UniProtKB - Q8NFG4 (FLCN_HUMAN)
Folliculin
FLCN
Functioni
Multi-functional protein, involved in both the cellular response to amino acid availability and in the regulation of glycolysis (PubMed:17028174, PubMed:18663353, PubMed:21209915, PubMed:24081491, PubMed:24095279, PubMed:31704029, PubMed:31672913, PubMed:34381247).
GTPase-activating protein that plays a key role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:17028174, PubMed:18663353, PubMed:21209915, PubMed:24081491, PubMed:24095279, PubMed:31704029, PubMed:31672913).
Regulates glycolysis by binding to lactate dehydrogenase LDHA, acting as an uncompetitive inhibitor (PubMed:34381247).
Activates mTORC1 by acting as a GTPase-activating protein: specifically stimulates GTP hydrolysis by RRAGC/RagC or RRAGD/RagD, promoting the conversion to the GDP-bound state of RRAGC/RagC or RRAGD/RagD, and thereby activating the kinase activity of mTORC1 (PubMed:24095279, PubMed:31704029, PubMed:31672913).
The GTPase-activating activity is inhibited during starvation and activated in presence of nutrients (PubMed:31672913).
Acts as a key component for mTORC1-dependent control of the MiT/TFE factors TFEB and TFE3, while it is not involved in mTORC1-dependent phosphorylation of canonical RPS6KB1/S6K1 and EIF4EBP1/4E-BP1 (PubMed:21209915, PubMed:24081491, PubMed:31672913).
In low-amino acid conditions, the lysosomal folliculin complex (LFC) is formed on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, inactivates mTORC1 and maximizes nuclear translocation of TFEB and TFE3 (PubMed:31672913).
Upon amino acid restimulation, RRAGA/RagA (or RRAGB/RagB) nucleotide exchange promotes disassembly of the LFC complex and liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent cytoplasmic retention of TFEB and TFE3 (PubMed:31672913).
Indirectly acts as a positive regulator of Wnt signaling by promoting mTOR-dependent cytoplasmic retention of MiT/TFE factor TFE3 (PubMed:31272105).
Required for the exit of hematopoietic stem cell from pluripotency by promoting mTOR-dependent cytoplasmic retention of TFE3, thereby increasing Wnt signaling (PubMed:30733432).
Acts as an inhibitor of browning of adipose tissue by regulating mTOR-dependent cytoplasmic retention of TFE3 (By similarity).
In response to flow stress, regulates STK11/LKB1 accumulation and mTORC1 activation through primary cilia: may act by recruiting STK11/LKB1 to primary cilia for activation of AMPK resided at basal bodies, causing mTORC1 down-regulation (PubMed:27072130).
Together with FNIP1 and/or FNIP2, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed:25126726).
Required for starvation-induced perinuclear clustering of lysosomes by promoting association of RILP with its effector RAB34 (PubMed:27113757).
By similarity13 PublicationsCaution
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 164 | Essential for GTPase activation (GAP) activity2 Publications | 1 |
GO - Molecular functioni
- GTPase activator activity Source: UniProtKB
- guanyl-nucleotide exchange factor activity Source: InterPro
- protein-containing complex binding Source: UniProtKB
GO - Biological processi
- cell-cell junction assembly Source: UniProtKB
- cellular response to amino acid starvation Source: UniProtKB
- cellular response to starvation Source: UniProtKB
- energy homeostasis Source: UniProtKB
- hemopoiesis Source: UniProtKB
- in utero embryonic development Source: UniProtKB
- lysosome localization Source: UniProtKB
- negative regulation of ATP biosynthetic process Source: UniProtKB
- negative regulation of brown fat cell differentiation Source: UniProtKB
- negative regulation of cell growth Source: UniProtKB
- negative regulation of cell migration Source: UniProtKB
- negative regulation of cell proliferation involved in kidney development Source: UniProtKB
- negative regulation of cellular respiration Source: Ensembl
- negative regulation of cold-induced thermogenesis Source: YuBioLab
- negative regulation of ERK1 and ERK2 cascade Source: UniProtKB
- negative regulation of gene expression Source: UniProtKB
- negative regulation of mitochondrial DNA metabolic process Source: Ensembl
- negative regulation of mitochondrion organization Source: UniProtKB
- negative regulation of muscle tissue development Source: Ensembl
- negative regulation of post-translational protein modification Source: Ensembl
- negative regulation of protein kinase B signaling Source: UniProtKB
- negative regulation of protein localization to nucleus Source: UniProtKB
- negative regulation of Rho protein signal transduction Source: UniProtKB
- negative regulation of TOR signaling Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of apoptotic process Source: UniProtKB
- positive regulation of autophagy Source: UniProtKB
- positive regulation of cell adhesion Source: UniProtKB
- positive regulation of GTPase activity Source: GO_Central
- positive regulation of intrinsic apoptotic signaling pathway Source: Ensembl
- positive regulation of protein phosphorylation Source: UniProtKB
- positive regulation of TORC1 signaling Source: GO_Central
- positive regulation of TOR signaling Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
- regulation of cytokinesis Source: UniProtKB
- regulation of histone acetylation Source: UniProtKB
- regulation of pro-B cell differentiation Source: UniProtKB
- regulation of protein phosphorylation Source: UniProtKB
- regulation of Ras protein signal transduction Source: UniProtKB
- regulation of TOR signaling Source: UniProtKB
- TOR signaling Source: UniProtKB
Keywordsi
Molecular function | GTPase activation |
Enzyme and pathway databases
PathwayCommonsi | Q8NFG4 |
Reactomei | R-HSA-9639288, Amino acids regulate mTORC1 |
SignaLinki | Q8NFG4 |
SIGNORi | Q8NFG4 |
Names & Taxonomyi
Protein namesi | Recommended name: Folliculin1 PublicationAlternative name(s): BHD skin lesion fibrofolliculoma protein1 Publication Birt-Hogg-Dube syndrome protein1 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:27310, FLCN |
MIMi | 607273, gene |
neXtProti | NX_Q8NFG4 |
VEuPathDBi | HostDB:ENSG00000154803 |
Subcellular locationi
Nucleus
- Nucleus 2 Publications
Cytoskeleton
- centrosome 1 Publication
- spindle 1 Publication
Cytoplasm and Cytosol
- cytosol 6 Publications
Lysosome
- Lysosome membrane 5 Publications
Other locations
- cilium 2 Publications
Note: Localizes to lysosome membrane in amino acid-depleted conditions and relocalizes to the cytosol upon refeeding (PubMed:24095279, PubMed:29848618, PubMed:31672913). Colocalizes with FNIP1 and FNIP2 in the cytoplasm (PubMed:17028174, PubMed:18663353). Also localizes to motile and non-motile cilia, centrosomes and the mitotic spindle (PubMed:23784378).6 Publications
Cytoskeleton
- centrosome Source: UniProtKB
- mitotic spindle Source: UniProtKB
Cytosol
- cytosol Source: UniProtKB
Lysosome
- lysosomal membrane Source: UniProtKB
- lysosome Source: ParkinsonsUK-UCL
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: HPA
Other locations
Keywords - Cellular componenti
Cell projection, Cytoplasm, Cytoskeleton, Lysosome, Membrane, NucleusPathology & Biotechi
Involvement in diseasei
Birt-Hogg-Dube syndrome (BHD)6 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_066023 | 108 | S → I in BHD. 1 Publication | 1 | |
Natural variantiVAR_066025 | 157 | Missing in PSP and BHD; impaired protein stability. 3 PublicationsCorresponds to variant dbSNP:rs786203218Ensembl. | 1 | |
Natural variantiVAR_083269 | 220 – 579 | Missing in BHD. 1 PublicationAdd BLAST | 360 | |
Natural variantiVAR_083271 | 339 – 579 | Missing in BHD. 1 PublicationAdd BLAST | 241 | |
Natural variantiVAR_083272 | 409 – 579 | Missing in BHD. 1 PublicationAdd BLAST | 171 | |
Natural variantiVAR_066029 | 508 | K → R in BHD; does not impair protein stability, growth suppression activity or intracellular localization of folliculin. 2 PublicationsCorresponds to variant dbSNP:rs199643834EnsemblClinVar. | 1 | |
Natural variantiVAR_083275 | 511 – 579 | Missing in BHD. 1 PublicationAdd BLAST | 69 | |
Natural variantiVAR_083276 | 533 – 579 | Missing in BHD. 1 PublicationAdd BLAST | 47 |
Primary spontaneous pneumothorax (PSP)9 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_066024 | 132 | E → K in PSP. 1 Publication | 1 | |
Natural variantiVAR_066025 | 157 | Missing in PSP and BHD; impaired protein stability. 3 PublicationsCorresponds to variant dbSNP:rs786203218Ensembl. | 1 | |
Natural variantiVAR_083268 | 170 – 579 | Missing in PSP. 1 PublicationAdd BLAST | 410 | |
Natural variantiVAR_083270 | 315 – 579 | Missing in PSP. 1 PublicationAdd BLAST | 265 | |
Natural variantiVAR_083273 | 425 – 579 | Missing in PSP. 1 PublicationAdd BLAST | 155 | |
Natural variantiVAR_066028 | 429 | H → Y in PSP. 1 PublicationCorresponds to variant dbSNP:rs375082054EnsemblClinVar. | 1 | |
Natural variantiVAR_083274 | 477 – 579 | Missing in PSP. 1 PublicationAdd BLAST | 103 |
Renal cell carcinoma (RCC)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_066026 | 239 | R → C in RCC; impaired protein stability. 2 PublicationsCorresponds to variant dbSNP:rs78683075EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 118 | F → D: Does not assemble into a stable folliculin complex (LFC), preventing localization to the lysosomal membrane upon amino acid starvation. 1 Publication | 1 | |
Mutagenesisi | 164 | R → A: Abolished GTPase activation (GAP) activity. 2 Publications | 1 | |
Mutagenesisi | 406 | S → A: Impaired ability to regulate autophagy; when associated with A-537 and A-542. 1 Publication | 1 | |
Mutagenesisi | 537 | S → A: Impaired ability to regulate autophagy; when associated with A-406 and A-542. 1 Publication | 1 | |
Mutagenesisi | 542 | S → A: Impaired ability to regulate autophagy; when associated with A-406 and A-537. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, Tumor suppressorOrganism-specific databases
DisGeNETi | 201163 |
GeneReviewsi | FLCN |
MalaCardsi | FLCN |
MIMi | 135150, phenotype 144700, phenotype 173600, phenotype |
OpenTargetsi | ENSG00000154803 |
Orphaneti | 122, Birt-Hogg-Dube syndrome 2903, Familial spontaneous pneumothorax 422526, Hereditary clear cell renal cell carcinoma |
PharmGKBi | PA134901005 |
Miscellaneous databases
Pharosi | Q8NFG4, Tbio |
Genetic variation databases
BioMutai | FLCN |
DMDMi | 74751276 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000223940 | 1 – 579 | FolliculinAdd BLAST | 579 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 62 | PhosphoserineCombined sources | 1 | |
Modified residuei | 73 | PhosphoserineCombined sources | 1 | |
Modified residuei | 302 | PhosphoserineCombined sources | 1 | |
Modified residuei | 406 | Phosphoserine; by ULK11 Publication | 1 | |
Modified residuei | 537 | Phosphoserine; by ULK11 Publication | 1 | |
Modified residuei | 542 | Phosphoserine; by ULK11 Publication | 1 | |
Modified residuei | 571 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q8NFG4 |
jPOSTi | Q8NFG4 |
MassIVEi | Q8NFG4 |
MaxQBi | Q8NFG4 |
PaxDbi | Q8NFG4 |
PeptideAtlasi | Q8NFG4 |
PRIDEi | Q8NFG4 |
ProteomicsDBi | 73302 [Q8NFG4-1] 73303 [Q8NFG4-2] 73304 [Q8NFG4-3] |
PTM databases
iPTMneti | Q8NFG4 |
MetOSitei | Q8NFG4 |
PhosphoSitePlusi | Q8NFG4 |
Expressioni
Tissue specificityi
Developmental stagei
Gene expression databases
Bgeei | ENSG00000154803, Expressed in right hemisphere of cerebellum and 226 other tissues |
ExpressionAtlasi | Q8NFG4, baseline and differential |
Genevisiblei | Q8NFG4, HS |
Organism-specific databases
HPAi | ENSG00000154803, Low tissue specificity |
Interactioni
Subunit structurei
Interacts (via C-terminus) with FNIP1 or FNIP2 (via C-terminus) (PubMed:17028174, PubMed:18403135, PubMed:18663353, PubMed:27353360).
Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RRAGA/RagA or RRAGB/RagB GDP-bound, RRAGC/RagC or RRAGD/RagD GTP-bound, and Ragulator (PubMed:31704029, PubMed:31672913). Interaction with FNIP1 or FNIP2 mediates indirect interaction with the PRKAA1, PRKAB1 and PRKAG1 subunits of 5'-AMP-activated protein kinase (AMPK) (PubMed:17028174).
Interacts with HSP90AA1 in the presence of FNIP1 (PubMed:27353360).
Interacts with HSP70, STUB1, CDC37, AHSA1, CCT2, STIP1, PTGES3 and PPP5C (PubMed:27353360).
Interacts with GABARAP; interaction takes place in the presence of FNIP1 and/or FNIP2 (PubMed:25126726).
Interacts with RILP; the interaction is direct and promotes association between RILP and RAB34 (PubMed:27113757).
Interacts with KIF3A and KIF3B (PubMed:27072130).
Interacts with lactate dehydrogenase LDHA, but not LDHB; the interaction is direct, may preferentially bind LDHA dimers rather than tetramers, and regulates LDHA activity, acting as an uncompetitive inhibitor (PubMed:34381247).
10 PublicationsBinary interactionsi
Q8NFG4
With | #Exp. | IntAct |
---|---|---|
FNIP1 [Q8TF40] | 5 | EBI-2970160,EBI-2946919 |
FNIP2 [Q9P278] | 7 | EBI-2970160,EBI-7597109 |
Isoform 1 [Q8NFG4-1]
With | #Exp. | IntAct |
---|---|---|
FNIP1 - isoform 1 [Q8TF40-1] | 7 | EBI-15604776,EBI-15604805 |
Protein-protein interaction databases
BioGRIDi | 128366, 94 interactors |
CORUMi | Q8NFG4 |
DIPi | DIP-61287N |
IntActi | Q8NFG4, 27 interactors |
MINTi | Q8NFG4 |
STRINGi | 9606.ENSP00000285071 |
Miscellaneous databases
RNActi | Q8NFG4, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q8NFG4 |
SMRi | Q8NFG4 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 86 – 242 | uDENN FLCN/SMCR8-typePROSITE-ProRule annotationAdd BLAST | 157 | |
Domaini | 339 – 491 | cDENN FLCN/SMCR8-typePROSITE-ProRule annotationAdd BLAST | 153 | |
Domaini | 493 – 558 | dDENN FLCN/SMCR8-typePROSITE-ProRule annotationAdd BLAST | 66 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 30 – 81 | DisorderedSequence analysisAdd BLAST | 52 | |
Regioni | 210 – 220 | Essential for interaction with LDHA1 PublicationAdd BLAST | 11 | |
Regioni | 294 – 337 | DisorderedSequence analysisAdd BLAST | 44 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 287 – 310 | Sequence analysisAdd BLAST | 24 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 322 – 337 | Polar residuesSequence analysisAdd BLAST | 16 |
Sequence similaritiesi
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | KOG3715, Eukaryota |
GeneTreei | ENSGT00390000009864 |
HOGENOMi | CLU_035854_2_0_1 |
InParanoidi | Q8NFG4 |
OMAi | WKNKVTC |
OrthoDBi | 188544at2759 |
PhylomeDBi | Q8NFG4 |
TreeFami | TF315084 |
Family and domain databases
Gene3Di | 1.10.10.1730, 1 hit |
InterProi | View protein in InterPro IPR037521, FLCN/SMCR8_DENN IPR044886, FLCN_DENN_C_sf IPR021713, Folliculin IPR037520, Folliculin/SMCR8_longin IPR032035, Folliculin_DENN |
PANTHERi | PTHR31441, PTHR31441, 1 hit |
Pfami | View protein in Pfam PF11704, Folliculin, 1 hit PF16692, Folliculin_C, 1 hit |
PROSITEi | View protein in PROSITE PS51834, DENN_FLCN_SMCR8, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9J4C4 | C9J4C4_HUMAN | Folliculin | FLCN | 153 | Annotation score: | ||
J3QQZ7 | J3QQZ7_HUMAN | Folliculin | FLCN | 37 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_025356 | 79 | S → W in a sporadic colorectal carcinoma; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs137852930EnsemblClinVar. | 1 | |
Natural variantiVAR_066023 | 108 | S → I in BHD. 1 Publication | 1 | |
Natural variantiVAR_066024 | 132 | E → K in PSP. 1 Publication | 1 | |
Natural variantiVAR_066025 | 157 | Missing in PSP and BHD; impaired protein stability. 3 PublicationsCorresponds to variant dbSNP:rs786203218Ensembl. | 1 | |
Natural variantiVAR_083268 | 170 – 579 | Missing in PSP. 1 PublicationAdd BLAST | 410 | |
Natural variantiVAR_083269 | 220 – 579 | Missing in BHD. 1 PublicationAdd BLAST | 360 | |
Natural variantiVAR_025357 | 238 | A → V in a renal cell carcinoma cell line. 1 Publication | 1 | |
Natural variantiVAR_066026 | 239 | R → C in RCC; impaired protein stability. 2 PublicationsCorresponds to variant dbSNP:rs78683075EnsemblClinVar. | 1 | |
Natural variantiVAR_083270 | 315 – 579 | Missing in PSP. 1 PublicationAdd BLAST | 265 | |
Natural variantiVAR_025358 | 320 | R → Q in a primary colorectal cancer. 1 PublicationCorresponds to variant dbSNP:rs143483053EnsemblClinVar. | 1 | |
Natural variantiVAR_083271 | 339 – 579 | Missing in BHD. 1 PublicationAdd BLAST | 241 | |
Natural variantiVAR_066027 | 362 | R → C Found in a colorectal cell line; impaired protein stability. 1 PublicationCorresponds to variant dbSNP:rs557336321EnsemblClinVar. | 1 | |
Natural variantiVAR_025359 | 392 | R → G in a primary colorectal cancer; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1060502374Ensembl. | 1 | |
Natural variantiVAR_083272 | 409 – 579 | Missing in BHD. 1 PublicationAdd BLAST | 171 | |
Natural variantiVAR_083273 | 425 – 579 | Missing in PSP. 1 PublicationAdd BLAST | 155 | |
Natural variantiVAR_066028 | 429 | H → Y in PSP. 1 PublicationCorresponds to variant dbSNP:rs375082054EnsemblClinVar. | 1 | |
Natural variantiVAR_025360 | 444 | A → S in a primary clear-cell renal cell carcinoma; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_025361 | 445 | A → T in a sporadic colorectal carcinoma; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs41419545EnsemblClinVar. | 1 | |
Natural variantiVAR_083274 | 477 – 579 | Missing in PSP. 1 PublicationAdd BLAST | 103 | |
Natural variantiVAR_066029 | 508 | K → R in BHD; does not impair protein stability, growth suppression activity or intracellular localization of folliculin. 2 PublicationsCorresponds to variant dbSNP:rs199643834EnsemblClinVar. | 1 | |
Natural variantiVAR_083275 | 511 – 579 | Missing in BHD. 1 PublicationAdd BLAST | 69 | |
Natural variantiVAR_083276 | 533 – 579 | Missing in BHD. 1 PublicationAdd BLAST | 47 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_017312 | 134 – 197 | CPGRE…VRGII → SLVATEPVSVGAHMLPGALG GLGASIAQGGRHWSSLRADP QISTAQGTGRLPCPELREES CWTC in isoform 3. 1 PublicationAdd BLAST | 64 | |
Alternative sequenceiVSP_017313 | 198 – 579 | Missing in isoform 3. 1 PublicationAdd BLAST | 382 | |
Alternative sequenceiVSP_017314 | 291 – 342 | DLEEE…WQPRK → GEAGVLLPGPWPGWPWGGTS CLLSWQESLREGNAALNQPR TSLREAHPPISV in isoform 2. 1 PublicationAdd BLAST | 52 | |
Alternative sequenceiVSP_017315 | 343 – 579 | Missing in isoform 2. 1 PublicationAdd BLAST | 237 |
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 |
CCDSi | CCDS32579.1 [Q8NFG4-1] CCDS32580.1 [Q8NFG4-2] |
RefSeqi | NP_653207.1, NM_144606.5 [Q8NFG4-2] NP_659434.2, NM_144997.5 [Q8NFG4-1] XP_016879795.1, XM_017024306.1 XP_016879796.1, XM_017024307.1 XP_016879797.1, XM_017024308.1 [Q8NFG4-1] |
Genome annotation databases
Ensembli | ENST00000285071.9; ENSP00000285071.4; ENSG00000154803.13 ENST00000389169.9; ENSP00000373821.5; ENSG00000154803.13 [Q8NFG4-2] |
GeneIDi | 201163 |
KEGGi | hsa:201163 |
MANE-Selecti | ENST00000285071.9; ENSP00000285071.4; NM_144997.7; NP_659434.2 |
UCSCi | uc002gra.5, human [Q8NFG4-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Leiden Open Variation Database Folliculin (FLCN) |
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 |
CCDSi | CCDS32579.1 [Q8NFG4-1] CCDS32580.1 [Q8NFG4-2] |
RefSeqi | NP_653207.1, NM_144606.5 [Q8NFG4-2] NP_659434.2, NM_144997.5 [Q8NFG4-1] XP_016879795.1, XM_017024306.1 XP_016879796.1, XM_017024307.1 XP_016879797.1, XM_017024308.1 [Q8NFG4-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3V42 | X-ray | 2.00 | A/B | 341-566 | [»] | |
6NZD | electron microscopy | 3.60 | H | 1-579 | [»] | |
6ULG | electron microscopy | 3.31 | L | 1-579 | [»] | |
AlphaFoldDBi | Q8NFG4 | |||||
SMRi | Q8NFG4 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 128366, 94 interactors |
CORUMi | Q8NFG4 |
DIPi | DIP-61287N |
IntActi | Q8NFG4, 27 interactors |
MINTi | Q8NFG4 |
STRINGi | 9606.ENSP00000285071 |
PTM databases
iPTMneti | Q8NFG4 |
MetOSitei | Q8NFG4 |
PhosphoSitePlusi | Q8NFG4 |
Genetic variation databases
BioMutai | FLCN |
DMDMi | 74751276 |
Proteomic databases
EPDi | Q8NFG4 |
jPOSTi | Q8NFG4 |
MassIVEi | Q8NFG4 |
MaxQBi | Q8NFG4 |
PaxDbi | Q8NFG4 |
PeptideAtlasi | Q8NFG4 |
PRIDEi | Q8NFG4 |
ProteomicsDBi | 73302 [Q8NFG4-1] 73303 [Q8NFG4-2] 73304 [Q8NFG4-3] |
Protocols and materials databases
Antibodypediai | 4192, 311 antibodies from 37 providers |
DNASUi | 201163 |
Genome annotation databases
Ensembli | ENST00000285071.9; ENSP00000285071.4; ENSG00000154803.13 ENST00000389169.9; ENSP00000373821.5; ENSG00000154803.13 [Q8NFG4-2] |
GeneIDi | 201163 |
KEGGi | hsa:201163 |
MANE-Selecti | ENST00000285071.9; ENSP00000285071.4; NM_144997.7; NP_659434.2 |
UCSCi | uc002gra.5, human [Q8NFG4-1] |
Organism-specific databases
CTDi | 201163 |
DisGeNETi | 201163 |
GeneCardsi | FLCN |
GeneReviewsi | FLCN |
HGNCi | HGNC:27310, FLCN |
HPAi | ENSG00000154803, Low tissue specificity |
MalaCardsi | FLCN |
MIMi | 135150, phenotype 144700, phenotype 173600, phenotype 607273, gene |
neXtProti | NX_Q8NFG4 |
OpenTargetsi | ENSG00000154803 |
Orphaneti | 122, Birt-Hogg-Dube syndrome 2903, Familial spontaneous pneumothorax 422526, Hereditary clear cell renal cell carcinoma |
PharmGKBi | PA134901005 |
VEuPathDBi | HostDB:ENSG00000154803 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3715, Eukaryota |
GeneTreei | ENSGT00390000009864 |
HOGENOMi | CLU_035854_2_0_1 |
InParanoidi | Q8NFG4 |
OMAi | WKNKVTC |
OrthoDBi | 188544at2759 |
PhylomeDBi | Q8NFG4 |
TreeFami | TF315084 |
Enzyme and pathway databases
PathwayCommonsi | Q8NFG4 |
Reactomei | R-HSA-9639288, Amino acids regulate mTORC1 |
SignaLinki | Q8NFG4 |
SIGNORi | Q8NFG4 |
Miscellaneous databases
BioGRID-ORCSi | 201163, 88 hits in 1077 CRISPR screens |
ChiTaRSi | FLCN, human |
GeneWikii | Folliculin |
GenomeRNAii | 201163 |
Pharosi | Q8NFG4, Tbio |
PROi | PR:Q8NFG4 |
RNActi | Q8NFG4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000154803, Expressed in right hemisphere of cerebellum and 226 other tissues |
ExpressionAtlasi | Q8NFG4, baseline and differential |
Genevisiblei | Q8NFG4, HS |
Family and domain databases
Gene3Di | 1.10.10.1730, 1 hit |
InterProi | View protein in InterPro IPR037521, FLCN/SMCR8_DENN IPR044886, FLCN_DENN_C_sf IPR021713, Folliculin IPR037520, Folliculin/SMCR8_longin IPR032035, Folliculin_DENN |
PANTHERi | PTHR31441, PTHR31441, 1 hit |
Pfami | View protein in Pfam PF11704, Folliculin, 1 hit PF16692, Folliculin_C, 1 hit |
PROSITEi | View protein in PROSITE PS51834, DENN_FLCN_SMCR8, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | FLCN_HUMAN | |
Accessioni | Q8NFG4Primary (citable) accession number: Q8NFG4 Secondary accession number(s): A6NJJ8 Q96BE4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 21, 2006 |
Last sequence update: | October 1, 2002 | |
Last modified: | May 25, 2022 | |
This is version 159 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 17
Human chromosome 17: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families