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Protein

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

Gene

Clcn3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (By similarity).By similarity1 Publication

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

  • antiporter activity Source: UniProtKB-KW
  • ATP binding Source: UniProtKB-KW
  • chloride channel activity Source: RGD
  • ion channel activity Source: RGD
  • PDZ domain binding Source: UniProtKB
  • voltage-gated chloride channel activity Source: UniProtKB
  • voltage-gated ion channel activity Source: RGD

GO - Biological processi

  • chloride transmembrane transport Source: GOC
  • chloride transport Source: RGD
  • ion transmembrane transport Source: GOC
  • ion transport Source: RGD
  • regulation of anion transmembrane transport Source: GOC
  • regulation of ion transmembrane transport Source: GOC
Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Transport

Keywords - Ligandi

ATP-binding, Chloride, Nucleotide-binding

Protein family/group databases

TCDBi2.A.49.2.3. the chloride carrier/channel (clc) family.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 16

Organism-specific databases

RGDi621219. 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

  • apical plasma membrane Source: RGD
  • early endosome Source: UniProtKB
  • early endosome membrane Source: UniProtKB-SubCell
  • Golgi apparatus Source: UniProtKB
  • inhibitory synapse Source: MGI
  • integral component of membrane Source: RGD
  • intracellular Source: UniProtKB
  • late endosome Source: UniProtKB
  • late endosome membrane Source: UniProtKB-SubCell
  • membrane Source: RGD
  • plasma membrane Source: UniProtKB
  • synapse Source: GO_Central
  • synaptic vesicle Source: MGI
  • transport vesicle membrane Source: UniProtKB-SubCell
  • vesicle membrane Source: UniProtKB
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_0000094442Add
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

PaxDbiP51792.

PTM databases

iPTMnetiP51792.

Expressioni

Tissue specificityi

Abundant in brain, especially in the olfactory bulb, hippocampus, and cerebellum. A moderate expression is seen in the lung, kidney and adrenal gland.1 Publication

Gene expression databases

ExpressionAtlasiP51792. baseline and differential.
GenevisibleiP51792. RN.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000045523.

Structurei

3D structure databases

ProteinModelPortaliP51792.
SMRiP51792. Positions 650-811.
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.
InParanoidiP51792.
KOiK05012.
OMAiDGDTAVX.
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: P51792-1) [UniParc]FASTAAdd to basket

Also known as: long

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 KKQEGVVGSS RVCFAQHTPS LPAESPRPLK
760 770 780 790 800
LRSILDMSPF TVTDHTPMEI VVDIFRKLGL RQCLVTHNGR LLGIITKKDI
810
LRHMAQTANQ DPASIMFN
Length:818
Mass (Da):90,855
Last modified:April 14, 2009 - v2
Checksum:i0651B441484AAC6F
GO
Isoform 2 (identifier: P51792-2) [UniParc]FASTAAdd to basket

Also known as: short

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

Show »
Length:760
Mass (Da):84,461
Checksum:i8A826FCA3DBF840F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti774 – 7741I → V in BAA04471 (PubMed:8155321).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5858Missing in isoform 2. 1 PublicationVSP_036900Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D17521 mRNA. Translation: BAA04471.1.
AF142778 mRNA. Translation: AAD29440.1.
RefSeqiNP_445815.2. NM_053363.2. [P51792-1]
UniGeneiRn.4175.

Genome annotation databases

EnsembliENSRNOT00000050549; ENSRNOP00000045523; ENSRNOG00000010682. [P51792-1]
GeneIDi84360.
KEGGirno:84360.
UCSCiRGD:621219. rat. [P51792-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D17521 mRNA. Translation: BAA04471.1.
AF142778 mRNA. Translation: AAD29440.1.
RefSeqiNP_445815.2. NM_053363.2. [P51792-1]
UniGeneiRn.4175.

3D structure databases

ProteinModelPortaliP51792.
SMRiP51792. Positions 650-811.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000045523.

Protein family/group databases

TCDBi2.A.49.2.3. the chloride carrier/channel (clc) family.

PTM databases

iPTMnetiP51792.

Proteomic databases

PaxDbiP51792.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000050549; ENSRNOP00000045523; ENSRNOG00000010682. [P51792-1]
GeneIDi84360.
KEGGirno:84360.
UCSCiRGD:621219. rat. [P51792-1]

Organism-specific databases

CTDi1182.
RGDi621219. Clcn3.

Phylogenomic databases

eggNOGiKOG0475. Eukaryota.
COG0038. LUCA.
GeneTreeiENSGT00760000119109.
HOGENOMiHOG000164493.
HOVERGENiHBG050984.
InParanoidiP51792.
KOiK05012.
OMAiDGDTAVX.
OrthoDBiEOG7MWGXT.

Miscellaneous databases

NextBioi616697.
PROiP51792.

Gene expression databases

ExpressionAtlasiP51792. baseline and differential.
GenevisibleiP51792. RN.

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

  1. "Cloning and expression of a protein kinase C-regulated chloride channel abundantly expressed in rat brain neuronal cells."
    Kawasaki M., Uchida S., Monkawa T., Miyawaki A., Mikoshiba K., Marumo F., Sasaki S.
    Neuron 12:597-604(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Tissue: Kidney.
  2. "Expression and canalicular localization of two isoforms of the ClC-3 chloride channel from rat hepatocytes."
    Shimada K., Li X., Xu G., Nowak D.E., Showalter L.A., Weinman S.A.
    Am. J. Physiol. 279:G268-G276(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Strain: Sprague-Dawley.
  3. "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.

Entry informationi

Entry nameiCLCN3_RAT
AccessioniPrimary (citable) accession number: P51792
Secondary accession number(s): Q9R287
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: April 14, 2009
Last modified: May 11, 2016
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The presence of conserved gating glutamate residues is typical for family members that function as antiporters (By similarity).By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.