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Protein

H(+)/Cl(-) exchange transporter 3

Gene

Clcn3

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

Functioni

Mediates the exchange of chloride ions against protons. Functions as antiporter and contributes to the acidification of the endosome and synaptic vesicle lumen, and may thereby affect vesicle trafficking and exocytosis. May play an important role in neuronal cell function through regulation of membrane excitability by protein kinase C. It could help neuronal cells to establish short-term memory.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei239 – 2391ChlorideBy similarity
Sitei282 – 2821Mediates proton transfer from the outer aqueous phase to the interior of the protein; involved in linking H(+) and Cl(-) transportBy similarity
Sitei339 – 3391Mediates proton transfer from the protein to the inner aqueous phaseBy similarity
Binding sitei527 – 5271Chloride; via amide nitrogenBy similarity
Binding sitei630 – 6301ChlorideBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi689 – 6913ATPBy similarity
Nucleotide bindingi796 – 7994ATPBy similarity

GO - Molecular functioni

GO - Biological processi

  • adult locomotory behavior Source: MGI
  • chloride transmembrane transport Source: MGI
  • ion transmembrane transport Source: Reactome
  • negative regulation of cell volume Source: MGI
  • neuron cellular homeostasis Source: MGI
  • phagocytosis, engulfment Source: MGI
  • photoreceptor cell maintenance Source: MGI
  • positive regulation of reactive oxygen species biosynthetic process Source: MGI
  • regulation of anion transmembrane transport Source: GOC
  • synaptic transmission, GABAergic Source: MGI
  • synaptic transmission, glutamatergic Source: MGI
  • synaptic vesicle lumen acidification Source: MGI
Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Transport

Keywords - Ligandi

ATP-binding, Chloride, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-2672351. Stimuli-sensing channels.

Names & Taxonomyi

Protein namesi
Recommended name:
H(+)/Cl(-) exchange transporter 3
Alternative name(s):
Chloride channel protein 3
Short name:
ClC-3
Chloride transporter ClC-3
Gene namesi
Name:Clcn3
Synonyms:Clc3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:103555. Clcn3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 125125CytoplasmicBy similarityAdd
BLAST
Transmembranei126 – 16338HelicalBy similarityAdd
BLAST
Transmembranei209 – 23224HelicalBy similarityAdd
BLAST
Intramembranei241 – 2488HelicalBy similarity
Transmembranei258 – 27619HelicalBy similarityAdd
BLAST
Transmembranei282 – 30120HelicalBy similarityAdd
BLAST
Intramembranei313 – 32513HelicalBy similarityAdd
BLAST
Intramembranei329 – 3379HelicalBy similarity
Transmembranei349 – 36719HelicalBy similarityAdd
BLAST
Transmembranei391 – 41626HelicalBy similarityAdd
BLAST
Transmembranei423 – 44321HelicalBy similarityAdd
BLAST
Transmembranei500 – 52021HelicalBy similarityAdd
BLAST
Transmembranei525 – 54420HelicalBy similarityAdd
BLAST
Intramembranei572 – 58615HelicalBy similarityAdd
BLAST
Intramembranei590 – 60112HelicalBy similarityAdd
BLAST
Intramembranei602 – 6054Note=Loop between two helicesBy similarity
Transmembranei606 – 62419HelicalBy similarityAdd
BLAST
Topological domaini625 – 818194CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 818818H(+)/Cl(-) exchange transporter 3PRO_0000094439Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi177 – 1771N-linked (GlcNAc...)Sequence analysis
Glycosylationi451 – 4511N-linked (GlcNAc...)Sequence analysis
Glycosylationi479 – 4791N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiP51791.
MaxQBiP51791.
PaxDbiP51791.
PRIDEiP51791.

PTM databases

iPTMnetiP51791.
PhosphoSiteiP51791.

Expressioni

Tissue specificityi

Detected in kidney, in the apical part of proximal tubule cells (at protein level). Expressed at high levels in the kidney while a low level expression is seen in the brain. Within the brain, it is prominent in the hippocampus, cerebral cortex and olfactory bulb.1 Publication

Developmental stagei

At 10.5 days of development it is expressed throughout the embryo. Later in development (12.5 to 14.5 days of gestation), expression is progressively up-regulated in neurons of the brain and the spinal cord, in all cranial sensory ganglia and in the sympathetic dorsal root ganglia.

Gene expression databases

BgeeiP51791.
CleanExiMM_CLCN3.
ExpressionAtlasiP51791. baseline and differential.
GenevisibleiP51791. MM.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

IntActiP51791. 1 interaction.
MINTiMINT-4090894.
STRINGi10090.ENSMUSP00000004430.

Structurei

3D structure databases

ProteinModelPortaliP51791.
SMRiP51791. Positions 211-811.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini658 – 72265CBS 1PROSITE-ProRule annotationAdd
BLAST
Domaini755 – 81258CBS 2PROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi238 – 2425Selectivity filter part_1By similarity
Motifi280 – 2845Selectivity filter part_2By similarity
Motifi525 – 5295Selectivity filter part_3By similarity

Sequence similaritiesi

Contains 2 CBS domains.PROSITE-ProRule annotation

Keywords - Domaini

CBS domain, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0475. Eukaryota.
COG0038. LUCA.
GeneTreeiENSGT00760000119109.
HOGENOMiHOG000164493.
HOVERGENiHBG050984.
InParanoidiP51791.
KOiK05012.
OrthoDBiEOG7MWGXT.

Family and domain databases

Gene3Di1.10.3080.10. 3 hits.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002245. Cl_channel-3.
[Graphical view]
PfamiPF00571. CBS. 2 hits.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
PR01114. CLCHANNEL3.
SMARTiSM00116. CBS. 2 hits.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 3 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: P51791-1) [UniParc]FASTAAdd to basket

Also known as: b

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
MESEQLFHRG YYRNSYNSIT SASSDEELLD GAGAIMDFQT SEDDNLLDGD
60 70 80 90 100
TAAGTHYTMT NGGSINSSTH LLDLLDEPIP GVGTYDDFHT IDWVREKCKD
110 120 130 140 150
RERHRRINSK KKESAWEMTK SLYDAWSGWL VVTLTGLASG ALAGLIDIAA
160 170 180 190 200
DWMTDLKEGI CLSALWYNHE QCCWGSNETT FEERDKCPQW KTWAELIIGQ
210 220 230 240 250
AEGPGSYIMN YIMYIFWALS FAFLAVSLVK VFAPYACGSG IPEIKTILSG
260 270 280 290 300
FIIRGYLGKW TLMIKTITLV LAVASGLSLG KEGPLVHVAC CCGNIFSYLF
310 320 330 340 350
PKYSTNEAKK REVLSAASAA GVSVAFGAPI GGVLFSLEEV SYYFPLKTLW
360 370 380 390 400
RSFFAALVAA FVLRSINPFG NSRLVLFYVE YHTPWYLFEL FPFILLGVFG
410 420 430 440 450
GLWGAFFIRA NIAWCRRRKS TKFGKYPVLE VIIVAAITAV IAFPNPYTRL
460 470 480 490 500
NTSELIKELF TDCGPLESSS LCDYRNDMNA SKIVDDIPDR PAGVGVYSAI
510 520 530 540 550
WQLCLALIFK IIMTVFTFGI KVPSGLFIPS MAIGAIAGRI VGIAVEQLAY
560 570 580 590 600
YHHDWFIFKE WCEVGADCIT PGLYAMVGAA ACLGGVTRMT VSLVVIVFEL
610 620 630 640 650
TGGLEYIVPL MAAVMTSKWV GDAFGREGIY EAHIRLNGYP FLDAKEEFTH
660 670 680 690 700
TTLAADVMRP RRSDPPLAVL TQDNMTVDDI ENMINETSYN GFPVIMSKES
710 720 730 740 750
QRLVGFALRR DLTIAIESAR KKQEGIVGSS RVCFAQHTPS LPAESPRPLK
760 770 780 790 800
LRSILDMSPF TVTDHTPMEI VVDIFRKLGL RQCLVTHNGR LLGIITKKDI
810
LRHMAQTANQ DPASIMFN
Length:818
Mass (Da):90,869
Last modified:April 14, 2009 - v2
Checksum:i8DD21FD156A5B29E
GO
Isoform 2 (identifier: P51791-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-58: Missing.

Show »
Length:760
Mass (Da):84,475
Checksum:i0101C45A23509AFE
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5858Missing in isoform 2. 1 PublicationVSP_036899Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X78874 mRNA. Translation: CAA55476.1.
AF029347 mRNA. Translation: AAB95162.1.
AF347688
, AF347682, AF347683, AF347684, AF347685, AF347686 Genomic DNA. Translation: AAM89113.1.
AK141136 mRNA. Translation: BAE24568.1.
AK159698 mRNA. Translation: BAE35298.1.
AK162639 mRNA. Translation: BAE37002.1.
CH466569 Genomic DNA. Translation: EDL28642.1.
CCDSiCCDS22323.1. [P51791-2]
CCDS52554.1. [P51791-1]
PIRiI48295. S55473.
RefSeqiNP_031737.1. NM_007711.3. [P51791-2]
NP_776298.1. NM_173873.1. [P51791-1]
UniGeneiMm.25263.
Mm.259751.

Genome annotation databases

EnsembliENSMUST00000093490; ENSMUSP00000091202; ENSMUSG00000004319. [P51791-2]
ENSMUST00000110301; ENSMUSP00000105930; ENSMUSG00000004319. [P51791-1]
GeneIDi12725.
KEGGimmu:12725.
UCSCiuc009ltl.2. mouse. [P51791-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X78874 mRNA. Translation: CAA55476.1.
AF029347 mRNA. Translation: AAB95162.1.
AF347688
, AF347682, AF347683, AF347684, AF347685, AF347686 Genomic DNA. Translation: AAM89113.1.
AK141136 mRNA. Translation: BAE24568.1.
AK159698 mRNA. Translation: BAE35298.1.
AK162639 mRNA. Translation: BAE37002.1.
CH466569 Genomic DNA. Translation: EDL28642.1.
CCDSiCCDS22323.1. [P51791-2]
CCDS52554.1. [P51791-1]
PIRiI48295. S55473.
RefSeqiNP_031737.1. NM_007711.3. [P51791-2]
NP_776298.1. NM_173873.1. [P51791-1]
UniGeneiMm.25263.
Mm.259751.

3D structure databases

ProteinModelPortaliP51791.
SMRiP51791. Positions 211-811.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP51791. 1 interaction.
MINTiMINT-4090894.
STRINGi10090.ENSMUSP00000004430.

PTM databases

iPTMnetiP51791.
PhosphoSiteiP51791.

Proteomic databases

EPDiP51791.
MaxQBiP51791.
PaxDbiP51791.
PRIDEiP51791.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000093490; ENSMUSP00000091202; ENSMUSG00000004319. [P51791-2]
ENSMUST00000110301; ENSMUSP00000105930; ENSMUSG00000004319. [P51791-1]
GeneIDi12725.
KEGGimmu:12725.
UCSCiuc009ltl.2. mouse. [P51791-1]

Organism-specific databases

CTDi1182.
MGIiMGI:103555. Clcn3.

Phylogenomic databases

eggNOGiKOG0475. Eukaryota.
COG0038. LUCA.
GeneTreeiENSGT00760000119109.
HOGENOMiHOG000164493.
HOVERGENiHBG050984.
InParanoidiP51791.
KOiK05012.
OrthoDBiEOG7MWGXT.

Enzyme and pathway databases

ReactomeiR-MMU-2672351. Stimuli-sensing channels.

Miscellaneous databases

ChiTaRSiClcn3. mouse.
PROiP51791.
SOURCEiSearch...

Gene expression databases

BgeeiP51791.
CleanExiMM_CLCN3.
ExpressionAtlasiP51791. baseline and differential.
GenevisibleiP51791. MM.

Family and domain databases

Gene3Di1.10.3080.10. 3 hits.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002245. Cl_channel-3.
[Graphical view]
PfamiPF00571. CBS. 2 hits.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
PR01114. CLCHANNEL3.
SMARTiSM00116. CBS. 2 hits.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 3 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization of a human and murine gene (CLCN3) sharing similarities to voltage-gated chloride channels and to a yeast integral membrane protein."
    Borsani G., Rugarli E.I., Taglialatela M., Wong C., Ballabio A.
    Genomics 27:131-141(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Tissue: Thymus.
  2. "Ion transporters and receptors in cDNA libraries from lens and cornea epithelia."
    Shepard A.R., Rae J.L.
    Curr. Eye Res. 17:708-719(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Lens epithelium.
  3. "Diversity at the N- and C-termini for the predicted protein product of the mouse Clcn3 chloride channel gene is caused by alternative splicing."
    Schutte B.C., Zimmerman C.K., Swarz S., Malik M.I., Barna T.J., Lamb F.S.
    Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 129/Sv.
  4. "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] (ISOFORM 1).
    Strain: C57BL/6J.
    Tissue: Bone and Cerebellum.
  5. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "ClC-3 chloride channels facilitate endosomal acidification and chloride accumulation."
    Hara-Chikuma M., Yang B., Sonawane N.D., Sasaki S., Uchida S., Verkman A.S.
    J. Biol. Chem. 280:1241-1247(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Intracellular localization of ClC chloride channels and their ability to form hetero-oligomers."
    Suzuki T., Rai T., Hayama A., Sohara E., Suda S., Itoh T., Sasaki S., Uchida S.
    J. Cell. Physiol. 206:792-798(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  8. "Role of the vesicular chloride transporter ClC-3 in neuroendocrine tissue."
    Maritzen T., Keating D.J., Neagoe I., Zdebik A.A., Jentsch T.J.
    J. Neurosci. 28:10587-10598(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiCLCN3_MOUSE
AccessioniPrimary (citable) accession number: P51791
Secondary accession number(s): Q8K4X0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: April 14, 2009
Last modified: June 8, 2016
This is version 132 of the entry and version 2 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.