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VHLL Gene

protein-coding   GIFtS: 37
GCID: GC01M156268

Von Hippel-Lindau Tumor Suppressor-Like

(Previous name: VHL pseudogene)
(Previous symbol: VHLP)
  See VHLL-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)
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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, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 hypoxia. 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 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000001.10  NC_018912.2  NT_004487.20  
Regulatory elements:
   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
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Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing 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 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, 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, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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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


See VHLL Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_001004319.1  
ENSEMBL proteins: 
 ENSP00000464258  

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

Graphical View of Domain Structure for InterPro Entry Q6RSH7

ProtoNet protein and cluster: Q6RSH7


Find genes that share domains with VHLL           About GenesLikeMe


(According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

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

Phenotypes:
     1 GenomeRNAi human phenotype for VHLL:

 Decreased cilium length after  

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(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Gene Ontology (GO): 1 cellular component term:    About this table

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

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(SuperPaths according to PathCards, Pathways according to 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 QIAGEN, 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 Apr 2014 via Entrez Gene).
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    Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for VHLL
Interactions:

    Search GeneGlobe Interaction Network 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 biological process terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0001525angiogenesis ----
GO:0010498proteasomal protein catabolic process ----
GO:0016567protein ubiquitination IEA--
GO:0030198extracellular matrix organization ----
GO:0043534blood vessel endothelial cell migration ----

Find genes that share ontologies with VHLL           About GenesLikeMe



(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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(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,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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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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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™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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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

VHLL Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

VHLL Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.532378

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

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(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)
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This gene was present in the common ancestor of chordates.

Orthologs for VHLL gene from Selected species (see all 6)    About this table
Organism Taxonomic
classification
Gene Description Human
Similarity
Orthology
Type
Details
chicken
(Gallus gallus)
Aves --
Uncharacterized protein
25(a)
1 → many
12(19414582-19417180)
lizard
(Anolis carolinensis)
Reptilia --
Uncharacterized protein
34(a)
1 → many
GL343273.1(939833-946315)
zebrafish
(Danio rerio)
Actinopterygii vhl6
von Hippel-Lindau tumor suppressor
26(a)
1 → many
6(40382134-40385973) ENSDARG00000070617
        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)
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Paralogs for VHLL gene
VHL2  
1 SIMAP similar gene for VHLL using alignment to 1 protein entry:     VHLL_HUMAN:
VHL

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(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), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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Selected SNPs for VHLL (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

Site Specific Mutation Identification with PCR Assays
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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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2 diseases for VHLL:    
About MalaCards
kidney cancer    hypoxia


Find genes that share disorders with VHLL           About GenesLikeMe


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)
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PubMed articles for VHLL gene integrated from 10 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. (Mol. Cancer Res. 2004)
  2. Genome-wide association study of hematological and biochemical traits in a Japanese population. (PubMed id 20139978)1 Kamatani Y....Kamatani N. (Nat. Genet. 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. (Genome Res. 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. (Proc. Natl. Acad. Sci. U.S.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. (Diagn. Mol. Pathol. 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. (Nature 1995)

(in PubMed, OMIM, and NCBI Bookshelf)
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 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)
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Entrez Gene: 391104 HGNC: 30666 AceView: VHLL Ensembl:ENSG00000189030 euGenes: HUgn391104
ECgene: VHLL H-InvDB: VHLL

(According to HUGE)
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  --

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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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.)
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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, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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 Browse ProSpec Recombinant Proteins
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 Browse ESI BIO Cell Lines and PureStem Progenitors for VHLL
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 SwitchGear 3'UTR luciferase reporter plasmids for VHLL
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 Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat VHLL
 Browse compounds at ApexBio
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 genOway: Develop your customized and physiologically relevant rodent model for VHLL
 antibodies-online antibodies for VHLL (9 products)
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 antibodies-online proteins for VHLL (10 products)
       
GeneCards Homepage - Last full update: 7 May 2014 - Incrementals: 9 May 2014 , 2 Jun 2014 , 26 Jun 2014 , 30 Jun 2014 , 21 Aug 2014 , 8 Sep 2014 , 7 Oct 2014

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