CLIC3_HUMAN
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 03-AUG-2022, entry version 187.
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; Q8N865: C7orf31; NbExp=3; IntAct=EBI-10192241, EBI-10174456;
CC O95833; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-10192241, EBI-742054;
CC O95833; Q5JST6: EFHC2; NbExp=4; IntAct=EBI-10192241, EBI-2349927;
CC O95833; A8MTA8-2: FAM166B; NbExp=3; IntAct=EBI-10192241, EBI-12160437;
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; Q8NCR6: SMRP1; 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 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};
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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; 71.
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; O95833; -.
DR PeptideAtlas; O95833; -.
DR PRIDE; O95833; -.
DR ProteomicsDB; 51078; -.
DR Antibodypedia; 991; 233 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 CTD; 9022; -.
DR DisGeNET; 9022; -.
DR GeneCards; CLIC3; -.
DR HGNC; HGNC:2064; CLIC3.
DR HPA; ENSG00000169583; Group enriched (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; HYRRFGI; -.
DR OrthoDB; 974249at2759; -.
DR PhylomeDB; O95833; -.
DR TreeFam; TF315438; -.
DR PathwayCommons; O95833; -.
DR SignaLink; O95833; -.
DR BioGRID-ORCS; 9022; 11 hits in 1073 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 tissues.
DR Genevisible; O95833; HS.
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:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0006821; P:chloride transport; IMP:UniProtKB.
DR GO; GO:0006749; P:glutathione metabolic process; IEA:InterPro.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR002946; CLIC.
DR InterPro; IPR030261; CLIC-3.
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; PTHR43920:SF3; PTHR43920:SF3; 1.
DR Pfam; PF13417; GST_N_3; 1.
DR PRINTS; PR01263; INTCLCHANNEL.
DR SFLD; SFLDS00019; Glutathione_Transferase_(cytos; 1.
DR SUPFAM; SSF47616; SSF47616; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS50405; GST_CTER; 1.
DR PROSITE; PS50404; GST_NTER; 1.
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
