TBCD5_MOUSE
ID TBCD5_MOUSE Reviewed; 815 AA.
AC Q80XQ2; E9PZJ9;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=TBC1 domain family member 5;
GN Name=Tbc1d5;
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 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-565 AND SER-568, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-578, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-565; SER-568 AND SER-608, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Spleen, and
RC 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 [6]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-448, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: May act as a GTPase-activating protein for Rab family
CC protein(s). May act as a GAP for RAB7A. Can displace RAB7A and retromer
CC CSC subcomplex from the endosomal membrane to the cytosol; at least
CC retromer displacement seems to require its catalytic activity. Required
CC for retrograde transport of cargo proteins from endosomes to the trans-
CC Golgi network (TGN); the function seems to require its catalytic
CC activity. Involved in regulation of autophagy. May act as a molecular
CC switch between endosomal and autophagosomal transport and is involved
CC in reprogramming vesicle trafficking upon autophagy induction. Involved
CC in the trafficking of ATG9A upon activation of autophagy. May regulate
CC the recruitment of ATG9A-AP2-containing vesicles to autophagic
CC membranes (By similarity). {ECO:0000250|UniProtKB:Q92609}.
CC -!- SUBUNIT: Interacts with MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAP,
CC GABARAPL1, GABARAPL2. Interacts with VPS29 and VPS35; indicative for an
CC association with retromer CSC subcomplex. MAP1LC3A and VPS29 compete
CC for binding to TBC1D5. Interacts with AP2M1; indicative for an
CC association with the AP2 complex. Interacts with ULK1 and ATG13
CC (phosphorylated); indicative for an association with the activated
CC ULK1-ATG13-FIP200 complex. Interacts with ATG9A; the interactions seems
CC to be restricted to the AP2-clathrin-associated fraction of ATG9A.
CC {ECO:0000250|UniProtKB:Q92609}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:Q92609}.
CC Cytoplasmic vesicle, autophagosome {ECO:0000250|UniProtKB:Q92609}.
CC Note=During starvation induced autophagy is relocalized from endosomal
CC localization to LC3-positive autophagosomes (By similarity).
CC {ECO:0000250|UniProtKB:Q92609}.
CC -!- DOMAIN: The arginine and glutamine fingers are critical for the GTPase-
CC activating mechanism, they pull out Rab's 'switch 2' glutamine and
CC insert in Rab's active site. {ECO:0000250|UniProtKB:Q96BZ9}.
CC -!- DOMAIN: The LIR (LC3-interacting region) motif mediates the interaction
CC with ATG8 family proteins. LIR 1 is also implicated in interaction with
CC retromer; LIR 2 is only implicated in interaction with ATG8 family
CC proteins. {ECO:0000250|UniProtKB:Q92609}.
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DR EMBL; AC099694; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC110168; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC125140; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC154214; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CT025541; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC043113; AAH43113.1; -; mRNA.
DR CCDS; CCDS37650.1; -.
DR RefSeq; NP_001272922.1; NM_001285993.1.
DR RefSeq; NP_082438.3; NM_028162.4.
DR AlphaFoldDB; Q80XQ2; -.
DR SMR; Q80XQ2; -.
DR BioGRID; 215243; 16.
DR IntAct; Q80XQ2; 1.
DR STRING; 10090.ENSMUSP00000024717; -.
DR iPTMnet; Q80XQ2; -.
DR PhosphoSitePlus; Q80XQ2; -.
DR EPD; Q80XQ2; -.
DR jPOST; Q80XQ2; -.
DR MaxQB; Q80XQ2; -.
DR PaxDb; Q80XQ2; -.
DR PRIDE; Q80XQ2; -.
DR ProteomicsDB; 262947; -.
DR Antibodypedia; 45185; 49 antibodies from 18 providers.
DR DNASU; 72238; -.
DR Ensembl; ENSMUST00000024717; ENSMUSP00000024717; ENSMUSG00000023923.
DR GeneID; 72238; -.
DR KEGG; mmu:72238; -.
DR UCSC; uc008cyy.3; mouse.
DR CTD; 9779; -.
DR MGI; MGI:1919488; Tbc1d5.
DR VEuPathDB; HostDB:ENSMUSG00000023923; -.
DR eggNOG; KOG1091; Eukaryota.
DR GeneTree; ENSGT00940000157121; -.
DR HOGENOM; CLU_020460_1_0_1; -.
DR InParanoid; Q80XQ2; -.
DR OMA; YPPMGDV; -.
DR PhylomeDB; Q80XQ2; -.
DR TreeFam; TF105784; -.
DR BioGRID-ORCS; 72238; 10 hits in 76 CRISPR screens.
DR ChiTaRS; Tbc1d5; mouse.
DR PRO; PR:Q80XQ2; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q80XQ2; protein.
DR Bgee; ENSMUSG00000023923; Expressed in embryonic post-anal tail and 216 other tissues.
DR ExpressionAtlas; Q80XQ2; baseline and differential.
DR Genevisible; Q80XQ2; MM.
DR GO; GO:0030122; C:AP-2 adaptor complex; ISO:MGI.
DR GO; GO:1990316; C:Atg1/ULK1 kinase complex; ISO:MGI.
DR GO; GO:0005776; C:autophagosome; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0010008; C:endosome membrane; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0030904; C:retromer complex; ISO:MGI.
DR GO; GO:0035612; F:AP-2 adaptor complex binding; ISO:MGI.
DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:1905394; F:retromer complex binding; ISO:MGI.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; ISO:MGI.
DR GO; GO:0016236; P:macroautophagy; ISO:MGI.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISO:MGI.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0042594; P:response to starvation; ISO:MGI.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISO:MGI.
DR InterPro; IPR000195; Rab-GTPase-TBC_dom.
DR InterPro; IPR035969; Rab-GTPase_TBC_sf.
DR Pfam; PF00566; RabGAP-TBC; 1.
DR SMART; SM00164; TBC; 1.
DR SUPFAM; SSF47923; SSF47923; 2.
DR PROSITE; PS50086; TBC_RABGAP; 1.
PE 1: Evidence at protein level;
KW Autophagy; Cytoplasmic vesicle; Endosome; GTPase activation; Membrane;
KW Methylation; Phosphoprotein; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1..815
FT /note="TBC1 domain family member 5"
FT /id="PRO_0000208029"
FT DOMAIN 81..359
FT /note="Rab-GAP TBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT REGION 56..64
FT /note="Required for interaction with retromer; involved in
FT interaction with ATG8 family proteins"
FT /evidence="ECO:0000250|UniProtKB:Q92609"
FT REGION 475..591
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 702..733
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 754..815
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 806..811
FT /note="Required for interaction with ATG8 family proteins"
FT /evidence="ECO:0000250|UniProtKB:Q92609"
FT MOTIF 57..62
FT /note="LIR 1"
FT /evidence="ECO:0000250|UniProtKB:Q92609"
FT MOTIF 805..809
FT /note="LIR 2"
FT /evidence="ECO:0000250|UniProtKB:Q92609"
FT COMPBIAS 480..569
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 702..725
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 754..768
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 783..808
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 169
FT /note="Arginine finger"
FT /evidence="ECO:0000250|UniProtKB:Q96BZ9"
FT SITE 204
FT /note="Glutamine finger"
FT /evidence="ECO:0000250|UniProtKB:Q96BZ9"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92609"
FT MOD_RES 448
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 448
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 460
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92609"
FT MOD_RES 546
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92609"
FT MOD_RES 563
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92609"
FT MOD_RES 565
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 568
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 578
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 608
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 811
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92609"
FT CONFLICT 770
FT /note="A -> S (in Ref. 2; AAH43113)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 815 AA; 91837 MW; 62E6D23B36398E9F CRC64;
MYKSVSETRH PLQSEEQEVG IDPLFSYSNK TRGDLSQNGR GSNSTLDTEG TFNSYMKEWE
ELFVNNNYLA TVRQKGINGQ LRSSRFRSIC WKLFLCVLPQ DKSQWISKIK ELRAWYSSIK
EIHITNPRKA AGQQDLMINN PLSQDEGSLW NKFFQDKELR SMIEQDVKRT FPEMQFFQQE
NVRKILTDVL FCYARENEQL LYKQGMHELL APIIFTLHCD HQAFLHASES AQPSEEMKTL
LNPEYLEHDA YAMFSQLMET AEPWFSTFEH DGQKGKETLM APIPFARPQD LGPTVAIVTK
VNQIQDHLLK KHDIELYMHL NRLEIAPQIY GLRWVRLLFG REFPLQDLLV VWDALFADSL
NLSLVDYVFT AMLLYIRDAL ISSNYQTCLG LLMHYPIIGD IHSLILKALF LRDPKRNPRP
ATYQFHPNLD YYKARGADLM NKSRTNARGA PLNIHKVSNS LINFGRKLIS PASAPGSMGG
PVPGNNSSSS FSAAIPTRTS TEAPRHHLLQ QQQQQQHQQQ QQQQPQQQQQ QHQQQQQQQR
LMKSESMPVQ LNKGQSSKTI SSSPSIESLP GGREFTGSPP PSATKKDSFF SNIARSRSHS
KTMGRKESEE ELEAQISFLQ GQLNDLDAMC KYCAKVMDMH LVNIQDVVLQ ENLEKEDQIL
VSLAGLKQIK DILKGSLRFN QSQLEAGENE QITIADDHYC SSGQDQGSQV PRAAKQASSE
MPGCTGGTTP DDFILVSKED EGHRARGAFS GQAQPLLTLR STSGKSRAPA CSPLLFSDPL
MGPASASASS SNPSSSPDDD SSKESGFTIV SPLDI
