O00170 (AIP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
AH receptor-interacting protein
Short name=AIP

Alternative name(s):
Aryl-hydrocarbon receptor-interacting protein
HBV X-associated protein 2
Short name=XAP-2
Immunophilin homolog ARA9

Gene names

Name:	AIP
Synonyms:	XAP2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	330 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling, possibly by influencing its receptivity for ligand and/or its nuclear targeting. Cellular negative regulator of the hepatitis B virus (HBV) X protein.
Subunit structure	Interacts with RET in the pituitary gland; this interaction prevents the formation of the AIP-survivin complex. Ref.10
Subcellular location	Cytoplasm.
Tissue specificity	Widely expressed. Higher levels seen in the heart, placenta and skeletal muscle. Not expressed in the liver.
Involvement in disease	Defects in AIP are a cause of growth hormone-secreting pituitary adenoma (GHSPA) [MIM:102200]; also known as familial isolated somatotropinomas (FIS) or isolated familial somatotropinoma (IFS) or familial somatotrophinoma or acromegaly due to pituitary adenoma. Ref.4 Ref.8 Ref.11 Ref.13 Defects in AIP are a cause of ACTH-secreting pituitary adenoma (ASPA) [MIM:219090]; also known as pituitary Cushing disease. A pituary adenoma resulting in excessive production of adrenocorticotropic hormone. This leads to hypersecretion of cortisol by the adrenal glands and ACTH-dependent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and trunkal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. Defects in AIP are a cause of prolactin-secreting pituitary adenoma (PSPA) [MIM:600634]; also known as prolactinoma. Prolactin-secreting pituitary adenoma is the most common type of hormonally active pituitary adenoma.
Sequence similarities	Contains 1 PPIase FKBP-type domain. Contains 2 TPR repeats.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Cushing syndrome
Domain	Repeat TPR repeat
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	protein maturation by protein folding Inferred from direct assay. Source: HGNC protein targeting to mitochondrion Inferred from direct assay. Source: HGNC
Cellular component	nucleus Inferred from direct assay. Source: HPA
Molecular function	GAF domain binding Inferred from direct assay. Source: UniProtKB signal transducer activity Traceable author statement. Source: ProtInc transcription coactivator activity Traceable author statement. Source: ProtInc transcription factor binding Traceable author statement. Source: ProtInc unfolded protein binding Inferred from direct assay. Source: HGNC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PDE2A	O00408	6	EBI-704197,EBI-1785967

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 330	329	AH receptor-interacting protein		PRO_0000075339
Regions
	Domain	31 – 121	91	PPIase FKBP-type
	Repeat	179 – 212	34	TPR 1
	Repeat	265 – 298	34	TPR 2
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.9
	Modified residue	248	1	Phosphotyrosine Ref.6
Natural variations
	Natural variant	16	1	R → H. Ref.4 Ref.11		VAR_043908
	Natural variant	47 – 54	8	Missing in patients with pituitary adenoma; uncertain pathogenicity.		VAR_058407
	Natural variant	228	1	Q → K. Ref.2 Ref.3 Ref.5 Ref.8 Corresponds to variant rs641081 [ dbSNP | Ensembl ].		VAR_043909
	Natural variant	241	1	K → E in patients with pituitary adenoma; uncertain pathogenicity. Ref.4		VAR_043910
	Natural variant	248	1	Missing in a ACTH-secreting pituitary adenoma patient; uncertain pathogenicity. Ref.6 Ref.13		VAR_043911
	Natural variant	271	1	R → W in patients with pituitary adenoma; uncertain pathogenicity. Ref.4		VAR_043912
	Natural variant	304	1	R → Q in a ACTH-secreting pituitary adenoma patient. Ref.11		VAR_043913
	Natural variant	307	1	Q → R. Ref.1 Ref.2 Ref.3 Ref.5 Corresponds to variant rs4930199 [ dbSNP | Ensembl ].		VAR_061545

Sequences

	Sequence		Length	Mass (Da)
	O00170 [UniParc]. Last modified July 28, 2009. Version 2. Checksum: 9302AA6D0F8D8F51	FASTA	330	37,636
	10 20 30 40 50 60 MADIIARLRE DGIQKRVIQE GRGELPDFQD GTKATFHYRT LHSDDEGTVL DDSRARGKPM 70 80 90 100 110 120 ELIIGKKFKL PVWETIVCTM REGEIAQFLC DIKHVVLYPL VAKSLRNIAV GKDPLEGQRH 130 140 150 160 170 180 CCGVAQMREH SSLGHADLDA LQQNPQPLIF HMEMLKVESP GTYQQDPWAM TDEEKAKAVP 190 200 210 220 230 240 LIHQEGNRLY REGHVKEAAA KYYDAIACLK NLQMKEQPGS PEWIQLDQQI TPLLLNYCQC 250 260 270 280 290 300 KLVVEEYYEV LDHCSSILNK YDDNVKAYFK RGKAHAAVWN AQEAQADFAK VLELDPALAP 310 320 330 VVSRELQALE ARIRQKDEED KARFRGIFSH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation." Kuzhandaivelu N., Cong Y.-S., Inouye C., Yang W.-M., Seto E. Nucleic Acids Res. 24:4741-4750(1996) [PubMed: 8972861] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-307. Tissue: Lymphoma.
[2]	"Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo." Carver L.A., Bradfield C.A. J. Biol. Chem. 272:11452-11456(1997) [PubMed: 9111057] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LYS-228 AND ARG-307. Tissue: B-cell.
[3]	"Pituitary adenoma predisposition caused by germline mutations in the AIP gene." Vierimaa O., Georgitsi M., Lehtonen R., Vahteristo P., Kokko A., Raitila A., Tuppurainen K., Ebeling T.M.L., Salmela P.I., Paschke R., Gundogdu S., de Menis E., Jaervinen M.J., Launonen V., Karhu A., Aaltonen L.A. Science 312:1228-1230(2006) [PubMed: 16728643] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LYS-228 AND ARG-307, INVOLVEMENT IN PITUITARY ADENOMAS.
[4]	"Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families." Daly A.F., Vanbellinghen J.-F., Khoo S.K., Jaffrain-Rea M.-L., Naves L.A., Guitelman M.A., Murat A., Emy P., Gimenez-Roqueplo A.-P., Tamburrano G., Raverot G., Barlier A., De Herder W., Penfornis A., Ciccarelli E., Estour B., Lecomte P., Gatta B. , Chabre O., Sabate M.I., Bertagna X., Garcia Basavilbaso N., Stalldecker G., Colao A., Ferolla P., Wemeau J.-L., Caron P., Sadoul J.-L., Oneto A., Archambeaud F., Calender A., Sinilnikova O., Montanana C.F., Cavagnini F., Hana V., Solano A., Delettieres D., Luccio-Camelo D.C., Basso A., Rohmer V., Brue T., Bours V., Teh B.T., Beckers A. J. Clin. Endocrinol. Metab. 92:1891-1896(2007) [PubMed: 17244780] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS 47-GLY--ARG-54 DEL; HIS-16; GLU-241 AND TRP-271, INVOLVEMENT IN GHSPA.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS LYS-228 AND ARG-307. Tissue: Brain.
[6]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-248, MASS SPECTROMETRY.
[7]	"Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma." Toledo R.A., Lourenco D.M. Jr., Liberman B., Cunha-Neto M.B.C., Cavalcanti M.G., Moyses C.B., Toledo S.P.A., Dahia P.L.M. J. Clin. Endocrinol. Metab. 92:1934-1937(2007) [PubMed: 17341560] [Abstract] Cited for: INVOLVEMENT IN PAP.
[8]	"Mutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas." Barlier A., Vanbellinghen J.-F., Daly A.F., Silvy M., Jaffrain-Rea M.-L., Trouillas J., Tamagno G., Cazabat L., Bours V., Brue T., Enjalbert A., Beckers A. J. Clin. Endocrinol. Metab. 92:1952-1955(2007) [PubMed: 17299063] [Abstract] Cited for: INVOLVEMENT IN GHSPA, VARIANT LYS-228.
[9]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[10]	"The tyrosine kinase receptor RET interacts in vivo with aryl hydrocarbon receptor-interacting protein to alter survivin availability." Vargiolu M., Fusco D., Kurelac I., Dirnberger D., Baumeister R., Morra I., Melcarne A., Rimondini R., Romeo G., Bonora E. J. Clin. Endocrinol. Metab. 94:2571-2578(2009) [PubMed: 19366855] [Abstract] Cited for: INTERACTION WITH RET.
[11]	"Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations." Georgitsi M., Raitila A., Karhu A., Tuppurainen K., Maekinen M.J., Vierimaa O., Paschke R., Saeger W., van der Luijt R.B., Sane T., Robledo M., De Menis E., Weil R.J., Wasik A., Zielinski G., Lucewicz O., Lubinski J., Launonen V., Vahteristo P., Aaltonen L.A. Proc. Natl. Acad. Sci. U.S.A. 104:4101-4105(2007) [PubMed: 17360484] [Abstract] Cited for: VARIANTS HIS-16 AND GLN-304, INVOLVEMENT IN ACTH-SECRETING PITUITARY ADENOMA, INVOLVEMENT IN GHSPA.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Aryl hydrocarbon receptor interacting protein (AIP) gene mutation analysis in children and adolescents with sporadic pituitary adenomas." Georgitsi M., De Menis E., Cannavo S., Maekinen M.J., Tuppurainen K., Pauletto P., Curto L., Weil R.J., Paschke R., Zielinski G., Wasik A., Lubinski J., Vahteristo P., Karhu A., Aaltonen L.A. Clin. Endocrinol. (Oxf.) 69:621-627(2008) [PubMed: 18410548] [Abstract] Cited for: VARIANT TYR-248 DEL, INVOLVEMENT IN GHSPA.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	U31913 mRNA. Translation: AAB39923.1. U78521 mRNA. Translation: AAB59004.1. AM236341 Genomic DNA. Translation: CAJ85657.1. EF066502 Genomic DNA. Translation: ABK60081.1. EF066504 Genomic DNA. Translation: ABK60082.1. EF066505 Genomic DNA. Translation: ABK60083.1. EF066510 Genomic DNA. Translation: ABK60084.1. BC104827 mRNA. Translation: AAI04828.1. BC104797 mRNA. Translation: AAI04798.1.
IPI	IPI00953925.
RefSeq	NP_003968.2. NM_003977.2.
UniGene	Hs.412433.
3D structure databases
ProteinModelPortal	O00170.
SMR	O00170. Positions 3-320.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-34068N.
IntAct	O00170. 6 interactions.
MINT	MINT-5000425.
STRING	O00170.
PTM databases
PhosphoSite	O00170.
Proteomic databases
PRIDE	O00170.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000279146; ENSP00000279146; ENSG00000110711.
GeneID	9049.
KEGG	hsa:9049.
UCSC	uc001olv.1. human.
Organism-specific databases
CTD	9049.
GeneCards	GC11P067251.
H-InvDB	HIX0036007.
HGNC	HGNC:358. AIP.
HPA	HPA004063.
MIM	102200. phenotype. 219090. phenotype. 600634. phenotype. 605555. gene.
neXtProt	NX_O00170.
Orphanet	963. Acromegaly. 96254. Familial prolactinoma.
PharmGKB	PA24652.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00390000001289.
HOVERGEN	HBG004198.
InParanoid	O00170.
OMA	DWIQLDL.
OrthoDB	EOG4B5P5R.
PhylomeDB	O00170.
Gene expression databases
ArrayExpress	O00170.
Bgee	O00170.
CleanEx	HS_AIP.
Genevestigator	O00170.
GermOnline	ENSG00000110711. Homo sapiens.
Family and domain databases
InterPro	IPR001179. PPIase_FKBP_dom. IPR013026. TPR-contain. IPR011990. TPR-like_helical. IPR019734. TPR_repeat. [Graphical view]
Gene3D	G3DSA:1.25.40.10. TPR-like_helical. 1 hit.
Pfam	PF00254. FKBP_C. 1 hit. [Graphical view]
PROSITE	PS50059. FKBP_PPIASE. 1 hit. PS50005. TPR. 1 hit. PS50293. TPR_REGION. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	33903.
SOURCE	Search...

Entry information

Entry name

AIP_HUMAN

Accession

Primary (citable) accession number: O00170
Secondary accession number(s): A0SZW3 , A0SZW4, A0SZW5, A0SZW6, Q2M3Q2, Q99606

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	July 28, 2009
Last modified:	January 25, 2012
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.