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FLASH GENE
Symbol AIP contributors: mct/npt - updated : 30-10-2018
HGNC name aryl hydrocarbon receptor interacting protein
HGNC id 358
Corresponding disease
CUDP Cushing disease pituitary
Location 11q13.2      Physical location : 67.250.504 - 67.258.578
Synonym name
  • hepatitis virus B X-associated protein 2
  • AhR-associated protein 9
  • immunophilin homolog ARA9
  • Synonym symbol(s) ARA9, XAP2, FKBP37, FKBP16, SMTPHN, PITA1, XAP-2,
    EC.number 5.2.1.8
    DNA
    TYPE functioning gene
    STRUCTURE 8.08 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D11S913 - AIP - ADRBK1 - GSTP1 - FGF4 - ALDH3B1 - D11S1337 - ALDH3B2 - D11S916 - qter
    Authors Gene Map (98)
    Physical map
    FBXL11 11q12.2 F-box and leucine-rich repeat protein 11 PRO1880 11q13.2-q13.4 F-box and leucine-rich repeat protein 11 ADRBK1 11q13.3 adrenergic, beta, receptor kinase 1 LOC338692 11q13.1 hypothetical protein LOC338692 SSH-3 11q13.1 slingshot 3 POLD4 11q13 polymerase (DNA-directed), delta 4 CLC 19q13.1 Charot-Leyden crystal protein RAD9A 11q13.1-q13.2 RAD9 homolog (S. pombe) PPP1CA 11q13.3 protein phosphatase 1, catalytic subunit, alpha isoform RPS6KB2 11q13.3 ribosomal protein S6 kinase, 70kDa, polypeptide 2 FLJ00332 11q13.1 FLJ00332 protein KIAA1394 11q13.1 KIAA1394 protein PTPRCAP 11q13 protein tyrosine phosphatase, receptor type, C-associated protein CORO1B 11q12.2 coronin, actin-binding protein, 1B LOC390212 11 similar to putative G-protein coupled receptor CABP4 11q13.1-q13.4 calcium binding protein 4 FLJ21749 11q13.1 hypothetical protein FLJ21749 AIP 11q13.3 aryl hydrocarbon receptor interacting protein PITPNM1 11q13 phosphatidylinositol transfer protein, membrane-associated 1 DOC-1R 11q13 tumor suppressor deleted in oral cancer-related 1 CABP2 11q13.1 calcium binding protein 2 GSTP1 11q13.3 glutathione S-transferase pi FLJ90834 11q13.1 hypothetical protein FLJ90834 NDUFV1 11q13 NADH dehydrogenase (ubiquinone) flavoprotein 1, 51kDa LOC390213 11 similar to Double C2, gamma NUDT8 11q13.1 nudix (nucleoside diphosphate linked moiety X)-type motif 8 TBX10 11q13 T-box 10 ACY-3 11q13.1 aspartoacylase-3 ALDH3B2 11q13 aldehyde dehydrogenase 3 family, member B2 RPL37P2 11q13 ribosomal protein L37 pseudogene 2 LOC132740 11q13.1 similar to unc-93 homolog B1; unc93 (C.elegans) homolog B; unc-93 related protein LOC390215 11 similar to seven transmembrane helix receptor OR7E11P 11q11 olfactory receptor, family 7, subfamily E, member 11 pseudogene LOC390216 11 similar to mannosyltransferase LOC158490 11q13.1 similar to hypothetical protein FLJ10661
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 1250 37.64 330 - 1997 9111057
    6 - 1247 - 283 - 1997 9111057
    6 - 1221 - 271 - 1997 9111057
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon moderately
     intestinesmall intestine  moderately
     mouthtongue  moderately
     pancreas exocrine   moderately
     salivary gland   moderately
     stomach   moderately
    Endocrineparathyroid   highly
    Lymphoid/Immunetonsils   moderately
    Nervousnerve   moderately
    Reproductivefemale systemovary  moderately
    Visualeye   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Connectivebone  predominantly
    cell lineage
    cell lines
    fluid/secretion blood, lymph
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three TPR-domains and a PPIase-like domain FKBP-type in the N-terminus (Laenger 2009)
  • conjugated PhosphoP
    HOMOLOGY
    interspecies ortholog to rattus Aip (94.2pc)
    ortholog to murine Aip (94.6pc)
    intraspecies homolog to immunophilin
    homolog to the 52kDa,FK506 binding protein (FKBP52)
    homolog to FKBP51
    Homologene
    FAMILY
  • TPR protein interaction motif family
  • CATEGORY receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text nuclear translocation after phosphorylation
    basic FUNCTION
  • may play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling
  • acting as a cellular negative regulator of the hepatitis B virus (HBV) X protein
  • inhibits glucocorticoid receptor by reducing its responsiveness to hormone in transcriptional activation (requires its interaction with Hsp90 through the TPR motif)(Laenger 2009)
  • reduce ubiquitination of the receptor and to regulate its subcellular distribution (Laenger 2009)
  • involved in the development of pituitary tumors, especially involving the somatomammotroph lineage (Cazabat 2009)
  • expression of AIP in hepatocytes is essential to maintain high levels of functional cytosolic AHR protein in the mammalian liver, and expression of the AIP protein is essential for dioxin-induced hepatotoxicity
  • has a major role in the pathogenesis of familial isolated pituitary adenoma, but is rarely involved in parathyroid adenomas
  • AIP is a novel inhibitor of IRF7 and a negative regulator of innate antiviral signaling
  • AIP mutations affect the AIP protein level and alter AHR transcriptional activity in a gene- and tissue-dependent manner
  • encodes for a co-chaperone protein endowed with tumor suppressor properties in somatotroph cells
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • HSP90-AHR complex
  • AIP-TOMM20 recognition contributes to cell survival in development and cancer by mediating the mitochondrial import of BIRC5
  • negative regulator of the hepatitis B virus X-associated protein
  • AIP exerts a negative effect on ESR1 transcriptional activity and may thus prevent ESR1-dependent events
  • interactions with the aryl hydrocarbon receptor (AHR, also known as dioxin receptor), two HSP90 proteins, PDE4A, PPAR, and survivin
  • AIP augments CARMA1-BCL10-MALT1 complex formation to facilitate NFKB1 signaling upon T cell activation
  • AIP (aryl hydrocarbon receptor interacting protein) is a new binding partner of IRF7
  • interaction with over-expressed AIP does not seem to affect PDE2A function, but the reported effect on PDE4A is, in contrast, reduced enzymatic activity
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) CUDP
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral germinal mutation      
    pituitary adenomas (Cazabat 2009)
    tumoral   LOH    
    in sporadic and familial pituitary adenomas
    tumoral germinal mutation     loss of function
    in about 20 p100 of familial isolated pituitary adenoma (FIPA)
    Susceptibility
  • to pituitary hyperplasia and tumorigenesis
  • to familial isolated pituitary adenoma
  • to acromegaly
  • Variant & Polymorphism other
  • Y268X, in a Brazilian family increases the risk of familial acromegaly/pituitary adenoma syndrome
  • germinal mutations in familial isolated pituitary adenoma, with lower mean age at diagnosis
  • heterozygous AIP gene variants have been found in 3.2 p100 of acromegaly
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS