AT2C1_MOUSE
ID AT2C1_MOUSE Reviewed; 918 AA.
AC Q80XR2; E9QMB9; Q80YZ2;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Calcium-transporting ATPase type 2C member 1;
DE Short=ATPase 2C1;
DE EC=7.2.2.10 {ECO:0000250|UniProtKB:P98194};
DE AltName: Full=ATP-dependent Ca(2+) pump PMR1;
DE AltName: Full=Ca(2+)/Mn(2+)-ATPase 2C1 {ECO:0000250|UniProtKB:P98194};
DE AltName: Full=Secretory pathway Ca(2+)-transporting ATPase type 1;
DE Short=SPCA1 {ECO:0000303|PubMed:17597066};
GN Name=Atp2c1 {ECO:0000303|PubMed:17597066, ECO:0000312|MGI:MGI:1889008};
GN Synonyms=Pmr1;
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], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=14747290; DOI=10.2337/diabetes.53.2.393;
RA Mitchell K.J., Tsuboi T., Rutter G.A.;
RT "Role for plasma membrane-related Ca2+-ATPase-1 (ATP2C1) in pancreatic
RT beta-cell Ca2+ homeostasis revealed by RNA silencing.";
RL Diabetes 53:393-400(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 127-133, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=17597066; DOI=10.1074/jbc.m703029200;
RA Okunade G.W., Miller M.L., Azhar M., Andringa A., Sanford L.P.,
RA Doetschman T., Prasad V., Shull G.E.;
RT "Loss of the Atp2c1 secretory pathway Ca(2+)-ATPase (SPCA1) in mice causes
RT Golgi stress, apoptosis, and midgestational death in homozygous embryos and
RT squamous cell tumors in adult heterozygotes.";
RL J. Biol. Chem. 282:26517-26527(2007).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19793975; DOI=10.1523/jneurosci.2014-09.2009;
RA Sepulveda M.R., Vanoevelen J., Raeymaekers L., Mata A.M., Wuytack F.;
RT "Silencing the SPCA1 (secretory pathway Ca2+-ATPase isoform 1) impairs Ca2+
RT homeostasis in the Golgi and disturbs neural polarity.";
RL J. Neurosci. 29:12174-12182(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (By
CC similarity). Within a catalytic cycle, acquires Ca(2+) or Mn(2+) ions
CC on the cytoplasmic side of the membrane and delivers them to the
CC lumenal side. The transfer of ions across the membrane is coupled to
CC ATP hydrolysis and is associated with a transient phosphorylation that
CC shifts the pump conformation from inward-facing to outward-facing state
CC (By similarity). Plays a primary role in the maintenance of Ca(2+)
CC homeostasis in the trans-Golgi compartment with a functional impact on
CC Golgi and post-Golgi protein sorting as well as a structural impact on
CC cisternae morphology. Responsible for loading the Golgi stores with
CC Ca(2+) ions in keratinocytes, contributing to keratinocyte
CC differentiation and epidermis integrity (By similarity). Participates
CC in Ca(2+) and Mn(2+) ions uptake into the Golgi store of hippocampal
CC neurons and regulates protein trafficking required for neural polarity
CC (PubMed:19793975). May also play a role in the maintenance of Ca(2+)
CC and Mn(2+) homeostasis and signaling in the cytosol while preventing
CC cytotoxicity (By similarity). {ECO:0000250|UniProtKB:P98194,
CC ECO:0000269|PubMed:19793975}.
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:P98194};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106;
CC Evidence={ECO:0000250|UniProtKB:P98194};
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:P98194};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66821;
CC Evidence={ECO:0000250|UniProtKB:P98194};
CC -!- SUBUNIT: Monomer. Homodimer. {ECO:0000250|UniProtKB:P98194}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000250|UniProtKB:P98194}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus, Golgi stack membrane
CC {ECO:0000269|PubMed:19793975}; Multi-pass membrane protein
CC {ECO:0000255}. Note=During neuron differentiation, shifts from
CC juxtanuclear Golgi position to multiple Golgi structures distributed
CC over the neural soma with a predominance in the apical dendritic trunk.
CC {ECO:0000269|PubMed:19793975}.
CC -!- TISSUE SPECIFICITY: Expressed in hippocampal neurons in the CA3 region
CC of the Amon's horn (at protein level) (PubMed:19793975). Expressed in
CC brain, heart, lung, stomach, liver, colon and mammary gland
CC (PubMed:17597066). {ECO:0000269|PubMed:17597066,
CC ECO:0000269|PubMed:19793975}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice, born at the expected Mendelian rate,
CC show growth retardation and exencephaly by 9.5 dpc and die by 10.5 dpc.
CC {ECO:0000269|PubMed:17597066}.
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; AJ551270; CAD82864.1; -; mRNA.
DR EMBL; AC113016; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC117679; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC043091; AAH43091.1; -; mRNA.
DR CCDS; CCDS40752.1; -.
DR RefSeq; NP_001240760.1; NM_001253831.1.
DR RefSeq; NP_001240763.1; NM_001253834.1.
DR RefSeq; NP_778190.3; NM_175025.4.
DR AlphaFoldDB; Q80XR2; -.
DR SMR; Q80XR2; -.
DR BioGRID; 231683; 4.
DR STRING; 10090.ENSMUSP00000039103; -.
DR iPTMnet; Q80XR2; -.
DR PhosphoSitePlus; Q80XR2; -.
DR SwissPalm; Q80XR2; -.
DR EPD; Q80XR2; -.
DR jPOST; Q80XR2; -.
DR MaxQB; Q80XR2; -.
DR PaxDb; Q80XR2; -.
DR PRIDE; Q80XR2; -.
DR ProteomicsDB; 277125; -.
DR Antibodypedia; 4128; 347 antibodies from 33 providers.
DR DNASU; 235574; -.
DR Ensembl; ENSMUST00000038118; ENSMUSP00000039103; ENSMUSG00000032570.
DR Ensembl; ENSMUST00000112558; ENSMUSP00000108177; ENSMUSG00000032570.
DR GeneID; 235574; -.
DR KEGG; mmu:235574; -.
DR UCSC; uc009rif.3; mouse.
DR CTD; 27032; -.
DR MGI; MGI:1889008; Atp2c1.
DR VEuPathDB; HostDB:ENSMUSG00000032570; -.
DR eggNOG; KOG0202; Eukaryota.
DR GeneTree; ENSGT00940000156421; -.
DR InParanoid; Q80XR2; -.
DR OMA; GVHRMAK; -.
DR OrthoDB; 100699at2759; -.
DR TreeFam; TF354251; -.
DR Reactome; R-MMU-936837; Ion transport by P-type ATPases.
DR BioGRID-ORCS; 235574; 4 hits in 75 CRISPR screens.
DR ChiTaRS; Atp2c1; mouse.
DR PRO; PR:Q80XR2; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q80XR2; protein.
DR Bgee; ENSMUSG00000032570; Expressed in secondary oocyte and 258 other tissues.
DR ExpressionAtlas; Q80XR2; baseline and differential.
DR Genevisible; Q80XR2; MM.
DR GO; GO:0033106; C:cis-Golgi network membrane; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0032580; C:Golgi cisterna membrane; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0030173; C:integral component of Golgi membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; TAS:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0030141; C:secretory granule; ISO:MGI.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0030133; C:transport vesicle; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006816; P:calcium ion transport; ISS:UniProtKB.
DR GO; GO:0016339; P:calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; ISS:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISS:UniProtKB.
DR GO; GO:0030026; P:cellular manganese ion homeostasis; ISS:UniProtKB.
DR GO; GO:0008544; P:epidermis development; ISS:UniProtKB.
DR GO; GO:0032468; P:Golgi calcium ion homeostasis; IMP:UniProtKB.
DR GO; GO:0032472; P:Golgi calcium ion transport; ISS:UniProtKB.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006828; P:manganese ion transport; ISS:UniProtKB.
DR GO; GO:0042998; P:positive regulation of Golgi to plasma membrane protein transport; IMP:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0098629; P:trans-Golgi network membrane organization; ISS:UniProtKB.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR030336; ATP2C1.
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:SF2; PTHR42861:SF2; 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; Direct protein sequencing;
KW Golgi apparatus; Ion transport; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Reference proteome; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..918
FT /note="Calcium-transporting ATPase type 2C member 1"
FT /id="PRO_0000046224"
FT TOPO_DOM 1..78
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 79..95
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 96..99
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..121
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 122..262
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 263..282
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 283..294
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..316
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 317..699
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 700..722
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 723..727
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 728..751
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 752..775
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 776..794
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 795..801
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 802..827
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 828..842
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 843..862
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 863..875
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 876..892
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 893..918
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 349
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 643
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 647
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT CONFLICT 156
FT /note="V -> A (in Ref. 1; CAD82864)"
FT /evidence="ECO:0000305"
FT CONFLICT 189
FT /note="T -> I (in Ref. 3; AAH43091)"
FT /evidence="ECO:0000305"
FT CONFLICT 217
FT /note="F -> S (in Ref. 1; CAD82864)"
FT /evidence="ECO:0000305"
FT CONFLICT 280
FT /note="M -> T (in Ref. 1; CAD82864)"
FT /evidence="ECO:0000305"
FT CONFLICT 743
FT /note="P -> S (in Ref. 3; AAH43091)"
FT /evidence="ECO:0000305"
FT CONFLICT 813
FT /note="C -> R (in Ref. 1; CAD82864)"
FT /evidence="ECO:0000305"
FT CONFLICT 902
FT /note="E -> G (in Ref. 1; CAD82864)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 918 AA; 100299 MW; 8C57096C69AA7C15 CRC64;
MKVARFQKIP NVENETMIPV LTSKRASELA VSEVAGLLQA DLQNGLNKSE VSHRRAFHGW
NEFDISEDEP LWKKYISQFK NPLIMLLLAS AVISILMRQF DDAVSITVAI VIVVTVAFVQ
EYRSEKSLEE LSKLVPPECH CVREGKLEHT LARDLVPGDT VCLSVGDRVP ADLRLFEAVD
LSVDESSLTG ETAPCSKVTA PQPAANGDLA SRSNIAFMGT LVRCGKAKGI VIGTGENSEF
GEVFKMMQAE EAPKTPLQKS MDLLGKQLSF YSFGIIGIIM LVGWLLGKDI LEMFTISVSL
AVAAIPEGLP IVVTVTLALG VMRMVKKRAI VKKLPIVETL GCCNVICSDK TGTLTKNEMT
VTHILTSDGL HAEVTGVGYN QFGEVIVDGD VVHGFYNPAV SRIVEAGCVC NDAVIRNNTL
MGKPTEGALI ALAMKMGLDG LQQDYIRKAE YPFSSEQKWM AVKCVHRTQQ DRPEICFMKG
AYEQVIKYCT TYNSKGQTLA LTQQQRDLYQ QEKARMGSAG LRVLALASGP ELGQLTFLGL
VGIIDPPRTG VKEAVTTLIA SGVSIKMITG DSQETAIAIA SRLGLYSKTS QSVSGEEVDT
MEVQHLSQIV PKVAVFYRAS PRHKMKIIKS LQKNGAVVAM TGDGVNDAVA LKAADIGVAM
GQTGTDVCKE AADMILVDDD FQTIMSAIEE GKGIYNNIKN FVRFQLSTSI AALTLISLAT
LMNFPNPLNA MQILWINIIM DGPPAQSLGV EPVDKDVIRK PPRNWKDSIL TKNLILKILV
SSIIIVCGTL FVFWRELRDN VITPRDTTMT FTCFVFFDMF NALSSRSQTK SVFEIGLCSN
KMFCYAVLGS IMGQLLVIYF PPLQKVFQTE SLSILDLLFL LGLTSSVCIV SEIIKKVERS
REKVQKNAGS ASSSFLEV
