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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)DescriptionActionsGraphical viewLength
Binding sitei239ChlorideBy similarity1
Sitei282Mediates proton transfer from the outer aqueous phase to the interior of the protein; involved in linking H(+) and Cl(-) transportBy similarity1
Sitei339Mediates proton transfer from the protein to the inner aqueous phaseBy similarity1
Binding sitei527Chloride; via amide nitrogenBy similarity1
Binding sitei630ChlorideBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi689 – 691ATPBy similarity3
Nucleotide bindingi796 – 799ATPBy similarity4

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
  • 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)DescriptionActionsGraphical viewLength
Topological domaini1 – 125CytoplasmicBy similarityAdd BLAST125
Transmembranei126 – 163HelicalBy similarityAdd BLAST38
Transmembranei209 – 232HelicalBy similarityAdd BLAST24
Intramembranei241 – 248HelicalBy similarity8
Transmembranei258 – 276HelicalBy similarityAdd BLAST19
Transmembranei282 – 301HelicalBy similarityAdd BLAST20
Intramembranei313 – 325HelicalBy similarityAdd BLAST13
Intramembranei329 – 337HelicalBy similarity9
Transmembranei349 – 367HelicalBy similarityAdd BLAST19
Transmembranei391 – 416HelicalBy similarityAdd BLAST26
Transmembranei423 – 443HelicalBy similarityAdd BLAST21
Transmembranei500 – 520HelicalBy similarityAdd BLAST21
Transmembranei525 – 544HelicalBy similarityAdd BLAST20
Intramembranei572 – 586HelicalBy similarityAdd BLAST15
Intramembranei590 – 601HelicalBy similarityAdd BLAST12
Intramembranei602 – 605Note=Loop between two helicesBy similarity4
Transmembranei606 – 624HelicalBy similarityAdd BLAST19
Topological domaini625 – 818CytoplasmicBy similarityAdd BLAST194

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000944391 – 818H(+)/Cl(-) exchange transporter 3Add BLAST818

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi177N-linked (GlcNAc...)Sequence analysis1
Glycosylationi451N-linked (GlcNAc...)Sequence analysis1
Glycosylationi479N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiP51791.
PaxDbiP51791.
PeptideAtlasiP51791.
PRIDEiP51791.

PTM databases

iPTMnetiP51791.
PhosphoSitePlusiP51791.

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

BgeeiENSMUSG00000004319.
CleanExiMM_CLCN3.
ExpressionAtlasiP51791. baseline and differential.
GenevisibleiP51791. MM.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliP51791.
SMRiP51791.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini658 – 722CBS 1PROSITE-ProRule annotationAdd BLAST65
Domaini755 – 812CBS 2PROSITE-ProRule annotationAdd BLAST58

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi238 – 242Selectivity filter part_1By similarity5
Motifi280 – 284Selectivity filter part_2By similarity5
Motifi525 – 529Selectivity filter part_3By similarity5

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.

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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0368991 – 58Missing in isoform 2. 1 PublicationAdd BLAST58

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiP51791.
PhosphoSitePlusiP51791.

Proteomic databases

MaxQBiP51791.
PaxDbiP51791.
PeptideAtlasiP51791.
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.

Enzyme and pathway databases

ReactomeiR-MMU-2672351. Stimuli-sensing channels.

Miscellaneous databases

ChiTaRSiClcn3. mouse.
PROiP51791.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000004319.
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...

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: November 2, 2016
This is version 136 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.