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   13-OCT-2009, entry version 88.
DE   RecName: Full=AH receptor-interacting protein;
DE            Short=AIP;
DE   AltName: Full=Aryl-hydrocarbon receptor-interacting protein;
DE   AltName: Full=Immunophilin homolog ARA9;
DE   AltName: Full=HBV X-associated protein 2;
DE            Short=XAP-2;
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].
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 VARIANT LYS-228.
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], VARIANT LYS-228, AND INVOLVEMENT IN
RP   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, INVOLVEMENT IN GROWTH HORMONE-SECRETING
RP   PITUITARY ADENOMA, AND INVOLVEMENT IN FIPA.
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 VARIANT LYS-228.
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   IDENTIFICATION BY MASS SPECTROMETRY.
RA   Colinge J., Superti-Furga G., Bennett K.L.;
RL   Submitted (OCT-2008) to UniProtKB.
RN   [8]
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   [9]
RP   INVOLVEMENT IN GROWTH HORMONE-SECRETING PITUITARY ADENOMA, AND VARIANT
RP   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   [10]
RP   VARIANTS HIS-16 AND GLN-304, INVOLVEMENT IN ACTH-SECRETING PITUITARY
RP   ADENOMA, AND INVOLVEMENT IN GROWTH HORMONE-SECRETING PITUITARY
RP   ADENOMA.
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   [11]
RP   VARIANT TYR-248 DEL, AND INVOLVEMENT IN GROWTH HORMONE-SECRETING
RP   PITUITARY ADENOMA.
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   -!- INTERACTION:
CC       P35869:AHR; NbExp=1; IntAct=EBI-704197, EBI-80780;
CC       O00408:PDE2A; NbExp=4; 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 pituitary adenoma
CC       predisposition (PAP) [MIM:102200]. Pituitary adenomas include
CC       somatotropinoma and prolactinoma.
CC   -!- DISEASE: Defects in AIP are a cause of familial isolated pituitary
CC       adenoma (FIPA) [MIM:102200].
CC   -!- DISEASE: Defects in AIP are a cause of growth hormone-secreting
CC       pituitary adenoma [MIM:102200]; also known as familial isolated
CC       somatotropinomas (FIS) or isolated familial somatotropinoma (IFS)
CC       or familial somatotrophinoma or acromegaly due to pituitary
CC       adenoma.
CC   -!- DISEASE: Defects in AIP are a cause of ACTH-secreting pituitary
CC       adenoma [MIM:219090]; also known as pituitary Cushing disease.
CC       Cushing disease is a condition associated with increased blood
CC       cortisol resulting from adrenocorticotropic hormone (ACTH)-
CC       producing pituitary tumors that are resistant to glucocorticoid
CC       negative feedback.
CC   -!- DISEASE: Defects in AIP are a cause of prolactin-secreting
CC       pituitary adenoma [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";
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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; IPI00010460; -.
DR   RefSeq; NP_003968.2; -.
DR   UniGene; Hs.412433; -.
DR   IntAct; O00170; 3.
DR   STRING; O00170; -.
DR   PhosphoSite; O00170; -.
DR   PRIDE; O00170; -.
DR   Ensembl; ENST00000279146; ENSP00000279146; ENSG00000110711; Homo sapiens.
DR   GeneID; 9049; -.
DR   KEGG; hsa:9049; -.
DR   UCSC; uc001olv.1; human.
DR   GeneCards; GC11P067007; -.
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   PharmGKB; PA24652; -.
DR   HOGENOM; O00170; -.
DR   HOVERGEN; 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:0005829; C:cytosol; TAS:HGNC.
DR   GO; GO:0003713; F:transcription coactivator activity; 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.
DR   InterPro; IPR011990; TPR-like_helical.
DR   InterPro; IPR013105; TPR_2.
DR   InterPro; IPR013026; TPR_region.
DR   InterPro; IPR019734; TPR_repeat.
DR   Gene3D; G3DSA:1.25.40.10; TPR-like_helical; 1.
DR   Pfam; PF00254; FKBP_C; 1.
DR   Pfam; PF07719; TPR_2; 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   Complete proteome; Cytoplasm; Phosphoprotein; Polymorphism; Repeat;
KW   TPR repeat.
FT   CHAIN         1    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     248    248       Phosphotyrosine.
FT   VARIANT      16     16       R -> H.
FT                                /FTId=VAR_043908.
FT   VARIANT      47     54       Missing (in FIPA patients; uncertain
FT                                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 FIPA patients; uncertain
FT                                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 FIPA patients; uncertain
FT                                pathogenicity).
FT                                /FTId=VAR_043912.
FT   VARIANT     304    304       R -> Q (in a ACTH-secreting pituitary
FT                                adenoma patient).
FT                                /FTId=VAR_043913.
FT   CONFLICT    307    307       Q -> R (in Ref. 1; AAB59004, 2; AAB39923,
FT                                3; CAJ85657 and 5; AAI04828/AAI04798).
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
//