIC4) in tubular morphogenesis. J Biol Chem. 2005 Dec 23;280(51):42397-404. Epub 2005 Oct 20. [PubMed:16239224 ]
  12. Suh KS, Crutchley JM, Koochek A, Ryscavage A, Bhat K, Tanaka T, Oshima A, Fitzgerald P, Yuspa SH: Reciprocal modifications of CLIC4 in tumor epithelium and stroma mark malignant progression of multiple human cancers. Clin Cancer Res. 2007 Jan 1;13(1):121-31. [PubMed:17200346 ]
  13. Suh KS, Mutoh M, Mutoh T, Li L, Ryscavage A, Crutchley JM, Dumont RA, Cheng C, Yuspa SH: CLIC4 mediates and is required for Ca2+-induced keratinocyte differentiation. J Cell Sci. 2007 Aug 1;120(Pt 15):2631-40. Epub 2007 Jul 17. [PubMed:17636002 ]
  14. Maeda K, Haraguchi M, Kuramasu A, Sato T, Ariake K, Sakagami H, Kondo H, Yanai K, Fukunaga K, Yanagisawa T, Sukegawa J: CLIC4 interacts with histamine H3 receptor and enhances the receptor cell surface expression. Biochem Biophys Res Commun. 2008 May 2;369(2):603-8. doi: 10.1016/j.bbrc.2008.02.071. Epub 2008 Feb 25. [PubMed:18302930 ]
  15. Tung JJ, Hobert O, Berryman M, Kitajewski J: Chloride intracellular channel 4 is involved in endothelial proliferation and morphogenesis in vitro. Angiogenesis. 2009;12(3):209-20. doi: 10.1007/s10456-009-9139-3. Epub 2009 Feb 27. [PubMed:19247789 ]
  16. Littler DR, Assaad NN, Harrop SJ, Brown LJ, Pankhurst GJ, Luciani P, Aguilar MI, Mazzanti M, Berryman MA, Breit SN, Curmi PM: Crystal structure of the soluble form of the redox-regulated chloride ion channel protein CLIC4. FEBS J. 2005 Oct;272(19):4996-5007. [PubMed:16176272 ]
  17. Li Y, Li D, Zeng Z, Wang D: Trimeric structure of the wild soluble chloride intracellular ion channel CLIC4 observed in crystals. Biochem Biophys Res Commun. 2006 May 19;343(4):1272-8. Epub 2006 Mar 27. [PubMed:16581025 ]