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P40338

- VHL_MOUSE

UniProt

P40338 - VHL_MOUSE

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
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    • History
      Entry version 118 (01 Oct 2014)
      Sequence version 1 (01 Feb 1995)
      Previous versions | rss
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    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 binding Source: MGI
    2. 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. proteasomal protein catabolic process Source: MGI
    8. protein catabolic process Source: MGI
    9. protein heterooligomerization Source: Ensembl
    10. protein ubiquitination Source: UniProtKB-UniPathway
    11. regulation of apoptotic signaling pathway Source: MGI
    12. regulation of catecholamine metabolic process Source: Ensembl
    13. regulation of thymocyte apoptotic process Source: MGI
    14. response to ethanol Source: Ensembl
    15. response to hypoxia Source: Ensembl

    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. cytosol Source: Ensembl
    3. membrane Source: UniProtKB-SubCell
    4. mitochondrion Source: Ensembl
    5. nucleus Source: UniProtKB-SubCell
    6. VCB complex Source: Ensembl

    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

    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

    ArrayExpressiP40338.
    BgeeiP40338.
    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. Tumour_suppress_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

    MPRKAASPEE AAGEPGPEEM EAGRPRPVLR SVNSREPSQV IFCNRSPRVV    50
    LPLWLNFDGE PQPYPILPPG TGRRIHSYRG HLWLFRDAGT HDGLLVNQTE 100
    LFVPSLNVDG QPIFANITLP VYTLKERCLQ VVRSLVKPEN YRRLDIVRSL 150
    YEDLEDYPSV RKDIQRLSQE HLESQHLEEE P 181
    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

    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

    ArrayExpressi P40338.
    Bgeei P40338.
    Genevestigatori P40338.

    Family and domain databases

    Gene3Di 1.10.750.10. 1 hit.
    2.60.40.780. 1 hit.
    InterProi IPR002714. Tumour_suppress_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

    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 1, 2014
    This is version 118 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