Full text data of ATP2B1
ATP2B1
(PMCA1)
[Confidence: high (present in two of the MS resources)]
Plasma membrane calcium-transporting ATPase 1; PMCA1; 3.6.3.8 (Plasma membrane calcium ATPase isoform 1; Plasma membrane calcium pump isoform 1)
Plasma membrane calcium-transporting ATPase 1; PMCA1; 3.6.3.8 (Plasma membrane calcium ATPase isoform 1; Plasma membrane calcium pump isoform 1)
hRBCD
IPI00021695
IPI00021695 Splice isoform B of P20020 Plasma membrane calcium-transporting ATPase 1 Splice isoform B of P20020 Plasma membrane calcium-transporting ATPase 1 membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 3 8 n/a n/a n/a 3 n/a n/a integral membrane protein different splice isoforms found at its expected molecular weight found at molecular weight
IPI00021695 Splice isoform B of P20020 Plasma membrane calcium-transporting ATPase 1 Splice isoform B of P20020 Plasma membrane calcium-transporting ATPase 1 membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 3 8 n/a n/a n/a 3 n/a n/a integral membrane protein different splice isoforms found at its expected molecular weight found at molecular weight
Comments
Isoform P20020-3 was detected.
Isoform P20020-3 was detected.
UniProt
P20020
ID AT2B1_HUMAN Reviewed; 1258 AA.
AC P20020; Q12992; Q12993; Q13819; Q13820; Q13821; Q16504; Q93082;
read moreDT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 3.
DT 22-JAN-2014, entry version 153.
DE RecName: Full=Plasma membrane calcium-transporting ATPase 1;
DE Short=PMCA1;
DE EC=3.6.3.8;
DE AltName: Full=Plasma membrane calcium ATPase isoform 1;
DE AltName: Full=Plasma membrane calcium pump isoform 1;
GN Name=ATP2B1; Synonyms=PMCA1;
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 [MRNA] (ISOFORM B).
RC TISSUE=Erythrocyte;
RX PubMed=2844759;
RA Verma A.K., Filoteo A.G., Stanford D.R., Wieben E.D., Penniston J.T.,
RA Strehler E.E., Fischer R., Heim R., Vogel G., Mathews S.,
RA Strehler-Page M.-A., James P., Vorherr T.E., Krebs J., Carafoli E.;
RT "Complete primary structure of a human plasma membrane Ca2+ pump.";
RL J. Biol. Chem. 263:14152-14159(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RC TISSUE=Osteoblast;
RX PubMed=8386431;
RA Kumar R., Haugen J.D., Penniston J.T.;
RT "Molecular cloning of a plasma membrane calcium pump from human
RT osteoblasts.";
RL J. Bone Miner. Res. 8:505-513(1993).
RN [3]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A AND B).
RC TISSUE=Leukocyte;
RX PubMed=8396145;
RA Hilfiker H., Strehler-Page M.-A., Stauffer T.P., Carafoli E.,
RA Strehler E.E.;
RT "Structure of the gene encoding the human plasma membrane calcium pump
RT isoform 1.";
RL J. Biol. Chem. 268:19717-19725(1993).
RN [4]
RP SEQUENCE REVISION.
RA Strehler E.E., Strehler-Page M.-A.;
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A; C AND D).
RC TISSUE=Fetal skeletal muscle;
RX PubMed=2528729; DOI=10.1073/pnas.86.18.6908;
RA Strehler E.E., Strehler-Page M.-A., Vogel G., Carafoli E.;
RT "mRNAs for plasma membrane calcium pump isoforms differing in their
RT regulatory domain are generated by alternative splicing that involves
RT two internal donor sites in a single exon.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:6908-6912(1989).
RN [6]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC TISSUE=Fetal brain;
RX PubMed=1332771; DOI=10.1021/bi00162a016;
RA Kessler F., Falchetto R., Heim R., Meili R., Vorherr T.E.,
RA Strehler E.E., Carafoli E.;
RT "Study of calmodulin binding to the alternatively spliced C-terminal
RT domain of the plasma membrane Ca2+ pump.";
RL Biochemistry 31:11785-11792(1992).
RN [7]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND E).
RC TISSUE=Brain cortex;
RX PubMed=8245032;
RA Stauffer T.P., Hilfiker H., Carafoli E., Strehler E.E.;
RT "Quantitative analysis of alternative splicing options of human plasma
RT membrane calcium pump genes.";
RL J. Biol. Chem. 268:25993-26003(1993).
RN [8]
RP ERRATUM.
RX PubMed=7989379;
RA Stauffer T.P., Hilfiker H., Carafoli E., Strehler E.E.;
RL J. Biol. Chem. 269:32022-32022(1994).
RN [9]
RP ALTERNATIVE SPLICING (ISOFORM K).
RC TISSUE=Small intestine mucosa;
RX PubMed=7694502;
RA Howard A., Legon S., Walters J.R.;
RT "Human and rat intestinal plasma membrane calcium pump isoforms.";
RL Am. J. Physiol. 265:G917-G925(1993).
RN [10]
RP PHOSPHORYLATION BY CAMP KINASE.
RX PubMed=2548572; DOI=10.1021/bi00436a020;
RA James P.H., Pruschy M., Vorherr T.E., Penniston J.T., Carafoli E.;
RT "Primary structure of the cAMP-dependent phosphorylation site of the
RT plasma membrane calcium pump.";
RL Biochemistry 28:4253-4258(1989).
RN [11]
RP PHOSPHORYLATION BY PROTEIN KINASE C.
RX PubMed=1827443;
RA Wang K.K.W., Wright L.C., Machan C.L., Allen B.G., Conigrave A.D.,
RA Roufogalis B.D.;
RT "Protein kinase C phosphorylates the carboxyl terminus of the plasma
RT membrane Ca(2+)-ATPase from human erythrocytes.";
RL J. Biol. Chem. 266:9078-9085(1991).
RN [12]
RP INTERACTION WITH PDZD11.
RX PubMed=12763866;
RA Goellner G.M., DeMarco S.J., Strehler E.E.;
RT "Characterization of PISP, a novel single-PDZ protein that binds to
RT all plasma membrane Ca2+-ATPase b-splice variants.";
RL Ann. N. Y. Acad. Sci. 986:461-471(2003).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1193 AND SER-1220, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17; SER-1193; THR-1203;
RP SER-1216; SER-1220; SER-1246; SER-1249; SER-1253 AND SER-1257, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT GLY-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-1193 AND THR-1203, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1193; SER-1216 AND
RP SER-1220, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP VARIANT ARG-267.
RX PubMed=9020386; DOI=10.1007/s001090050088;
RA Benkwitz C., Kubsisch C., Kraft K., Neyses L.;
RT "Investigation of the Met-267 Arg exchange in isoform 1 of the human
RT plasma membrane calcium pump in patients with essential hypertension
RT by the amplification-created restriction site technique.";
RL J. Mol. Med. 75:62-66(1997).
CC -!- FUNCTION: This magnesium-dependent enzyme catalyzes the hydrolysis
CC of ATP coupled with the transport of calcium out of the cell.
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O + Ca(2+)(Side 1) = ADP + phosphate
CC + Ca(2+)(Side 2).
CC -!- SUBUNIT: Interacts with PDZD11.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=D; Synonyms=CIV;
CC IsoId=P20020-1; Sequence=Displayed;
CC Name=A; Synonyms=CII;
CC IsoId=P20020-2; Sequence=VSP_000375;
CC Name=B; Synonyms=CI;
CC IsoId=P20020-3; Sequence=VSP_000373;
CC Name=C; Synonyms=CIII;
CC IsoId=P20020-4; Sequence=VSP_000374;
CC Name=E; Synonyms=CV;
CC IsoId=P20020-5; Sequence=VSP_000376;
CC Name=K;
CC IsoId=P20020-6; Sequence=VSP_000372, VSP_000373;
CC -!- TISSUE SPECIFICITY: Isoform B is ubiquitously expressed. Isoform C
CC is found in brain cortex, skeletal muscle and heart muscle.
CC Isoform D has only been found in fetal skeletal muscle. Isoform K
CC has been found in small intestine and liver.
CC -!- DOMAIN: The calmodulin-binding subdomain B is different in the
CC different splice variants and shows pH dependent calmodulin
CC binding properties in isoforms A, C, D and E.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type)
CC (TC 3.A.3) family. Type IIB subfamily.
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DR EMBL; J04027; AAA74511.1; -; mRNA.
DR EMBL; M95541; AAA35999.1; -; mRNA.
DR EMBL; M95542; AAA36000.1; -; mRNA.
DR EMBL; L14561; AAD09924.1; -; Genomic_DNA.
DR EMBL; L14561; AAD09925.1; -; Genomic_DNA.
DR EMBL; M25824; AAA58383.1; -; Genomic_DNA.
DR EMBL; M25824; AAA58382.1; -; Genomic_DNA.
DR EMBL; M25824; AAA58381.1; -; Genomic_DNA.
DR EMBL; S49852; AAB24324.1; -; mRNA.
DR EMBL; U15686; AAA60983.1; -; mRNA.
DR EMBL; U15687; AAA60984.1; -; mRNA.
DR PIR; A30802; A30802.
DR PIR; E49570; E49570.
DR PIR; I55491; I55491.
DR PIR; I70165; I70165.
DR RefSeq; NP_001001323.1; NM_001001323.1.
DR RefSeq; NP_001673.2; NM_001682.2.
DR RefSeq; XP_005268975.1; XM_005268918.1.
DR RefSeq; XP_005268976.1; XM_005268919.1.
DR RefSeq; XP_005268977.1; XM_005268920.1.
DR RefSeq; XP_005268978.1; XM_005268921.1.
DR UniGene; Hs.506276; -.
DR ProteinModelPortal; P20020; -.
DR SMR; P20020; 66-946, 1100-1126.
DR IntAct; P20020; 4.
DR MINT; MINT-5004114; -.
DR STRING; 9606.ENSP00000261173; -.
DR TCDB; 3.A.3.2.25; the p-type atpase (p-atpase) superfamily.
DR PhosphoSite; P20020; -.
DR DMDM; 14286104; -.
DR PaxDb; P20020; -.
DR PRIDE; P20020; -.
DR Ensembl; ENST00000261173; ENSP00000261173; ENSG00000070961.
DR Ensembl; ENST00000348959; ENSP00000343599; ENSG00000070961.
DR Ensembl; ENST00000359142; ENSP00000352054; ENSG00000070961.
DR Ensembl; ENST00000428670; ENSP00000392043; ENSG00000070961.
DR GeneID; 490; -.
DR KEGG; hsa:490; -.
DR CTD; 490; -.
DR GeneCards; GC12M089981; -.
DR HGNC; HGNC:814; ATP2B1.
DR HPA; CAB005605; -.
DR HPA; HPA011166; -.
DR HPA; HPA012945; -.
DR MIM; 108731; gene.
DR neXtProt; NX_P20020; -.
DR PharmGKB; PA25107; -.
DR eggNOG; COG0474; -.
DR HOVERGEN; HBG061286; -.
DR KO; K05850; -.
DR OMA; SESVMND; -.
DR OrthoDB; EOG7SN8BN; -.
DR PhylomeDB; P20020; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR Reactome; REACT_604; Hemostasis.
DR GeneWiki; ATP2B1; -.
DR GenomeRNAi; 490; -.
DR NextBio; 2053; -.
DR PRO; PR:P20020; -.
DR ArrayExpress; P20020; -.
DR Bgee; P20020; -.
DR CleanEx; HS_ATP2B1; -.
DR Genevestigator; P20020; -.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
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; -; 1.
DR Gene3D; 2.70.150.10; -; 2.
DR Gene3D; 3.40.1110.10; -; 1.
DR InterPro; IPR022141; ATP_Ca_trans_C.
DR InterPro; IPR006408; ATPase_P-typ_Ca-transp_plasma.
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; PF12424; ATP_Ca_trans_C; 2.
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 SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 2.
DR SUPFAM; SSF81660; SSF81660; 1.
DR TIGRFAMs; TIGR01517; ATPase-IIB_Ca; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 3.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Calcium;
KW Calcium transport; Calmodulin-binding; Cell membrane;
KW Complete proteome; Hydrolase; Ion transport; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 1258 Plasma membrane calcium-transporting
FT ATPase 1.
FT /FTId=PRO_0000046209.
FT TOPO_DOM 2 97 Cytoplasmic (Potential).
FT TRANSMEM 98 118 Helical; (Potential).
FT TOPO_DOM 119 154 Extracellular (Potential).
FT TRANSMEM 155 175 Helical; (Potential).
FT TOPO_DOM 176 366 Cytoplasmic (Potential).
FT TRANSMEM 367 386 Helical; (Potential).
FT TOPO_DOM 387 419 Extracellular (Potential).
FT TRANSMEM 420 437 Helical; (Potential).
FT TOPO_DOM 438 852 Cytoplasmic (Potential).
FT TRANSMEM 853 872 Helical; (Potential).
FT TOPO_DOM 873 882 Extracellular (Potential).
FT TRANSMEM 883 903 Helical; (Potential).
FT TOPO_DOM 904 923 Cytoplasmic (Potential).
FT TRANSMEM 924 946 Helical; (Potential).
FT TOPO_DOM 947 964 Extracellular (Potential).
FT TRANSMEM 965 986 Helical; (Potential).
FT TOPO_DOM 987 1005 Cytoplasmic (Potential).
FT TRANSMEM 1006 1027 Helical; (Potential).
FT TOPO_DOM 1028 1037 Extracellular (Potential).
FT TRANSMEM 1038 1059 Helical; (Potential).
FT TOPO_DOM 1060 1258 Cytoplasmic (Potential).
FT REGION 1100 1117 Calmodulin-binding subdomain A.
FT REGION 1118 1127 Calmodulin-binding subdomain B.
FT COMPBIAS 296 299 Poly-Glu.
FT ACT_SITE 475 475 4-aspartylphosphate intermediate.
FT METAL 797 797 Magnesium (By similarity).
FT METAL 801 801 Magnesium (By similarity).
FT MOD_RES 2 2 N-acetylglycine.
FT MOD_RES 17 17 Phosphoserine.
FT MOD_RES 1116 1116 Phosphothreonine; by PKC.
FT MOD_RES 1193 1193 Phosphoserine.
FT MOD_RES 1203 1203 Phosphothreonine.
FT MOD_RES 1216 1216 Phosphoserine; by PKA.
FT MOD_RES 1220 1220 Phosphoserine.
FT MOD_RES 1246 1246 Phosphoserine.
FT MOD_RES 1249 1249 Phosphoserine.
FT MOD_RES 1253 1253 Phosphoserine.
FT MOD_RES 1257 1257 Phosphoserine.
FT VAR_SEQ 1021 1056 Missing (in isoform K).
FT /FTId=VSP_000372.
FT VAR_SEQ 1118 1155 Missing (in isoform B and isoform K).
FT /FTId=VSP_000373.
FT VAR_SEQ 1147 1155 Missing (in isoform C).
FT /FTId=VSP_000374.
FT VAR_SEQ 1156 1258 IRVVNAFRSSLYEGLEKPESRSSIHNFMTHPEFRIEDSEPH
FT IPLIDDTDAEDDAPTKRNSSPPPSPNKNNNAVDSGIHLTIE
FT MNKSATSSSPGSPLHSLETSL -> VVFSSSTASTTVGYSS
FT GECIS (in isoform A).
FT /FTId=VSP_000375.
FT VAR_SEQ 1156 1258 IRVVNAFRSSLYEGLEKPESRSSIHNFMTHPEFRIEDSEPH
FT IPLIDDTDAEDDAPTKRNSSPPPSPNKNNNAVDSGIHLTIE
FT MNKSATSSSPGSPLHSLETSL -> VVFSSSTASTTVGFEW
FT (in isoform E).
FT /FTId=VSP_000376.
FT VARIANT 267 267 M -> R (rare polymorphism).
FT /FTId=VAR_000698.
FT CONFLICT 259 262 LLLS -> MSAT (in Ref. 2; AAA36000).
SQ SEQUENCE 1258 AA; 138755 MW; 7037112747FC9B0A CRC64;
MGDMANNSVA YSGVKNSLKE ANHDGDFGIT LAELRALMEL RSTDALRKIQ ESYGDVYGIC
TKLKTSPNEG LSGNPADLER REAVFGKNFI PPKKPKTFLQ LVWEALQDVT LIILEIAAIV
SLGLSFYQPP EGDNALCGEV SVGEEEGEGE TGWIEGAAIL LSVVCVVLVT AFNDWSKEKQ
FRGLQSRIEQ EQKFTVIRGG QVIQIPVADI TVGDIAQVKY GDLLPADGIL IQGNDLKIDE
SSLTGESDHV KKSLDKDPLL LSGTHVMEGS GRMVVTAVGV NSQTGIIFTL LGAGGEEEEK
KDEKKKEKKN KKQDGAIENR NKAKAQDGAA MEMQPLKSEE GGDGDEKDKK KANLPKKEKS
VLQGKLTKLA VQIGKAGLLM SAITVIILVL YFVIDTFWVQ KRPWLAECTP IYIQYFVKFF
IIGVTVLVVA VPEGLPLAVT ISLAYSVKKM MKDNNLVRHL DACETMGNAT AICSDKTGTL
TMNRMTVVQA YINEKHYKKV PEPEAIPPNI LSYLVTGISV NCAYTSKILP PEKEGGLPRH
VGNKTECALL GLLLDLKRDY QDVRNEIPEE ALYKVYTFNS VRKSMSTVLK NSDGSYRIFS
KGASEIILKK CFKILSANGE AKVFRPRDRD DIVKTVIEPM ASEGLRTICL AFRDFPAGEP
EPEWDNENDI VTGLTCIAVV GIEDPVRPEV PDAIKKCQRA GITVRMVTGD NINTARAIAT
KCGILHPGED FLCLEGKDFN RRIRNEKGEI EQERIDKIWP KLRVLARSSP TDKHTLVKGI
IDSTVSDQRQ VVAVTGDGTN DGPALKKADV GFAMGIAGTD VAKEASDIIL TDDNFTSIVK
AVMWGRNVYD SISKFLQFQL TVNVVAVIVA FTGACITQDS PLKAVQMLWV NLIMDTLASL
ALATEPPTES LLLRKPYGRN KPLISRTMMK NILGHAFYQL VVVFTLLFAG EKFFDIDSGR
NAPLHAPPSE HYTIVFNTFV LMQLFNEINA RKIHGERNVF EGIFNNAIFC TIVLGTFVVQ
IIIVQFGGKP FSCSELSIEQ WLWSIFLGMG TLLWGQLIST IPTSRLKFLK EAGHGTQKEE
IPEEELAEDV EEIDHAEREL RRGQILWFRG LNRIQTQMDV VNAFQSGSSI QGALRRQPSI
ASQHHDVTNI STPTHIRVVN AFRSSLYEGL EKPESRSSIH NFMTHPEFRI EDSEPHIPLI
DDTDAEDDAP TKRNSSPPPS PNKNNNAVDS GIHLTIEMNK SATSSSPGSP LHSLETSL
//
ID AT2B1_HUMAN Reviewed; 1258 AA.
AC P20020; Q12992; Q12993; Q13819; Q13820; Q13821; Q16504; Q93082;
read moreDT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 3.
DT 22-JAN-2014, entry version 153.
DE RecName: Full=Plasma membrane calcium-transporting ATPase 1;
DE Short=PMCA1;
DE EC=3.6.3.8;
DE AltName: Full=Plasma membrane calcium ATPase isoform 1;
DE AltName: Full=Plasma membrane calcium pump isoform 1;
GN Name=ATP2B1; Synonyms=PMCA1;
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 [MRNA] (ISOFORM B).
RC TISSUE=Erythrocyte;
RX PubMed=2844759;
RA Verma A.K., Filoteo A.G., Stanford D.R., Wieben E.D., Penniston J.T.,
RA Strehler E.E., Fischer R., Heim R., Vogel G., Mathews S.,
RA Strehler-Page M.-A., James P., Vorherr T.E., Krebs J., Carafoli E.;
RT "Complete primary structure of a human plasma membrane Ca2+ pump.";
RL J. Biol. Chem. 263:14152-14159(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RC TISSUE=Osteoblast;
RX PubMed=8386431;
RA Kumar R., Haugen J.D., Penniston J.T.;
RT "Molecular cloning of a plasma membrane calcium pump from human
RT osteoblasts.";
RL J. Bone Miner. Res. 8:505-513(1993).
RN [3]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A AND B).
RC TISSUE=Leukocyte;
RX PubMed=8396145;
RA Hilfiker H., Strehler-Page M.-A., Stauffer T.P., Carafoli E.,
RA Strehler E.E.;
RT "Structure of the gene encoding the human plasma membrane calcium pump
RT isoform 1.";
RL J. Biol. Chem. 268:19717-19725(1993).
RN [4]
RP SEQUENCE REVISION.
RA Strehler E.E., Strehler-Page M.-A.;
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A; C AND D).
RC TISSUE=Fetal skeletal muscle;
RX PubMed=2528729; DOI=10.1073/pnas.86.18.6908;
RA Strehler E.E., Strehler-Page M.-A., Vogel G., Carafoli E.;
RT "mRNAs for plasma membrane calcium pump isoforms differing in their
RT regulatory domain are generated by alternative splicing that involves
RT two internal donor sites in a single exon.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:6908-6912(1989).
RN [6]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC TISSUE=Fetal brain;
RX PubMed=1332771; DOI=10.1021/bi00162a016;
RA Kessler F., Falchetto R., Heim R., Meili R., Vorherr T.E.,
RA Strehler E.E., Carafoli E.;
RT "Study of calmodulin binding to the alternatively spliced C-terminal
RT domain of the plasma membrane Ca2+ pump.";
RL Biochemistry 31:11785-11792(1992).
RN [7]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND E).
RC TISSUE=Brain cortex;
RX PubMed=8245032;
RA Stauffer T.P., Hilfiker H., Carafoli E., Strehler E.E.;
RT "Quantitative analysis of alternative splicing options of human plasma
RT membrane calcium pump genes.";
RL J. Biol. Chem. 268:25993-26003(1993).
RN [8]
RP ERRATUM.
RX PubMed=7989379;
RA Stauffer T.P., Hilfiker H., Carafoli E., Strehler E.E.;
RL J. Biol. Chem. 269:32022-32022(1994).
RN [9]
RP ALTERNATIVE SPLICING (ISOFORM K).
RC TISSUE=Small intestine mucosa;
RX PubMed=7694502;
RA Howard A., Legon S., Walters J.R.;
RT "Human and rat intestinal plasma membrane calcium pump isoforms.";
RL Am. J. Physiol. 265:G917-G925(1993).
RN [10]
RP PHOSPHORYLATION BY CAMP KINASE.
RX PubMed=2548572; DOI=10.1021/bi00436a020;
RA James P.H., Pruschy M., Vorherr T.E., Penniston J.T., Carafoli E.;
RT "Primary structure of the cAMP-dependent phosphorylation site of the
RT plasma membrane calcium pump.";
RL Biochemistry 28:4253-4258(1989).
RN [11]
RP PHOSPHORYLATION BY PROTEIN KINASE C.
RX PubMed=1827443;
RA Wang K.K.W., Wright L.C., Machan C.L., Allen B.G., Conigrave A.D.,
RA Roufogalis B.D.;
RT "Protein kinase C phosphorylates the carboxyl terminus of the plasma
RT membrane Ca(2+)-ATPase from human erythrocytes.";
RL J. Biol. Chem. 266:9078-9085(1991).
RN [12]
RP INTERACTION WITH PDZD11.
RX PubMed=12763866;
RA Goellner G.M., DeMarco S.J., Strehler E.E.;
RT "Characterization of PISP, a novel single-PDZ protein that binds to
RT all plasma membrane Ca2+-ATPase b-splice variants.";
RL Ann. N. Y. Acad. Sci. 986:461-471(2003).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1193 AND SER-1220, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17; SER-1193; THR-1203;
RP SER-1216; SER-1220; SER-1246; SER-1249; SER-1253 AND SER-1257, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT GLY-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-1193 AND THR-1203, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1193; SER-1216 AND
RP SER-1220, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP VARIANT ARG-267.
RX PubMed=9020386; DOI=10.1007/s001090050088;
RA Benkwitz C., Kubsisch C., Kraft K., Neyses L.;
RT "Investigation of the Met-267 Arg exchange in isoform 1 of the human
RT plasma membrane calcium pump in patients with essential hypertension
RT by the amplification-created restriction site technique.";
RL J. Mol. Med. 75:62-66(1997).
CC -!- FUNCTION: This magnesium-dependent enzyme catalyzes the hydrolysis
CC of ATP coupled with the transport of calcium out of the cell.
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O + Ca(2+)(Side 1) = ADP + phosphate
CC + Ca(2+)(Side 2).
CC -!- SUBUNIT: Interacts with PDZD11.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=D; Synonyms=CIV;
CC IsoId=P20020-1; Sequence=Displayed;
CC Name=A; Synonyms=CII;
CC IsoId=P20020-2; Sequence=VSP_000375;
CC Name=B; Synonyms=CI;
CC IsoId=P20020-3; Sequence=VSP_000373;
CC Name=C; Synonyms=CIII;
CC IsoId=P20020-4; Sequence=VSP_000374;
CC Name=E; Synonyms=CV;
CC IsoId=P20020-5; Sequence=VSP_000376;
CC Name=K;
CC IsoId=P20020-6; Sequence=VSP_000372, VSP_000373;
CC -!- TISSUE SPECIFICITY: Isoform B is ubiquitously expressed. Isoform C
CC is found in brain cortex, skeletal muscle and heart muscle.
CC Isoform D has only been found in fetal skeletal muscle. Isoform K
CC has been found in small intestine and liver.
CC -!- DOMAIN: The calmodulin-binding subdomain B is different in the
CC different splice variants and shows pH dependent calmodulin
CC binding properties in isoforms A, C, D and E.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type)
CC (TC 3.A.3) family. Type IIB subfamily.
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DR EMBL; J04027; AAA74511.1; -; mRNA.
DR EMBL; M95541; AAA35999.1; -; mRNA.
DR EMBL; M95542; AAA36000.1; -; mRNA.
DR EMBL; L14561; AAD09924.1; -; Genomic_DNA.
DR EMBL; L14561; AAD09925.1; -; Genomic_DNA.
DR EMBL; M25824; AAA58383.1; -; Genomic_DNA.
DR EMBL; M25824; AAA58382.1; -; Genomic_DNA.
DR EMBL; M25824; AAA58381.1; -; Genomic_DNA.
DR EMBL; S49852; AAB24324.1; -; mRNA.
DR EMBL; U15686; AAA60983.1; -; mRNA.
DR EMBL; U15687; AAA60984.1; -; mRNA.
DR PIR; A30802; A30802.
DR PIR; E49570; E49570.
DR PIR; I55491; I55491.
DR PIR; I70165; I70165.
DR RefSeq; NP_001001323.1; NM_001001323.1.
DR RefSeq; NP_001673.2; NM_001682.2.
DR RefSeq; XP_005268975.1; XM_005268918.1.
DR RefSeq; XP_005268976.1; XM_005268919.1.
DR RefSeq; XP_005268977.1; XM_005268920.1.
DR RefSeq; XP_005268978.1; XM_005268921.1.
DR UniGene; Hs.506276; -.
DR ProteinModelPortal; P20020; -.
DR SMR; P20020; 66-946, 1100-1126.
DR IntAct; P20020; 4.
DR MINT; MINT-5004114; -.
DR STRING; 9606.ENSP00000261173; -.
DR TCDB; 3.A.3.2.25; the p-type atpase (p-atpase) superfamily.
DR PhosphoSite; P20020; -.
DR DMDM; 14286104; -.
DR PaxDb; P20020; -.
DR PRIDE; P20020; -.
DR Ensembl; ENST00000261173; ENSP00000261173; ENSG00000070961.
DR Ensembl; ENST00000348959; ENSP00000343599; ENSG00000070961.
DR Ensembl; ENST00000359142; ENSP00000352054; ENSG00000070961.
DR Ensembl; ENST00000428670; ENSP00000392043; ENSG00000070961.
DR GeneID; 490; -.
DR KEGG; hsa:490; -.
DR CTD; 490; -.
DR GeneCards; GC12M089981; -.
DR HGNC; HGNC:814; ATP2B1.
DR HPA; CAB005605; -.
DR HPA; HPA011166; -.
DR HPA; HPA012945; -.
DR MIM; 108731; gene.
DR neXtProt; NX_P20020; -.
DR PharmGKB; PA25107; -.
DR eggNOG; COG0474; -.
DR HOVERGEN; HBG061286; -.
DR KO; K05850; -.
DR OMA; SESVMND; -.
DR OrthoDB; EOG7SN8BN; -.
DR PhylomeDB; P20020; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR Reactome; REACT_604; Hemostasis.
DR GeneWiki; ATP2B1; -.
DR GenomeRNAi; 490; -.
DR NextBio; 2053; -.
DR PRO; PR:P20020; -.
DR ArrayExpress; P20020; -.
DR Bgee; P20020; -.
DR CleanEx; HS_ATP2B1; -.
DR Genevestigator; P20020; -.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
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; -; 1.
DR Gene3D; 2.70.150.10; -; 2.
DR Gene3D; 3.40.1110.10; -; 1.
DR InterPro; IPR022141; ATP_Ca_trans_C.
DR InterPro; IPR006408; ATPase_P-typ_Ca-transp_plasma.
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; PF12424; ATP_Ca_trans_C; 2.
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 SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 2.
DR SUPFAM; SSF81660; SSF81660; 1.
DR TIGRFAMs; TIGR01517; ATPase-IIB_Ca; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 3.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Calcium;
KW Calcium transport; Calmodulin-binding; Cell membrane;
KW Complete proteome; Hydrolase; Ion transport; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 1258 Plasma membrane calcium-transporting
FT ATPase 1.
FT /FTId=PRO_0000046209.
FT TOPO_DOM 2 97 Cytoplasmic (Potential).
FT TRANSMEM 98 118 Helical; (Potential).
FT TOPO_DOM 119 154 Extracellular (Potential).
FT TRANSMEM 155 175 Helical; (Potential).
FT TOPO_DOM 176 366 Cytoplasmic (Potential).
FT TRANSMEM 367 386 Helical; (Potential).
FT TOPO_DOM 387 419 Extracellular (Potential).
FT TRANSMEM 420 437 Helical; (Potential).
FT TOPO_DOM 438 852 Cytoplasmic (Potential).
FT TRANSMEM 853 872 Helical; (Potential).
FT TOPO_DOM 873 882 Extracellular (Potential).
FT TRANSMEM 883 903 Helical; (Potential).
FT TOPO_DOM 904 923 Cytoplasmic (Potential).
FT TRANSMEM 924 946 Helical; (Potential).
FT TOPO_DOM 947 964 Extracellular (Potential).
FT TRANSMEM 965 986 Helical; (Potential).
FT TOPO_DOM 987 1005 Cytoplasmic (Potential).
FT TRANSMEM 1006 1027 Helical; (Potential).
FT TOPO_DOM 1028 1037 Extracellular (Potential).
FT TRANSMEM 1038 1059 Helical; (Potential).
FT TOPO_DOM 1060 1258 Cytoplasmic (Potential).
FT REGION 1100 1117 Calmodulin-binding subdomain A.
FT REGION 1118 1127 Calmodulin-binding subdomain B.
FT COMPBIAS 296 299 Poly-Glu.
FT ACT_SITE 475 475 4-aspartylphosphate intermediate.
FT METAL 797 797 Magnesium (By similarity).
FT METAL 801 801 Magnesium (By similarity).
FT MOD_RES 2 2 N-acetylglycine.
FT MOD_RES 17 17 Phosphoserine.
FT MOD_RES 1116 1116 Phosphothreonine; by PKC.
FT MOD_RES 1193 1193 Phosphoserine.
FT MOD_RES 1203 1203 Phosphothreonine.
FT MOD_RES 1216 1216 Phosphoserine; by PKA.
FT MOD_RES 1220 1220 Phosphoserine.
FT MOD_RES 1246 1246 Phosphoserine.
FT MOD_RES 1249 1249 Phosphoserine.
FT MOD_RES 1253 1253 Phosphoserine.
FT MOD_RES 1257 1257 Phosphoserine.
FT VAR_SEQ 1021 1056 Missing (in isoform K).
FT /FTId=VSP_000372.
FT VAR_SEQ 1118 1155 Missing (in isoform B and isoform K).
FT /FTId=VSP_000373.
FT VAR_SEQ 1147 1155 Missing (in isoform C).
FT /FTId=VSP_000374.
FT VAR_SEQ 1156 1258 IRVVNAFRSSLYEGLEKPESRSSIHNFMTHPEFRIEDSEPH
FT IPLIDDTDAEDDAPTKRNSSPPPSPNKNNNAVDSGIHLTIE
FT MNKSATSSSPGSPLHSLETSL -> VVFSSSTASTTVGYSS
FT GECIS (in isoform A).
FT /FTId=VSP_000375.
FT VAR_SEQ 1156 1258 IRVVNAFRSSLYEGLEKPESRSSIHNFMTHPEFRIEDSEPH
FT IPLIDDTDAEDDAPTKRNSSPPPSPNKNNNAVDSGIHLTIE
FT MNKSATSSSPGSPLHSLETSL -> VVFSSSTASTTVGFEW
FT (in isoform E).
FT /FTId=VSP_000376.
FT VARIANT 267 267 M -> R (rare polymorphism).
FT /FTId=VAR_000698.
FT CONFLICT 259 262 LLLS -> MSAT (in Ref. 2; AAA36000).
SQ SEQUENCE 1258 AA; 138755 MW; 7037112747FC9B0A CRC64;
MGDMANNSVA YSGVKNSLKE ANHDGDFGIT LAELRALMEL RSTDALRKIQ ESYGDVYGIC
TKLKTSPNEG LSGNPADLER REAVFGKNFI PPKKPKTFLQ LVWEALQDVT LIILEIAAIV
SLGLSFYQPP EGDNALCGEV SVGEEEGEGE TGWIEGAAIL LSVVCVVLVT AFNDWSKEKQ
FRGLQSRIEQ EQKFTVIRGG QVIQIPVADI TVGDIAQVKY GDLLPADGIL IQGNDLKIDE
SSLTGESDHV KKSLDKDPLL LSGTHVMEGS GRMVVTAVGV NSQTGIIFTL LGAGGEEEEK
KDEKKKEKKN KKQDGAIENR NKAKAQDGAA MEMQPLKSEE GGDGDEKDKK KANLPKKEKS
VLQGKLTKLA VQIGKAGLLM SAITVIILVL YFVIDTFWVQ KRPWLAECTP IYIQYFVKFF
IIGVTVLVVA VPEGLPLAVT ISLAYSVKKM MKDNNLVRHL DACETMGNAT AICSDKTGTL
TMNRMTVVQA YINEKHYKKV PEPEAIPPNI LSYLVTGISV NCAYTSKILP PEKEGGLPRH
VGNKTECALL GLLLDLKRDY QDVRNEIPEE ALYKVYTFNS VRKSMSTVLK NSDGSYRIFS
KGASEIILKK CFKILSANGE AKVFRPRDRD DIVKTVIEPM ASEGLRTICL AFRDFPAGEP
EPEWDNENDI VTGLTCIAVV GIEDPVRPEV PDAIKKCQRA GITVRMVTGD NINTARAIAT
KCGILHPGED FLCLEGKDFN RRIRNEKGEI EQERIDKIWP KLRVLARSSP TDKHTLVKGI
IDSTVSDQRQ VVAVTGDGTN DGPALKKADV GFAMGIAGTD VAKEASDIIL TDDNFTSIVK
AVMWGRNVYD SISKFLQFQL TVNVVAVIVA FTGACITQDS PLKAVQMLWV NLIMDTLASL
ALATEPPTES LLLRKPYGRN KPLISRTMMK NILGHAFYQL VVVFTLLFAG EKFFDIDSGR
NAPLHAPPSE HYTIVFNTFV LMQLFNEINA RKIHGERNVF EGIFNNAIFC TIVLGTFVVQ
IIIVQFGGKP FSCSELSIEQ WLWSIFLGMG TLLWGQLIST IPTSRLKFLK EAGHGTQKEE
IPEEELAEDV EEIDHAEREL RRGQILWFRG LNRIQTQMDV VNAFQSGSSI QGALRRQPSI
ASQHHDVTNI STPTHIRVVN AFRSSLYEGL EKPESRSSIH NFMTHPEFRI EDSEPHIPLI
DDTDAEDDAP TKRNSSPPPS PNKNNNAVDS GIHLTIEMNK SATSSSPGSP LHSLETSL
//
MIM
108731
*RECORD*
*FIELD* NO
108731
*FIELD* TI
*108731 ATPase, Ca(2+)-TRANSPORTING, PLASMA MEMBRANE, 1; ATP2B1
;;PLASMA MEMBRANE Ca(2+)-ATPase, TYPE 1; PMCA1
read more*FIELD* TX
DESCRIPTION
The Ca(2+)-ATPases are a family of plasma membrane pumps encoded by at
least 4 genes: ATP2B1; ATP2B2 (108733) on chromosome 3p26; ATP2B3
(300014) on Xq28; and ATP2B4 (108732) on 1q25. The diversity of these
enzymes is further increased by alternative splicing of transcripts.
CLONING
Verma et al. (1988) isolated a cDNA corresponding to a Ca(2+) plasma
membrane pump from a human teratoma cDNA library. The 1,220-amino acid
protein has a calculated molecular mass of 134.6 kD. The translated
sequence contains a putative calmodulin-binding domain near the C
terminus and domains matching those of cAMP-dependent protein kinase
substrates.
Kumar et al. (1993) isolated a cDNA corresponding to the ATP2B1 gene
from a human osteoblast cDNA library. The cDNA encoded a deduced
1,220-amino acid protein.
Brandt et al. (1992) described 4 PMCA1 splice variants, which they
referred to as PMCA1a through PMCA1d, and examined their expression
using PCR. PMCA1a was expressed in spinal cord, brain, skeletal muscle,
and heart. PMCA1b was expressed in all tissues examined. PMCA1c was
expressed in skeletal muscle, heart, spinal cord, and brain. PMCA1d was
expressed in heart and skeletal muscle.
By RT-PCR, Santiago-Garcia et al. (1996) found variable expression of
the PMCA and SERCA (see 108730) genes during human fetal heart
development. PMCA1 and PMCA4 (ATP2B4) were expressed in 8-, 12-, and
20-week fetal heart and in adult heart.
Okunade et al. (2004) examined Pmca1 and Pmca4 expression in mouse
tissues. Pmca1 was expressed in all tissues examined, and Pmca4 was
expressed in all tissues examined except liver. Pmca1 predominated in
brain, intestine, kidney, lung, and stomach, whereas Pmca4 predominated
in aorta, portal vein, bladder, diaphragm, seminal vesicles, and testis.
GENE FUNCTION
The Ca(2+)-ATPases are members of the P class of ion-motive ATPases;
they form an acylphosphate intermediate as part of the reaction
mechanism. PMCA removes bivalent calcium ions from eukaryotic cells and
plays a critical role in intracellular calcium homeostasis by its
capacity for removing calcium ions from cells against very large
concentration gradients (Olson et al., 1991).
Mammalian PMCA1 is expressed in calcium-transporting epithelia and bone
mesenchymal cells, and it is upregulated by 1,25-dihydroxyvitamin D3 in
both tissues. Glendenning et al. (2000) presented evidence showing
tissue-specific sensitivity of the PMCA1 promoter to direct
transcriptional downregulation by 1,25-dihydroxyvitamin D3. Their
results suggested that any positive regulatory vitamin D response
element in PMCA1 must lie outside the core promoter.
GENE STRUCTURE
Hilfiker et al. (1993) determined that the PMCA1 gene contains 22 exons
and a putative alternative exon 1 that they called exon 1*. The ATG
start codon is in exon 2. The promoter and 5-prime flanking region is
embedded in a CpG island and is characterized by numerous Sp1
(189906)-binding sites and the absence of a TATA box. The PMCA1 gene
spans more than 100 kb.
MAPPING
Olson et al. (1991) mapped the ATP2B1 gene to chromosome 12q21-q23 by 3
independent methods: Southern analysis of human-rodent somatic cell
hybrids, in situ hybridization of human metaphase spreads, and genetic
linkage analysis in the CEPH pedigrees.
ANIMAL MODEL
Okunade et al. (2004) found that loss of both copies of the Atp2b1 gene
caused embryonic lethality in mice, whereas heterozygous mutants had no
overt phenotype.
*FIELD* RF
1. Brandt, P.; Neve, R. L.; Kammesheidt, A.; Rhoads, R. E.; Vanaman,
T. C.: Analysis of the tissue-specific distribution of mRNAs encoding
the plasma membrane calcium-pumping ATPases and characterization of
an alternately spliced form of PMCA4 at the cDNA and genomic levels. J.
Biol. Chem. 267: 4376-4385, 1992.
2. Glendenning, P.; Ratajczak, T.; Prince, R. L.; Garamszegi, N.;
Strehler, E. E.: The promoter region of the human PMCA1 gene mediates
transcriptional downregulation by 1,25-dihydroxyvitamin D3. Biochem.
Biophys. Res. Commun. 277: 722-728, 2000.
3. Hilfiker, H.; Strehler-Page, M.-A.; Stauffer, T. P.; Carafoli,
E.; Strehler, E. E.: Structure of the gene encoding the human plasma
membrane calcium pump isoform 1. J. Biol. Chem. 268: 19717-19725,
1993.
4. Kumar, R.; Haugen, J. D.; Penniston, J. T.: Molecular cloning
of a plasma membrane calcium pump from human osteoblasts. J. Bone
Miner. Res. 8: 505-513, 1993.
5. Okunade, G. W.; Miller, M. L.; Pyne, G. J.; Sutliff, R. L.; O'Connor,
K. T.; Neumann, J. C.; Andringa, A.; Miller, D. A.; Prasad, V.; Doetschman,
T.; Paul, R. J.; Shull, G. E.: Targeted ablation of plasma membrane
Ca(2+)-ATPase (PMCA) 1 and 4 indicates a major housekeeping function
for PMCA1 and a critical role in hyperactivated sperm motility and
male fertility for PMCA4. J. Biol. Chem. 279: 33742-33750, 2004.
6. Olson, S.; Wang, M. G.; Carafoli, E.; Strehler, E. E.; McBride,
O. W.: Localization of two genes encoding plasma membrane Ca(2+)-transporting
ATPases to human chromosomes 1q25-32 and 12q21-23. Genomics 9: 629-641,
1991.
7. 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.
8. Verma, A. K.; Filoteo, A. G.; Stanford, D. R.; Wieben, E. D.; Penniston,
J. T.; Strehler, E. E.; Fischer, R.; Heim, R.; Vogel, G.; Mathews,
S.; Strehler-Page, M.-A.; James, P.; Vorherr, T.; Krebs, J.; Carafoli,
E.: Complete primary structure of a human plasma membrane Ca(2+)
pump. J. Biol. Chem. 263: 14152-14159, 1988.
*FIELD* CN
Patricia A. Hartz - updated: 2/8/2005
Cassandra L. Kniffin - reorganized: 11/29/2004
Cassandra L. Kniffin - updated: 11/22/2004
*FIELD* CD
Victor A. McKusick: 2/1/1991
*FIELD* ED
terry: 12/16/2009
terry: 12/20/2005
mgross: 2/9/2005
mgross: 2/8/2005
tkritzer: 11/29/2004
ckniffin: 11/22/2004
carol: 10/15/1992
supermim: 3/16/1992
carol: 2/27/1992
carol: 7/2/1991
carol: 3/22/1991
carol: 2/4/1991
*RECORD*
*FIELD* NO
108731
*FIELD* TI
*108731 ATPase, Ca(2+)-TRANSPORTING, PLASMA MEMBRANE, 1; ATP2B1
;;PLASMA MEMBRANE Ca(2+)-ATPase, TYPE 1; PMCA1
read more*FIELD* TX
DESCRIPTION
The Ca(2+)-ATPases are a family of plasma membrane pumps encoded by at
least 4 genes: ATP2B1; ATP2B2 (108733) on chromosome 3p26; ATP2B3
(300014) on Xq28; and ATP2B4 (108732) on 1q25. The diversity of these
enzymes is further increased by alternative splicing of transcripts.
CLONING
Verma et al. (1988) isolated a cDNA corresponding to a Ca(2+) plasma
membrane pump from a human teratoma cDNA library. The 1,220-amino acid
protein has a calculated molecular mass of 134.6 kD. The translated
sequence contains a putative calmodulin-binding domain near the C
terminus and domains matching those of cAMP-dependent protein kinase
substrates.
Kumar et al. (1993) isolated a cDNA corresponding to the ATP2B1 gene
from a human osteoblast cDNA library. The cDNA encoded a deduced
1,220-amino acid protein.
Brandt et al. (1992) described 4 PMCA1 splice variants, which they
referred to as PMCA1a through PMCA1d, and examined their expression
using PCR. PMCA1a was expressed in spinal cord, brain, skeletal muscle,
and heart. PMCA1b was expressed in all tissues examined. PMCA1c was
expressed in skeletal muscle, heart, spinal cord, and brain. PMCA1d was
expressed in heart and skeletal muscle.
By RT-PCR, Santiago-Garcia et al. (1996) found variable expression of
the PMCA and SERCA (see 108730) genes during human fetal heart
development. PMCA1 and PMCA4 (ATP2B4) were expressed in 8-, 12-, and
20-week fetal heart and in adult heart.
Okunade et al. (2004) examined Pmca1 and Pmca4 expression in mouse
tissues. Pmca1 was expressed in all tissues examined, and Pmca4 was
expressed in all tissues examined except liver. Pmca1 predominated in
brain, intestine, kidney, lung, and stomach, whereas Pmca4 predominated
in aorta, portal vein, bladder, diaphragm, seminal vesicles, and testis.
GENE FUNCTION
The Ca(2+)-ATPases are members of the P class of ion-motive ATPases;
they form an acylphosphate intermediate as part of the reaction
mechanism. PMCA removes bivalent calcium ions from eukaryotic cells and
plays a critical role in intracellular calcium homeostasis by its
capacity for removing calcium ions from cells against very large
concentration gradients (Olson et al., 1991).
Mammalian PMCA1 is expressed in calcium-transporting epithelia and bone
mesenchymal cells, and it is upregulated by 1,25-dihydroxyvitamin D3 in
both tissues. Glendenning et al. (2000) presented evidence showing
tissue-specific sensitivity of the PMCA1 promoter to direct
transcriptional downregulation by 1,25-dihydroxyvitamin D3. Their
results suggested that any positive regulatory vitamin D response
element in PMCA1 must lie outside the core promoter.
GENE STRUCTURE
Hilfiker et al. (1993) determined that the PMCA1 gene contains 22 exons
and a putative alternative exon 1 that they called exon 1*. The ATG
start codon is in exon 2. The promoter and 5-prime flanking region is
embedded in a CpG island and is characterized by numerous Sp1
(189906)-binding sites and the absence of a TATA box. The PMCA1 gene
spans more than 100 kb.
MAPPING
Olson et al. (1991) mapped the ATP2B1 gene to chromosome 12q21-q23 by 3
independent methods: Southern analysis of human-rodent somatic cell
hybrids, in situ hybridization of human metaphase spreads, and genetic
linkage analysis in the CEPH pedigrees.
ANIMAL MODEL
Okunade et al. (2004) found that loss of both copies of the Atp2b1 gene
caused embryonic lethality in mice, whereas heterozygous mutants had no
overt phenotype.
*FIELD* RF
1. Brandt, P.; Neve, R. L.; Kammesheidt, A.; Rhoads, R. E.; Vanaman,
T. C.: Analysis of the tissue-specific distribution of mRNAs encoding
the plasma membrane calcium-pumping ATPases and characterization of
an alternately spliced form of PMCA4 at the cDNA and genomic levels. J.
Biol. Chem. 267: 4376-4385, 1992.
2. Glendenning, P.; Ratajczak, T.; Prince, R. L.; Garamszegi, N.;
Strehler, E. E.: The promoter region of the human PMCA1 gene mediates
transcriptional downregulation by 1,25-dihydroxyvitamin D3. Biochem.
Biophys. Res. Commun. 277: 722-728, 2000.
3. Hilfiker, H.; Strehler-Page, M.-A.; Stauffer, T. P.; Carafoli,
E.; Strehler, E. E.: Structure of the gene encoding the human plasma
membrane calcium pump isoform 1. J. Biol. Chem. 268: 19717-19725,
1993.
4. Kumar, R.; Haugen, J. D.; Penniston, J. T.: Molecular cloning
of a plasma membrane calcium pump from human osteoblasts. J. Bone
Miner. Res. 8: 505-513, 1993.
5. Okunade, G. W.; Miller, M. L.; Pyne, G. J.; Sutliff, R. L.; O'Connor,
K. T.; Neumann, J. C.; Andringa, A.; Miller, D. A.; Prasad, V.; Doetschman,
T.; Paul, R. J.; Shull, G. E.: Targeted ablation of plasma membrane
Ca(2+)-ATPase (PMCA) 1 and 4 indicates a major housekeeping function
for PMCA1 and a critical role in hyperactivated sperm motility and
male fertility for PMCA4. J. Biol. Chem. 279: 33742-33750, 2004.
6. Olson, S.; Wang, M. G.; Carafoli, E.; Strehler, E. E.; McBride,
O. W.: Localization of two genes encoding plasma membrane Ca(2+)-transporting
ATPases to human chromosomes 1q25-32 and 12q21-23. Genomics 9: 629-641,
1991.
7. 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.
8. Verma, A. K.; Filoteo, A. G.; Stanford, D. R.; Wieben, E. D.; Penniston,
J. T.; Strehler, E. E.; Fischer, R.; Heim, R.; Vogel, G.; Mathews,
S.; Strehler-Page, M.-A.; James, P.; Vorherr, T.; Krebs, J.; Carafoli,
E.: Complete primary structure of a human plasma membrane Ca(2+)
pump. J. Biol. Chem. 263: 14152-14159, 1988.
*FIELD* CN
Patricia A. Hartz - updated: 2/8/2005
Cassandra L. Kniffin - reorganized: 11/29/2004
Cassandra L. Kniffin - updated: 11/22/2004
*FIELD* CD
Victor A. McKusick: 2/1/1991
*FIELD* ED
terry: 12/16/2009
terry: 12/20/2005
mgross: 2/9/2005
mgross: 2/8/2005
tkritzer: 11/29/2004
ckniffin: 11/22/2004
carol: 10/15/1992
supermim: 3/16/1992
carol: 2/27/1992
carol: 7/2/1991
carol: 3/22/1991
carol: 2/4/1991