Folliculin (FLCN)

BHD; FLCL; BHD skin lesion fibrofolliculoma protein; Birt-Hogg-Dube syndrome protein

SPN	O651
HGNC	27310
MGI	2442184
PubMed	24081491
RGD	735088
UniProt	Q8NFG4
Wiki	Folliculin

Using coimmunoprecipitation of FNIP1 and FLCN expressed in HEK293 cells and in vitro binding assays, the C-terminus of FLCN and amino acids 300 to 1166 of FNIP1 were shown to be required for optimal FLCN-FNIP1 binding. FLCN and FNIP1 colocalized to the cytoplasm in a reticular pattern. FNIP1 was phosphorylated by AMPK and its phosphorylation was inhibited in a dose-dependent manner by an AMPK inhibitor, resulting in reduced FNIP1 expression. FLCN phosphorylation was diminished by rapamycin and amino acid starvation and facilitated by FNIP1 overexpression, suggesting that FLCN phosphorylation may be regulated by mTOR and AMPK signaling. FLCN and FNIP1 may be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways.

Reference

"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."
Cancer Cell 2:157-164(2002) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Alterations of the Birt-Hogg-Dube gene (BHD) in sporadic colorectal tumours."
J. Med. Genet. 40:511-515(2003) [PubMed] [Europe PMC] [Abstract]

"Analysis of the Birt-Hogg-Dube (BHD) tumour suppressor gene in sporadic renal cell carcinoma and colorectal cancer."
J. Med. Genet. 40:820-824(2003) [PubMed] [Europe PMC] [Abstract]

"A 4-bp deletion in the Birt-Hogg-Dube gene (FLCN) causes dominantly inherited spontaneous pneumothorax."
Am. J. Hum. Genet. 76:522-527(2005) [PubMed] [Europe PMC] [Abstract]

"Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dube syndrome."
Am. J. Hum. Genet. 76:1023-1033(2005) [PubMed] [Europe PMC] [Abstract]

"Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling."
Proc. Natl. Acad. Sci. U.S.A. 103:15552-15557(2006) [PubMed] [Europe PMC] [Abstract]

"Identification and characterization of a novel folliculin-interacting protein FNIP2."
Gene 415:60-67(2008) [PubMed] [Europe PMC] [Abstract]

"Interaction of folliculin (Birt-Hogg-Dube gene product) with a novel Fnip1-like (FnipL/Fnip2) protein."
Oncogene 27:5339-5347(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]

"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]

"Familial non-VHL clear cell (conventional) renal cell carcinoma: clinical features, segregation analysis, and mutation analysis of FLCN."
Clin. Cancer Res. 14:5925-5930(2008) [PubMed] [Europe PMC] [Abstract]

"Mutation analysis of the FLCN gene in Chinese patients with sporadic and familial isolated primary spontaneous pneumothorax."
Clin. Genet. 74:178-183(2008) [PubMed] [Europe PMC] [Abstract]

"Novel mutations in the folliculin gene associated with spontaneous pneumothorax."
Eur. Respir. J. 32:1316-1320(2008) [PubMed] [Europe PMC] [Abstract]

"BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dube syndrome: a new series of 50 families and a review of published reports."
J. Med. Genet. 45:321-331(2008) [PubMed] [Europe PMC] [Abstract]

"Birt-Hogg-Dube syndrome: clinical and genetic studies of 10 French families."
Br. J. Dermatol. 162:527-537(2010) [PubMed] [Europe PMC] [Abstract]

"Birt Hogg-Dube syndrome-associated FLCN mutations disrupt protein stability."
Hum. Mutat. 32:921-929(2011) [PubMed] [Europe PMC] [Abstract]