Full text data of ATP2B2
ATP2B2
(PMCA2)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Plasma membrane calcium-transporting ATPase 2; PMCA2; 3.6.3.8 (Plasma membrane calcium ATPase isoform 2; Plasma membrane calcium pump isoform 2)
Plasma membrane calcium-transporting ATPase 2; PMCA2; 3.6.3.8 (Plasma membrane calcium ATPase isoform 2; Plasma membrane calcium pump isoform 2)
UniProt
Q01814
ID AT2B2_HUMAN Reviewed; 1243 AA.
AC Q01814; O00766; Q12994; Q16818;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-2001, sequence version 2.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=Plasma membrane calcium-transporting ATPase 2;
DE Short=PMCA2;
DE EC=3.6.3.8;
DE AltName: Full=Plasma membrane calcium ATPase isoform 2;
DE AltName: Full=Plasma membrane calcium pump isoform 2;
GN Name=ATP2B2; Synonyms=PMCA2;
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 ZB).
RC TISSUE=Brain;
RX PubMed=1427863; DOI=10.1016/S0888-7543(05)80246-0;
RA Brandt P., Ibrahim E., Bruns G.A.P., Neve R.L.;
RT "Determination of the nucleotide sequence and chromosomal localization
RT of the ATP2B2 gene encoding human Ca(2+)-pumping ATPase isoform
RT PMCA2.";
RL Genomics 14:484-487(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ZB), AND ALTERNATIVE SPLICING.
RX PubMed=8428366;
RA Latif F., Duh F.-M., Gnarra J., Tory K., Kuzmin I., Yao M.,
RA Stackhouse T., Modi W., Geil L., Schmidt L., Li H., Orcutt M.L.,
RA Maher E., Richards F., Phipps M., Ferguson-Smith M., le Paslier D.,
RA Linehan W.M., Zbar B., Lerman M.I.;
RT "von Hippel-Lindau syndrome: cloning and identification of the plasma
RT membrane Ca(++)-transporting ATPase isoform 2 gene that resides in the
RT von Hippel-Lindau gene region.";
RL Cancer Res. 53:861-867(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM WB), AND ALTERNATIVE SPLICING.
RC TISSUE=Brain, and Skeletal muscle;
RX PubMed=1313367; DOI=10.1111/j.1432-1033.1992.tb16784.x;
RA Heim R., Hug M., Iwata T., Strehler E.E., Carafoli E.;
RT "Microdiversity of human-plasma-membrane calcium-pump isoform 2
RT generated by alternative RNA splicing in the N-terminal coding
RT region.";
RL Eur. J. Biochem. 205:333-340(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS WA/YA/ZA).
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 [6]
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 [7]
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1231; SER-1234; SER-1238
RP AND SER-1242, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1177
RP (ISOFORM WA), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1146
RP (ISOFORM XA), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1163
RP (ISOFORM YA), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1132
RP (ISOFORM ZA), AND 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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1242, AND MASS
RP SPECTROMETRY.
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 [11]
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).
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 -!- INTERACTION:
CC P01258:CALCA; NbExp=2; IntAct=EBI-1174243, EBI-1018474;
CC Q63622:Dlg2 (xeno); NbExp=2; IntAct=EBI-1174262, EBI-396947;
CC Q8SQG9:SLC9A3R2 (xeno); NbExp=3; IntAct=EBI-1174262, EBI-1174758;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Comment=There is a combination of two alternative spliced
CC domains at N-terminal site A (Z, X, Y and W) and at C-terminal
CC site C (A and B). So far the splice sites have only been studied
CC independently. Experimental confirmation may be lacking for some
CC isoforms;
CC Name=WB; Synonyms=AIIICI;
CC IsoId=Q01814-1; Sequence=Displayed;
CC Name=WA; Synonyms=AIIICII;
CC IsoId=Q01814-2; Sequence=VSP_000386;
CC Note=Contains a phosphoserine at position 1177;
CC Name=YA; Synonyms=AIICII;
CC IsoId=Q01814-3; Sequence=VSP_000385, VSP_000386;
CC Note=Contains a phosphoserine at position 1163;
CC Name=ZA; Synonyms=AICII;
CC IsoId=Q01814-4; Sequence=VSP_000384, VSP_000386;
CC Note=Contains a phosphoserine at position 1132;
CC Name=YB; Synonyms=AIICI;
CC IsoId=Q01814-5; Sequence=VSP_000385;
CC Name=ZB; Synonyms=AICI;
CC IsoId=Q01814-6; Sequence=VSP_000384;
CC Name=XA;
CC IsoId=Q01814-7; Sequence=VSP_040837, VSP_000386;
CC Note=Contains a phosphoserine at position 1146;
CC Name=XB;
CC IsoId=Q01814-8; Sequence=VSP_040837;
CC -!- TISSUE SPECIFICITY: Mainly expressed in brain cortex. Found in low
CC levels in skeletal muscle, heart muscle, stomach, liver, kidney
CC and lung. Isoforms containing segment B are found in brain cortex
CC and at low levels in other tissues. Isoforms containing segments X
CC and W are found at low levels in all tissues. Isoforms containing
CC segment A and segment Z are found at low levels in skeletal muscle
CC and heart muscle.
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; M97260; AAA36456.1; -; mRNA.
DR EMBL; L20977; AAA50877.1; -; mRNA.
DR EMBL; L00620; AAA51893.1; -; mRNA.
DR EMBL; X63575; CAA45131.1; -; mRNA.
DR EMBL; AC018839; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090841; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U15688; AAA60985.1; -; mRNA.
DR PIR; S22393; S22393.
DR RefSeq; NP_001001331.1; NM_001001331.2.
DR RefSeq; NP_001674.2; NM_001683.3.
DR RefSeq; XP_005265236.1; XM_005265179.1.
DR RefSeq; XP_005265237.1; XM_005265180.1.
DR RefSeq; XP_005265239.1; XM_005265182.1.
DR RefSeq; XP_005265240.1; XM_005265183.1.
DR UniGene; Hs.268942; -.
DR ProteinModelPortal; Q01814; -.
DR SMR; Q01814; 70-310, 364-948, 1123-1150.
DR IntAct; Q01814; 8.
DR MINT; MINT-470839; -.
DR STRING; 9606.ENSP00000324172; -.
DR PhosphoSite; Q01814; -.
DR DMDM; 14286115; -.
DR PaxDb; Q01814; -.
DR PRIDE; Q01814; -.
DR Ensembl; ENST00000343816; ENSP00000344677; ENSG00000157087.
DR Ensembl; ENST00000352432; ENSP00000324172; ENSG00000157087.
DR Ensembl; ENST00000360273; ENSP00000353414; ENSG00000157087.
DR Ensembl; ENST00000383800; ENSP00000373311; ENSG00000157087.
DR Ensembl; ENST00000397077; ENSP00000380267; ENSG00000157087.
DR Ensembl; ENST00000460129; ENSP00000424494; ENSG00000157087.
DR GeneID; 491; -.
DR KEGG; hsa:491; -.
DR UCSC; uc003bvt.3; human.
DR CTD; 491; -.
DR GeneCards; GC03M010365; -.
DR HGNC; HGNC:815; ATP2B2.
DR HPA; CAB005606; -.
DR MIM; 108733; gene.
DR neXtProt; NX_Q01814; -.
DR PharmGKB; PA25108; -.
DR eggNOG; COG0474; -.
DR HOGENOM; HOG000265623; -.
DR HOVERGEN; HBG061286; -.
DR InParanoid; Q01814; -.
DR KO; K05850; -.
DR OMA; MADNTES; -.
DR OrthoDB; EOG7SN8BN; -.
DR PhylomeDB; Q01814; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; Atp2b2; human.
DR GeneWiki; ATP2B2; -.
DR GenomeRNAi; 491; -.
DR NextBio; 2059; -.
DR PRO; PR:Q01814; -.
DR ArrayExpress; Q01814; -.
DR Bgee; Q01814; -.
DR CleanEx; HS_ATP2B2; -.
DR Genevestigator; Q01814; -.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0005929; C:cilium; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0030899; F:calcium-dependent ATPase activity; IEA:Ensembl.
DR GO; GO:0005388; F:calcium-transporting ATPase activity; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030165; F:PDZ domain binding; IDA:UniProtKB.
DR GO; GO:0060088; P:auditory receptor cell stereocilium organization; IEA:Ensembl.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0021707; P:cerebellar granule cell differentiation; IEA:Ensembl.
DR GO; GO:0021702; P:cerebellar Purkinje cell differentiation; IEA:Ensembl.
DR GO; GO:0046068; P:cGMP metabolic process; IEA:Ensembl.
DR GO; GO:0090102; P:cochlea development; IEA:Ensembl.
DR GO; GO:0051480; P:cytosolic calcium ion homeostasis; IMP:DFLAT.
DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; IEA:Ensembl.
DR GO; GO:0007595; P:lactation; IEA:Ensembl.
DR GO; GO:0040011; P:locomotion; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IDA:UniProtKB.
DR GO; GO:0006996; P:organelle organization; IEA:Ensembl.
DR GO; GO:0045299; P:otolith mineralization; IEA:Ensembl.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:0008361; P:regulation of cell size; IEA:Ensembl.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
DR GO; GO:0042428; P:serotonin metabolic process; IEA:Ensembl.
DR GO; GO:0050808; P:synapse organization; IEA:Ensembl.
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; 1.
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 Alternative splicing; ATP-binding; Calcium; Calcium transport;
KW Calmodulin-binding; Cell membrane; Complete proteome; Hydrolase;
KW Ion transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1 1243 Plasma membrane calcium-transporting
FT ATPase 2.
FT /FTId=PRO_0000046214.
FT TOPO_DOM 1 94 Cytoplasmic (Potential).
FT TRANSMEM 95 115 Helical; (Potential).
FT TOPO_DOM 116 152 Extracellular (Potential).
FT TRANSMEM 153 173 Helical; (Potential).
FT TOPO_DOM 174 390 Cytoplasmic (Potential).
FT TRANSMEM 391 410 Helical; (Potential).
FT TOPO_DOM 411 443 Extracellular (Potential).
FT TRANSMEM 444 461 Helical; (Potential).
FT TOPO_DOM 462 875 Cytoplasmic (Potential).
FT TRANSMEM 876 895 Helical; (Potential).
FT TOPO_DOM 896 905 Extracellular (Potential).
FT TRANSMEM 906 926 Helical; (Potential).
FT TOPO_DOM 927 946 Cytoplasmic (Potential).
FT TRANSMEM 947 969 Helical; (Potential).
FT TOPO_DOM 970 987 Extracellular (Potential).
FT TRANSMEM 988 1009 Helical; (Potential).
FT TOPO_DOM 1010 1028 Cytoplasmic (Potential).
FT TRANSMEM 1029 1050 Helical; (Potential).
FT TOPO_DOM 1051 1060 Extracellular (Potential).
FT TRANSMEM 1061 1082 Helical; (Potential).
FT TOPO_DOM 1083 1243 Cytoplasmic (Potential).
FT REGION 1123 1140 Calmodulin-binding subdomain A (By
FT similarity).
FT REGION 1141 1150 Calmodulin-binding subdomain B (By
FT similarity).
FT COMPBIAS 294 297 Poly-Glu.
FT ACT_SITE 499 499 4-aspartylphosphate intermediate.
FT METAL 820 820 Magnesium (By similarity).
FT METAL 824 824 Magnesium (By similarity).
FT MOD_RES 1139 1139 Phosphothreonine; by PKC (By similarity).
FT MOD_RES 1201 1201 Phosphoserine; by PKA (By similarity).
FT MOD_RES 1231 1231 Phosphoserine.
FT MOD_RES 1234 1234 Phosphoserine.
FT MOD_RES 1238 1238 Phosphoserine.
FT MOD_RES 1242 1242 Phosphoserine.
FT VAR_SEQ 303 347 Missing (in isoform ZA and isoform ZB).
FT /FTId=VSP_000384.
FT VAR_SEQ 304 334 Missing (in isoform XA and isoform XB).
FT /FTId=VSP_040837.
FT VAR_SEQ 334 347 Missing (in isoform YA and isoform YB).
FT /FTId=VSP_000385.
FT VAR_SEQ 1141 1243 IRVVKAFRSSLYEGLEKPESRTSIHNFMAHPEFRIEDSQPH
FT IPLIDDTDLEEDAALKQNSSPPSSLNKNNSAIDSGINLTTD
FT TSKSATSSSPGSPIHSLETSL -> IEVVNTFKSGASFQGA
FT LRRQSSVTSQSQDVANLSSPSRVSLSNALSSPTSLPPAAAG
FT QG (in isoform WA, isoform XA, isoform YA
FT and isoform ZA).
FT /FTId=VSP_000386.
FT CONFLICT 92 94 PKT -> AKP (in Ref. 1; AAA36456).
FT CONFLICT 126 126 P -> R (in Ref. 2; AAA50877/AAA51893).
FT CONFLICT 517 517 G -> D (in Ref. 2; AAA50877/AAA51893).
FT CONFLICT 667 668 DG -> EW (in Ref. 1; AAA36456).
FT CONFLICT 1212 1212 A -> S (in Ref. 1; AAA36456).
SQ SEQUENCE 1243 AA; 136876 MW; 7F10221B7B9AC3A2 CRC64;
MGDMTNSDFY SKNQRNESSH GGEFGCTMEE LRSLMELRGT EAVVKIKETY GDTEAICRRL
KTSPVEGLPG TAPDLEKRKQ IFGQNFIPPK KPKTFLQLVW EALQDVTLII LEIAAIISLG
LSFYHPPGEG NEGCATAQGG AEDEGEAEAG WIEGAAILLS VICVVLVTAF NDWSKEKQFR
GLQSRIEQEQ KFTVVRAGQV VQIPVAEIVV GDIAQVKYGD LLPADGLFIQ GNDLKIDESS
LTGESDQVRK SVDKDPMLLS GTHVMEGSGR MLVTAVGVNS QTGIIFTLLG AGGEEEEKKD
KKGVKKGDGL QLPAADGAAA SNAADSANAS LVNGKMQDGN VDASQSKAKQ QDGAAAMEMQ
PLKSAEGGDA DDRKKASMHK KEKSVLQGKL TKLAVQIGKA GLVMSAITVI ILVLYFTVDT
FVVNKKPWLP ECTPVYVQYF VKFFIIGVTV LVVAVPEGLP LAVTISLAYS VKKMMKDNNL
VRHLDACETM GNATAICSDK TGTLTTNRMT VVQAYVGDVH YKEIPDPSSI NTKTMELLIN
AIAINSAYTT KILPPEKEGA LPRQVGNKTE CGLLGFVLDL KQDYEPVRSQ MPEEKLYKVY
TFNSVRKSMS TVIKLPDESF RMYSKGASEI VLKKCCKILN GAGEPRVFRP RDRDEMVKKV
IEPMACDGLR TICVAYRDFP SSPEPDWDNE NDILNELTCI CVVGIEDPVR PEVPEAIRKC
QRAGITVRMV TGDNINTARA IAIKCGIIHP GEDFLCLEGK EFNRRIRNEK GEIEQERIDK
IWPKLRVLAR SSPTDKHTLV KGIIDSTHTE QRQVVAVTGD GTNDGPALKK ADVGFAMGIA
GTDVAKEASD IILTDDNFSS IVKAVMWGRN VYDSISKFLQ FQLTVNVVAV IVAFTGACIT
QDSPLKAVQM LWVNLIMDTF ASLALATEPP TETLLLRKPY GRNKPLISRT MMKNILGHAV
YQLALIFTLL FVGEKMFQID SGRNAPLHSP PSEHYTIIFN TFVMMQLFNE INARKIHGER
NVFDGIFRNP IFCTIVLGTF AIQIVIVQFG GKPFSCSPLQ LDQWMWCIFI GLGELVWGQV
IATIPTSRLK FLKEAGRLTQ KEEIPEEELN EDVEEIDHAE RELRRGQILW FRGLNRIQTQ
IRVVKAFRSS LYEGLEKPES RTSIHNFMAH PEFRIEDSQP HIPLIDDTDL EEDAALKQNS
SPPSSLNKNN SAIDSGINLT TDTSKSATSS SPGSPIHSLE TSL
//
ID AT2B2_HUMAN Reviewed; 1243 AA.
AC Q01814; O00766; Q12994; Q16818;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-2001, sequence version 2.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=Plasma membrane calcium-transporting ATPase 2;
DE Short=PMCA2;
DE EC=3.6.3.8;
DE AltName: Full=Plasma membrane calcium ATPase isoform 2;
DE AltName: Full=Plasma membrane calcium pump isoform 2;
GN Name=ATP2B2; Synonyms=PMCA2;
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 ZB).
RC TISSUE=Brain;
RX PubMed=1427863; DOI=10.1016/S0888-7543(05)80246-0;
RA Brandt P., Ibrahim E., Bruns G.A.P., Neve R.L.;
RT "Determination of the nucleotide sequence and chromosomal localization
RT of the ATP2B2 gene encoding human Ca(2+)-pumping ATPase isoform
RT PMCA2.";
RL Genomics 14:484-487(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ZB), AND ALTERNATIVE SPLICING.
RX PubMed=8428366;
RA Latif F., Duh F.-M., Gnarra J., Tory K., Kuzmin I., Yao M.,
RA Stackhouse T., Modi W., Geil L., Schmidt L., Li H., Orcutt M.L.,
RA Maher E., Richards F., Phipps M., Ferguson-Smith M., le Paslier D.,
RA Linehan W.M., Zbar B., Lerman M.I.;
RT "von Hippel-Lindau syndrome: cloning and identification of the plasma
RT membrane Ca(++)-transporting ATPase isoform 2 gene that resides in the
RT von Hippel-Lindau gene region.";
RL Cancer Res. 53:861-867(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM WB), AND ALTERNATIVE SPLICING.
RC TISSUE=Brain, and Skeletal muscle;
RX PubMed=1313367; DOI=10.1111/j.1432-1033.1992.tb16784.x;
RA Heim R., Hug M., Iwata T., Strehler E.E., Carafoli E.;
RT "Microdiversity of human-plasma-membrane calcium-pump isoform 2
RT generated by alternative RNA splicing in the N-terminal coding
RT region.";
RL Eur. J. Biochem. 205:333-340(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS WA/YA/ZA).
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 [6]
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 [7]
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1231; SER-1234; SER-1238
RP AND SER-1242, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1177
RP (ISOFORM WA), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1146
RP (ISOFORM XA), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1163
RP (ISOFORM YA), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1132
RP (ISOFORM ZA), AND 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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1242, AND MASS
RP SPECTROMETRY.
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 [11]
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).
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 -!- INTERACTION:
CC P01258:CALCA; NbExp=2; IntAct=EBI-1174243, EBI-1018474;
CC Q63622:Dlg2 (xeno); NbExp=2; IntAct=EBI-1174262, EBI-396947;
CC Q8SQG9:SLC9A3R2 (xeno); NbExp=3; IntAct=EBI-1174262, EBI-1174758;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Comment=There is a combination of two alternative spliced
CC domains at N-terminal site A (Z, X, Y and W) and at C-terminal
CC site C (A and B). So far the splice sites have only been studied
CC independently. Experimental confirmation may be lacking for some
CC isoforms;
CC Name=WB; Synonyms=AIIICI;
CC IsoId=Q01814-1; Sequence=Displayed;
CC Name=WA; Synonyms=AIIICII;
CC IsoId=Q01814-2; Sequence=VSP_000386;
CC Note=Contains a phosphoserine at position 1177;
CC Name=YA; Synonyms=AIICII;
CC IsoId=Q01814-3; Sequence=VSP_000385, VSP_000386;
CC Note=Contains a phosphoserine at position 1163;
CC Name=ZA; Synonyms=AICII;
CC IsoId=Q01814-4; Sequence=VSP_000384, VSP_000386;
CC Note=Contains a phosphoserine at position 1132;
CC Name=YB; Synonyms=AIICI;
CC IsoId=Q01814-5; Sequence=VSP_000385;
CC Name=ZB; Synonyms=AICI;
CC IsoId=Q01814-6; Sequence=VSP_000384;
CC Name=XA;
CC IsoId=Q01814-7; Sequence=VSP_040837, VSP_000386;
CC Note=Contains a phosphoserine at position 1146;
CC Name=XB;
CC IsoId=Q01814-8; Sequence=VSP_040837;
CC -!- TISSUE SPECIFICITY: Mainly expressed in brain cortex. Found in low
CC levels in skeletal muscle, heart muscle, stomach, liver, kidney
CC and lung. Isoforms containing segment B are found in brain cortex
CC and at low levels in other tissues. Isoforms containing segments X
CC and W are found at low levels in all tissues. Isoforms containing
CC segment A and segment Z are found at low levels in skeletal muscle
CC and heart muscle.
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; M97260; AAA36456.1; -; mRNA.
DR EMBL; L20977; AAA50877.1; -; mRNA.
DR EMBL; L00620; AAA51893.1; -; mRNA.
DR EMBL; X63575; CAA45131.1; -; mRNA.
DR EMBL; AC018839; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090841; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U15688; AAA60985.1; -; mRNA.
DR PIR; S22393; S22393.
DR RefSeq; NP_001001331.1; NM_001001331.2.
DR RefSeq; NP_001674.2; NM_001683.3.
DR RefSeq; XP_005265236.1; XM_005265179.1.
DR RefSeq; XP_005265237.1; XM_005265180.1.
DR RefSeq; XP_005265239.1; XM_005265182.1.
DR RefSeq; XP_005265240.1; XM_005265183.1.
DR UniGene; Hs.268942; -.
DR ProteinModelPortal; Q01814; -.
DR SMR; Q01814; 70-310, 364-948, 1123-1150.
DR IntAct; Q01814; 8.
DR MINT; MINT-470839; -.
DR STRING; 9606.ENSP00000324172; -.
DR PhosphoSite; Q01814; -.
DR DMDM; 14286115; -.
DR PaxDb; Q01814; -.
DR PRIDE; Q01814; -.
DR Ensembl; ENST00000343816; ENSP00000344677; ENSG00000157087.
DR Ensembl; ENST00000352432; ENSP00000324172; ENSG00000157087.
DR Ensembl; ENST00000360273; ENSP00000353414; ENSG00000157087.
DR Ensembl; ENST00000383800; ENSP00000373311; ENSG00000157087.
DR Ensembl; ENST00000397077; ENSP00000380267; ENSG00000157087.
DR Ensembl; ENST00000460129; ENSP00000424494; ENSG00000157087.
DR GeneID; 491; -.
DR KEGG; hsa:491; -.
DR UCSC; uc003bvt.3; human.
DR CTD; 491; -.
DR GeneCards; GC03M010365; -.
DR HGNC; HGNC:815; ATP2B2.
DR HPA; CAB005606; -.
DR MIM; 108733; gene.
DR neXtProt; NX_Q01814; -.
DR PharmGKB; PA25108; -.
DR eggNOG; COG0474; -.
DR HOGENOM; HOG000265623; -.
DR HOVERGEN; HBG061286; -.
DR InParanoid; Q01814; -.
DR KO; K05850; -.
DR OMA; MADNTES; -.
DR OrthoDB; EOG7SN8BN; -.
DR PhylomeDB; Q01814; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; Atp2b2; human.
DR GeneWiki; ATP2B2; -.
DR GenomeRNAi; 491; -.
DR NextBio; 2059; -.
DR PRO; PR:Q01814; -.
DR ArrayExpress; Q01814; -.
DR Bgee; Q01814; -.
DR CleanEx; HS_ATP2B2; -.
DR Genevestigator; Q01814; -.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0005929; C:cilium; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0030899; F:calcium-dependent ATPase activity; IEA:Ensembl.
DR GO; GO:0005388; F:calcium-transporting ATPase activity; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030165; F:PDZ domain binding; IDA:UniProtKB.
DR GO; GO:0060088; P:auditory receptor cell stereocilium organization; IEA:Ensembl.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0021707; P:cerebellar granule cell differentiation; IEA:Ensembl.
DR GO; GO:0021702; P:cerebellar Purkinje cell differentiation; IEA:Ensembl.
DR GO; GO:0046068; P:cGMP metabolic process; IEA:Ensembl.
DR GO; GO:0090102; P:cochlea development; IEA:Ensembl.
DR GO; GO:0051480; P:cytosolic calcium ion homeostasis; IMP:DFLAT.
DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; IEA:Ensembl.
DR GO; GO:0007595; P:lactation; IEA:Ensembl.
DR GO; GO:0040011; P:locomotion; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IDA:UniProtKB.
DR GO; GO:0006996; P:organelle organization; IEA:Ensembl.
DR GO; GO:0045299; P:otolith mineralization; IEA:Ensembl.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:0008361; P:regulation of cell size; IEA:Ensembl.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
DR GO; GO:0042428; P:serotonin metabolic process; IEA:Ensembl.
DR GO; GO:0050808; P:synapse organization; IEA:Ensembl.
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; 1.
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 Alternative splicing; ATP-binding; Calcium; Calcium transport;
KW Calmodulin-binding; Cell membrane; Complete proteome; Hydrolase;
KW Ion transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1 1243 Plasma membrane calcium-transporting
FT ATPase 2.
FT /FTId=PRO_0000046214.
FT TOPO_DOM 1 94 Cytoplasmic (Potential).
FT TRANSMEM 95 115 Helical; (Potential).
FT TOPO_DOM 116 152 Extracellular (Potential).
FT TRANSMEM 153 173 Helical; (Potential).
FT TOPO_DOM 174 390 Cytoplasmic (Potential).
FT TRANSMEM 391 410 Helical; (Potential).
FT TOPO_DOM 411 443 Extracellular (Potential).
FT TRANSMEM 444 461 Helical; (Potential).
FT TOPO_DOM 462 875 Cytoplasmic (Potential).
FT TRANSMEM 876 895 Helical; (Potential).
FT TOPO_DOM 896 905 Extracellular (Potential).
FT TRANSMEM 906 926 Helical; (Potential).
FT TOPO_DOM 927 946 Cytoplasmic (Potential).
FT TRANSMEM 947 969 Helical; (Potential).
FT TOPO_DOM 970 987 Extracellular (Potential).
FT TRANSMEM 988 1009 Helical; (Potential).
FT TOPO_DOM 1010 1028 Cytoplasmic (Potential).
FT TRANSMEM 1029 1050 Helical; (Potential).
FT TOPO_DOM 1051 1060 Extracellular (Potential).
FT TRANSMEM 1061 1082 Helical; (Potential).
FT TOPO_DOM 1083 1243 Cytoplasmic (Potential).
FT REGION 1123 1140 Calmodulin-binding subdomain A (By
FT similarity).
FT REGION 1141 1150 Calmodulin-binding subdomain B (By
FT similarity).
FT COMPBIAS 294 297 Poly-Glu.
FT ACT_SITE 499 499 4-aspartylphosphate intermediate.
FT METAL 820 820 Magnesium (By similarity).
FT METAL 824 824 Magnesium (By similarity).
FT MOD_RES 1139 1139 Phosphothreonine; by PKC (By similarity).
FT MOD_RES 1201 1201 Phosphoserine; by PKA (By similarity).
FT MOD_RES 1231 1231 Phosphoserine.
FT MOD_RES 1234 1234 Phosphoserine.
FT MOD_RES 1238 1238 Phosphoserine.
FT MOD_RES 1242 1242 Phosphoserine.
FT VAR_SEQ 303 347 Missing (in isoform ZA and isoform ZB).
FT /FTId=VSP_000384.
FT VAR_SEQ 304 334 Missing (in isoform XA and isoform XB).
FT /FTId=VSP_040837.
FT VAR_SEQ 334 347 Missing (in isoform YA and isoform YB).
FT /FTId=VSP_000385.
FT VAR_SEQ 1141 1243 IRVVKAFRSSLYEGLEKPESRTSIHNFMAHPEFRIEDSQPH
FT IPLIDDTDLEEDAALKQNSSPPSSLNKNNSAIDSGINLTTD
FT TSKSATSSSPGSPIHSLETSL -> IEVVNTFKSGASFQGA
FT LRRQSSVTSQSQDVANLSSPSRVSLSNALSSPTSLPPAAAG
FT QG (in isoform WA, isoform XA, isoform YA
FT and isoform ZA).
FT /FTId=VSP_000386.
FT CONFLICT 92 94 PKT -> AKP (in Ref. 1; AAA36456).
FT CONFLICT 126 126 P -> R (in Ref. 2; AAA50877/AAA51893).
FT CONFLICT 517 517 G -> D (in Ref. 2; AAA50877/AAA51893).
FT CONFLICT 667 668 DG -> EW (in Ref. 1; AAA36456).
FT CONFLICT 1212 1212 A -> S (in Ref. 1; AAA36456).
SQ SEQUENCE 1243 AA; 136876 MW; 7F10221B7B9AC3A2 CRC64;
MGDMTNSDFY SKNQRNESSH GGEFGCTMEE LRSLMELRGT EAVVKIKETY GDTEAICRRL
KTSPVEGLPG TAPDLEKRKQ IFGQNFIPPK KPKTFLQLVW EALQDVTLII LEIAAIISLG
LSFYHPPGEG NEGCATAQGG AEDEGEAEAG WIEGAAILLS VICVVLVTAF NDWSKEKQFR
GLQSRIEQEQ KFTVVRAGQV VQIPVAEIVV GDIAQVKYGD LLPADGLFIQ GNDLKIDESS
LTGESDQVRK SVDKDPMLLS GTHVMEGSGR MLVTAVGVNS QTGIIFTLLG AGGEEEEKKD
KKGVKKGDGL QLPAADGAAA SNAADSANAS LVNGKMQDGN VDASQSKAKQ QDGAAAMEMQ
PLKSAEGGDA DDRKKASMHK KEKSVLQGKL TKLAVQIGKA GLVMSAITVI ILVLYFTVDT
FVVNKKPWLP ECTPVYVQYF VKFFIIGVTV LVVAVPEGLP LAVTISLAYS VKKMMKDNNL
VRHLDACETM GNATAICSDK TGTLTTNRMT VVQAYVGDVH YKEIPDPSSI NTKTMELLIN
AIAINSAYTT KILPPEKEGA LPRQVGNKTE CGLLGFVLDL KQDYEPVRSQ MPEEKLYKVY
TFNSVRKSMS TVIKLPDESF RMYSKGASEI VLKKCCKILN GAGEPRVFRP RDRDEMVKKV
IEPMACDGLR TICVAYRDFP SSPEPDWDNE NDILNELTCI CVVGIEDPVR PEVPEAIRKC
QRAGITVRMV TGDNINTARA IAIKCGIIHP GEDFLCLEGK EFNRRIRNEK GEIEQERIDK
IWPKLRVLAR SSPTDKHTLV KGIIDSTHTE QRQVVAVTGD GTNDGPALKK ADVGFAMGIA
GTDVAKEASD IILTDDNFSS IVKAVMWGRN VYDSISKFLQ FQLTVNVVAV IVAFTGACIT
QDSPLKAVQM LWVNLIMDTF ASLALATEPP TETLLLRKPY GRNKPLISRT MMKNILGHAV
YQLALIFTLL FVGEKMFQID SGRNAPLHSP PSEHYTIIFN TFVMMQLFNE INARKIHGER
NVFDGIFRNP IFCTIVLGTF AIQIVIVQFG GKPFSCSPLQ LDQWMWCIFI GLGELVWGQV
IATIPTSRLK FLKEAGRLTQ KEEIPEEELN EDVEEIDHAE RELRRGQILW FRGLNRIQTQ
IRVVKAFRSS LYEGLEKPES RTSIHNFMAH PEFRIEDSQP HIPLIDDTDL EEDAALKQNS
SPPSSLNKNN SAIDSGINLT TDTSKSATSS SPGSPIHSLE TSL
//
MIM
108733
*RECORD*
*FIELD* NO
108733
*FIELD* TI
*108733 ATPase, Ca(2+)-TRANSPORTING, PLASMA MEMBRANE, 2; ATP2B2
;;PLASMA MEMBRANE Ca(2+)-ATPase, TYPE 2; PMCA2
read more*FIELD* TX
DESCRIPTION
The Ca(2+)-ATPases are a family of plasma membrane pumps encoded by at
least 4 genes: ATP2B1 (108731) on chromosome 12q21; ATP2B2; ATP2B3
(300014) on Xq28; and ATP2B4 (108732) on 1q25.
CLONING
Brandt et al. (1992) isolated and characterized a cDNA for the human
PMCA2 gene from a human fetal brain cDNA library. The 1,190-amino acid
protein showed greater than 98% sequence identity to the rat protein.
By PCR, Brandt et al. (1992) detected PMCA2 expression in brain, liver,
spinal cord, and adrenal gland. There were 2 PCR products in spinal
cord, suggesting the presence of PMCA2 splice variants.
By RT-PCR, Santiago-Garcia et al. (1996) found variable expression of
the PMCA and SERCA (see 108730) genes during development of human fetal
heart. PMCA2 was not detected in placenta or in fetal heart at the 3
stages tested, but 3 splice variants of PMCA2 were detected in adult
atrium.
Street et al. (1998) noted that the ATP2B2 gene undergoes alternative
splicing. All 4 ATP2B proteins are predicted to have 10
transmembrane-spanning domains with approximately 80% of the protein
mass located in the cytoplasm. The intracellular loop between T2 and T3
encodes the transducing domain that couples ATP hydrolysis with calcium
translocation. The largest intracellular loop, between T4 and T5,
includes the phosphoenzyme-forming residue and the nucleotide-binding
domain. The intracellular C terminus contains the calmodulin-binding,
protein kinase C, cAMP-dependent kinase and acidic phospholipid
regulatory domains.
GENE FUNCTION
Elwess et al. (1997) found that the alternative splice variants PMCA2a
and PMCA2b had much higher affinity for calmodulin than the
corresponding forms of PMCA4. At a high calmodulin concentration, PMCA2b
showed higher calcium affinity. The calcium affinity was localized to
the C terminus. Elwess et al. (1997) concluded that the PMCA2 variants
maintain a low free cytosolic calcium concentration.
Street et al. (1998) found Atp2b2 expression in mouse auditory and
vestibular hair cells, suggesting that the channel provides the means to
remove calcium from stereocilia.
By yeast 2-hybrid analysis of a human brain cDNA expression library,
DeMarco et al. (2002) found that PCMA2b interacted with NHERF2
(SLC9A3R2; 606553). Coimmunoprecipitation analysis indicated that the
interaction was specific and selective, in that PCMA4b did not interact
with either NHERF2 or NHERF1 (SLC9A3R1; 604990), and PCMA2b preferred
NHERF2 over NHERF1. Fluorescence-tagged PCMA2b was expressed at the
apical membrane of canine kidney epithelial cells, where it colocalized
with apically targeted NHERF2. DeMarco et al. (2002) hypothesized that
the PCMA2b-NHERF2 interaction may allow the assembly of PMCA2b in a
multiprotein Ca(2+) signaling complex.
Chicka and Strehler (2003) found that PMCA2b localized to both the
apical and basolateral membranes of polarized epithelial cells.
Different splice variants of the protein showed differential membrane
targeting.
MAPPING
Using the PMCA2 cDNA to probe Southern blots of human-rodent somatic
cell hybrid DNAs, Brandt et al. (1992) mapped the PMCA2 gene to human
chromosome 3. By a combination of fluorescence in situ hybridization,
analysis of somatic cell hybrids, and genetic linkage analysis in CEPH
families, Wang et al. (1994) confirmed assignment of the ATP2B2 gene to
3p26-p25.
Richards et al. (1993) reported that the PMCA2 gene, which is located on
3p, is situated centromeric to the gene (VHL; 608537) for von
Hippel-Lindau disease (193300). They reported other results that
excluded PMCA2 as the site of the mutation in VHL.
ANIMAL MODEL
Street et al. (1998) demonstrated that the deafwaddler (dfw) mouse
mutant, which is deaf and displays vestibular/motor imbalance, has a
mutation in the Atp2b2 gene. An A-to-G nucleotide transition in dfw DNA
caused a glycine-to-serine substitution at a highly conserved amino acid
position, whereas a second mutant allele carried a 2-bp deletion that
caused a frameshift predicted to result in a truncated protein. In the
cochlea, the Atp2b2 protein was localized to stereocilia and the
basolateral wall of hair cells in wildtype mice, but was not detected in
deafwaddler mice. The findings indicated that mutation of Atp2b2 may
cause deafness and imbalance by affecting sensory transduction in
stereocilia as well as neurotransmitter release from the basolateral
membrane. These mutations affecting Atp2b2 were the first to be found in
a mammalian plasma membrane calcium pump and defined a new class of
deafness genes that directly affect hair-cell physiology.
PMCA2 exhibits a highly restricted tissue distribution, suggesting that
it serves more specialized physiologic functions than some of the other
PMCA isoforms. A unique role in hearing is suggested by the high levels
of PMCA2 expression in cochlear outer hair cells and spiral ganglion
cells. To analyze the physiologic role of PMCA2, Kozel et al. (1998)
produced PMCA2-deficient mice by gene targeting. Homozygous PMCA2-null
mice grew more slowly than heterozygous and wildtype mice and exhibited
an unsteady gait and difficulties in maintaining balance. Histologic
analysis of the cerebellum and inner ear of mutant and wildtype mice
showed that null mutants have slightly increased numbers of Purkinje
neurons (in which PMCA2 is highly expressed), a decreased thickness of
the molecular layer, an absence of otoconia in the vestibular system,
and a range of abnormalities of the organ of Corti. Analysis of
auditory-evoked brainstem responses showed that homozygous mutants were
deaf and that heterozygous mice had a significant hearing loss. These
data demonstrated that PMCA2 is required for both balance and hearing
and suggested that it may be a major source of the calcium used in the
formation and maintenance of otoconia.
Reinhardt et al. (2004) noted that the PMCA2bw isoform is expressed
approximately 100-fold during lactation, and that expression levels
correlate with milk production and calcium secretion. They found that
mice homozygous for the loss of Pmca2 produced milk with 60% less
calcium than that of heterozygous or wildtype mice. There was no
alteration in whole-body calcium metabolism in the null mice. The
findings indicated that the Pmca2bw isoform, which allows the enzyme to
function as a high affinity calcium extrusion system on the apical
membrane, is necessary to produce the high levels of calcium in milk,
and that it occurs by direct secretion by the calcium pump.
Bortolozzi et al. (2010) characterized Tommy (tmy) mutant mice, which
were generated in an N-ethyl-N-nitrosurea mutagenesis screen. Tmy/tmy
mice were profoundly deaf at birth and were smaller than their
littermates. They developed severe ataxia, with hesitant wobbly gait and
frequent hyperextension of the rear limbs. Tmy heterozygous mice
developed deafness by 12 weeks of age, with full penetrance by 30 weeks.
Bortolozzi et al. (2010) identified the tmy mutation as a
nonconservative G-to-A transition in exon 7 of the Atp2b2 gene,
resulting in a gln629-to-lys (E629K) substitution in Atp2b2 w/a, the
Atp2b2 isoform expressed in hair cells (the substitution corresponds to
E584K in the Atp2b2 z/b isoform, which lacks the 45-amino acid insertion
in Atp2b2 w/a). Expression of mutant Atp2b2 in Chinese hamster ovary
cells caused impaired calcium extrusion, with inhibition of long-term,
nonstimulated calcium export. Recordings of neonate organotypic cultures
of utricle sensory epithelium confirmed impaired calcium export in both
tmy/tmy and tmy/+ mice following rapid calcium release.
Immunofluorescence analysis of the organ of Corti in tmy/tmy mice showed
a progressive base to apex degeneration of hair cells after postnatal
day 40.
*FIELD* AV
.0001
DEAFNESS, AUTOSOMAL RECESSIVE 12, MODIFIER OF
ATP2B2, VAL586MET
In 3 of 5 sibs, born of consanguineous parents, with autosomal recessive
deafness (DFNB12; 601386) caused by a homozygous phe1888-to-ser
substitution in the CDH23 gene (F1888S; 605516.0010), Schultz et al.
(2005) identified a heterozygous 2075G-A transition in exon 12 of the
ATP2B2 gene, resulting in a val586-to-met (V586M) substitution. The 3
sibs heterozygous for V586M had severe to profound hearing loss
affecting all frequencies, whereas the other 2 sibs had high-frequency
hearing loss. Schultz et al. (2005) suggested that V586M modifies the
severity of sensorineural hearing loss.
*FIELD* RF
1. Bortolozzi, M.; Brini, M.; Parkinson, N.; Crispino, G.; Scimemi,
P.; De Siati, R. D.; Di Leva, F.; Parker, A.; Ortolano, S.; Arslan,
E.; Brown, S. D.; Carafoli, E.; Mammano, F.: The novel PMCA2 pump
mutation Tommy impairs cytosolic calcium clearance in hair cells and
links to deafness in mice. J. Biol. Chem. 285: 37693-37703, 2010.
2. Brandt, P.; Ibrahim, E.; Bruns, G. A. P.; Neve, R. L.: Determination
of the nucleotide sequence and chromosomal localization of the ATP2B2
gene encoding human Ca(2+)-pumping ATPase isoform PMCA2. Genomics 14:
484-487, 1992.
3. 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.
4. Chicka, M. C.; Strehler, E. E.: Alternative splicing of the first
intracellular loop of plasma membrane Ca2+-ATPase isoform 2 alters
its membrane targeting. J. Biol. Chem. 278: 18464-18470, 2003.
5. DeMarco, S. J.; Chicka, M. C.; Strehler, E. E.: Plasma membrane
Ca(2+) ATPase isoform 2b interacts preferentially with Na+/H+ exchanger
regulatory factor 2 in apical plasma membranes. J. Biol. Chem. 277:
10506-10511, 2002.
6. Elwess, N. L.; Filoteo, A. G.; Enyedi, A.; Penniston, J. T.: Plasma
membrane Ca2+ pump isoforms 2a and 2b are unusually responsive to
calmodulin and Ca2+. J. Biol. Chem. 272: 17981-17986, 1997.
7. Kozel, P. J.; Friedman, R. A.; Erway, L. C.; Yamoah, E. N.; Liu,
L. H.; Riddle, T.; Duffy, J. J.; Doetschman, T.; Miller, M. L.; Cardell,
E. L.; Shull, G. E.: Balance and hearing deficits in mice with a
null mutation in the gene encoding plasma membrane Ca(2+)-ATPase isoform
2. J. Biol. Chem. 273: 18693-18696, 1998.
8. Reinhardt, T. A.; Lippolis, J. D.; Shull, G. E.; Horst, R. L.:
Null mutation in the gene encoding plasma membrane Ca(2+)-ATPase isoform
2 impairs calcium transport into milk. J. Biol. Chem. 279: 42369-42373,
2004.
9. Richards, F. M.; Phipps, M. E.; Latif, F.; Yao, M.; Crossey, P.
A.; Foster, K.; Linehan, W. M.; Affara, N. A.; Lerman, M. I.; Zbar,
B.; Ferguson-Smith, M. A.; Maher, E. R.: Mapping the von Hippel-Lindau
disease tumour suppressor gene: identification of germline deletions
by pulsed field gel electrophoresis. Hum. Molec. Genet. 2: 879-882,
1993.
10. 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. Biochem. 155:
173-182, 1996.
11. Schultz, J. M.; Yang, Y.; Caride, A. J.; Filoteo, A. G.; Penheiter,
A. R.; Lagziel, A.; Morell, R. J.; Mohiddin, S. A.; Fananapazir, L.;
Madeo, A. C.; Penniston, J. T.; Griffith, A. J.: Modification of
human hearing loss by plasma-membrane calcium pump PMCA2. New Eng.
J. Med. 352: 1557-1564, 2005. Note: Erratum: New Eng. J. Med. 352:
2362 only, 2005.
12. Street, V. A.; McKee-Johnson, J. W.; Fonseca, R. C.; Tempel, B.
L.; Noben-Trauth, K.: Mutations in a plasma membrane Ca(2+)-ATPase
gene cause deafness in deafwaddler mice. Nature Genet. 19: 390-394,
1998.
13. Wang, M. G.; Yi, H.; Hilfiker, H.; Carafoli, E.; Strehler, E.
E.; McBride, O. W.: Localization of two genes encoding plasma membrane
Ca(2+)-ATPases isoforms 2 (ATP2B2) and 3 (ATP2B3) to human chromosomes
3p26-p25 and Xq28, respectively. Cytogenet. Cell Genet. 67: 41-45,
1994.
*FIELD* CN
Patricia A. Hartz - updated: 3/7/2011
Victor A. McKusick - updated: 4/21/2005
Patricia A. Hartz - updated: 2/8/2005
Cassandra L. Kniffin - reorganized: 11/29/2004
Cassandra L. Kniffin - updated: 11/22/2004
Victor A. McKusick - updated: 8/18/1998
Victor A. McKusick - updated: 7/28/1998
*FIELD* CD
Victor A. McKusick: 10/15/1992
*FIELD* ED
carol: 01/07/2014
terry: 3/16/2011
mgross: 3/14/2011
terry: 3/7/2011
wwang: 5/5/2009
tkritzer: 4/28/2005
terry: 4/21/2005
terry: 2/22/2005
mgross: 2/8/2005
tkritzer: 11/29/2004
ckniffin: 11/22/2004
ckniffin: 3/23/2004
dkim: 11/13/1998
carol: 8/18/1998
terry: 8/18/1998
alopez: 7/31/1998
terry: 7/28/1998
terry: 10/10/1994
jason: 7/5/1994
carol: 8/17/1993
carol: 10/15/1992
*RECORD*
*FIELD* NO
108733
*FIELD* TI
*108733 ATPase, Ca(2+)-TRANSPORTING, PLASMA MEMBRANE, 2; ATP2B2
;;PLASMA MEMBRANE Ca(2+)-ATPase, TYPE 2; PMCA2
read more*FIELD* TX
DESCRIPTION
The Ca(2+)-ATPases are a family of plasma membrane pumps encoded by at
least 4 genes: ATP2B1 (108731) on chromosome 12q21; ATP2B2; ATP2B3
(300014) on Xq28; and ATP2B4 (108732) on 1q25.
CLONING
Brandt et al. (1992) isolated and characterized a cDNA for the human
PMCA2 gene from a human fetal brain cDNA library. The 1,190-amino acid
protein showed greater than 98% sequence identity to the rat protein.
By PCR, Brandt et al. (1992) detected PMCA2 expression in brain, liver,
spinal cord, and adrenal gland. There were 2 PCR products in spinal
cord, suggesting the presence of PMCA2 splice variants.
By RT-PCR, Santiago-Garcia et al. (1996) found variable expression of
the PMCA and SERCA (see 108730) genes during development of human fetal
heart. PMCA2 was not detected in placenta or in fetal heart at the 3
stages tested, but 3 splice variants of PMCA2 were detected in adult
atrium.
Street et al. (1998) noted that the ATP2B2 gene undergoes alternative
splicing. All 4 ATP2B proteins are predicted to have 10
transmembrane-spanning domains with approximately 80% of the protein
mass located in the cytoplasm. The intracellular loop between T2 and T3
encodes the transducing domain that couples ATP hydrolysis with calcium
translocation. The largest intracellular loop, between T4 and T5,
includes the phosphoenzyme-forming residue and the nucleotide-binding
domain. The intracellular C terminus contains the calmodulin-binding,
protein kinase C, cAMP-dependent kinase and acidic phospholipid
regulatory domains.
GENE FUNCTION
Elwess et al. (1997) found that the alternative splice variants PMCA2a
and PMCA2b had much higher affinity for calmodulin than the
corresponding forms of PMCA4. At a high calmodulin concentration, PMCA2b
showed higher calcium affinity. The calcium affinity was localized to
the C terminus. Elwess et al. (1997) concluded that the PMCA2 variants
maintain a low free cytosolic calcium concentration.
Street et al. (1998) found Atp2b2 expression in mouse auditory and
vestibular hair cells, suggesting that the channel provides the means to
remove calcium from stereocilia.
By yeast 2-hybrid analysis of a human brain cDNA expression library,
DeMarco et al. (2002) found that PCMA2b interacted with NHERF2
(SLC9A3R2; 606553). Coimmunoprecipitation analysis indicated that the
interaction was specific and selective, in that PCMA4b did not interact
with either NHERF2 or NHERF1 (SLC9A3R1; 604990), and PCMA2b preferred
NHERF2 over NHERF1. Fluorescence-tagged PCMA2b was expressed at the
apical membrane of canine kidney epithelial cells, where it colocalized
with apically targeted NHERF2. DeMarco et al. (2002) hypothesized that
the PCMA2b-NHERF2 interaction may allow the assembly of PMCA2b in a
multiprotein Ca(2+) signaling complex.
Chicka and Strehler (2003) found that PMCA2b localized to both the
apical and basolateral membranes of polarized epithelial cells.
Different splice variants of the protein showed differential membrane
targeting.
MAPPING
Using the PMCA2 cDNA to probe Southern blots of human-rodent somatic
cell hybrid DNAs, Brandt et al. (1992) mapped the PMCA2 gene to human
chromosome 3. By a combination of fluorescence in situ hybridization,
analysis of somatic cell hybrids, and genetic linkage analysis in CEPH
families, Wang et al. (1994) confirmed assignment of the ATP2B2 gene to
3p26-p25.
Richards et al. (1993) reported that the PMCA2 gene, which is located on
3p, is situated centromeric to the gene (VHL; 608537) for von
Hippel-Lindau disease (193300). They reported other results that
excluded PMCA2 as the site of the mutation in VHL.
ANIMAL MODEL
Street et al. (1998) demonstrated that the deafwaddler (dfw) mouse
mutant, which is deaf and displays vestibular/motor imbalance, has a
mutation in the Atp2b2 gene. An A-to-G nucleotide transition in dfw DNA
caused a glycine-to-serine substitution at a highly conserved amino acid
position, whereas a second mutant allele carried a 2-bp deletion that
caused a frameshift predicted to result in a truncated protein. In the
cochlea, the Atp2b2 protein was localized to stereocilia and the
basolateral wall of hair cells in wildtype mice, but was not detected in
deafwaddler mice. The findings indicated that mutation of Atp2b2 may
cause deafness and imbalance by affecting sensory transduction in
stereocilia as well as neurotransmitter release from the basolateral
membrane. These mutations affecting Atp2b2 were the first to be found in
a mammalian plasma membrane calcium pump and defined a new class of
deafness genes that directly affect hair-cell physiology.
PMCA2 exhibits a highly restricted tissue distribution, suggesting that
it serves more specialized physiologic functions than some of the other
PMCA isoforms. A unique role in hearing is suggested by the high levels
of PMCA2 expression in cochlear outer hair cells and spiral ganglion
cells. To analyze the physiologic role of PMCA2, Kozel et al. (1998)
produced PMCA2-deficient mice by gene targeting. Homozygous PMCA2-null
mice grew more slowly than heterozygous and wildtype mice and exhibited
an unsteady gait and difficulties in maintaining balance. Histologic
analysis of the cerebellum and inner ear of mutant and wildtype mice
showed that null mutants have slightly increased numbers of Purkinje
neurons (in which PMCA2 is highly expressed), a decreased thickness of
the molecular layer, an absence of otoconia in the vestibular system,
and a range of abnormalities of the organ of Corti. Analysis of
auditory-evoked brainstem responses showed that homozygous mutants were
deaf and that heterozygous mice had a significant hearing loss. These
data demonstrated that PMCA2 is required for both balance and hearing
and suggested that it may be a major source of the calcium used in the
formation and maintenance of otoconia.
Reinhardt et al. (2004) noted that the PMCA2bw isoform is expressed
approximately 100-fold during lactation, and that expression levels
correlate with milk production and calcium secretion. They found that
mice homozygous for the loss of Pmca2 produced milk with 60% less
calcium than that of heterozygous or wildtype mice. There was no
alteration in whole-body calcium metabolism in the null mice. The
findings indicated that the Pmca2bw isoform, which allows the enzyme to
function as a high affinity calcium extrusion system on the apical
membrane, is necessary to produce the high levels of calcium in milk,
and that it occurs by direct secretion by the calcium pump.
Bortolozzi et al. (2010) characterized Tommy (tmy) mutant mice, which
were generated in an N-ethyl-N-nitrosurea mutagenesis screen. Tmy/tmy
mice were profoundly deaf at birth and were smaller than their
littermates. They developed severe ataxia, with hesitant wobbly gait and
frequent hyperextension of the rear limbs. Tmy heterozygous mice
developed deafness by 12 weeks of age, with full penetrance by 30 weeks.
Bortolozzi et al. (2010) identified the tmy mutation as a
nonconservative G-to-A transition in exon 7 of the Atp2b2 gene,
resulting in a gln629-to-lys (E629K) substitution in Atp2b2 w/a, the
Atp2b2 isoform expressed in hair cells (the substitution corresponds to
E584K in the Atp2b2 z/b isoform, which lacks the 45-amino acid insertion
in Atp2b2 w/a). Expression of mutant Atp2b2 in Chinese hamster ovary
cells caused impaired calcium extrusion, with inhibition of long-term,
nonstimulated calcium export. Recordings of neonate organotypic cultures
of utricle sensory epithelium confirmed impaired calcium export in both
tmy/tmy and tmy/+ mice following rapid calcium release.
Immunofluorescence analysis of the organ of Corti in tmy/tmy mice showed
a progressive base to apex degeneration of hair cells after postnatal
day 40.
*FIELD* AV
.0001
DEAFNESS, AUTOSOMAL RECESSIVE 12, MODIFIER OF
ATP2B2, VAL586MET
In 3 of 5 sibs, born of consanguineous parents, with autosomal recessive
deafness (DFNB12; 601386) caused by a homozygous phe1888-to-ser
substitution in the CDH23 gene (F1888S; 605516.0010), Schultz et al.
(2005) identified a heterozygous 2075G-A transition in exon 12 of the
ATP2B2 gene, resulting in a val586-to-met (V586M) substitution. The 3
sibs heterozygous for V586M had severe to profound hearing loss
affecting all frequencies, whereas the other 2 sibs had high-frequency
hearing loss. Schultz et al. (2005) suggested that V586M modifies the
severity of sensorineural hearing loss.
*FIELD* RF
1. Bortolozzi, M.; Brini, M.; Parkinson, N.; Crispino, G.; Scimemi,
P.; De Siati, R. D.; Di Leva, F.; Parker, A.; Ortolano, S.; Arslan,
E.; Brown, S. D.; Carafoli, E.; Mammano, F.: The novel PMCA2 pump
mutation Tommy impairs cytosolic calcium clearance in hair cells and
links to deafness in mice. J. Biol. Chem. 285: 37693-37703, 2010.
2. Brandt, P.; Ibrahim, E.; Bruns, G. A. P.; Neve, R. L.: Determination
of the nucleotide sequence and chromosomal localization of the ATP2B2
gene encoding human Ca(2+)-pumping ATPase isoform PMCA2. Genomics 14:
484-487, 1992.
3. 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.
4. Chicka, M. C.; Strehler, E. E.: Alternative splicing of the first
intracellular loop of plasma membrane Ca2+-ATPase isoform 2 alters
its membrane targeting. J. Biol. Chem. 278: 18464-18470, 2003.
5. DeMarco, S. J.; Chicka, M. C.; Strehler, E. E.: Plasma membrane
Ca(2+) ATPase isoform 2b interacts preferentially with Na+/H+ exchanger
regulatory factor 2 in apical plasma membranes. J. Biol. Chem. 277:
10506-10511, 2002.
6. Elwess, N. L.; Filoteo, A. G.; Enyedi, A.; Penniston, J. T.: Plasma
membrane Ca2+ pump isoforms 2a and 2b are unusually responsive to
calmodulin and Ca2+. J. Biol. Chem. 272: 17981-17986, 1997.
7. Kozel, P. J.; Friedman, R. A.; Erway, L. C.; Yamoah, E. N.; Liu,
L. H.; Riddle, T.; Duffy, J. J.; Doetschman, T.; Miller, M. L.; Cardell,
E. L.; Shull, G. E.: Balance and hearing deficits in mice with a
null mutation in the gene encoding plasma membrane Ca(2+)-ATPase isoform
2. J. Biol. Chem. 273: 18693-18696, 1998.
8. Reinhardt, T. A.; Lippolis, J. D.; Shull, G. E.; Horst, R. L.:
Null mutation in the gene encoding plasma membrane Ca(2+)-ATPase isoform
2 impairs calcium transport into milk. J. Biol. Chem. 279: 42369-42373,
2004.
9. Richards, F. M.; Phipps, M. E.; Latif, F.; Yao, M.; Crossey, P.
A.; Foster, K.; Linehan, W. M.; Affara, N. A.; Lerman, M. I.; Zbar,
B.; Ferguson-Smith, M. A.; Maher, E. R.: Mapping the von Hippel-Lindau
disease tumour suppressor gene: identification of germline deletions
by pulsed field gel electrophoresis. Hum. Molec. Genet. 2: 879-882,
1993.
10. 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. Biochem. 155:
173-182, 1996.
11. Schultz, J. M.; Yang, Y.; Caride, A. J.; Filoteo, A. G.; Penheiter,
A. R.; Lagziel, A.; Morell, R. J.; Mohiddin, S. A.; Fananapazir, L.;
Madeo, A. C.; Penniston, J. T.; Griffith, A. J.: Modification of
human hearing loss by plasma-membrane calcium pump PMCA2. New Eng.
J. Med. 352: 1557-1564, 2005. Note: Erratum: New Eng. J. Med. 352:
2362 only, 2005.
12. Street, V. A.; McKee-Johnson, J. W.; Fonseca, R. C.; Tempel, B.
L.; Noben-Trauth, K.: Mutations in a plasma membrane Ca(2+)-ATPase
gene cause deafness in deafwaddler mice. Nature Genet. 19: 390-394,
1998.
13. Wang, M. G.; Yi, H.; Hilfiker, H.; Carafoli, E.; Strehler, E.
E.; McBride, O. W.: Localization of two genes encoding plasma membrane
Ca(2+)-ATPases isoforms 2 (ATP2B2) and 3 (ATP2B3) to human chromosomes
3p26-p25 and Xq28, respectively. Cytogenet. Cell Genet. 67: 41-45,
1994.
*FIELD* CN
Patricia A. Hartz - updated: 3/7/2011
Victor A. McKusick - updated: 4/21/2005
Patricia A. Hartz - updated: 2/8/2005
Cassandra L. Kniffin - reorganized: 11/29/2004
Cassandra L. Kniffin - updated: 11/22/2004
Victor A. McKusick - updated: 8/18/1998
Victor A. McKusick - updated: 7/28/1998
*FIELD* CD
Victor A. McKusick: 10/15/1992
*FIELD* ED
carol: 01/07/2014
terry: 3/16/2011
mgross: 3/14/2011
terry: 3/7/2011
wwang: 5/5/2009
tkritzer: 4/28/2005
terry: 4/21/2005
terry: 2/22/2005
mgross: 2/8/2005
tkritzer: 11/29/2004
ckniffin: 11/22/2004
ckniffin: 3/23/2004
dkim: 11/13/1998
carol: 8/18/1998
terry: 8/18/1998
alopez: 7/31/1998
terry: 7/28/1998
terry: 10/10/1994
jason: 7/5/1994
carol: 8/17/1993
carol: 10/15/1992