NAC1_CAVPO
ID NAC1_CAVPO Reviewed; 970 AA.
AC P48766;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Sodium/calcium exchanger 1;
DE AltName: Full=Na(+)/Ca(2+)-exchange protein 1;
DE AltName: Full=Solute carrier family 8 member 1;
DE Flags: Precursor;
GN Name=SLC8A1;
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], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Heart;
RX PubMed=7986817; DOI=10.1016/0005-2736(94)90301-8;
RA Tsuruya Y., Bersohn M.M., Li Z., Nicoll D.A., Philipson K.D.;
RT "Molecular cloning and functional expression of the guinea pig cardiac
RT Na(+)-Ca2+ exchanger.";
RL Biochim. Biophys. Acta 1196:97-99(1994).
RN [2]
RP REVIEW.
RX PubMed=23506867; DOI=10.1016/j.mam.2012.07.003;
RA Khananshvili D.;
RT "The SLC8 gene family of sodium-calcium exchangers (NCX) - structure,
RT function, and regulation in health and disease.";
RL Mol. Aspects Med. 34:220-235(2013).
CC -!- FUNCTION: Mediates the exchange of one Ca(2+) ion against three to four
CC Na(+) ions across the cell membrane, and thereby contributes to the
CC regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular
CC processes (PubMed:7986817). Contributes to Ca(2+) transport during
CC excitation-contraction coupling in muscle. In a first phase, voltage-
CC gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels
CC due to release of Ca(2+) stores from the endoplasmic reticulum. SLC8A1
CC mediates the export of Ca(2+) from the cell during the next phase, so
CC that cytoplasmic Ca(2+) levels rapidly return to baseline. Required for
CC normal embryonic heart development and the onset of heart contractions
CC (By similarity). {ECO:0000250|UniProtKB:P70414,
CC ECO:0000269|PubMed:7986817}.
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:P32418};
CC -!- ACTIVITY REGULATION: Activated by micromolar levels of Ca(2+).
CC {ECO:0000250|UniProtKB:Q01728}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:7986817};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- DOMAIN: The cytoplasmic Calx-beta domains bind the regulatory Ca(2+).
CC The first Calx-beta domain can bind up to four Ca(2+) ions. The second
CC domain can bind another two Ca(2+) ions that are essential for calcium-
CC regulated ion exchange. {ECO:0000250|UniProtKB:P23685}.
CC -!- SIMILARITY: Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19)
CC family. SLC8 subfamily. {ECO:0000305}.
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DR EMBL; U04955; AAA73904.1; -; mRNA.
DR PIR; I48097; I48097.
DR RefSeq; NP_001166490.1; NM_001173019.1.
DR RefSeq; XP_013011147.1; XM_013155693.1.
DR AlphaFoldDB; P48766; -.
DR SMR; P48766; -.
DR STRING; 10141.ENSCPOP00000002023; -.
DR ChEMBL; CHEMBL3494; -.
DR Ensembl; ENSCPOT00000002262; ENSCPOP00000002023; ENSCPOG00000002233.
DR GeneID; 100135620; -.
DR KEGG; cpoc:100135620; -.
DR CTD; 6546; -.
DR eggNOG; KOG1306; Eukaryota.
DR GeneTree; ENSGT00940000155129; -.
DR HOGENOM; CLU_012872_1_0_1; -.
DR InParanoid; P48766; -.
DR OrthoDB; 490546at2759; -.
DR PRO; PR:P48766; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR Bgee; ENSCPOG00000002233; Expressed in heart left ventricle and 12 other tissues.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:Ensembl.
DR GO; GO:0014704; C:intercalated disc; IDA:BHF-UCL.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0042383; C:sarcolemma; IDA:BHF-UCL.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0030315; C:T-tubule; IDA:BHF-UCL.
DR GO; GO:0030018; C:Z disc; IDA:BHF-UCL.
DR GO; GO:0030506; F:ankyrin binding; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0005432; F:calcium:sodium antiporter activity; ISS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0055074; P:calcium ion homeostasis; IDA:BHF-UCL.
DR GO; GO:0070509; P:calcium ion import; IEA:Ensembl.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; IDA:BHF-UCL.
DR GO; GO:0007154; P:cell communication; IEA:InterPro.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; IEA:Ensembl.
DR GO; GO:0030501; P:positive regulation of bone mineralization; IEA:Ensembl.
DR GO; GO:0098735; P:positive regulation of the force of heart contraction; IEA:Ensembl.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IC:BHF-UCL.
DR GO; GO:0055119; P:relaxation of cardiac muscle; IC:BHF-UCL.
DR GO; GO:0035994; P:response to muscle stretch; IEA:Ensembl.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; IEA:Ensembl.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISS:UniProtKB.
DR Gene3D; 1.20.1420.30; -; 2.
DR Gene3D; 2.60.40.2030; -; 2.
DR InterPro; IPR038081; CalX-like_sf.
DR InterPro; IPR003644; Calx_beta.
DR InterPro; IPR001623; DnaJ_domain.
DR InterPro; IPR004836; Na_Ca_Ex.
DR InterPro; IPR032452; Na_Ca_Ex_C-exten.
DR InterPro; IPR002987; NaCa_exhngr1.
DR InterPro; IPR004837; NaCa_Exmemb.
DR InterPro; IPR044880; NCX_ion-bd_dom_sf.
DR Pfam; PF03160; Calx-beta; 2.
DR Pfam; PF01699; Na_Ca_ex; 2.
DR Pfam; PF16494; Na_Ca_ex_C; 1.
DR PRINTS; PR01259; NACAEXCHNGR.
DR PRINTS; PR01260; NACAEXCHNGR1.
DR SMART; SM00237; Calx_beta; 2.
DR SUPFAM; SSF141072; SSF141072; 2.
DR TIGRFAMs; TIGR00845; caca; 1.
PE 2: Evidence at transcript level;
KW Antiport; Calcium; Calcium transport; Calmodulin-binding; Cell membrane;
KW Glycoprotein; Ion transport; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; Signal; Sodium; Sodium transport;
KW Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..970
FT /note="Sodium/calcium exchanger 1"
FT /id="PRO_0000019377"
FT TOPO_DOM 33..71
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 72..92
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 93..133
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 134..154
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 155..167
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 189..201
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 223..228
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..249
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 250..797
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 798..818
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 819..821
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 822..842
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 843..871
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 872..892
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 893..903
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 904..924
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 925..941
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 942..962
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 963..970
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REPEAT 138..178
FT /note="Alpha-1"
FT DOMAIN 393..493
FT /note="Calx-beta 1"
FT DOMAIN 524..624
FT /note="Calx-beta 2"
FT REPEAT 839..875
FT /note="Alpha-2"
FT REGION 251..270
FT /note="Putative calmodulin-binding region"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 417
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 417
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 417
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 453
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 453
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 478
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 479
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 479
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 479
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 479
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 481
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 483
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 483
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 483
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 486
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 530
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 531
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 532
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 532
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 548
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 584
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 610
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 610
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 611
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 612
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 612
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 715
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT MOD_RES 282
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70414"
FT MOD_RES 389
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70414, ECO:0000255"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 970 AA; 108072 MW; 72D364CB8D157739 CRC64;
MLRLSLSPTY SLGFHLLAMM TLLISHVDHI TAETEMVEEG NETGECTGSY YCKKGVILPI
WEPQDPSFGD KIARATVYFV AMVYMFLGVS IIADRFMSSI EVITSQEKEI TIKKPNGETT
KTTVRIWNET VSNLTLMALG SSAPEILLSV IEVCGHNFTA GDLGPSTIVG SAAFNMFIII
ALCVYVVPDG ETRKIKHLRV FFVTAAWSIF AYTWLYIILS VISPGVVEVW EGLLTFFFFP
ICVVFAWVAD RRLLFYKYVY KRYRAGKQRG MIIEHEGDRP SSKTEIEMDG KVVNSHVENF
LDGALVLEVD ERDQDDEEAR REMARILKEL KQKHPEKEIE QLIELANYQV LSQQQKSRAF
YRIQATRLMT GAGNILKRHA ADQARKAVSM HEVNTEVAEN DPVSKIFFEQ GTYQCLENCG
TVALTIIRRG GDLTNTVFVD FRTEDGTANA GSDYEFTEGT VVFKPGETQK EIRVGIIDDD
IFEEDENFLV HLSNVKVSSE ASEDGILEAN HISTLACLGS PSTATVTIFD DDHAGIFTFE
EPVTHVSESI GIMEVKVLRT SGARGNVIVP YKTIEGTARG GGEDFEDTCG ELEFQNDEIV
KTISVKVIDD EEYEKNKTFF LEIGEPRLVE MSEKKALLLN ELGGFTITGK HLYGQPVLRK
VHARDHPIPS TVITIADEYD DKQPLTSKEE EERRIAELGR PILGEHTKLE VIIEESYEFK
STVDKLIKKT NLALVVGTNS WREQFIEAIT VSAGEDDDDD ECGEEKLPSC FDYVMHFLTV
FWKVLFAFVP PTEYWNGWAC FIVSILMIGL LTAFIGDLAS HFGCTIGLKD SVTAVVFVAL
GTSVPDTFAS KVAATQDQYA DASIGNVTGS NAVNVFLGIG VAWSIAAIYH AANGEQFKVS
PGTLAFSVTL FTIFAFINVG VLLYRRRPEI GGELGGPRTA KLLTSCLFVL LWLLYIFFSS
LEAYCHIKGF
