VHL_CAEEL
ID VHL_CAEEL Reviewed; 174 AA.
AC Q19213;
DT 24-JUN-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=von Hippel-Lindau tumor suppressor homolog {ECO:0000312|WormBase:F08G12.4};
GN Name=vhl-1 {ECO:0000312|WormBase:F08G12.4};
GN ORFNames=F08G12.4 {ECO:0000312|WormBase:F08G12.4};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH HIF-1.
RX PubMed=11595184; DOI=10.1016/s0092-8674(01)00507-4;
RA Epstein A.C.R., Gleadle J.M., McNeill L.A., Hewitson K.S., O'Rourke J.,
RA Mole D.R., Mukherji M., Metzen E., Wilson M.I., Dhanda A., Tian Y.M.,
RA Masson N., Hamilton D.L., Jaakkola P., Barstead R., Hodgkin J.,
RA Maxwell P.H., Pugh C.W., Schofield C.J., Ratcliffe P.J.;
RT "C. elegans EGL-9 and mammalian homologs define a family of dioxygenases
RT that regulate HIF by prolyl hydroxylation.";
RL Cell 107:43-54(2001).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12686697; DOI=10.1152/physiolgenomics.00179.2002;
RA Treinin M., Shliar J., Jiang H., Powell-Coffman J.A., Bromberg Z.,
RA Horowitz M.;
RT "HIF-1 is required for heat acclimation in the nematode Caenorhabditis
RT elegans.";
RL Physiol. Genomics 14:17-24(2003).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16091039; DOI=10.1111/j.1365-2958.2005.04739.x;
RA Anyanful A., Dolan-Livengood J.M., Lewis T., Sheth S., Dezalia M.N.,
RA Sherman M.A., Kalman L.V., Benian G.M., Kalman D.;
RT "Paralysis and killing of Caenorhabditis elegans by enteropathogenic
RT Escherichia coli requires the bacterial tryptophanase gene.";
RL Mol. Microbiol. 57:988-1007(2005).
RN [5] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20011506; DOI=10.1371/journal.ppat.1000689;
RA Bellier A., Chen C.S., Kao C.Y., Cinar H.N., Aroian R.V.;
RT "Hypoxia and the hypoxic response pathway protect against pore-forming
RT toxins in C. elegans.";
RL PLoS Pathog. 5:E1000689-E1000689(2009).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19372390; DOI=10.1126/science.1173507;
RA Mehta R., Steinkraus K.A., Sutphin G.L., Ramos F.J., Shamieh L.S., Huh A.,
RA Davis C., Chandler-Brown D., Kaeberlein M.;
RT "Proteasomal regulation of the hypoxic response modulates aging in C.
RT elegans.";
RL Science 324:1196-1198(2009).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=20865124; DOI=10.1371/journal.ppat.1001075;
RA Shao Z., Zhang Y., Ye Q., Saldanha J.N., Powell-Coffman J.A.;
RT "C. elegans SWAN-1 Binds to EGL-9 and regulates HIF-1-mediated resistance
RT to the bacterial pathogen Pseudomonas aeruginosa PAO1.";
RL PLoS Pathog. 6:E1001075-E1001075(2010).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=22396654; DOI=10.1371/journal.pgen.1002498;
RA Ackerman D., Gems D.;
RT "Insulin/IGF-1 and hypoxia signaling act in concert to regulate iron
RT homeostasis in Caenorhabditis elegans.";
RL PLoS Genet. 8:E1002498-E1002498(2012).
CC -!- FUNCTION: Involved in the response to variation in environmental oxygen
CC levels by targeting the hypoxia-inducible transcription factor hif-1
CC for proteasomal degradation when oxygen levels are normal (around 20%)
CC (PubMed:11595184). By regulating hif-1 expression, plays a role in iron
CC homeostasis, aging, heat acclimation and progeny size (PubMed:12686697,
CC PubMed:19372390, PubMed:22396654). Mediates resistance to
CC enteropathogenic E.coli (PubMed:16091039). Mediates susceptibility to
CC B.thuringiensis pore-forming toxins (PubMed:20011506). Not involved in
CC P.aeruginosa susceptibility (PubMed:20865124).
CC {ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:12686697,
CC ECO:0000269|PubMed:16091039, ECO:0000269|PubMed:19372390,
CC ECO:0000269|PubMed:20011506, ECO:0000269|PubMed:20865124,
CC ECO:0000269|PubMed:22396654}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:P40337}.
CC -!- SUBUNIT: Interacts with hif-1 (hydroxylated on 'Pro-621'); the
CC interaction induces hif-1 degradation (PubMed:11595184). May be a
CC component of the cullin E3 ubiquitin ligase complex (By similarity).
CC {ECO:0000250|UniProtKB:P40337, ECO:0000269|PubMed:11595184}.
CC -!- DISRUPTION PHENOTYPE: Increased mortality induced by B.thuringiensis
CC pore-forming toxins Cry21A and Cry21B (PubMed:20011506). Increased
CC mortality and sensitivity to paralysis induced by enteropathogenic
CC E.coli infection (PubMed:16091039). Increased mortality upon heat
CC stress (PubMed:12686697). RNAi-mediated knockdown causes an enhanced
CC resistance to polyglutamine or amyloid-beta-mediated paralysis and an
CC increase in adult life span. {ECO:0000269|PubMed:12686697,
CC ECO:0000269|PubMed:16091039, ECO:0000269|PubMed:19372390,
CC ECO:0000269|PubMed:20011506}.
CC -!- SIMILARITY: Belongs to the VHL family. {ECO:0000305}.
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DR EMBL; Z66561; CAA91456.1; -; Genomic_DNA.
DR PIR; T20589; T20589.
DR RefSeq; NP_509889.1; NM_077488.3.
DR AlphaFoldDB; Q19213; -.
DR SMR; Q19213; -.
DR IntAct; Q19213; 4.
DR MINT; Q19213; -.
DR STRING; 6239.F08G12.4; -.
DR EPD; Q19213; -.
DR PaxDb; Q19213; -.
DR PRIDE; Q19213; -.
DR EnsemblMetazoa; F08G12.4.1; F08G12.4.1; WBGene00006922.
DR GeneID; 181321; -.
DR KEGG; cel:CELE_F08G12.4; -.
DR UCSC; F08G12.4; c. elegans.
DR CTD; 181321; -.
DR WormBase; F08G12.4; CE03169; WBGene00006922; vhl-1.
DR eggNOG; KOG4710; Eukaryota.
DR HOGENOM; CLU_116090_1_0_1; -.
DR InParanoid; Q19213; -.
DR OMA; NHPWVAR; -.
DR OrthoDB; 1509532at2759; -.
DR PhylomeDB; Q19213; -.
DR Reactome; R-CEL-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-CEL-8951664; Neddylation.
DR Reactome; R-CEL-9706019; RHOBTB3 ATPase cycle.
DR Reactome; R-CEL-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q19213; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00006922; Expressed in embryo and 4 other tissues.
DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; IPI:WormBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0030891; C:VCB complex; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0001666; P:response to hypoxia; IMP:WormBase.
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 Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..174
FT /note="von Hippel-Lindau tumor suppressor homolog"
FT /evidence="ECO:0000305"
FT /id="PRO_0000433368"
SQ SEQUENCE 174 AA; 20345 MW; A082698EF932EAC6 CRC64;
MSDGSMDDDG RLFPDLGSST HDNREIRVRF LNRCAYPVDV FWLNPSKQPT KYGTLAQKKY
LDIKTFKDHP WVARRSFDGC KVLVNEKEVF WPEPAPRMNL IVRNHCVITM KVQSLREIAG
RSFLRHNPTE VPNKIKGLPR ELQFEVKHFL DRKQEYSEIV CRSIPPPGPQ RPQQ
