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 transf... See more...

Aliases for AGR2 Gene

Aliases for AGR2 Gene

  • Anterior Gradient 2, Protein Disulphide Isomerase Family Member 2 3 5
  • HAG-2 2 3 4
  • AG2 2 3 4
  • Protein Disulfide Isomerase Family A, Member 17 2 3
  • Secreted Cement Gland Protein XAG-2 Homolog 3 4
  • Anterior Gradient Protein 2 Homolog 3 4
  • PDIA17 2 3
  • XAG-2 2 3
  • AG-2 3 4
  • HPC8 3 4
  • Anterior Gradient 2 Homolog (Xenopus Laevis) 2
  • Epididymis Secretory Protein Li 116 3
  • Secreted Cement Gland Homolog 3
  • Anterior Gradient Homolog 2 3
  • HEL-S-116 3
  • GOB-4 3
  • AGR2 5

External Ids for AGR2 Gene

Previous GeneCards Identifiers for AGR2 Gene

  • GC07M016476
  • GC07M016575
  • GC07M016605
  • GC07M016797
  • GC07M016719
  • GC07M016831
  • GC07M016805
  • GC07M016818

Summaries for AGR2 Gene

Entrez Gene Summary for AGR2 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]

CIViC Summary for AGR2 Gene

GeneCards Summary for AGR2 Gene

AGR2 (Anterior Gradient 2, Protein Disulphide Isomerase Family Member) is a Protein Coding gene. Diseases associated with AGR2 include Ampulla Of Vater Cancer and Ileocolitis. Among its related pathways are Tyrosine Kinases / Adaptors and Adhesion. Gene Ontology (GO) annotations related to this gene include dystroglycan binding. An important paralog of this gene is AGR3.

UniProtKB/Swiss-Prot Summary for AGR2 Gene

  • Required for MUC2 post-transcriptional synthesis and secretion. May play a role in the production of mucus by intestinal cells (By similarity). Proto-oncogene that may play a role in cell migration, cell differentiation and cell growth. Promotes cell adhesion (PubMed:23274113).

Gene Wiki entry for AGR2 Gene

Additional gene information for AGR2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for AGR2 Gene

Genomics for AGR2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for AGR2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH07J016801 Promoter/Enhancer 1.4 EPDnew Ensembl ENCODE 622.7 +29.4 29396 5.9 CTCF ZHX2 FOXA1 REST RAD21 GTF2F1 ZFX SP1 CEBPB ZNF444 AGR2 lnc-AGR3-2 AGR3 TSPAN13 ENSG00000270593 piR-50308-576
GH07J016810 Enhancer 0.8 Ensembl ENCODE 23.1 +21.4 21432 4 RNF2 CREB1 RFX1 FOXA1 PRDM1 ATF7 CEBPB SP1 BMI1 NR3C1 AGR2 AGR3 ENSG00000270593 TSPAN13 lnc-AGR3-2
GH07J016913 Enhancer 1 Ensembl ENCODE 14.8 -82.4 -82371 5.1 GATAD2A CTCF PRDM10 TFE3 NFKBIZ RCOR2 JUND FOXA1 RXRB REST AHR AGR3 AGR2 TSPAN13 lnc-AHR-1 LOC100131425
GH07J016739 Enhancer 1.1 Ensembl ENCODE 10.1 +90.8 90832 7.2 PRDM10 ZNF629 LEF1 IKZF1 ZNF692 JUND GABPA DDX20 PKNOX1 ZNF24 BZW2 AGR2 ANKMY2 TSPAN13 RF00017-6063 piR-56038-011
GH07J016878 Promoter/Enhancer 1 EPDnew ENCODE 11.2 -47.2 -47226 4.4 ZNF512 FOXA1 RFX1 ZFX ZNF512B BMI1 CTBP1 ZNF217 NR2F2 MBD2 AGR3 lnc-AGR2-1 AGR2 TSPAN13 RAD17P1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around AGR2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for AGR2

Top Transcription factor binding sites by QIAGEN in the AGR2 gene promoter:
  • AML1a
  • CUTL1
  • FOXI1
  • GATA-1
  • HFH-3
  • Max1
  • Pax-3
  • Pax-4a
  • Spz1

Genomic Locations for AGR2 Gene

Genomic Locations for AGR2 Gene
chr7:16,791,811-16,833,433
(GRCh38/hg38)
Size:
41,623 bases
Orientation:
Minus strand
chr7:16,831,435-16,873,057
(GRCh37/hg19)
Size:
41,623 bases
Orientation:
Minus strand

Genomic View for AGR2 Gene

Genes around AGR2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
AGR2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for AGR2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for AGR2 Gene

Proteins for AGR2 Gene

  • Protein details for AGR2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95994-AGR2_HUMAN
    Recommended name:
    Anterior gradient protein 2 homolog
    Protein Accession:
    O95994

    Protein attributes for AGR2 Gene

    Size:
    175 amino acids
    Molecular mass:
    19979 Da
    Quaternary structure:
    • Monomer and homodimer (PubMed:23274113). Interacts with LYPD3 and DAG1 (alphaDAG1). Interacts with MUC2; disulfide-linked.

    Three dimensional structures from OCA and Proteopedia for AGR2 Gene

neXtProt entry for AGR2 Gene

Post-translational modifications for AGR2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for AGR2 Gene

Antibody Products

No data available for DME Specific Peptides for AGR2 Gene

Domains & Families for AGR2 Gene

Gene Families for AGR2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for AGR2 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for AGR2 Gene

GenScript: Design optimal peptide antigens:
  • Secreted cement gland protein XAG-2 homolog (AGR2_HUMAN)
  • Anterior gradient 2 homolog (Xenopus laevis), isoform CRA_a (Q4JM46_HUMAN)
  • AGR2 (Q4JM47_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O95994

UniProtKB/Swiss-Prot:

AGR2_HUMAN :
  • Belongs to the AGR family.
Family:
  • Belongs to the AGR family.
genes like me logo Genes that share domains with AGR2: view

Function for AGR2 Gene

Molecular function for AGR2 Gene

UniProtKB/Swiss-Prot Function:
Required for MUC2 post-transcriptional synthesis and secretion. May play a role in the production of mucus by intestinal cells (By similarity). Proto-oncogene that may play a role in cell migration, cell differentiation and cell growth. Promotes cell adhesion (PubMed:23274113).

Phenotypes From GWAS Catalog for AGR2 Gene

Gene Ontology (GO) - Molecular Function for AGR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002162 dystroglycan binding IBA,IDA 12592373
GO:0005154 epidermal growth factor receptor binding IPI 25666625
GO:0005515 protein binding IPI 12592373
GO:0042802 identical protein binding IPI 23220234
genes like me logo Genes that share ontologies with AGR2: view
genes like me logo Genes that share phenotypes with AGR2: view

Animal Models for AGR2 Gene

MGI Knock Outs for AGR2:
  • Agr2 Agr2<tm1.2Erle>
  • Agr2 Agr2<tm1.2Lpkn>
  • Agr2 Agr2<tm1.1Lex>

Animal Model Products

  • Taconic Biosciences Mouse Models for AGR2

CRISPR Products

miRNA for AGR2 Gene

miRTarBase miRNAs that target AGR2

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for AGR2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for AGR2 Gene

Localization for AGR2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for AGR2 Gene

Secreted. Endoplasmic reticulum.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for AGR2 gene
Compartment Confidence
extracellular 5
endoplasmic reticulum 5
plasma membrane 2
cytoskeleton 2
nucleus 2
mitochondrion 1
peroxisome 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Endoplasmic reticulum (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for AGR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IDA 22184114
GO:0005783 endoplasmic reticulum IBA,ISS --
genes like me logo Genes that share ontologies with AGR2: view

Pathways & Interactions for AGR2 Gene

PathCards logo

SuperPathways for AGR2 Gene

genes like me logo Genes that share pathways with AGR2: view

Pathways by source for AGR2 Gene

2 Cell Signaling Technology pathways for AGR2 Gene

Gene Ontology (GO) - Biological Process for AGR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0010628 positive regulation of gene expression IMP 22184114
GO:0010811 positive regulation of cell-substrate adhesion IMP 23274113
GO:0034976 NOT response to endoplasmic reticulum stress IMP 25666625
GO:0045742 positive regulation of epidermal growth factor receptor signaling pathway IMP 25666625
GO:0048546 digestive tract morphogenesis IEA,ISS --
genes like me logo Genes that share ontologies with AGR2: view

No data available for SIGNOR curated interactions for AGR2 Gene

Drugs & Compounds for AGR2 Gene

(1) Drugs for AGR2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with AGR2: view

Transcripts for AGR2 Gene

mRNA/cDNA for AGR2 Gene

1 REFSEQ mRNAs :
19 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for AGR2

Alternative Splicing Database (ASD) splice patterns (SP) for AGR2 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4 ^ 5a · 5b · 5c ^ 6 ^ 7 ^ 8a · 8b ^ 9a · 9b · 9c
SP1: - - -
SP2: - - - -
SP3: -
SP4: - - -
SP5:
SP6: - - - -

Relevant External Links for AGR2 Gene

GeneLoc Exon Structure for
AGR2

Expression for AGR2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for AGR2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for AGR2 Gene

This gene is overexpressed in Stomach (x15.9), Colon - Transverse (x13.8), and Small Intestine - Terminal Ileum (x6.3).

Protein differential expression in normal tissues from HIPED for AGR2 Gene

This gene is overexpressed in Oral epithelium (25.4) and Stomach (10.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for AGR2 Gene



Protein tissue co-expression partners for AGR2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for AGR2

SOURCE GeneReport for Unigene cluster for AGR2 Gene:

Hs.530009

mRNA Expression by UniProt/SwissProt for AGR2 Gene:

O95994-AGR2_HUMAN
Tissue specificity: Expressed strongly in trachea, lung, stomach, colon, prostate and small intestine. Expressed weakly in pituitary gland, salivary gland, mammary gland, bladder, appendix, ovary, fetal lung, uterus, pancreas, kidney, fetal kidney, testis, placenta, thyroid gland and in estrogen receptor (ER)-positive breast cancer cell lines.

Evidence on tissue expression from TISSUES for AGR2 Gene

  • Intestine(4.9)
  • Stomach(4.8)
  • Pancreas(4.7)
  • Lung(3.1)
  • Gall bladder(3)
  • Liver(2)
genes like me logo Genes that share expression patterns with AGR2: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for AGR2 Gene

Orthologs for AGR2 Gene

This gene was present in the common ancestor of animals.

Orthologs for AGR2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia AGR2 30 31
  • 99.81 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia AGR2 30 31
  • 92.57 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia AGR2 30 31
  • 90.29 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Agr2 30 17 31
  • 87.81 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Agr2 30
  • 87.81 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia AGR2 31
  • 82 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia AGR2 31
  • 62 (a)
OneToOne
Chicken
(Gallus gallus)
Aves AGR2 30 31
  • 75.49 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia AGR2 31
  • 79 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia agr2 30
  • 68.7 (n)
African clawed frog
(Xenopus laevis)
Amphibia MGC53762 30
Zebrafish
(Danio rerio)
Actinopterygii agr2 30 31
  • 68.89 (n)
OneToOne
Dr.25277 30
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8969 30
Worm
(Caenorhabditis elegans)
Secernentea Y57A10A.23 31
  • 26 (a)
ManyToMany
F49H12.5 31
  • 17 (a)
ManyToMany
Species where no ortholog for AGR2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for AGR2 Gene

ENSEMBL:
Gene Tree for AGR2 (if available)
TreeFam:
Gene Tree for AGR2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for AGR2: view image

Paralogs for AGR2 Gene

Paralogs for AGR2 Gene

(2) SIMAP similar genes for AGR2 Gene using alignment to 6 proteins:

  • AGR2_HUMAN
  • B5MC07_HUMAN
  • C9J3E2_HUMAN
  • H7C3Z9_HUMAN
  • Q4JM46_HUMAN
  • Q4JM47_HUMAN
genes like me logo Genes that share paralogs with AGR2: view

Variants for AGR2 Gene

Additional dbSNP identifiers (rs#s) for AGR2 Gene

Structural Variations from Database of Genomic Variants (DGV) for AGR2 Gene

Variant ID Type Subtype PubMed ID
dgv6289n100 CNV gain 25217958
esv3891076 CNV gain 25118596
nsv1028125 CNV gain 25217958

Variation tolerance for AGR2 Gene

Residual Variation Intolerance Score: 47.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.07; 21.86% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for AGR2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
AGR2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for AGR2 Gene

Disorders for AGR2 Gene

MalaCards: The human disease database

(5) MalaCards diseases for AGR2 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
ampulla of vater cancer
  • malignant tumour of ampulla of vater
ileocolitis
  • iieocolitis
inflammatory bowel disease
  • inflammatory bowel diseases
breast cancer
  • breast lobular carcinoma
lynch syndrome
  • colorectal cancer, hereditary nonpolyposis, type 1
- elite association - COSMIC cancer census association via MalaCards
Search AGR2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for AGR2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with AGR2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for AGR2 Gene

Publications for AGR2 Gene

  1. hAG-2, the human homologue of the Xenopus laevis cement gland gene XAG-2, is coexpressed with estrogen receptor in breast cancer cell lines. (PMID: 9790916) Thompson DA … Weigel RJ (Biochemical and biophysical research communications 1998) 2 3 4 23
  2. hAG-2 and hAG-3, human homologues of genes involved in differentiation, are associated with oestrogen receptor-positive breast tumours and interact with metastasis gene C4.4a and dystroglycan. (PMID: 12592373) Fletcher GC … Terrett JA (British journal of cancer 2003) 3 4 23
  3. Metastasis-promoting anterior gradient 2 protein has a dimeric thioredoxin fold structure and a role in cell adhesion. (PMID: 23274113) Patel P … Lian LY (Journal of molecular biology 2013) 3 4
  4. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 41
  5. The protein disulfide isomerase AGR2 is essential for production of intestinal mucus. (PMID: 19359471) Park SW … Erle DJ (Proceedings of the National Academy of Sciences of the United States of America 2009) 3 4

Products for AGR2 Gene

Sources for AGR2 Gene