DEPDC5

Protein identityUniProt · HPA

UniProt accession

O75140

Gene

DEPDC5

Ensembl

ENSG00000100150

Chromosome

22

Canonical length

1603 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

OverviewNCBI Gene

This gene encodes a member of the IML1 family of proteins involved in G-protein signaling pathways. The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth by sensing the availability of nutrients. The protein encoded by this gene is a component of the GATOR1 (GAP activity toward Rags) complex which inhibits the amino acid-sensing branch of the mTORC1 pathway. Mutations in this gene are associated with autosomal dominant familial focal epilepsy with variable foci. A single nucleotide polymorphism in an intron of this gene has been associated with an increased risk of hepatocellular carcinoma in individuals with chronic hepatitis C virus infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

Canonical amino-acid sequenceUniProt

1603 residues, UniProt reviewed canonical sequence.

>O75140|DEPDC5
     1  MRTTKVYKLV IHKKGFGGSD DELVVNPKVF PHIKLGDIVE IAHPNDEYSP LLLQVKSLKE
    61  DLQKETISVD QTVTQVFRLR PYQDVYVNVV DPKDVTLDLV ELTFKDQYIG RGDMWRLKKS
   121  LVSTCAYITQ KVEFAGIRAQ AGELWVKNEK VMCGYISEDT RVVFRSTSAM VYIFIQMSCE
   181  MWDFDIYGDL YFEKAVNGFL ADLFTKWKEK NCSHEVTVVL FSRTFYDAKS VDEFPEINRA
   241  SIRQDHKGRF YEDFYKVVVQ NERREEWTSL LVTIKKLFIQ YPVLVRLEQA EGFPQGDNST
   301  SAQGNYLEAI NLSFNVFDKH YINRNFDRTG QMSVVITPGV GVFEVDRLLM ILTKQRMIDN
   361  GIGVDLVCMG EQPLHAVPLF KLHNRSAPRD SRLGDDYNIP HWINHSFYTS KSQLFCNSFT
   421  PRIKLAGKKP ASEKAKNGRD TSLGSPKESE NALPIQVDYD AYDAQVFRLP GPSRAQCLTT
   481  CRSVRERESH SRKSASSCDV SSSPSLPSRT LPTEEVRSQA SDDSSLGKSA NILMIPHPHL
   541  HQYEVSSSLG YTSTRDVLEN MMEPPQRDSS APGRFHVGSA ESMLHVRPGG YTPQRALINP
   601  FAPSRMPMKL TSNRRRWMHT FPVGPSGEAI QIHHQTRQNM AELQGSGQRD PTHSSAELLE
   661  LAYHEAAGRH SNSRQPGDGM SFLNFSGTEE LSVGLLSNSG AGMNPRTQNK DSLEDSVSTS
   721  PDPILTLSAP PVVPGFCCTV GVDWKSLTTP ACLPLTTDYF PDRQGLQNDY TEGCYDLLPE
   781  ADIDRRDEDG VQMTAQQVFE EFICQRLMQG YQIIVQPKTQ KPNPAVPPPL SSSPLYSRGL
   841  VSRNRPEEED QYWLSMGRTF HKVTLKDKMI TVTRYLPKYP YESAQIHYTY SLCPSHSDSE
   901  FVSCWVEFSH ERLEEYKWNY LDQYICSAGS EDFSLIESLK FWRTRFLLLP ACVTATKRIT
   961  EGEAHCDIYG DRPRADEDEW QLLDGFVRFV EGLNRIRRRH RSDRMMRKGT AMKGLQMTGP
  1021  ISTHSLESTA PPVGKKGTSA LSALLEMEAS QKCLGEQQAA VHGGKSSAQS AESSSVAMTP
  1081  TYMDSPRKDG AFFMEFVRSP RTASSAFYPQ VSVDQTATPM LDGTSLGICT GQSMDRGNSQ
  1141  TFGNSQNIGE QGYSSTNSSD SSSQQLVASS LTSSSTLTEI LEAMKHPSTG VQLLSEQKGL
  1201  SPYCFISAEV VHWLVNHVEG IQTQAMAIDI MQKMLEEQLI THASGEAWRT FIYGFYFYKI
  1261  VTDKEPDRVA MQQPATTWHT AGVDDFASFQ RKWFEVAFVA EELVHSEIPA FLLPWLPSRP
  1321  ASYASRHSSF SRSFGGRSQA AALLAATVPE QRTVTLDVDV NNRTDRLEWC SCYYHGNFSL
  1381  NAAFEIKLHW MAVTAAVLFE MVQGWHRKAT SCGFLLVPVL EGPFALPSYL YGDPLRAQLF
  1441  IPLNISCLLK EGSEHLFDSF EPETYWDRMH LFQEAIAHRF GFVQDKYSAS AFNFPAENKP
  1501  QYIHVTGTVF LQLPYSKRKF SGQQRRRRNS TSSTNQNMFC EERVGYNWAY NTMLTKTWRS
  1561  SATGDEKFAD RLLKDFTDFC INRDNRLVTF WTSCLEKMHA SAP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DEPDC5 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.4

Highest tissue expression

8.9 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DEPDC5.

Disease | AllUniProt

Conditions DEPDC5 is implicated in, by any mechanism.

• Epilepsy, familial focal, with variable foci 1 (FFEVF1) MIM:604364
• Developmental and epileptic encephalopathy 111 (DEE111) MIM:620504

Disease | GeneticClinVar

398 pathogenic / likely-pathogenic of 2,732 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Familial focal epilepsy with variable foci
• Epilepsy, familial focal, with variable foci 1
• Inborn genetic diseases
• Seizure
• DEPDC5-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.33

gnomAD pLI

0.12

gnomAD missense Z

2.65

DepMap mean gene effect

0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to amino acid starvation
• intracellular signal transduction
• negative regulation of TORC1 signaling
• positive regulation of autophagy

Molecular functions

• GTPase activator activity
• protein-containing complex binding
• small GTPase binding

Cellular components

• cytosol
• GATOR1 complex
• lysosomal membrane
• lysosome
• perinuclear region of cytoplasm

Protein domainsUniProt · Pfam · InterPro

• DEP domain
• Winged helix-like DNA-binding domain superfamily
• Winged helix DNA-binding domain superfamily
• Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP)
• Vacuolar membrane-associated protein Iml1
• DEPDC5, C-terminal
• Vacuolar membrane-associated protein Iml1, N-terminal domain
• IML1/DEPDC5, N-terminal double psi beta-barrel domain
• Vacuolar membrane-associated protein Iml1, N-terminal domain
• DEPDC5 protein C-terminal region
• IML1 N-terminal double psi beta barrel domain

KeywordsUniProt

• Cytoplasm
• Epilepsy
• GTPase activation
• Intellectual disability
• Lysosome
• Membrane
• Phosphoprotein
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of DEPDC5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SAMTOR
• KLHL22