TBWKD_DROME
ID TBWKD_DROME Reviewed; 363 AA.
AC Q9VGL8;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=TBC1 domain family member whacked {ECO:0000303|PubMed:22407366};
GN Name=wkd {ECO:0000303|PubMed:22407366, ECO:0000312|FlyBase:FBgn0037917};
GN ORFNames=CG5344 {ECO:0000312|FlyBase:FBgn0037917};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AAQ23581.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAQ23581.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAQ23581.1};
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., Celniker S.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP 6-ARG--LEU-363 AND MET-133.
RX PubMed=22407366; DOI=10.1038/ncb2454;
RA Schottenfeld-Roames J., Ghabrial A.S.;
RT "Whacked and Rab35 polarize dynein-motor-complex-dependent seamless tube
RT growth.";
RL Nat. Cell Biol. 14:386-393(2012).
CC -!- FUNCTION: Essential for ensuring the polarized growth of tracheal
CC seamless tubes. During seamless tube morphogenesis, likely to act as a
CC GTPase-activating protein (GAP) for Rab35 to regulate vesicle
CC trafficking from the recycling endosomes to the lumenal apical membrane
CC to ensure the polarized dynein motor complex-dependent growth of
CC seamless tubes along the proximodistal axis in tracheal terminal cells.
CC When the terminal branch lumen is growing, Rab35-GTP is active and
CC likely directs the transport of apical membrane vesicles from the soma
CC to the distal tip of elongating terminal cell branches thus providing a
CC continuous supply of apical membrane components as the lumen grows.
CC Whereas when Rab35-GDP is inactivated, presumably by this GAP, apical
CC membrane vesicles are transported to a central location adjacent to the
CC terminal cell nucleus. {ECO:0000269|PubMed:22407366}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane; Peripheral membrane protein
CC {ECO:0000269|PubMed:22407366}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:22407366}. Cell projection, filopodium
CC {ECO:0000269|PubMed:22407366}. Note=Restricted to the lumenal membrane
CC of tracheal terminal cells with increased accumulation at the growing
CC tips of seamless tubes. Colocalizes with Rab35 at the apical membrane,
CC cytoplasmic puncta (likely to be vesicles) and filopodia.
CC {ECO:0000269|PubMed:22407366}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in the trachea results in
CC a U-turn phenotype in which the seamless tubes undergo a series of 180
CC degree turns in terminal tip cells. {ECO:0000269|PubMed:22407366}.
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DR EMBL; AE014297; AAF54659.1; -; Genomic_DNA.
DR EMBL; AE014297; AAN13513.1; -; Genomic_DNA.
DR EMBL; BT010263; AAQ23581.1; -; mRNA.
DR RefSeq; NP_650089.1; NM_141832.4.
DR RefSeq; NP_731593.1; NM_169402.3.
DR AlphaFoldDB; Q9VGL8; -.
DR SMR; Q9VGL8; -.
DR IntAct; Q9VGL8; 2.
DR STRING; 7227.FBpp0081889; -.
DR PaxDb; Q9VGL8; -.
DR PRIDE; Q9VGL8; -.
DR DNASU; 41390; -.
DR EnsemblMetazoa; FBtr0082413; FBpp0081889; FBgn0037917.
DR EnsemblMetazoa; FBtr0082414; FBpp0081890; FBgn0037917.
DR GeneID; 41390; -.
DR KEGG; dme:Dmel_CG5344; -.
DR UCSC; CG5344-RA; d. melanogaster.
DR CTD; 41390; -.
DR FlyBase; FBgn0037917; wkd.
DR VEuPathDB; VectorBase:FBgn0037917; -.
DR eggNOG; KOG2221; Eukaryota.
DR GeneTree; ENSGT00940000171809; -.
DR HOGENOM; CLU_005350_2_2_1; -.
DR InParanoid; Q9VGL8; -.
DR OMA; KWLYMID; -.
DR OrthoDB; 976276at2759; -.
DR PhylomeDB; Q9VGL8; -.
DR Reactome; R-DME-6798695; Neutrophil degranulation.
DR Reactome; R-DME-8854214; TBC/RABGAPs.
DR BioGRID-ORCS; 41390; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 41390; -.
DR PRO; PR:Q9VGL8; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0037917; Expressed in adult hindgut (Drosophila) and 26 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0098592; C:cytoplasmic side of apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0030175; C:filopodium; IDA:FlyBase.
DR GO; GO:0005096; F:GTPase activator activity; ISS:FlyBase.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0035149; P:lumen formation, open tracheal system; IMP:FlyBase.
DR GO; GO:0010085; P:polarity specification of proximal/distal axis; IMP:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; ISS:FlyBase.
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 Cell membrane; Cell projection; Cytoplasmic vesicle; GTPase activation;
KW Membrane; Reference proteome.
FT CHAIN 1..363
FT /note="TBC1 domain family member whacked"
FT /id="PRO_0000445426"
FT DOMAIN 77..265
FT /note="Rab-GAP TBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT REGION 335..363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 345..363
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 6..363
FT /note="Missing: Seamless tube overgrowth at terminal cell
FT tip branches."
FT /evidence="ECO:0000269|PubMed:22407366"
FT MUTAGEN 133
FT /note="M->K: Seamless tube overgrowth at terminal cell tip
FT branches."
FT /evidence="ECO:0000269|PubMed:22407366"
SQ SEQUENCE 363 AA; 42051 MW; F93B866B848FB640 CRC64;
MATAPRSLDT ISLCSTVSSC PDRNGFYGGF QRTDKPKEPL SKAQIIAREK KWLYMIDNWS
IYMSKNYKKI RDRCRKGIPK SVRPKAWFYL SGAYLLKKKN PNVYNELLEK PGNPTTIEEI
KKDKHRQFPF HEMFLDEQKV GQIELFNVLK AYSIYNPKVG FCQAQAPIAA FLLMHLPAED
AFWVFVSVCD VYLQDYFIPG LEVIQNDAGI LEGLLKKTCP PVYRHLQKHK VEPLLYMTDW
FLCAMTRTLP WETLLRVWDC FLAEGIRVIF KVALVIIGAS LSRHKVRKTC TGLCETLAVL
RSPEEHIVEE EFIINNMMRL NLRVEDFQIE HTRQKARRAK QKAQQEAESS GSGNGHRRNM
PTL
