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P40338

- VHL_MOUSE

UniProt

P40338 - VHL_MOUSE

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Protein

Von Hippel-Lindau disease tumor suppressor

Gene

Vhl

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

Pathwayi

GO - Molecular functioni

  1. protein complex binding Source: MGI

GO - Biological processi

  1. angiogenesis Source: MGI
  2. blood vessel endothelial cell migration Source: MGI
  3. extracellular matrix organization Source: MGI
  4. negative regulation of thymocyte apoptotic process Source: MGI
  5. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  6. neuron differentiation Source: Ensembl
  7. NLS-bearing protein import into nucleus Source: MGI
  8. proteasomal protein catabolic process Source: MGI
  9. protein catabolic process Source: MGI
  10. protein heterooligomerization Source: Ensembl
  11. protein transport Source: MGI
  12. protein ubiquitination Source: UniProtKB-UniPathway
  13. regulation of apoptotic signaling pathway Source: MGI
  14. regulation of catecholamine metabolic process Source: Ensembl
  15. regulation of thymocyte apoptotic process Source: MGI
  16. response to ethanol Source: Ensembl
  17. response to hypoxia Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiREACT_199108. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
REACT_199115. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Von Hippel-Lindau disease tumor suppressor
Alternative name(s):
pVHL
Gene namesi
Name:Vhl
Synonyms:Vhlh
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 6

Organism-specific databases

MGIiMGI:103223. Vhl.

Subcellular locationi

Cytoplasm By similarity. Membrane By similarity; Peripheral membrane protein By similarity. Nucleus By similarity
Note: Colocalizes with ADRB2 at the cell membrane.By similarity

GO - Cellular componenti

  1. cilium Source: MGI
  2. Cul2-RING ubiquitin ligase complex Source: MGI
  3. cytoplasm Source: MGI
  4. cytosol Source: Ensembl
  5. membrane Source: UniProtKB-KW
  6. mitochondrion Source: Ensembl
  7. nucleolus Source: MGI
  8. nucleoplasm Source: MGI
  9. nucleus Source: MGI
  10. VCB complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 181181Von Hippel-Lindau disease tumor suppressorPRO_0000065810Add
BLAST

Proteomic databases

MaxQBiP40338.
PaxDbiP40338.
PRIDEiP40338.

PTM databases

PhosphoSiteiP40338.

Expressioni

Developmental stagei

Expressed throughout fetal nephrogenesis, abdominal and thoracic organogenesis, and nervous system development between day 10.5 and day 16.5. In the developing lung, differential expression within the endodermally derived cuboidal epithelial lining of the terminal and respiratory bronchioles. In the developing eye, high expression in both the inner and outer neuroblastic layers of the retina and lens.1 Publication

Gene expression databases

BgeeiP40338.
ExpressionAtlasiP40338. baseline and differential.
GenevestigatoriP40338.

Interactioni

Subunit structurei

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 JADE1 (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. Interacts with CARD9 (By similarity).By similarity

Protein-protein interaction databases

BioGridi204518. 8 interactions.
IntActiP40338. 7 interactions.
STRINGi10090.ENSMUSP00000039418.

Structurei

Secondary structure

1
181
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi124 – 13613

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HV2NMR-B123-137[»]
ProteinModelPortaliP40338.
SMRiP40338. Positions 28-170.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni123 – 13210Interaction with Elongin BC complexBy similarity

Domaini

The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV].

Phylogenomic databases

eggNOGiNOG327868.
HOGENOMiHOG000030904.
HOVERGENiHBG044781.
InParanoidiP40338.
KOiK03871.
OMAiNTREPSQ.
OrthoDBiEOG7VMP7B.
PhylomeDBiP40338.
TreeFamiTF318985.

Family and domain databases

Gene3Di1.10.750.10. 1 hit.
2.60.40.780. 1 hit.
InterProiIPR002714. VHL.
IPR024048. VHL_alpha_dom.
IPR024053. VHL_beta_dom.
IPR022772. VHL_tumour_suppress_b/a_dom.
[Graphical view]
PANTHERiPTHR15160:SF0. PTHR15160:SF0. 1 hit.
PfamiPF01847. VHL. 1 hit.
[Graphical view]
SUPFAMiSSF49468. SSF49468. 1 hit.

Sequencei

Sequence statusi: Complete.

P40338-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MPRKAASPEE AAGEPGPEEM EAGRPRPVLR SVNSREPSQV IFCNRSPRVV
60 70 80 90 100
LPLWLNFDGE PQPYPILPPG TGRRIHSYRG HLWLFRDAGT HDGLLVNQTE
110 120 130 140 150
LFVPSLNVDG QPIFANITLP VYTLKERCLQ VVRSLVKPEN YRRLDIVRSL
160 170 180
YEDLEDYPSV RKDIQRLSQE HLESQHLEEE P
Length:181
Mass (Da):20,770
Last modified:February 1, 1995 - v1
Checksum:iAE8B2E8DDD3EE987
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U12570 mRNA. Translation: AAA20662.1.
S76748 mRNA. Translation: AAB33363.1.
AF513984 Genomic DNA. Translation: AAM53645.1.
BC052417 mRNA. Translation: AAH52417.2.
CCDSiCCDS20429.1.
RefSeqiNP_033533.1. NM_009507.3.
UniGeneiMm.29407.

Genome annotation databases

EnsembliENSMUST00000035673; ENSMUSP00000039418; ENSMUSG00000033933.
GeneIDi22346.
KEGGimmu:22346.
UCSCiuc009dha.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U12570 mRNA. Translation: AAA20662.1 .
S76748 mRNA. Translation: AAB33363.1 .
AF513984 Genomic DNA. Translation: AAM53645.1 .
BC052417 mRNA. Translation: AAH52417.2 .
CCDSi CCDS20429.1.
RefSeqi NP_033533.1. NM_009507.3.
UniGenei Mm.29407.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1HV2 NMR - B 123-137 [» ]
ProteinModelPortali P40338.
SMRi P40338. Positions 28-170.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 204518. 8 interactions.
IntActi P40338. 7 interactions.
STRINGi 10090.ENSMUSP00000039418.

PTM databases

PhosphoSitei P40338.

Proteomic databases

MaxQBi P40338.
PaxDbi P40338.
PRIDEi P40338.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000035673 ; ENSMUSP00000039418 ; ENSMUSG00000033933 .
GeneIDi 22346.
KEGGi mmu:22346.
UCSCi uc009dha.1. mouse.

Organism-specific databases

CTDi 7428.
MGIi MGI:103223. Vhl.

Phylogenomic databases

eggNOGi NOG327868.
HOGENOMi HOG000030904.
HOVERGENi HBG044781.
InParanoidi P40338.
KOi K03871.
OMAi NTREPSQ.
OrthoDBi EOG7VMP7B.
PhylomeDBi P40338.
TreeFami TF318985.

Enzyme and pathway databases

UniPathwayi UPA00143 .
Reactomei REACT_199108. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
REACT_199115. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

NextBioi 302621.
PROi P40338.
SOURCEi Search...

Gene expression databases

Bgeei P40338.
ExpressionAtlasi P40338. baseline and differential.
Genevestigatori P40338.

Family and domain databases

Gene3Di 1.10.750.10. 1 hit.
2.60.40.780. 1 hit.
InterProi IPR002714. VHL.
IPR024048. VHL_alpha_dom.
IPR024053. VHL_beta_dom.
IPR022772. VHL_tumour_suppress_b/a_dom.
[Graphical view ]
PANTHERi PTHR15160:SF0. PTHR15160:SF0. 1 hit.
Pfami PF01847. VHL. 1 hit.
[Graphical view ]
SUPFAMi SSF49468. SSF49468. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Expression of the Von Hippel-Lindau tumor suppressor gene, VHL, in human fetal kidney and during mouse embryogenesis."
    Kessler P.M., Vasavada S.P., Rackley R.R., Stackhouse T., Duh F.-M., Latif F., Lerman M.I., Zbar B., Williams B.R.
    Mol. Med. 1:457-466(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.
    Strain: ICR.
    Tissue: Brain.
  2. "Cloning and characterization of a mouse gene with homology to the human von Hippel-Lindau disease tumor suppressor gene: implications for the potential organization of the human von Hippel-Lindau disease gene."
    Gao J., Naglich J.G., Laidlaw J., Whaley J.M., Seizinger B.R., Kley N.
    Cancer Res. 55:743-747(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Human DNA blueprints protecting the VHL promoter and CpG island from methylation are functional in the mouse."
    Kuzmin I., Geil L., Schmidt L., Duh F.-M., Feigenbaum L., Nickerson M.L., Ma W., Stanbridge E.J., Zbar B., Lerman M.I.
    Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE.
    Strain: 129/SvJ.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6.

Entry informationi

Entry nameiVHL_MOUSE
AccessioniPrimary (citable) accession number: P40338
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: October 29, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

External Data

Dasty 3