Reviewed, UniProtKB/Swiss-Prot O00170 (AIP_HUMAN)

Names and origin

Protein names

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

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 not processed.
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.
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 pituitary adenoma predisposition (PAP) [MIM:102200]. Defects in AIP are a cause of familial isolated pituitary adenoma (FIPA) [MIM:102200]. Defects in AIP are a cause of growth hormone-secreting pituitary adenoma [MIM:102200]; also known as familial isolated somatotropinomas (FIS) or isolated familial somatotropinoma (IFS) or familial somatotrophinoma or acromegaly due to pituitary adenoma. Defects in AIP are a cause of ACTH-secreting pituitary adenoma [MIM:219090]; also known as pituitary Cushing disease. Cushing disease is a condition associated with increased blood cortisol resulting from adrenocorticotropic hormone (ACTH)-producing pituitary tumors that are resistant to glucocorticoid negative feedback.
Sequence similarities	Contains 1 PPIase FKBP-type domain. Contains 2 TPR repeats.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	Repeat TPR repeat
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	protein import into mitochondrion Inferred from direct assay. Source: HGNC protein maturation via protein folding Inferred from direct assay. Source: HGNC
Cellular component	cytosol Traceable author statement. Source: HGNC nucleus Inferred from direct assay. Source: HPA
Molecular function	signal transducer activity Ref.1 Traceable author statement. Source: ProtInc transcription coactivator activity Traceable author statement. Source: ProtInc unfolded protein binding Inferred from direct assay. Source: HGNC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AHR	P35869	1	EBI-704197,EBI-80780
PDE2A	O00408	4	EBI-704197,EBI-1785967

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 330	330	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	248	1	Phosphotyrosine
Natural variations
	Natural variant	16	1	R → H		VAR_043908
	Natural variant	228	1	K → Q: dbSNP rs641081.		VAR_043909
	Natural variant	241	1	K → E in FIPA patients; uncertain pathogenicity.		VAR_043910
	Natural variant	248	1	Missing in a ACTH-secreting pituitary adenoma patient; uncertain pathogenicity.		VAR_043911
	Natural variant	271	1	R → W in FIPA patients; uncertain pathogenicity.		VAR_043912
	Natural variant	304	1	R → Q in a ACTH-secreting pituitary adenoma patient.		VAR_043913

Sequences

	Sequence		Length	Mass (Da)
	O00170-1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 5C0D59A22E5F9BF8	FASTA	330	37,664
	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 PEWIQLDKQI TPLLLNYCQC 250 260 270 280 290 300 KLVVEEYYEV LDHCSSILNK YDDNVKAYFK RGKAHAAVWN AQEAQADFAK VLELDPALAP 310 320 330 VVSRELRALE ARIRQKDEED KARFRGIFSH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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]. Tissue: B-cell.
[2]	"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 GLN-228. Tissue: Lymphoma.
[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], INVOLVEMENT IN PAP, INVOLVEMENT IN GROWTH HORMONE-SECRETING PITUITARY ADENOMA.
[4]	"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]. Tissue: Brain.
[5]	"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.
[6]	"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: VARIANTS HIS-16; GLU-241 AND TRP-271, INVOLVEMENT IN GROWTH HORMONE-SECRETING PITUITARY ADENOMA, INVOLVEMENT IN FIPA.
[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 GROWTH HORMONE-SECRETING PITUITARY ADENOMA, VARIANT GLN-228.
[9]	"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 GROWTH HORMONE-SECRETING PITUITARY ADENOMA.
[10]	"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 GROWTH HORMONE-SECRETING PITUITARY ADENOMA.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U78521 mRNA. Translation: AAB59004.1. U31913 mRNA. Translation: AAB39923.1. AM236341 Genomic DNA. Translation: CAJ85657.1. BC104827 mRNA. Translation: AAI04828.1. BC104797 mRNA. Translation: AAI04798.1.
UniGene	Hs.412433
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O00170.
PTM databases
PhosphoSite	O00170.
Genome annotation databases
Ensembl	ENSG00000110711. Homo sapiens. [Contig view]
KEGG	hsa:9049.
Organism-specific databases
H-InvDB	HIX0036007.
HGNC	HGNC:358. AIP.
HPA	HPA004063.
MIM	102200. phenotype. 219090. phenotype. 605555. gene.
PharmGKB	PA24652.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	O00170.
HOVERGEN	O00170.
Gene expression databases
ArrayExpress	O00170.
CleanEx	HS_AIP.
GermOnline	ENSG00000110711. Homo sapiens.
Family and domain databases
InterPro	IPR001179. PPIase_FKBP. IPR011990. TPR-like_helical. IPR013105. TPR_2. IPR013026. TPR_region. [Graphical view]
Gene3D	G3DSA:1.25.40.10. TPR-like_helical. 1 hit.
Pfam	PF00254. FKBP_C. 1 hit. PF07719. TPR_2. 1 hit. [Graphical view]
PROSITE	PS50059. FKBP_PPIASE. 1 hit. PS50005. TPR. 1 hit. PS50293. TPR_REGION. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	33903.
SOURCE	Search...

Entry information

Entry name

AIP_HUMAN

Accession

Primary (citable) accession number: O00170
Secondary accession number(s): Q2M3Q2, Q99606

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	July 1, 1997
Last modified:	November 25, 2008
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)