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Protein

Chloride intracellular channel protein 6

Gene

CLIC6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

May insert into membranes and form chloride ion channels. May play a critical role in water-secreting cells, possibly through the regulation of chloride ion transport (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chloride channel, Ion channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Transport

Keywords - Ligandi

Chloride

Protein family/group databases

TCDBi1.A.12.1.4. the intracellular chloride channel (clic) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Chloride intracellular channel protein 6
Alternative name(s):
Parchorin
Gene namesi
Name:CLIC6
Synonyms:CLIC1L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:2065. CLIC6.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei489 – 50921Helical; Note=After insertion into the membraneSequence analysisAdd
BLAST

GO - Cellular componenti

  • chloride channel complex Source: UniProtKB-KW
  • cytoplasm Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA26593.

Polymorphism and mutation databases

BioMutaiCLIC6.
DMDMi38372885.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 704704Chloride intracellular channel protein 6PRO_0000144217Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei44 – 441PhosphoserineBy similarity
Modified residuei397 – 3971PhosphoserineBy similarity
Modified residuei442 – 4421PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96NY7.
MaxQBiQ96NY7.
PaxDbiQ96NY7.
PRIDEiQ96NY7.

PTM databases

PhosphoSiteiQ96NY7.

Expressioni

Tissue specificityi

Expressed in brain, placenta, pancreas and liver.1 Publication

Gene expression databases

BgeeiQ96NY7.
CleanExiHS_CLIC6.
GenevisibleiQ96NY7. HS.

Organism-specific databases

HPAiHPA055123.
HPA065285.

Interactioni

Subunit structurei

Interacts with dopamine receptors DRD2, DRD3 and DRD4.By similarity

Protein-protein interaction databases

BioGridi119900. 4 interactions.
STRINGi9606.ENSP00000290332.

Structurei

3D structure databases

ProteinModelPortaliQ96NY7.
SMRiQ96NY7. Positions 471-703.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati157 – 166101
Repeati167 – 176102
Repeati177 – 186103
Repeati187 – 196104
Repeati197 – 206105
Repeati207 – 216106
Repeati217 – 226107
Repeati227 – 236108
Repeati237 – 246109
Repeati247 – 2561010
Repeati257 – 2661011
Repeati267 – 2761012
Repeati277 – 2861013
Domaini556 – 704149GST C-terminalAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni157 – 28212613 X 10 AA tandem repeat of G-D-[SNG]-[VIM]-[DEQ]-A-[EAG]-[GDVE]-[PRG]-[LAVP]Add
BLAST

Domaini

Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion (By similarity).By similarity

Sequence similaritiesi

Belongs to the chloride channel CLIC family.Curated
Contains 1 GST C-terminal domain.Curated

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1422. Eukaryota.
ENOG410ZRK6. LUCA.
GeneTreeiENSGT00550000074477.
HOGENOMiHOG000013008.
HOVERGENiHBG050996.
InParanoidiQ96NY7.
KOiK05026.
OMAiCSRIAIK.
OrthoDBiEOG7X3QR3.
PhylomeDBiQ96NY7.
TreeFamiTF315438.

Family and domain databases

Gene3Di1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProiIPR002946. CLIC.
IPR030263. CLIC-6.
IPR010987. Glutathione-S-Trfase_C-like.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11260:SF142. PTHR11260:SF142. 3 hits.
PRINTSiPR01263. INTCLCHANNEL.
SUPFAMiSSF47616. SSF47616. 1 hit.
SSF52833. SSF52833. 1 hit.
TIGRFAMsiTIGR00862. O-ClC. 1 hit.
PROSITEiPS50405. GST_CTER. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform B (identifier: Q96NY7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAEAAEPEGV APGPQGPPEV PAPLAERPGE PGAAGGEAEG PEGSEGAEEA
60 70 80 90 100
PRGAAAVKEA GGGGPDRGPE AEARGTRGAH GETEAEEGAP EGAEVPQGGE
110 120 130 140 150
ETSGAQQVEG ASPGRGAQGE PRGEAQREPE DSAAPERQEE AEQRPEVPEG
160 170 180 190 200
SASGEAGDSV DAEGPLGDNI EAEGPAGDSV EAEGRVGDSV DAEGPAGDSV
210 220 230 240 250
DAEGPLGDNI QAEGPAGDSV DAEGRVGDSV DAEGPAGDSV DAEGRVGDSV
260 270 280 290 300
EAGDPAGDGV EAGVPAGDSV EAEGPAGDSM DAEGPAGRAR RVSGEPQQSG
310 320 330 340 350
DGSLSPQAEA IEVAAGESAG RSPGELAWDA AEEAEVPGVK GSEEAAPGDA
360 370 380 390 400
RADAGEDRVG DGPQQEPGED EERRERSPEG PREEEAAGGE EESPDSSPHG
410 420 430 440 450
EASRGAAEPE AQLSNHLAEE GPAEGSGEAA RVNGRREDGE ASEPRALGQE
460 470 480 490 500
HDITLFVKVK LTALGCSRIA IKKYLRAGYD GESIGNCPFS QRLFMILWLK
510 520 530 540 550
GVIFNVTTVD LKRKPADLQN LAPGTNPPFM TFDGEVKTDV NKIEEFLEEK
560 570 580 590 600
LAPPRYPKLG TQHPESNSAG NDVFAKFSAF IKNTKKDANE IHEKNLLKAL
610 620 630 640 650
RKLDNYLNSP LPDEIDAYST EDVTVSGRKF LDGDELTLAD CNLLPKLHII
660 670 680 690 700
KIVAKKYRDF EFPSEMTGIW RYLNNAYARD EFTNTCPADQ EIEHAYSDVA

KRMK
Length:704
Mass (Da):73,012
Last modified:November 14, 2003 - v3
Checksum:iA58F30E099BFE357
GO
Isoform A (identifier: Q96NY7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     459-476: Missing.

Show »
Length:686
Mass (Da):70,996
Checksum:iCA7F2571EB91490D
GO

Sequence cautioni

The sequence BAC03959.1 differs from that shown. Reason: Erroneous initiation. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti632 – 6321D → G.
Corresponds to variant rs3171439 [ dbSNP | Ensembl ].
VAR_014139

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei459 – 47618Missing in isoform A. 4 PublicationsVSP_008963Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF448439 mRNA. Translation: AAN76730.1.
AF448438 mRNA. Translation: AAN76729.1.
AF426169 mRNA. Translation: AAL24813.1.
AK092733 mRNA. Translation: BAC03959.1. Different initiation.
AK289663 mRNA. Translation: BAF82352.1.
AP001720 Genomic DNA. No translation available.
CH471079 Genomic DNA. Translation: EAX09775.1.
BC040196 mRNA. Translation: AAH40196.1.
CCDSiCCDS13638.1. [Q96NY7-2]
RefSeqiNP_001303938.1. NM_001317009.1. [Q96NY7-1]
NP_444507.1. NM_053277.2. [Q96NY7-2]
UniGeneiHs.473695.

Genome annotation databases

EnsembliENST00000349499; ENSP00000290332; ENSG00000159212. [Q96NY7-2]
ENST00000360731; ENSP00000353959; ENSG00000159212. [Q96NY7-1]
GeneIDi54102.
KEGGihsa:54102.
UCSCiuc002yuf.2. human. [Q96NY7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF448439 mRNA. Translation: AAN76730.1.
AF448438 mRNA. Translation: AAN76729.1.
AF426169 mRNA. Translation: AAL24813.1.
AK092733 mRNA. Translation: BAC03959.1. Different initiation.
AK289663 mRNA. Translation: BAF82352.1.
AP001720 Genomic DNA. No translation available.
CH471079 Genomic DNA. Translation: EAX09775.1.
BC040196 mRNA. Translation: AAH40196.1.
CCDSiCCDS13638.1. [Q96NY7-2]
RefSeqiNP_001303938.1. NM_001317009.1. [Q96NY7-1]
NP_444507.1. NM_053277.2. [Q96NY7-2]
UniGeneiHs.473695.

3D structure databases

ProteinModelPortaliQ96NY7.
SMRiQ96NY7. Positions 471-703.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119900. 4 interactions.
STRINGi9606.ENSP00000290332.

Protein family/group databases

TCDBi1.A.12.1.4. the intracellular chloride channel (clic) family.

PTM databases

PhosphoSiteiQ96NY7.

Polymorphism and mutation databases

BioMutaiCLIC6.
DMDMi38372885.

Proteomic databases

EPDiQ96NY7.
MaxQBiQ96NY7.
PaxDbiQ96NY7.
PRIDEiQ96NY7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000349499; ENSP00000290332; ENSG00000159212. [Q96NY7-2]
ENST00000360731; ENSP00000353959; ENSG00000159212. [Q96NY7-1]
GeneIDi54102.
KEGGihsa:54102.
UCSCiuc002yuf.2. human. [Q96NY7-1]

Organism-specific databases

CTDi54102.
GeneCardsiCLIC6.
H-InvDBHIX0016092.
HGNCiHGNC:2065. CLIC6.
HPAiHPA055123.
HPA065285.
MIMi615321. gene.
neXtProtiNX_Q96NY7.
PharmGKBiPA26593.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1422. Eukaryota.
ENOG410ZRK6. LUCA.
GeneTreeiENSGT00550000074477.
HOGENOMiHOG000013008.
HOVERGENiHBG050996.
InParanoidiQ96NY7.
KOiK05026.
OMAiCSRIAIK.
OrthoDBiEOG7X3QR3.
PhylomeDBiQ96NY7.
TreeFamiTF315438.

Miscellaneous databases

ChiTaRSiCLIC6. human.
GeneWikiiCLIC6.
GenomeRNAii54102.
NextBioi56458.
PROiQ96NY7.
SOURCEiSearch...

Gene expression databases

BgeeiQ96NY7.
CleanExiHS_CLIC6.
GenevisibleiQ96NY7. HS.

Family and domain databases

Gene3Di1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProiIPR002946. CLIC.
IPR030263. CLIC-6.
IPR010987. Glutathione-S-Trfase_C-like.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11260:SF142. PTHR11260:SF142. 3 hits.
PRINTSiPR01263. INTCLCHANNEL.
SUPFAMiSSF47616. SSF47616. 1 hit.
SSF52833. SSF52833. 1 hit.
TIGRFAMsiTIGR00862. O-ClC. 1 hit.
PROSITEiPS50405. GST_CTER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of a novel member of the CLIC family, CLIC6, mapping to 21q22.12."
    Friedli M., Guipponi M., Bertrand S., Bertrand D., Neerman-Arbez M., Scott H.S., Antonarakis S.E., Reymond A.
    Gene 320:31-40(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), ALTERNATIVE SPLICING.
  2. "Segmental paralogy in the human genome: a large-scale triplication on 1p, 6p, and 21q."
    Strippoli P., D'Addabbo P., Lenzi L., Giannone S., Canaider S., Casadei R., Vitale L., Carinci P., Zannotti M.
    Mamm. Genome 13:456-462(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), TISSUE SPECIFICITY.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
    Tissue: Amygdala and Small intestine.
  4. "The DNA sequence of human chromosome 21."
    Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A.
    , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.
    Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 279-704 (ISOFORM A).
    Tissue: Brain.

Entry informationi

Entry nameiCLIC6_HUMAN
AccessioniPrimary (citable) accession number: Q96NY7
Secondary accession number(s): A8K0U8, Q8IX31
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 19, 2002
Last sequence update: November 14, 2003
Last modified: May 11, 2016
This is version 140 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.