TBCD1_MOUSE
ID TBCD1_MOUSE Reviewed; 1255 AA.
AC Q60949; E9QLW9; Q80TJ9; Q923F8;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=TBC1 domain family member 1;
GN Name=Tbc1d1; Synonyms=Kiaa1108, Tbc1;
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 [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=7566974;
RA Richardson P.M., Zon L.I.;
RT "Molecular cloning of a cDNA with a novel domain present in the tre-2
RT oncogene and the yeast cell cycle regulators BUB2 and cdc16.";
RL Oncogene 11:1139-1148(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 762-1255.
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 [5]
RP FUNCTION, AND PHOSPHORYLATION AT SER-146; SER-229; SER-231; SER-489;
RP SER-497; THR-499; SER-501; SER-519; SER-521; SER-559; SER-565; THR-590;
RP SER-608; SER-621; SER-660; SER-661; SER-697; SER-698; SER-699; SER-700;
RP SER-1028; TYR-1039 AND THR-1218.
RX PubMed=19740738; DOI=10.1074/jbc.m109.035568;
RA Peck G.R., Chavez J.A., Roach W.G., Budnik B.A., Lane W.S., Karlsson H.K.,
RA Zierath J.R., Lienhard G.E.;
RT "Insulin-stimulated phosphorylation of the Rab GTPase-activating protein
RT TBC1D1 regulates GLUT4 translocation.";
RL J. Biol. Chem. 284:30016-30023(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-497; SER-501; SER-559;
RP SER-560; THR-590; SER-621; SER-660; SER-700 AND SER-782, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, 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).
CC -!- FUNCTION: May act as a GTPase-activating protein for Rab family
CC protein(s). May play a role in the cell cycle and differentiation of
CC various tissues. Involved in the trafficking and translocation of
CC GLUT4-containing vesicles and insulin-stimulated glucose uptake into
CC cells. {ECO:0000269|PubMed:19740738}.
CC -!- SUBUNIT: Interacts with APPL2 (via BAR domain); interaction is
CC dependent of TBC1D1 phosphorylation at Ser-229; interaction diminishes
CC the phosphorylation of TBC1D1 at Thr-590, resulting in inhibition of
CC SLC2A4/GLUT4 translocation and glucose uptake.
CC {ECO:0000250|UniProtKB:Q86TI0}.
CC -!- INTERACTION:
CC Q60949; Q8K3G9: Appl2; NbExp=2; IntAct=EBI-21012140, EBI-647007;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:7566974}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q60949-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q60949-2; Sequence=VSP_008473;
CC -!- TISSUE SPECIFICITY: Expressed in highest levels in hematopoietic cells,
CC testis and kidney. {ECO:0000269|PubMed:7566974}.
CC -!- PTM: Insulin-stimulated phosphorylation by AKT family kinases
CC stimulates SLC2A4/GLUT4 translocation. {ECO:0000269|PubMed:19740738}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA85223.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC65727.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U33005; AAA85223.1; ALT_FRAME; mRNA.
DR EMBL; AK122445; BAC65727.1; ALT_INIT; mRNA.
DR EMBL; AC131679; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC132271; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004675; AAH04675.1; -; mRNA.
DR CCDS; CCDS39094.1; -. [Q60949-2]
DR CCDS; CCDS80287.1; -. [Q60949-1]
DR PIR; T29104; T29104.
DR RefSeq; NP_001297540.1; NM_001310611.1. [Q60949-1]
DR RefSeq; XP_011239059.1; XM_011240757.2. [Q60949-1]
DR RefSeq; XP_011239060.1; XM_011240758.2. [Q60949-1]
DR AlphaFoldDB; Q60949; -.
DR SMR; Q60949; -.
DR BioGRID; 208365; 2.
DR IntAct; Q60949; 1.
DR STRING; 10090.ENSMUSP00000044577; -.
DR iPTMnet; Q60949; -.
DR PhosphoSitePlus; Q60949; -.
DR EPD; Q60949; -.
DR jPOST; Q60949; -.
DR MaxQB; Q60949; -.
DR PaxDb; Q60949; -.
DR PRIDE; Q60949; -.
DR ProteomicsDB; 254657; -. [Q60949-1]
DR ProteomicsDB; 254658; -. [Q60949-2]
DR Antibodypedia; 10398; 222 antibodies from 34 providers.
DR DNASU; 57915; -.
DR Ensembl; ENSMUST00000043893; ENSMUSP00000044577; ENSMUSG00000029174. [Q60949-1]
DR Ensembl; ENSMUST00000101195; ENSMUSP00000098756; ENSMUSG00000029174. [Q60949-2]
DR Ensembl; ENSMUST00000121370; ENSMUSP00000112493; ENSMUSG00000029174. [Q60949-2]
DR GeneID; 57915; -.
DR KEGG; mmu:57915; -.
DR UCSC; uc008xmm.2; mouse. [Q60949-1]
DR CTD; 23216; -.
DR MGI; MGI:1889508; Tbc1d1.
DR VEuPathDB; HostDB:ENSMUSG00000029174; -.
DR eggNOG; KOG4436; Eukaryota.
DR GeneTree; ENSGT00940000157949; -.
DR HOGENOM; CLU_005350_13_0_1; -.
DR InParanoid; Q60949; -.
DR OMA; CERIEXK; -.
DR OrthoDB; 323342at2759; -.
DR PhylomeDB; Q60949; -.
DR TreeFam; TF317184; -.
DR BioGRID-ORCS; 57915; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Tbc1d1; mouse.
DR PRO; PR:Q60949; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q60949; protein.
DR Bgee; ENSMUSG00000029174; Expressed in hindlimb stylopod muscle and 245 other tissues.
DR ExpressionAtlas; Q60949; baseline and differential.
DR Genevisible; Q60949; MM.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:MGI.
DR GO; GO:0032880; P:regulation of protein localization; ISO:MGI.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR021785; DUF3350.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006020; PTB/PI_dom.
DR InterPro; IPR000195; Rab-GTPase-TBC_dom.
DR InterPro; IPR035969; Rab-GTPase_TBC_sf.
DR Pfam; PF11830; DUF3350; 1.
DR Pfam; PF00640; PID; 1.
DR Pfam; PF00566; RabGAP-TBC; 1.
DR SMART; SM00462; PTB; 2.
DR SMART; SM00164; TBC; 1.
DR SUPFAM; SSF47923; SSF47923; 2.
DR PROSITE; PS01179; PID; 1.
DR PROSITE; PS50086; TBC_RABGAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; GTPase activation; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1255
FT /note="TBC1 domain family member 1"
FT /id="PRO_0000208023"
FT DOMAIN 238..398
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT DOMAIN 887..1081
FT /note="Rab-GAP TBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT REGION 208..228
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 509..544
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 559..581
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 595..614
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 621..681
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 764..786
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1233..1255
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 520..540
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 621..635
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 659..681
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1241..1255
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 146
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19740738"
FT MOD_RES 229
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:19740738"
FT MOD_RES 231
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:19740738"
FT MOD_RES 489
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:19740738"
FT MOD_RES 497
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19740738,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 499
FT /note="Phosphothreonine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:19740738"
FT MOD_RES 501
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19740738,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 519
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19740738"
FT MOD_RES 521
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19740738"
FT MOD_RES 559
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19740738,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 560
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 564
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86TI0"
FT MOD_RES 565
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19740738"
FT MOD_RES 579
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86TI0"
FT MOD_RES 590
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:19740738,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 608
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19740738"
FT MOD_RES 621
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:19740738,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 660
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19740738,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 661
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19740738"
FT MOD_RES 697
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:19740738"
FT MOD_RES 698
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19740738"
FT MOD_RES 699
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19740738"
FT MOD_RES 700
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:19740738,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 782
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1028
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19740738"
FT MOD_RES 1039
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:19740738"
FT MOD_RES 1218
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:19740738"
FT VAR_SEQ 631..724
FT /note="NVDHLPGGESQGCPGQPSAPPPPRLNPSASSPNFFKYLKHNSSGEQSGNAVP
FT KSVSYRNALRKKLHSSSSVPNFLKFLAPVDENNTCDFKNTNR -> K (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:7566974"
FT /id="VSP_008473"
FT CONFLICT 174
FT /note="E -> K (in Ref. 2; BAC65727)"
FT /evidence="ECO:0000305"
FT CONFLICT 289
FT /note="Q -> P (in Ref. 1; AAA85223)"
FT /evidence="ECO:0000305"
FT CONFLICT 462
FT /note="E -> A (in Ref. 1; AAA85223)"
FT /evidence="ECO:0000305"
FT CONFLICT 848
FT /note="E -> D (in Ref. 4; AAH04675)"
FT /evidence="ECO:0000305"
FT CONFLICT 1047
FT /note="I -> T (in Ref. 1; AAA85223)"
FT /evidence="ECO:0000305"
FT CONFLICT 1050..1051
FT /note="SL -> PT (in Ref. 1; AAA85223)"
FT /evidence="ECO:0000305"
FT CONFLICT 1143
FT /note="A -> P (in Ref. 4; AAH04675)"
FT /evidence="ECO:0000305"
FT CONFLICT 1151
FT /note="L -> V (in Ref. 1; AAA85223)"
FT /evidence="ECO:0000305"
FT CONFLICT 1176
FT /note="S -> T (in Ref. 1; AAA85223)"
FT /evidence="ECO:0000305"
FT CONFLICT 1215
FT /note="A -> R (in Ref. 1; AAA85223)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1255 AA; 142026 MW; 8AC3121224B310D2 CRC64;
MEAITFTARK HPFPNEVSVD FGLQLVGSLP VHSLTTMPML PWVVAEVRRL SGQCSKKEPR
TKQVRLWVSP SGLRCEPDLE KSQPWDPLIC SSIFECKPQR VHKLIHNSHD PSYFACLIKE
DAAHRQSLCY VFKADDQTKV PEIISSIRQA GKIARQEELR CPSEFDDTFA KKFEVLFCGR
VTVAHKKAPP ALIDECIEKF NHVSCGRRTD WEAPTGQPSA PGPRPMRKSF SQPGLRSLAF
RKEFQDASLR SSTFSSFDND IENHLIGGHN VVQPTDMEEN RTMLFTIGQS EVYLISPDTK
KIALEKNFKE ISFCSQGIRH VDHFGFICRE CSGGGSGGFH FVCYVFQCTN EALVDEIMMT
LKQAFTVAAV QQTAKAPAQL CEGCPLQGLH KLCERIEGMN SSKTKLELQK HLTTLTNQEQ
ATIFEEVQKL RPRNEQRENE LIISFLRCLY EEKQKEHSHT GEPKQTLQVA AENIGSDLPP
SASRFRLDSL KNRAKRSLTE SLESILSRGN KARGLQDHSA SVDLDSSTSS TLSNTSKELS
MGDKEAFPVS ETSFKLLGSS DDLSSDSEGH IAEESALLSP QQAFRRRANT LSHFPVECPA
PPEPAQSSPG VSQRKLMRYH SVSTETPHER NVDHLPGGES QGCPGQPSAP PPPRLNPSAS
SPNFFKYLKH NSSGEQSGNA VPKSVSYRNA LRKKLHSSSS VPNFLKFLAP VDENNTCDFK
NTNRDFESKA NHLGDTDGTP VKTRRHSWRQ QIFLRVATPQ KACDSPSRYE DYSELGELPP
RSPLEPVCED GPFGPVQEEK RKTSRELREL WKKAILQQIL LLRMEKENQK LQASENDLLN
KRLKLDYEEI TPCLKEVTTV WEKMLSTPGR SKIKFDMEKV HSAVGQGVPR HHRGEIWKFL
AEQFHLKHPF PSKQQPKDVP YKELLKKLTS QQHAILIDLG RTFPTHPYFS AQLGAGQLSL
YNILKAYSLL DQEVGYCQGL SFVAGILLLH MSEEEAFKML KFLMFDMGLR KQYRPDMIIL
QIQMYQLSRL LHDYHRDLYN HLEEHEIGPS LYAAPWFLTV FASQFPLGFV ARVFDMIFLQ
GSEVIFKVAL SLLGSHKPLI LQHENLETIV DFIKNTLPNL GLVQMEKTIS QVFEMDIAKQ
LQAYEVEYHV LQEELIESSP LSDNQRMEKL EKTNSSLRKQ NLDLLEQLQV ANARIQSLEA
TVEKLLTSES KLKQAALTLE VERSALLQMV EELRRQSARP STPEPDCTQL EPTGD
