Reviewed,
UniProtKB/Swiss-Prot Q8NFG4 (FLCN_HUMAN)
Last modified
June 16, 2009.
Version 45.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
Customize display | text xml rdf/xml gff fasta |
Names and origin
| Protein names | Recommended name: Folliculin Alternative name(s): Birt-Hogg-Dube syndrome protein BHD skin lesion fibrofolliculoma protein | ||||
| Gene names |
| ||||
| 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 | 579 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 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. Ref.1 Ref.10 |
| Subunit structure | Interacts (via C-terminus) with FNIP1 and FNIP2. This mediates indirect interaction with the PRKAA1, PRKAB1 and PRKAG1 subunits of 5'-AMP-activated protein kinase. Ref.10 Ref.11 |
| Subcellular location | |
| 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 Ref.12 |
| Involvement in disease | Defects in FLCN are the cause of Birt-Hogg-Dube syndrome (BHD) [MIM:135150]. BHD is a rare autosomal dominant genodermatosis characterized by hair follicle hamartomas (fibrofolliculomas), kidney tumors, and spontaneous pneumothorax. Fibrofolliculomas are part of the triad of BHD skin lesions that also includes trichodiscomas and acrochordons. Onset of this dermatologic condition is invariably in adulthood. BHD 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 patients affected with this disease. The majority of mutations are predicted to prematurely terminate the protein. Defects in FLCN are in some cases a cause of primary spontaneous pneumothorax (PSP) [MIM:173600]. PSP is a 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. Ref.8 Defects in FLCN may be involved in renal cell carcinoma. |
| Sequence similarities | Belongs to the folliculin family. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Cell cycle |
| Cellular component | Cytoplasm |
| Coding sequence diversity | Alternative splicing |
| Disease | Disease mutation |
| Domain | Coiled coil |
| Molecular function | Anti-oncogene |
| PTM | Phosphoprotein |
| Gene Ontology (GO) | |
| Biological process | cell cycle Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell cycleInferred from electronic annotation. Source: UniProtKB-KW |
| Cellular component | cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | protein binding Ref.11 Inferred from physical interaction. 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.12 | ||||||
| Modified residue | 73 | 1 | Phosphoserine Ref.12 | ||||||
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 | 238 | 1 | A → V in a renal cell carcinoma cell line. Ref.7 | VAR_025357 | |||||
| Natural variant | 320 | 1 | R → Q in a primary colorectal cancer. Ref.7 | VAR_025358 | |||||
| Natural variant | 392 | 1 | R → G in a primary colorectal cancer; somatic mutation. Ref.7 | VAR_025359 | |||||
| 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. | VAR_025361 | |||||
Sequences
| ||||||||||||||||||||||||||||||
References
| « Hide '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: 12204536] [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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [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. Nusbaum C.Nature 440:1045-1049(2006) [PubMed: 16625196] [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. 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: 15489334] [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: 12843323] [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: 14627671] [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: 15657874] [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: 15852235] [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: 17028174] [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: 18403135] [Abstract] Cited for: INTERACTION WITH FNIP2. |
| [12] | "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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-73, MASS SPECTROMETRY. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| 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. NP_659434.2. |
| UniGene | Hs.513975 |
3D structure databases | |
| ModBase | Search... |
PTM databases | |
| PhosphoSite | Q8NFG4. |
Proteomic databases | |
| PRIDE | Q8NFG4. |
Genome annotation databases | |
| Ensembl | ENSG00000154803. Homo sapiens. [Contig view] |
| GeneID | 201163. |
| KEGG | hsa:201163. |
Organism-specific databases | |
| GeneCards | GC17M017056. |
| H-InvDB | HIX0013581. |
| HGNC | HGNC:27310. FLCN. |
| HPA | CAB015158. |
| MIM | 135150. phenotype. 173600. phenotype. 607273. gene. |
| Orphanet | 122. Birt-Hogg-Dube syndrome. 2903. Spontaneous pneumothorax familial type. |
| PharmGKB | PA134901005. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | Q8NFG4. |
| OMA | Q8NFG4. KEEWMNK. |
Gene expression databases | |
| ArrayExpress | Q8NFG4. |
| Bgee | Q8NFG4. |
| CleanEx | HS_FLCN. |
| GermOnline | ENSG00000154803. Homo sapiens. |
Family and domain databases | |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 90061. |
| SOURCE | Search... |
Entry information
| Entry name | FLCN_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q8NFG4 Secondary accession number(s): A6NJJ8 Q96BE4 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 17 Human chromosome 17: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


