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2.A.19.3.4
Sodium/calcium exchanger 1 (Na+/Ca2+-exchange protein 1).  The cardiac isoform, CAX1.1, like the archaeal homologues for which high resolution 3-d structures are available (TC#s 2.A.19.5.3 and 2.A.19.8.2), have two aqueous ion permeation channels with cavities that can face the cytoplasm or the external medium (John et al. 2013). It exchanges one Ca2+ ion against three to four Na+ ions, and thereby contributes to the regulation of cytoplasmic Ca2+ levels and Ca2+-dependent cellular processes (Komuro et al. 1992; , Van Eylen et al. 2001; Kofuji et al. 1992). It also contributes to Ca2+ transport during excitation-contraction coupling in muscle. In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca2+ levels due to release of Ca2+ stores from the endoplasmic reticulum. SLC8A1 mediates the export of Ca2+ from the cell during the next phase, so that cytoplasmic Ca2+ levels rapidly return to baseline. It is also required for normal embryonic heart development and the onset of heart contractions. Both NCX1 and NCX2 play important roles in the motility of the gastric fundus, ileum and distal colon (Nishiyama et al. 2016). An amphipathic α-helix in the NCX1 large intracellular loop controls NCX1 palmitoylation. Thus, NCX1 palmitoylation is governed by a distal secondary structure element rather than by local primary sequence (Plain et al. 2017).

Accession Number:P32418
Protein Name:Sodium/calcium exchanger 1
Length:973
Molecular Weight:108547.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate Ca2+, Na+

Cross database links:

Genevestigator: P32418
eggNOG: COG0530
DIP: DIP-48356N
Entrez Gene ID: 6546   
Pfam: PF03160    PF01699   
Drugbank: Drugbank Link   
KEGG: hsa:6546   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0015085 F:calcium ion transmembrane transporter activity
GO:0005432 F:calcium:sodium antiporter activity
GO:0046872 F:metal ion binding
GO:0015081 F:sodium ion transmembrane transporter activity
GO:0007596 P:blood coagulation
GO:0007154 P:cell communication
GO:0060401 P:cytosolic calcium ion transport
GO:0006936 P:muscle contraction

References (7)

[1] “Molecular cloning and characterization of the human cardiac Na+/Ca2+ exchanger cDNA.”  Komuro I.et.al.   1374913
[2] “NCX1 Na/Ca exchanger splice variants in pancreatic islet cells.”  Van Eylen F.et.al.   11241183
[3] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[4] “Generation and annotation of the DNA sequences of human chromosomes 2 and 4.”  Hillier L.W.et.al.   15815621
[5] “Na+/Ca2+ exchanger isoforms of rat odontoblasts and osteoblasts.”  Lundquist P.et.al.   10908415
[6] “Functional expression of human renal Na+/Ca2+ exchanger in insect cells.”  Loo T.W.et.al.   8048567
[7] “Expression of the Na-Ca exchanger in diverse tissues: a study using the cloned human cardiac Na-Ca exchanger.”  Kofuji P.et.al.   1476165

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MYNMRRLSLS PTFSMGFHLL VTVSLLFSHV DHVIAETEME GEGNETGECT GSYYCKKGVI 
61:	LPIWEPQDPS FGDKIARATV YFVAMVYMFL GVSIIADRFM SSIEVITSQE KEITIKKPNG 
121:	ETTKTTVRIW NETVSNLTLM ALGSSAPEIL LSVIEVCGHN FTAGDLGPST IVGSAAFNMF 
181:	IIIALCVYVV PDGETRKIKH LRVFFVTAAW SIFAYTWLYI ILSVISPGVV EVWEGLLTFF 
241:	FFPICVVFAW VADRRLLFYK YVYKRYRAGK QRGMIIEHEG DRPSSKTEIE MDGKVVNSHV 
301:	ENFLDGALVL EVDERDQDDE EARREMARIL KELKQKHPDK EIEQLIELAN YQVLSQQQKS 
361:	RAFYRIQATR LMTGAGNILK RHAADQARKA VSMHEVNTEV TENDPVSKIF FEQGTYQCLE 
421:	NCGTVALTII RRGGDLTNTV FVDFRTEDGT ANAGSDYEFT EGTVVFKPGD TQKEIRVGII 
481:	DDDIFEEDEN FLVHLSNVKV SSEASEDGIL EANHVSTLAC LGSPSTATVT IFDDDHAGIF 
541:	TFEEPVTHVS ESIGIMEVKV LRTSGARGNV IVPYKTIEGT ARGGGEDFED TCGELEFQND 
601:	EIVKTISVKV IDDEEYEKNK TFFLEIGEPR LVEMSEKKAL LLNELGGFTI TGKYLFGQPV 
661:	FRKVHAREHP ILSTVITIAD EYDDKQPLTS KEEEERRIAE MGRPILGEHT KLEVIIEESY 
721:	EFKSTVDKLI KKTNLALVVG TNSWREQFIE AITVSAGEDD DDDECGEEKL PSCFDYVMHF 
781:	LTVFWKVLFA FVPPTEYWNG WACFIVSILM IGLLTAFIGD LASHFGCTIG LKDSVTAVVF 
841:	VALGTSVPDT FASKVAATQD QYADASIGNV TGSNAVNVFL GIGVAWSIAA IYHAANGEQF 
901:	KVSPGTLAFS VTLFTIFAFI NVGVLLYRRR PEIGGELGGP RTAKLLTSCL FVLLWLLYIF 
961:	FSSLEAYCHI KGF