DEPD5_MOUSE
ID DEPD5_MOUSE Reviewed; 1591 AA.
AC P61460; E9Q5J2; E9Q5Y0;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2013, sequence version 2.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=GATOR complex protein DEPDC5 {ECO:0000305};
DE AltName: Full=DEP domain-containing protein 5 {ECO:0000312|MGI:MGI:2141101};
GN Name=Depdc5 {ECO:0000312|MGI:MGI:2141101};
GN Synonyms=Kiaa0645 {ECO:0000312|EMBL:BAC97990.1};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23542697; DOI=10.1038/ng.2599;
RA Dibbens L.M., de Vries B., Donatello S., Heron S.E., Hodgson B.L.,
RA Chintawar S., Crompton D.E., Hughes J.N., Bellows S.T., Klein K.M.,
RA Callenbach P.M., Corbett M.A., Gardner A.E., Kivity S., Iona X.,
RA Regan B.M., Weller C.M., Crimmins D., O'Brien T.J., Guerrero-Lopez R.,
RA Mulley J.C., Dubeau F., Licchetta L., Bisulli F., Cossette P., Thomas P.Q.,
RA Gecz J., Serratosa J., Brouwer O.F., Andermann F., Andermann E.,
RA van den Maagdenberg A.M., Pandolfo M., Berkovic S.F., Scheffer I.E.;
RT "Mutations in DEPDC5 cause familial focal epilepsy with variable foci.";
RL Nat. Genet. 45:546-551(2013).
CC -!- FUNCTION: As a component of the GATOR1 complex functions as an
CC inhibitor of the amino acid-sensing branch of the TORC1 pathway. The
CC GATOR1 complex strongly increases GTP hydrolysis by RRAGA and RRAGB
CC within RRAGC-containing heterodimers, thereby deactivating RRAGs,
CC releasing mTORC1 from lysosomal surface and inhibiting mTORC1
CC signaling. The GATOR1 complex is negatively regulated by GATOR2 the
CC other GATOR subcomplex in this amino acid-sensing branch of the TORC1
CC pathway. {ECO:0000250|UniProtKB:O75140}.
CC -!- SUBUNIT: Within the GATOR complex, component of the GATOR1 subcomplex,
CC made of DEPDC5, NPRL2 and NPRL3. GATOR1 mediates the strong interaction
CC of the GATOR complex with RRAGA/RRAGC and RRAGB/RRAGC heterodimers.
CC Interacts (via DEP domain) with KLHL22; the interaction depends on
CC amino acid availability. {ECO:0000250|UniProtKB:O75140}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:23542697}.
CC Cytoplasm, perinuclear region {ECO:0000269|PubMed:23542697}. Lysosome
CC membrane {ECO:0000250|UniProtKB:O75140}. Note=Localization to lysosomes
CC is amino acid-independent. {ECO:0000250|UniProtKB:O75140}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P61460-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P61460-2; Sequence=VSP_046542;
CC -!- TISSUE SPECIFICITY: Expressed at low levels in all brain regions.
CC Expressed throughout brain development, including in midgestation
CC embryonic head (11.5 dpc), neonatal brain and whole adult brain.
CC Present in neurons and absent in non-neuronal cells, including
CC astrocytes (at protein level). {ECO:0000269|PubMed:23542697}.
CC -!- DOMAIN: The DEP domain mediates the interaction with KLHL22.
CC {ECO:0000250|UniProtKB:O75140}.
CC -!- PTM: Ubiquitinated. Amino acid-induced 'Lys-48'-linked
CC polyubiquitination of DEPDC5 by the BCR(KLHL22) ubiquitin ligase
CC complex leads to DEPDC5 proteasomal degradation and inhibition of the
CC GATOR1 complex. Ubiquitination may occur at multiple lysines.
CC {ECO:0000250|UniProtKB:O75140}.
CC -!- SIMILARITY: Belongs to the IML1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC97990.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK129180; BAC97990.1; ALT_INIT; Transcribed_RNA.
DR EMBL; AC108773; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC122203; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS51463.1; -. [P61460-1]
DR RefSeq; NP_001164038.1; NM_001170567.1. [P61460-1]
DR RefSeq; XP_006504047.1; XM_006503984.3. [P61460-1]
DR RefSeq; XP_006504050.1; XM_006503987.3. [P61460-2]
DR AlphaFoldDB; P61460; -.
DR SMR; P61460; -.
DR BioGRID; 234959; 4.
DR IntAct; P61460; 1.
DR STRING; 10090.ENSMUSP00000113862; -.
DR iPTMnet; P61460; -.
DR PhosphoSitePlus; P61460; -.
DR EPD; P61460; -.
DR MaxQB; P61460; -.
DR PaxDb; P61460; -.
DR PRIDE; P61460; -.
DR ProteomicsDB; 279513; -. [P61460-1]
DR ProteomicsDB; 279514; -. [P61460-2]
DR ABCD; P61460; 1 sequenced antibody.
DR DNASU; 277854; -.
DR Ensembl; ENSMUST00000119705; ENSMUSP00000113862; ENSMUSG00000037426. [P61460-1]
DR Ensembl; ENSMUST00000120902; ENSMUSP00000113980; ENSMUSG00000037426. [P61460-2]
DR GeneID; 277854; -.
DR KEGG; mmu:277854; -.
DR UCSC; uc008xae.2; mouse. [P61460-1]
DR UCSC; uc008xaf.2; mouse. [P61460-2]
DR CTD; 9681; -.
DR MGI; MGI:2141101; Depdc5.
DR VEuPathDB; HostDB:ENSMUSG00000037426; -.
DR eggNOG; KOG3572; Eukaryota.
DR GeneTree; ENSGT00390000016559; -.
DR InParanoid; P61460; -.
DR OMA; RMYDLQM; -.
DR OrthoDB; 45642at2759; -.
DR PhylomeDB; P61460; -.
DR Reactome; R-MMU-9639288; Amino acids regulate mTORC1.
DR BioGRID-ORCS; 277854; 8 hits in 73 CRISPR screens.
DR ChiTaRS; Depdc5; mouse.
DR PRO; PR:P61460; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P61460; protein.
DR Bgee; ENSMUSG00000037426; Expressed in spermatocyte and 209 other tissues.
DR ExpressionAtlas; P61460; baseline and differential.
DR Genevisible; P61460; MM.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:1990130; C:GATOR1 complex; ISO:MGI.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0034198; P:cellular response to amino acid starvation; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0032007; P:negative regulation of TOR signaling; ISO:MGI.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; ISS:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IBA:GO_Central.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR000591; DEP_dom.
DR InterPro; IPR045838; DEPDC5_CTD.
DR InterPro; IPR027244; IML1.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR13179; PTHR13179; 1.
DR Pfam; PF00610; DEP; 1.
DR Pfam; PF19418; DEPDC5_CTD; 1.
DR Pfam; PF12257; IML1; 1.
DR SMART; SM00049; DEP; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS50186; DEP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; GTPase activation; Lysosome; Membrane;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..1591
FT /note="GATOR complex protein DEPDC5"
FT /id="PRO_0000079866"
FT DOMAIN 1175..1250
FT /note="DEP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00066"
FT REGION 427..455
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 478..532
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 695..720
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1040..1064
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1118..1153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 427..443
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 494..532
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 695..718
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1041..1064
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 505
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75140"
FT VAR_SEQ 1078..1099
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14621295"
FT /id="VSP_046542"
FT CONFLICT 106..161
FT /note="DQYIGRGDMWRLKKSLVSTCAYITQKVEFAGIRAQAGELWVKNEKVMCGYIS
FT EETR -> LCLYHSKSGICWHQ (in Ref. 1; BAC97990)"
FT /evidence="ECO:0000305"
FT CONFLICT 1018..1019
FT /note="AA -> ST (in Ref. 1; BAC97990)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1591 AA; 180379 MW; B41891718FF11CBF CRC64;
MRTTKVYKLV IHKKGFGGSD DELVVNPKVF PHIKLGDIVE IAHPNDEYSP LLLQVKSLKE
DLQKETISVD QTVTQVFRLR PYQDVYVNVV DPKDVTLDLV ELTFKDQYIG RGDMWRLKKS
LVSTCAYITQ KVEFAGIRAQ AGELWVKNEK VMCGYISEET RVVFRSTSAM VYIFIQMSCE
MWDFDIYGDL YFEKAVNGFL ADLFTKWKEK NCSHEVTVVL FSRTFYDAKS IDEFPEINRA
SIQEDHKGRF YEDFYKVVVQ NERREEWTSL LVTIKKLFIQ YPVLVRLEQA GGFPQGDNST
SAQGNYLEAI NLSFNVFDKH YINRNFDRTG QMSVVITPGV GVFEVDRLLM ILTKQRMIDN
GIGVDLVCMG EQPLHAVPLF KLHNRSVPRD SRLGDDYNIP HWINHSFYTS KSQLFCNSFT
PRIKLAGKKS ASEKTKNGRD TSLGTPKESE NTLPIQVDYD AYDAQVFRLP GPSRAQRLAT
CRSVREQENH SRKSASSCDV SSSPSLPSRA LPTEEVRSQA SDDSSLGKST NILMIPNPHL
HQYEVSSSLG YTSTRDVLEN MIEPPQRDSS APGRFHVGSA ESMLHVRPGG YTPQRALINP
FAPSRMPMKL TSNRRRWMHT FPVGPSGEAI QIHHQTRQNM AELQGSRQRD PTHSSAELLE
LAYHEAAGRH STSRQPGDSM SLNFSGTEEL SVSLLSNSST GVNPRTQNKD SLEDSVSTSP
DPMPGFCCTV GVDWKSLTTP ACLPLTTDYF PDRQGLQNDY TEGCYDLLPE ADMDRRDEEG
VQMTAQQVFE EFICQRLMQG YQIIVQPKTQ KPNTTVPPPL SSSPLYSRGL VSRNRPEEEG
QYWLSMGRTF HKVTLKDKMI TVTRYLPKYP YESAQIHYTY SLCPSHSDSE FVSCWVDFCH
ERLEEYKWNY LDQYICSAGS EDFSLIESLK FWRTRFLLLP ACVTATKRIT EGEVHCDIYG
DKPRADEDEW QLLDGFIRFV EGLNRIRRRH RSDRMIRKGT AMKGLQMTGP ISAHSLEAAG
PPVGKKGTSA LSALLEMEAS QKSLGEQQTT VHGKSSTQPA ENSSVAMTPT YVDSPRKDGA
FFMEFVRSPR TASSAFYPQA SVDQTAPLVL DSTSLGVSTG QPMDRGNNQT FGNSQNIEQA
FPSANSGDYS SQQHVASSLT SSSTLVEILE AMKHPSTGVQ LLSEQKGLSP CCFISAEVVH
WLMNNVEGVQ TQAMGIDIMQ KMLEEQLITH ASGEAWRTFI YGFYFYKIVM DKEPERVAMQ
QPSAPWYTAG ADDFASFQRK WFEVAFVAEE LVHSEIPAFL LPWLPSRPAS YASRHSSFSR
SFGGRSQAAA LLAATVPEQR TVTLDVDVNN RTDRLEWCSC YYHGNFSLNA AFEIKLHWMA
VTATVLFEMV QGWHRKATSC GFLLVPVLEG PFALPSYLYG DPLRAQLFIP LNLSCLLKEG
SEHLFDSFEP ETYWDRMHLF QEAIAHRFGF VQDKYSVSAF NFPAENKPQY IHVTGTVFLQ
LPYSKRKFSG QQRRRRNSTS STNQNMFCEE RVGYNWAYNT MLTKTWRSSA TGDEKFADRL
LKDFTDFCIN RDNRLVTFWT NCLEKMHASA P
