Seroatlas · Human Serome Atlas

NHERF2

Na(+)/H(+) exchange regulatory cofactor NHE-RF2

Also known as: E3KARP, NHERF-2, NHRF2_HUMAN, SIP-1, SLC9A3R2, TKA-1

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

Protein identityUniProt · HPA

UniProt accession
Q15599
Gene
NHERF2
Ensembl
ENSG00000065054
Chromosome
16
Canonical length
337 aa
Protein class
Predicted intracellular proteins, Transporters
Subcellular location
Plasma membrane
Quaternary structure
Homodimer

OverviewNCBI Gene

This gene encodes a member of the NHERF family of PDZ scaffolding proteins. These proteins mediate many cellular processes by binding to and regulating the membrane expression and protein-protein interactions of membrane receptors and transport proteins. The encoded protein plays a role in intestinal sodium absorption by regulating the activity of the sodium/hydrogen exchanger 3, and may also regulate the cystic fibrosis transmembrane regulator (CFTR) ion channel. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

Canonical amino-acid sequenceUniProt

337 residues, UniProt reviewed canonical sequence.

>Q15599|NHERF2
     1  MAAPEPLRPR LCRLVRGEQG YGFHLHGEKG RRGQFIRRVE PGSPAEAAAL RAGDRLVEVN
    61  GVNVEGETHH QVVQRIKAVE GQTRLLVVDQ ETDEELRRRQ LTCTEEMAQR GLPPAHDPWE
   121  PKPDWAHTGS HSSEAGKKDV SGPLRELRPR LCHLRKGPQG YGFNLHSDKS RPGQYIRSVD
   181  PGSPAARSGL RAQDRLIEVN GQNVEGLRHA EVVASIKARE DEARLLVVDP ETDEHFKRLR
   241  VTPTEEHVEG PLPSPVTNGT SPAQLNGGSA CSSRSDLPGS DKDTEDGSAW KQDPFQESGL
   301  HLSPTAAEAK EKARAMRVNK RAPQMDWNRK REIFSNF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NHERF2 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
0
Mean surface accessibility (rSASA)
0.46
Highest tissue expression
572 nTPM

Expression across tissuesHPA

Tissue

  • heart muscle: 572 nTPM
  • liver: 398 nTPM
  • lung: 278 nTPM
  • kidney: 240 nTPM
  • adipose tissue: 220 nTPM
  • thyroid gland: 182 nTPM

Single-cell type

  • vascular endothelial cells: 487 nCPM
  • lymphatic endothelial cells: 301 nCPM
  • hepatocytes: 251 nCPM
  • respiratory secretory cells: 222 nCPM
  • breast lactating cells: 200 nCPM
  • endometrial secretory cells: 138 nCPM

Immune cell

  • myeloid DC: 3.9 nTPM
  • plasmacytoid DC: 2.9 nTPM
  • classical monocyte: 2.2 nTPM
  • intermediate monocyte: 1.6 nTPM
  • total PBMC: 0.7 nTPM
  • gdT-cell: 0.5 nTPM

Brain region

  • thalamus: 157 nTPM
  • amygdala: 134 nTPM
  • pons: 118 nTPM
  • basal ganglia: 114 nTPM
  • medulla oblongata: 111 nTPM
  • midbrain: 108 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)
0.7
gnomAD pLI
0.04
DepMap mean gene effect
-0.06
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% 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 NHERF2 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 NHERF2 as an antibody target. Whether an autoantibody or antibody against NHERF2 could matter depends on whether native NHERF2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

NHERF2 is annotated at the cell surface, where native NHERF2 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 NHERF2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/NHERF2. 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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