TBC23_MOUSE
ID TBC23_MOUSE Reviewed; 684 AA.
AC Q8K0F1; Q3TAW9; Q8VE48;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=TBC1 domain family member 23;
GN Name=Tbc1d23;
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] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Czech II, and FVB/N; TISSUE=Liver, and Mammary tumor;
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-469, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, 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).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ARG-50.
RX PubMed=22312129; DOI=10.4049/jimmunol.1102595;
RA De Arras L., Yang I.V., Lackford B., Riches D.W., Prekeris R.,
RA Freedman J.H., Schwartz D.A., Alper S.;
RT "Spatiotemporal inhibition of innate immunity signaling by the Tbc1d23 RAB-
RT GAP.";
RL J. Immunol. 188:2905-2913(2012).
RN [5]
RP FUNCTION.
RX PubMed=28823707; DOI=10.1016/j.ajhg.2017.07.010;
RA Ivanova E.L., Mau-Them F.T., Riazuddin S., Kahrizi K., Laugel V.,
RA Schaefer E., de Saint Martin A., Runge K., Iqbal Z., Spitz M.A., Laura M.,
RA Drouot N., Gerard B., Deleuze J.F., de Brouwer A.P.M., Razzaq A.,
RA Dollfus H., Assir M.Z., Nitchke P., Hinckelmann M.V., Ropers H.,
RA Riazuddin S., Najmabadi H., van Bokhoven H., Chelly J.;
RT "Homozygous truncating variants in TBC1D23 cause pontocerebellar hypoplasia
RT and alter cortical development.";
RL Am. J. Hum. Genet. 101:428-440(2017).
RN [6]
RP FUNCTION, AND INTERACTION WITH C17ORF75; FAM91A1; FKBP15; GOLGA1; GOLGA4;
RP WASHC2 AND WDR11.
RX PubMed=29084197; DOI=10.1038/ncb3627;
RA Shin J.J.H., Gillingham A.K., Begum F., Chadwick J., Munro S.;
RT "TBC1D23 is a bridging factor for endosomal vesicle capture by golgins at
RT the trans-Golgi.";
RL Nat. Cell Biol. 19:1424-1432(2017).
CC -!- FUNCTION: Putative Rab GTPase-activating protein which plays a role in
CC vesicular trafficking. Involved in endosome-to-Golgi trafficking. Acts
CC as a bridging protein by binding simultaneously to golgins, including
CC GOLGA1 and GOLGA4, located at the trans-Golgi, and to the WASH complex,
CC located on endosome-derived vesicles (PubMed:29084197). Together with
CC WDR11 complex facilitates the golgin-mediated capture of vesicles
CC generated using AP-1 (By similarity). Plays a role in brain
CC development, including in cortical neuron positioning. May also be
CC important for neurite outgrowth, possibly through its involvement in
CC membrane trafficking and cargo delivery, 2 processes which are
CC essential for axonal and dendritic growth (PubMed:28823707). May act as
CC a general inhibitor of innate immunity signaling, strongly inhibiting
CC multiple TLR and dectin/CLEC7A-signaling pathways. Does not alter
CC initial activation events, but instead affects maintenance of
CC inflammatory gene expression several hours after bacterial
CC lipopolysaccharide (LPS) challenge (PubMed:22312129).
CC {ECO:0000250|UniProtKB:Q9NUY8, ECO:0000269|PubMed:22312129,
CC ECO:0000269|PubMed:28823707, ECO:0000269|PubMed:29084197}.
CC -!- SUBUNIT: Directly interacts with GOLGA1 and GOLGA4 (PubMed:29084197).
CC Interacts with FAM91A1, C17ORF75 and WDR11; the interaction recruits
CC TBC1D23 to AP-1-derived vesicles (PubMed:29084197). Directly interacts
CC with WASHC1 and WASHC2/FAM21 (PubMed:29084197). Interacts with FKBP15
CC (PubMed:29084197). {ECO:0000269|PubMed:29084197}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network
CC {ECO:0000269|PubMed:29084197}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:Q9NUY8}. Note=Localization to the trans-Golgi
CC (TGN) is regulated by ARL1 and ARL5B/ARL8. ARL1 increases Golgi
CC localization, while ARL5B decreases it. Recruitment to the trans-Golgi
CC network requires the presence of GOLGA1 and GOLGA4, but not that of
CC FAM91A1 (By similarity). Recruited on AP-1-derived vesicles by WDR11
CC complex (By similarity). {ECO:0000250|UniProtKB:Q9NUY8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8K0F1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8K0F1-2; Sequence=VSP_025520, VSP_025521;
CC -!- DISRUPTION PHENOTYPE: Mutant mice exhibit increased inflammatory
CC cytokine production and recruit more inflammatory cells to the
CC peritoneum, when challenged with different pathogen-associated
CC molecular patterns (PAMPs), including LPS.
CC {ECO:0000269|PubMed:22312129}.
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DR EMBL; AK155142; BAE33073.1; -; mRNA.
DR EMBL; AK171591; BAE42547.1; -; mRNA.
DR EMBL; BC019762; AAH19762.1; -; mRNA.
DR EMBL; BC031706; AAH31706.1; -; mRNA.
DR CCDS; CCDS28228.1; -. [Q8K0F1-1]
DR RefSeq; NP_080530.2; NM_026254.2. [Q8K0F1-1]
DR AlphaFoldDB; Q8K0F1; -.
DR SMR; Q8K0F1; -.
DR STRING; 10090.ENSMUSP00000023431; -.
DR iPTMnet; Q8K0F1; -.
DR PhosphoSitePlus; Q8K0F1; -.
DR EPD; Q8K0F1; -.
DR MaxQB; Q8K0F1; -.
DR PaxDb; Q8K0F1; -.
DR PeptideAtlas; Q8K0F1; -.
DR PRIDE; Q8K0F1; -.
DR ProteomicsDB; 254823; -. [Q8K0F1-1]
DR ProteomicsDB; 254824; -. [Q8K0F1-2]
DR Antibodypedia; 46507; 72 antibodies from 22 providers.
DR DNASU; 67581; -.
DR Ensembl; ENSMUST00000023431; ENSMUSP00000023431; ENSMUSG00000022749. [Q8K0F1-1]
DR GeneID; 67581; -.
DR KEGG; mmu:67581; -.
DR UCSC; uc007znb.1; mouse. [Q8K0F1-1]
DR UCSC; uc007znd.1; mouse. [Q8K0F1-2]
DR CTD; 55773; -.
DR MGI; MGI:1914831; Tbc1d23.
DR VEuPathDB; HostDB:ENSMUSG00000022749; -.
DR eggNOG; KOG3636; Eukaryota.
DR GeneTree; ENSGT00390000000191; -.
DR HOGENOM; CLU_026555_0_0_1; -.
DR InParanoid; Q8K0F1; -.
DR OMA; YNAGHLP; -.
DR PhylomeDB; Q8K0F1; -.
DR TreeFam; TF105892; -.
DR BioGRID-ORCS; 67581; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Tbc1d23; mouse.
DR PRO; PR:Q8K0F1; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q8K0F1; protein.
DR Bgee; ENSMUSG00000022749; Expressed in granulocyte and 254 other tissues.
DR ExpressionAtlas; Q8K0F1; baseline and differential.
DR Genevisible; Q8K0F1; MM.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0071203; C:WASH complex; ISO:MGI.
DR GO; GO:0007420; P:brain development; ISS:UniProtKB.
DR GO; GO:1990403; P:embryonic brain development; IMP:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; IMP:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:MGI.
DR GO; GO:0050727; P:regulation of inflammatory response; IMP:MGI.
DR GO; GO:0032680; P:regulation of tumor necrosis factor production; IMP:MGI.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISO:MGI.
DR GO; GO:0099041; P:vesicle tethering to Golgi; ISS:UniProtKB.
DR GO; GO:0016192; P:vesicle-mediated transport; IMP:UniProtKB.
DR Gene3D; 3.40.250.10; -; 1.
DR InterPro; IPR000195; Rab-GTPase-TBC_dom.
DR InterPro; IPR035969; Rab-GTPase_TBC_sf.
DR InterPro; IPR001763; Rhodanese-like_dom.
DR InterPro; IPR036873; Rhodanese-like_dom_sf.
DR InterPro; IPR039755; TBC1D23.
DR InterPro; IPR045799; TBC1D23_C.
DR PANTHER; PTHR13297; PTHR13297; 1.
DR Pfam; PF00566; RabGAP-TBC; 1.
DR Pfam; PF00581; Rhodanese; 1.
DR Pfam; PF19430; TBC1D23_C; 1.
DR SMART; SM00164; TBC; 1.
DR SUPFAM; SSF47923; SSF47923; 2.
DR SUPFAM; SSF52821; SSF52821; 1.
DR PROSITE; PS50206; RHODANESE_3; 1.
DR PROSITE; PS50086; TBC_RABGAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasmic vesicle; Developmental protein;
KW Golgi apparatus; Phosphoprotein; Reference proteome.
FT CHAIN 1..684
FT /note="TBC1 domain family member 23"
FT /id="PRO_0000287498"
FT DOMAIN 44..225
FT /note="Rab-GAP TBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT DOMAIN 334..446
FT /note="Rhodanese"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173"
FT REGION 514..684
FT /note="May mediate the interaction with WASHC1"
FT /evidence="ECO:0000269|PubMed:29084197"
FT REGION 514..558
FT /note="May mediate the interaction with C17orf75, FAM91A1
FT and WDR11"
FT /evidence="ECO:0000269|PubMed:29084197"
FT REGION 559..684
FT /note="May mediate the interaction with FKBP15 and WASHC2;
FT required for endosome to Golgi trafficking"
FT /evidence="ECO:0000269|PubMed:29084197"
FT MOD_RES 300
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NUY8"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 474
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NUY8"
FT MOD_RES 507
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NUY8"
FT MOD_RES 514
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NUY8"
FT MOD_RES 556
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NUY8"
FT VAR_SEQ 201..203
FT /note="LGS -> VIK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_025520"
FT VAR_SEQ 204..684
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_025521"
FT MUTAGEN 50
FT /note="R->A: Fails to inhibit LPS-induced cytokine
FT production."
FT /evidence="ECO:0000269|PubMed:22312129"
SQ SEQUENCE 684 AA; 76426 MW; B1DE9548FFB0A7FE CRC64;
MAEGEELLPL STSGGDSWEK DLEEALEAGG CDLETLRNII QGRPLPAELR AKVWKIALNV
AGKGDSLASW DGILDLPEQN TIHKDCLEFI EQLSVPEEKA AELLLDIESV ITFYCKSRSV
KYSTSLSWIH LLKPLICLQL PRSDLYNCFY AVMNKYIPRD CSLKGRPFHL FRLLIQYHEP
ELCSFLDTKK ITPDSYALNW LGSLFAHYCS TEVTQAIWDG YLQQADPFFI YFLMLIILVN
TKEVILAQES DSKEEVIRFL ESTPASLNLE DIEDLFSLAQ YYCSKTPASF RKDNHHLFGS
TLLGIKDDEA DLSQALCLAV SVSEILQANQ LQGEGVRFFV VDCRPAEQYN AGHLATAFHL
DSDLMLQNPS EFAQSVKSLL EAQKQSIESG SIAGGEHLCF MGSGREEEDM YMNMVLAHFL
QKNKEYVSIA SGGFMALQQH LADINVEGPE SGYGHWIAST SGSRGSISSV DGESCNGSND
RGMKSLVSKM TVALKTKSVT VREKVISFIE NSSTPVDRHV SSSDRVGKPY RGVKPVFSIG
DEEEYDTDEI DSSSMSDDDR KEVVNIQTWI NKPDIKHHFP CKEVKESGHM FPSHLLVTAT
HMYCLREILS RKGLAYIQSR QALNSVVKIT SKKKHPELIT FKYGNSSASG IEILAIERYL
IPNAGDATRA IKQQIMKVLD ALES
