AGR2
Anterior gradient protein 2 homolog
Also known as: AG2, AGR2_HUMAN, HAG-2, PDIA17, XAG-2
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O95994
- Gene
- AGR2
- Ensembl
- ENSG00000106541
- Chromosome
- 7
- Canonical length
- 175 aa
- Protein class
- Predicted intracellular proteins
- Subcellular location
- Endoplasmic reticulum
- Secretome location
- Intracellular and membrane
- Quaternary structure
- Homodimer
OverviewNCBI Gene
This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal ER-signal sequence, a catalytically active thioredoxin domain, and a C-terminal ER-retention sequence. This protein plays a role in cell migration, cellular transformation and metastasis and is as a p53 inhibitor. As an ER-localized molecular chaperone, it plays a role in the folding, trafficking, and assembly of cysteine-rich transmembrane receptors and the cysteine-rich intestinal gylcoprotein mucin. This gene has been implicated in inflammatory bowel disease and cancer progression. [provided by RefSeq, Mar 2017]
Canonical amino-acid sequenceUniProt
175 residues, UniProt reviewed canonical sequence.
>O95994|AGR2
1 MEKIPVSAFL LLVALSYTLA RDTTVKPGAK KDTKDSRPKL PQTLSRGWGD QLIWTQTYEE
61 ALYKSKTSNK PLMIIHHLDE CPHSQALKKV FAENKEIQKL AEQFVLLNLV YETTDKHLSP
121 DGQYVPRIMF VDPSLTVRAD ITGRYSNRLY AYEPADTALL LDNMKKALKL LKTELLocalizationUniProt · AlphaFold · HPA
Whether an antibody against AGR2 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
- Secreted
- Secreted
- Yes
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.36
- Highest tissue expression
- 1,324 nTPM
Expression across tissuesHPA
Tissue
- stomach: 1,324 nTPM
- rectum: 1,148 nTPM
- colon: 719 nTPM
- cervix: 600 nTPM
- salivary gland: 514 nTPM
- duodenum: 458 nTPM
Single-cell type
- goblet cells: 6,675 nCPM
- gastric progenitor cells: 5,670 nCPM
- conjunctival goblet cells: 5,150 nCPM
- foveolar cells: 3,725 nCPM
- respiratory secretory cells: 3,712 nCPM
- fallopian tube ciliated cells: 2,565 nCPM
Immune cell
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
- MAIT T-cell: 0 nTPM
Brain region
- cerebral cortex: 1.6 nTPM
- cerebellum: 0.9 nTPM
- white matter: 0.8 nTPM
- basal ganglia: 0.6 nTPM
- amygdala: 0.5 nTPM
- hippocampal formation: 0.5 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about AGR2.
Disease | AllUniProt
Conditions AGR2 is implicated in, by any mechanism.
- Respiratory infections, recurrent, and failure to thrive with or without diarrhea (RIFTD) MIM:620233
Disease | GeneticClinVar
9 pathogenic / likely-pathogenic of 34 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Respiratory infections, recurrent, and failure to thrive with or without diarrhea
- Respiratory ciliopathies including non-CF bronchiectasis
- AGR2-related disorder
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)
- 1.58
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.84
- DepMap mean gene effect
- -0.04
- DepMap dependency class
- selective
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
- cell chemotaxis
- digestive tract morphogenesis
- endoplasmic reticulum unfolded protein response
- inflammatory response
- lung goblet cell differentiation
- mucus secretion
- positive regulation of cell-substrate adhesion
- positive regulation of developmental growth
- positive regulation of epidermal growth factor receptor signaling pathway
- positive regulation of gene expression
- positive regulation of IRE1-mediated unfolded protein response
- positive regulation of PERK-mediated unfolded protein response
- positive regulation of protein localization to plasma membrane
- protein folding in endoplasmic reticulum
Molecular functions
- dystroglycan binding
- epidermal growth factor receptor binding
- identical protein binding
- protein homodimerization activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of AGR2 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 AGR2 as an antibody target. Whether an autoantibody or antibody against AGR2 could matter depends on whether native AGR2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
AGR2 is annotated as secreted, so native AGR2 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.
Annotation status
The present source text does not explicitly label AGR2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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