CLCN3_CAVPO
ID CLCN3_CAVPO Reviewed; 818 AA.
AC Q9R279; A0A286X8Y6;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 12-AUG-2020, sequence version 2.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=H(+)/Cl(-) exchange transporter 3;
DE AltName: Full=Chloride channel protein 3;
DE Short=ClC-3;
DE AltName: Full=Chloride transporter ClC-3;
GN Name=CLCN3;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Small intestine;
RA Varela D., Cid L.P., Sepulveda F.V.;
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=2N;
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
CC -!- FUNCTION: Strongly outwardly rectifying, electrogenic
CC H(+)/Cl(-)exchanger which mediates the exchange of chloride ions
CC against protons (By similarity). The CLC channel family contains both
CC chloride channels and proton-coupled anion transporters that exchange
CC chloride or another anion for protons (By similarity). The presence of
CC conserved gating glutamate residues is typical for family members that
CC function as antiporters (By similarity). {ECO:0000250|UniProtKB:P51790,
CC ECO:0000250|UniProtKB:P51791}.
CC -!- SUBUNIT: Monomer and homodimer (By similarity). Forms heterodimers with
CC CLCN4 (By similarity). {ECO:0000250|UniProtKB:P51791}.
CC -!- SUBCELLULAR LOCATION: Early endosome membrane
CC {ECO:0000250|UniProtKB:P51790}; Multi-pass membrane protein
CC {ECO:0000255}. Late endosome membrane {ECO:0000250|UniProtKB:P51790};
CC Multi-pass membrane protein {ECO:0000255}. Lysosome membrane
CC {ECO:0000250|UniProtKB:P51791}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:P51792}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9R279-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9R279-2; Sequence=VSP_060626;
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P51790}.
CC -!- SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family. ClC-
CC 3/CLCN3 subfamily. {ECO:0000305}.
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DR EMBL; AF133214; AAD33599.1; -; mRNA.
DR EMBL; AAKN02036435; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAKN02036434; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_005003429.1; XM_005003372.2. [Q9R279-1]
DR AlphaFoldDB; Q9R279; -.
DR SMR; Q9R279; -.
DR STRING; 10141.ENSCPOP00000000815; -.
DR PRIDE; Q9R279; -.
DR Ensembl; ENSCPOT00000035694; ENSCPOP00000021887; ENSCPOG00000000904. [Q9R279-1]
DR GeneID; 100135501; -.
DR CTD; 1182; -.
DR eggNOG; KOG0475; Eukaryota.
DR GeneTree; ENSGT00940000153763; -.
DR HOGENOM; CLU_003181_2_1_1; -.
DR InParanoid; Q9R279; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR Bgee; ENSCPOG00000000904; Expressed in pituitary gland and 13 other tissues.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0055037; C:recycling endosome; ISS:UniProtKB.
DR GO; GO:0012506; C:vesicle membrane; ISS:UniProtKB.
DR GO; GO:0015297; F:antiporter activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0030165; F:PDZ domain binding; ISS:UniProtKB.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; ISS:UniProtKB.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR InterPro; IPR014743; Cl-channel_core.
DR InterPro; IPR001807; Cl-channel_volt-gated.
DR InterPro; IPR002245; Cl_channel-3.
DR Pfam; PF00571; CBS; 2.
DR Pfam; PF00654; Voltage_CLC; 1.
DR PRINTS; PR00762; CLCHANNEL.
DR PRINTS; PR01114; CLCHANNEL3.
DR SMART; SM00116; CBS; 2.
DR SUPFAM; SSF54631; SSF54631; 1.
DR SUPFAM; SSF81340; SSF81340; 1.
DR PROSITE; PS51371; CBS; 2.
PE 2: Evidence at transcript level;
KW Alternative splicing; Antiport; ATP-binding; CBS domain; Cell membrane;
KW Chloride; Endosome; Glycoprotein; Ion transport; Lysosome; Membrane;
KW Nucleotide-binding; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..818
FT /note="H(+)/Cl(-) exchange transporter 3"
FT /id="PRO_0000094437"
FT TOPO_DOM 1..125
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 126..163
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 209..232
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 241..248
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 258..276
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 282..301
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 313..325
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 329..337
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 349..367
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 391..416
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 423..443
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 500..520
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 525..544
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 572..586
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 590..601
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 602..605
FT /note="Note=Loop between two helices"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 606..624
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TOPO_DOM 625..818
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT DOMAIN 658..722
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 755..812
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT MOTIF 28..29
FT /note="Di-leucine internalization motif; mediates targeting
FT to late endosome and lysosome membranes"
FT /evidence="ECO:0000250|UniProtKB:P51791"
FT MOTIF 46..47
FT /note="Di-leucine internalization motif; mediates targeting
FT to late endosome and lysosome membranes"
FT /evidence="ECO:0000250|UniProtKB:P51791"
FT MOTIF 71..75
FT /note="Di-leucine internalization motif; mediates targeting
FT to late endosome and lysosome membranes"
FT /evidence="ECO:0000250|UniProtKB:P51791"
FT MOTIF 238..242
FT /note="Selectivity filter part_1"
FT /evidence="ECO:0000250"
FT MOTIF 280..284
FT /note="Selectivity filter part_2"
FT /evidence="ECO:0000250"
FT MOTIF 525..529
FT /note="Selectivity filter part_3"
FT /evidence="ECO:0000250"
FT BINDING 239
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 527
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 630
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 689..691
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 796..799
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT SITE 282
FT /note="Mediates proton transfer from the outer aqueous
FT phase to the interior of the protein; involved in linking
FT H(+) and Cl(-) transport"
FT /evidence="ECO:0000250"
FT SITE 339
FT /note="Mediates proton transfer from the protein to the
FT inner aqueous phase"
FT /evidence="ECO:0000250"
FT CARBOHYD 177
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 451
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 479
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..58
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_060626"
SQ SEQUENCE 818 AA; 90936 MW; 17BCFAB2BA660F62 CRC64;
MESEQLFHRG YYRNSYNSIT SASSDEELLD GAGVIMDFQT SEDDNLLDGD TAVGTHYTMT
NGGSINSSTH LLDLLDEPIP GVGTYDDFHT IDWVREKCKD RERHRRINSK KKESAWEMTK
SLYDAWSGWL VVTLTGLASG ALAGLIDIAA DWMTDLKEGI CLSALWYNHE QCCWGSNETT
FEERDKCPQW KTWAELIIGQ AEGPGSYIMN YIMYIFWALS FAFLAVSLVK VFAPYACGSG
IPEIKTILSG FIIRGYLGKW TLMIKTITLV LAVASGLSLG KEGPLVHVAC CCGNIFSYLF
PKYSTNEAKK REVLSAASAA GVSVAFGAPI GGVLFSLEEV SYYFPLKTLW RSFFAALVAA
FVLRSINPFG NSRLVLFYVE YHTPWYLFEL FPFILLGVFG GLWGAFFIRA NIAWCRRRKS
TKFGKYPVLE VIIVAAITAV IAFPNPYTRL NTSELIKELF TDCGPLESSS LCDYRNDMNA
SKIVDDIPDR PAGVGVYSAI WQLCLALIFK IIMTVFTFGI KVPSGLFIPS MAIGAIAGRI
VGIAVEQLAY FHHDWFIFKE WCEVGADCIT PGLYAMVGAA ACLGGVTRMT VSLVVIVFEL
TGGLEYIVPL MAAVMTSKWV GDAFGREGIY EAHIRLNGYP FLDAKEEFTH TTLAADVMRP
RRNDPPLAVL TQDNMTVDDI ENMINETSYN GFPVIMSKES QRLVGFALRR DLTIAIESAR
KKQEGIVGSS RVCFAQHTPS LPAESPRPLK LRSILDMSPF TVTDHTPMEI VVDIFRKLGL
RQCLVTHNGR LLGIITKKDI LRHMAQTANQ DPASIMFN
