Seroatlas · Human Serome Atlas

FXYD5

FXYD domain-containing ion transport regulator 5

Also known as: FXYD5_HUMAN, OIT2

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

Protein identityUniProt · HPA

UniProt accession
Q96DB9
Gene
FXYD5
Ensembl
ENSG00000089327
Chromosome
19
Canonical length
178 aa
Protein class
Plasma proteins, Predicted membrane proteins, Transporters
Subcellular location
Endoplasmic reticulum

OverviewNCBI Gene

This gene encodes a member of a family of small membrane proteins that share a 35-amino acid signature sequence domain, beginning with the sequence PFXYD and containing 7 invariant and 6 highly conserved amino acids. The approved human gene nomenclature for the family is FXYD-domain containing ion transport regulator. Mouse FXYD5 has been termed RIC (Related to Ion Channel). FXYD2, also known as the gamma subunit of the Na,K-ATPase, regulates the properties of that enzyme. FXYD1 (phospholemman), FXYD2 (gamma), FXYD3 (MAT-8), FXYD4 (CHIF), and FXYD5 (RIC) have been shown to induce channel activity in experimental expression systems. Transmembrane topology has been established for two family members (FXYD1 and FXYD2), with the N-terminus extracellular and the C-terminus on the cytoplasmic side of the membrane. This gene product, FXYD5, is a glycoprotein that functions in the up-regulation of chemokine production, and it is involved in the reduction of cell adhesion via its ability to down-regulate E-cadherin. It also promotes metastasis, and has been linked to a variety of cancers. Alternative splicing results in multiple transcript variants. [RefSeq curation by Kathleen J. Sweadner, Ph.D., sweadner@helix.mgh.harvard.edu., Sep 2009]

Canonical amino-acid sequenceUniProt

178 residues, UniProt reviewed canonical sequence.

>Q96DB9|FXYD5
     1  MSPSGRLCLL TIVGLILPTR GQTLKDTTSS SSADSTIMDI QVPTRAPDAV YTELQPTSPT
    61  PTWPADETPQ PQTQTQQLEG TDGPLVTDPE THKSTKAAHP TDDTTTLSER PSPSTDVQTD
   121  PQTLKPSGFH EDDPFFYDEH TLRKRGLLVA AVLFITGIII LTSGKCRQLS RLCRNRCR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FXYD5 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
1
Mean surface accessibility (rSASA)
0.65
Highest tissue expression
260 nTPM

Expression across tissuesHPA

Tissue

  • bone marrow: 260 nTPM
  • spleen: 226 nTPM
  • cervix: 195 nTPM
  • blood vessel: 193 nTPM
  • adipose tissue: 191 nTPM
  • vagina: 178 nTPM

Single-cell type

  • esophageal apical cells: 1,087 nCPM
  • extravillous trophoblasts: 668 nCPM
  • innate lymphoid cells: 529 nCPM
  • platelets: 470 nCPM
  • mast cells: 451 nCPM
  • hofbauer cells: 342 nCPM

Immune cell

  • total PBMC: 934 nTPM
  • T-reg: 897 nTPM
  • NK-cell: 843 nTPM
  • memory CD4 T-cell: 759 nTPM
  • myeloid DC: 720 nTPM
  • basophil: 647 nTPM

Brain region

  • medulla oblongata: 48 nTPM
  • thalamus: 40 nTPM
  • white matter: 40 nTPM
  • pons: 35 nTPM
  • choroid plexus: 34 nTPM
  • hypothalamus: 34 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)
1.01
gnomAD pLI
0
gnomAD missense Z
0.17
DepMap mean gene effect
0
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% 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

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads FXYD5 as an antibody target. Whether an autoantibody or antibody against FXYD5 could matter depends on whether native FXYD5 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

FXYD5 is annotated at the cell surface, where native FXYD5 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 FXYD5 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/FXYD5. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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