Q8NFG4 (FLCN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Folliculin

Alternative name(s):
BHD skin lesion fibrofolliculoma protein
Birt-Hogg-Dube syndrome protein

Gene names

Name:	FLCN
Synonyms:	BHD

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	579 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a role in the pathogenesis of an uncommon form of kidney cancer through its association with an inherited disorder of the hair follicle (fibrofolliculomas). May be a tumor suppressor. May be involved in colorectal tumorigenesis. May be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. May regulate phosphorylation of RPS6KB1. Ref.1 Ref.10 Ref.12
Subunit structure	Interacts (via C-terminus) with FNIP1 and FNIP2 (via C-terminus). This mediates indirect interaction with the PRKAA1, PRKAB1 and PRKAG1 subunits of 5'-AMP-activated protein kinase. Ref.10 Ref.11 Ref.12
Subcellular location	Cytoplasm. Nucleus. Note: Mainly localized in the nucleus. Co-localizes with FNIP1 and FNIP2 in the cytoplasm. Ref.10 Ref.12
Tissue specificity	Expressed in most tissues tested, including skin, lung, kidney, heart, testis and stomach. Ref.1
Developmental stage	Expressed in fetal lung, kidney, liver, and brain. Ref.1
Post-translational modification	Phosphorylated. Several different phosphorylated forms exist. Ref.10
Involvement in disease	Birt-Hogg-Dube syndrome (BHD) [MIM:135150]: A rare autosomal dominant genodermatosis characterized by hair follicle hamartomas (fibrofolliculomas), kidney tumors, and spontaneous pneumothorax. Fibrofolliculomas are part of the triad of Birt-Hogg-Dube syndrome skin lesions that also includes trichodiscomas and acrochordons. Onset of this dermatologic condition is invariably in adulthood. Birt-Hogg-Dube syndrome is associated with a variety of histologic types of renal tumors, including chromophobe renal cell carcinoma (RCC), benign renal oncocytoma, clear-cell RCC and papillary type I RCC. Multiple lipomas, angiolipomas, and parathyroid adenomas are also seen in Birt-Hogg-Dube syndrome patients. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18 Ref.19 Primary spontaneous pneumothorax (PSP) [MIM:173600]: Condition in which air is present in the pleural space in the absence of a precipitating event, such as trauma or lung disease. This results in secondary collapse of the lung, either partially or completely, and some degree of hypoxia. PSP is relatively common, with an incidence between 7.4-18/100'000 for men and 1.2-6/100'000 for women and a dose-dependent, increased risk among smokers. Most cases are sporadic, typically occurring in tall, thin men aged 10-30 years and generally while at rest. Familial PSP is rarer and usually is inherited as an autosomal dominant condition with reduced penetrance, although X-linked recessive and autosomal recessive inheritance have also been suggested. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.16 Ref.17 Renal cell carcinoma (RCC) [MIM:144700]: Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype. Note: The gene represented in this entry may be involved in disease pathogenesis. Ref.15
Sequence similarities	Belongs to the folliculin family.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Tumor suppressor
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	TOR signaling cascade Inferred from mutant phenotype Ref.10. Source: UniProtKB cell-cell junction assembly Inferred from sequence or structural similarity. Source: UniProtKB hemopoiesis Inferred from sequence or structural similarity. Source: UniProtKB in utero embryonic development Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of ATP biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of ERK1 and ERK2 cascade Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of Rho protein signal transduction Inferred from mutant phenotype PubMed 22965878. Source: UniProtKB negative regulation of TOR signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell growth Inferred from direct assay PubMed 20573232. Source: UniProtKB negative regulation of cell migration Inferred from mutant phenotype PubMed 22965878. Source: UniProtKB negative regulation of cell proliferation involved in kidney development Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of energy homeostasis Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of mitochondrion organization Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein kinase B signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein localization to nucleus Inferred from direct assay PubMed 21209915. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 20573232. Source: UniProtKB positive regulation of TOR signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell adhesion Inferred from mutant phenotype PubMed 21209915. Source: UniProtKB positive regulation of protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 20573232. Source: UniProtKB positive regulation of transforming growth factor beta receptor signaling pathway Inferred from direct assay PubMed 20573232. Source: UniProtKB regulation of cell cycle cytokinesis Inferred from mutant phenotype PubMed 22965878. Source: UniProtKB regulation of histone acetylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of pro-B cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB response to stress Inferred from mutant phenotype Ref.10. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay Ref.10Ref.12PubMed 22965878. Source: UniProtKB nucleus Inferred from direct assay Ref.10Ref.12. Source: UniProtKB plasma membrane Inferred from direct assay. Source: HPA
Molecular_function	protein complex binding Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8NFG4-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8NFG4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     291-342: DLEEESESWD...SGCGSWQPRK → GEAGVLLPGP...LREAHPPISV
     343-579: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q8NFG4-3)

The sequence of this isoform differs from the canonical sequence as follows:
     134-197: CPGREGPIFF...FLLGKVRGII → SLVATEPVSV...ELREESCWTC
     198-579: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 579

579

Folliculin

PRO_0000223940

Regions

Coiled coil

287 – 310

24

Potential

Amino acid modifications

Modified residue

62

1

Phosphoserine Ref.13 Ref.14

Natural variations

Alternative sequence

134 – 197

64

CPGRE…VRGII → SLVATEPVSVGAHMLPGALG GLGASIAQGGRHWSSLRADP QISTAQGTGRLPCPELREES CWTC in isoform 3.

VSP_017312

Alternative sequence

198 – 579

382

Missing in isoform 3.

VSP_017313

Alternative sequence

291 – 342

52

DLEEE…WQPRK → GEAGVLLPGPWPGWPWGGTS CLLSWQESLREGNAALNQPR TSLREAHPPISV in isoform 2.

VSP_017314

Alternative sequence

343 – 579

237

Missing in isoform 2.

VSP_017315

Natural variant

79

1

S → W in a sporadic colorectal carcinoma; somatic mutation.

VAR_025356

Natural variant

108

1

S → I in BHD. Ref.19

VAR_066023

Natural variant

132

1

E → K in PSP. Ref.17

VAR_066024

Natural variant

157

1

Missing in PSP; impaired protein stability. Ref.16 Ref.20

VAR_066025

Natural variant

238

1

A → V in a renal cell carcinoma cell line. Ref.7

VAR_025357

Natural variant

239

1

R → C in RCC; impaired protein stability. Ref.15 Ref.20

VAR_066026

Natural variant

320

1

R → Q in a primary colorectal cancer. Ref.7

VAR_025358

Natural variant

362

1

R → C Found in a colorectal cell line; impaired protein stability. Ref.20

VAR_066027

Natural variant

392

1

R → G in a primary colorectal cancer; somatic mutation. Ref.7

VAR_025359

Natural variant

429

1

H → Y in PSP. Ref.16

VAR_066028

Natural variant

444

1

A → S in a primary clear-cell renal cell carcinoma; somatic mutation. Ref.7

VAR_025360

Natural variant

445

1

A → T in a sporadic colorectal carcinoma; somatic mutation.
Corresponds to variant rs41419545 [ dbSNP | Ensembl ].

VAR_025361

Natural variant

508

1

K → R in BHD; does not impair protein stability, growth suppression activity or intracellular localization of folliculin. Ref.18 Ref.20

VAR_066029

Secondary structure

1

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579

Helix Strand Turn

Details...

Helix

349 – 356

8

Helix

358 – 370

13

Beta strand

373 – 377

5

Helix

381 – 391

11

Helix

392 – 394

3

Helix

397 – 399

3

Beta strand

402 – 408

7

Turn

412 – 414

3

Beta strand

416 – 420

5

Helix

428 – 431

4

Beta strand

436 – 443

8

Beta strand

463 – 469

7

Helix

481 – 491

11

Helix

497 – 521

25

Helix

530 – 538

9

Helix

544 – 553

10

Helix

554 – 556

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: E168EB34544C6336	FASTA	579	64,473
	10 20 30 40 50 60 MNAIVALCHF CELHGPRTLF CTEVLHAPLP QGDGNEDSPG QGEQAEEEEG GIQMNSRMRA 70 80 90 100 110 120 HSPAEGASVE SSSPGPKKSD MCEGCRSLAA GHPGYISHDK ETSIKYVSHQ HPSHPQLFSI 130 140 150 160 170 180 VRQACVRSLS CEVCPGREGP IFFGDEQHGF VFSHTFFIKD SLARGFQRWY SIITIMMDRI 190 200 210 220 230 240 YLINSWPFLL GKVRGIIDEL QGKALKVFEA EQFGCPQRAQ RMNTAFTPFL HQRNGNAARS 250 260 270 280 290 300 LTSLTSDDNL WACLHTSFAW LLKACGSRLT EKLLEGAPTE DTLVQMEKLA DLEEESESWD 310 320 330 340 350 360 NSEAEEEEKA PVLPESTEGR ELTQGPAESS SLSGCGSWQP RKLPVFKSLR HMRQVLGAPS 370 380 390 400 410 420 FRMLAWHVLM GNQVIWKSRD VDLVQSAFEV LRTMLPVGCV RIIPYSSQYE EAYRCNFLGL 430 440 450 460 470 480 SPHVQIPPHV LSSEFAVIVE VHAAARSTLH PVGCEDDQSL SKYEFVVTSG SPVAADRVGP 490 500 510 520 530 540 TILNKIEAAL TNQNLSVDVV DQCLVCLKEE WMNKVKVLFK FTKVDSRPKE DTQKLLSILG 550 560 570 ASEEDNVKLL KFWMTGLSKT YKSHLMSTVR SPTASESRN
	Isoform 2 [UniParc]. Checksum: 3147596F8D7DF849	FASTA	342	37,742
	10 20 30 40 50 60 MNAIVALCHF CELHGPRTLF CTEVLHAPLP QGDGNEDSPG QGEQAEEEEG GIQMNSRMRA 70 80 90 100 110 120 HSPAEGASVE SSSPGPKKSD MCEGCRSLAA GHPGYISHDK ETSIKYVSHQ HPSHPQLFSI 130 140 150 160 170 180 VRQACVRSLS CEVCPGREGP IFFGDEQHGF VFSHTFFIKD SLARGFQRWY SIITIMMDRI 190 200 210 220 230 240 YLINSWPFLL GKVRGIIDEL QGKALKVFEA EQFGCPQRAQ RMNTAFTPFL HQRNGNAARS 250 260 270 280 290 300 LTSLTSDDNL WACLHTSFAW LLKACGSRLT EKLLEGAPTE DTLVQMEKLA GEAGVLLPGP 310 320 330 340 WPGWPWGGTS CLLSWQESLR EGNAALNQPR TSLREAHPPI SV
	Isoform 3 [UniParc]. Checksum: 8B2D060B096D7F7B	FASTA	197	20,877
	10 20 30 40 50 60 MNAIVALCHF CELHGPRTLF CTEVLHAPLP QGDGNEDSPG QGEQAEEEEG GIQMNSRMRA 70 80 90 100 110 120 HSPAEGASVE SSSPGPKKSD MCEGCRSLAA GHPGYISHDK ETSIKYVSHQ HPSHPQLFSI 130 140 150 160 170 180 VRQACVRSLS CEVSLVATEP VSVGAHMLPG ALGGLGASIA QGGRHWSSLR ADPQISTAQG 190 TGRLPCPELR EESCWTC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dube syndrome." Nickerson M.L., Warren M.B., Toro J.R., Matrosova V., Glenn G., Turner M.L., Duray P., Merino M., Choyke P.L., Pavlovich C.P., Sharma N., Walther M.M., Munroe D., Hill R., Maher E., Greenberg C., Lerman M.I., Linehan W.M., Zbar B., Schmidt L.S. Cancer Cell 2:157-164(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INVOLVEMENT IN BIRT-HOGG-DUBE SYNDROME. Tissue: Lung.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Spleen.
[3]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 267-579 (ISOFORM 1). Tissue: Skin.
[6]	"Alterations of the Birt-Hogg-Dube gene (BHD) in sporadic colorectal tumours." Kahnoski K., Khoo S.K., Nassif N.T., Chen J., Lobo G.P., Segelov E., Teh B.T. J. Med. Genet. 40:511-515(2003) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN COLORECTAL CANCER, VARIANTS TRP-79 AND THR-445.
[7]	"Analysis of the Birt-Hogg-Dube (BHD) tumour suppressor gene in sporadic renal cell carcinoma and colorectal cancer." da Silva N.F., Gentle D., Hesson L.B., Morton D.G., Latif F., Maher E.R. J. Med. Genet. 40:820-824(2003) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN RENAL CELL CARCINOMA AND COLORECTAL CANCER, VARIANTS VAL-238; GLN-320; GLY-392 AND SER-444.
[8]	"A 4-bp deletion in the Birt-Hogg-Dube gene (FLCN) causes dominantly inherited spontaneous pneumothorax." Painter J.N., Tapanainen H., Somer M., Tukiainen P., Aittomaeki K. Am. J. Hum. Genet. 76:522-527(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PSP.
[9]	"Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dube syndrome." Schmidt L.S., Nickerson M.L., Warren M.B., Glenn G.M., Toro J.R., Merino M.J., Turner M.L., Choyke P.L., Sharma N., Peterson J., Morrison P., Maher E.R., Walther M.M., Zbar B., Linehan W.M. Am. J. Hum. Genet. 76:1023-1033(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN BIRT-HOGG-DUBE SYNDROME.
[10]	"Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling." Baba M., Hong S.-B., Sharma N., Warren M.B., Nickerson M.L., Iwamatsu A., Esposito D., Gillette W.K., Hopkins R.F. III, Hartley J.L., Furihata M., Oishi S., Zhen W., Burke T.R. Jr., Linehan W.M., Schmidt L.S., Zbar B. Proc. Natl. Acad. Sci. U.S.A. 103:15552-15557(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, INTERACTION WITH FNIP1, IDENTIFICATION BY MASS SPECTROMETRY.
[11]	"Identification and characterization of a novel folliculin-interacting protein FNIP2." Hasumi H., Baba M., Hong S.-B., Hasumi Y., Huang Y., Yao M., Valera V.A., Linehan W.M., Schmidt L.S. Gene 415:60-67(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FNIP2.
[12]	"Interaction of folliculin (Birt-Hogg-Dube gene product) with a novel Fnip1-like (FnipL/Fnip2) protein." Takagi Y., Kobayashi T., Shiono M., Wang L., Piao X., Sun G., Zhang D., Abe M., Hagiwara Y., Takahashi K., Hino O. Oncogene 27:5339-5347(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FNIP2.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, MASS SPECTROMETRY.
[15]	"Familial non-VHL clear cell (conventional) renal cell carcinoma: clinical features, segregation analysis, and mutation analysis of FLCN." Woodward E.R., Ricketts C., Killick P., Gad S., Morris M.R., Kavalier F., Hodgson S.V., Giraud S., Bressac-de Paillerets B., Chapman C., Escudier B., Latif F., Richard S., Maher E.R. Clin. Cancer Res. 14:5925-5930(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT RCC CYS-239.
[16]	"Mutation analysis of the FLCN gene in Chinese patients with sporadic and familial isolated primary spontaneous pneumothorax." Ren H.Z., Zhu C.C., Yang C., Chen S.L., Xie J., Hou Y.Y., Xu Z.F., Wang D.J., Mu D.K., Ma D.H., Wang Y., Ye M.H., Ye Z.R., Chen B.F., Wang C.G., Lin J., Qiao D., Yi L. Clin. Genet. 74:178-183(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PSP PHE-157 DEL AND TYR-429.
[17]	"Novel mutations in the folliculin gene associated with spontaneous pneumothorax." Frohlich B.A., Zeitz C., Matyas G., Alkadhi H., Tuor C., Berger W., Russi E.W. Eur. Respir. J. 32:1316-1320(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PSP LYS-132.
[18]	"BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dube syndrome: a new series of 50 families and a review of published reports." Toro J.R., Wei M.H., Glenn G.M., Weinreich M., Toure O., Vocke C., Turner M., Choyke P., Merino M.J., Pinto P.A., Steinberg S.M., Schmidt L.S., Linehan W.M. J. Med. Genet. 45:321-331(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BHD ARG-508.
[19]	"Birt-Hogg-Dube syndrome: clinical and genetic studies of 10 French families." Kluger N., Giraud S., Coupier I., Avril M.F., Dereure O., Guillot B., Richard S., Bessis D. Br. J. Dermatol. 162:527-537(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BHD ILE-108.
[20]	"Birt Hogg-Dube syndrome-associated FLCN mutations disrupt protein stability." Nahorski M.S., Reiman A., Lim D.H., Nookala R.K., Seabra L., Lu X., Fenton J., Boora U., Nordenskjold M., Latif F., Hurst L.D., Maher E.R. Hum. Mutat. 32:921-929(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CYS-362, CHARACTERIZATION OF VARIANTS PHE-157 DEL; CYS-239; CYS-362 AND ARG-508.
+	Additional computationally mapped references.

Web resources

GeneReviews

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Leiden Open Variation Database

Folliculin (FLCN)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF517523 mRNA. Translation: AAM94803.1.
AK127912 mRNA. Translation: BAC87186.1.
AK126951 mRNA. Translation: BAC86760.1.
AC055811 Genomic DNA. No translation available.
CH471196 Genomic DNA. Translation: EAW55716.1.
BC015687 mRNA. Translation: AAH15687.1.
BC015725 mRNA. Translation: AAH15725.2.

IPI

IPI00185096.
IPI00329635.
IPI00444197.

RefSeq

NP_653207.1. NM_144606.5.
NP_659434.2. NM_144997.5.

UniGene

Hs.31652.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3V42	X-ray	2.00	A/B	341-566	[»]

ProteinModelPortal

Q8NFG4.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q8NFG4. 4 interactions.

STRING

9606.ENSP00000285071.

PTM databases

PhosphoSite

Q8NFG4.

Polymorphism databases

DMDM

74751276.

Proteomic databases

PaxDb

Q8NFG4.

PRIDE

Q8NFG4.

Protocols and materials databases

DNASU

201163.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000285071; ENSP00000285071; ENSG00000154803.
ENST00000389169; ENSP00000373821; ENSG00000154803.

GeneID

201163.

KEGG

hsa:201163.

UCSC

uc002gra.4. human.
uc002grb.4. human.
uc002grc.2. human.

Organism-specific databases

CTD

201163.

GeneCards

GC17M017115.

HGNC

HGNC:27310. FLCN.

HPA

CAB015158.
HPA028760.

MIM

135150. phenotype.
144700. phenotype.
173600. phenotype.
607273. gene.

neXtProt

NX_Q8NFG4.

Orphanet

122. Birt-Hogg-Dube syndrome.
2903. Familial spontaneous pneumothorax.

PharmGKB

PA134901005.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG319853.

HOGENOM

HOG000052507.

HOVERGEN

HBG081531.

InParanoid

Q8NFG4.

KO

K09594.

OMA

DENLWAC.

OrthoDB

EOG4P8FHW.

Gene expression databases

ArrayExpress

Q8NFG4.

Bgee

Q8NFG4.

CleanEx

HS_FLCN.

Genevestigator

Q8NFG4.

GermOnline

ENSG00000154803. Homo sapiens.

Family and domain databases

InterPro

IPR021713. Folliculin.
[Graphical view]

Pfam

PF11704. Folliculin. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

201163.

NextBio

90061.

SOURCE

Search...

Entry information

Entry name

FLCN_HUMAN

Accession

Primary (citable) accession number: Q8NFG4
Secondary accession number(s): A6NJJ8 , Q6ZRX1, Q96BD2, Q96BE4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2006
Last sequence update:	October 1, 2002
Last modified:	May 1, 2013
This is version 86 of the entry and version 1 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.