Details for: ATP2C2

Gene ID: 9914

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ATP2C2

Ensembl ID: ENSG00000064270

Description: ATPase secretory pathway Ca2+ transporting 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • small intestine goblet cell CL1000495
    CSI 12.19
    rCSI 26.69%
    PRS 93.56
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 7.96
    rCSI 30.07%
    PRS 79.97
  • squamous epithelial cell CL0000076
    CSI 7.09
    rCSI 16.82%
    PRS 88.84
  • deuterosomal cell CL4033044
    CSI 6.66
    rCSI 22.53%
    PRS 86.53
  • L6b glutamatergic cortical neuron CL4023038
    CSI 4.75
    rCSI 14.83%
    PRS 81.08
  • multi-ciliated epithelial cell CL0005012
    CSI 4.24
    rCSI 4.23%
    PRS 86.44
  • duct epithelial cell CL0000068
    CSI 3.95
    rCSI 5.78%
    PRS 94.51
  • lung secretory cell CL1000272
    CSI 3.92
    rCSI 9.7%
    PRS 92.31
  • epithelial cell of lower respiratory tract CL0002632
    CSI 3.72
    rCSI 2.89%
    PRS 93.67
  • lung ciliated cell CL1000271
    CSI 3.72
    rCSI 4.3%
    PRS 86.65
  • enterocyte of epithelium of large intestine CL0002071
    CSI 3.71
    rCSI 19.5%
    PRS 93.21
  • ciliated cell CL0000064
    CSI 3.37
    rCSI 5.45%
    PRS 86.12
  • colon goblet cell CL0009039
    CSI 3.33
    rCSI 7.91%
    PRS 93.15
  • intestine goblet cell CL0019031
    CSI 3.27
    rCSI 2.9%
    PRS 89.36
  • secretory cell CL0000151
    CSI 3.26
    rCSI 3.41%
    PRS 90.69
  • brush cell of tracheobronchial tree CL0002075
    CSI 3.23
    rCSI 9.57%
    PRS 96.2
  • epithelial cell of lung CL0000082
    CSI 3.01
    rCSI 2.49%
    PRS 92.49
  • enteroendocrine cell CL0000164
    CSI 2.81
    rCSI 3.83%
    PRS 89.97
  • ciliated epithelial cell CL0000067
    CSI 2.71
    rCSI 2.38%
    PRS 83.57
  • goblet cell CL0000160
    CSI 2.61
    rCSI 2.46%
    PRS 89.66
  • mucus secreting cell CL0000319
    CSI 2.55
    rCSI 4.04%
    PRS 95.27
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 2.49
    rCSI 4.53%
    PRS 85.73
  • enteroendocrine cell of small intestine CL0009006
    CSI 2.46
    rCSI 5.42%
    PRS 93.99
  • BEST4+ enteroycte CL4030026
    CSI 2.41
    rCSI 2.99%
    PRS 91.31
  • transit amplifying cell of colon CL0009011
    CSI 2.38
    rCSI 2.79%
    PRS 91.58
  • nasal mucosa goblet cell CL0002480
    CSI 2.31
    rCSI 2.68%
    PRS 91.92
  • colon epithelial cell CL0011108
    CSI 2.3
    rCSI 2.41%
    PRS 89.58
  • bronchial goblet cell CL1000312
    CSI 2.05
    rCSI 8.19%
    PRS 94.31
  • respiratory suprabasal cell CL4033048
    CSI 2.02
    rCSI 2.6%
    PRS 93.01
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 2
    rCSI 5.4%
    PRS 93.52
  • club cell CL0000158
    CSI 1.95
    rCSI 2.85%
    PRS 87.8
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.93
    rCSI 6.94%
    PRS 77.84
  • epithelial cell of proximal tubule CL0002306
    CSI 1.89
    rCSI 4.62%
    PRS 85.72
  • pulmonary alveolar type 2 cell CL0002063
    CSI 1.81
    rCSI 2.8%
    PRS 92.26
  • respiratory basal cell CL0002633
    CSI 1.72
    rCSI 1.78%
    PRS 93.02
  • glandular epithelial cell CL0000150
    CSI 1.71
    rCSI 4.49%
    PRS 96.72
  • basal cell of epidermis CL0002187
    CSI 1.7
    rCSI 3.01%
    PRS 64.2
  • transit amplifying cell CL0009010
    CSI 1.69
    rCSI 2.59%
    PRS 94.76
  • renal beta-intercalated cell CL0002201
    CSI 1.61
    rCSI 3.83%
    PRS 91.73
  • tracheal goblet cell CL1000329
    CSI 1.56
    rCSI 3.4%
    PRS 93.54
  • transit amplifying cell of small intestine CL0009012
    CSI 1.53
    rCSI 6.7%
    PRS 94.55
  • intestinal crypt stem cell of colon CL0009043
    CSI 1.5
    rCSI 11.25%
    PRS 95.48
  • intestinal tuft cell CL0019032
    CSI 1.42
    rCSI 2.17%
    PRS 93.08
  • pulmonary alveolar type 1 cell CL0002062
    CSI 1.41
    rCSI 8.1%
    PRS 89.09
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.36
    rCSI 2.4%
    PRS 79.14
  • paneth cell of epithelium of small intestine CL1000343
    CSI 1.18
    rCSI 3.31%
    PRS 94.22
  • respiratory goblet cell CL0002370
    CSI 1.08
    rCSI 11.72%
    PRS 93.86
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.06
    rCSI 2.41%
    PRS 85.16
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 0.88
    rCSI 1.07%
    PRS 73.29
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.64
    rCSI 3.78%
    PRS 80.2
  • acinar cell of salivary gland CL0002623
    CSI 0.25
    rCSI 5.91%
    PRS 95.9

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [ATP2C2](/details-gene/9914), or ATPase Secretory Pathway Ca2+ Transporting 2, encodes a P-type ATPase that functions as a calcium and manganese ion pump. It is primarily localized to the Golgi apparatus and plays a crucial role in maintaining ion homeostasis within the secretory pathway, a process essential for correct protein processing, sorting, and secretion. The gene's expression profile reveals high significance in a variety of specialized epithelial cells, particularly those with high secretory functions like [small intestine goblet cell](/details-cell/CL1000495)s and ciliated cells. Additionally, notable expression in specific neuronal subtypes, such as [near-projecting glutamatergic cortical neuron](/details-cell/CL4023012), suggests a specialized role in neural calcium signaling. Its function has been linked to lactation and mammary gland development, with some evidence suggesting a role in store-independent calcium entry in certain cancer types ([Link](https://doi.org/10.1016/j.cell.2010.08.040)). ## Cellular Roles and Expression Landscape **Overall**, the expression pattern of [ATP2C2](/details-gene/9914) highlights its importance in cells characterized by high rates of protein secretion, vesicular trafficking, and specialized transport functions. The most significant expression is observed in secretory epithelial populations. It is a top marker in [small intestine goblet cell](/details-cell/CL1000495) (CSI: 12.19) and also highly significant in [colon goblet cell](/details-cell/CL0009039) and [lung secretory cell](/details-cell/CL1000272). This is consistent with its function in the Golgi, where precise calcium concentrations are required for the proper folding and packaging of secreted products like mucins. Its high significance in other epithelial cell types, including [squamous epithelial cell](/details-cell/CL0000076) and [duct epithelial cell](/details-cell/CL0000068), further underscores a fundamental role in maintaining epithelial integrity and function. A second major cellular context for [ATP2C2](/details-gene/9914) is ciliated epithelium. The gene shows high significance in [multi-ciliated epithelial cell](/details-cell/CL0005012) and their precursors, [deuterosomal cell](/details-cell/CL4033044), as well as [lung ciliated cell](/details-cell/CL1000271). This suggests its role in ion homeostasis may also be critical for the assembly, maintenance, or function of cilia. Finally, a distinct role in the nervous system is indicated by its high significance in specific neuronal populations, including [near-projecting glutamatergic cortical neuron](/details-cell/CL4023012) and [L6b glutamatergic cortical neuron](/details-cell/CL4023038). This is supported by research identifying a brain-expressed isoform of the protein ([Link](https://doi.org/10.1074/jbc.m413116200)), suggesting a specialized function in regulating calcium-dependent processes at the synapse, such as neurotransmitter packaging or release. ## Pathways and Molecular Function The molecular functions of [ATP2C2](/details-gene/9914) are centered on ATP-dependent ion transport across membranes. It is annotated with [P-type calcium transporter activity](/details-go/GO:0005388) and [P-type manganese transporter activity](/details-go/GO:0140613), requiring [ATP binding](/details-go/GO:0005524) for its function. These activities contribute directly to the biological processes of [calcium ion transmembrane transport](/details-go/GO:0070588) and [intracellular calcium ion homeostasis](/details-go/GO:0006874). Its cellular localization is predominantly within the secretory pathway, with annotations for the [Golgi membrane](/details-go/GO:0000139), [trans-Golgi network membrane](/details-go/GO:0032588), and [endoplasmic reticulum](/details-go/GO:0005783). This placement is critical for its function, as it pumps calcium ions from the cytosol into the lumen of these organelles. This function is essential for the Reactome pathway [Ion transport by p-type ATPases](/details-reactome/R-HSA-936837). The requirement for precise Golgi calcium levels for protein maturation and secretion directly explains the high expression of [ATP2C2](/details-gene/9914) in secretory cells like goblet cells. Furthermore, its involvement in [mammary gland epithelium development](/details-go/GO:0061180) has been mechanistically linked to its ability to regulate Orai1 trafficking and store-independent Ca2+ entry, a critical signaling pathway during lactation ([Link](https'://doi.org/10.1371/journal.pone.0067348)). ## Research Directions The well-defined role of [ATP2C2](/details-gene/9914) in Golgi Ca2+ homeostasis, combined with its specific expression patterns, provides a foundation for several testable hypotheses regarding its role in health and disease. 1. **Hypothesis 1:** Given its exceptionally high significance in [small intestine goblet cell](/details-cell/CL1000495)s, dysfunction or downregulation of [ATP2C2](/details-gene/9914) may be a contributing factor in inflammatory bowel diseases (IBD). A failure to maintain Golgi Ca2+ levels could lead to misfolding and aggregation of mucin proteins, triggering an unfolded protein response and compromising the integrity of the protective intestinal mucus layer. 2. **Hypothesis 2:** The specific expression of [ATP2C2](/details-gene/9914) in glutamatergic neurons suggests it is critical for managing local Ca2+ dynamics related to synaptic transmission. Aberrant [ATP2C2](/details-gene/9914) activity could disrupt the packaging of neurotransmitters into synaptic vesicles or alter postsynaptic signaling, potentially contributing to synaptic dysfunction seen in certain neurodegenerative or psychiatric disorders. **Proposed Experiment to Test Hypothesis 1:** To test the role of [ATP2C2](/details-gene/9914) in goblet cell function and intestinal barrier integrity, an intestinal organoid model could be employed. Organoids would be generated from both wild-type and `Atp2c2`-knockout mice. These organoids would be challenged with inflammatory cytokines (e.g., IL-13) or an ER/Golgi stress-inducing agent (e.g., tunicamycin). The impact on goblet cell function would be assessed by quantifying MUC2 production via immunohistochemistry and ELISA, measuring organoid swelling as an indicator of secretion, and evaluating the activation of cellular stress pathways (e.g., XBP1 splicing) using RT-qPCR. **Therapeutic Potential:** The involvement of [ATP2C2](/details-gene/9914) in promoting store-independent calcium entry via Orai1 in mammary tumors suggests it could be a therapeutic target ([Link](https://doi.org/10.1016/j.cell.2010.08.040)). In cancers where this pathway is hijacked to drive proliferation or metastasis, **inhibition** of [ATP2C2](/details-gene/9914) could represent a viable strategy. However, its broad expression in healthy secretory epithelial and neuronal tissues poses a significant challenge for systemic therapy, raising the potential for off-target toxicity. The development of highly specific small molecule inhibitors or targeted delivery systems (e.g., antibody-drug conjugates if a suitable surface marker co-expresses) would be necessary to exploit this potential therapeutically.

Genular Protein ID: 3189373408

Symbol: AT2C2_HUMAN

Name: Secretory pathway Ca(2+)-transporting ATPase type 2

UniProtKB Accession Codes:

O75185 B4DU76 E7ES94 Q5HYC3 Q5S053 Q68CQ2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 20 ChiTaRS 1 DNASU 1 DisGeNET 1 DrugBank 3 EC 1 EMBL 7 Ensembl 2 ExpressionAtlas 1 GO 19 Gene3D 4 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 11 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 2 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 5 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 1 RefSeq 3 Rhea 4 SABIO-RK 1 SFLD 2 SMART 1 SMR 1 STRING 1 SUPFAM 4 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 15831496

Title: The secretory pathway Ca2+/Mn2+-ATPase 2 is a Golgi-localized pump with high affinity for Ca2+ ions.

PubMed ID: 15831496

DOI: 10.1074/jbc.m501026200

PubMed ID: 9734811

Title: Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.

PubMed ID: 9734811

DOI: 10.1093/dnares/5.3.169

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 15616553

Title: The sequence and analysis of duplication-rich human chromosome 16.

PubMed ID: 15616553

DOI: 10.1038/nature03187

PubMed ID: 15677451

Title: A novel isoform of the secretory pathway Ca2+,Mn(2+)-ATPase, hSPCA2, has unusual properties and is expressed in the brain.

PubMed ID: 15677451

DOI: 10.1074/jbc.m413116200

PubMed ID: 16332677

Title: Dissection of the functional differences between human secretory pathway Ca2+/Mn2+-ATPase (SPCA) 1 and 2 isoenzymes by steady-state and transient kinetic analyses.

PubMed ID: 16332677

DOI: 10.1074/jbc.m511547200

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 20887894

Title: Store-independent activation of Orai1 by SPCA2 in mammary tumors.

PubMed ID: 20887894

DOI: 10.1016/j.cell.2010.08.040

PubMed ID: 23840669

Title: SPCA2 regulates Orai1 trafficking and store independent Ca2+ entry in a model of lactation.

PubMed ID: 23840669

DOI: 10.1371/journal.pone.0067348

PubMed ID: 30923126

Title: An N-terminal Ca2+-binding motif regulates the secretory pathway Ca2+/Mn2+-transport ATPase SPCA1.

PubMed ID: 30923126

DOI: 10.1074/jbc.ra118.006250

Sequence Information:

  • Length: 946
  • Mass: 103169
  • Checksum: E270F10EAAD185E3
  • Sequence:
    • 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

Genular Protein ID: 332761828

Symbol: B3KR57_HUMAN

Name: N/A

UniProtKB Accession Codes:

B3KR57

Database IDs:

ARBA 10 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChEBI 12 DNASU 1 DisGeNET 1 EC 1 EMBL 2 GO 8 Gene3D 4 InterPro 10 NCBI Taxonomy 1 NCBIfam 2 OrthoDB 1 PANTHER 2 PRINTS 2 PROSITE 1 PeptideAtlas 1 Pfam 5 RefSeq 1 Rhea 4 RuleBase 1 SFLD 2 SUPFAM 4

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

Sequence Information:

  • Length: 795
  • Mass: 86145
  • Checksum: 16702E7EE70F7AB3
  • Sequence:
    • MRTPSASPRQ CLSWSLSPSS SLREGKLQHL LARELVPGDV VSLSIGDRIP ADIRLTEVTD 
LLVDESSFTG EAEPCSKTDS PLTGGGDLTT LSNIVFMGTL VQYGRGQGVV IGTGESSQFG 
EVFKMMQAEE TPKTPLQKSM DRLGKQLTLF SFGIIGLIML IGWSQGKQLL SMFTIGVSLA 
VAAIPEGLPI VVMVTLVLGV LRMAKKRVIV KKLPIVETLG CCSVLCSDKT GTLTANEMTV 
TQLVTSDGLR AEVSGVGYDS QGTVCLLPSK EVIKEFSNVS VGKLVEAGCV ANNAVIRKNA 
VMGQPTEGAL MALAMKMDLS DIKNSYIRKK EIPFSSEQKW MAVKCSLKTE DQEDIYFMKG 
ALEEVIRYCT MYNNGGIPLP LTPQQRSFCL QEEKRMGSLG LRVLALASGP ELGRLTFLGL 
VGIIDPPRVG VKEAVQVLSE SGVSVKMITG DAQETALAIG RNIGLCNGKL QAMSGEEVDS 
VEKGELADRV GKVSVFFRTS PKHKLKIIKA LQESGAIVAM TGDGVNDAVA LKSADIGIAM 
GQTGTDVSKE AANMILVDDD FSATMNAVEE GKGIFYNIKN FVRFQLSTSI SALSLITLST 
VFNLPSPLNA MQILWINIIM DGPPAQSLGV EPVDKDAFRQ PPRSVRDTIL SRALILKILM 
SAAIIISGTL FIFWKEMPED RASTPRTTTM TFTCFVFFDL FNALTCRSQT KLIFEIGFLR 
NHMFLYSVLG SILGQLAVIY IPPLQRVFQT ENLGALDLLF LTGLASSVFI LSELLKLCEK 
YCCSPKRVQM HPEDV