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Protein

Chloride intracellular channel protein 4

Gene

Clic4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Can insert into membranes and form poorly selective ion channels that may also transport chloride ions. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Promotes cell-surface expression of HRH3 (By similarity). May play a role in angiogenesis.By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

  • angiogenesis Source: MGI
  • apoptotic process Source: InterPro
  • branching morphogenesis of an epithelial tube Source: MGI
  • cellular response to calcium ion Source: MGI
  • chloride transport Source: MGI
  • endothelial cell morphogenesis Source: MGI
  • fertilization Source: MGI
  • keratinocyte differentiation Source: UniProtKB
  • multicellular organism growth Source: MGI
  • negative regulation of cell migration Source: UniProtKB
  • retina vasculature morphogenesis in camera-type eye Source: MGI
  • vacuolar acidification Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Chloride channel, Ion channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Transport

Keywords - Ligandi

Chloride

Names & Taxonomyi

Protein namesi
Recommended name:
Chloride intracellular channel protein 4
Short name:
mc3s5/mtCLIC
Gene namesi
Name:Clic4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1352754. Clic4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei37 – 5721Helical; Note=After insertion into the membraneSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoplasmic vesicle, Membrane, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 253252Chloride intracellular channel protein 4PRO_0000144211Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei4 – 41PhosphoserineBy similarity
Modified residuei130 – 1301N6-acetyllysineBy similarity
Modified residuei236 – 2361PhosphoserineCombined sources

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9QYB1.
MaxQBiQ9QYB1.
PaxDbiQ9QYB1.
PRIDEiQ9QYB1.

2D gel databases

UCD-2DPAGEQ9QYB1.

PTM databases

iPTMnetiQ9QYB1.
PhosphoSiteiQ9QYB1.
SwissPalmiQ9QYB1.

Expressioni

Tissue specificityi

Detected in blood vessels in the retina (at protein level). Expressed to the greatest extent in vivo in heart, lung, liver, kidney, and skin.3 Publications

Inductioni

Up-regulated by calcium ions in differentiating keratinocytes.1 Publication

Gene expression databases

BgeeiQ9QYB1.
CleanExiMM_CLIC4.
ExpressionAtlasiQ9QYB1. baseline and differential.
GenevisibleiQ9QYB1. MM.

Interactioni

Subunit structurei

Monomer. Interacts with HRH30. Interacts with AKAP9 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Pip5k1bP701814EBI-645175,EBI-645167

Protein-protein interaction databases

IntActiQ9QYB1. 5 interactions.
MINTiMINT-1651993.
STRINGi10090.ENSMUSP00000041453.

Structurei

3D structure databases

ProteinModelPortaliQ9QYB1.
SMRiQ9QYB1. Positions 6-253.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini104 – 244141GST C-terminalAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 101100Required for insertion into the membraneBy similarityAdd
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

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1422. Eukaryota.
ENOG410ZRK6. LUCA.
GeneTreeiENSGT00550000074477.
HOGENOMiHOG000231548.
HOVERGENiHBG050994.
InParanoidiQ9QYB1.
KOiK05024.
OMAiFLEDVLC.
OrthoDBiEOG7X3QR3.
PhylomeDBiQ9QYB1.
TreeFamiTF315438.

Family and domain databases

Gene3Di1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProiIPR002946. CLIC.
IPR030257. CLIC-4.
IPR010987. Glutathione-S-Trfase_C-like.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11260:SF185. PTHR11260:SF185. 2 hits.
PRINTSiPR01263. INTCLCHANNEL.
SUPFAMiSSF47616. SSF47616. 1 hit.
SSF52833. SSF52833. 1 hit.
TIGRFAMsiTIGR00862. O-ClC. 1 hit.
PROSITEiPS50405. GST_CTER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9QYB1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALSMPLNGL KEEDKEPLIE LFVKAGSDGE SIGNCPFSQR LFMILWLKGV
60 70 80 90 100
VFSVTTVDLK RKPADLQNLA PGTHPPFITF NSEVKTDVNK IEEFLEEVLC
110 120 130 140 150
PPKYLKLSPK HPESNTAGMD IFAKFSAYIK NSRPEANEAL ERGLLKTLQK
160 170 180 190 200
LDEYLNSPLP DEIDENSMED IKFSTRRFLD GDEMTLADCN LLPKLHIVKV
210 220 230 240 250
VAKKYRNFDI PKGMTGIWRY LTNAYSRDEF TNTCPSDKEV EIAYSDVAKR

LTK
Length:253
Mass (Da):28,729
Last modified:January 23, 2007 - v3
Checksum:i809568B37B441BB4
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti180 – 1801D → Y in BAC27301 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF102578 mRNA. Translation: AAF19055.1.
AK031211 mRNA. Translation: BAC27301.1.
BC046384 mRNA. Translation: AAH46384.1.
BC052890 mRNA. Translation: AAH52890.1.
CCDSiCCDS18783.1.
RefSeqiNP_038913.1. NM_013885.2.
UniGeneiMm.257765.

Genome annotation databases

EnsembliENSMUST00000037099; ENSMUSP00000041453; ENSMUSG00000037242.
GeneIDi29876.
KEGGimmu:29876.
UCSCiuc008vgd.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF102578 mRNA. Translation: AAF19055.1.
AK031211 mRNA. Translation: BAC27301.1.
BC046384 mRNA. Translation: AAH46384.1.
BC052890 mRNA. Translation: AAH52890.1.
CCDSiCCDS18783.1.
RefSeqiNP_038913.1. NM_013885.2.
UniGeneiMm.257765.

3D structure databases

ProteinModelPortaliQ9QYB1.
SMRiQ9QYB1. Positions 6-253.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9QYB1. 5 interactions.
MINTiMINT-1651993.
STRINGi10090.ENSMUSP00000041453.

PTM databases

iPTMnetiQ9QYB1.
PhosphoSiteiQ9QYB1.
SwissPalmiQ9QYB1.

2D gel databases

UCD-2DPAGEQ9QYB1.

Proteomic databases

EPDiQ9QYB1.
MaxQBiQ9QYB1.
PaxDbiQ9QYB1.
PRIDEiQ9QYB1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000037099; ENSMUSP00000041453; ENSMUSG00000037242.
GeneIDi29876.
KEGGimmu:29876.
UCSCiuc008vgd.1. mouse.

Organism-specific databases

CTDi25932.
MGIiMGI:1352754. Clic4.

Phylogenomic databases

eggNOGiKOG1422. Eukaryota.
ENOG410ZRK6. LUCA.
GeneTreeiENSGT00550000074477.
HOGENOMiHOG000231548.
HOVERGENiHBG050994.
InParanoidiQ9QYB1.
KOiK05024.
OMAiFLEDVLC.
OrthoDBiEOG7X3QR3.
PhylomeDBiQ9QYB1.
TreeFamiTF315438.

Miscellaneous databases

ChiTaRSiClic4. mouse.
PROiQ9QYB1.
SOURCEiSearch...

Gene expression databases

BgeeiQ9QYB1.
CleanExiMM_CLIC4.
ExpressionAtlasiQ9QYB1. baseline and differential.
GenevisibleiQ9QYB1. MM.

Family and domain databases

Gene3Di1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProiIPR002946. CLIC.
IPR030257. CLIC-4.
IPR010987. Glutathione-S-Trfase_C-like.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11260:SF185. PTHR11260:SF185. 2 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. "p53 and tumor necrosis factor alpha regulate the expression of a mitochondrial chloride channel protein."
    Fernandez-Salas E., Sagar M., Cheng C., Yuspa S.H., Weinberg W.C.
    J. Biol. Chem. 274:36488-36497(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Forelimb.
  3. "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].
    Strain: C3H/He.
    Tissue: Mammary gland and Osteoblast.
  4. "CLIC4 mediates and is required for Ca2+-induced keratinocyte differentiation."
    Suh K.S., Mutoh M., Mutoh T., Li L., Ryscavage A., Crutchley J.M., Dumont R.A., Cheng C., Yuspa S.H.
    J. Cell Sci. 120:2631-2640(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, INDUCTION, SUBCELLULAR LOCATION.
  5. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-236, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  6. "Chloride intracellular channel protein-4 functions in angiogenesis by supporting acidification of vacuoles along the intracellular tubulogenic pathway."
    Ulmasov B., Bruno J., Gordon N., Hartnett M.E., Edwards J.C.
    Am. J. Pathol. 174:1084-1096(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.

Entry informationi

Entry nameiCLIC4_MOUSE
AccessioniPrimary (citable) accession number: Q9QYB1
Secondary accession number(s): Q8BMG5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 19, 2002
Last sequence update: January 23, 2007
Last modified: June 8, 2016
This is version 143 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.