ID  O75140;
PN  GATOR complex protein DEPDC5;
GN  DEPDC5;
OS  9606;
SL  Nucleus Position: SL-0198;
SL  Comments: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P61460}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:P61460}. Lysosome membrane {ECO:0000269|PubMed:28199306}. Note=Localization to lysosomes is amino acid-independent. {ECO:0000269|PubMed:28199306}.
DR  UNIPROT: O75140;
DR  UNIPROT: A6H8V6;
DR  UNIPROT: A8MPX9;
DR  UNIPROT: B4DH93;
DR  UNIPROT: B9EGN9;
DR  UNIPROT: Q5K3V5;
DR  UNIPROT: Q5THY9;
DR  UNIPROT: Q5THZ0;
DR  UNIPROT: Q5THZ1;
DR  UNIPROT: Q5THZ3;
DR  UNIPROT: Q68DR1;
DR  UNIPROT: Q6MZX3;
DR  UNIPROT: Q6PEZ1;
DR  UNIPROT: Q9UGV8;
DR  UNIPROT: Q9UH13;
DR  PDB: 6CES;
DR  PDB: 6CET;
DR  PDB: 7T3A;
DR  PDB: 7T3B;
DR  PDB: 7T3C;
DR  Pfam: PF00610;
DR  Pfam: PF19418;
DR  Pfam: PF12257;
DR  PROSITE: PS50186;
DR  OMIM: 604364;
DR  OMIM: 614191;
DR  DisGeNET: 9681;
DE  Function: As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway. The GATOR1 complex strongly increases GTP hydrolysis by RRAGA and RRAGB within RRAGC-containing heterodimers, thereby deactivating RRAGs, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling. The GATOR1 complex is negatively regulated by GATOR2 the other GATOR subcomplex in this amino acid-sensing branch of the TORC1 pathway. {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:29769719}.
DE  Disease: Epilepsy, familial focal, with variable foci 1 (FFEVF1) [MIM:604364]: An autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions in different family members. Many patients have an aura and show automatisms during the seizures, whereas others may have nocturnal seizures. There is often secondary generalization. Some patients show abnormal interictal EEG, and some patients may have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. Penetrance of the disorder is incomplete. {ECO:0000269|PubMed:23542697, ECO:0000269|PubMed:23542701, ECO:0000269|PubMed:24283814, ECO:0000269|PubMed:24591017, ECO:0000269|PubMed:25366275, ECO:0000269|PubMed:26505888, ECO:0000269|PubMed:27173016}. Note=The disease is caused by variants affecting the gene represented in this entry. Note=Inactivating mutations and truncating deletions in the genes encoding GATOR1 proteins, including DEPDC5, are detected in glioblastoma and ovarian tumors and are associated with loss of heterozygosity events. Inactivation of GATOR1 proteins promotes constitutive localization of mTORC1 to the lysosomal membrane and blocks mTORC1 inactivation following amino acid withdrawal (PubMed:23723238). {ECO:0000269|PubMed:23723238}.
DE  Reference Proteome: Yes;
DE  Interaction: P05412; IntAct: EBI-11323169; Score: 0.35
DE  Interaction: P58043; IntAct: EBI-11102804; Score: 0.35
DE  Interaction: Q6W0C5; IntAct: EBI-24665620; Score: 0.56
DE  Interaction: O75604; IntAct: EBI-24681385; Score: 0.56
DE  Interaction: Q13257; IntAct: EBI-24703582; Score: 0.56
DE  Interaction: P49368; IntAct: EBI-24741275; Score: 0.56
DE  Interaction: Q6FHY5; IntAct: EBI-24434236; Score: 0.56
DE  Interaction: Q9BSW7; IntAct: EBI-24642109; Score: 0.56
DE  Interaction: Q96QG7; IntAct: EBI-24656502; Score: 0.56
DE  Interaction: Q9UI95; IntAct: EBI-24775208; Score: 0.56
DE  Interaction: Q1RMZ1; IntAct: EBI-21587773; Score: 0.35
DE  Interaction: Q8WTW4; IntAct: EBI-21720164; Score: 0.53
DE  Interaction: Q9Y664; IntAct: EBI-21890520; Score: 0.35
DE  Interaction: Q96MD2; IntAct: EBI-21890520; Score: 0.35
DE  Interaction: Q969R8; IntAct: EBI-21890520; Score: 0.35
DE  Interaction: Q5T011; IntAct: EBI-21890520; Score: 0.35
DE  Interaction: Q12980; IntAct: EBI-16126226; Score: 0.35
DE  Interaction: Q9HB90; IntAct: EBI-16126252; Score: 0.35
DE  Interaction: Q7L523; IntAct: EBI-16126252; Score: 0.35
DE  Interaction: Q5VZM2; IntAct: EBI-16752640; Score: 0.35
DE  Interaction: Q96S15; IntAct: EBI-16752640; Score: 0.35
DE  Interaction: Q9NXC5; IntAct: EBI-16752640; Score: 0.35
DE  Interaction: Q93079; IntAct: EBI-20935716; Score: 0.40
DE  Interaction: Q99459; IntAct: EBI-21392827; Score: 0.00
DE  Interaction: P63010; IntAct: EBI-30815544; Score: 0.44
GO  GO:0005829;
GO  GO:1990130;
GO  GO:0005765;
GO  GO:0005764;
GO  GO:0048471;
GO  GO:0005096;
GO  GO:0044877;
GO  GO:0034198;
GO  GO:0035556;
GO  GO:0032007;
GO  GO:1904262;
GO  GO:0010508;
TP  Membrane Topology: Unknown; Source: UniProt - Sequence Analysis;
SQ  MRTTKVYKLVIHKKGFGGSDDELVVNPKVFPHIKLGDIVEIAHPNDEYSPLLLQVKSLKEDLQKETISVDQTVTQVFRLR
SQ  PYQDVYVNVVDPKDVTLDLVELTFKDQYIGRGDMWRLKKSLVSTCAYITQKVEFAGIRAQAGELWVKNEKVMCGYISEDT
SQ  RVVFRSTSAMVYIFIQMSCEMWDFDIYGDLYFEKAVNGFLADLFTKWKEKNCSHEVTVVLFSRTFYDAKSVDEFPEINRA
SQ  SIRQDHKGRFYEDFYKVVVQNERREEWTSLLVTIKKLFIQYPVLVRLEQAEGFPQGDNSTSAQGNYLEAINLSFNVFDKH
SQ  YINRNFDRTGQMSVVITPGVGVFEVDRLLMILTKQRMIDNGIGVDLVCMGEQPLHAVPLFKLHNRSAPRDSRLGDDYNIP
SQ  HWINHSFYTSKSQLFCNSFTPRIKLAGKKPASEKAKNGRDTSLGSPKESENALPIQVDYDAYDAQVFRLPGPSRAQCLTT
SQ  CRSVRERESHSRKSASSCDVSSSPSLPSRTLPTEEVRSQASDDSSLGKSANILMIPHPHLHQYEVSSSLGYTSTRDVLEN
SQ  MMEPPQRDSSAPGRFHVGSAESMLHVRPGGYTPQRALINPFAPSRMPMKLTSNRRRWMHTFPVGPSGEAIQIHHQTRQNM
SQ  AELQGSGQRDPTHSSAELLELAYHEAAGRHSNSRQPGDGMSFLNFSGTEELSVGLLSNSGAGMNPRTQNKDSLEDSVSTS
SQ  PDPILTLSAPPVVPGFCCTVGVDWKSLTTPACLPLTTDYFPDRQGLQNDYTEGCYDLLPEADIDRRDEDGVQMTAQQVFE
SQ  EFICQRLMQGYQIIVQPKTQKPNPAVPPPLSSSPLYSRGLVSRNRPEEEDQYWLSMGRTFHKVTLKDKMITVTRYLPKYP
SQ  YESAQIHYTYSLCPSHSDSEFVSCWVEFSHERLEEYKWNYLDQYICSAGSEDFSLIESLKFWRTRFLLLPACVTATKRIT
SQ  EGEAHCDIYGDRPRADEDEWQLLDGFVRFVEGLNRIRRRHRSDRMMRKGTAMKGLQMTGPISTHSLESTAPPVGKKGTSA
SQ  LSALLEMEASQKCLGEQQAAVHGGKSSAQSAESSSVAMTPTYMDSPRKDGAFFMEFVRSPRTASSAFYPQVSVDQTATPM
SQ  LDGTSLGICTGQSMDRGNSQTFGNSQNIGEQGYSSTNSSDSSSQQLVASSLTSSSTLTEILEAMKHPSTGVQLLSEQKGL
SQ  SPYCFISAEVVHWLVNHVEGIQTQAMAIDIMQKMLEEQLITHASGEAWRTFIYGFYFYKIVTDKEPDRVAMQQPATTWHT
SQ  AGVDDFASFQRKWFEVAFVAEELVHSEIPAFLLPWLPSRPASYASRHSSFSRSFGGRSQAAALLAATVPEQRTVTLDVDV
SQ  NNRTDRLEWCSCYYHGNFSLNAAFEIKLHWMAVTAAVLFEMVQGWHRKATSCGFLLVPVLEGPFALPSYLYGDPLRAQLF
SQ  IPLNISCLLKEGSEHLFDSFEPETYWDRMHLFQEAIAHRFGFVQDKYSASAFNFPAENKPQYIHVTGTVFLQLPYSKRKF
SQ  SGQQRRRRNSTSSTNQNMFCEERVGYNWAYNTMLTKTWRSSATGDEKFADRLLKDFTDFCINRDNRLVTFWTSCLEKMHA
SQ  SAP
//