ID AIP_HUMAN Reviewed; 330 AA. AC O00170; A0SZW3; A0SZW4; A0SZW5; A0SZW6; Q2M3Q2; Q99606; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 28-JUL-2009, sequence version 2. DT 25-JAN-2012, entry version 108. DE RecName: Full=AH receptor-interacting protein; DE Short=AIP; DE AltName: Full=Aryl-hydrocarbon receptor-interacting protein; DE AltName: Full=HBV X-associated protein 2; DE Short=XAP-2; DE AltName: Full=Immunophilin homolog ARA9; GN Name=AIP; Synonyms=XAP2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-307. RC TISSUE=Lymphoma; RX MEDLINE=97128268; PubMed=8972861; DOI=10.1093/nar/24.23.4741; RA Kuzhandaivelu N., Cong Y.-S., Inouye C., Yang W.-M., Seto E.; RT "XAP2, a novel hepatitis B virus X-associated protein that inhibits X RT transactivation."; RL Nucleic Acids Res. 24:4741-4750(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS LYS-228 AND ARG-307. RC TISSUE=B-cell; RX MEDLINE=97269057; PubMed=9111057; DOI=10.1074/jbc.272.17.11452; RA Carver L.A., Bradfield C.A.; RT "Ligand-dependent interaction of the aryl hydrocarbon receptor with a RT novel immunophilin homolog in vivo."; RL J. Biol. Chem. 272:11452-11456(1997). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LYS-228 AND ARG-307, AND RP INVOLVEMENT IN PITUITARY ADENOMAS. RX PubMed=16728643; DOI=10.1126/science.1126100; RA Vierimaa O., Georgitsi M., Lehtonen R., Vahteristo P., Kokko A., RA Raitila A., Tuppurainen K., Ebeling T.M.L., Salmela P.I., Paschke R., RA Gundogdu S., de Menis E., Jaervinen M.J., Launonen V., Karhu A., RA Aaltonen L.A.; RT "Pituitary adenoma predisposition caused by germline mutations in the RT AIP gene."; RL Science 312:1228-1230(2006). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS 47-GLY--ARG-54 DEL; RP HIS-16; GLU-241 AND TRP-271, AND INVOLVEMENT IN GHSPA. RX PubMed=17244780; DOI=10.1210/jc.2006-2513; RA Daly A.F., Vanbellinghen J.-F., Khoo S.K., Jaffrain-Rea M.-L., RA Naves L.A., Guitelman M.A., Murat A., Emy P., Gimenez-Roqueplo A.-P., RA Tamburrano G., Raverot G., Barlier A., De Herder W., Penfornis A., RA Ciccarelli E., Estour B., Lecomte P., Gatta B., Chabre O., RA Sabate M.I., Bertagna X., Garcia Basavilbaso N., Stalldecker G., RA Colao A., Ferolla P., Wemeau J.-L., Caron P., Sadoul J.-L., Oneto A., RA Archambeaud F., Calender A., Sinilnikova O., Montanana C.F., RA Cavagnini F., Hana V., Solano A., Delettieres D., Luccio-Camelo D.C., RA Basso A., Rohmer V., Brue T., Bours V., Teh B.T., Beckers A.; RT "Aryl hydrocarbon receptor-interacting protein gene mutations in RT familial isolated pituitary adenomas: analysis in 73 families."; RL J. Clin. Endocrinol. Metab. 92:1891-1896(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LYS-228 AND RP ARG-307. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-248, AND MASS RP SPECTROMETRY. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer RT cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [7] RP INVOLVEMENT IN PAP. RX PubMed=17341560; DOI=10.1210/jc.2006-2394; RA Toledo R.A., Lourenco D.M. Jr., Liberman B., Cunha-Neto M.B.C., RA Cavalcanti M.G., Moyses C.B., Toledo S.P.A., Dahia P.L.M.; RT "Germline mutation in the aryl hydrocarbon receptor interacting RT protein gene in familial somatotropinoma."; RL J. Clin. Endocrinol. Metab. 92:1934-1937(2007). RN [8] RP INVOLVEMENT IN GHSPA, AND VARIANT LYS-228. RX PubMed=17299063; DOI=10.1210/jc.2006-2702; RA Barlier A., Vanbellinghen J.-F., Daly A.F., Silvy M., RA Jaffrain-Rea M.-L., Trouillas J., Tamagno G., Cazabat L., Bours V., RA Brue T., Enjalbert A., Beckers A.; RT "Mutations in the aryl hydrocarbon receptor interacting protein gene RT are not highly prevalent among subjects with sporadic pituitary RT adenomas."; RL J. Clin. Endocrinol. Metab. 92:1952-1955(2007). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY. RC TISSUE=Embryonic kidney; RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [10] RP INTERACTION WITH RET. RX PubMed=19366855; DOI=10.1210/jc.2008-1980; RA Vargiolu M., Fusco D., Kurelac I., Dirnberger D., Baumeister R., RA Morra I., Melcarne A., Rimondini R., Romeo G., Bonora E.; RT "The tyrosine kinase receptor RET interacts in vivo with aryl RT hydrocarbon receptor-interacting protein to alter survivin RT availability."; RL J. Clin. Endocrinol. Metab. 94:2571-2578(2009). RN [11] RP VARIANTS HIS-16 AND GLN-304, INVOLVEMENT IN ACTH-SECRETING PITUITARY RP ADENOMA, AND INVOLVEMENT IN GHSPA. RX PubMed=17360484; DOI=10.1073/pnas.0700004104; RA Georgitsi M., Raitila A., Karhu A., Tuppurainen K., Maekinen M.J., RA Vierimaa O., Paschke R., Saeger W., van der Luijt R.B., Sane T., RA Robledo M., De Menis E., Weil R.J., Wasik A., Zielinski G., RA Lucewicz O., Lubinski J., Launonen V., Vahteristo P., Aaltonen L.A.; RT "Molecular diagnosis of pituitary adenoma predisposition caused by RT aryl hydrocarbon receptor-interacting protein gene mutations."; RL Proc. Natl. Acad. Sci. U.S.A. 104:4101-4105(2007). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [13] RP VARIANT TYR-248 DEL, AND INVOLVEMENT IN GHSPA. RX PubMed=18410548; DOI=10.1111/j.1365-2265.2008.03266.x; RA Georgitsi M., De Menis E., Cannavo S., Maekinen M.J., Tuppurainen K., RA Pauletto P., Curto L., Weil R.J., Paschke R., Zielinski G., Wasik A., RA Lubinski J., Vahteristo P., Karhu A., Aaltonen L.A.; RT "Aryl hydrocarbon receptor interacting protein (AIP) gene mutation RT analysis in children and adolescents with sporadic pituitary RT adenomas."; RL Clin. Endocrinol. (Oxf.) 69:621-627(2008). CC -!- FUNCTION: May play a positive role in AHR-mediated (aromatic CC hydrocarbon receptor) signaling, possibly by influencing its CC receptivity for ligand and/or its nuclear targeting. CC -!- FUNCTION: Cellular negative regulator of the hepatitis B virus CC (HBV) X protein. CC -!- SUBUNIT: Interacts with RET in the pituitary gland; this CC interaction prevents the formation of the AIP-survivin complex. CC -!- INTERACTION: CC O00408:PDE2A; NbExp=6; IntAct=EBI-704197, EBI-1785967; CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- TISSUE SPECIFICITY: Widely expressed. Higher levels seen in the CC heart, placenta and skeletal muscle. Not expressed in the liver. CC -!- DISEASE: Defects in AIP are a cause of growth hormone-secreting CC pituitary adenoma (GHSPA) [MIM:102200]; also known as familial CC isolated somatotropinomas (FIS) or isolated familial CC somatotropinoma (IFS) or familial somatotrophinoma or acromegaly CC due to pituitary adenoma. CC -!- DISEASE: Defects in AIP are a cause of ACTH-secreting pituitary CC adenoma (ASPA) [MIM:219090]; also known as pituitary Cushing CC disease. A pituary adenoma resulting in excessive production of CC adrenocorticotropic hormone. This leads to hypersecretion of CC cortisol by the adrenal glands and ACTH-dependent Cushing CC syndrome. Clinical manifestations of Cushing syndrome include CC facial and trunkal obesity, abdominal striae, muscular weakness, CC osteoporosis, arterial hypertension, diabetes. CC -!- DISEASE: Defects in AIP are a cause of prolactin-secreting CC pituitary adenoma (PSPA) [MIM:600634]; also known as prolactinoma. CC Prolactin-secreting pituitary adenoma is the most common type of CC hormonally active pituitary adenoma. CC -!- SIMILARITY: Contains 1 PPIase FKBP-type domain. CC -!- SIMILARITY: Contains 2 TPR repeats. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/AIP"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; U31913; AAB39923.1; -; mRNA. DR EMBL; U78521; AAB59004.1; -; mRNA. DR EMBL; AM236341; CAJ85657.1; -; Genomic_DNA. DR EMBL; EF066502; ABK60081.1; -; Genomic_DNA. DR EMBL; EF066504; ABK60082.1; -; Genomic_DNA. DR EMBL; EF066505; ABK60083.1; -; Genomic_DNA. DR EMBL; EF066510; ABK60084.1; -; Genomic_DNA. DR EMBL; BC104827; AAI04828.1; -; mRNA. DR EMBL; BC104797; AAI04798.1; -; mRNA. DR IPI; IPI00953925; -. DR RefSeq; NP_003968.2; NM_003977.2. DR UniGene; Hs.412433; -. DR ProteinModelPortal; O00170; -. DR SMR; O00170; 3-320. DR DIP; DIP-34068N; -. DR IntAct; O00170; 6. DR MINT; MINT-5000425; -. DR STRING; O00170; -. DR PhosphoSite; O00170; -. DR PRIDE; O00170; -. DR Ensembl; ENST00000279146; ENSP00000279146; ENSG00000110711. DR GeneID; 9049; -. DR KEGG; hsa:9049; -. DR UCSC; uc001olv.1; human. DR CTD; 9049; -. DR GeneCards; GC11P067251; -. DR H-InvDB; HIX0036007; -. DR HGNC; HGNC:358; AIP. DR HPA; HPA004063; -. DR MIM; 102200; phenotype. DR MIM; 219090; phenotype. DR MIM; 600634; phenotype. DR MIM; 605555; gene. DR neXtProt; NX_O00170; -. DR Orphanet; 963; Acromegaly. DR Orphanet; 96254; Familial prolactinoma. DR PharmGKB; PA24652; -. DR GeneTree; ENSGT00390000001289; -. DR HOVERGEN; HBG004198; -. DR InParanoid; O00170; -. DR OMA; DWIQLDL; -. DR OrthoDB; EOG4B5P5R; -. DR PhylomeDB; O00170; -. DR NextBio; 33903; -. DR ArrayExpress; O00170; -. DR Bgee; O00170; -. DR CleanEx; HS_AIP; -. DR Genevestigator; O00170; -. DR GermOnline; ENSG00000110711; Homo sapiens. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0036004; F:GAF domain binding; IDA:UniProtKB. DR GO; GO:0004871; F:signal transducer activity; TAS:ProtInc. DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc. DR GO; GO:0008134; F:transcription factor binding; TAS:ProtInc. DR GO; GO:0051082; F:unfolded protein binding; IDA:HGNC. DR GO; GO:0022417; P:protein maturation by protein folding; IDA:HGNC. DR GO; GO:0006626; P:protein targeting to mitochondrion; IDA:HGNC. DR InterPro; IPR001179; PPIase_FKBP_dom. DR InterPro; IPR013026; TPR-contain. DR InterPro; IPR011990; TPR-like_helical. DR InterPro; IPR019734; TPR_repeat. DR Gene3D; G3DSA:1.25.40.10; TPR-like_helical; 1. DR Pfam; PF00254; FKBP_C; 1. DR PROSITE; PS50059; FKBP_PPIASE; 1. DR PROSITE; PS50005; TPR; 1. DR PROSITE; PS50293; TPR_REGION; 1. PE 1: Evidence at protein level; KW Acetylation; Complete proteome; Cushing syndrome; Cytoplasm; KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; TPR repeat. FT INIT_MET 1 1 Removed. FT CHAIN 2 330 AH receptor-interacting protein. FT /FTId=PRO_0000075339. FT DOMAIN 31 121 PPIase FKBP-type. FT REPEAT 179 212 TPR 1. FT REPEAT 265 298 TPR 2. FT MOD_RES 2 2 N-acetylalanine. FT MOD_RES 248 248 Phosphotyrosine. FT VARIANT 16 16 R -> H. FT /FTId=VAR_043908. FT VARIANT 47 54 Missing (in patients with pituitary FT adenoma; uncertain pathogenicity). FT /FTId=VAR_058407. FT VARIANT 228 228 Q -> K (in dbSNP:rs641081). FT /FTId=VAR_043909. FT VARIANT 241 241 K -> E (in patients with pituitary FT adenoma; uncertain pathogenicity). FT /FTId=VAR_043910. FT VARIANT 248 248 Missing (in a ACTH-secreting pituitary FT adenoma patient; uncertain FT pathogenicity). FT /FTId=VAR_043911. FT VARIANT 271 271 R -> W (in patients with pituitary FT adenoma; uncertain pathogenicity). FT /FTId=VAR_043912. FT VARIANT 304 304 R -> Q (in a ACTH-secreting pituitary FT adenoma patient). FT /FTId=VAR_043913. FT VARIANT 307 307 Q -> R (in dbSNP:rs4930199). FT /FTId=VAR_061545. SQ SEQUENCE 330 AA; 37636 MW; 9302AA6D0F8D8F51 CRC64; MADIIARLRE DGIQKRVIQE GRGELPDFQD GTKATFHYRT LHSDDEGTVL DDSRARGKPM ELIIGKKFKL PVWETIVCTM REGEIAQFLC DIKHVVLYPL VAKSLRNIAV GKDPLEGQRH CCGVAQMREH SSLGHADLDA LQQNPQPLIF HMEMLKVESP GTYQQDPWAM TDEEKAKAVP LIHQEGNRLY REGHVKEAAA KYYDAIACLK NLQMKEQPGS PEWIQLDQQI TPLLLNYCQC KLVVEEYYEV LDHCSSILNK YDDNVKAYFK RGKAHAAVWN AQEAQADFAK VLELDPALAP VVSRELQALE ARIRQKDEED KARFRGIFSH //