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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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)

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003977 6 - 1250 NM_002309 37.64 330 - 1997 9111057 NM_001302960 6 - 1247 NP_001289889 - 283 - 1997 9111057 NM_001302959 6 - 1221 NP_001289888 - 271 - 1997 9111057

EXPRESSION

Type

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine colon   moderately   intestine small intestine     moderately   mouth tongue     moderately   pancreas exocrine       moderately   salivary gland       moderately   stomach       moderately Endocrine parathyroid       highly Lymphoid/Immune tonsils       moderately Nervous nerve       moderately Reproductive female system ovary     moderately Visual eye       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Connective bone     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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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