ID CLIC3_HUMAN Reviewed; 236 AA. AC O95833; Q5SPZ7; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 13-APR-2004, sequence version 2. DT 27-MAR-2024, entry version 196. DE RecName: Full=Chloride intracellular channel protein 3; GN Name=CLIC3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Urinary bladder; 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 NUCLEOTIDE SEQUENCE [MRNA] OF 5-236, SUBCELLULAR LOCATION, FUNCTION, TISSUE RP SPECIFICITY, AND INTERACTION WITH MAPK15. RC TISSUE=Fetal brain; RX PubMed=9880541; DOI=10.1074/jbc.274.3.1621; RA Qian Z., Okuhara D., Abe M.K., Rosner M.R.; RT "Molecular cloning and characterization of a mitogen-activated protein RT kinase-associated intracellular chloride channel."; RL J. Biol. Chem. 274:1621-1627(1999). RN [5] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=17027078; DOI=10.1016/j.placenta.2006.08.002; RA Money T.T., King R.G., Wong M.H., Stevenson J.L., Kalionis B., RA Erwich J.J.H.M., Huisman M.A., Timmer A., Hiden U., Desoye G., Gude N.M.; RT "Expression and cellular localisation of chloride intracellular channel 3 RT in human placenta and fetal membranes."; RL Placenta 28:429-436(2007). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-49 AND SER-159, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [7] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1-230, AND DISULFIDE BOND. RX PubMed=20146363; DOI=10.1002/prot.22675; RA Littler D.R., Brown L.J., Breit S.N., Perrakis A., Curmi P.M.; RT "Structure of human CLIC3 at 2 A resolution."; RL Proteins 78:1594-1600(2010). CC -!- FUNCTION: Can insert into membranes and form chloride ion channels. May CC participate in cellular growth control. {ECO:0000269|PubMed:9880541}. CC -!- SUBUNIT: Associated with the C-terminal of MAPK15. CC {ECO:0000269|PubMed:9880541}. CC -!- INTERACTION: CC O95833; O95994: AGR2; NbExp=3; IntAct=EBI-10192241, EBI-712648; CC O95833; Q15699: ALX1; NbExp=3; IntAct=EBI-10192241, EBI-750671; CC O95833; Q86SG2: ANKRD23; NbExp=3; IntAct=EBI-10192241, EBI-5661893; CC O95833; Q3KP44: ANKRD55; NbExp=3; IntAct=EBI-10192241, EBI-14493093; CC O95833; A8MTA8-2: CIMIP2B; NbExp=3; IntAct=EBI-10192241, EBI-12160437; CC O95833; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-10192241, EBI-742054; CC O95833; Q5JST6: EFHC2; NbExp=4; IntAct=EBI-10192241, EBI-2349927; CC O95833; Q49A26-4: GLYR1; NbExp=3; IntAct=EBI-10192241, EBI-12143817; CC O95833; Q0VD86: INCA1; NbExp=3; IntAct=EBI-10192241, EBI-6509505; CC O95833; Q9H079: KATNBL1; NbExp=3; IntAct=EBI-10192241, EBI-715394; CC O95833; P78386: KRT85; NbExp=3; IntAct=EBI-10192241, EBI-1049371; CC O95833; Q3SY46: KRTAP13-3; NbExp=5; IntAct=EBI-10192241, EBI-10241252; CC O95833; Q5T871: LELP1; NbExp=3; IntAct=EBI-10192241, EBI-18115868; CC O95833; Q8WWY6: MBD3L1; NbExp=3; IntAct=EBI-10192241, EBI-12516603; CC O95833; Q03112-9: MECOM; NbExp=3; IntAct=EBI-10192241, EBI-23820194; CC O95833; Q5JRA6: MIA3; NbExp=3; IntAct=EBI-10192241, EBI-2291868; CC O95833; P35548: MSX2; NbExp=3; IntAct=EBI-10192241, EBI-6447480; CC O95833; Q9NUX5: POT1; NbExp=2; IntAct=EBI-10192241, EBI-752420; CC O95833; Q86WR7-2: PROSER2; NbExp=5; IntAct=EBI-10192241, EBI-13089670; CC O95833; Q8N228-3: SCML4; NbExp=3; IntAct=EBI-10192241, EBI-17182094; CC O95833; Q8N865: SPMIP4; NbExp=3; IntAct=EBI-10192241, EBI-10174456; CC O95833; Q8NCR6: SPMIP6; NbExp=3; IntAct=EBI-10192241, EBI-10269322; CC O95833; Q9NZ72: STMN3; NbExp=3; IntAct=EBI-10192241, EBI-725557; CC O95833; A6NER0: TBC1D3F; NbExp=3; IntAct=EBI-10192241, EBI-18393978; CC O95833; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-10192241, EBI-11139477; CC O95833; Q08117-2: TLE5; NbExp=3; IntAct=EBI-10192241, EBI-11741437; CC O95833; Q9UN37: VPS4A; NbExp=3; IntAct=EBI-10192241, EBI-1171942; CC O95833; B2RXF5: ZBTB42; NbExp=3; IntAct=EBI-10192241, EBI-12287587; CC O95833; Q53FD0-2: ZC2HC1C; NbExp=3; IntAct=EBI-10192241, EBI-14104088; CC O95833; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-10192241, EBI-4395669; CC -!- SUBCELLULAR LOCATION: Nucleus. Membrane; Single-pass membrane protein. CC Cytoplasm. Note=Predominantly nuclear. Some protein was found in the CC cytoplasm. Exists both as soluble cytoplasmic protein and as membrane CC protein with probably a single transmembrane domain (By similarity). CC {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Detected in placenta (at protein level). Widely CC expressed. High expression is found in placenta followed by lung and CC heart. Low expression in skeletal muscle, kidney and pancreas. CC {ECO:0000269|PubMed:17027078, ECO:0000269|PubMed:9880541}. 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 a 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}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD16450.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AL807752; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471090; EAW88329.1; -; Genomic_DNA. DR EMBL; BC007012; AAH07012.2; -; mRNA. DR EMBL; AF102166; AAD16450.1; ALT_FRAME; mRNA. DR CCDS; CCDS7021.1; -. DR RefSeq; NP_004660.2; NM_004669.2. DR RefSeq; XP_016870771.1; XM_017015282.1. DR PDB; 3FY7; X-ray; 1.95 A; A/B=1-230. DR PDB; 3KJY; X-ray; 1.95 A; A/B=1-230. DR PDBsum; 3FY7; -. DR PDBsum; 3KJY; -. DR AlphaFoldDB; O95833; -. DR SMR; O95833; -. DR BioGRID; 114489; 72. DR IntAct; O95833; 31. DR STRING; 9606.ENSP00000419378; -. DR TCDB; 1.A.12.1.7; the intracellular chloride channel (clic) family. DR iPTMnet; O95833; -. DR PhosphoSitePlus; O95833; -. DR BioMuta; CLIC3; -. DR EPD; O95833; -. DR jPOST; O95833; -. DR MassIVE; O95833; -. DR MaxQB; O95833; -. DR PaxDb; 9606-ENSP00000419378; -. DR PeptideAtlas; O95833; -. DR PRIDE; O95833; -. DR ProteomicsDB; 51078; -. DR Pumba; O95833; -. DR Antibodypedia; 991; 250 antibodies from 31 providers. DR DNASU; 9022; -. DR Ensembl; ENST00000494426.2; ENSP00000419378.1; ENSG00000169583.13. DR GeneID; 9022; -. DR KEGG; hsa:9022; -. DR MANE-Select; ENST00000494426.2; ENSP00000419378.1; NM_004669.3; NP_004660.2. DR UCSC; uc004ckj.2; human. DR AGR; HGNC:2064; -. DR CTD; 9022; -. DR DisGeNET; 9022; -. DR GeneCards; CLIC3; -. DR HGNC; HGNC:2064; CLIC3. DR HPA; ENSG00000169583; Tissue enhanced (esophagus, skin, thyroid gland, vagina). DR MIM; 606533; gene. DR neXtProt; NX_O95833; -. DR OpenTargets; ENSG00000169583; -. DR PharmGKB; PA26590; -. DR VEuPathDB; HostDB:ENSG00000169583; -. DR eggNOG; KOG1422; Eukaryota. DR GeneTree; ENSGT00940000161243; -. DR HOGENOM; CLU_061051_1_0_1; -. DR InParanoid; O95833; -. DR OMA; VQVVCQH; -. DR OrthoDB; 103277at2759; -. DR PhylomeDB; O95833; -. DR TreeFam; TF315438; -. DR PathwayCommons; O95833; -. DR SignaLink; O95833; -. DR BioGRID-ORCS; 9022; 26 hits in 1153 CRISPR screens. DR EvolutionaryTrace; O95833; -. DR GeneWiki; CLIC3; -. DR GenomeRNAi; 9022; -. DR Pharos; O95833; Tbio. DR PRO; PR:O95833; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; O95833; Protein. DR Bgee; ENSG00000169583; Expressed in lower esophagus mucosa and 125 other cell types or tissues. DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005254; F:chloride channel activity; IMP:UniProtKB. DR GO; GO:0006821; P:chloride transport; IMP:UniProtKB. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd10299; GST_C_CLIC3; 1. DR CDD; cd03061; GST_N_CLIC; 1. DR Gene3D; 1.20.1050.10; -; 1. DR Gene3D; 3.40.30.10; Glutaredoxin; 1. DR InterPro; IPR002946; CLIC. DR InterPro; IPR010987; Glutathione-S-Trfase_C-like. DR InterPro; IPR036282; Glutathione-S-Trfase_C_sf. DR InterPro; IPR040079; Glutathione_S-Trfase. DR InterPro; IPR004045; Glutathione_S-Trfase_N. DR InterPro; IPR036249; Thioredoxin-like_sf. DR PANTHER; PTHR45476:SF2; CHLORIDE INTRACELLULAR CHANNEL PROTEIN; 1. DR PANTHER; PTHR45476; CHLORIDE INTRACELLULAR CHANNEL PROTEIN 6-RELATED; 1. DR Pfam; PF13410; GST_C_2; 1. DR Pfam; PF13409; GST_N_2; 1. DR PRINTS; PR01263; INTCLCHANNEL. DR SFLD; SFLDS00019; Glutathione_Transferase_(cytos; 1. DR SUPFAM; SSF47616; GST C-terminal domain-like; 1. DR SUPFAM; SSF52833; Thioredoxin-like; 1. DR PROSITE; PS50405; GST_CTER; 1. DR PROSITE; PS50404; GST_NTER; 1. DR Genevisible; O95833; HS. PE 1: Evidence at protein level; KW 3D-structure; Chloride; Chloride channel; Cytoplasm; Disulfide bond; KW Ion channel; Ion transport; Membrane; Nucleus; Phosphoprotein; KW Reference proteome; Transmembrane; Transmembrane helix; Transport; KW Voltage-gated channel. FT CHAIN 1..236 FT /note="Chloride intracellular channel protein 3" FT /id="PRO_0000144207" FT TRANSMEM 24..44 FT /note="Helical" FT /evidence="ECO:0000255" FT DOMAIN 12..90 FT /note="GST N-terminal" FT DOMAIN 91..235 FT /note="GST C-terminal" FT REGION 1..88 FT /note="Required for insertion into the membrane" FT /evidence="ECO:0000250" FT MOD_RES 49 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 159 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT DISULFID 22..25 FT /note="In soluble form" FT /evidence="ECO:0000269|PubMed:20146363" FT VARIANT 38 FT /note="P -> H (in dbSNP:rs2292923)" FT /id="VAR_020424" FT STRAND 6..12 FT /evidence="ECO:0007829|PDB:3FY7" FT STRAND 16..19 FT /evidence="ECO:0007829|PDB:3FY7" FT HELIX 23..35 FT /evidence="ECO:0007829|PDB:3FY7" FT STRAND 40..44 FT /evidence="ECO:0007829|PDB:3FY7" FT STRAND 64..67 FT /evidence="ECO:0007829|PDB:3FY7" FT STRAND 70..72 FT /evidence="ECO:0007829|PDB:3FY7" FT HELIX 75..85 FT /evidence="ECO:0007829|PDB:3FY7" FT TURN 88..90 FT /evidence="ECO:0007829|PDB:3FY7" FT HELIX 99..103 FT /evidence="ECO:0007829|PDB:3FY7" FT TURN 104..107 FT /evidence="ECO:0007829|PDB:3FY7" FT HELIX 108..117 FT /evidence="ECO:0007829|PDB:3FY7" FT HELIX 121..123 FT /evidence="ECO:0007829|PDB:3FY7" FT HELIX 124..143 FT /evidence="ECO:0007829|PDB:3FY7" FT HELIX 147..152 FT /evidence="ECO:0007829|PDB:3FY7" FT STRAND 162..168 FT /evidence="ECO:0007829|PDB:3FY7" FT HELIX 171..191 FT /evidence="ECO:0007829|PDB:3FY7" FT HELIX 200..210 FT /evidence="ECO:0007829|PDB:3FY7" FT HELIX 213..216 FT /evidence="ECO:0007829|PDB:3FY7" FT HELIX 222..229 FT /evidence="ECO:0007829|PDB:3FY7" SQ SEQUENCE 236 AA; 26648 MW; CA20E66195950886 CRC64; MAETKLQLFV KASEDGESVG HCPSCQRLFM VLLLKGVPFT LTTVDTRRSP DVLKDFAPGS QLPILLYDSD AKTDTLQIED FLEETLGPPD FPSLAPRYRE SNTAGNDVFH KFSAFIKNPV PAQDEALYQQ LLRALARLDS YLRAPLEHEL AGEPQLRESR RRFLDGDRLT LADCSLLPKL HIVDTVCAHF RQAPIPAELR GVRRYLDSAM QEKEFKYTCP HSAEILAAYR PAVHPR //