NAC1_BOVIN
ID NAC1_BOVIN Reviewed; 970 AA.
AC P48765;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 140.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Heart;
RX PubMed=1416984; DOI=10.1016/0003-9861(92)90449-7;
RA Aceto J.F., Condrescu M., Kroupis C., Nelson H., Nelson N., Nicoll D.A.,
RA Philipson K.D., Reeves J.P.;
RT "Cloning and expression of the bovine cardiac sodium-calcium exchanger.";
RL Arch. Biochem. Biophys. 298:553-560(1992).
RN [2]
RP PROTEIN SEQUENCE OF 33-40 AND 42-44.
RC TISSUE=Heart;
RX PubMed=1929404; DOI=10.1016/0003-9861(91)90553-u;
RA Durkin J.T., Ahrens D.C., Pan Y.-C.E., Reeves J.P.;
RT "Purification and amino-terminal sequence of the bovine cardiac sodium-
RT calcium exchanger: evidence for the presence of a signal sequence.";
RL Arch. Biochem. Biophys. 290:369-375(1991).
RN [3]
RP SUBCELLULAR LOCATION.
RC TISSUE=Retinal rod cell;
RX PubMed=2334719; DOI=10.1021/bi00458a035;
RA Reid D.M., Friedel U., Molday R.S., Cook N.J.;
RT "Identification of the sodium-calcium exchanger as the major ricin-binding
RT glycoprotein of bovine rod outer segments and its localization to the
RT plasma membrane.";
RL Biochemistry 29:1601-1607(1990).
RN [4]
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:1416984). 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 {ECO:0000250|UniProtKB:P70414, ECO:0000269|PubMed:1416984}.
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:1416984,
CC ECO:0000269|PubMed:2334719}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:2334719}.
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; L06438; AAA30509.1; -; mRNA.
DR PIR; S27114; S27114.
DR RefSeq; NP_788805.1; NM_176632.2.
DR AlphaFoldDB; P48765; -.
DR SMR; P48765; -.
DR STRING; 9913.ENSBTAP00000022795; -.
DR TCDB; 2.A.19.3.1; the ca(2+):cation antiporter (caca) family.
DR PaxDb; P48765; -.
DR PRIDE; P48765; -.
DR GeneID; 337925; -.
DR KEGG; bta:337925; -.
DR CTD; 6546; -.
DR eggNOG; KOG1306; Eukaryota.
DR InParanoid; P48765; -.
DR OrthoDB; 490546at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005901; C:caveola; IDA:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:AgBase.
DR GO; GO:0042383; C:sarcolemma; ISS:AgBase.
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:0070588; P:calcium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; ISS:AgBase.
DR GO; GO:0007154; P:cell communication; IEA:InterPro.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISS:AgBase.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:AgBase.
DR GO; GO:0051924; P:regulation of calcium ion transport; ISS:AgBase.
DR GO; GO:0002028; P:regulation of sodium ion transport; ISS:AgBase.
DR GO; GO:0002026; P:regulation of the force of heart contraction; ISS:AgBase.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006814; P:sodium ion transport; ISS:AgBase.
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 1: Evidence at protein level;
KW Antiport; Calcium; Calcium transport; Calmodulin-binding; Cell membrane;
KW Direct protein sequencing; Glycoprotein; Ion transport; Membrane;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; Signal; Sodium;
KW Sodium transport; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..32
FT /evidence="ECO:0000269|PubMed:1929404"
FT CHAIN 33..970
FT /note="Sodium/calcium exchanger 1"
FT /id="PRO_0000019375"
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; 108027 MW; 7C29153D1F87DDBE CRC64;
MLQFSLSPTL SMGFHVIAMV ALLFSHVDHI SAETEMEGEG NETGECTGSY YCKKGVILPI
WEPQDPSFGD KIARATVYFV AMVYMFLGVS IIADRFMSSI EVITSQEKEI TIKKPNGETT
KTTVRIWNET VSNLTLMALG SSAPEILLSV IEVCGHNFTA GDLGPSTIVG SAAFNMFIII
ALCVYVVPDG ETRKIKHLRV FFVTAAWSIF AYTWLYIILS VSSPGVVEVW EGLLTFFFFP
ICVVFAWVAD RRLLFYKYVY KRYRAGKQRG MIIEHEGDRP SSKTEIEMDG KVVNSHVDSF
LDGALVLEVD ERDQDDEEAR REMARILKEL KQKHPEKEIE QLIELANYQV LSQQQKSRAF
YRIQATRLMT GAGNILKRHA ADQARKAVSM HEVNTEVAEN DPVSKIFFEQ GTYQCLENCG
TVALTIIRRG GDLTNTVFVD FRTEDGTANA GSDYEFTEGT VVFKPGETQK EIRVGIIDDD
IFEEDENFLV HLSNVKVSLE ASEDGILEAS HVSTLACLGS PSTATVTIFD DDHAGIFTFE
EPVTHVSESI GIMEVKVLRT SGARGNVIVP YKTIEGTARG GGEDFEDTCG ELEFQNDEIV
KTISVKVIDD EEYEKNKTFF LEIGEPRLVE MSEKKALLLN ELGGFTITGK YLYGQPVFRK
VHAREHPLPS TIITIADEYD DKQPLTSKEE EERRIAEMGR PILGEHTRLE VIIEESYEFK
STVDKLIKKT NLALVVGTNS WREQFIEAIT VSAGEDDDDD ECGEEKLPSC FDYVMHFLTV
FWKVLFAFVP PTEYWNGWAC FIVSILMIGL LTAFIGDLAS HFACTIALKD SVTAVVFVAL
GTSVPDTFAS KVAATQDQYA DASIGNVTGS NAVNVFLGIG VAWSIAAIYH AANGEQFKVS
PGTLAFSVTL FTIFAFINVG VLLYRRRPEI GGELGGPRTA KLLTSCLFVL LWLLYIFFSS
LEAYCHIKGF
