AT2C2_MOUSE
ID AT2C2_MOUSE Reviewed; 944 AA.
AC A7L9Z8; Q5DU19;
DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Calcium-transporting ATPase type 2C member 2;
DE Short=ATPase 2C2;
DE EC=7.2.2.10 {ECO:0000250|UniProtKB:O75185};
DE AltName: Full=Ca(2+)/Mn(2+)-ATPase 2C2 {ECO:0000303|PubMed:15677451};
DE AltName: Full=Secretory pathway Ca(2+)-transporting ATPase type 2;
DE Short=SPCA2 {ECO:0000303|PubMed:15677451};
GN Name=Atp2c2 {ECO:0000312|MGI:MGI:1916297}; Synonyms=Kiaa0703, Spca2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=SWR/J;
RA Sepulveda M.R., Vanoevelen J., Raeymaekers L., Wuytack F.;
RT "SPCA2 of Mus musculus.";
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 88-897.
RC TISSUE=Brain;
RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The
RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT screening of terminal sequences of cDNA clones randomly sampled from size-
RT fractionated libraries.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP SUBCELLULAR LOCATION, 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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP ORAI1.
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).
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 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 (By
CC similarity). Induces Ca(2+) influx independently of its ATP-driven pump
CC function. At the basolateral membrane of mammary epithelial cells,
CC interacts with Ca(2+) channel ORAI1 and mediates Ca(2+) entry
CC independently of the Ca(2+) content of endoplasmic reticulum or Golgi
CC stores. May facilitate transepithelial transport of large quantities of
CC Ca(2+) for milk secretion via activation of Ca(2+) influx channels at
CC the plasma membrane and active Ca(2+) transport at the Golgi apparatus
CC (PubMed:23840669) (By similarity). {ECO:0000250|UniProtKB:O75185,
CC ECO:0000269|PubMed:23840669}.
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:0000250|UniProtKB:O75185};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106;
CC Evidence={ECO:0000250|UniProtKB:O75185};
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:0000250|UniProtKB:O75185};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66821;
CC Evidence={ECO:0000250|UniProtKB:O75185};
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:0000250|UniProtKB:O75185, ECO:0000269|PubMed:23840669}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000269|PubMed:15677451}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:O75185}; Multi-pass
CC membrane protein {ECO:0000255}. Basolateral cell membrane
CC {ECO:0000269|PubMed:23840669}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in hippocampal neurons (at protein level)
CC (PubMed:15677451). Expressed in lactating mammary epithelium (at
CC protein level) (PubMed:23840669). {ECO:0000269|PubMed:15677451,
CC ECO:0000269|PubMed:23840669}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IIA subfamily. {ECO:0000305}.
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DR EMBL; EF688288; ABS18966.1; -; mRNA.
DR EMBL; AK220351; BAD90414.1; -; mRNA.
DR CCDS; CCDS52684.1; -.
DR RefSeq; NP_081198.1; NM_026922.1.
DR AlphaFoldDB; A7L9Z8; -.
DR SMR; A7L9Z8; -.
DR STRING; 10090.ENSMUSP00000092794; -.
DR PhosphoSitePlus; A7L9Z8; -.
DR MaxQB; A7L9Z8; -.
DR PaxDb; A7L9Z8; -.
DR PeptideAtlas; A7L9Z8; -.
DR PRIDE; A7L9Z8; -.
DR ProteomicsDB; 281819; -.
DR Antibodypedia; 58367; 63 antibodies from 23 providers.
DR Ensembl; ENSMUST00000095171; ENSMUSP00000092794; ENSMUSG00000034112.
DR GeneID; 69047; -.
DR KEGG; mmu:69047; -.
DR UCSC; uc009nqg.1; mouse.
DR CTD; 9914; -.
DR MGI; MGI:1916297; Atp2c2.
DR VEuPathDB; HostDB:ENSMUSG00000034112; -.
DR eggNOG; KOG0202; Eukaryota.
DR GeneTree; ENSGT00940000160275; -.
DR HOGENOM; CLU_002360_3_1_1; -.
DR InParanoid; A7L9Z8; -.
DR OMA; IGWVQGK; -.
DR OrthoDB; 100699at2759; -.
DR PhylomeDB; A7L9Z8; -.
DR TreeFam; TF354251; -.
DR Reactome; R-MMU-936837; Ion transport by P-type ATPases.
DR BioGRID-ORCS; 69047; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Atp2c2; mouse.
DR PRO; PR:A7L9Z8; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; A7L9Z8; protein.
DR Bgee; ENSMUSG00000034112; Expressed in prostate gland ventral lobe and 71 other tissues.
DR ExpressionAtlas; A7L9Z8; baseline and differential.
DR Genevisible; A7L9Z8; MM.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
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; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032588; C:trans-Golgi network membrane; IDA: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; ISS:UniProtKB.
DR GO; GO:0015662; F:P-type ion transporter activity; IBA:GO_Central.
DR GO; GO:0140613; F:P-type manganese transporter activity; ISO:MGI.
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; IMP:MGI.
DR GO; GO:0006828; P:manganese ion transport; IBA:GO_Central.
DR GO; GO:0090280; P:positive regulation of calcium ion import; IMP:MGI.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:MGI.
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 ATP-binding; Calcium; Calcium transport; Cell membrane; Golgi apparatus;
KW Ion transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..944
FT /note="Calcium-transporting ATPase type 2C member 2"
FT /id="PRO_0000356156"
FT TOPO_DOM 1..104
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 105..125
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 126..127
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 128..148
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 149..229
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 230..250
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 251..291
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 292..312
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 313..329
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 330..350
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 351..748
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 749..769
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 770..802
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 803..823
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 824..835
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 836..853
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 854..872
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 873..893
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 894..903
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 904..924
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 925..944
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 69..93
FT /note="Interaction with ORAI1"
FT /evidence="ECO:0000250|UniProtKB:O75185"
FT ACT_SITE 377
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 330
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 331
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 672
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 676
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 766
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 770
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 262
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O75185"
FT MOD_RES 266
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75185"
SQ SEQUENCE 944 AA; 102528 MW; B585BFFB96AAA375 CRC64;
MGRRLKFLQK LAFLGQNHRY KALERDEVET LIDEQCELKA IEREKTVAAL PPGEACKCSR
EELARAFHVD LDSGLSEFAV AQRRLVHGWN EFVTDNAEPV WKKYLDQFRN PLILLLLGSS
VVSVLTKEYE DAVSIALAVL IVVTVGFIQE YRSEKSLEEL TKLVPPECNC LRDGKLRHML
ARDLVPGDIV SLSMGDRIPA DIRLTEVTDL LVDESSFTGE VEPCGKTDSP LADGGDLSTL
SNVVFMGTLV QCGKGQGVVI GTGEQSQFGE VFKMMRAEET PKTPLQKSMD KLGKQLTIFS
FGIIGLLMLV GWVQGKPFLS MFTVGVSLAV AAIPEGLPIV VMVTLVLGVL RMAKKRVIVK
KLPIVETLGC CNVICSDKTG TLTANEMTAT QLVTSDGFHA EVSGVGYSGE GTVCLLPSKE
VIKGFDNVSV GKLVEAGCVA NNAVIRKNAV MGQPTEGALV VLAMKMNLGS IKDSYVRKKE
IPFSSEQKWM AVRCGPKSED GEDIYFMKGA FEEVIHHCSM YNNGGIPLPL TPQQKSYCQQ
EEKKMGSLGL RVLALASGPE LGRLTFLGLV GIIDPPRAGV KEAVQVLSES GVSVKMVTGD
ALETALAIGR TIGLCNEKLK AMSGEEVEGT EQGALAARVR QVSVFFRTSP KHKVKIIKAL
QESGAIVAMT GDGVNDSVAL KSADIGIAMG QTGTDVSKEA ANMILVDDDF SAIMSAVEEG
KGIFYNIKNF VRFQLSTSIA ALSLITLSTV CNLPSPLNAM QILWVNIIMD GPPAQSLGVE
PVDRDALRRP PRSVGDTILN RALILRVLMS AAVIIGGTLF IFWREIPANG TSTPRTTTMA
FTCFVFFDLF NALSCRSQTK LIFEIGFFRN RMFLYSVLGS LLGQLAVIYA PPLQKVFQTE
NLSALDLLLL TGLASSVFIL SELLKLWEKF LSRARPTQML PEAV
