SLC8A1 (solute carrier family 8 member A1)

Gene

• Entrez ID: 6546
• Gene name: Solute carrier family 8 member A1
• Gene symbol: SLC8A1
• Synonyms: NCX1
• Chromosome: 2
• Chromosome location: 2p22.1
• Summary: In cardiac myocytes, Ca(2+) concentrations alternate between high levels during contraction and low levels during relaxation. The increase in Ca(2+) concentration during contraction is primarily due to release of Ca(2+) from intracellular stores. However, some Ca(2+) also enters the cell through the sarcolemma (plasma membrane). During relaxation, Ca(2+) is sequestered within the intracellular stores. To prevent overloading of intracellular stores, the Ca(2+) that entered across the sarcolemma must be extruded from the cell. The Na(+)-Ca(2+) exchanger is the primary mechanism by which the Ca(2+) is extruded from the cell during relaxation. In the heart, the exchanger may play a key role in digitalis action. The exchanger is the dominant mechanism in returning the cardiac myocyte to its resting state following excitation.[supplied by OMIM, Apr 2004]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006819	hsa-miR-1-3p	Luciferase reporter assay, Western blot	22362515
MIRT448462	hsa-miR-557	PAR-CLIP	22100165
MIRT448463	hsa-miR-507	PAR-CLIP	22100165
MIRT450666	hsa-miR-1273e	PAR-CLIP	22100165
MIRT510742	hsa-miR-3924	PAR-CLIP	23446348
MIRT510742	hsa-miR-3924	PAR-CLIP, HITS-CLIP	21572407
MIRT510743	hsa-miR-590-3p	PAR-CLIP	23446348
MIRT510743	hsa-miR-590-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT510744	hsa-miR-190a-3p	PAR-CLIP	23446348
MIRT510744	hsa-miR-190a-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT510745	hsa-miR-5011-5p	PAR-CLIP	23446348
MIRT510745	hsa-miR-5011-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT510746	hsa-miR-513c-3p	PAR-CLIP	23446348
MIRT510747	hsa-miR-513a-3p	PAR-CLIP	23446348
MIRT510748	hsa-miR-3606-3p	PAR-CLIP	23446348
MIRT510749	hsa-miR-410-3p	PAR-CLIP	23446348
MIRT510749	hsa-miR-410-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT521019	hsa-miR-4699-3p	PAR-CLIP	23446348
MIRT534165	hsa-miR-4683	PAR-CLIP	22012620
MIRT534166	hsa-miR-4784	PAR-CLIP	22012620
MIRT534167	hsa-miR-3150b-3p	PAR-CLIP	22012620
MIRT534168	hsa-miR-494-3p	PAR-CLIP	22012620
MIRT534169	hsa-miR-199b-5p	PAR-CLIP	22012620
MIRT534170	hsa-miR-199a-5p	PAR-CLIP	22012620
MIRT534171	hsa-miR-1825	PAR-CLIP	22012620
MIRT534172	hsa-miR-6847-5p	PAR-CLIP	22012620
MIRT534173	hsa-miR-512-3p	PAR-CLIP	22012620
MIRT534174	hsa-miR-6888-5p	PAR-CLIP	22012620
MIRT534175	hsa-miR-5693	PAR-CLIP	22012620
MIRT534176	hsa-miR-8057	PAR-CLIP	22012620
MIRT534177	hsa-miR-4423-3p	PAR-CLIP	22012620
MIRT534178	hsa-miR-760	PAR-CLIP	22012620
MIRT534179	hsa-miR-6822-3p	PAR-CLIP	22012620
MIRT534180	hsa-miR-3135a	PAR-CLIP	22012620
MIRT534181	hsa-miR-4766-5p	PAR-CLIP	22012620
MIRT534182	hsa-miR-146a-3p	PAR-CLIP	22012620
MIRT534183	hsa-miR-3622a-5p	PAR-CLIP	22012620
MIRT534184	hsa-miR-5582-5p	PAR-CLIP	22012620
MIRT554159	hsa-miR-4775	PAR-CLIP	21572407
MIRT622178	hsa-miR-4668-3p	HITS-CLIP	23824327
MIRT622179	hsa-miR-1305	HITS-CLIP	23824327
MIRT622180	hsa-miR-599	HITS-CLIP	23824327
MIRT636221	hsa-miR-3978	HITS-CLIP	23824327
MIRT636222	hsa-miR-3161	HITS-CLIP	23824327
MIRT636223	hsa-miR-6124	HITS-CLIP	23824327
MIRT636224	hsa-miR-4282	HITS-CLIP	23824327
MIRT636225	hsa-miR-3148	HITS-CLIP	23824327
MIRT641915	hsa-miR-501-5p	HITS-CLIP	23824327
MIRT641916	hsa-miR-500a-5p	HITS-CLIP	23824327
MIRT735112	hsa-miR-185-5p	Luciferase reporter assay, qRT-PCR, Western blot	25767890

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002026	Process	Regulation of the force of heart contraction	IC	19481548
GO:0002026	Process	Regulation of the force of heart contraction	ISS
GO:0002027	Process	Regulation of heart rate	ISS
GO:0002028	Process	Regulation of sodium ion transport	IEA
GO:0005432	Function	Calcium:sodium antiporter activity	IBA	21873635
GO:0005432	Function	Calcium:sodium antiporter activity	IDA	1374913
GO:0005432	Function	Calcium:sodium antiporter activity	IMP	25589784
GO:0005509	Function	Calcium ion binding	ISS
GO:0005515	Function	Protein binding	IPI	16292983, 25589784, 31837246
GO:0005516	Function	Calmodulin binding	IDA	26421717
GO:0005654	Component	Nucleoplasm	IDA
GO:0005739	Component	Mitochondrion	IEA
GO:0005874	Component	Microtubule	IEA
GO:0005886	Component	Plasma membrane	IDA	26421717
GO:0005886	Component	Plasma membrane	TAS	19095005
GO:0005887	Component	Integral component of plasma membrane	IBA	21873635
GO:0005887	Component	Integral component of plasma membrane	IDA	1374913
GO:0006811	Process	Ion transport	TAS
GO:0006874	Process	Cellular calcium ion homeostasis	ISS
GO:0006883	Process	Cellular sodium ion homeostasis	IDA	1374913
GO:0006936	Process	Muscle contraction	TAS	1374913
GO:0007584	Process	Response to nutrient	IEA
GO:0008092	Function	Cytoskeletal protein binding	IDA	16292983
GO:0009749	Process	Response to glucose	IEA
GO:0010468	Process	Regulation of gene expression	ISS
GO:0010649	Process	Regulation of cell communication by electrical coupling	TAS	17614935
GO:0010763	Process	Positive regulation of fibroblast migration	IEA
GO:0010881	Process	Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	ISS
GO:0010881	Process	Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	TAS	23608603
GO:0010882	Process	Regulation of cardiac muscle contraction by calcium ion signaling	TAS	23224879
GO:0014069	Component	Postsynaptic density	ISS
GO:0014704	Component	Intercalated disc	ISS
GO:0014704	Component	Intercalated disc	TAS	17614935
GO:0014829	Process	Vascular associated smooth muscle contraction	ISS
GO:0015491	Function	Cation:cation antiporter activity	IBA	21873635
GO:0016020	Component	Membrane	IBA	21873635
GO:0021537	Process	Telencephalon development	IEA
GO:0030001	Process	Metal ion transport	IBA	21873635
GO:0030018	Component	Z disc	ISS
GO:0030315	Component	T-tubule	ISS
GO:0030315	Component	T-tubule	TAS	17614935
GO:0030424	Component	Axon	IBA	21873635
GO:0030424	Component	Axon	ISS
GO:0030425	Component	Dendrite	ISS
GO:0030501	Process	Positive regulation of bone mineralization	IMP	25589784
GO:0030506	Function	Ankyrin binding	IPI	17178715
GO:0030506	Function	Ankyrin binding	ISS
GO:0033198	Process	Response to ATP	IEA
GO:0035725	Process	Sodium ion transmembrane transport	IBA	21873635
GO:0035725	Process	Sodium ion transmembrane transport	IGI	25589784
GO:0035725	Process	Sodium ion transmembrane transport	IMP	25589784
GO:0035902	Process	Response to immobilization stress	IEA
GO:0035994	Process	Response to muscle stretch	IMP	15105296
GO:0036376	Process	Sodium ion export across plasma membrane	IEA
GO:0042383	Component	Sarcolemma	IBA	21873635
GO:0042383	Component	Sarcolemma	ISS
GO:0042493	Process	Response to drug	IEA
GO:0042542	Process	Response to hydrogen peroxide	IEA
GO:0043025	Component	Neuronal cell body	ISS
GO:0043197	Component	Dendritic spine	IEA
GO:0043198	Component	Dendritic shaft	IEA
GO:0043679	Component	Axon terminus	ISS
GO:0044325	Function	Ion channel binding	ISS
GO:0044557	Process	Relaxation of smooth muscle	ISS
GO:0045202	Component	Synapse	IDA	21382638
GO:0045202	Component	Synapse	ISS
GO:0051481	Process	Negative regulation of cytosolic calcium ion concentration	ISS
GO:0055013	Process	Cardiac muscle cell development	ISS
GO:0055074	Process	Calcium ion homeostasis	ISS
GO:0055119	Process	Relaxation of cardiac muscle	IC	19481548
GO:0055119	Process	Relaxation of cardiac muscle	TAS	23224879
GO:0060048	Process	Cardiac muscle contraction	TAS	23224879
GO:0060401	Process	Cytosolic calcium ion transport	TAS	19095005
GO:0060402	Process	Calcium ion transport into cytosol	ISS
GO:0070509	Process	Calcium ion import	IDA	1374913
GO:0070588	Process	Calcium ion transmembrane transport	IGI	25589784
GO:0070588	Process	Calcium ion transmembrane transport	ISS
GO:0071313	Process	Cellular response to caffeine	ISS
GO:0071320	Process	Cellular response to cAMP	IEA
GO:0071456	Process	Cellular response to hypoxia	IEA
GO:0071901	Process	Negative regulation of protein serine/threonine kinase activity	ISS
GO:0071944	Component	Cell periphery	IDA	21321244
GO:0086012	Process	Membrane depolarization during cardiac muscle cell action potential	TAS	23608603
GO:0086064	Process	Cell communication by electrical coupling involved in cardiac conduction	ISS
GO:0098703	Process	Calcium ion import across plasma membrane	IBA	21873635
GO:0098719	Process	Sodium ion import across plasma membrane	IDA	1374913
GO:0098735	Process	Positive regulation of the force of heart contraction	IMP	15105296
GO:0098794	Component	Postsynapse	IBA	21873635
GO:0099055	Component	Integral component of postsynaptic membrane	IEA
GO:0099566	Process	Regulation of postsynaptic cytosolic calcium ion concentration	IEA
GO:0099580	Function	Ion antiporter activity involved in regulation of postsynaptic membrane potential	IEA
GO:1903779	Process	Regulation of cardiac conduction	TAS
GO:1905060	Function	Calcium:cation antiporter activity involved in regulation of postsynaptic cytosolic calcium ion concentration	IEA

Other IDs

• MIM: 182305
• HGNC: 11068
• e!Ensembl: ENSG00000183023

Protein

• UniProt ID: P32418
• Protein name: Sodium/calcium exchanger 1 (Na(+)/Ca(2+)-exchange protein 1) (Solute carrier family 8 member 1)
• Protein function: Mediates the exchange of one Ca(2+) ion against three to four Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes (PubMed:1374913, PubMed:11241183, PubMed:1476165). Contributes to Ca(2+) transport during excitation-contraction coupling in muscle. In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic reticulum. SLC8A1 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline. Required for normal embryonic heart development and the onset of heart contractions.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01699	Na_Ca_ex	80 → 251	Sodium/calcium exchanger protein	Family
  PF16494	Na_Ca_ex_C	254 → 390	C-terminal extension of sodium/calcium exchanger domain	Family
  PF03160	Calx-beta	396 → 496	Calx-beta domain	Domain
  PF03160	Calx-beta	527 → 627	Calx-beta domain	Domain
  PF01699	Na_Ca_ex	799 → 964	Sodium/calcium exchanger protein	Family

• Sequence:

  MYNMRRLSLSPTFSMGFHLLVTVSLLFSHVDHVIAETEMEGEGNETGECTGSYYCKKGVI
  LPIWEPQDPSFGDKIARATVYFVAMVYMFLGVSIIADRFMSSIEVITSQEKEITIKKPNG
  ETTKTTVRIWNETVSNLTLMALGSSAPEILLSVIEVCGHNFTAGDLGPSTIVGSAAFNMF
  IIIALCVYVVPDGETRKIKHLRVFFVTAAWSIFAYTWLYIILSVISPGVVEVWEGLLTFF
  FFPICVVFAWVADRRLLFYKYVYKRYRAGKQRGMIIEHEGDRPSSKTEIEMDGKVVNSHV
  ENFLDGALVLEVDERDQDDEEARREMARILKELKQKHPDKEIEQLIELANYQVLSQQQKS
  RAFYRIQATRLMTGAGNILKRHAADQARKAVSMHEVNTEVTENDPVSKIFFEQGTYQCLE
  NCGTVALTIIRRGGDLTNTVFVDFRTEDGTANAGSDYEFTEGTVVFKPGDTQKEIRVGII
  DDDIFEEDENFLVHLSNVKVSSEASEDGILEANHVSTLACLGSPSTATVTIFDDDHAGIF
  TFEEPVTHVSESIGIMEVKVLRTSGARGNVIVPYKTIEGTARGGGEDFEDTCGELEFQND
  EIVKTISVKVIDDEEYEKNKTFFLEIGEPRLVEMSEKKALLLNELGGFTITGKYLFGQPV
  FRKVHAREHPILSTVITIADEYDDKQPLTSKEEEERRIAEMGRPILGEHTKLEVIIEESY
  EFKSTVDKLIKKTNLALVVGTNSWREQFIEAITVSAGEDDDDDECGEEKLPSCFDYVMHF
  LTVFWKVLFAFVPPTEYWNGWACFIVSILMIGLLTAFIGDLASHFGCTIGLKDSVTAVVF
  VALGTSVPDTFASKVAATQDQYADASIGNVTGSNAVNVFLGIGVAWSIAAIYHAANGEQF
  KVSPGTLAFSVTLFTIFAFINVGVLLYRRRPEIGGELGGPRTAKLLTSCLFVLLWLLYIF
  FSSLEAYCHIKGF

• Sequence length: 973