CLIC4_MOUSE
ID CLIC4_MOUSE Reviewed; 253 AA.
AC Q9QYB1; Q8BMG5;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Chloride intracellular channel protein 4;
DE Short=mc3s5/mtCLIC;
GN Name=Clic4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10593946; DOI=10.1074/jbc.274.51.36488;
RA Fernandez-Salas E., Sagar M., Cheng C., Yuspa S.H., Weinberg W.C.;
RT "p53 and tumor necrosis factor alpha regulate the expression of a
RT mitochondrial chloride channel protein.";
RL J. Biol. Chem. 274:36488-36497(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Forelimb;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C3H/He; TISSUE=Mammary gland, and Osteoblast;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY, INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17636002; DOI=10.1242/jcs.002741;
RA Suh K.S., Mutoh M., Mutoh T., Li L., Ryscavage A., Crutchley J.M.,
RA Dumont R.A., Cheng C., Yuspa S.H.;
RT "CLIC4 mediates and is required for Ca2+-induced keratinocyte
RT differentiation.";
RL J. Cell Sci. 120:2631-2640(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-236, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19197003; DOI=10.2353/ajpath.2009.080625;
RA Ulmasov B., Bruno J., Gordon N., Hartnett M.E., Edwards J.C.;
RT "Chloride intracellular channel protein-4 functions in angiogenesis by
RT supporting acidification of vacuoles along the intracellular tubulogenic
RT pathway.";
RL Am. J. Pathol. 174:1084-1096(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Can insert into membranes and form poorly selective ion
CC channels that may also transport chloride ions. Channel activity
CC depends on the pH. Membrane insertion seems to be redox-regulated and
CC may occur only under oxydizing conditions. Promotes cell-surface
CC expression of HRH3 (By similarity). May play a role in angiogenesis.
CC {ECO:0000250, ECO:0000269|PubMed:19197003}.
CC -!- SUBUNIT: Monomer. Interacts with HRH30. Interacts with AKAP9 (By
CC similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9QYB1; P70181: Pip5k1b; NbExp=4; IntAct=EBI-645175, EBI-645167;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasmic vesicle
CC membrane {ECO:0000250}; Single-pass membrane protein {ECO:0000250}.
CC Nucleus {ECO:0000250}. Cell membrane {ECO:0000250}; Single-pass
CC membrane protein {ECO:0000250}. Mitochondrion
CC {ECO:0000269|PubMed:10593946, ECO:0000269|PubMed:17636002}. Note=Exists
CC both as soluble cytoplasmic protein and as membrane protein with
CC probably a single transmembrane domain. Present in an intracellular
CC vesicular compartment that likely represent trans-Golgi network
CC vesicles (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in blood vessels in the retina (at protein
CC level). Expressed to the greatest extent in vivo in heart, lung, liver,
CC kidney, and skin. {ECO:0000269|PubMed:10593946,
CC ECO:0000269|PubMed:17636002, ECO:0000269|PubMed:19197003}.
CC -!- INDUCTION: Up-regulated by calcium ions in differentiating
CC keratinocytes. {ECO:0000269|PubMed:17636002}.
CC -!- DOMAIN: Members of this family may change from a globular, soluble
CC state to a state where the N-terminal domain is inserted into the
CC membrane and functions as chloride channel. A conformation change of
CC the N-terminal domain is thought to expose hydrophobic surfaces that
CC trigger membrane insertion (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the chloride channel CLIC family. {ECO:0000305}.
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DR EMBL; AF102578; AAF19055.1; -; mRNA.
DR EMBL; AK031211; BAC27301.1; -; mRNA.
DR EMBL; BC046384; AAH46384.1; -; mRNA.
DR EMBL; BC052890; AAH52890.1; -; mRNA.
DR CCDS; CCDS18783.1; -.
DR RefSeq; NP_038913.1; NM_013885.2.
DR AlphaFoldDB; Q9QYB1; -.
DR SMR; Q9QYB1; -.
DR BioGRID; 205939; 5.
DR IntAct; Q9QYB1; 1.
DR STRING; 10090.ENSMUSP00000041453; -.
DR iPTMnet; Q9QYB1; -.
DR PhosphoSitePlus; Q9QYB1; -.
DR SwissPalm; Q9QYB1; -.
DR UCD-2DPAGE; Q9QYB1; -.
DR EPD; Q9QYB1; -.
DR jPOST; Q9QYB1; -.
DR MaxQB; Q9QYB1; -.
DR PaxDb; Q9QYB1; -.
DR PRIDE; Q9QYB1; -.
DR ProteomicsDB; 283301; -.
DR Antibodypedia; 1956; 367 antibodies from 41 providers.
DR DNASU; 29876; -.
DR Ensembl; ENSMUST00000037099; ENSMUSP00000041453; ENSMUSG00000037242.
DR GeneID; 29876; -.
DR KEGG; mmu:29876; -.
DR UCSC; uc008vgd.1; mouse.
DR CTD; 25932; -.
DR MGI; MGI:1352754; Clic4.
DR VEuPathDB; HostDB:ENSMUSG00000037242; -.
DR eggNOG; KOG1422; Eukaryota.
DR GeneTree; ENSGT00940000155017; -.
DR HOGENOM; CLU_061051_1_0_1; -.
DR InParanoid; Q9QYB1; -.
DR OMA; CHQIFMI; -.
DR OrthoDB; 974249at2759; -.
DR PhylomeDB; Q9QYB1; -.
DR TreeFam; TF315438; -.
DR BioGRID-ORCS; 29876; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Clic4; mouse.
DR PRO; PR:Q9QYB1; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9QYB1; protein.
DR Bgee; ENSMUSG00000037242; Expressed in gastrula and 266 other tissues.
DR ExpressionAtlas; Q9QYB1; baseline and differential.
DR Genevisible; Q9QYB1; MM.
DR GO; GO:0045177; C:apical part of cell; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005911; C:cell-cell junction; ISO:MGI.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0005902; C:microvillus; ISO:MGI.
DR GO; GO:0030496; C:midbody; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0016363; C:nuclear matrix; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005254; F:chloride channel activity; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:MGI.
DR GO; GO:0071277; P:cellular response to calcium ion; ISO:MGI.
DR GO; GO:0006821; P:chloride transport; ISO:MGI.
DR GO; GO:0001886; P:endothelial cell morphogenesis; IMP:MGI.
DR GO; GO:0009566; P:fertilization; IMP:MGI.
DR GO; GO:0030216; P:keratinocyte differentiation; IMP:UniProtKB.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0061299; P:retina vasculature morphogenesis in camera-type eye; IMP:MGI.
DR GO; GO:0007035; P:vacuolar acidification; IMP:MGI.
DR InterPro; IPR002946; CLIC.
DR InterPro; IPR030257; CLIC-4/6.
DR InterPro; IPR010987; Glutathione-S-Trfase_C-like.
DR InterPro; IPR036282; Glutathione-S-Trfase_C_sf.
DR InterPro; IPR040079; Glutathione_S-Trfase.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR PANTHER; PTHR45476:SF1; PTHR45476:SF1; 1.
DR PRINTS; PR01263; INTCLCHANNEL.
DR SFLD; SFLDS00019; Glutathione_Transferase_(cytos; 1.
DR SUPFAM; SSF47616; SSF47616; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR TIGRFAMs; TIGR00862; O-ClC; 1.
DR PROSITE; PS50405; GST_CTER; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell membrane; Chloride; Chloride channel; Cytoplasm;
KW Cytoplasmic vesicle; Ion channel; Ion transport; Membrane; Mitochondrion;
KW Nucleus; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9Y696"
FT CHAIN 2..253
FT /note="Chloride intracellular channel protein 4"
FT /id="PRO_0000144211"
FT TRANSMEM 37..57
FT /note="Helical; Note=After insertion into the membrane"
FT /evidence="ECO:0000255"
FT DOMAIN 104..244
FT /note="GST C-terminal"
FT REGION 2..101
FT /note="Required for insertion into the membrane"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y696"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y696"
FT MOD_RES 24
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O00299"
FT MOD_RES 130
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y696"
FT MOD_RES 132
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00299"
FT MOD_RES 167
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00299"
FT MOD_RES 236
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 244
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1Q5"
FT CONFLICT 180
FT /note="D -> Y (in Ref. 2; BAC27301)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 253 AA; 28729 MW; 809568B37B441BB4 CRC64;
MALSMPLNGL KEEDKEPLIE LFVKAGSDGE SIGNCPFSQR LFMILWLKGV VFSVTTVDLK
RKPADLQNLA PGTHPPFITF NSEVKTDVNK IEEFLEEVLC PPKYLKLSPK HPESNTAGMD
IFAKFSAYIK NSRPEANEAL ERGLLKTLQK LDEYLNSPLP DEIDENSMED IKFSTRRFLD
GDEMTLADCN LLPKLHIVKV VAKKYRNFDI PKGMTGIWRY LTNAYSRDEF TNTCPSDKEV
EIAYSDVAKR LTK
