ID AT2B2_HUMAN Reviewed; 1243 AA. AC Q01814; O00766; Q12994; Q16818; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 2. DT 19-MAR-2014, entry version 149. 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-1177 (ISOFORM WA), RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1146 (ISOFORM XA), RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1163 (ISOFORM YA), RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1132 (ISOFORM ZA), AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. 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). 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. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 52-1087, 1123-1150. DR BioGrid; 106981; 9. 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. [Q01814-5] DR Ensembl; ENST00000352432; ENSP00000324172; ENSG00000157087. [Q01814-1] DR Ensembl; ENST00000360273; ENSP00000353414; ENSG00000157087. [Q01814-1] DR Ensembl; ENST00000383800; ENSP00000373311; ENSG00000157087. [Q01814-6] DR Ensembl; ENST00000397077; ENSP00000380267; ENSG00000157087. [Q01814-6] DR Ensembl; ENST00000460129; ENSP00000424494; ENSG00000157087. [Q01814-4] DR GeneID; 491; -. DR KEGG; hsa:491; -. DR UCSC; uc003bvt.3; human. [Q01814-1] DR UCSC; uc003bvv.3; human. [Q01814-6] 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 TreeFam; TF300330; -. 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 component of 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 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 //