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FLASH GENE
Symbol AGR2 contributors: mct - updated : 11-01-2012
HGNC name anterior gradient 2 homolog (Xenopus laevis)
HGNC id 328
Location 7p21.1      Physical location : 16.832.265 - 16.844.738
Synonym name
  • secreted cement gland homolog
  • androgen-inducible secretory protein
  • protein disulfide isomerase family A, member 17
  • Synonym symbol(s) AG2, XAG2, HAGZ, HAG2, HAG-2/R, HAG-2/C, HPC8, PDIA17
    DNA
    TYPE functioning gene
    STRUCTURE 12.47 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif repetitive sequence   ALU   long interspersed repetitive elements
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC392637 7 similar to RIKEN cDNA 4930579E17 MET 7q31.2-q31.3 met proto-oncogene (hepatocyte growth factor receptor) SOSTDC1 7p21.2 sclerostin domain containing 1 LOC392638 7 similar to RIKEN cDNA 4933421E18 CAPZA2 7q31.2-q31.3 capping protein (actin filament) muscle Z-line, alpha 2 LOC346380 7p21.2 similar to ataxin 2 related protein isoform D; ataxin-2 domain protein DKFZP564O043 7p21 hypothetical protein DKFZp564O043 ST7 7q31.1-q31.3 suppression of tumorigenicity 7 LOC389467 7 similar to RIKEN cDNA 4930579E17 BZW2 7p21.3 basic leucine zipper and W2 domains 2 FZD1 7q21 frizzled homolog 1 (Drosophila) TM4SF13 7p21.1 transmembrane 4 superfamily member 13 AGR2 7p21.3 anterior gradient 2 homolog (Xenepus laevis) LOC392746 7 LOC392746 SOSTDC1 7p21.2 sclerostin domain containing 1 BCMP11 7p21.2 breast cancer membrane protein 11 LOC389468 7 similar to RIKEN cDNA 4933421E18 WNT2 7q31 wingless-type MMTV integration site family member 2 LOC317727 7p21 ataxin 2 related protein pseudogene DKFZP564O043 7p21 hypothetical protein DKFZp564O043 GASZ 7q31.31 GASZ BZW2 7p21.3 basic leucine zipper and W2 domains 2 TM4SF13 7p21.1 transmembrane 4 superfamily member 13 CFTR 7q31.3 cystic fibrosis transmembrane conductance regulator, ATP-binding cassette (sub-family C, member 7) AGR2 7p21.3 anterior gradient 2 homolog (Xenepus laevis) BCMP11 7p21.2 breast cancer membrane protein 11 RAD17P1 7p21 RAD17 homolog (S. pombe) pseudogene 1 AHR 7p21-p15 aryl hydrocarbon receptor MTERF 7q21-q22 aryl hydrocarbon receptor CORTBP2 7q31.3 cortactin binding protein 2 AKAP9 7q21-q22 a kinase (PRKA) anchor protein (yotiao) 9 CYP51A1 7q21.2-q21.3 cytochrome P450, family 51, subfamily A, polypeptide 1 LOC392747 7 similar to hypothetical protein 4932412H11 CCM1 7q21-q22 cerebral cavernous malformations 1 AHR 7p21-p15 aryl hydrocarbon receptor SNX13 7p21.3 sorting nexin 13 LSM8 7q31.1-q31.3 LSM8 homolog, U6 small nuclear RNA associated (S. cerevisiae) LOC392951 7 similar to RIKEN cDNA 4930500J03 ANKRD7 7q31 ankyrin repeat domain 7 LOC392952 7 similar to RIKEN cDNA 2810014D17 ODAG 7q21-q22 ocular development-associated gene PEX1 7q21-q22 peroxisome biogenesis factor 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 996 19 175 - 2005 15834940
    AGR2S
    - - 1701 19 175 - 2005 15834940
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly Homo sapiens
     stomach   highly
    Endocrinepancreas   highly
    Reproductivefemale systembreastmammary gland  
     male systemprostate   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    not specificepithelial cell
    cell lineage
    cell lines estrogen receptor-positive breast cancer cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminus contains a sequence motif characteristic of signal peptides, which results in protein targeting to the secretory pathway of the cell
  • a thioredoxin-like motif
  • C-terminal ER retention motif (KTEL) , variations in ER localization sequences may serve a specific functional role, and this role is served specifically by KTEL
  • mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to murine Agr2
    homolog to xenopus xag2
    intraspecies homolog to ERP29, TXNDC12
    Homologene
    FAMILY disulfide isomerase family
    CATEGORY secretory , protooncogene , signaling
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • localizes to the lumen of the ER and indirectly associates with ER membrane-bound ribosomes through nascent protein chains
  • basic FUNCTION
  • putative signaling molecule involved in cell differentiation and/or in secretory functions of the prostate gland
  • unique member of the PDI family, with a specialized and nonredundant role in intestinal mucus production
  • estrogen-responsive secreted protein
  • functions in a range of biological systems, including goblet cell formation, limb regeneration, inhibition of TP53, and metastasis (
  • induces expression of amphiregulin (AREG), a growth promoting EGFR ligand
  • may function in a non-cell autonomous fashion
  • promotes growth by regulating the Hippo and EGF receptor signaling pathways
  • induces AREG expression through YAP1
  • promotes dissemination of pancreatic cancer and its cell surface targeting may permit new strategies for early detection as well as therapeutic management
  • extracellular role for AGR2 as a secreted protein as well as an intracellular role as a protein chaperone or stress response factor
  • pro-oncogenic and may thus represent a mechanistic intermediate in the connection between ERAD, ERQC and cancer development
  • might play an essential role for in vivo production of the intestinal mucus protein mucin 2 (MUC2), a large cysteine-rich glycoprotein
  • by regulating the ER capacity to adapt, might have an impact on cell survival, consequently contributing to the development and progression of cancers
  • promotes tumor growth and metastasis
  • its localization in the ER by KTEL is required for its ability to induce AREG or CDX2 expression
  • dimerization of AGR2 is critical step to modulate UPR signaling pathway
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • homo-dimerizes through an intermolecular disulfide bond
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • estrogen receptor
  • RUVBL2 is an AGR2-interacting protein
  • regulates AREG RNA and protein expression
  • interacting with CTSB, CTSD (promotes the dissemination of pancreatic cancer cells through regulation of cathepsins IRE1B and D)
  • expression is under the control of both ATF6 and ERN1 arms of the UPR, which might suggest tight maintenance of AGR2 levels in the cell
  • dimerization of AGR2 attenuates ER stress-induced cell death through the association with HSPA5
  • cell & other
    REGULATION
    induced by various stresses such as hypoxia, serum depletion, and ER stress
    Other regulated by androgens
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in early stage mucinous ovarian tumors compared to normal ovarian tissues and serous type ovarian tumors
    tumoral     --over  
    in prostate cancer compared to non-malignant cells, but relatively lower levels of AGR2 are highly predictive of disease recurrence following radical prostatectomy
    tumoral     --over  
    in breast cancer
    Susceptibility to ulcerative colitis
    Variant & Polymorphism
    Candidate gene
    Marker
  • potential biomarker for the diagnosis of mucinous ovarian cancer
  • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    utility of anti-AGR2 therapy in ER-positive breast cancers because of its impact on cancer-relevant pathways
    cancerdigestivepancreas
    may be a useful molecular target in pancreatic cancer
    ANIMAL & CELL MODELS
  • mice lacking Agr2 were viable but were highly susceptible to colitis, indicating a critical role for Agr2 in protection from disease