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Protein

Folliculin

Gene

FLCN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May be a tumor suppressor. May be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. May regulate phosphorylation of RPS6KB1.3 Publications

GO - Molecular functioni

  • guanyl-nucleotide exchange factor activity Source: InterPro
  • protein complex binding Source: UniProtKB

GO - Biological processi

Names & Taxonomyi

Protein namesi
Recommended name:
Folliculin
Alternative name(s):
BHD skin lesion fibrofolliculoma protein
Birt-Hogg-Dube syndrome protein
Gene namesi
Name:FLCN
Synonyms:BHD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000154803.12.
HGNCiHGNC:27310. FLCN.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Birt-Hogg-Dube syndrome (BHD)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:135150
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_066023108S → I in BHD. 1 Publication1
Natural variantiVAR_066029508K → R in BHD; does not impair protein stability, growth suppression activity or intracellular localization of folliculin. 2 PublicationsCorresponds to variant dbSNP:rs199643834Ensembl.1
Primary spontaneous pneumothorax (PSP)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCondition 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.
See also OMIM:173600
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_066024132E → K in PSP. 1 Publication1
Natural variantiVAR_066025157Missing in PSP; impaired protein stability. 2 Publications1
Natural variantiVAR_066028429H → Y in PSP. 1 PublicationCorresponds to variant dbSNP:rs375082054Ensembl.1
Renal cell carcinoma (RCC)1 Publication
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionRenal 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.
See also OMIM:144700
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_066026239R → C in RCC; impaired protein stability. 2 PublicationsCorresponds to variant dbSNP:rs78683075Ensembl.1

Keywords - Diseasei

Disease mutation, Tumor suppressor

Organism-specific databases

DisGeNETi201163.
GeneReviewsiFLCN.
MalaCardsiFLCN.
MIMi135150. phenotype.
144700. phenotype.
173600. phenotype.
OpenTargetsiENSG00000154803.
Orphaneti122. Birt-Hogg-Dube syndrome.
2903. Familial spontaneous pneumothorax.
PharmGKBiPA134901005.

Polymorphism and mutation databases

BioMutaiFLCN.
DMDMi74751276.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002239401 – 579FolliculinAdd BLAST579

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei62PhosphoserineCombined sources1
Modified residuei73PhosphoserineCombined sources1
Modified residuei302PhosphoserineCombined sources1
Modified residuei571PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated. Several different phosphorylated forms exist.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8NFG4.
MaxQBiQ8NFG4.
PaxDbiQ8NFG4.
PeptideAtlasiQ8NFG4.
PRIDEiQ8NFG4.

PTM databases

iPTMnetiQ8NFG4.
PhosphoSitePlusiQ8NFG4.

Expressioni

Tissue specificityi

Expressed in most tissues tested, including skin, lung, kidney, heart, testis and stomach.1 Publication

Developmental stagei

Expressed in fetal lung, kidney, liver, and brain.1 Publication

Gene expression databases

BgeeiENSG00000154803.
CleanExiHS_FLCN.
ExpressionAtlasiQ8NFG4. baseline and differential.
GenevisibleiQ8NFG4. HS.

Organism-specific databases

HPAiCAB015158.
HPA028760.

Interactioni

Subunit structurei

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 (PubMed:17028174, PubMed:18403135, PubMed:18663353, PubMed:27353360). Interacts with HSP90AA1 in the presence of FNIP1. Interacts with HSP70, STUB1, CDC37, AHSA1, CCT2, STIP1, PTGES3 and PPP5C (PubMed:27353360).4 Publications

GO - Molecular functioni

  • protein complex binding Source: UniProtKB

Protein-protein interaction databases

BioGridi128366. 40 interactors.
DIPiDIP-61287N.
IntActiQ8NFG4. 12 interactors.
STRINGi9606.ENSP00000285071.

Structurei

Secondary structure

1579
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi349 – 356Combined sources8
Helixi358 – 370Combined sources13
Beta strandi373 – 377Combined sources5
Helixi381 – 391Combined sources11
Helixi392 – 394Combined sources3
Helixi397 – 399Combined sources3
Beta strandi402 – 408Combined sources7
Turni412 – 414Combined sources3
Beta strandi416 – 420Combined sources5
Helixi428 – 431Combined sources4
Beta strandi436 – 443Combined sources8
Beta strandi463 – 469Combined sources7
Turni473 – 476Combined sources4
Helixi481 – 491Combined sources11
Helixi497 – 521Combined sources25
Helixi530 – 538Combined sources9
Helixi544 – 553Combined sources10
Helixi554 – 556Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3V42X-ray2.00A/B341-566[»]
ProteinModelPortaliQ8NFG4.
SMRiQ8NFG4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini86 – 242uDENN FLCN/SMCR8-typePROSITE-ProRule annotationAdd BLAST157
Domaini339 – 491cDENN FLCN/SMCR8-typePROSITE-ProRule annotationAdd BLAST153
Domaini493 – 558dDENN FLCN/SMCR8-typePROSITE-ProRule annotationAdd BLAST66

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili287 – 310Sequence analysisAdd BLAST24

Sequence similaritiesi

Belongs to the folliculin family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG3715. Eukaryota.
ENOG410XQ9Y. LUCA.
GeneTreeiENSGT00390000009864.
HOGENOMiHOG000052507.
HOVERGENiHBG081531.
InParanoidiQ8NFG4.
KOiK09594.
OMAiCYCALTG.
OrthoDBiEOG091G0C9Z.
PhylomeDBiQ8NFG4.
TreeFamiTF315084.

Family and domain databases

InterProiView protein in InterPro
IPR021713. Folliculin.
IPR032035. Folliculin_C.
PANTHERiPTHR31441. PTHR31441. 1 hit.
PfamiView protein in Pfam
PF16692. Folliculin_C. 1 hit.
PROSITEiView protein in PROSITE
PS51834. DENN_FLCN_SMCR8. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8NFG4-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MNAIVALCHF CELHGPRTLF CTEVLHAPLP QGDGNEDSPG QGEQAEEEEG
60 70 80 90 100
GIQMNSRMRA HSPAEGASVE SSSPGPKKSD MCEGCRSLAA GHPGYISHDK
110 120 130 140 150
ETSIKYVSHQ HPSHPQLFSI VRQACVRSLS CEVCPGREGP IFFGDEQHGF
160 170 180 190 200
VFSHTFFIKD SLARGFQRWY SIITIMMDRI YLINSWPFLL GKVRGIIDEL
210 220 230 240 250
QGKALKVFEA EQFGCPQRAQ RMNTAFTPFL HQRNGNAARS LTSLTSDDNL
260 270 280 290 300
WACLHTSFAW LLKACGSRLT EKLLEGAPTE DTLVQMEKLA DLEEESESWD
310 320 330 340 350
NSEAEEEEKA PVLPESTEGR ELTQGPAESS SLSGCGSWQP RKLPVFKSLR
360 370 380 390 400
HMRQVLGAPS FRMLAWHVLM GNQVIWKSRD VDLVQSAFEV LRTMLPVGCV
410 420 430 440 450
RIIPYSSQYE EAYRCNFLGL SPHVQIPPHV LSSEFAVIVE VHAAARSTLH
460 470 480 490 500
PVGCEDDQSL SKYEFVVTSG SPVAADRVGP TILNKIEAAL TNQNLSVDVV
510 520 530 540 550
DQCLVCLKEE WMNKVKVLFK FTKVDSRPKE DTQKLLSILG ASEEDNVKLL
560 570
KFWMTGLSKT YKSHLMSTVR SPTASESRN
Length:579
Mass (Da):64,473
Last modified:October 1, 2002 - v1
Checksum:iE168EB34544C6336
GO
Isoform 2 (identifier: Q8NFG4-2) [UniParc]FASTAAdd to basket

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.
Show »
Length:342
Mass (Da):37,742
Checksum:i3147596F8D7DF849
GO
Isoform 3 (identifier: Q8NFG4-3) [UniParc]FASTAAdd to basket

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.
Show »
Length:197
Mass (Da):20,877
Checksum:i8B2D060B096D7F7B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02535679S → W in a sporadic colorectal carcinoma; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs137852930Ensembl.1
Natural variantiVAR_066023108S → I in BHD. 1 Publication1
Natural variantiVAR_066024132E → K in PSP. 1 Publication1
Natural variantiVAR_066025157Missing in PSP; impaired protein stability. 2 Publications1
Natural variantiVAR_025357238A → V in a renal cell carcinoma cell line. 1 Publication1
Natural variantiVAR_066026239R → C in RCC; impaired protein stability. 2 PublicationsCorresponds to variant dbSNP:rs78683075Ensembl.1
Natural variantiVAR_025358320R → Q in a primary colorectal cancer. 1 PublicationCorresponds to variant dbSNP:rs143483053Ensembl.1
Natural variantiVAR_066027362R → C Found in a colorectal cell line; impaired protein stability. 1 PublicationCorresponds to variant dbSNP:rs557336321Ensembl.1
Natural variantiVAR_025359392R → G in a primary colorectal cancer; somatic mutation. 1 Publication1
Natural variantiVAR_066028429H → Y in PSP. 1 PublicationCorresponds to variant dbSNP:rs375082054Ensembl.1
Natural variantiVAR_025360444A → S in a primary clear-cell renal cell carcinoma; somatic mutation. 1 Publication1
Natural variantiVAR_025361445A → T in a sporadic colorectal carcinoma; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs41419545Ensembl.1
Natural variantiVAR_066029508K → R in BHD; does not impair protein stability, growth suppression activity or intracellular localization of folliculin. 2 PublicationsCorresponds to variant dbSNP:rs199643834Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_017312134 – 197CPGRE…VRGII → SLVATEPVSVGAHMLPGALG GLGASIAQGGRHWSSLRADP QISTAQGTGRLPCPELREES CWTC in isoform 3. 1 PublicationAdd BLAST64
Alternative sequenceiVSP_017313198 – 579Missing in isoform 3. 1 PublicationAdd BLAST382
Alternative sequenceiVSP_017314291 – 342DLEEE…WQPRK → GEAGVLLPGPWPGWPWGGTS CLLSWQESLREGNAALNQPR TSLREAHPPISV in isoform 2. 1 PublicationAdd BLAST52
Alternative sequenceiVSP_017315343 – 579Missing in isoform 2. 1 PublicationAdd BLAST237

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS32579.1. [Q8NFG4-1]
CCDS32580.1. [Q8NFG4-2]
RefSeqiNP_653207.1. NM_144606.5. [Q8NFG4-2]
NP_659434.2. NM_144997.5. [Q8NFG4-1]
XP_016879795.1. XM_017024306.1. [Q8NFG4-1]
XP_016879796.1. XM_017024307.1. [Q8NFG4-1]
XP_016879797.1. XM_017024308.1. [Q8NFG4-1]
UniGeneiHs.31652.

Genome annotation databases

EnsembliENST00000285071; ENSP00000285071; ENSG00000154803. [Q8NFG4-1]
ENST00000389169; ENSP00000373821; ENSG00000154803. [Q8NFG4-2]
GeneIDi201163.
KEGGihsa:201163.
UCSCiuc002gra.5. human. [Q8NFG4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiFLCN_HUMAN
AccessioniPrimary (citable) accession number: Q8NFG4
Secondary accession number(s): A6NJJ8
, Q6ZRX1, Q96BD2, Q96BE4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2006
Last sequence update: October 1, 2002
Last modified: September 27, 2017
This is version 126 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families