NCLX_RAT
ID NCLX_RAT Reviewed; 585 AA.
AC Q6AXS0;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Mitochondrial sodium/calcium exchanger protein {ECO:0000305};
DE AltName: Full=Na(+)/K(+)/Ca(2+)-exchange protein 6 {ECO:0000303|PubMed:14625281};
DE AltName: Full=Sodium/calcium exchanger protein, mitochondrial {ECO:0000303|PubMed:15060069};
DE AltName: Full=Sodium/potassium/calcium exchanger 6 {ECO:0000303|PubMed:14625281};
DE AltName: Full=Solute carrier family 24 member 6 {ECO:0000312|RGD:1565818};
DE AltName: Full=Solute carrier family 8 member B1 {ECO:0000312|RGD:1565818};
DE Flags: Precursor;
GN Name=Slc8b1 {ECO:0000312|RGD:1565818};
GN Synonyms=Nckx6 {ECO:0000303|PubMed:14625281},
GN Nclx {ECO:0000303|PubMed:15060069}, Slc24a6 {ECO:0000312|RGD:1565818};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=14625281; DOI=10.1074/jbc.m310908200;
RA Cai X., Lytton J.;
RT "Molecular cloning of a sixth member of the K+-dependent Na+/Ca2+ exchanger
RT gene family, NCKX6.";
RL J. Biol. Chem. 279:5867-5876(2004).
RN [3]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15060069; DOI=10.1074/jbc.m401229200;
RA Palty R., Ohana E., Hershfinkel M., Volokita M., Elgazar V., Beharier O.,
RA Silverman W.F., Argaman M., Sekler I.;
RT "Lithium-calcium exchange is mediated by a distinct potassium-independent
RT sodium-calcium exchanger.";
RL J. Biol. Chem. 279:25234-25240(2004).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=20018762; DOI=10.1073/pnas.0908099107;
RA Palty R., Silverman W.F., Hershfinkel M., Caporale T., Sensi S.L.,
RA Parnis J., Nolte C., Fishman D., Shoshan-Barmatz V., Herrmann S.,
RA Khananshvili D., Sekler I.;
RT "NCLX is an essential component of mitochondrial Na+/Ca2+ exchange.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:436-441(2010).
CC -!- FUNCTION: Mitochondrial sodium/calcium antiporter that mediates sodium-
CC dependent calcium efflux from mitochondrion, by mediating the exchange
CC of 3 sodium ions per 1 calcium ion. Plays a central role in
CC mitochondrial calcium homeostasis by mediating mitochondrial calcium
CC extrusion: calcium efflux is essential for mitochondrial function and
CC cell survival, notably in cardiomyocytes (By similarity). Regulates
CC rates of glucose-dependent insulin secretion in pancreatic beta-cells
CC during the first phase of insulin secretion: acts by mediating efflux
CC of calcium from mitochondrion, thereby affecting cytoplasmic calcium
CC responses. Required for store-operated Ca(2+) entry (SOCE) and Ca(2+)
CC release-activated Ca(2+) (CRAC) channel regulation: sodium transport by
CC SLC8B1 leads to promote calcium-shuttling that modulates mitochondrial
CC redox status, thereby regulating SOCE activity (By similarity).
CC Involved in B-lymphocyte chemotaxis (By similarity). Able to transport
CC Ca(2+) in exchange of either Li(+) or Na(+), explaining how Li(+)
CC catalyzes Ca(2+) exchange. In contrast to other members of the family
CC its function is independent of K(+) (By similarity).
CC {ECO:0000250|UniProtKB:Q6J4K2, ECO:0000250|UniProtKB:Q925Q3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Ca(2+)(in) + 3 Na(+)(out) = Ca(2+)(out) + 3 Na(+)(in);
CC Xref=Rhea:RHEA:69955, ChEBI:CHEBI:29101, ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:Q6J4K2};
CC -!- ACTIVITY REGULATION: Inhibited by the sodium/calcium exchanger
CC inhibitor CGP-37157. Strongly inhibited by zinc.
CC {ECO:0000250|UniProtKB:Q6J4K2}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:15060069, ECO:0000269|PubMed:20018762}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:15060069,
CC ECO:0000269|PubMed:20018762}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Present at higher level in
CC pancreas, stomach, skeletal muscle and skin (at protein level).
CC Ubiquitously expressed. {ECO:0000269|PubMed:14625281,
CC ECO:0000269|PubMed:15060069}.
CC -!- PTM: Phosphorylation at Ser-258 by PKA prevents calcium overload.
CC {ECO:0000250|UniProtKB:Q6J4K2}.
CC -!- SIMILARITY: Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19)
CC family. SLC24A subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC079350; AAH79350.1; -; mRNA.
DR RefSeq; NP_001017488.1; NM_001017488.1.
DR AlphaFoldDB; Q6AXS0; -.
DR STRING; 10116.ENSRNOP00000034026; -.
DR GlyGen; Q6AXS0; 1 site.
DR PaxDb; Q6AXS0; -.
DR PRIDE; Q6AXS0; -.
DR Ensembl; ENSRNOT00000038736; ENSRNOP00000034026; ENSRNOG00000001383.
DR GeneID; 498185; -.
DR KEGG; rno:498185; -.
DR UCSC; RGD:1565818; rat.
DR CTD; 80024; -.
DR RGD; 1565818; Slc8b1.
DR eggNOG; KOG2399; Eukaryota.
DR GeneTree; ENSGT00940000157433; -.
DR HOGENOM; CLU_004979_3_2_1; -.
DR InParanoid; Q6AXS0; -.
DR OMA; IYLWQAV; -.
DR OrthoDB; 478735at2759; -.
DR PhylomeDB; Q6AXS0; -.
DR TreeFam; TF323444; -.
DR Reactome; R-RNO-425561; Sodium/Calcium exchangers.
DR Reactome; R-RNO-8949215; Mitochondrial calcium ion transport.
DR PRO; PR:Q6AXS0; -.
DR Proteomes; UP000002494; Chromosome 12.
DR Bgee; ENSRNOG00000001383; Expressed in spleen and 19 other tissues.
DR Genevisible; Q6AXS0; RN.
DR GO; GO:0032592; C:integral component of mitochondrial membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0030061; C:mitochondrial crista; IDA:BHF-UCL.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0042383; C:sarcolemma; IDA:MGI.
DR GO; GO:0005432; F:calcium:sodium antiporter activity; ISS:UniProtKB.
DR GO; GO:0086038; F:calcium:sodium antiporter activity involved in regulation of cardiac muscle cell membrane potential; ISS:UniProtKB.
DR GO; GO:0008324; F:cation transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IDA:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0099093; P:calcium export from the mitochondrion; ISS:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISO:RGD.
DR GO; GO:0006812; P:cation transport; IBA:GO_Central.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; ISS:UniProtKB.
DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; ISS:BHF-UCL.
DR GO; GO:0050796; P:regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:1901623; P:regulation of lymphocyte chemotaxis; ISS:UniProtKB.
DR GO; GO:2001256; P:regulation of store-operated calcium entry; ISS:UniProtKB.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISO:RGD.
DR Gene3D; 1.20.1420.30; -; 2.
DR InterPro; IPR004837; NaCa_Exmemb.
DR InterPro; IPR044880; NCX_ion-bd_dom_sf.
DR Pfam; PF01699; Na_Ca_ex; 2.
PE 1: Evidence at protein level;
KW Antiport; Calcium; Calcium transport; Glycoprotein; Ion transport; Lithium;
KW Membrane; Mitochondrion; Mitochondrion inner membrane; Phosphoprotein;
KW Reference proteome; Sensory transduction; Sodium; Sodium transport;
KW Transit peptide; Transmembrane; Transmembrane helix; Transport.
FT TRANSIT 1..26
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 27..585
FT /note="Mitochondrial sodium/calcium exchanger protein"
FT /id="PRO_0000045758"
FT TOPO_DOM 27..95
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 96..116
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 117..140
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 141..161
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..168
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 169..189
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 190..205
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 206..226
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 227
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 228..247
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 248..325
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 326..346
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 347..360
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 361..381
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 382..383
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 384..404
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 405..416
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 417..437
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 438..445
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 446..466
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 467..491
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 492..512
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 513..525
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 526..546
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 547..559
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 560..580
FT /note="Helical; Name=13"
FT /evidence="ECO:0000255"
FT TOPO_DOM 581..585
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 258
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q6J4K2"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 585 AA; 63992 MW; 08BA7C6580B4F174 CRC64;
MAGRWLDPLW APGFLCVALI LETASGAGDL STKAHGHIQF SARGVNQTAM ADCRAVCSLN
TSDRCDFVKR NPDCHSEGGY LDYLKGIFCY FPPNLLPLAI TLYVFWLLYL FLILGVTAAK
FFCPNLSAIS TSLKLSHNVA GVTFLAFGNG APDIFSALVA FSDPRTAGLA IGALFGAGVL
VTTVVAGGIT ILRPFMAASR PFLRDITFYM VAVFLTFTAL YLGRITLVWA LGYLGLYVFY
VVTVIICTWV YQRQRSRSLV HSISETPELL TDSEEDQMSS NTNSYDYGEE YRPLLLGEET
TGQILLQALN PLDYRKWRTQ SISCKLLKVA KLPVEFLLLL TVPVVDPDKD DRNWKRPLNC
LQLVISPLVL VLTLQSGVYG IYEIGGLLPV WAVVVIVGTA LASVTFFATS NSEPPRLHWL
FAFLGFLTSA LWINAAATEV VNILRSLGVV FRLSNTVLGL TLLAWGNSIG DAFSDFTLAR
QGYPRMAFSA CFGGIIFNIL VGVGLGCLLQ IVRSHASEVK LEPDGLLVWV LASALGLSLV
FSLVSVPLQC FQLSKAYGLC LLLFYICFIV VVLLTEFGVI HLKAD
