AT2C2_HUMAN
ID AT2C2_HUMAN Reviewed; 946 AA.
AC O75185; B4DU76; E7ES94; Q5HYC3; Q5S053; Q68CQ2;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 3.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Calcium-transporting ATPase type 2C member 2 {ECO:0000305};
DE Short=ATPase 2C2;
DE EC=7.2.2.10 {ECO:0000269|PubMed:15677451, ECO:0000269|PubMed:15831496, ECO:0000269|PubMed:16332677, ECO:0000269|PubMed:30923126};
DE AltName: Full=Ca(2+)/Mn(2+)-ATPase 2C2 {ECO:0000303|PubMed:15831496};
DE AltName: Full=Secretory pathway Ca(2+)-transporting ATPase type 2;
DE Short=SPCA2 {ECO:0000303|PubMed:15677451};
GN Name=ATP2C2 {ECO:0000312|HGNC:HGNC:29103}; Synonyms=KIAA0703, SPCA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-165, FUNCTION,
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15831496; DOI=10.1074/jbc.m501026200;
RA Vanoevelen J., Dode L., Van Baelen K., Fairclough R.J., Missiaen L.,
RA Raeymaekers L., Wuytack F.;
RT "The secretory pathway Ca2+/Mn2+-ATPase 2 is a Golgi-localized pump with
RT high affinity for Ca2+ ions.";
RL J. Biol. Chem. 280:22800-22808(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-466.
RC TISSUE=Prostate;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP GLN-604.
RC TISSUE=Endometrium, and Small intestine;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=15677451; DOI=10.1074/jbc.m413116200;
RA Xiang M., Mohamalawari D., Rao R.;
RT "A novel isoform of the secretory pathway Ca2+,Mn(2+)-ATPase, hSPCA2, has
RT unusual properties and is expressed in the brain.";
RL J. Biol. Chem. 280:11608-11614(2005).
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16332677; DOI=10.1074/jbc.m511547200;
RA Dode L., Andersen J.P., Vanoevelen J., Raeymaekers L., Missiaen L.,
RA Vilsen B., Wuytack F.;
RT "Dissection of the functional differences between human secretory pathway
RT Ca2+/Mn2+-ATPase (SPCA) 1 and 2 isoenzymes by steady-state and transient
RT kinetic analyses.";
RL J. Biol. Chem. 281:3182-3189(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-264; SER-267 AND SER-268, 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).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ORAI1, AND MUTAGENESIS OF
RP ASP-379 AND ASP-772.
RX PubMed=20887894; DOI=10.1016/j.cell.2010.08.040;
RA Feng M., Grice D.M., Faddy H.M., Nguyen N., Leitch S., Wang Y., Muend S.,
RA Kenny P.A., Sukumar S., Roberts-Thomson S.J., Monteith G.R., Rao R.;
RT "Store-independent activation of Orai1 by SPCA2 in mammary tumors.";
RL Cell 143:84-98(2010).
RN [10]
RP FUNCTION.
RX PubMed=23840669; DOI=10.1371/journal.pone.0067348;
RA Cross B.M., Hack A., Reinhardt T.A., Rao R.;
RT "SPCA2 regulates Orai1 trafficking and store independent Ca2+ entry in a
RT model of lactation.";
RL PLoS ONE 8:e67348-e67348(2013).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=30923126; DOI=10.1074/jbc.ra118.006250;
RA Chen J., Smaardijk S., Mattelaer C.A., Pamula F., Vandecaetsbeek I.,
RA Vanoevelen J., Wuytack F., Lescrinier E., Eggermont J., Vangheluwe P.;
RT "An N-terminal Ca2+-binding motif regulates the secretory pathway
RT Ca2+/Mn2+-transport ATPase SPCA1.";
RL J. Biol. Chem. 294:7878-7891(2019).
CC -!- FUNCTION: ATP-driven pump that supplies the Golgi apparatus with Ca(2+)
CC and Mn(2+) ions, both essential cofactors for processing and
CC trafficking of newly synthesized proteins in the secretory pathway
CC (PubMed:15831496, PubMed:16332677, PubMed:30923126, PubMed:15677451).
CC Within a catalytic cycle, acquires Ca(2+) or Mn(2+) ions on the
CC cytoplasmic side of the membrane and delivers them to the lumenal side.
CC The transfer of ions across the membrane is coupled to ATP hydrolysis
CC and is associated with a transient phosphorylation that shifts the pump
CC conformation from inward-facing to outward-facing state
CC (PubMed:15831496, PubMed:16332677). Induces Ca(2+) influx independently
CC of its ATP-driven pump function. At the basolateral membrane of mammary
CC epithelial cells, interacts with Ca(2+) channel ORAI1 and mediates
CC Ca(2+) entry independently of the Ca(2+) content of endoplasmic
CC reticulum or Golgi stores. May facilitate transepithelial transport of
CC large quantities of Ca(2+) for milk secretion via activation of Ca(2+)
CC influx channels at the plasma membrane and active Ca(2+) transport at
CC the Golgi apparatus (PubMed:23840669, PubMed:20887894).
CC {ECO:0000269|PubMed:15677451, ECO:0000269|PubMed:15831496,
CC ECO:0000269|PubMed:16332677, ECO:0000269|PubMed:20887894,
CC ECO:0000269|PubMed:23840669, ECO:0000269|PubMed:30923126}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + Ca(2+)(in) + H2O = ADP + Ca(2+)(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:18105, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29108, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456216; EC=7.2.2.10;
CC Evidence={ECO:0000269|PubMed:15677451, ECO:0000269|PubMed:15831496,
CC ECO:0000269|PubMed:16332677, ECO:0000269|PubMed:30923126};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106;
CC Evidence={ECO:0000305|PubMed:15677451, ECO:0000305|PubMed:15831496,
CC ECO:0000305|PubMed:16332677, ECO:0000305|PubMed:30923126};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + Mn(2+)(in) = ADP + H(+) + Mn(2+)(out) + phosphate;
CC Xref=Rhea:RHEA:66820, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29035, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:15831496,
CC ECO:0000269|PubMed:30923126};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66821;
CC Evidence={ECO:0000269|PubMed:30923126, ECO:0000305|PubMed:15831496};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.03 uM for Ca(2+) (Ca(2+)-dependent ATP hydrolysis)
CC {ECO:0000269|PubMed:30923126};
CC KM=0.06 uM for Mn(2+) (Mn(2+)-dependent ATP hydrolysis)
CC {ECO:0000269|PubMed:30923126};
CC -!- SUBUNIT: Interacts (via N-terminus) with ORAI1 (via N- and C-termini);
CC this interaction regulates Ca(2+) influx at the plasma membrane.
CC {ECO:0000269|PubMed:20887894}.
CC -!- INTERACTION:
CC O75185; Q96D31: ORAI1; NbExp=10; IntAct=EBI-2939806, EBI-2291476;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000269|PubMed:15831496}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:20887894}; Multi-pass
CC membrane protein {ECO:0000255}. Basolateral cell membrane
CC {ECO:0000250|UniProtKB:A7L9Z8}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O75185-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75185-2; Sequence=VSP_035989;
CC Name=3;
CC IsoId=O75185-3; Sequence=VSP_054679;
CC -!- TISSUE SPECIFICITY: Highly expressed in the gastrointestinal and
CC respiratory tracts, prostate, thyroid, salivary, and mammary glands
CC (PubMed:15831496). Expressed in colon epithelial cells (at protein
CC level). Expressed in brain and testis (at protein level)
CC (PubMed:15677451). {ECO:0000269|PubMed:15677451,
CC ECO:0000269|PubMed:15831496}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IIA subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA31678.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY791884; AAV54193.1; -; mRNA.
DR EMBL; AB014603; BAA31678.2; ALT_INIT; mRNA.
DR EMBL; AK300526; BAG62238.1; -; mRNA.
DR EMBL; BX648333; CAI46049.1; -; mRNA.
DR EMBL; CR749829; CAH18686.1; -; mRNA.
DR EMBL; AC010551; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022165; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS42207.1; -. [O75185-1]
DR CCDS; CCDS67088.1; -. [O75185-3]
DR RefSeq; NP_001273456.2; NM_001286527.2. [O75185-3]
DR RefSeq; NP_001278383.1; NM_001291454.1.
DR RefSeq; NP_055676.3; NM_014861.3. [O75185-1]
DR AlphaFoldDB; O75185; -.
DR SMR; O75185; -.
DR BioGRID; 115243; 2.
DR IntAct; O75185; 2.
DR STRING; 9606.ENSP00000397925; -.
DR DrugBank; DB01189; Desflurane.
DR TCDB; 3.A.3.2.9; the p-type atpase (p-atpase) superfamily.
DR iPTMnet; O75185; -.
DR PhosphoSitePlus; O75185; -.
DR BioMuta; ATP2C2; -.
DR jPOST; O75185; -.
DR MassIVE; O75185; -.
DR PaxDb; O75185; -.
DR PeptideAtlas; O75185; -.
DR PRIDE; O75185; -.
DR ProteomicsDB; 17939; -.
DR ProteomicsDB; 49858; -. [O75185-1]
DR ProteomicsDB; 49859; -. [O75185-2]
DR Antibodypedia; 58367; 63 antibodies from 23 providers.
DR DNASU; 9914; -.
DR Ensembl; ENST00000262429.9; ENSP00000262429.4; ENSG00000064270.13. [O75185-1]
DR Ensembl; ENST00000416219.6; ENSP00000397925.2; ENSG00000064270.13. [O75185-3]
DR GeneID; 9914; -.
DR KEGG; hsa:9914; -.
DR MANE-Select; ENST00000262429.9; ENSP00000262429.4; NM_014861.4; NP_055676.3.
DR UCSC; uc002fhx.4; human. [O75185-1]
DR CTD; 9914; -.
DR DisGeNET; 9914; -.
DR GeneCards; ATP2C2; -.
DR HGNC; HGNC:29103; ATP2C2.
DR HPA; ENSG00000064270; Tissue enhanced (intestine, skin).
DR MIM; 613082; gene.
DR neXtProt; NX_O75185; -.
DR OpenTargets; ENSG00000064270; -.
DR PharmGKB; PA162377204; -.
DR VEuPathDB; HostDB:ENSG00000064270; -.
DR eggNOG; KOG0202; Eukaryota.
DR GeneTree; ENSGT00940000160275; -.
DR HOGENOM; CLU_002360_3_1_1; -.
DR InParanoid; O75185; -.
DR OMA; IGWVQGK; -.
DR OrthoDB; 100699at2759; -.
DR PhylomeDB; O75185; -.
DR TreeFam; TF354251; -.
DR BRENDA; 7.2.2.10; 2681.
DR PathwayCommons; O75185; -.
DR Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR SignaLink; O75185; -.
DR BioGRID-ORCS; 9914; 10 hits in 1060 CRISPR screens.
DR ChiTaRS; ATP2C2; human.
DR GenomeRNAi; 9914; -.
DR Pharos; O75185; Tbio.
DR PRO; PR:O75185; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O75185; protein.
DR Bgee; ENSG00000064270; Expressed in rectum and 131 other tissues.
DR ExpressionAtlas; O75185; baseline and differential.
DR Genevisible; O75185; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IEA:Ensembl.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032588; C:trans-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005388; F:P-type calcium transporter activity; IDA:UniProtKB.
DR GO; GO:0015662; F:P-type ion transporter activity; IBA:GO_Central.
DR GO; GO:0140613; F:P-type manganese transporter activity; IDA:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0061180; P:mammary gland epithelium development; IEA:Ensembl.
DR GO; GO:0006828; P:manganese ion transport; IBA:GO_Central.
DR GO; GO:0090280; P:positive regulation of calcium ion import; IEA:Ensembl.
DR GO; GO:0072659; P:protein localization to plasma membrane; IEA:Ensembl.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR030334; ATP2C2.
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_dom_N.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR006413; P-type_ATPase_IIA_PMR1.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR PANTHER; PTHR42861:SF23; PTHR42861:SF23; 1.
DR Pfam; PF00689; Cation_ATPase_C; 1.
DR Pfam; PF00690; Cation_ATPase_N; 1.
DR PRINTS; PR00120; HATPASE.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01522; ATPase-IIA2_Ca; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 2.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Calcium; Calcium transport;
KW Cell membrane; Golgi apparatus; Ion transport; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..946
FT /note="Calcium-transporting ATPase type 2C member 2"
FT /id="PRO_0000046207"
FT TOPO_DOM 1..106
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 107..127
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 128..129
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 130..150
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 151..231
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 232..252
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 253..293
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 294..314
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 315..331
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 332..352
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 353..750
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 751..771
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 772..804
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 805..825
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 826..837
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 838..855
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 856..874
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 875..895
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 896..905
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 906..926
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 927..946
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 71..95
FT /note="Interaction with ORAI1"
FT /evidence="ECO:0000269|PubMed:20887894"
FT ACT_SITE 379
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 332
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 333
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 335
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 337
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 674
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 678
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 768
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 772
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 264
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 1..70
FT /note="MVEGRVSEFLKKLGFSGGGRQYQALEKDEEEALIDEQSELKAIEKEKKVTAL
FT PPKEACKCQKEDLARAFC -> MLHFHLLKFKTRVVFSAVIIMVTGLCLFLLSLPHLHG
FT VFEQVPAPWWTSLCPWPIMEAAAFQSGSLYPVASFLAAPMSELVPDLSFQ (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:9734811"
FT /id="VSP_035989"
FT VAR_SEQ 778
FT /note="S -> RSSQKTEVCCTAVRLGVEGRGESTWAGRAG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_054679"
FT VARIANT 165
FT /note="L -> M (in dbSNP:rs247818)"
FT /evidence="ECO:0000269|PubMed:15831496"
FT /id="VAR_059137"
FT VARIANT 411
FT /note="G -> S (in dbSNP:rs2303853)"
FT /id="VAR_047935"
FT VARIANT 466
FT /note="M -> L (in dbSNP:rs247897)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_047936"
FT VARIANT 604
FT /note="L -> Q (in dbSNP:rs62640926)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_070929"
FT VARIANT 907
FT /note="L -> P (in dbSNP:rs16973859)"
FT /id="VAR_047937"
FT MUTAGEN 379
FT /note="D->N: Loss of calcium-dependent ATPase activity. Has
FT no effect on trafficking to the plasma membrane."
FT /evidence="ECO:0000269|PubMed:20887894"
FT MUTAGEN 772
FT /note="D->A: Loss of calcium-dependent ATPase activity."
FT /evidence="ECO:0000269|PubMed:20887894"
FT CONFLICT 171
FT /note="N -> D (in Ref. 4; CAI46049)"
FT /evidence="ECO:0000305"
FT CONFLICT 361
FT /note="V -> A (in Ref. 4; CAI46049)"
FT /evidence="ECO:0000305"
FT CONFLICT 880
FT /note="L -> R (in Ref. 4; CAI46049)"
FT /evidence="ECO:0000305"
FT CONFLICT O75185-2:12
FT /note="R -> I (in Ref. 2; BAA31678)"
FT /evidence="ECO:0000305"
FT CONFLICT O75185-3:789
FT /note="A -> G (in Ref. 4; CAI46049)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 946 AA; 103169 MW; E270F10EAAD185E3 CRC64;
MVEGRVSEFL KKLGFSGGGR QYQALEKDEE EALIDEQSEL KAIEKEKKVT ALPPKEACKC
QKEDLARAFC VDLHTGLSEF SVTQRRLAHG WNEFVADNSE PVWKKYLDQF KNPLILLLLG
SALVSVLTKE YEDAVSIATA VLVVVTVAFI QEYRSEKSLE ELTKLVPPEC NCLREGKLQH
LLARELVPGD VVSLSIGDRI PADIRLTEVT DLLVDESSFT GEAEPCSKTD SPLTGGGDLT
TLSNIVFMGT LVQYGRGQGV VIGTGESSQF GEVFKMMQAE ETPKTPLQKS MDRLGKQLTL
FSFGIIGLIM LIGWSQGKQL LSMFTIGVSL AVAAIPEGLP IVVMVTLVLG VLRMAKKRVI
VKKLPIVETL GCCSVLCSDK TGTLTANEMT VTQLVTSDGL RAEVSGVGYD GQGTVCLLPS
KEVIKEFSNV SVGKLVEAGC VANNAVIRKN AVMGQPTEGA LMALAMKMDL SDIKNSYIRK
KEIPFSSEQK WMAVKCSLKT EDQEDIYFMK GALEEVIRYC TMYNNGGIPL PLTPQQRSFC
LQEEKRMGSL GLRVLALASG PELGRLTFLG LVGIIDPPRV GVKEAVQVLS ESGVSVKMIT
GDALETALAI GRNIGLCNGK LQAMSGEEVD SVEKGELADR VGKVSVFFRT SPKHKLKIIK
ALQESGAIVA MTGDGVNDAV ALKSADIGIA MGQTGTDVSK EAANMILVDD DFSAIMNAVE
EGKGIFYNIK NFVRFQLSTS ISALSLITLS TVFNLPSPLN AMQILWINII MDGPPAQSLG
VEPVDKDAFR QPPRSVRDTI LSRALILKIL MSAAIIISGT LFIFWKEMPE DRASTPRTTT
MTFTCFVFFD LFNALTCRSQ TKLIFEIGFL RNHMFLYSVL GSILGQLAVI YIPPLQRVFQ
TENLGALDLL FLTGLASSVF ILSELLKLCE KYCCSPKRVQ MHPEDV
