RBCC

Full text data of ATP2A3

ATP2A3 [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Sarcoplasmic/endoplasmic reticulum calcium ATPase 3; SERCA3; SR Ca(2+)-ATPase 3; 3.6.3.8 (Calcium pump 3)

Comments
Isoform Q93084-2 was detected.

UniProt Q93084
ID AT2A3_HUMAN Reviewed; 1043 AA.
AC Q93084; A8MZG0; D3DTJ8; O60900; O60901; O75501; O75502; Q16115;
read moreAC Q6JHX1; Q8TEX5; Q8TEX6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 18-OCT-2001, sequence version 2.
DT 22-JAN-2014, entry version 142.
DE RecName: Full=Sarcoplasmic/endoplasmic reticulum calcium ATPase 3;
DE Short=SERCA3;
DE Short=SR Ca(2+)-ATPase 3;
DE EC=3.6.3.8;
DE AltName: Full=Calcium pump 3;
GN Name=ATP2A3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM SERCA3A).
RC TISSUE=Leukemic T-cell;
RX PubMed=8809064;
RA Dode L., Wuytack F., Kools P.F.J., Baba-Aissa F., Raeymaekers L.,
RA Brik F., van de Ven W.J.M., Casteels R.;
RT "cDNA cloning, expression and chromosomal localization of the human
RT sarco/endoplasmic reticulum Ca(2+)-ATPase 3 gene.";
RL Biochem. J. 318:689-699(1996).
RN [2]
RP ERRATUM.
RA Dode L., Wuytack F., Kools P.F.J., Baba-Aissa F., Raeymaekers L.,
RA Brik F., van de Ven W.J.M., Casteels R.;
RL Biochem. J. 319:1008-1008(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS SERCA3B AND SERCA3C).
RX PubMed=9593748; DOI=10.1074/jbc.273.22.13982;
RA Dode L., De Greef C., Mountian I., Attard M., Town M.M., Casteels R.,
RA Wuytack F.;
RT "Structure of the human sarco/endoplasmic reticulum Ca2+-ATPase 3
RT gene. Promoter analysis and alternative splicing of the SERCA3 pre-
RT mRNA.";
RL J. Biol. Chem. 273:13982-13994(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS SERCA3A; SERCA3C AND SERCA3G).
RC TISSUE=Kidney, and Leukemic T-cell;
RX PubMed=9843705;
RA Poch E., Leach S., Snape S., Cacic T., McLennan D.H., Lytton J.;
RT "Functional characterization of alternatively spliced human SERCA3
RT transcripts.";
RL Am. J. Physiol. 275:C1449-C1458(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SERCA3A).
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 1-14, AND ACETYLATION AT MET-1.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [9]
RP PROTEIN SEQUENCE OF 1-33; 111-120; 219-234; 482-489; 516-524; 549-560
RP AND 657-667, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (NOV-2005) to UniProtKB.
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 454-509.
RX PubMed=8288608;
RA Wuytack F., Papp B., Verboomen H., Raeymaekers L., Dode L., Bobe R.,
RA Enouf J., Bokkala S., Authi K.S., Casteels R.;
RT "A sarco/endoplasmic reticulum Ca(2+)-ATPase 3-type Ca2+ pump is
RT expressed in platelets, in lymphoid cells, and in mast cells.";
RL J. Biol. Chem. 269:1410-1416(1994).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 892-1043 (ISOFORMS SERCA3D AND SERCA3E),
RP ALTERNATIVE SPLICING, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11956212; DOI=10.1074/jbc.M202011200;
RA Martin V., Bredoux R., Corvazier E., Van Gorp R., Kovacs T.,
RA Gelebart P., Enouf J.;
RT "Three novel sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 3
RT isoforms. Expression, regulation, and function of the membranes of the
RT SERCA3 family.";
RL J. Biol. Chem. 277:24442-24452(2002).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 892-1043 (ISOFORM SERCA3F), ALTERNATIVE
RP SPLICING, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15028735; DOI=10.1074/jbc.M314286200;
RA Bobe R., Bredoux R., Corvazier E., Andersen J.P., Clausen J.D.,
RA Dode L., Kovacs T., Enouf J.;
RT "Identification, expression, function, and localization of a novel
RT (sixth) isoform of the human sarco/endoplasmic reticulum Ca2+ATPase 3
RT gene.";
RL J. Biol. Chem. 279:24297-24306(2004).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-662, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-674.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: This magnesium-dependent enzyme catalyzes the hydrolysis
CC of ATP coupled with the transport of calcium. Transports calcium
CC ions from the cytosol into the sarcoplasmic/endoplasmic reticulum
CC lumen. Contributes to calcium sequestration involved in muscular
CC excitation/contraction.
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O + Ca(2+)(Side 1) = ADP + phosphate
CC + Ca(2+)(Side 2).
CC -!- SUBCELLULAR LOCATION: Nucleus membrane; Multi-pass membrane
CC protein. Endoplasmic reticulum membrane; Multi-pass membrane
CC protein. Sarcoplasmic reticulum membrane; Multi-pass membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Comment=The same names have been attributed to different
CC isoforms;
CC Name=SERCA3B;
CC IsoId=Q93084-1; Sequence=Displayed;
CC Name=SERCA3A; Synonyms=HuS3-II;
CC IsoId=Q93084-2; Sequence=VSP_000364;
CC Name=SERCA3C; Synonyms=HuS3-IV;
CC IsoId=Q93084-3; Sequence=VSP_000366;
CC Name=SERCA3G; Synonyms=HuS3-I;
CC IsoId=Q93084-4; Sequence=VSP_000365;
CC Name=SERCA3E;
CC IsoId=Q93084-5; Sequence=VSP_000367;
CC Name=SERCA3D;
CC IsoId=Q93084-6; Sequence=VSP_000368;
CC Name=SERCA3F;
CC IsoId=Q93084-7; Sequence=VSP_042296;
CC -!- TISSUE SPECIFICITY: Found in most tissues. Most abundant in
CC thymus, trachea, salivary gland, spleen, bone marrow, lymph node,
CC peripheral leukocytes, pancreas and colon. Also detected in fetal
CC tissues. Expressed in cell lineages of hematopoietic, epithelial,
CC or embryonic origin and also expressed in several cancer cell
CC lines.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type)
CC (TC 3.A.3) family. Type IIA subfamily.
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DR EMBL; Z69881; CAA93737.1; -; mRNA.
DR EMBL; Z69880; CAA93736.1; -; Genomic_DNA.
DR EMBL; Y15724; CAA75739.1; -; Genomic_DNA.
DR EMBL; Y15725; CAA75739.1; JOINED; Genomic_DNA.
DR EMBL; Y15726; CAA75739.1; JOINED; Genomic_DNA.
DR EMBL; Y15727; CAA75739.1; JOINED; Genomic_DNA.
DR EMBL; Y15728; CAA75739.1; JOINED; Genomic_DNA.
DR EMBL; Y15729; CAA75739.1; JOINED; Genomic_DNA.
DR EMBL; Y15730; CAA75739.1; JOINED; Genomic_DNA.
DR EMBL; Y15738; CAA75748.1; -; Genomic_DNA.
DR EMBL; Y15737; CAA75747.1; -; Genomic_DNA.
DR EMBL; AF068220; AAC24525.1; -; mRNA.
DR EMBL; AF068221; AAC24526.1; -; mRNA.
DR EMBL; AC005940; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90468.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90463.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90469.1; -; Genomic_DNA.
DR EMBL; BC035729; AAH35729.1; -; mRNA.
DR EMBL; S68239; AAB29700.1; -; mRNA.
DR EMBL; AF458228; AAL78967.1; -; mRNA.
DR EMBL; AF458229; AAL78968.1; -; mRNA.
DR EMBL; AY460339; AAR15415.1; -; mRNA.
DR PIR; I55399; I55399.
DR PIR; S72267; S72267.
DR RefSeq; NP_005164.2; NM_005173.3.
DR RefSeq; NP_777613.1; NM_174953.2.
DR RefSeq; NP_777614.1; NM_174954.2.
DR RefSeq; NP_777615.1; NM_174955.2.
DR RefSeq; NP_777616.1; NM_174956.2.
DR RefSeq; NP_777617.1; NM_174957.2.
DR RefSeq; NP_777618.1; NM_174958.2.
DR RefSeq; XP_005256715.1; XM_005256658.1.
DR UniGene; Hs.513870; -.
DR ProteinModelPortal; Q93084; -.
DR SMR; Q93084; 1-992.
DR IntAct; Q93084; 6.
DR STRING; 9606.ENSP00000353072; -.
DR PhosphoSite; Q93084; -.
DR DMDM; 19864659; -.
DR PaxDb; Q93084; -.
DR PRIDE; Q93084; -.
DR DNASU; 489; -.
DR Ensembl; ENST00000309890; ENSP00000312577; ENSG00000074370.
DR Ensembl; ENST00000352011; ENSP00000301387; ENSG00000074370.
DR Ensembl; ENST00000359983; ENSP00000353072; ENSG00000074370.
DR Ensembl; ENST00000397035; ENSP00000380229; ENSG00000074370.
DR Ensembl; ENST00000397041; ENSP00000380234; ENSG00000074370.
DR Ensembl; ENST00000397043; ENSP00000380236; ENSG00000074370.
DR Ensembl; ENST00000570845; ENSP00000461480; ENSG00000074370.
DR Ensembl; ENST00000572116; ENSP00000458865; ENSG00000074370.
DR GeneID; 489; -.
DR KEGG; hsa:489; -.
DR UCSC; uc002fxb.2; human.
DR CTD; 489; -.
DR GeneCards; GC17M003822; -.
DR HGNC; HGNC:813; ATP2A3.
DR HPA; CAB010882; -.
DR HPA; HPA007180; -.
DR MIM; 601929; gene.
DR neXtProt; NX_Q93084; -.
DR PharmGKB; PA25106; -.
DR eggNOG; COG0474; -.
DR HOGENOM; HOG000078632; -.
DR HOVERGEN; HBG105648; -.
DR KO; K05853; -.
DR OMA; QQRQACR; -.
DR OrthoDB; EOG73Z2SF; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR Reactome; REACT_604; Hemostasis.
DR GeneWiki; ATP2A3; -.
DR GenomeRNAi; 489; -.
DR NextBio; 2037; -.
DR PRO; PR:Q93084; -.
DR ArrayExpress; Q93084; -.
DR Bgee; Q93084; -.
DR CleanEx; HS_ATP2A3; -.
DR Genevestigator; Q93084; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031095; C:platelet dense tubular network membrane; TAS:Reactome.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005388; F:calcium-transporting ATPase activity; TAS:ProtInc.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR Gene3D; 1.20.1110.10; -; 2.
DR Gene3D; 2.70.150.10; -; 2.
DR Gene3D; 3.40.1110.10; -; 1.
DR InterPro; IPR005782; ATPase_P-typ_Ca-transp_IIA.
DR InterPro; IPR006068; ATPase_P-typ_cation-transptr_C.
DR InterPro; IPR004014; ATPase_P-typ_cation-transptr_N.
DR InterPro; IPR023299; ATPase_P-typ_cyto_domN.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A.
DR InterPro; IPR001757; Cation_transp_P_typ_ATPase.
DR InterPro; IPR023214; HAD-like_dom.
DR Pfam; PF00689; Cation_ATPase_C; 1.
DR Pfam; PF00690; Cation_ATPase_N; 1.
DR Pfam; PF00122; E1-E2_ATPase; 1.
DR Pfam; PF00702; Hydrolase; 1.
DR PRINTS; PR00119; CATATPASE.
DR PRINTS; PR00120; HATPASE.
DR SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR TIGRFAMs; TIGR01116; ATPase-IIA1_Ca; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 2.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Calcium;
KW Calcium transport; Complete proteome; Direct protein sequencing;
KW Endoplasmic reticulum; Hydrolase; Ion transport; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Polymorphism; Reference proteome; Sarcoplasmic reticulum;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1 1043 Sarcoplasmic/endoplasmic reticulum
FT calcium ATPase 3.
FT /FTId=PRO_0000046202.
FT TOPO_DOM 1 48 Cytoplasmic (By similarity).
FT TRANSMEM 49 69 Helical; Name=1; (By similarity).
FT TOPO_DOM 70 89 Lumenal (By similarity).
FT TRANSMEM 90 110 Helical; Name=2; (By similarity).
FT TOPO_DOM 111 253 Cytoplasmic (By similarity).
FT TRANSMEM 254 273 Helical; Name=3; (By similarity).
FT TOPO_DOM 274 295 Lumenal (By similarity).
FT TRANSMEM 296 313 Helical; Name=4; (By similarity).
FT TOPO_DOM 314 757 Cytoplasmic (By similarity).
FT TRANSMEM 758 777 Helical; Name=5; (By similarity).
FT TOPO_DOM 778 787 Lumenal (By similarity).
FT TRANSMEM 788 808 Helical; Name=6; (By similarity).
FT TOPO_DOM 809 828 Cytoplasmic (By similarity).
FT TRANSMEM 829 851 Helical; Name=7; (By similarity).
FT TOPO_DOM 852 897 Lumenal (By similarity).
FT TRANSMEM 898 917 Helical; Name=8; (By similarity).
FT TOPO_DOM 918 930 Cytoplasmic (By similarity).
FT TRANSMEM 931 949 Helical; Name=9; (By similarity).
FT TOPO_DOM 950 964 Lumenal (By similarity).
FT TRANSMEM 965 985 Helical; Name=10; (By similarity).
FT TOPO_DOM 986 1043 Cytoplasmic (By similarity).
FT ACT_SITE 351 351 4-aspartylphosphate intermediate (By
FT similarity).
FT METAL 304 304 Calcium 2; via carbonyl oxygen (By
FT similarity).
FT METAL 305 305 Calcium 2; via carbonyl oxygen (By
FT similarity).
FT METAL 307 307 Calcium 2; via carbonyl oxygen (By
FT similarity).
FT METAL 309 309 Calcium 2 (By similarity).
FT METAL 703 703 Magnesium (By similarity).
FT METAL 707 707 Magnesium (By similarity).
FT METAL 768 768 Calcium 1 (By similarity).
FT METAL 771 771 Calcium 1 (By similarity).
FT METAL 796 796 Calcium 2 (By similarity).
FT METAL 799 799 Calcium 1 (By similarity).
FT METAL 800 800 Calcium 1 (By similarity).
FT METAL 800 800 Calcium 2 (By similarity).
FT METAL 908 908 Calcium 1 (By similarity).
FT BINDING 515 515 ATP (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 662 662 Phosphoserine.
FT VAR_SEQ 994 1043 ACLYPGLLRTVSQAWSRQPLTTSWTPDHTGRNEPEVSAGNR
FT VESPVCTSD -> EEMSQK (in isoform SERCA3A).
FT /FTId=VSP_000364.
FT VAR_SEQ 994 1043 ACLYPGLLRTVSQAWSRQPLTTSWTPDHTGRNEPEVSAGNR
FT VESPVCTSD -> EMSQK (in isoform SERCA3G).
FT /FTId=VSP_000365.
FT VAR_SEQ 994 1022 ACLYPGLLRTVSQAWSRQPLTTSWTPDHT -> GPGTQHRL
FT AVRAAQRGRKQ (in isoform SERCA3F).
FT /FTId=VSP_042296.
FT VAR_SEQ 1024 1043 RNEPEVSAGNRVESPVCTSD -> LASLKK (in
FT isoform SERCA3C).
FT /FTId=VSP_000366.
FT VAR_SEQ 1024 1043 RNEPEVSAGNRVESPVCTSD -> ARDTASSRCQSCSEREE
FT AGKK (in isoform SERCA3D).
FT /FTId=VSP_000368.
FT VAR_SEQ 1024 1043 RNEPEVSAGNRVESPVCTSD -> LASLGQGHSIVSLSELL
FT REGGSREEMSQK (in isoform SERCA3E).
FT /FTId=VSP_000367.
FT VARIANT 674 674 R -> H (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036498.
FT VARIANT 869 869 Q -> H (in dbSNP:rs11654827).
FT /FTId=VAR_048372.
FT CONFLICT 673 673 A -> T (in Ref. 4; AAC24525).
FT CONFLICT 802 802 L -> H (in Ref. 3; CAA75739).
FT CONFLICT 817 817 M -> I (in Ref. 1; CAA93737).
SQ SEQUENCE 1043 AA; 113977 MW; CB6514B36E00E091 CRC64;
MEAAHLLPAA DVLRHFSVTA EGGLSPAQVT GARERYGPNE LPSEEGKSLW ELVLEQFEDL
LVRILLLAAL VSFVLAWFEE GEETTTAFVE PLVIMLILVA NAIVGVWQER NAESAIEALK
EYEPEMGKVI RSDRKGVQRI RARDIVPGDI VEVAVGDKVP ADLRLIEIKS TTLRVDQSIL
TGESVSVTKH TEAIPDPRAV NQDKKNMLFS GTNITSGKAV GVAVATGLHT ELGKIRSQMA
AVEPERTPLQ RKLDEFGRQL SHAISVICVA VWVINIGHFA DPAHGGSWLR GAVYYFKIAV
ALAVAAIPEG LPAVITTCLA LGTRRMARKN AIVRSLPSVE TLGCTSVICS DKTGTLTTNQ
MSVCRMFVVA EADAGSCLLH EFTISGTTYT PEGEVRQGDQ PVRCGQFDGL VELATICALC
NDSALDYNEA KGVYEKVGEA TETALTCLVE KMNVFDTDLQ ALSRVERAGA CNTVIKQLMR
KEFTLEFSRD RKSMSVYCTP TRPHPTGQGS KMFVKGAPES VIERCSSVRV GSRTAPLTPT
SREQILAKIR DWGSGSDTLR CLALATRDAP PRKEDMELDD CSKFVQYETD LTFVGCVGML
DPPRPEVAAC ITRCYQAGIR VVMITGDNKG TAVAICRRLG IFGDTEDVAG KAYTGREFDD
LSPEQQRQAC RTARCFARVE PAHKSRIVEN LQSFNEITAM TGDGVNDAPA LKKAEIGIAM
GSGTAVAKSA AEMVLSDDNF ASIVAAVEEG RAIYSNMKQF IRYLISSNVG EVVCIFLTAI
LGLPEALIPV QLLWVNLVTD GLPATALGFN PPDLDIMEKL PRSPREALIS GWLFFRYLAI
GVYVGLATVA AATWWFVYDA EGPHINFYQL RNFLKCSEDN PLFAGIDCEV FESRFPTTMA
LSVLVTIEMC NALNSVSENQ SLLRMPPWMN PWLLVAVAMS MALHFLILLV PPLPLIFQVT
PLSGRQWVVV LQISLPVILL DEALKYLSRN HMHACLYPGL LRTVSQAWSR QPLTTSWTPD
HTGRNEPEVS AGNRVESPVC TSD
//

MIM 601929
*RECORD*
*FIELD* NO
601929
*FIELD* TI
*601929 ATPase, Ca(2+)-TRANSPORTING, UBIQUITOUS; ATP2A3
;;SARCOPLASMIC RETICULUM Ca(2+)-ATPase 3; SERCA3
read more*FIELD* TX

DESCRIPTION

Sarcoplasmic reticulum Ca(2+)-ATPases (SERCAs), such as ATP2A3, are
membrane-spanning proteins that transport Ca(2+) across membranes
bordering Ca(2+)-sequestering stores, such as the sarcoplasmic or
endoplasmic reticulum (ER). Isoform diversity results by alternative
processing of the primary gene transcripts in a developmentally
modulated or tissue-specific manner.

CLONING

Dode et al. (1996) isolated cDNA and genomic clones of human SERCA3. The
deduced 109,237-Da protein contains 999 amino acids and is 94% similar
to rat SERCA3. Northern blot analysis provided evidence for alternative
processing of the SERCA3 transcript.

By RT-PCR, Santiago-Garcia et al. (1996) found variable expression of
the PMCA (see 108731) and SERCA genes during human fetal heart
development. SERCA3 was expressed at relatively constant levels at all
stages of fetal heart development examined and in adult heart and
placenta.

Poch et al. (1998) cloned 2 SERCA3 splice variants from a kidney cDNA
library and a Jurkat T-cell line cDNA library. The deduced proteins,
which contain 999 and 1,029 amino acids, both have 10 transmembrane
domains but differ at their C termini. They also cloned a third variant
encoding a 998-amino acid protein that differs from the 999-amino acid
protein at 3 amino acids; however, the origin of this variant was
unclear. Northern blot analysis detected a major transcript of about 5
kb expressed at highest levels in thymus, colon, pancreas, and spleen.
Intermediate to low expression was detected in all other tissues
examined. The SERCA3 proteins localized in the nuclear envelope and in
the ER throughout human embryonic kidney and Jurkat T-cell lines.

Dode et al. (1998) identified 3 SERCA3 splice variants that encode
proteins with 999, 1,043, and 1,024 amino acids. The proteins, which the
authors designated SERCA3a, SERCA3b, and SERCA3c, respectively, differ
only in their C termini. Mouse Serca3 is also expressed as 3 variants of
similar size.

By RT-PCR of human platelets, Martin et al. (2002) identified and cloned
2 additional SERCA3 splice variants, which they designated SERCA3d and
SERCA3e. The deduced proteins contain 1,044 and 1,052 amino acids,
respectively, and differ from each other and the previously identified
SERCA3 isoforms only in their C termini. RT-PCR detected all 5 SERCA3
splice variants in platelets, lung, and pancreas. Heart, brain,
placenta, and kidney expressed 3 or 4 splice variants, and skeletal
muscle expressed only 1 variant. Variation was also found in the
expression of SERCA3 variants in established cell lines.

Bobe et al. (2004) identified a sixth SERCA3 variant, which they
designated SERCA3f, that lacks exon 21 but retains exon 22. The deduced
SERCA3f protein contains 1,033-amino acids and differs from the other
SERCA3 isoforms at the C terminus. RT-PCR detected SERCA3f expression in
all tissues and cell lines examined.

GENE FUNCTION

Following isolation of the microsome fraction of transfected human
embryonic kidney cells, Poch et al. (1998) demonstrated that proteins
encoded by 2 SERCA3 splice variants supported Ca(2+) uptake and ATPase
activity.

Martin et al. (2002) found that all 5 SERCA3 isoforms pumped Ca(2+) with
similar affinities, and all pumped Ca(2+) toward the ER. However, the
isoforms modulated cytosolic Ca(2+) concentrations and ER Ca(2+)
concentrations differently. Martin et al. (2002) concluded that the
SERCA3 isoforms have widespread roles in cellular Ca(2+) signaling.

Gelebart et al. (2002) found that expression of SERCA3 was significantly
reduced or lost in colon carcinomas compared with normal colonic
epithelial cells. Treatment of tumor cells with butyrate or other
differentiation inducers resulted in increased SERCA3 expression,
whereas SERCA2 (ATP2A2; 108740) expression was unaltered or was reduced.
SERCA3 expression was increased along with other differentiation markers
during spontaneous post-confluence differentiation of a colon carcinoma
cell line.

Because the SERCA3b and SERCA3f isoforms diverge at the beginning of the
C-terminal domain but share the same last 21 amino acids, Bobe et al.
(2004) investigated the relationship between structure, function, and
location of these isoforms. Immunofluorescence and/or confocal
microscopy showed that SERCA3f and SERCA3b localized in overlapping but
distinct ER locations. By transfection in human embryonic kidney cells,
Bobe et al. (2004) found that SERCA3b and SERCA3f created distinct
resting cytosolic Ca(2+) concentrations and ER Ca(2+) content. SERCA3b
and SERCA3f showed similar sensitivity to a SERCA inhibitor and similar
kinetics of Ca(2+) release and reuptake. They both demonstrated low
apparent Ca(2+) affinity and enhanced rates of dephosphorylation of the
phosphoenzyme intermediate relative to other SERCA Ca(2+) channels.

GENE STRUCTURE

Dode et al. (1998) determined that the ATP2A3 gene contains 22 exons and
spans more than 50 kb. Exon 21 is subject to alternative splicing and
may be included, partially included, or excluded. The promoter region
has no TATA box, but it has 14 putative Sp1 (189906) sites, 11 CACCC
boxes, 5 AP2 (107580)-binding motifs, 3 GGCTGGGG motifs, 3 CANNTG boxes,
a GATA (see 305371) site, and single sites for ETS1 (164720), MYC
(190080), and TFIIIC (see 603246). The authors showed that the GC-rich
region was critical for SERCA3 transcription in Jurkat cells.

Martin et al. (2002) identified a novel exon within what was previously
reported as the last intron of ATP2A3, indicating that the ATP2A3 gene
contains 23 exons.

MAPPING

Dode et al. (1996) assigned the ATP2A3 gene to human chromosome 17p13.3
by fluorescence in situ hybridization.

ANIMAL MODEL

Liu et al. (1997) found that Serca3-null mice were viable, fertile, and
did not exhibit an overt disease phenotype. However, mutant aortic ring
preparations showed diminished acetylcholine-induced intracellular
Ca(2+) signaling and relaxation, with reduced Ca(2+) transient and
nitric oxide production. Their response to other modifiers of vascular
tone was unaltered. Liu et al. (1997) concluded that SERCA3 plays a role
in Ca(2+) signaling mechanisms that mediate endothelium-dependent
relaxation of vascular smooth muscle.

Serca3 expression is restricted to beta cells in mouse pancreas.
Arredouani et al. (2002) found the Serca3 ablation was insufficient in
itself to alter glucose homeostasis or impair insulin secretion in mice.
However, Serca3 ablation altered the reuptake of Ca(2+) into the ER and
increased the insulin response of islets to glucose.

*FIELD* RF
1. Arredouani, A.; Guiot, Y.; Jonas, J.-C.; Liu, L. H.; Nenquin, M.;
Pertusa, J. A.; Rahier, J.; Rolland, J.-F.; Shull, G. E.; Stevens,
M.; Wuytack, F.; Henquin, J.-C.; Gilon, P.: SERCA3 ablation does
not impair insulin secretion but suggests distinct roles for different
sarcoendoplasmic reticulum Ca(2+) pumps for Ca(2+) homeostasis in
pancreatic beta-cells. Diabetes 51: 3245-3253, 2002.

2. Bobe, R.; Bredoux, R.; Corvazier, E.; Andersen, J. P.; Clausen,
J. D.; Dode, L.; Kovacs, T.; Enouf, J.: Identification, expression,
function, and localization of a novel (sixth) isoform of the human
sarco/endoplasmic reticulum Ca(2+) ATPase 3 gene. J. Biol. Chem. 279:
24297-24306, 2004.

3. Dode, L.; De Greef, C.; Mountian, I.; Attard, M.; Town, M. M.;
Casteels, R.; Wuytack, F.: Structure of the human sarco/endoplasmic
reticulum Ca(2+)-ATPase 3 gene: promoter analysis and alternative
splicing of the SERCA3 pre-mRNA. J. Biol. Chem. 273: 13982-13994,
1998.

4. Dode, L.; Wuytack, F.; Kools, P. F. J.; Baba-Aissa, F.; Raeymaekers,
L.; Brike, F.; Van de Ven, W. J. M.; Casteels, R.: cDNA cloning,
expression and chromosomal localization of the human sarco/endoplasmic
reticulum Ca(2+)-ATPase 3 gene. Biochem. J. 318: 689-699, 1996.
Note: Erratum: Biochem. J. 319: 1008 only, 1996.

5. Gelebart, P.; Kovacs, T.; Brouland, J.-P.; van Gorp, R.; Grossmann,
J.; Rivard, N.; Panis, Y.; Martin, V.; Bredoux, R.; Enouf, J.; Papp,
B.: Expression of endomembrane calcium pumps in colon and gastric
cancer cells: induction of SERCA3 expression during differentiation. J.
Biol. Chem. 277: 26310-26320, 2002.

6. Liu, L. H.; Paul, R. J.; Sutliff, R. L.; Miller, M. L.; Lorenz,
J. N.; Pun, R. Y. K.; Duffy, J. J.; Doetschman, T.; Kimura, Y.; MacLennan,
D. H.; Hoying, J. B.; Shull, G. E.: Defective endothelium-dependent
relaxation of vascular smooth muscle and endothelial cell Ca(2+) signaling
in mice lacking sarco(endo)plasmic reticulum Ca(2+)-ATPase isoform
3. J. Biol. Chem. 272: 30538-30545, 1997.

7. Martin, V.; Bredoux, R.; Corvazier, E.; van Gorp, R.; Kovacs, T.;
Gelebart, P.; Enouf, J.: Three novel sarco/endoplasmic reticulum
Ca(2+)-ATPase (SERCA) 3 isoforms: expression, regulation, and function
of the members of the SERCA3 family. J. Biol. Chem. 277: 24442-24452,
2002.

8. Poch, E.; Leach, S.; Snape, S.; Cacic, T.; MacLennan, D. H.; Lytton,
J.: Functional characterization of alternatively spliced human SERCA3
transcripts. Am. J. Physiol. 275: C1449-C1458, 1998.

9. Santiago-Garcia, J.; Mas-Oliva, J.; Saavedra, D.; Zarain-Herzberg,
A.: Analysis of mRNA expression and cloning of a novel plasma membrane
Ca(2+)-ATPase splice variant in human heart. Molec. Cell. Biol. 155:
173-182, 1996.

*FIELD* CN
Patricia A. Hartz - updated: 2/7/2005

*FIELD* CD
Lori M. Kelman: 8/6/1997

*FIELD* ED
alopez: 03/08/2013
terry: 4/5/2005
carol: 2/16/2005
mgross: 2/8/2005
mgross: 2/7/2005
carol: 8/12/1998
dholmes: 10/21/1997
dholmes: 8/12/1997
dholmes: 8/11/1997
joanna: 8/6/1997
dholmes: 8/6/1997

RBCC Red Blood Cell Collection

Full text data of ATP2A3