DEPDC5
entrez
9681
canonical
uniprot
O75140
canonical
ensembl
ENSG00000100150
resolver
ensp
ENSP00000371546
resolver
ensp
ENSP00000383101
resolver
ensp
ENSP00000383107
resolver
ensp
ENSP00000383108
resolver
ensp
ENSP00000410544
resolver
ensp
ENSP00000440210
resolver
ensp
ENSP00000493489
resolver
ensp
ENSP00000494406
resolver
ensp
ENSP00000494484
resolver
ensp
ENSP00000494700
resolver
ensp
ENSP00000494879
resolver
ensp
ENSP00000495496
resolver
ensp
ENSP00000495544
resolver
ensp
ENSP00000495917
resolver
ensp
ENSP00000496281
resolver
ensp
ENSP00000496724
resolver
ensp
ENSP00000498382
resolver
ensp
ENSP00000573786
resolver
ensp
ENSP00000573788
resolver
ensp
ENSP00000585064
resolver
ensp
ENSP00000585067
resolver
ensp
ENSP00000585069
resolver
ensp
ENSP00000740690
resolver
enst
ENST00000433147
resolver
enst
ENST00000643751
resolver
enst
ENST00000645560
resolver
enst
ENST00000646515
resolver
enst
ENST00000646969
resolver
genesymbol
DEPDC5
resolver
genesymbol_syn
KIAA0645
resolver
hgnc
HGNC:18423
resolver
uniprot
A0A2R8Y5T1
resolver
uniprot
A0A2R8Y6H3
resolver
uniprot
A0A2R8Y6V4
resolver
uniprot
A6H8V6
resolver
uniprot
A8MPX9
resolver
uniprot
B4DH93
resolver
uniprot
B9EGN9
resolver
uniprot
H0Y770
resolver
uniprot
Q5K3V5
resolver
uniprot
Q5THY9
resolver
uniprot
Q5THZ0
resolver
uniprot
Q5THZ1
resolver
uniprot
Q5THZ3
resolver
uniprot
Q68DR1
resolver
uniprot
Q6MZX3
resolver
uniprot
Q6PEZ1
resolver
uniprot
Q9UGV8
resolver
uniprot
Q9UH13
resolver
uniprot_entry
A0A2R8Y5T1_HUMAN
resolver
uniprot_entry
A0A2R8Y6H3_HUMAN
resolver
uniprot_entry
A0A2R8Y6V4_HUMAN
resolver
uniprot_entry
DEPD5_HUMAN
resolver
uniprot_entry
H0Y770_HUMAN
resolver
uniprot_sec
A6H8V6
resolver
uniprot_sec
A8MPX9
resolver
uniprot_sec
B4DH93
resolver
uniprot_sec
B9EGN9
resolver
uniprot_sec
Q5K3V5
resolver
uniprot_sec
Q5THY9
resolver
uniprot_sec
Q5THZ0
resolver
uniprot_sec
Q5THZ1
resolver
uniprot_sec
Q5THZ3
resolver
uniprot_sec
Q68DR1
resolver
uniprot_sec
Q6MZX3
resolver
uniprot_sec
Q6PEZ1
resolver
uniprot_sec
Q9UGV8
resolver
uniprot_sec
Q9UH13
resolver
amino_acid_sequence
MRTTKVYKLVIHKKGFGGSDDELVVNPKVFPHIKLGDIVEIAHPNDEYSPLLLQVKSLKEDLQKETISVDQTVTQVFRLRPYQDVYVNVVDPKDVTLDLVELTFKDQYIGRGDMWRLKKSLVSTCAYITQKVEFAGIRAQAGELWVKNEKVMCGYISEDTRVVFRSTSAMVYIFIQMSCEMWDFDIYGDLYFEKAVNGFLADLFTKWKEKNCSHEVTVVLFSRTFYDAKSVDEFPEINRASIRQDHKGRFYEDFYKVVVQNERREEWTSLLVTIKKLFIQYPVLVRLEQAEGFPQGDNSTSAQGNYLEAINLSFNVFDKHYINRNFDRTGQMSVVITPGVGVFEVDRLLMILTKQRMIDNGIGVDLVCMGEQPLHAVPLFKLHNRSAPRDSRLGDDYNIPHWINHSFYTSKSQLFCNSFTPRIKLAGKKPASEKAKNGRDTSLGSPKESENALPIQVDYDAYDAQVFRLPGPSRAQCLTTCRSVRERESHSRKSASSCDVSSSPSLPSRTLPTEEVRSQASDDSSLGKSANILMIPHPHLHQYEVSSSLGYTSTRDVLENMMEPPQRDSSAPGRFHVGSAESMLHVRPGGYTPQRALINPFAPSRMPMKLTSNRRRWMHTFPVGPSGEAIQIHHQTRQNMAELQGSGQRDPTHSSAELLELAYHEAAGRHSNSRQPGDGMSFLNFSGTEELSVGLLSNSGAGMNPRTQNKDSLEDSVSTSPDPILTLSAPPVVPGFCCTVGVDWKSLTTPACLPLTTDYFPDRQGLQNDYTEGCYDLLPEADIDRRDEDGVQMTAQQVFEEFICQRLMQGYQIIVQPKTQKPNPAVPPPLSSSPLYSRGLVSRNRPEEEDQYWLSMGRTFHKVTLKDKMITVTRYLPKYPYESAQIHYTYSLCPSHSDSEFVSCWVEFSHERLEEYKWNYLDQYICSAGSEDFSLIESLKFWRTRFLLLPACVTATKRITEGEAHCDIYGDRPRADEDEWQLLDGFVRFVEGLNRIRRRHRSDRMMRKGTAMKGLQMTGPISTHSLESTAPPVGKKGTSALSALLEMEASQKCLGEQQAAVHGGKSSAQSAESSSVAMTPTYMDSPRKDGAFFMEFVRSPRTASSAFYPQVSVDQTATPMLDGTSLGICTGQSMDRGNSQTFGNSQNIGEQGYSSTNSSDSSSQQLVASSLTSSSTLTEILEAMKHPSTGVQLLSEQKGLSPYCFISAEVVHWLVNHVEGIQTQAMAIDIMQKMLEEQLITHASGEAWRTFIYGFYFYKIVTDKEPDRVAMQQPATTWHTAGVDDFASFQRKWFEVAFVAEELVHSEIPAFLLPWLPSRPASYASRHSSFSRSFGGRSQAAALLAATVPEQRTVTLDVDVNNRTDRLEWCSCYYHGNFSLNAAFEIKLHWMAVTAAVLFEMVQGWHRKATSCGFLLVPVLEGPFALPSYLYGDPLRAQLFIPLNISCLLKEGSEHLFDSFEPETYWDRMHLFQEAIAHRFGFVQDKYSASAFNFPAENKPQYIHVTGTVFLQLPYSKRKFSGQQRRRRNSTSSTNQNMFCEERVGYNWAYNTMLTKTWRSSATGDEKFADRLLKDFTDFCINRDNRLVTFWTSCLEKMHASAP
uniprot
proteins
disease_involvement
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.; DISEASE: Developmental and epileptic encephalopathy 111 (DEE111) [MIM:620504]: A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE111 is an autosomal recessive form characterized by the onset of seizures in the first days, months, or years of life. Brain imaging shows frontal, parietal, and perisylvian polymicrogyria, dysmorphic basal ganglia and corpus callosum, and hypoplastic pons. Death in early childhood may occur. {ECO:0000269|PubMed:36067010}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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}.
uniprot
proteins
function
FUNCTION: As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway (PubMed:23723238, PubMed:25457612, PubMed:29590090, PubMed:29769719, PubMed:31548394, PubMed:35338845). In response to amino acid depletion, the GATOR1 complex has GTPase activating protein (GAP) activity and strongly increases GTP hydrolysis by RagA/RRAGA (or RagB/RRAGB) within heterodimeric Rag complexes, thereby turning them into their inactive GDP-bound form, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling (PubMed:23723238, PubMed:25457612, PubMed:29590090, PubMed:29769719, PubMed:35338845). In the presence of abundant amino acids, the GATOR1 complex is negatively regulated by GATOR2, the other GATOR subcomplex, in this amino acid-sensing branch of the TORC1 pathway (PubMed:23723238, PubMed:25457612, PubMed:29769719). Within the GATOR1 complex, DEPDC5 mediates direct interaction with the nucleotide-binding pocket of small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD) and coordinates their nucleotide loading states by promoting RagA/RRAGA or RagB/RRAGB into their GDP-binding state and RagC/RRAGC or RagD/RRAGD into their GTP-binding state (PubMed:29590090, PubMed:35338845). However, it does not execute the GAP activity, which is mediated by NPRL2 (PubMed:29590090). {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:29590090, ECO:0000269|PubMed:29769719, ECO:0000269|PubMed:31548394, ECO:0000269|PubMed:35338845}.
uniprot
proteins
mass_dalton
181264
uniprot
proteins
mutagenesis
MUTAGEN 185..189; /note="DIYGD->GSGSG: In mutant AB; abolished interaction with NPRL2 and NPRL3; when associated with 371-G--G-375."; /evidence="ECO:0000269|PubMed:29590090"; MUTAGEN 371..375; /note="EQPLH->GSGSG: In mutant AB; abolished interaction with NPRL2 and NPRL3; when associated with 185-G--G-189."; /evidence="ECO:0000269|PubMed:29590090"; MUTAGEN 447; /note="K->R: No effect on ubiquitination. Loss of interaction with KLHL22 and ubiquitination; when associated with R-710, R-1065, R-1088 and R-1574."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 710; /note="K->R: No effect on ubiquitination. Loss of interaction with KLHL22 and ubiquitination; when associated with R-447, R-1065, R-1088 and R-1574."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 775..779; /note="YDLLP->GSGSG: In mutant P; strongly decreased interaction with RagA/RRAGA."; /evidence="ECO:0000269|PubMed:29590090"; MUTAGEN 775; /note="Y->A: Strongly decreased interaction with RagA/RRAGA."; /evidence="ECO:0000269|PubMed:29590090, ECO:0000269|PubMed:35338845"; MUTAGEN 1002; /note="S->A: Abolished phosphorylation by PIM1; when associated with A-1530."; /evidence="ECO:0000269|PubMed:31548394"; MUTAGEN 1065; /note="K->R: No effect on ubiquitination. Loss of interaction with KLHL22 and ubiquitination; when associated with R-447, R-710, R-1088 and R-1574."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 1088; /note="K->R: No effect on ubiquitination. Loss of interaction with KLHL22 and ubiquitination; when associated with R-447, R-710, R-1065 and R-1574."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 1188; /note="S->A: No effect on interaction with KLHL22."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 1189; /note="T->A: No effect on interaction with KLHL22."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 1195; /note="S->A: No effect on interaction with KLHL22."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 1201; /note="S->A: No effect on interaction with KLHL22."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 1203; /note="Y->A: No effect on interaction with KLHL22."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 1207; /note="S->A: No effect on interaction with KLHL22."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 1223; /note="T->A: No effect on interaction with KLHL22."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 1241; /note="T->A: No effect on interaction with KLHL22."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 1244; /note="S->A: No effect on interaction with KLHL22."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 1250; /note="T->A: No effect on interaction with KLHL22."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 1253; /note="Y->A: No effect on interaction with KLHL22."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 1256; /note="Y->A: No effect on interaction with KLHL22."; /evidence="ECO:0000269|PubMed:29769719"; MUTAGEN 1530; /note="S->A: Abolished phosphorylation by PIM1; when associated with A-1002."; /evidence="ECO:0000269|PubMed:31548394"; MUTAGEN 1574; /note="K->R: No effect on ubiquitination. Loss of ubiquitination; when associated with R-447, R-710, R-1065 and R-1088."; /evidence="ECO:0000269|PubMed:29769719
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-1002 and Ser-1530 by AKT1 and PIM1 inhibit the activity of DEPDC5, releasing inhibition of the mTORC1 pathway. {ECO:0000269|PubMed:31548394}.; PTM: Ubiquitinated (PubMed:29769719). Amino acid-induced 'Lys-48'-linked polyubiquitination of DEPDC5 by the BCR(KLHL22) ubiquitin ligase complex leads to DEPDC5 proteasomal degradation and inhibition of the GATOR1 complex (PubMed:29769719). Ubiquitination may occur at multiple lysines (PubMed:29769719). {ECO:0000269|PubMed:29769719}.
uniprot
proteins
protein_family
IML1 family
uniprot
proteins
pubmed
10591208
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15770670
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
23542697
uniprot
proteins
pubmed
23542701
uniprot
proteins
pubmed
23723238
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24283814
uniprot
proteins
pubmed
24591017
uniprot
proteins
pubmed
25366275
uniprot
proteins
pubmed
25457612
uniprot
proteins
pubmed
26505888
uniprot
proteins
pubmed
27173016
uniprot
proteins
pubmed
28199306
uniprot
proteins
pubmed
29590090
uniprot
proteins
pubmed
29769719
uniprot
proteins
pubmed
31548394
uniprot
proteins
pubmed
35338845
uniprot
proteins
pubmed
36067010
uniprot
proteins
pubmed
9734811
uniprot
proteins
sequence_length
1603
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:28199306}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:P61460}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:P61460}. Note=Localization to lysosomes is mediated by the KICSTOR complex and is amino acid-independent. {ECO:0000269|PubMed:28199306}.
uniprot
proteins