Q64259 (VHL_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Von Hippel-Lindau disease tumor suppressor

Alternative name(s):
pVHL

Gene names

Name:

Vhl

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	185 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2 By similarity.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Component of the VCB (VHL-Elongin BC-CUL2) complex; this complex acts as a ubiquitin-ligase E3 and directs proteasome-dependent degradation of targeted proteins. Interacts with CUL2; this interaction is dependent on the integrity of the trimeric VBC complex. Interacts (via the beta domain) with HIF1A (via the NTAD domain); this interaction mediates degradation of HIF1A in normoxia and, in hypoxia, prevents ubiqitination and degradation of HIF1A by mediating hypoxia-induced translocation to the nucleus, a process which requires a hypoxia-dependent regulatory signal. Interacts with ADRB2; the interaction, in normoxia, is dependent on hydroxylation of ADRB2 and the subsequent VCB-mediated ubiquitination and degradation of ADRB2. Under hypoxia, hydroxylation, interaction with VHL, ubiquitination and subsequent degradation of ADRB2 are dramatically decreased. Interacts with RNF139, USP33 and PHF17 By similarity. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 AND CUL2. Interacts with LIMD1 (via LIM zinc-binding 2). Interacts with AJUBA (via LIM domains) and WTIP (via LIM domains) By similarity. Interacts with EPAS1 By similarity.
Subcellular location	Cytoplasm By similarity. Membrane; Peripheral membrane protein By similarity. Nucleus By similarity. Note: Colocalizes with ADRB2 at the cell membrane By similarity.
Domain	The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV].

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Membrane Nucleus
Disease	Tumor suppressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: Compara blood vessel endothelial cell migration Inferred from electronic annotation. Source: Compara extracellular matrix organization Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 11912140. Source: RGD neuron differentiation Inferred from direct assay PubMed 20125055. Source: RGD proteasomal protein catabolic process Inferred from electronic annotation. Source: Compara protein heterooligomerization Inferred from physical interaction PubMed 9122164. Source: RGD protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway regulation of catecholamine metabolic process Inferred from mutant phenotype PubMed 11912140. Source: RGD response to ethanol Inferred from expression pattern PubMed 15507234. Source: RGD response to hypoxia Inferred from mutant phenotype PubMed 11912140. Source: RGD
Cellular_component	VCB complex Inferred from direct assay PubMed 10213691PubMed 9122164. Source: RGD cytosol Inferred from direct assay Ref.1. Source: RGD membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay PubMed 10850420. Source: RGD transcription factor complex Traceable author statement PubMed 1966765. Source: RGD
Molecular_function	transcription factor binding Traceable author statement PubMed 1966765. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 185	185	Von Hippel-Lindau disease tumor suppressor		PRO_0000065811
Regions
	Region	123 – 132	10	Interaction with Elongin BC complex By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q64259 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 3AD15FD9EF139E13	FASTA	185	21,215
	10 20 30 40 50 60 MPRKAASPEE AERMPGSEEI EAGRPRPVLR SVNSREPSQV IFCNRSPRVV LPLWLNFDGE 70 80 90 100 110 120 PQPYPTLPPG TGRRIHSYRG HLWLFRDAGT HDGLLVNQTE LFVPSLNVDG QPIFANITLP 130 140 150 160 170 180 VYTLKERCLQ VVRSLVKPEN YRRLDIVRSL YEDLEDHPNV RKDIQRLTQE HLENQALGEE PEGVH

References

[1]	"Characterization of the VHL tumor suppressor gene product: localization, complex formation, and the effect of natural inactivating mutations." Duan D.R., Humphrey J.S., Chen D.Y., Weng Y., Sukegawa J., Lee S., Gnarra J.R., Linehan W.M., Klausner R.D. Proc. Natl. Acad. Sci. U.S.A. 92:6459-6463(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of the rat homologue of the von Hippel-Lindau tumor suppressor gene and its non-somatic mutation in rat renal cell carcinomas." Kikuchi Y., Kobayashi E., Nishizawa M., Hamazaki S., Okada S., Hino O. Jpn. J. Cancer Res. 86:905-909(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Renal cell carcinoma development in the rat independent of alterations at the VHL gene locus." Walker C., Ahn Y.T., Everitt J., Yuan X. Mol. Carcinog. 15:154-161(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 31-153.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U14746 mRNA. Translation: AAA86874.1. S80345 mRNA. Translation: AAB35675.1. S81658 mRNA. Translation: AAP32238.1.
IPI	IPI00210924.
PIR	T10752.
RefSeq	NP_434688.1. NM_052801.1.
UniGene	Rn.11059.
3D structure databases
ProteinModelPortal	Q64259.
SMR	Q64259. Positions 26-175.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000013727.
Proteomic databases
PRIDE	Q64259.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000013727; ENSRNOP00000013727; ENSRNOG00000010258.
GeneID	24874.
KEGG	rno:24874.
UCSC	RGD:3960. rat.
Organism-specific databases
CTD	7428.
RGD	3960. Vhl.
Phylogenomic databases
eggNOG	NOG327868.
GeneTree	ENSGT00390000014353.
HOGENOM	HOG000030904.
HOVERGEN	HBG044781.
InParanoid	Q64259.
KO	K03871.
OMA	NTREPSQ.
OrthoDB	EOG4J119K.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
Genevestigator	Q64259.
GermOnline	ENSRNOG00000010258. Rattus norvegicus.
Family and domain databases
Gene3D	1.10.750.10. 1 hit. 2.60.40.780. 1 hit.
InterPro	IPR002714. Tumour_suppress_VHL-disease. IPR024048. VHL_alpha_dom. IPR024053. VHL_beta_dom. IPR022772. VHL_tumour_suppress_b/a_dom. [Graphical view]
PANTHER	PTHR15160. PTHR15160. 1 hit.
Pfam	PF01847. VHL. 1 hit. [Graphical view]
SUPFAM	SSF49468. SSF49468. 1 hit.
ProtoNet	Search...
Other
NextBio	604702.

Entry information

Entry name

VHL_RAT

Accession

Primary (citable) accession number: Q64259
Secondary accession number(s): Q64197, Q80WY8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 3, 2003
Last sequence update:	November 1, 1996
Last modified:	April 3, 2013
This is version 104 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program