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P57103 (NAC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium/calcium exchanger 3
Alternative name(s):
Na(+)/Ca(2+)-exchange protein 3
Solute carrier family 8 member 3
Gene names
Name:SLC8A3
Synonyms:NCX3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length927 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Rapidly transports Ca2+ during excitation-contraction coupling. Ca2+ is extruded from the cell during relaxation so as to prevent overloading of intracellular stores By similarity.

Enzyme regulation

By intracellular calcium ions By similarity.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Isoform 2 is expressed in brain and skeletal muscle. Isoform 3 is expressed in excitable cells of brain, retina and skeletal muscle. Isoform 4 is expressed in skeletal muscle. Ref.3

Sequence similarities

Belongs to the sodium/potassium/calcium exchanger family. SLC8 subfamily.

Contains 2 Calx-beta domains.

Ontologies

Keywords
   Biological processAntiport
Calcium transport
Ion transport
Sodium transport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandCalcium
Calmodulin-binding
Sodium
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processblood coagulation

Traceable author statement. Source: Reactome

calcium ion export from cell

Inferred from electronic annotation. Source: Ensembl

calcium ion import into cell

Inferred from electronic annotation. Source: Ensembl

calcium ion transport into cytosol

Inferred from electronic annotation. Source: Ensembl

cell communication

Inferred from electronic annotation. Source: InterPro

cellular response to cAMP

Inferred from electronic annotation. Source: Ensembl

ion transport

Traceable author statement. Source: Reactome

telencephalon development

Inferred from electronic annotation. Source: Ensembl

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentdendritic spine

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

microtubule

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

sarcolemma

Inferred from electronic annotation. Source: Ensembl

   Molecular_functioncalcium:sodium antiporter activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]
Isoform 3 (identifier: P57103-1)

Also known as: NCX3.3;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P57103-2)

Also known as: NCX3.2;

The sequence of this isoform differs from the canonical sequence as follows:
     630-635: Missing.
Isoform 4 (identifier: P57103-3)

Also known as: NCX3.4;

The sequence of this isoform differs from the canonical sequence as follows:
     596-620: KTIRVKIVDEEEYERQENFFIALGE → CDRQEADYGRRGGQEDSRDGKASIG
     621-927: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.
Isoform 5 (identifier: P57103-4)

Also known as: NCX3-tN.1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-643: Missing.
Note: Expressed in fetal brain.
Isoform 6 (identifier: P57103-5)

Also known as: NCX3-tN.2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-623: Missing.
     630-635: Missing.
Note: Expressed in fetal brain.
Isoform 7 (identifier: P57103-6)

The sequence of this isoform differs from the canonical sequence as follows:
     636-638: Missing.
Isoform 8 (identifier: P57103-7)

The sequence of this isoform differs from the canonical sequence as follows:
     599-638: RVKIVDEEEY...SALLLSPDVT → HIKVIDDEAY...SFQKALLLSP

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3030 Potential
Chain31 – 927897Sodium/calcium exchanger 3
PRO_0000019384

Regions

Topological domain31 – 7343Extracellular Potential
Transmembrane74 – 9421Helical; Potential
Topological domain95 – 14753Cytoplasmic Potential
Transmembrane148 – 16821Helical; Potential
Topological domain1691Extracellular Potential
Transmembrane170 – 19021Helical; Potential
Topological domain191 – 20212Cytoplasmic Potential
Transmembrane203 – 22321Helical; Potential
Topological domain224 – 2307Extracellular Potential
Transmembrane231 – 25121Helical; Potential
Topological domain252 – 726475Cytoplasmic Potential
Transmembrane727 – 74721Helical; Potential
Topological domain748 – 7547Extracellular Potential
Transmembrane755 – 77521Helical; Potential
Topological domain776 – 7783Cytoplasmic Potential
Transmembrane779 – 79921Helical; Potential
Topological domain800 – 82829Extracellular Potential
Transmembrane829 – 84921Helical; Potential
Topological domain850 – 86011Cytoplasmic Potential
Transmembrane861 – 88121Helical; Potential
Topological domain882 – 90322Extracellular Potential
Transmembrane904 – 92421Helical; Potential
Topological domain925 – 9273Cytoplasmic Potential
Repeat140 – 18041Alpha-1
Domain386 – 485100Calx-beta 1
Domain519 – 619101Calx-beta 2
Repeat796 – 83237Alpha-2
Region253 – 27220Calmodulin-binding By similarity

Amino acid modifications

Glycosylation451N-linked (GlcNAc...) Potential
Glycosylation8231N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 643643Missing in isoform 5.
VSP_043125
Alternative sequence1 – 623623Missing in isoform 6.
VSP_043126
Alternative sequence596 – 62025KTIRV…IALGE → CDRQEADYGRRGGQEDSRDG KASIG in isoform 4.
VSP_008117
Alternative sequence599 – 63840RVKIV…SPDVT → HIKVIDDEAYEKNKNYFIEM MGPRMVDMSFQKALLLSP in isoform 8.
VSP_044502
Alternative sequence621 – 927307Missing in isoform 4.
VSP_008118
Alternative sequence630 – 6356Missing in isoform 2 and isoform 6.
VSP_008116
Alternative sequence636 – 6383Missing in isoform 7.
VSP_043850
Natural variant6121E → Q in a breast cancer sample; somatic mutation. Ref.8
VAR_036463

Sequences

Sequence LengthMass (Da)Tools
Isoform 3 (NCX3.3) [UniParc].

Last modified August 29, 2003. Version 2.
Checksum: 7B43CB6A9D77615E

FASTA927103,010
        10         20         30         40         50         60 
MAWLRLQPLT SAFLHFGLVT FVLFLNGLRA EAGGSGDVPS TGQNNESCSG SSDCKEGVIL 

        70         80         90        100        110        120 
PIWYPENPSL GDKIARVIVY FVALIYMFLG VSIIADRFMA SIEVITSQER EVTIKKPNGE 

       130        140        150        160        170        180 
TSTTTIRVWN ETVSNLTLMA LGSSAPEILL SLIEVCGHGF IAGDLGPSTI VGSAAFNMFI 

       190        200        210        220        230        240 
IIGICVYVIP DGETRKIKHL RVFFITAAWS IFAYIWLYMI LAVFSPGVVQ VWEGLLTLFF 

       250        260        270        280        290        300 
FPVCVLLAWV ADKRLLFYKY MHKKYRTDKH RGIIIETEGD HPKGIEMDGK MMNSHFLDGN 

       310        320        330        340        350        360 
LVPLEGKEVD ESRREMIRIL KDLKQKHPEK DLDQLVEMAN YYALSHQQKS RAFYRIQATR 

       370        380        390        400        410        420 
MMTGAGNILK KHAAEQAKKA SSMSEVHTDE PEDFISKVFF DPCSYQCLEN CGAVLLTVVR 

       430        440        450        460        470        480 
KGGDMSKTMY VDYKTEDGSA NAGADYEFTE GTVVLKPGET QKEFSVGIID DDIFEEDEHF 

       490        500        510        520        530        540 
FVRLSNVRIE EEQPEEGMPP AIFNSLPLPR AVLASPCVAT VTILDDDHAG IFTFECDTIH 

       550        560        570        580        590        600 
VSESIGVMEV KVLRTSGARG TVIVPFRTVE GTAKGGGEDF EDTYGELEFK NDETVKTIRV 

       610        620        630        640        650        660 
KIVDEEEYER QENFFIALGE PKWMERGISA LLLSPDVTDR KLTMEEEEAK RIAEMGKPVL 

       670        680        690        700        710        720 
GEHPKLEVII EESYEFKTTV DKLIKKTNLA LVVGTHSWRD QFMEAITVSA AGDEDEDESG 

       730        740        750        760        770        780 
EERLPSCFDY VMHFLTVFWK VLFACVPPTE YCHGWACFAV SILIIGMLTA IIGDLASHFG 

       790        800        810        820        830        840 
CTIGLKDSVT AVVFVAFGTS VPDTFASKAA ALQDVYADAS IGNVTGSNAV NVFLGIGLAW 

       850        860        870        880        890        900 
SVAAIYWALQ GQEFHVSAGT LAFSVTLFTI FAFVCISVLL YRRRPHLGGE LGGPRGCKLA 

       910        920 
TTWLFVSLWL LYILFATLEA YCYIKGF 

« Hide

Isoform 2 (NCX3.2) [UniParc].

Checksum: 9E7E932E8EAE13F7
Show »

FASTA921102,415
Isoform 4 (NCX3.4) [UniParc].

Checksum: 0FBEC381D196FD7C
Show »

FASTA62068,947
Isoform 5 (NCX3-tN.1) [UniParc].

Checksum: 14B4A98B3DE17144
Show »

FASTA28431,142
Isoform 6 (NCX3-tN.2) [UniParc].

Checksum: 6B91455189B786D7
Show »

FASTA29832,745
Isoform 7 [UniParc].

Checksum: A0A556B753998A07
Show »

FASTA924102,694
Isoform 8 [UniParc].

Checksum: 0CCF8DA0881C4FDA
Show »

FASTA925102,804

References

« Hide 'large scale' references
[1]"The human SLC8A3 gene and the tissue-specific Na+/Ca2+ exchanger 3 isoforms."
Gabellini N., Bortoluzzi S., Danieli G.A., Carafoli E.
Gene 298:1-7(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 2; 3; 4; 7 AND 8).
[2]"Control of the Na+/Ca2+ exchanger 3 promoter by cyclic adenosine monophosphate and Ca2+ in differentiating neurons."
Gabellini N., Bortoluzzi S., Danieli G.A., Carafoli E.
J. Neurochem. 84:282-293(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3).
[3]"Molecular cloning and characterization of two novel truncated isoforms of human Na+/Ca2+ exchanger 3, expressed in fetal brain."
Lindgren R.M., Zhao J., Heller S., Berglind H., Nister M.
Gene 348:143-155(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 6), TISSUE SPECIFICITY.
Tissue: Brain.
[4]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
[7]"The organization of the human gene of the sodium-calcium exchanger."
Kraev A.S., Chumakov I.M., Carafoli E.
Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-595.
[8]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-612.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF510501 mRNA. Translation: AAN60790.1.
AF510502 mRNA. Translation: AAN60791.1.
AF510503 mRNA. Translation: AAN60792.1.
AF508982 Genomic DNA. Translation: AAM90955.1.
AJ304852 mRNA. Translation: CAC40984.1.
AJ304853 mRNA. Translation: CAC40985.1.
AJ745101 mRNA. Translation: CAG33739.1.
AJ745102 mRNA. Translation: CAG33740.1.
AL135747 Genomic DNA. No translation available.
AL160191 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW81019.1.
CH471061 Genomic DNA. Translation: EAW81021.1.
CH471061 Genomic DNA. Translation: EAW81026.1.
BC142969 mRNA. Translation: AAI42970.1.
X93017 Genomic DNA. No translation available.
RefSeqNP_001123889.1. NM_001130417.2.
NP_150287.1. NM_033262.4.
NP_489479.1. NM_058240.3.
NP_891977.1. NM_182932.2.
NP_891981.1. NM_182936.2.
NP_892114.1. NM_183002.2.
UniGeneHs.337696.

3D structure databases

ProteinModelPortalP57103.
SMRP57103. Positions 395-681, 758-872.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000370669.

Protein family/group databases

TCDB2.A.19.3.3. the ca(2+):cation antiporter (caca) family.

PTM databases

PhosphoSiteP57103.

Polymorphism databases

DMDM34395973.

Proteomic databases

PaxDbP57103.
PRIDEP57103.

Protocols and materials databases

DNASU6547.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000216568; ENSP00000216568; ENSG00000100678. [P57103-5]
ENST00000356921; ENSP00000349392; ENSG00000100678. [P57103-2]
ENST00000357887; ENSP00000350560; ENSG00000100678. [P57103-7]
ENST00000381269; ENSP00000370669; ENSG00000100678. [P57103-1]
ENST00000394330; ENSP00000377863; ENSG00000100678. [P57103-4]
ENST00000494208; ENSP00000436332; ENSG00000100678. [P57103-3]
ENST00000528359; ENSP00000433531; ENSG00000100678. [P57103-7]
ENST00000534137; ENSP00000436688; ENSG00000100678. [P57103-6]
GeneID6547.
KEGGhsa:6547.
UCSCuc001xlu.3. human. [P57103-4]
uc001xlv.3. human. [P57103-5]
uc001xlw.3. human. [P57103-6]
uc001xlx.3. human. [P57103-7]
uc001xly.3. human. [P57103-1]
uc001xlz.3. human. [P57103-2]

Organism-specific databases

CTD6547.
GeneCardsGC14M070510.
HGNCHGNC:11070. SLC8A3.
HPAHPA001669.
MIM607991. gene.
neXtProtNX_P57103.
PharmGKBPA315.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG241889.
HOGENOMHOG000266971.
HOVERGENHBG006441.
InParanoidP57103.
KOK05849.
OMACGHGFIA.
OrthoDBEOG7S4X56.
PhylomeDBP57103.
TreeFamTF314308.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressP57103.
BgeeP57103.
CleanExHS_SLC8A3.
GenevestigatorP57103.

Family and domain databases

InterProIPR003644. Calx_beta.
IPR004836. Na_Ca_Ex.
IPR004837. NaCa_Exmemb.
[Graphical view]
PfamPF03160. Calx-beta. 2 hits.
PF01699. Na_Ca_ex. 2 hits.
[Graphical view]
PRINTSPR01259. NACAEXCHNGR.
SMARTSM00237. Calx_beta. 2 hits.
[Graphical view]
TIGRFAMsTIGR00845. caca. 1 hit.
ProtoNetSearch...

Other

ChiTaRSSLC8A3. human.
GenomeRNAi6547.
NextBio25473.
PROP57103.
SOURCESearch...

Entry information

Entry nameNAC3_HUMAN
AccessionPrimary (citable) accession number: P57103
Secondary accession number(s): Q5K3P6 expand/collapse secondary AC list , Q5K3P7, Q8IUE9, Q8IUF0, Q8NFI7, Q96QG1, Q96QG2
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: August 29, 2003
Last modified: April 16, 2014
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM