ATP2C1

Protein identityUniProt · HPA

UniProt accession

P98194

Gene

ATP2C1

Ensembl

ENSG00000017260

Chromosome

3

Canonical length

919 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted membrane proteins, Transporters

Subcellular location

Golgi apparatus

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene belongs to the family of P-type cation transport ATPases. This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium ions. Defects in this gene cause Hailey-Hailey disease, an autosomal dominant disorder. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

Canonical amino-acid sequenceUniProt

919 residues, UniProt reviewed canonical sequence.

>P98194|ATP2C1
     1  MKVARFQKIP NGENETMIPV LTSKKASELP VSEVASILQA DLQNGLNKCE VSHRRAFHGW
    61  NEFDISEDEP LWKKYISQFK NPLIMLLLAS AVISVLMHQF DDAVSITVAI LIVVTVAFVQ
   121  EYRSEKSLEE LSKLVPPECH CVREGKLEHT LARDLVPGDT VCLSVGDRVP ADLRLFEAVD
   181  LSIDESSLTG ETTPCSKVTA PQPAATNGDL ASRSNIAFMG TLVRCGKAKG VVIGTGENSE
   241  FGEVFKMMQA EEAPKTPLQK SMDLLGKQLS FYSFGIIGII MLVGWLLGKD ILEMFTISVS
   301  LAVAAIPEGL PIVVTVTLAL GVMRMVKKRA IVKKLPIVET LGCCNVICSD KTGTLTKNEM
   361  TVTHIFTSDG LHAEVTGVGY NQFGEVIVDG DVVHGFYNPA VSRIVEAGCV CNDAVIRNNT
   421  LMGKPTEGAL IALAMKMGLD GLQQDYIRKA EYPFSSEQKW MAVKCVHRTQ QDRPEICFMK
   481  GAYEQVIKYC TTYQSKGQTL TLTQQQRDVY QQEKARMGSA GLRVLALASG PELGQLTFLG
   541  LVGIIDPPRT GVKEAVTTLI ASGVSIKMIT GDSQETAVAI ASRLGLYSKT SQSVSGEEID
   601  AMDVQQLSQI VPKVAVFYRA SPRHKMKIIK SLQKNGSVVA MTGDGVNDAV ALKAADIGVA
   661  MGQTGTDVCK EAADMILVDD DFQTIMSAIE EGKGIYNNIK NFVRFQLSTS IAALTLISLA
   721  TLMNFPNPLN AMQILWINII MDGPPAQSLG VEPVDKDVIR KPPRNWKDSI LTKNLILKIL
   781  VSSIIIVCGT LFVFWRELRD NVITPRDTTM TFTCFVFFDM FNALSSRSQT KSVFEIGLCS
   841  NRMFCYAVLG SIMGQLLVIY FPPLQKVFQT ESLSILDLLF LLGLTSSVCI VAEIIKKVER
   901  SREKIQKHVS STSSSFLEV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATP2C1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

10

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

81 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ATP2C1.

Disease | AllUniProt

Conditions ATP2C1 is implicated in, by any mechanism.

• Hailey-Hailey disease (HHD) MIM:169600

Disease | GeneticClinVar

54 pathogenic / likely-pathogenic of 321 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Familial benign pemphigus
• Melanoma

ReferencesPubMed · IEDB

Publications for ATP2C1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.18

gnomAD pLI

1

gnomAD missense Z

3.67

DepMap mean gene effect

-0.11

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 9% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• actin cytoskeleton organization
• calcium ion transmembrane transport
• calcium ion transport
• calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules
• epidermis development
• Golgi calcium ion homeostasis
• Golgi calcium ion transport
• intracellular calcium ion homeostasis
• intracellular manganese ion homeostasis
• manganese ion transport
• positive regulation of canonical NF-kappaB signal transduction
• positive regulation of Golgi to plasma membrane protein transport
• trans-Golgi network membrane organization

Molecular functions

• ATP binding
• ATP hydrolysis activity
• calcium ion binding
• manganese ion binding
• metal ion binding
• P-type calcium transporter activity
• P-type manganese transporter activity

Cellular components

• cis-Golgi network membrane
• endoplasmic reticulum
• Golgi apparatus
• Golgi cisterna membrane
• Golgi membrane
• membrane
• plasma membrane
• trans-Golgi network

Protein domainsUniProt · Pfam · InterPro

• P-type ATPase
• Cation-transporting P-type ATPase, N-terminal
• Cation-transporting P-type ATPase, C-terminal
• P-type ATPase, subfamily IIA, PMR1-type
• P-type ATPase, A domain superfamily
• P-type ATPase, phosphorylation site
• HAD superfamily
• P-type ATPase, transmembrane domain superfamily
• P-type ATPase, cytoplasmic domain N
• HAD-like superfamily
• P-type ATPase, haloacid dehalogenase domain
• P-type ATPase, A domain
• P-type ATPase actuator domain
• Cation transporting ATPase, C-terminus
• Cation transporter/ATPase, N-terminus
• P-type ATPase, cytoplasmic domain N

KeywordsUniProt

• ATP-binding
• Calcium
• Calcium transport
• Golgi apparatus
• Ion transport
• Magnesium
• Membrane
• Metal-binding
• Nucleotide-binding
• Translocase
• Transmembrane
• Transmembrane helix
• Transport