AH receptor-interacting protein

AH receptor-interacting protein (AIP) also known as aryl hydrocarbon receptor-interacting protein, immunophilin homolog ARA9, or HBV X-associated protein 2 (XAP-2) is a protein that in humans is encoded by the AIP gene.[4][5][6] The protein is a member of the FKBP family.

For the similarly named protein encoded by the AHR gene, see aryl hydrocarbon receptor.

AIP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LKN, 4AIF, 4APO
Identifiers
Aliases	AIP, ARA9, FKBP16, FKBP37, SMTPHN, XAP-2, XAP2, aryl hydrocarbon receptor interacting protein, PITA1
External IDs	OMIM: 605555 MGI: 109622 HomoloGene: 2959 GeneCards: AIP
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q13.2 Start 67,483,026 bp[1] End 67,491,103 bp[1]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • signal transducer activity • GO:0001104 transcription cofactor activity • unfolded protein binding • transcription factor binding • GAF domain binding • GO:0001105 transcription coactivator activity • aryl hydrocarbon receptor binding • peptidyl-prolyl cis-trans isomerase activity Cellular component • aryl hydrocarbon receptor complex • membrane • cell membrane • cytosol • nucleoplasm • cytoplasm Biological process • protein targeting to mitochondrion • negative regulation of cyclic-nucleotide phosphodiesterase activity • regulation of protein kinase A signaling • protein maturation by protein folding • xenobiotic metabolic process • interleukin-12-mediated signaling pathway • regulation of nucleic acid-templated transcription • positive regulation of nucleic acid-templated transcription • protein peptidyl-prolyl isomerization Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	9049	11632
Ensembl	ENSG00000110711	n/a
UniProt	O00170	O08915
RefSeq (mRNA)	NM_003977 NM_001302959 NM_001302960	NM_001276284 NM_016666
RefSeq (protein)	NP_001289888 NP_001289889 NP_003968	NP_001263213 NP_057875
Location (UCSC)	Chr 11: 67.48 – 67.49 Mb	n/a
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

Function

AIP may play a positive role in aryl hydrocarbon receptor-mediated signalling possibly by influencing its receptivity for ligand and/or its nuclear targeting. AIP is the cellular negative regulator of the hepatitis B virus (HBV) X protein.[4] Further, it's been known to suppress antiviral signaling and the induction of type I interferon by targeting IRF7, a key player in the antiviral signal pathways.[7] AIP consists of an N-terminal FKBP52 like domain and a C-terminal TPR domain. [8]

Mutations and role in disease

AIP mutations may be the cause of a familial form of acromegaly, familial isolated pituitary adenoma (FIPA). Somatotropinomas (i.e. GH-producing pituitary adenomas), sometimes associated with prolactinomas, are present in most AIP mutated patients.[9]

Interactions

AIP has been shown to interact with the aryl hydrocarbon receptor,[6][10][11] peroxisome proliferator-activated receptor alpha[12] and the aryl hydrocarbon receptor nuclear translocator.[6][13] Further, it has shown that AIP can interact with IRF7 to exert its novel function of negatively regulating antiviral signal pathways.[7]

References

1. GRCh38: Ensembl release 89: ENSG00000110711 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Entrez Gene: AIP aryl hydrocarbon receptor interacting protein".
5. Kuzhandaivelu N, Cong YS, Inouye C, Yang WM, Seto E (December 1996). "XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation". Nucleic Acids Res. 24 (23): 4741–50. doi:10.1093/nar/24.23.4741. PMC 146319. PMID 8972861.
6. Carver LA, Bradfield CA (April 1997). "Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo". J. Biol. Chem. 272 (17): 11452–6. doi:10.1074/jbc.272.17.11452. PMID 9111057.
7. Zhou Q, Lavorgna A, Bowman M, Hiscott J, Harhaj EW (June 2015). "Aryl Hydrocarbon Receptor Interacting Protein Targets IRF7 to Suppress Antiviral Signaling and the Induction of Type I Interferon". The Journal of Biological Chemistry. 290 (23): 14729–39. doi:10.1074/jbc.M114.633065. PMC 4505538. PMID 25911105.
8. Petrulis JR, Perdew GH (2002). "The role of chaperone proteins in the aryl hydrocarbon receptor core complex". Chemico-Biological Interactions. 141 (1–2): 25–40. doi:10.1016/S0009-2797(02)00064-9. PMID 12213383.
9. Occhi G, Trivellin G, Ceccato F, et al. (2010). "Prevalence of AIP mutations in a large series of sporadic Italian acromegalic patients and evaluation of CDKN1B status in acromegalic patients with multiple endocrine neoplasia". Eur. J. Endocrinol. 163 (3): 369–376. doi:10.1530/EJE-10-0327. PMID 20530095. Archived from the original on 2013-04-14. Retrieved 2012-03-22.
10. Petrulis JR, Hord NG, Perdew GH (December 2000). "Subcellular localization of the aryl hydrocarbon receptor is modulated by the immunophilin homolog hepatitis B virus X-associated protein 2". J. Biol. Chem. 275 (48): 37448–53. doi:10.1074/jbc.M006873200. PMID 10986286.
11. Ma Q, Whitlock JP (April 1997). "A novel cytoplasmic protein that interacts with the Ah receptor, contains tetratricopeptide repeat motifs, and augments the transcriptional response to 2,3,7,8-tetrachlorodibenzo-p-dioxin". J. Biol. Chem. 272 (14): 8878–84. doi:10.1074/jbc.272.14.8878. PMID 9083006.
12. Sumanasekera WK, Tien ES, Turpey R, Vanden Heuvel JP, Perdew GH (February 2003). "Evidence that peroxisome proliferator-activated receptor alpha is complexed with the 90-kDa heat shock protein and the hepatitis virus B X-associated protein 2". J. Biol. Chem. 278 (7): 4467–73. doi:10.1074/jbc.M211261200. PMID 12482853.
13. Kazlauskas A, Sundström S, Poellinger L, Pongratz I (April 2001). "The hsp90 chaperone complex regulates intracellular localization of the dioxin receptor". Mol. Cell. Biol. 21 (7): 2594–607. doi:10.1128/MCB.21.7.2594-2607.2001. PMC 86890. PMID 11259606.

Further reading

• Zhou Q, Lavorgna A, et al. (2015). "Aryl Hydrocarbon Receptor Interacting Protein Targets IRF7 to Suppress Antiviral Signaling and the Induction of Type I Interferon". Journal of Biological Chemistry. 290 (23): 14729–14739. doi:10.1074/jbc.M114.633065. PMC 4505538. PMID 25911105.
• Chen HS, Perdew GH (1994). "Subunit composition of the heteromeric cytosolic aryl hydrocarbon receptor complex". J. Biol. Chem. 269 (44): 27554–8. PMID 7961671.
• Ma Q, Whitlock JP (1997). "A novel cytoplasmic protein that interacts with the Ah receptor, contains tetratricopeptide repeat motifs, and augments the transcriptional response to 2,3,7,8-tetrachlorodibenzo-p-dioxin". J. Biol. Chem. 272 (14): 8878–84. doi:10.1074/jbc.272.14.8878. PMID 9083006.
• Meyer BK, Pray-Grant MG, Vanden Heuvel JP, Perdew GH (1998). "Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity". Mol. Cell. Biol. 18 (2): 978–88. doi:10.1128/MCB.18.2.978. PMC 108810. PMID 9447995.
• Carver LA, LaPres JJ, Jain S, et al. (1999). "Characterization of the Ah receptor-associated protein, ARA9". J. Biol. Chem. 273 (50): 33580–7. doi:10.1074/jbc.273.50.33580. PMID 9837941.
• Gadelha MR, Une KN, Rohde K, et al. (2000). "Isolated familial somatotropinomas: establishment of linkage to chromosome 11q13.1-11q13.3 and evidence for a potential second locus at chromosome 2p16-12". J. Clin. Endocrinol. Metab. 85 (2): 707–14. doi:10.1210/jc.85.2.707. PMID 10690880.
• Petrulis JR, Hord NG, Perdew GH (2001). "Subcellular localization of the aryl hydrocarbon receptor is modulated by the immunophilin homolog hepatitis B virus X-associated protein 2". J. Biol. Chem. 275 (48): 37448–53. doi:10.1074/jbc.M006873200. PMID 10986286.
• Kazlauskas A, Poellinger L, Pongratz I (2001). "The immunophilin-like protein XAP2 regulates ubiquitination and subcellular localization of the dioxin receptor". J. Biol. Chem. 275 (52): 41317–24. doi:10.1074/jbc.M007765200. PMID 11013261.
• Kazlauskas A, Sundström S, Poellinger L, Pongratz I (2001). "The hsp90 chaperone complex regulates intracellular localization of the dioxin receptor". Mol. Cell. Biol. 21 (7): 2594–607. doi:10.1128/MCB.21.7.2594-2607.2001. PMC 86890. PMID 11259606.
• Kazlauskas A, Poellinger L, Pongratz I (2002). "Two distinct regions of the immunophilin-like protein XAP2 regulate dioxin receptor function and interaction with hsp90". J. Biol. Chem. 277 (14): 11795–801. doi:10.1074/jbc.M200053200. PMID 11805120.
• Patterson CE, Gao J, Rooney AP, Davis EC (2002). "Genomic organization of mouse and human 65 kDa FK506-binding protein genes and evolution of the FKBP multigene family". Genomics. 79 (6): 881–9. doi:10.1006/geno.2002.6777. PMID 12036304.
• Berg P, Pongratz I (2002). "Two parallel pathways mediate cytoplasmic localization of the dioxin (aryl hydrocarbon) receptor". J. Biol. Chem. 277 (35): 32310–9. doi:10.1074/jbc.M203351200. PMID 12065584.
• Dull AB, Carlson DB, Petrulis JR, Perdew GH (2002). "Characterization of the phosphorylation status of the hepatitis B virus X-associated protein 2". Arch. Biochem. Biophys. 406 (2): 209–21. doi:10.1016/S0003-9861(02)00444-7. PMID 12361709.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Sumanasekera WK, Tien ES, Turpey R, et al. (2003). "Evidence that peroxisome proliferator-activated receptor alpha is complexed with the 90-kDa heat shock protein and the hepatitis virus B X-associated protein 2". J. Biol. Chem. 278 (7): 4467–73. doi:10.1074/jbc.M211261200. PMID 12482853.
• Zhao Y, Meng XM, Wei YJ, et al. (2004). "Cloning and characterization of a novel cardiac-specific kinase that interacts specifically with cardiac troponin I.". J. Mol. Med. 81 (5): 297–304. doi:10.1007/s00109-003-0427-x. PMID 12721663.
• Lees MJ, Peet DJ, Whitelaw ML (2003). "Defining the role for XAP2 in stabilization of the dioxin receptor". J. Biol. Chem. 278 (38): 35878–88. doi:10.1074/jbc.M302430200. PMID 12837759.
• Yano M, Terada K, Mori M (2003). "AIP is a mitochondrial import mediator that binds to both import receptor Tom20 and preproteins". J. Cell Biol. 163 (1): 45–56. doi:10.1083/jcb.200305051. PMC 2173431. PMID 14557246.
• Ramadoss P, Petrulis JR, Hollingshead BD, et al. (2004). "Divergent roles of hepatitis B virus X-associated protein 2 (XAP2) in human versus mouse Ah receptor complexes". Biochemistry. 43 (3): 700–9. doi:10.1021/bi035827v. PMID 14730974.
• Occhi G, Trivellin G, Ceccato F, et al. (2010). "Prevalence of AIP mutations in a large series of sporadic Italian acromegalic patients and evaluation of CDKN1B status in acromegalic patients with multiple endocrine neoplasia". Eur. J. Endocrinol. 163 (3): 369–376. doi:10.1530/EJE-10-0327. PMID 20530095. Archived from the original on 2013-04-14. Retrieved 2012-03-22.