Chloride intracellular channel protein 4

NameChloride intracellular channel protein 4
Synonyms
  • Intracellular chloride ion channel protein p64H1
Gene NameCLIC4
OrganismHuman
Amino acid sequence
>lcl|BSEQ0013584|Chloride intracellular channel protein 4
MALSMPLNGLKEEDKEPLIELFVKAGSDGESIGNCPFSQRLFMILWLKGVVFSVTTVDLK
RKPADLQNLAPGTHPPFITFNSEVKTDVNKIEEFLEEVLCPPKYLKLSPKHPESNTAGMD
IFAKFSAYIKNSRPEANEALERGLLKTLQKLDEYLNSPLPDEIDENSMEDIKFSTRKFLD
GNEMTLADCNLLPKLHIVKVVAKKYRNFDIPKEMTGIWRYLTNAYSRDEFTNTCPSDKEV
EIAYSDVAKRLTK
Number of residues253
Molecular Weight28771.8
Theoretical pINot Available
GO Classification
Functions
  • voltage-gated ion channel activity
  • chloride channel activity
Processes
  • vacuolar acidification
  • branching morphogenesis of an epithelial tube
  • keratinocyte differentiation
  • cell differentiation
  • endothelial cell morphogenesis
  • multicellular organism growth
  • regulation of cytoskeleton organization
  • apoptotic process
  • angiogenesis
  • establishment or maintenance of apical/basal cell polarity
  • chloride transmembrane transport
  • fertilization
  • retina vasculature morphogenesis in camera-type eye
  • cellular response to calcium ion
  • negative regulation of cell migration
  • chloride transport
Components
  • plasma membrane
  • cytoplasmic vesicle membrane
  • cell surface
  • actin cytoskeleton
  • chloride channel complex
  • cytosol
  • extracellular exosome
  • microvillus
  • perinuclear region of cytoplasm
  • centrosome
  • midbody
  • intracellular
  • cytoplasm
  • nuclear matrix
  • mitochondrion
  • apical part of cell
  • cell-cell junction
General FunctionVoltage-gated ion channel activity
Specific FunctionCan 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).
Pfam Domain Function
Transmembrane Regions37-57
GenBank Protein IDNot Available
UniProtKB IDQ9Y696
UniProtKB Entry NameCLIC4_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0013585|Chloride intracellular channel protein 4 (CLIC4)
ATGGCGTTGTCGATGCCGCTGAATGGGCTGAAGGAGGAGGACAAAGAGCCCCTCATCGAG
CTCTTCGTCAAGGCTGGCAGTGATGGTGAAAGCATAGGAAACTGCCCCTTTTCCCAGAGG
CTCTTCATGATTCTTTGGCTCAAAGGAGTTGTATTTAGTGTGACGACTGTTGACCTGAAA
AGGAAGCCAGCAGACCTGCAGAACTTGGCTCCCGGGACCCACCCACCATTTATAACTTTC
AACAGTGAAGTCAAAACGGATGTAAATAAGATTGAGGAATTTCTTGAAGAAGTCTTATGC
CCTCCCAAGTACTTAAAGCTTTCACCAAAACACCCAGAATCAAATACTGCTGGAATGGAC
ATCTTTGCCAAATTCTCTGCATATATCAAGAATTCAAGGCCAGAGGCTAATGAAGCACTG
GAGAGGGGTCTCCTGAAAACCCTGCAGAAACTGGATGAATATCTGAATTCTCCTCTCCCT
GATGAAATTGATGAAAATAGTATGGAGGACATAAAGTTTTCTACACGTAAATTTCTGGAT
GGCAATGAAATGACATTAGCTGATTGCAACCTGCTGCCCAAACTGCATATTGTCAAGGTG
GTGGCCAAAAAATATCGCAACTTTGATATTCCAAAAGAAATGACTGGCATCTGGAGATAC
CTAACTAATGCATACAGTAGGGACGAGTTCACCAATACCTGTCCCAGTGATAAGGAGGTT
GAAATAGCATATAGTGATGTAGCCAAAAGACTCACCAAGTAA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:13518
Chromosome Location1
LocusNot Available
References
  1. 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. 10070163
  2. 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. 10191309
  3. 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. 11230166
  4. 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. 15489334
  5. 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. 10793131
  6. 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. 12163372
  7. 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. 12163479
  8. 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. 14569596
  9. 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. 16239224
  10. 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. 17200346
  11. 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. 17636002
  12. 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. 18302930
  13. 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. 19413330
  14. 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. 19247789
  15. 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. 19608861
  16. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  17. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. 21406692
  18. Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C: Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-alpha-acetylation features. Mol Cell Proteomics. 2012 Jun;11(6):M111.015131. doi: 10.1074/mcp.M111.015131. Epub 2012 Jan 5. 22223895
  19. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  20. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. 25944712
  21. 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. 16176272
  22. 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. 16581025