AH receptor-interacting protein

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; OMA:AIP - orthologs
Gene location (Human)
Chr.	Chromosome 11 (human)
End	67,491,154 bp
Gene location (Mouse)
Chr.	Chromosome 19 (mouse)
End	4,175,858 bp
RNA expression pattern
	Top expressed in
	granulocyte; ; popliteal artery; ; tibial arteries; ; Descending thoracic aorta; ; right coronary artery; ; ascending aorta; ; left coronary artery; ; canal of the cervix; ; body of uterus; ; muscle layer of sigmoid colon;
	Top expressed in
	neural layer of retina; ; dentate gyrus of hippocampal formation granule cell; ; granulocyte; ; quadriceps femoris muscle; ; yolk sac; ; muscle tissue; ; skeletal muscle tissue; ; cerebellum; ; hypothalamus; ; olfactory bulb;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	protein binding ; signal transducer activity ; transcription coregulator activity ; unfolded protein binding ; transcription factor binding ; GAF domain binding ; transcription coactivator activity ; aryl hydrocarbon receptor binding ; peptidyl-prolyl cis-trans isomerase activity ;
Cellular component	aryl hydrocarbon receptor complex ; membrane ; plasma 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
	9049
	11632
	ENSG00000110711
	ENSMUSG00000024847
	O00170
	O08915
	NM_003977 ; NM_001302959 ; NM_001302960
	NM_001276284 ; NM_016666
	NP_001289888 ; NP_001289889 ; NP_003968
	NP_001263213 ; NP_057875
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated November 16, 2024

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.^[5]^[6]^[7] The protein is a member of the FKBP family.

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.^[5] 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.^[8] AIP consists of an N-terminal FKBP52 like domain and a C-terminal TPR domain.^[9]

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.^[10]

Interactions

AIP has been shown to interact with the aryl hydrocarbon receptor,^[7]^[11]^[12] peroxisome proliferator-activated receptor alpha ^[13] and the aryl hydrocarbon receptor nuclear translocator.^[7]^[14] Further, it has shown that AIP can interact with IRF7 to exert its novel function of negatively regulating antiviral signal pathways.^[8]

Related Research Articles

The aryl hydrocarbon receptor is a protein that in humans is encoded by the AHR gene. The aryl hydrocarbon receptor is a transcription factor that regulates gene expression. It was originally thought to function primarily as a sensor of xenobiotic chemicals and also as the regulator of enzymes such as cytochrome P450s that metabolize these chemicals. The most notable of these xenobiotic chemicals are aromatic (aryl) hydrocarbons from which the receptor derives its name.

The ARNT gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor (AhR), and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF1). A t(1;12)(q21;p13) translocation, which results in a TEL–ARNT fusion protein, is associated with acute myeloblastic leukemia. Three alternatively spliced variants encoding different isoforms have been described for this gene.

The aryl-hydrocarbon receptor repressor also known as AHRR is a human gene.

A Tax Gene Product (Tax) is a nuclear protein that has a molecular weight of about 37,000 to 40,000 daltons.

Growth factor receptor-bound protein 10 also known as insulin receptor-binding protein Grb-IR is a protein that in humans is encoded by the GRB10 gene.

Lymphotoxin beta receptor (LTBR), also known as tumor necrosis factor receptor superfamily member 3 (TNFRSF3), is a cell surface receptor for lymphotoxin involved in apoptosis and cytokine release. It is a member of the tumor necrosis factor receptor superfamily.

The nuclear receptor coactivator 2 also known as NCoA-2 is a protein that in humans is encoded by the NCOA2 gene. NCoA-2 is also frequently called glucocorticoid receptor-interacting protein 1 (GRIP1), steroid receptor coactivator-2 (SRC-2), or transcriptional mediators/intermediary factor 2 (TIF2).

NPAS1 is a basic helix-loop-helix transcription factor.

Retinoid X receptor alpha (RXR-alpha), also known as NR2B1 is a nuclear receptor that in humans is encoded by the RXRA gene.

Peroxisome proliferator-activated receptor alpha (PPAR-α), also known as NR1C1, is a nuclear receptor protein functioning as a transcription factor that in humans is encoded by the PPARA gene. Together with peroxisome proliferator-activated receptor delta and peroxisome proliferator-activated receptor gamma, PPAR-alpha is part of the subfamily of peroxisome proliferator-activated receptors. It was the first member of the PPAR family to be cloned in 1990 by Stephen Green and has been identified as the nuclear receptor for a diverse class of rodent hepatocarcinogens that causes proliferation of peroxisomes.

Protein arginine N-methyltransferase 1 is an enzyme that in humans is encoded by the PRMT1 gene. The HRMT1L2 gene encodes a protein arginine methyltransferase that functions as a histone methyltransferase specific for histone H4.

Nuclear receptor-interacting protein 1 (NRIP1) also known as receptor-interacting protein 140 (RIP140) is a protein that in humans is encoded by the NRIP1 gene.

Interferon regulatory factor 7, also known as IRF7, is a member of the interferon regulatory factor family of transcription factors.

Prostaglandin E synthase 3 (cytosolic) is an enzyme that in humans is encoded by the PTGES3 gene.

CD81 molecule, also known as CD81, is a protein which in humans is encoded by the CD81 gene. It is also known as 26 kDa cell surface protein, TAPA-1, and Tetraspanin-28 (Tspan-28).

E3 SUMO-protein ligase PIAS2 is an enzyme that in humans is encoded by the PIAS2 gene.

A-kinase anchor protein 5 is a protein that in humans is encoded by the AKAP5 gene.

Nuclear receptor coactivator 6 is a protein that in humans is encoded by the NCOA6 gene.

General transcription factor IIF subunit 2 is a protein that in humans is encoded by the GTF2F2 gene.

Asialoglycoprotein receptor 1 is a protein that in humans is encoded by the ASGR1 gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000110711 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000024847 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 "Entrez Gene: AIP aryl hydrocarbon receptor interacting protein".
↑ 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.
1 2 3 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.
1 2 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.
↑ 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. Bibcode:2002CBI...141...25P. doi:10.1016/S0009-2797(02)00064-9. PMID 12213383.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.

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. doi: 10.1016/S0021-9258(18)47020-2 . 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/jcem.85.2.6386 . 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. Bibcode:2002PNAS...9916899M. 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. S2CID 13468188.
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.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000110711 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000024847 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] 1 2 "Entrez Gene: AIP aryl hydrocarbon receptor interacting protein".

[pmid8972861-6] 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.

[pmid9111057-7] 1 2 3 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.

[Zhou_2005-8] 1 2 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.

[Petrulis_2002-9] 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. Bibcode:2002CBI...141...25P. doi:10.1016/S0009-2797(02)00064-9. PMID 12213383.

[pmid20530095-10] 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.

[pmid10986286-11] 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.

[pmid9083006-12] 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.

[pmid12482853-13] 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.

[pmid11259606-14] 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.

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