VHL_DROME
ID VHL_DROME Reviewed; 178 AA.
AC Q9V3C1;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Protein Vhl;
GN Name=Vhl {ECO:0000312|FlyBase:FBgn0041174}; ORFNames=CG13221;
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;
RN [1] {ECO:0000305, ECO:0000312|PIR:JC7399}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, IDENTIFICATION IN A COMPLEX WITH
RP CUL2; ROX1A AND ELONGINS B AND C, INTERACTION WITH SIMA, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=11006129; DOI=10.1006/bbrc.2000.3451;
RA Aso T., Yamazaki K., Aigaki T., Kitajima S.;
RT "Drosophila von Hippel-Lindau tumor suppressor complex possesses E3
RT ubiquitin ligase activity.";
RL Biochem. Biophys. Res. Commun. 276:355-361(2000).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAF29377.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION AS A UBIQUITIN LIGASE, INTERACTION
RP WITH ELONGIN C, AND DEVELOPMENTAL STAGE.
RC TISSUE=Ovary {ECO:0000312|EMBL:AAF29377.1};
RX PubMed=10851083; DOI=10.1038/sj.onc.1203611;
RA Adryan B., Decker H.-J., Papas T.S., Hsu T.;
RT "Tracheal development and the von Hippel-Lindau tumor suppressor homolog in
RT Drosophila.";
RL Oncogene 19:2803-2811(2000).
RN [3] {ECO:0000312|EMBL:AAF58684.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAF58684.1};
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 [4] {ECO:0000312|EMBL:AAF58684.1}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
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 [5] {ECO:0000312|EMBL:AAL68362.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL68362.1};
RC TISSUE=Head {ECO:0000312|EMBL:AAL68362.1};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [6]
RP FUNCTION, SELF-ASSOCIATION, AND INTERACTION WITH MGR; BETATUB56D; TUBULIN
RP ALPHA-BETA HETERODIMER AND MICROTUBULES.
RX PubMed=22451918; DOI=10.1073/pnas.1108537109;
RA Delgehyr N., Wieland U., Rangone H., Pinson X., Mao G., Dzhindzhev N.S.,
RA McLean D., Riparbelli M.G., Llamazares S., Callaini G., Gonzalez C.,
RA Glover D.M.;
RT "Drosophila Mgr, a Prefoldin subunit cooperating with von Hippel Lindau to
RT regulate tubulin stability.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:5729-5734(2012).
CC -!- FUNCTION: Involved in development of tracheal vasculature. Probably
CC involved in halting cell migration at the end of vascular tube
CC outgrowth. Possesses E3 ubiquitin ligase activity when in complex with
CC Elongin BC complex, Cul2 and Rox1a/Rbx1, and can target sima/Hif1a for
CC ubiquitination. May play a critical role in promoting microtubule
CC stabilization when tubulins are correctly folded by the prefoldin
CC complex. If tubulin is incorrectly folded, may promote its degradation.
CC {ECO:0000269|PubMed:10851083, ECO:0000269|PubMed:11006129,
CC ECO:0000269|PubMed:22451918}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Part of a complex with Cul2, Roc1a/Rbx1 and the elongin BC
CC complex. Interacts with sima/Hif1a. Interacts with itself. Interacts
CC with mgr and betaTub56D/tubulin beta-1 chain. Interacts with tubulin
CC alpha-beta heterodimers by itself or in complex with mgr. Interacts
CC with microtubules (MTs). {ECO:0000269|PubMed:10851083,
CC ECO:0000269|PubMed:11006129, ECO:0000269|PubMed:22451918}.
CC -!- INTERACTION:
CC Q9V3C1; Q7KRW1: Trc8; NbExp=3; IntAct=EBI-169514, EBI-1011633;
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development. During
CC embryogenesis specifically expressed in developing tracheal regions.
CC {ECO:0000269|PubMed:10851083, ECO:0000269|PubMed:11006129}.
CC -!- SIMILARITY: Belongs to the VHL family. {ECO:0000305}.
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DR EMBL; AF195836; AAF29377.1; -; mRNA.
DR EMBL; AE013599; AAF58684.1; -; Genomic_DNA.
DR EMBL; AY075555; AAL68362.1; -; mRNA.
DR EMBL; BT023867; AAZ86788.1; -; mRNA.
DR PIR; JC7399; JC7399.
DR RefSeq; NP_001260885.1; NM_001273956.1.
DR RefSeq; NP_524986.1; NM_080247.3.
DR AlphaFoldDB; Q9V3C1; -.
DR SMR; Q9V3C1; -.
DR BioGRID; 72721; 14.
DR IntAct; Q9V3C1; 1.
DR STRING; 7227.FBpp0087216; -.
DR PaxDb; Q9V3C1; -.
DR DNASU; 53433; -.
DR EnsemblMetazoa; FBtr0088115; FBpp0087216; FBgn0041174.
DR EnsemblMetazoa; FBtr0332420; FBpp0304693; FBgn0041174.
DR GeneID; 53433; -.
DR KEGG; dme:Dmel_CG13221; -.
DR CTD; 7428; -.
DR FlyBase; FBgn0041174; Vhl.
DR VEuPathDB; VectorBase:FBgn0041174; -.
DR eggNOG; KOG4710; Eukaryota.
DR GeneTree; ENSGT00390000014353; -.
DR HOGENOM; CLU_116090_1_0_1; -.
DR InParanoid; Q9V3C1; -.
DR OMA; RWLIRTS; -.
DR OrthoDB; 1509532at2759; -.
DR PhylomeDB; Q9V3C1; -.
DR Reactome; R-DME-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-DME-8951664; Neddylation.
DR Reactome; R-DME-9706019; RHOBTB3 ATPase cycle.
DR Reactome; R-DME-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 53433; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 53433; -.
DR PRO; PR:Q9V3C1; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0041174; Expressed in crop (Drosophila) and 24 other tissues.
DR ExpressionAtlas; Q9V3C1; baseline and differential.
DR Genevisible; Q9V3C1; DM.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0030891; C:VCB complex; IDA:FlyBase.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007098; P:centrosome cycle; IGI:FlyBase.
DR GO; GO:0007427; P:epithelial cell migration, open tracheal system; IMP:FlyBase.
DR GO; GO:0016334; P:establishment or maintenance of polarity of follicular epithelium; IMP:FlyBase.
DR GO; GO:0035149; P:lumen formation, open tracheal system; IMP:FlyBase.
DR GO; GO:0090307; P:mitotic spindle assembly; IGI:FlyBase.
DR GO; GO:0007026; P:negative regulation of microtubule depolymerization; IMP:FlyBase.
DR GO; GO:0007424; P:open tracheal system development; IMP:FlyBase.
DR GO; GO:0006611; P:protein export from nucleus; IMP:FlyBase.
DR GO; GO:0016567; P:protein ubiquitination; IDA:FlyBase.
DR GO; GO:1900037; P:regulation of cellular response to hypoxia; IMP:FlyBase.
DR GO; GO:0060438; P:trachea development; IMP:FlyBase.
DR CDD; cd05468; pVHL; 1.
DR Gene3D; 2.60.40.780; -; 1.
DR InterPro; IPR024053; VHL_beta_dom.
DR InterPro; IPR037140; VHL_beta_dom_sf.
DR InterPro; IPR036208; VHL_sf.
DR InterPro; IPR022772; VHL_tumour_suppress_b/a_dom.
DR Pfam; PF01847; VHL; 1.
DR SUPFAM; SSF49468; SSF49468; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; Developmental protein; Differentiation; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1..178
FT /note="Protein Vhl"
FT /id="PRO_0000076363"
SQ SEQUENCE 178 AA; 21240 MW; EF0AE70597F9F279 CRC64;
MALQIAQNNR DGQQLVGADQ GKVEVYVLFA NTTYRTLDLY WVCERERENM YLTLKPFEEV
RVNTFTTHSW LFRDYYTGER MHVRSQRIFQ PIRVRVPKSQ QSPDQLVDVR SEVLIHFPMR
SLRENCLWLV ARWLIRTSNA PRRIIHGYHI PSTLKQQLLS LLTCIESYSR VAGTRRRR
