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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	330 AA.
Sequence status	Complete.
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.9
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	Growth hormone-secreting pituitary adenoma (GHSPA) [MIM:102200]: Pituitary adenomas include somatotropinoma and prolactinoma. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.8 Ref.10 Ref.11 ACTH-secreting pituitary adenoma (ASPA) [MIM:219090]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Prolactin-secreting pituitary adenoma (PSPA) [MIM:600634]: Most common type of hormonally active pituitary adenoma. Note: The disease is caused by mutations affecting the gene represented in this entry.
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
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of cyclic-nucleotide phosphodiesterase activity Inferred from electronic annotation. Source: Compara protein maturation by protein folding Inferred from direct assay PubMed 14557246. Source: HGNC protein targeting to mitochondrion Inferred from direct assay PubMed 14557246. Source: HGNC regulation of protein kinase A signaling cascade Inferred from electronic annotation. Source: Compara xenobiotic metabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from direct assay PubMed 17329248. Source: UniProtKB cytosolic part Inferred from electronic annotation. Source: Compara membrane Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay. Source: HPA
Molecular_function	GAF domain binding Inferred from direct assay PubMed 17329248. Source: UniProtKB signal transducer activity Traceable author statement Ref.2. Source: ProtInc transcription coactivator activity Traceable author statement PubMed 9447995. Source: ProtInc transcription factor binding Traceable author statement PubMed 9447995. Source: ProtInc unfolded protein binding Inferred from direct assay PubMed 14557246. Source: HGNC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IRF7	Q92985	2	EBI-704197,EBI-968267
PDE2A	O00408	6	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

Natural variations

Natural variant

16

1

R → H. Ref.4 Ref.10

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 Ref.12
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.11

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.10

VAR_043913

Natural variant

307

1

Q → R. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs4930199 [ dbSNP | Ensembl ].

VAR_061545

Secondary structure

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330

Helix Strand Turn

Details...

Helix

4 – 9

6

Beta strand

17 – 19

3

Beta strand

33 – 37

5

Beta strand

39 – 41

3

Beta strand

43 – 46

4

Beta strand

49 – 53

5

Turn

54 – 57

4

Beta strand

60 – 67

8

Helix

72 – 77

6

Beta strand

85 – 89

5

Helix

92 – 95

4

Helix

98 – 105

8

Helix

108 – 110

3

Turn

113 – 117

5

Turn

137 – 139

3

Helix

140 – 143

4

Beta strand

149 – 158

10

Turn

160 – 162

3

Helix

173 – 176

4

Helix

178 – 192

15

Helix

195 – 213

19

Helix

221 – 243

23

Helix

248 – 260

13

Helix

265 – 277

13

Helix

281 – 294

14

Helix

296 – 298

3

Helix

299 – 311

13

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN GHSPA, VARIANT LYS-228.
[9]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RET.
[10]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS HIS-16 AND GLN-304, INVOLVEMENT IN ACTH-SECRETING PITUITARY ADENOMA, INVOLVEMENT IN GHSPA.
[11]	"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] [Europe PMC] [Abstract] Cited for: VARIANT TYR-248 DEL, 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] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LYS-228, MASS SPECTROMETRY.
+	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

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LKN	NMR	-	A	2-166	[»]
4AIF	X-ray	2.01	A/B	173-315	[»]
4APO	X-ray	1.90	A/B	166-330	[»]

ProteinModelPortal

O00170.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34068N.

IntAct

O00170. 10 interactions.

MINT

MINT-5000425.

STRING

9606.ENSP00000279146.

PTM databases

PhosphoSite

O00170.

Proteomic databases

PaxDb

O00170.

PRIDE

O00170.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000279146; ENSP00000279146; ENSG00000110711.

GeneID

9049.

KEGG

hsa:9049.

UCSC

uc001olv.3. human.

Organism-specific databases

CTD

9049.

GeneCards

GC11P067251.

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

eggNOG

NOG250378.

HOVERGEN

HBG004198.

InParanoid

O00170.

OMA

SARDDFR.

OrthoDB

EOG4B5P5R.

PhylomeDB

O00170.

Gene expression databases

ArrayExpress

O00170.

Bgee

O00170.

CleanEx

HS_AIP.

Genevestigator

O00170.

GermOnline

ENSG00000110711. Homo sapiens.

Family and domain databases

Gene3D

1.25.40.10. 1 hit.

InterPro

IPR001179. PPIase_FKBP_dom.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR019734. TPR_repeat.
[Graphical view]

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

GenomeRNAi

9049.

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:	May 1, 2013
This is version 120 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.