Type |
Details |
Score |
HT Experiment |
|
Experiment Type: |
RNA-Seq |
Study Type: |
WT vs. Mutant |
Source: |
GEO |
|
•
•
•
•
•
|
Publication |
First Author: |
Betschinger J |
Year: |
2013 |
Journal: |
Cell |
Title: |
Exit from pluripotency is gated by intracellular redistribution of the bHLH transcription factor Tfe3. |
Volume: |
153 |
Issue: |
2 |
Pages: |
335-47 |
|
•
•
•
•
•
|
Protein Domain |
Type: |
Family |
Description: |
Birt-Hogg-Dube' syndrome, a disorder characterised by benign tumours of the hair follicle, lung cysts and renal neoplasia, is caused by germline mutations in the BHD(FLCN) gene; this encodes a tumour suppressor protein, folliculin (FLCN), of unknown function []. The folliculin- interacting protein, FNIP1, has also been identified and shown to interact with 5' AMP-activated protein kinase (AMPK), which plays a vital role in energy sensing []. Together, then, it is thought that folliculin (mutated in Birt-Hogg-Dube' syndrome) and its interaction partner, FNIP1, may be involved in energy and/or nutrient sensing via the AMPK and mTOR signalling pathways.FNIP1 has a homologue, FNIP2, which also interacts with FLCN and AMPK. C-terminally-deleted FLCN mutants, like those produced by germline mutations in BHD patients, do not bind FNIP2, suggesting that FLCN tumour-suppressor function may be facilitated by interactions with both FNIP1 and FNIP2 via its C terminus []. FNIP1 and FNIP2 are able to form homo- or heteromeric multimers, and may hence function either independently or cooperatively with FLCN [].This entry represents the FNIP family, including FNIP1 and FNIP2. |
|
•
•
•
•
•
|
Protein Domain |
Type: |
Homologous_superfamily |
Description: |
Folliculin (FLCN) is a tumor suppressor that enables nutrient-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) protein kinase via its guanosine triphosphatase (GTPase) Activating Protein (GAP) activity. It belong to the DENN module family of proteins and contains a divergent DENN module comprised of a N-terminal longin domain (also known as upstream DENN domain, u-DENN), followed by a DENN domain. It forms a complex with its partners, FNIP1 or FNIP2 (Folliculin interacting protein 1 or 2), which directly contacts the Rag GTPases RagC/D to stimulate GTP hydrolysis and thus promote the conversion to the GDP-bound state. FLCN-FNIP2 adopts an extended conformation with two pairs of heterodimerized domains. They contain longin domains that heterodimerize and contact both nucleotide binding domains of the Rag heterodimer, and C-terminal DENN domains which interact at the distal end of the structure [, , ].This is a subdomain found at the C terminus in the DENN domain of folliculin. |
|
•
•
•
•
•
|
Publication |
First Author: |
Brown PR |
Year: |
2003 |
Journal: |
Biol Reprod |
Title: |
A-kinase anchoring protein 4 binding proteins in the fibrous sheath of the sperm flagellum. |
Volume: |
68 |
Issue: |
6 |
Pages: |
2241-8 |
|
•
•
•
•
•
|
Publication |
First Author: |
Yang M |
Year: |
2016 |
Journal: |
Sci Adv |
Title: |
A C9ORF72/SMCR8-containing complex regulates ULK1 and plays a dual role in autophagy. |
Volume: |
2 |
Issue: |
9 |
Pages: |
e1601167 |
|
•
•
•
•
•
|
Publication |
First Author: |
Amick J |
Year: |
2016 |
Journal: |
Mol Biol Cell |
Title: |
C9orf72 binds SMCR8, localizes to lysosomes, and regulates mTORC1 signaling. |
Volume: |
27 |
Issue: |
20 |
Pages: |
3040-3051 |
|
•
•
•
•
•
|
Protein Domain |
Type: |
Domain |
Description: |
Folliculin (FLCN) is a tumor suppressor that enables nutrient-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) protein kinase via its guanosine triphosphatase (GTPase) Activating Protein (GAP) activity. It belong to the DENN module family of proteins and contains a divergent DENN module comprised of a N-terminal longin domain (also known as upstream DENN domain, u-DENN), followed by a DENN domain. It forms a complex with its partners, FNIP1 or FNIP2 (Folliculin interacting protein 1 or 2), which directly contacts the Rag GTPases RagC/D to stimulate GTP hydrolysis and thus promote the conversion to the GDP-bound state. FLCN-FNIP2 adopts an extended conformation with two pairs of heterodimerized domains. They contain longin domains that heterodimerize and contact both nucleotide binding domains of the Rag heterodimer, and C-terminal DENN domains which interact at the distal end of the structure [, , ].This is the DENN domain found at the C-terminal of folliculin. This domain shares structural similarity with DENN domain of DENN1B (a Rab GEF). It mediates contact with the longin domain in the heterodimers to ensure a strong intersubunit interaction [, , ]. |
|
•
•
•
•
•
|
Protein Domain |
Type: |
Domain |
Description: |
Folliculin (FLCN) is a tumor suppressor that enables nutrient-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) protein kinase via its guanosine triphosphatase (GTPase) Activating Protein (GAP) activity. It belong to the DENN module family of proteins and contains a divergent DENN module comprised of a N-terminal longin domain (also known as upstream DENN domain, u-DENN), followed by a DENN domain. It forms a complex with its partners, FNIP1 or FNIP2 (Folliculin interacting protein 1 or 2), which directly contacts the Rag GTPases RagC/D to stimulate GTP hydrolysis and thus promote the conversion to the GDP-bound state. FLCN-FNIP2 adopts an extended conformation with two pairs of heterodimerized domains. They contain longin domains that heterodimerize and contact both nucleotide binding domains of the Rag heterodimer, and C-terminal DENN domains which interact at the distal end of the structure [, , ].This is the N-terminal domain of folliculin, the longin domain [, , ]. An arginine residue located in this domain (Arg164) is catalytic residue for GAP activity [, ]. This domain can also be found in SMCR8, a component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy [, , , , , ]. |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
1165
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
1108
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
631
|
Fragment?: |
true |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
1138
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
677
|
Fragment?: |
true |
|
•
•
•
•
•
|
Publication |
First Author: |
Behrends C |
Year: |
2010 |
Journal: |
Nature |
Title: |
Network organization of the human autophagy system. |
Volume: |
466 |
Issue: |
7302 |
Pages: |
68-76 |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
579
|
Fragment?: |
false |
|
•
•
•
•
•
|
Publication |
First Author: |
Shen K |
Year: |
2019 |
Journal: |
Cell |
Title: |
Cryo-EM Structure of the Human FLCN-FNIP2-Rag-Ragulator Complex. |
Volume: |
179 |
Issue: |
6 |
Pages: |
1319-1329.e8 |
|
•
•
•
•
•
|
Publication |
First Author: |
Lawrence RE |
Year: |
2019 |
Journal: |
Science |
Title: |
Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex. |
Volume: |
366 |
Issue: |
6468 |
Pages: |
971-977 |
|
•
•
•
•
•
|
Publication |
First Author: |
Sullivan PM |
Year: |
2016 |
Journal: |
Acta Neuropathol Commun |
Title: |
The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway. |
Volume: |
4 |
Issue: |
1 |
Pages: |
51 |
|
•
•
•
•
•
|
Publication |
First Author: |
Jung J |
Year: |
2017 |
Journal: |
Elife |
Title: |
Multiplex image-based autophagy RNAi screening identifies SMCR8 as ULK1 kinase activity and gene expression regulator. |
Volume: |
6 |
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Zhang D |
Year: |
2012 |
Journal: |
Front Genet |
Title: |
Discovery of Novel DENN Proteins: Implications for the Evolution of Eukaryotic Intracellular Membrane Structures and Human Disease. |
Volume: |
3 |
|
Pages: |
283 |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
935
|
Fragment?: |
false |
|
•
•
•
•
•
|
Publication |
First Author: |
Sellier C |
Year: |
2016 |
Journal: |
EMBO J |
Title: |
Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death. |
Volume: |
35 |
Issue: |
12 |
Pages: |
1276-97 |
|
•
•
•
•
•
|
Publication |
First Author: |
Nookala RK |
Year: |
2012 |
Journal: |
Open Biol |
Title: |
Crystal structure of folliculin reveals a hidDENN function in genetically inherited renal cancer. |
Volume: |
2 |
Issue: |
8 |
Pages: |
120071 |
|
•
•
•
•
•
|
Publication |
First Author: |
Gerhard DS |
Year: |
2004 |
Journal: |
Genome Res |
Title: |
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |
Volume: |
14 |
Issue: |
10B |
Pages: |
2121-7 |
|
•
•
•
•
•
|