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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

VHLL Gene

protein-coding   GIFtS: 38
GCID: GC01M156268

Von Hippel-Lindau Tumor Suppressor-Like

(Previous name: VHL pseudogene)
(Previous symbol: VHLP)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
Von Hippel-Lindau Tumor Suppressor-Like1 2
VHLP1 2
VHL Pseudogene1 2
VLP2 3
VHL-Like Protein2 3
Von Hippel-Lindau-Like Protein2

External Ids:    HGNC: 306661   Entrez Gene: 3911042   Ensembl: ENSG000001890307   UniProtKB: Q6RSH73   

Export aliases for VHLL gene to outside databases

Previous GC identifers: GC01M153081 GC01M154535 GC01M127628


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for VHLL Gene:
Von Hippel-Lindau (VHL) tumor suppressor protein is a component of an E3 ubiquitin ligase complex that selectively
ubiquitinates the alpha subunit of the hypoxia-inducible factor (HIF) transcription factor for
proteasome-mediated degradation. Inactivation of VHL causes VHL disease and sporadic kidney cancer. This gene
encodes a VHL homolog that lacks one of two key domains necessary for VHL function. This gene may contribute to
the regulation of oxygen homeostasis and neovascularization during placenta development. This gene is intronless,
and can also be interpreted as a retrotransposed pseudogene of the VHL locus located on chromosome 3. However,
the protein is represented in this RefSeq due to evidence in PMID:14757845 that strongly suggests it is
translated. The same publication also indicates that this protein binds HIF alpha but fails to recruit the E3
ubiquitin ligase complex, and it therefore functions as a dominant-negative VHL protein and a protector of HIF
alpha. (provided by RefSeq, Jan 2010)

GeneCards Summary for VHLL Gene: 
VHLL (von Hippel-Lindau tumor suppressor-like) is a protein-coding gene. Diseases associated with VHLL include kidney cancer, and von hippel-lindau disease. An important paralog of this gene is VHL.

UniProtKB/Swiss-Prot: VHLL_HUMAN, Q6RSH7
Function: Functions as a dominant-negative VHL to serve as a protector of HIFalpha




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000001.10  NC_018912.2  NT_004487.19  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the VHLL gene promoter:
         SRF   SRF (504 AA)   Nkx2-5   CUTL1   YY1   Max   HOXA5   c-Myc   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidVHLL promoter sequence
   Search SABiosciences Chromatin IP Primers for VHLL

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat VHLL


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 1q22   Ensembl cytogenetic band:  1q22   HGNC cytogenetic band: 1q22

VHLL Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
VHLL gene location

GeneLoc information about chromosome 1         GeneLoc Exon Structure

GeneLoc location for GC01M156268:  view genomic region     (about GC identifiers)

Start:
156,268,415 bp from pter      End:
156,269,428 bp from pter
Size:
1,014 bases      Orientation:
minus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: VHLL_HUMAN, Q6RSH7 (See protein sequence)
Recommended Name: Von Hippel-Lindau-like protein  
Size: 139 amino acids; 15781 Da
Subunit: Interacts via the beta domain with the ODD domain of HIF1A This interaction is independent of prolyl
hydroxylation of HIF1A
Miscellaneous: Has little or no E3 ubiquitin ligase activity as it lacks the alpha domain required for nucleating
the multiprotein E3 ubiquitin ligase complex
Secondary accessions: A1L4M4

Explore the universe of human proteins at neXtProt for VHLL: NX_Q6RSH7

Explore proteomics data for VHLL at MOPED 

Post-translational modifications:

  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_Q6RSH7

  • VHLL Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    VHLL Protein Expression
    REFSEQ proteins: NP_001004319.1  
    ENSEMBL proteins: 
     ENSP00000464258  

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    Gene Ontology (GO): 1 cellular component term (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IEA--

    VHLL for ontologies           About GeneDecksing



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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    3 InterPro protein domains:
     IPR024053 VHL_beta_dom
     IPR002714 Tumour_suppress_VHL-disease
     IPR022772 VHL_tumour_suppress_b/a_dom

    Graphical View of Domain Structure for InterPro Entry Q6RSH7

    ProtoNet protein and cluster: Q6RSH7


    VHLL for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: VHLL_HUMAN, Q6RSH7
    Function: Functions as a dominant-negative VHL to serve as a protector of HIFalpha

         Gene Ontology (GO): 1 molecular function term (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005515protein binding ----
         
    VHLL for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for VHLL:
     Decreased cilium length after  

    Animal Models:
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    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene).
    About This Section



    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for VHLL

    1 Interacting protein for VHLL (Q6RSH73) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HIF1AQ166653I2D: score=2 
    About this table

    Gene Ontology (GO): 5/6 biological process terms (GO ID links to tree view) (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001525angiogenesis IEA--
    GO:0010498proteasomal protein catabolic process IEA--
    GO:0016567protein ubiquitination IEA--
    GO:0030163protein catabolic process ----
    GO:0030198extracellular matrix organization IEA--

    VHLL for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section
    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for VHLL

    Search CenterWatch for drugs/clinical trials and news about VHLL

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
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    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for VHLL gene: 
    NM_001004319.2  

    Unigene Cluster for VHLL:

    Von Hippel-Lindau tumor suppressor-like
    Hs.532378
    Unigene Representative Sequence: NM_001004319
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000339922(uc001fok.3)
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    Inhib. RNA
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    Additional mRNA sequence: 

    AY494836.1 BC130596.1 BC130598.1 

    1 DOTS entry:

    DT.102819423 

    3 AceView cDNA sequences:

    NM_001004319 AY494836 AA324790 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    VHLL expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ATAAGCTTCT
    VHLL Expression
    About this image


    See VHLL Protein Expression from SPIRE MOPED and PaxDB
    SOURCE GeneReport for Unigene cluster: Hs.532378

    UniProtKB/Swiss-Prot: VHLL_HUMAN, Q6RSH7
    Tissue specificity: Abundantly expressed in the placenta

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    In Situ
    Assay Products:
     

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for VHLL

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

    This gene was present in the common ancestor of chordates.

    Orthologs for VHLL gene from 3/7 species (see all 7)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    chicken
    (Gallus gallus)
    Aves VHL6
    Uncharacterized protein
    27(a)
    1 → many
    12(19414582-19417180)
    lizard
    (Anolis carolinensis)
    Reptilia --
    --
    34(a)
    1 → many
    GL343273.1(939833-946315)
    zebrafish
    (Danio rerio)
    Actinopterygii vhl6
    vhll6
    von Hippel-Lindau tumor suppressor like
    25(a)
    21(a)
    1 ↔ many
    possible ortholog
    6(40382134-40385973)
    4(12031164-12032545)
            Species with no ortholog for VHLL

    ENSEMBL Gene Tree for VHLL (if available)
    TreeFam Gene Tree for VHLL (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for VHLL gene
    VHL2  
    1 SIMAP similar gene for VHLL using alignment to 1 protein entry:     VHLL_HUMAN:
    VHL

    VHLL for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/104 SNPs in VHLL are shown (see all 104)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 1 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1886211631,2
    --127628045(+) GTTGTA/GTTTAA 1 -- ds50010--------
    rs2019888801,2
    C--156268038(+) AAAAA-/ATTCTT 1 -- ds50010--------
    rs599183111,2
    C--156271359(+) TTTTTT/-CTTTT 1 -- us2k11Minor allele frequency- -:0.50CSA 2
    rs1394189601,2
    --162768855(+) AAGAGC/TGAAAC 1 -- ds50010--------
    rs1439754761,2
    --162768885(+) AAATTC/TTTCAG 1 -- ds50010--------
    rs1459490131,2
    --162768970(+) TCTGTC/TGCCCA 1 -- ds50010--------
    rs1919052081,2
    --162768971(+) CTGTCA/GCCCAG 1 -- ds50010--------
    rs1825282651,2
    --162769079(+) GACATA/GTGCCA 1 -- ds50010--------
    rs1868951681,2
    --162769122(+) GGAGAC/TGGGTT 1 -- ds50010--------
    rs1913348731,2
    --162769124(+) AGACGA/GGTTTC 1 -- ds50010--------

    HapMap Linkage Disequilibrium report for VHLL (156268415 - 156269428 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for VHLL:    About this table     
    Variant IDTypeSubtypePubMed ID
    nsv509524CNV Insertion20534489

    SABiosciences Cancer Mutation PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    4 diseases for VHLL:    About MalaCards
    kidney cancer    von hippel-lindau disease    hypoxia    endotheliitis


    VHLL for disorders           About GeneDecksing


    Export disorders for VHLL gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for VHLL gene integrated from 9 sources:
    (articles sorted by number of sources associating them with VHLL)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Molecular cloning and characterization of the von Hippel-Lindau-like protein. (PubMed id 14757845)1, 2, 3 Qi H.... Ohh M. (2004)
    2. Genome-wide association study of hematological and bi ochemical traits in a Japanese population. (PubMed id 20139978)1 Kamatani Y....Kamatani N. (2010)
    3. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)2 Gerhard D.S....Malek J. (2004)
    4. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. (PubMed id 12477932)1 Strausberg R.L....Marra M.A. (2002)
    5. Processed pseudogene from the von Hippel-Lindau disease gene is located on human chromosome 1. (PubMed id 10475385)1 Bradley J.F. and Rothberg P.G. (1999)
    6. Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence. (PubMed id 7566098)1 Adams M.D....White O. (1995)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 391104 HGNC: 30666 AceView: VHLL Ensembl:ENSG00000189030 euGenes: HUgn391104
    ECgene: VHLL H-InvDB: VHLL

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for VHLL Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for VHLL Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for VHLL gene:
    Search GeneIP for patents involving VHLL

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0 and Sirion Biotech, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Sirion Biotech, Cell lines from GenScript, and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
    About This Section

     
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    GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 4 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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