6NZD

Cryo-EM Structure of the Lysosomal Folliculin Complex (FLCN-FNIP2-RagA-RagC-Ragulator)

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0001558	biological_process	regulation of cell growth
A	0001919	biological_process	regulation of receptor recycling
A	0005085	molecular_function	guanyl-nucleotide exchange factor activity
A	0005515	molecular_function	protein binding
A	0005764	cellular_component	lysosome
A	0005765	cellular_component	lysosomal membrane
A	0005768	cellular_component	endosome
A	0005886	cellular_component	plasma membrane
A	0007032	biological_process	endosome organization
A	0007040	biological_process	lysosome organization
A	0008104	biological_process	protein localization
A	0010874	biological_process	regulation of cholesterol efflux
A	0016020	cellular_component	membrane
A	0016197	biological_process	endosomal transport
A	0031669	biological_process	cellular response to nutrient levels
A	0031902	cellular_component	late endosome membrane
A	0032008	biological_process	positive regulation of TOR signaling
A	0032418	biological_process	lysosome localization
A	0035577	cellular_component	azurophil granule membrane
A	0035579	cellular_component	specific granule membrane
A	0038202	biological_process	TORC1 signaling
A	0042632	biological_process	cholesterol homeostasis
A	0043410	biological_process	positive regulation of MAPK cascade
A	0043495	molecular_function	protein-membrane adaptor activity
A	0045121	cellular_component	membrane raft
A	0051020	molecular_function	GTPase binding
A	0060090	molecular_function	molecular adaptor activity
A	0060620	biological_process	regulation of cholesterol import
A	0070062	cellular_component	extracellular exosome
A	0071230	biological_process	cellular response to amino acid stimulus
A	0071986	cellular_component	Ragulator complex
A	0072657	biological_process	protein localization to membrane
A	0101003	cellular_component	ficolin-1-rich granule membrane
A	0150032	biological_process	positive regulation of protein localization to lysosome
A	1904263	biological_process	positive regulation of TORC1 signaling
A	1990877	cellular_component	FNIP-folliculin RagC/D GAP
B	0001558	biological_process	regulation of cell growth
B	0005085	molecular_function	guanyl-nucleotide exchange factor activity
B	0005515	molecular_function	protein binding
B	0005764	cellular_component	lysosome
B	0005765	cellular_component	lysosomal membrane
B	0005768	cellular_component	endosome
B	0005770	cellular_component	late endosome
B	0005886	cellular_component	plasma membrane
B	0008104	biological_process	protein localization
B	0010008	cellular_component	endosome membrane
B	0010761	biological_process	fibroblast migration
B	0016020	cellular_component	membrane
B	0031902	cellular_component	late endosome membrane
B	0032008	biological_process	positive regulation of TOR signaling
B	0035579	cellular_component	specific granule membrane
B	0038202	biological_process	TORC1 signaling
B	0043410	biological_process	positive regulation of MAPK cascade
B	0060090	molecular_function	molecular adaptor activity
B	0070821	cellular_component	tertiary granule membrane
B	0071230	biological_process	cellular response to amino acid stimulus
B	0071986	cellular_component	Ragulator complex
B	0150116	biological_process	regulation of cell-substrate junction organization
B	1902414	biological_process	protein localization to cell junction
B	1904263	biological_process	positive regulation of TORC1 signaling
B	1990877	cellular_component	FNIP-folliculin RagC/D GAP
C	0005085	molecular_function	guanyl-nucleotide exchange factor activity
C	0005515	molecular_function	protein binding
C	0005765	cellular_component	lysosomal membrane
C	0005768	cellular_component	endosome
C	0005770	cellular_component	late endosome
C	0005886	cellular_component	plasma membrane
C	0005925	cellular_component	focal adhesion
C	0008104	biological_process	protein localization
C	0010008	cellular_component	endosome membrane
C	0016020	cellular_component	membrane
C	0019209	molecular_function	kinase activator activity
C	0031902	cellular_component	late endosome membrane
C	0032006	biological_process	regulation of TOR signaling
C	0032008	biological_process	positive regulation of TOR signaling
C	0035579	cellular_component	specific granule membrane
C	0038202	biological_process	TORC1 signaling
C	0043410	biological_process	positive regulation of MAPK cascade
C	0060090	molecular_function	molecular adaptor activity
C	0070062	cellular_component	extracellular exosome
C	0070821	cellular_component	tertiary granule membrane
C	0071230	biological_process	cellular response to amino acid stimulus
C	0071986	cellular_component	Ragulator complex
C	1902414	biological_process	protein localization to cell junction
C	1904263	biological_process	positive regulation of TORC1 signaling
C	1990877	cellular_component	FNIP-folliculin RagC/D GAP
D	0005085	molecular_function	guanyl-nucleotide exchange factor activity
D	0005515	molecular_function	protein binding
D	0005764	cellular_component	lysosome
D	0005765	cellular_component	lysosomal membrane
D	0008361	biological_process	regulation of cell size
D	0031902	cellular_component	late endosome membrane
D	0032008	biological_process	positive regulation of TOR signaling
D	0038202	biological_process	TORC1 signaling
D	0043231	cellular_component	intracellular membrane-bounded organelle
D	0060090	molecular_function	molecular adaptor activity
D	0061462	biological_process	protein localization to lysosome
D	0071230	biological_process	cellular response to amino acid stimulus
D	0071986	cellular_component	Ragulator complex
D	1904263	biological_process	positive regulation of TORC1 signaling
D	1990877	cellular_component	FNIP-folliculin RagC/D GAP
E	0005085	molecular_function	guanyl-nucleotide exchange factor activity
E	0005515	molecular_function	protein binding
E	0005737	cellular_component	cytoplasm
E	0005764	cellular_component	lysosome
E	0005765	cellular_component	lysosomal membrane
E	0005829	cellular_component	cytosol
E	0008361	biological_process	regulation of cell size
E	0009615	biological_process	response to virus
E	0010628	biological_process	positive regulation of gene expression
E	0019079	biological_process	viral genome replication
E	0031902	cellular_component	late endosome membrane
E	0032008	biological_process	positive regulation of TOR signaling
E	0032757	biological_process	positive regulation of interleukin-8 production
E	0032991	cellular_component	protein-containing complex
E	0038202	biological_process	TORC1 signaling
E	0043066	biological_process	negative regulation of apoptotic process
E	0043123	biological_process	positive regulation of canonical NF-kappaB signal transduction
E	0043154	biological_process	negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
E	0051092	biological_process	positive regulation of NF-kappaB transcription factor activity
E	0060090	molecular_function	molecular adaptor activity
E	0061462	biological_process	protein localization to lysosome
E	0071230	biological_process	cellular response to amino acid stimulus
E	0071986	cellular_component	Ragulator complex
E	1900182	biological_process	positive regulation of protein localization to nucleus
E	1904263	biological_process	positive regulation of TORC1 signaling
E	1905636	biological_process	positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding
E	1990877	cellular_component	FNIP-folliculin RagC/D GAP
F	0003924	molecular_function	GTPase activity
F	0005515	molecular_function	protein binding
F	0005525	molecular_function	GTP binding
F	0005634	cellular_component	nucleus
F	0005654	cellular_component	nucleoplasm
F	0005737	cellular_component	cytoplasm
F	0005764	cellular_component	lysosome
F	0005765	cellular_component	lysosomal membrane
F	0005829	cellular_component	cytosol
F	0006915	biological_process	apoptotic process
F	0008104	biological_process	protein localization
F	0009267	biological_process	cellular response to starvation
F	0010507	biological_process	negative regulation of autophagy
F	0016020	cellular_component	membrane
F	0016787	molecular_function	hydrolase activity
F	0031625	molecular_function	ubiquitin protein ligase binding
F	0031669	biological_process	cellular response to nutrient levels
F	0032008	biological_process	positive regulation of TOR signaling
F	0033209	biological_process	tumor necrosis factor-mediated signaling pathway
F	0034198	biological_process	cellular response to amino acid starvation
F	0035556	biological_process	intracellular signal transduction
F	0042593	biological_process	glucose homeostasis
F	0042803	molecular_function	protein homodimerization activity
F	0043495	molecular_function	protein-membrane adaptor activity
F	0046982	molecular_function	protein heterodimerization activity
F	0051219	molecular_function	phosphoprotein binding
F	0061462	biological_process	protein localization to lysosome
F	0071230	biological_process	cellular response to amino acid stimulus
F	0072657	biological_process	protein localization to membrane
F	1904263	biological_process	positive regulation of TORC1 signaling
F	1990130	cellular_component	GATOR1 complex
F	1990131	cellular_component	Gtr1-Gtr2 GTPase complex
F	1990877	cellular_component	FNIP-folliculin RagC/D GAP
G	0000287	molecular_function	magnesium ion binding
G	0003924	molecular_function	GTPase activity
G	0005515	molecular_function	protein binding
G	0005525	molecular_function	GTP binding
G	0005634	cellular_component	nucleus
G	0005654	cellular_component	nucleoplasm
G	0005737	cellular_component	cytoplasm
G	0005764	cellular_component	lysosome
G	0005765	cellular_component	lysosomal membrane
G	0005829	cellular_component	cytosol
G	0006351	biological_process	DNA-templated transcription
G	0006915	biological_process	apoptotic process
G	0007264	biological_process	small GTPase-mediated signal transduction
G	0008104	biological_process	protein localization
G	0008380	biological_process	RNA splicing
G	0009267	biological_process	cellular response to starvation
G	0010507	biological_process	negative regulation of autophagy
G	0016020	cellular_component	membrane
G	0016787	molecular_function	hydrolase activity
G	0019003	molecular_function	GDP binding
G	0031669	biological_process	cellular response to nutrient levels
G	0032006	biological_process	regulation of TOR signaling
G	0034198	biological_process	cellular response to amino acid starvation
G	0043200	biological_process	response to amino acid
G	0043231	cellular_component	intracellular membrane-bounded organelle
G	0043495	molecular_function	protein-membrane adaptor activity
G	0046982	molecular_function	protein heterodimerization activity
G	0051020	molecular_function	GTPase binding
G	0060090	molecular_function	molecular adaptor activity
G	0061462	biological_process	protein localization to lysosome
G	0071230	biological_process	cellular response to amino acid stimulus
G	0072657	biological_process	protein localization to membrane
G	0140767	molecular_function	enzyme-substrate adaptor activity
G	1903432	biological_process	regulation of TORC1 signaling
G	1904263	biological_process	positive regulation of TORC1 signaling
G	1990131	cellular_component	Gtr1-Gtr2 GTPase complex
G	1990877	cellular_component	FNIP-folliculin RagC/D GAP
H	0000122	biological_process	negative regulation of transcription by RNA polymerase II
H	0001701	biological_process	in utero embryonic development
H	0004857	molecular_function	enzyme inhibitor activity
H	0005096	molecular_function	GTPase activator activity
H	0005515	molecular_function	protein binding
H	0005634	cellular_component	nucleus
H	0005737	cellular_component	cytoplasm
H	0005764	cellular_component	lysosome
H	0005765	cellular_component	lysosomal membrane
H	0005813	cellular_component	centrosome
H	0005819	cellular_component	spindle
H	0005829	cellular_component	cytosol
H	0005856	cellular_component	cytoskeleton
H	0005886	cellular_component	plasma membrane
H	0005929	cellular_component	cilium
H	0007043	biological_process	cell-cell junction assembly
H	0007179	biological_process	transforming growth factor beta receptor signaling pathway
H	0008285	biological_process	negative regulation of cell population proliferation
H	0009267	biological_process	cellular response to starvation
H	0010508	biological_process	positive regulation of autophagy
H	0016020	cellular_component	membrane
H	0019899	molecular_function	enzyme binding
H	0030097	biological_process	hemopoiesis
H	0030496	cellular_component	midbody
H	0030511	biological_process	positive regulation of transforming growth factor beta receptor signaling pathway
H	0031929	biological_process	TOR signaling
H	0032006	biological_process	regulation of TOR signaling
H	0032007	biological_process	negative regulation of TOR signaling
H	0032008	biological_process	positive regulation of TOR signaling
H	0032418	biological_process	lysosome localization
H	0034198	biological_process	cellular response to amino acid starvation
H	0035024	biological_process	negative regulation of Rho protein signal transduction
H	0035556	biological_process	intracellular signal transduction
H	0042995	cellular_component	cell projection
H	0043065	biological_process	positive regulation of apoptotic process
H	0043491	biological_process	phosphatidylinositol 3-kinase/protein kinase B signal transduction
H	0044291	cellular_component	cell-cell contact zone
H	0044877	molecular_function	protein-containing complex binding
H	0045820	biological_process	negative regulation of glycolytic process
H	0045892	biological_process	negative regulation of DNA-templated transcription
H	0046578	biological_process	regulation of Ras protein signal transduction
H	0050673	biological_process	epithelial cell proliferation
H	0050680	biological_process	negative regulation of epithelial cell proliferation
H	0051898	biological_process	negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
H	0070371	biological_process	ERK1 and ERK2 cascade
H	0070373	biological_process	negative regulation of ERK1 and ERK2 cascade
H	0072111	biological_process	cell proliferation involved in kidney development
H	0072686	cellular_component	mitotic spindle
H	0097009	biological_process	energy homeostasis
H	0097193	biological_process	intrinsic apoptotic signaling pathway
H	0120163	biological_process	negative regulation of cold-induced thermogenesis
H	1901723	biological_process	negative regulation of cell proliferation involved in kidney development
H	1901874	biological_process	negative regulation of post-translational protein modification
H	1903444	biological_process	negative regulation of brown fat cell differentiation
H	1904263	biological_process	positive regulation of TORC1 signaling
H	1905672	biological_process	negative regulation of lysosome organization
H	1990877	cellular_component	FNIP-folliculin RagC/D GAP
H	2000973	biological_process	regulation of pro-B cell differentiation
H	2001244	biological_process	positive regulation of intrinsic apoptotic signaling pathway
I	0000122	biological_process	negative regulation of transcription by RNA polymerase II
I	0001932	biological_process	regulation of protein phosphorylation
I	0005515	molecular_function	protein binding
I	0005737	cellular_component	cytoplasm
I	0005764	cellular_component	lysosome
I	0005765	cellular_component	lysosomal membrane
I	0005829	cellular_component	cytosol
I	0006468	biological_process	protein phosphorylation
I	0006974	biological_process	DNA damage response
I	0008630	biological_process	intrinsic apoptotic signaling pathway in response to DNA damage
I	0016020	cellular_component	membrane
I	0031334	biological_process	positive regulation of protein-containing complex assembly
I	0033138	biological_process	positive regulation of peptidyl-serine phosphorylation
I	0034451	cellular_component	centriolar satellite
I	0042030	molecular_function	ATPase inhibitor activity
I	0051087	molecular_function	protein-folding chaperone binding
I	1904263	biological_process	positive regulation of TORC1 signaling
I	1990877	cellular_component	FNIP-folliculin RagC/D GAP

Functional Information from PDB Data

site_id	AC1
Number of Residues	16
Details	binding site for residue GDP F 500

Chain	Residue
F	LYS15
F	ASP130
F	SER163
F	ILE164
F	TRP165
H	ARG122
H	VAL126
I	ALA147
F	SER16
F	GLY17
F	SER18
F	GLY19
F	LYS20
F	THR21
F	HIS127
F	LYS128

---

site_id	AC2
Number of Residues	16
Details	binding site for residue L8S G 500

Chain	Residue
G	ARG70
G	ARG71
G	SER72
G	GLY73
G	LYS74
G	SER75
G	SER76
G	THR90
G	LEU91
G	THR96
G	PRO118
G	GLY119
G	HIS178
G	LYS179
G	ASN181
G	ILE220

---

Functional Information from PROSITE/UniProt

site_id	PS00214
Number of Residues	18
Details	FABP Cytosolic fatty-acid binding proteins signature. KAYkVnpDmNFEvFIHKV

Chain	Residue	Details
G	LYS163-VAL180

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	2
Details	MOD_RES: Phosphoserine => ECO:0007744|PubMed:23186163

Chain	Residue	Details
I	SER216
I	SER221
F	HIS127

---

site_id	SWS_FT_FI2
Number of Residues	2
Details	MOD_RES: Phosphoserine => ECO:0007744|PubMed:19690332

Chain	Residue	Details
I	SER723
I	SER726
A	SER98
A	SER141

---

site_id	SWS_FT_FI3
Number of Residues	3
Details	MOD_RES: Phosphoserine => ECO:0007744|PubMed:23186163

Chain	Residue	Details
H	SER73
H	SER302
H	SER571
F	ILE164

---

site_id	SWS_FT_FI4
Number of Residues	3
Details	MOD_RES: Phosphoserine; by ULK1 => ECO:0000269|PubMed:25126726

Chain	Residue	Details
H	SER406
H	SER537
H	SER542

---

site_id	SWS_FT_FI5
Number of Residues	1
Details	BINDING: BINDING => ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:31601764, ECO:0000269|PubMed:32868926, ECO:0000269|PubMed:35338845, ECO:0000269|PubMed:36697823, ECO:0007744|PDB:6SB0, ECO:0007744|PDB:6SB2, ECO:0007744|PDB:6U62, ECO:0007744|PDB:6WJ2, ECO:0007744|PDB:6WJ3, ECO:0007744|PDB:7T3B, ECO:0007744|PDB:7UX2, ECO:0007744|PDB:7UXC, ECO:0007744|PDB:7UXH

Chain	Residue	Details
G	SER75
F	GLY65

---

site_id	SWS_FT_FI6
Number of Residues	1
Details	BINDING: BINDING => ECO:0000269|PubMed:31601764, ECO:0000269|PubMed:35338845, ECO:0000269|PubMed:36697823, ECO:0007744|PDB:6SB0, ECO:0007744|PDB:6SB2, ECO:0007744|PDB:7T3C, ECO:0007744|PDB:7UX2, ECO:0007744|PDB:7UXC, ECO:0007744|PDB:7UXH

Chain	Residue	Details
G	SER76

---

site_id	SWS_FT_FI7
Number of Residues	3
Details	BINDING: BINDING => ECO:0000269|PubMed:32868926, ECO:0007744|PDB:6WJ2, ECO:0007744|PDB:6WJ3

Chain	Residue	Details
G	THR90
G	THR96
G	ASN181

---

site_id	SWS_FT_FI8
Number of Residues	1
Details	BINDING: BINDING => ECO:0000269|PubMed:35338845, ECO:0007744|PDB:7T3B, ECO:0007744|PDB:7T3C

Chain	Residue	Details
G	GLU94

---

site_id	SWS_FT_FI9
Number of Residues	1
Details	BINDING: BINDING => ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:32868926, ECO:0000269|PubMed:36697823, ECO:0007744|PDB:6U62, ECO:0007744|PDB:6WJ2, ECO:0007744|PDB:6WJ3, ECO:0007744|PDB:7UX2, ECO:0007744|PDB:7UXC, ECO:0007744|PDB:7UXH

Chain	Residue	Details
G	HIS178
F	LYS220
F	LYS230
F	LYS244

---

site_id	SWS_FT_FI10
Number of Residues	2
Details	BINDING: BINDING => ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:35338845, ECO:0000269|PubMed:36697823, ECO:0007744|PDB:6U62, ECO:0007744|PDB:7T3B, ECO:0007744|PDB:7UX2, ECO:0007744|PDB:7UXC, ECO:0007744|PDB:7UXH

Chain	Residue	Details
G	LYS179
G	ILE220

---

site_id	SWS_FT_FI11
Number of Residues	1
Details	BINDING: BINDING => ECO:0000269|PubMed:35338845, ECO:0000269|PubMed:36697823, ECO:0007744|PDB:7T3B, ECO:0007744|PDB:7UX2, ECO:0007744|PDB:7UXC, ECO:0007744|PDB:7UXH

Chain	Residue	Details
G	SER219

---

site_id	SWS_FT_FI12
Number of Residues	1
Details	MOD_RES: Phosphoserine => ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163

Chain	Residue	Details
G	SER2

---

site_id	SWS_FT_FI13
Number of Residues	1
Details	MOD_RES: Phosphoserine => ECO:0007744|PubMed:23186163

Chain	Residue	Details
G	SER15

---

site_id	SWS_FT_FI14
Number of Residues	1
Details	MOD_RES: Phosphothreonine => ECO:0000250|UniProtKB:Q99K70

Chain	Residue	Details
G	THR96

---