CPLM-023975

Genbank Nucleotide ID

Chloride intracellular channel protein 4

Protein Synonyms/Alias

Intracellular chloride ion channel protein p64H1

Homo sapiens (Human)

Position	Peptide	Type	References
11	SMPLNGLKEEDKEPL	ubiquitination	[1]
15	NGLKEEDKEPLIELF	ubiquitination	[1]
62	TTVDLKRKPADLQNL	ubiquitination	[2]
103	EEVLCPPKYLKLSPK	acetylation	[3]
130	AKFSAYIKNSRPEAN	acetylation	[4, 5, 6, 7]
130	AKFSAYIKNSRPEAN	ubiquitination	[1, 2]
146	ALERGLLKTLQKLDE	ubiquitination	[2]
150	GLLKTLQKLDEYLNS	acetylation	[6]
194	ADCNLLPKLHIVKVV	ubiquitination	[1, 2]
199	LPKLHIVKVVAKKYR	ubiquitination	[1, 7, 8, 9, 10]
212	YRNFDIPKEMTGIWR	ubiquitination	[1, 2]
249	IAYSDVAKRLTK***	acetylation	[6]

[1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[3] Monoclonal antibody cocktail as an enrichment tool for acetylome analysis.
Shaw PG, Chaerkady R, Zhang Z, Davidson NE, Pandey A.
Anal Chem. 2011 May 15;83(10):3623-6. [PMID: 21466224]
[4] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
[5] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
[6] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
PLoS One. 2012;7(12):e50545. [PMID: 23236377]
[7] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
[8] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
[9] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[10] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]

Functional Description

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).

DOMAIN 104 244 GST C-terminal.
REGION 2 101 Required for insertion into the membrane
MOD_RES 2 2 N-acetylalanine.
MOD_RES 4 4 Phosphoserine.
MOD_RES 130 130 N6-acetyllysine.

3D-structure; Acetylation; Cell junction; Cell membrane; Chloride; Chloride channel; Complete proteome; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Direct protein sequencing; Ion channel; Ion transport; Membrane; Mitochondrion; Nucleus; Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0015629; C:actin cytoskeleton; TAS:UniProtKB.
GO:0045177; C:apical part of cell; IDA:UniProtKB.
GO:0009986; C:cell surface; IDA:UniProtKB.
GO:0005911; C:cell-cell junction; IDA:UniProtKB.
GO:0005813; C:centrosome; IDA:UniProtKB.
GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
GO:0005829; C:cytosol; IDA:UniProtKB.
GO:0005902; C:microvillus; IDA:UniProtKB.
GO:0030496; C:midbody; IDA:UniProtKB.
GO:0005739; C:mitochondrion; IDA:UniProtKB.
GO:0016363; C:nuclear matrix; IDA:UniProtKB.
GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
GO:0005886; C:plasma membrane; IDA:UniProtKB.
GO:0005773; C:vacuole; IEA:Compara.
GO:0005254; F:chloride channel activity; TAS:ProtInc.
GO:0005247; F:voltage-gated chloride channel activity; IEA:InterPro.
GO:0001525; P:angiogenesis; IEA:Compara.
GO:0048754; P:branching morphogenesis of an epithelial tube; IEA:Compara.
GO:0071277; P:cellular response to calcium ion; IMP:UniProtKB.
GO:0001886; P:endothelial cell morphogenesis; IEA:Compara.
GO:0035088; P:establishment or maintenance of apical/basal cell polarity; NAS:UniProtKB.
GO:0009566; P:fertilization; IEA:Compara.
GO:0030216; P:keratinocyte differentiation; IMP:UniProtKB.
GO:0035264; P:multicellular organism growth; IEA:Compara.
GO:0030336; P:negative regulation of cell migration; IDA:UniProtKB.
GO:0051493; P:regulation of cytoskeleton organization; NAS:UniProtKB.
GO:0061299; P:retina vasculature morphogenesis in camera-type eye; IEA:Compara.
GO:0007035; P:vacuolar acidification; IEA:Compara.

IPR010987; Glutathione-S-Trfase_C-like.
IPR017933; Glutathione_S_Trfase/Cl_chnl_C.
IPR002946; Int_Cl_channel.
IPR012336; Thioredoxin-like_fold.

PR01263; INTCLCHANNEL.