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Protein

H(+)/Cl(-) exchange transporter 5

Gene

Clcn5

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons. Important for normal acidification of the endosome lumen. May play an important role in renal tubular function (By similarity).By similarity1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei168 – 1681ChlorideBy similarity
Sitei211 – 2111Mediates proton transfer from the outer aqueous phase to the interior of the protein; involved in linking H(+) and Cl(-) transportBy similarity
Sitei268 – 2681Mediates proton transfer from the protein to the inner aqueous phaseBy similarity
Binding sitei455 – 4551Chloride; via amide nitrogenBy similarity
Binding sitei558 – 5581ChlorideBy similarity
Binding sitei596 – 5961ATP; via amide nitrogen and carbonyl oxygenBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi617 – 6193ATPBy similarity
Nucleotide bindingi724 – 7274ATPBy similarity

GO - Molecular functioni

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

GO - Biological processi

  • chloride transport Source: RGD
Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Transport

Keywords - Ligandi

ATP-binding, Chloride, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-RNO-2672351. Stimuli-sensing channels.

Names & Taxonomyi

Protein namesi
Recommended name:
H(+)/Cl(-) exchange transporter 5
Alternative name(s):
Chloride channel protein 5
Short name:
ClC-5
Chloride transporter ClC-5
Gene namesi
Name:Clcn5
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome X

Organism-specific databases

RGDi2362. Clcn5.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 5454CytoplasmicBy similarityAdd
BLAST
Transmembranei55 – 9238HelicalBy similarityAdd
BLAST
Transmembranei138 – 16124HelicalBy similarityAdd
BLAST
Intramembranei170 – 1778HelicalBy similarity
Transmembranei186 – 20520HelicalBy similarityAdd
BLAST
Transmembranei211 – 23020HelicalBy similarityAdd
BLAST
Intramembranei242 – 25413HelicalBy similarityAdd
BLAST
Intramembranei258 – 2669HelicalBy similarity
Transmembranei278 – 29619HelicalBy similarityAdd
BLAST
Transmembranei319 – 34426HelicalBy similarityAdd
BLAST
Transmembranei352 – 37221HelicalBy similarityAdd
BLAST
Transmembranei428 – 44821HelicalBy similarityAdd
BLAST
Transmembranei453 – 47220HelicalBy similarityAdd
BLAST
Intramembranei500 – 51415HelicalBy similarityAdd
BLAST
Intramembranei515 – 5173Note=Loop between two helicesBy similarity
Intramembranei518 – 52912HelicalBy similarityAdd
BLAST
Intramembranei530 – 5345Note=Loop between two helicesBy similarity
Transmembranei535 – 55218HelicalBy similarityAdd
BLAST
Topological domaini553 – 746194CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  • apical part of cell Source: UniProtKB
  • endosome Source: RGD
  • endosome membrane Source: UniProtKB-SubCell
  • Golgi membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 746746H(+)/Cl(-) exchange transporter 5PRO_0000094448Add
BLAST

Post-translational modificationi

Ubiquitinated by NEDD4L in the presence of albumin; which promotes endocytosis and proteasomal degradation.By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiP51796.
PRIDEiP51796.

PTM databases

PhosphoSiteiP51796.

Expressioni

Tissue specificityi

Kidney specific.

Gene expression databases

ExpressionAtlasiP51796. baseline.
GenevisibleiP51796. RN.

Interactioni

Subunit structurei

Interacts with NEDD4 and NEDD4L.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000003895.

Structurei

3D structure databases

ProteinModelPortaliP51796.
SMRiP51796. Positions 578-746.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini586 – 65065CBS 1PROSITE-ProRule annotationAdd
BLAST
Domaini682 – 74160CBS 2PROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi167 – 1715Selectivity filter part_1By similarity
Motifi209 – 2135Selectivity filter part_2By similarity
Motifi453 – 4575Selectivity 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.
InParanoidiP51796.
KOiK05012.
OMAiLMDIPGT.
OrthoDBiEOG7MWGXT.
PhylomeDBiP51796.

Family and domain databases

Gene3Di1.10.3080.10. 3 hits.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002247. Cl_channel-5.
[Graphical view]
PfamiPF00571. CBS. 2 hits.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
PR01116. CLCHANNEL5.
SMARTiSM00116. CBS. 2 hits.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 3 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P51796-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDFLEEPIPG VGTYDDFNTI DWVREKSRDR DRHREITNKS KESTWALIHS
60 70 80 90 100
VSDAFSGWLL MLLIGLLSGS LAGLIDISAH WMTDLKEGIC TGGFWFNHEH
110 120 130 140 150
CCWNSEHVTF EDRDKCPEWN SWSQLIISTD QGAFAYIVNY FMYVLWALLF
160 170 180 190 200
AFLAVSLVKA FAPYACGSGI PEIKTILSGF IIRGYLGKWT LVIKTITLVL
210 220 230 240 250
AVSSGLSLGK EGPLVHVACC CGNILCHCFN KYRKNEAKRR EVLSAAAAAG
260 270 280 290 300
VSVAFGAPIG GVLFSLEEVS YYFPLKTLWR SFFAALVAAF TLRSINPFGN
310 320 330 340 350
SRLVLFYVEF HTPWHLFELV PFIVLGIFGG LWGALFIRTN IAWCRKRKTT
360 370 380 390 400
QLGKYPVVEV LIVTAITAIL AFPNEYTRMS TSELISELFN DCGLLDSSKL
410 420 430 440 450
CDYENHFNTS KGGELPDRPA GVGVYSAMWQ LALTLILKIV ITIFTFGMKI
460 470 480 490 500
PSGLFIPSMA VGAIAGRLLG VGMEQLAYYH HDWGIFNSWC SQGADCITPG
510 520 530 540 550
LYAMVGAAAC LGGVTRMTVS LVVIMFELTG GLEYIVPLMA AAMTSKWVAD
560 570 580 590 600
ALGREGIYDA HIRLNGYPFL EAKEEFAHKT LAMDVMKPRR NDPLLTVLTQ
610 620 630 640 650
DSMTVEDVET IISETTYSGF PVVVSRESQR LVGFVLRRDL IISIENARKK
660 670 680 690 700
QDGVVSTSII YFTEHSPPMP PYTPPTLKLR NILDLSPFTV TDLTPMEIVV
710 720 730 740
DIFRKLGLRQ CLVTHNGRLL GIITKKDVLK HIAQMANQDP ESILFN
Length:746
Mass (Da):83,068
Last modified:October 1, 1996 - v1
Checksum:i5F17D45F397003CE
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti315 – 3151H → Y in BAA09091 (PubMed:8626585).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z56277 mRNA. Translation: CAA91216.1.
D50497 mRNA. Translation: BAA09091.1.
RefSeqiNP_058802.1. NM_017106.1.
UniGeneiRn.10337.

Genome annotation databases

EnsembliENSRNOT00000003895; ENSRNOP00000003895; ENSRNOG00000002862.
GeneIDi25749.
KEGGirno:25749.
UCSCiRGD:2362. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z56277 mRNA. Translation: CAA91216.1.
D50497 mRNA. Translation: BAA09091.1.
RefSeqiNP_058802.1. NM_017106.1.
UniGeneiRn.10337.

3D structure databases

ProteinModelPortaliP51796.
SMRiP51796. Positions 578-746.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000003895.

PTM databases

PhosphoSiteiP51796.

Proteomic databases

PaxDbiP51796.
PRIDEiP51796.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000003895; ENSRNOP00000003895; ENSRNOG00000002862.
GeneIDi25749.
KEGGirno:25749.
UCSCiRGD:2362. rat.

Organism-specific databases

CTDi1184.
RGDi2362. Clcn5.

Phylogenomic databases

eggNOGiKOG0475. Eukaryota.
COG0038. LUCA.
GeneTreeiENSGT00760000119109.
HOGENOMiHOG000164493.
HOVERGENiHBG050984.
InParanoidiP51796.
KOiK05012.
OMAiLMDIPGT.
OrthoDBiEOG7MWGXT.
PhylomeDBiP51796.

Enzyme and pathway databases

ReactomeiR-RNO-2672351. Stimuli-sensing channels.

Miscellaneous databases

PROiP51796.

Gene expression databases

ExpressionAtlasiP51796. baseline.
GenevisibleiP51796. RN.

Family and domain databases

Gene3Di1.10.3080.10. 3 hits.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002247. Cl_channel-5.
[Graphical view]
PfamiPF00571. CBS. 2 hits.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
PR01116. CLCHANNEL5.
SMARTiSM00116. CBS. 2 hits.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 3 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Cloning and functional expression of rat CLC-5, a chloride channel related to kidney disease."
    Steinmeyer K., Schwappach B., Bens M., Vandewalle A., Jentsch T.J.
    J. Biol. Chem. 270:31172-31177(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  2. "Identification of a new outwardly rectifying Cl- channel that belongs to a subfamily of the ClC Cl- channels."
    Sakamoto H., Kawasaki M., Uchida S., Sasaki S., Marumo F.
    J. Biol. Chem. 271:10210-10216(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Kidney.
  3. "Residues important for nitrate/proton coupling in plant and mammalian CLC transporters."
    Bergsdorf E.-Y., Zdebik A.A., Jentsch T.J.
    J. Biol. Chem. 284:11184-11193(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiCLCN5_RAT
AccessioniPrimary (citable) accession number: P51796
Secondary accession number(s): P70642
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 6, 2016
This is version 124 of the entry and version 1 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 absence of conserved gating glutamate residues is typical for family members that function as channels (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.