Seroatlas · Human Serome Atlas

ATP2B4

Plasma membrane calcium-transporting ATPase 4

Also known as: AT2B4_HUMAN, ATP2B2, MXRA1, PMCA4

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: P23634
Gene: ATP2B4
Ensembl: ENSG00000058668
Chromosome: 1
Canonical length: 1241 aa
Protein class: Enzymes, FDA approved drug targets, Metabolic proteins, Predicted intracellular proteins, Predicted membrane proteins, Transporters
Subcellular location: Plasma membrane,Primary cilium,Mitochondria,Basal body

OverviewNCBI Gene

The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 4. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1241 residues, UniProt reviewed canonical sequence.

>P23634|ATP2B4
     1  MTNPSDRVLP ANSMAESREG DFGCTVMELR KLMELRSRDA LTQINVHYGG VQNLCSRLKT
    61  SPVEGLSGNP ADLEKRRQVF GHNVIPPKKP KTFLELVWEA LQDVTLIILE IAAIISLVLS
   121  FYRPAGEENE LCGQVATTPE DENEAQAGWI EGAAILFSVI IVVLVTAFND WSKEKQFRGL
   181  QCRIEQEQKF SIIRNGQLIQ LPVAEIVVGD IAQVKYGDLL PADGILIQGN DLKIDESSLT
   241  GESDHVKKSL DKDPMLLSGT HVMEGSGRMV VTAVGVNSQT GIILTLLGVN EDDEGEKKKK
   301  GKKQGVPENR NKAKTQDGVA LEIQPLNSQE GIDNEEKDKK AVKVPKKEKS VLQGKLTRLA
   361  VQIGKAGLLM SALTVFILIL YFVIDNFVIN RRPWLPECTP IYIQYFVKFF IIGITVLVVA
   421  VPEGLPLAVT ISLAYSVKKM MKDNNLVRHL DACETMGNAT AICSDKTGTL TMNRMTVVQA
   481  YIGGIHYRQI PSPDVFLPKV LDLIVNGISI NSAYTSKILP PEKEGGLPRQ VGNKTECALL
   541  GFVTDLKQDY QAVRNEVPEE KLYKVYTFNS VRKSMSTVIR NPNGGFRMYS KGASEIILRK
   601  CNRILDRKGE AVPFKNKDRD DMVRTVIEPM ACDGLRTICI AYRDFDDTEP SWDNENEILT
   661  ELTCIAVVGI EDPVRPEVPD AIAKCKQAGI TVRMVTGDNI NTARAIATKC GILTPGDDFL
   721  CLEGKEFNRL IRNEKGEVEQ EKLDKIWPKL RVLARSSPTD KHTLVKGIID STVGEHRQVV
   781  AVTGDGTNDG PALKKADVGF AMGIAGTDVA KEASDIILTD DNFTSIVKAV MWGRNVYDSI
   841  SKFLQFQLTV NVVAVIVAFT GACITQDSPL KAVQMLWVNL IMDTFASLAL ATEPPTESLL
   901  KRRPYGRNKP LISRTMMKNI LGHAFYQLIV IFILVFAGEK FFDIDSGRKA PLHSPPSQHY
   961  TIVFNTFVLM QLFNEINSRK IHGEKNVFSG IYRNIIFCSV VLGTFICQIF IVEFGGKPFS
  1021  CTSLSLSQWL WCLFIGIGEL LWGQFISAIP TRSLKFLKEA GHGTTKEEIT KDAEGLDEID
  1081  HAEMELRRGQ ILWFRGLNRI QTQIDVINTF QTGASFKGVL RRQNMGQHLD VKLVPSSSYI
  1141  KVVKAFHSSL HESIQKPYNQ KSIHSFMTHP EFAIEEELPR TPLLDEEEEE NPDKASKFGT
  1201  RVLLLDGEVT PYANTNNNAV DCNQVQLPQS DSSLQSLETS V

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATP2B4 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: Cell surface
Secreted: No
Transmembrane segments: 10
Mean surface accessibility (rSASA): 0.33
Highest tissue expression: 165 nTPM

Expression across tissuesHPA

Tissue

smooth muscle: 165 nTPM
endometrium: 98 nTPM
seminal vesicle: 66 nTPM
heart muscle: 56 nTPM
adipose tissue: 55 nTPM
skin: 52 nTPM

Single-cell type

suprabasal keratinocytes: 691 nCPM
basal keratinocytes: 497 nCPM
alveolar cells type 1: 486 nCPM
smooth muscle cells: 476 nCPM
ocular epithelial cells: 453 nCPM
müller glia: 373 nCPM

Immune cell

gdT-cell: 8.7 nTPM
memory CD8 T-cell: 7.2 nTPM
MAIT T-cell: 6.5 nTPM
T-reg: 5.8 nTPM
memory CD4 T-cell: 5.5 nTPM
neutrophil: 4.1 nTPM

Brain region

hypothalamus: 175 nTPM
amygdala: 166 nTPM
cerebral cortex: 164 nTPM
basal ganglia: 156 nTPM
hippocampal formation: 120 nTPM
pons: 110 nTPM

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): 0.44
gnomAD pLI: 0
gnomAD missense Z: 2.25
DepMap mean gene effect: -0.19
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of ATP2B4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ATP2B4 as an antibody target. Whether an autoantibody or antibody against ATP2B4 could matter depends on whether native ATP2B4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ATP2B4 is annotated at the cell surface, where native ATP2B4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label ATP2B4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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