CLIC6_HUMAN
ID CLIC6_HUMAN Reviewed; 704 AA.
AC Q96NY7; A8K0U8; Q8IX31;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2003, sequence version 3.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Chloride intracellular channel protein 6;
DE AltName: Full=Parchorin;
GN Name=CLIC6; Synonyms=CLIC1L;
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 [MRNA] (ISOFORMS A AND B), AND ALTERNATIVE SPLICING.
RX PubMed=14597386; DOI=10.1016/s0378-1119(03)00830-8;
RA Friedli M., Guipponi M., Bertrand S., Bertrand D., Neerman-Arbez M.,
RA Scott H.S., Antonarakis S.E., Reymond A.;
RT "Identification of a novel member of the CLIC family, CLIC6, mapping to
RT 21q22.12.";
RL Gene 320:31-40(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), AND TISSUE SPECIFICITY.
RX PubMed=12226712; DOI=10.1007/s00335-001-2157-0;
RA Strippoli P., D'Addabbo P., Lenzi L., Giannone S., Canaider S., Casadei R.,
RA Vitale L., Carinci P., Zannotti M.;
RT "Segmental paralogy in the human genome: a large-scale triplication on 1p,
RT 6p, and 21q.";
RL Mamm. Genome 13:456-462(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC TISSUE=Amygdala, and Small intestine;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 279-704 (ISOFORM A).
RC TISSUE=Brain;
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).
CC -!- FUNCTION: May insert into membranes and form chloride ion channels. May
CC play a critical role in water-secreting cells, possibly through the
CC regulation of chloride ion transport (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with dopamine receptors DRD2, DRD3 and DRD4.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Single-pass membrane protein {ECO:0000250}.
CC Note=Predominantly cytoplasmic. Upon chloride ion efflux from the cell,
CC it is translocated to the plasma membrane (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B;
CC IsoId=Q96NY7-1; Sequence=Displayed;
CC Name=A;
CC IsoId=Q96NY7-2; Sequence=VSP_008963;
CC -!- TISSUE SPECIFICITY: Expressed in brain, placenta, pancreas and liver.
CC {ECO:0000269|PubMed:12226712}.
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 -!- PTM: Phosphorylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the chloride channel CLIC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC03959.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF448439; AAN76730.1; -; mRNA.
DR EMBL; AF448438; AAN76729.1; -; mRNA.
DR EMBL; AF426169; AAL24813.1; -; mRNA.
DR EMBL; AK092733; BAC03959.1; ALT_INIT; mRNA.
DR EMBL; AK289663; BAF82352.1; -; mRNA.
DR EMBL; AP001720; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471079; EAX09775.1; -; Genomic_DNA.
DR EMBL; BC040196; AAH40196.1; -; mRNA.
DR CCDS; CCDS13638.1; -. [Q96NY7-2]
DR CCDS; CCDS82669.1; -. [Q96NY7-1]
DR RefSeq; NP_001303938.1; NM_001317009.1. [Q96NY7-1]
DR RefSeq; NP_444507.1; NM_053277.2. [Q96NY7-2]
DR AlphaFoldDB; Q96NY7; -.
DR SMR; Q96NY7; -.
DR BioGRID; 119900; 5.
DR IntAct; Q96NY7; 1.
DR STRING; 9606.ENSP00000290332; -.
DR TCDB; 1.A.12.1.4; the intracellular chloride channel (clic) family.
DR iPTMnet; Q96NY7; -.
DR PhosphoSitePlus; Q96NY7; -.
DR BioMuta; CLIC6; -.
DR DMDM; 38372885; -.
DR EPD; Q96NY7; -.
DR jPOST; Q96NY7; -.
DR MassIVE; Q96NY7; -.
DR MaxQB; Q96NY7; -.
DR PaxDb; Q96NY7; -.
DR PeptideAtlas; Q96NY7; -.
DR PRIDE; Q96NY7; -.
DR ProteomicsDB; 77576; -. [Q96NY7-1]
DR ProteomicsDB; 77577; -. [Q96NY7-2]
DR Antibodypedia; 8114; 197 antibodies from 26 providers.
DR DNASU; 54102; -.
DR Ensembl; ENST00000349499.3; ENSP00000290332.4; ENSG00000159212.13. [Q96NY7-2]
DR Ensembl; ENST00000360731.7; ENSP00000353959.3; ENSG00000159212.13. [Q96NY7-1]
DR GeneID; 54102; -.
DR KEGG; hsa:54102; -.
DR MANE-Select; ENST00000349499.3; ENSP00000290332.4; NM_053277.3; NP_444507.1. [Q96NY7-2]
DR UCSC; uc002yuf.2; human. [Q96NY7-1]
DR CTD; 54102; -.
DR DisGeNET; 54102; -.
DR GeneCards; CLIC6; -.
DR HGNC; HGNC:2065; CLIC6.
DR HPA; ENSG00000159212; Group enriched (choroid plexus, stomach).
DR MIM; 615321; gene.
DR neXtProt; NX_Q96NY7; -.
DR OpenTargets; ENSG00000159212; -.
DR PharmGKB; PA26593; -.
DR VEuPathDB; HostDB:ENSG00000159212; -.
DR eggNOG; KOG1422; Eukaryota.
DR GeneTree; ENSGT00940000159602; -.
DR HOGENOM; CLU_023994_0_0_1; -.
DR InParanoid; Q96NY7; -.
DR OMA; QGASMEA; -.
DR OrthoDB; 974249at2759; -.
DR PhylomeDB; Q96NY7; -.
DR TreeFam; TF315438; -.
DR PathwayCommons; Q96NY7; -.
DR SignaLink; Q96NY7; -.
DR BioGRID-ORCS; 54102; 10 hits in 1067 CRISPR screens.
DR ChiTaRS; CLIC6; human.
DR GeneWiki; CLIC6; -.
DR GenomeRNAi; 54102; -.
DR Pharos; Q96NY7; Tbio.
DR PRO; PR:Q96NY7; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; Q96NY7; protein.
DR Bgee; ENSG00000159212; Expressed in pigmented layer of retina and 132 other tissues.
DR Genevisible; Q96NY7; HS.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005254; F:chloride channel activity; IEA:UniProtKB-KW.
DR GO; GO:0031749; F:D2 dopamine receptor binding; IBA:GO_Central.
DR GO; GO:0031750; F:D3 dopamine receptor binding; IBA:GO_Central.
DR GO; GO:0031751; F:D4 dopamine receptor binding; IBA:GO_Central.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
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; 2.
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 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Chloride; Chloride channel; Cytoplasm;
KW Ion channel; Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT CHAIN 1..704
FT /note="Chloride intracellular channel protein 6"
FT /id="PRO_0000144217"
FT TRANSMEM 489..509
FT /note="Helical; Note=After insertion into the membrane"
FT /evidence="ECO:0000255"
FT REPEAT 157..166
FT /note="1"
FT REPEAT 167..176
FT /note="2"
FT REPEAT 177..186
FT /note="3"
FT REPEAT 187..196
FT /note="4"
FT REPEAT 197..206
FT /note="5"
FT REPEAT 207..216
FT /note="6"
FT REPEAT 217..226
FT /note="7"
FT REPEAT 227..236
FT /note="8"
FT REPEAT 237..246
FT /note="9"
FT REPEAT 247..256
FT /note="10"
FT REPEAT 257..266
FT /note="11"
FT REPEAT 267..276
FT /note="12"
FT REPEAT 277..286
FT /note="13"
FT DOMAIN 556..704
FT /note="GST C-terminal"
FT REGION 1..446
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 157..282
FT /note="13 X 10 AA tandem repeat of G-D-[SNG]-[VIM]-[DEQ]-A-
FT [EAG]-[GDVE]-[PRG]-[LAVP]"
FT COMPBIAS 11..25
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 70..87
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 121..146
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 346..384
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 430..446
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q811Q2"
FT MOD_RES 397
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q811Q2"
FT MOD_RES 442
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q811Q2"
FT VAR_SEQ 459..476
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000303|PubMed:12226712,
FT ECO:0000303|PubMed:14597386, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_008963"
FT VARIANT 632
FT /note="D -> G (in dbSNP:rs3171439)"
FT /id="VAR_014139"
SQ SEQUENCE 704 AA; 73012 MW; A58F30E099BFE357 CRC64;
MAEAAEPEGV APGPQGPPEV PAPLAERPGE PGAAGGEAEG PEGSEGAEEA PRGAAAVKEA
GGGGPDRGPE AEARGTRGAH GETEAEEGAP EGAEVPQGGE ETSGAQQVEG ASPGRGAQGE
PRGEAQREPE DSAAPERQEE AEQRPEVPEG SASGEAGDSV DAEGPLGDNI EAEGPAGDSV
EAEGRVGDSV DAEGPAGDSV DAEGPLGDNI QAEGPAGDSV DAEGRVGDSV DAEGPAGDSV
DAEGRVGDSV EAGDPAGDGV EAGVPAGDSV EAEGPAGDSM DAEGPAGRAR RVSGEPQQSG
DGSLSPQAEA IEVAAGESAG RSPGELAWDA AEEAEVPGVK GSEEAAPGDA RADAGEDRVG
DGPQQEPGED EERRERSPEG PREEEAAGGE EESPDSSPHG EASRGAAEPE AQLSNHLAEE
GPAEGSGEAA RVNGRREDGE ASEPRALGQE HDITLFVKVK LTALGCSRIA IKKYLRAGYD
GESIGNCPFS QRLFMILWLK GVIFNVTTVD LKRKPADLQN LAPGTNPPFM TFDGEVKTDV
NKIEEFLEEK LAPPRYPKLG TQHPESNSAG NDVFAKFSAF IKNTKKDANE IHEKNLLKAL
RKLDNYLNSP LPDEIDAYST EDVTVSGRKF LDGDELTLAD CNLLPKLHII KIVAKKYRDF
EFPSEMTGIW RYLNNAYARD EFTNTCPADQ EIEHAYSDVA KRMK
