AH receptor-interacting protein

Protein-coding gene in the species Homo sapiens
AIP
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2LKN, 4AIF, 4APO

Identifiers
AliasesAIP, ARA9, FKBP16, FKBP37, SMTPHN, XAP-2, XAP2, aryl hydrocarbon receptor interacting protein, PITA1
External IDsOMIM: 605555; MGI: 109622; HomoloGene: 2959; GeneCards: AIP; OMA:AIP - orthologs
Gene location (Human)
Chromosome 11 (human)
Chr.Chromosome 11 (human)[1]
Chromosome 11 (human)
Genomic location for AIP
Genomic location for AIP
Band11q13.2Start67,468,174 bp[1]
End67,491,154 bp[1]
Gene location (Mouse)
Chromosome 19 (mouse)
Chr.Chromosome 19 (mouse)[2]
Chromosome 19 (mouse)
Genomic location for AIP
Genomic location for AIP
Band19 A|19 3.82 cMStart4,164,446 bp[2]
End4,175,858 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
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
BioGPS


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
SpeciesHumanMouse
Entrez

9049

11632

Ensembl

ENSG00000110711

ENSMUSG00000024847

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: 67.47 – 67.49 MbChr 19: 4.16 – 4.18 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000110711 – Ensembl, May 2017
  2. ^ a b c 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.
  5. ^ a b "Entrez Gene: AIP aryl hydrocarbon receptor interacting protein".
  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.
  7. ^ a b c 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.
  8. ^ a b 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.
  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.
  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.
  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.
  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.
  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.
  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.

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. 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.