CPLM-007319

Genbank Nucleotide ID

Von Hippel-Lindau disease tumor suppressor

Protein Synonyms/Alias

Homo sapiens (Human)

Position	Peptide	Type	References
171	QVVRSLVKPENYRRL	sumoylation	[1, 2, 3]
171	QVVRSLVKPENYRRL	ubiquitination	[4]
196	EDHPNVQKDLERLTQ	ubiquitination	[4, 5, 6, 7]

[1] Hypoxia inactivates the VHL tumor suppressor through PIASy-mediated SUMO modification.
Cai Q, Verma SC, Kumar P, Ma M, Robertson ES.
PLoS One. 2010 Mar 16;5(3):e9720. [PMID: 20300531]
[2] Ubiquitin/SUMO modification regulates VHL protein stability and nucleocytoplasmic localization.
Cai Q, Robertson ES.
PLoS One. 2010 Sep 9;5(9). [PMID: 20844582]
[3] Von Hippel-Lindau gene product directs cytokinesis: a new tumor suppressor function.
Sinha S, Mondal G, Hwang EJ, Han da W, Dutta SK, Iyer S, Karumanchi SA, Kim KI, Couch FJ, Mukhopadhyay D.
J Cell Sci. 2011 Jul 1;124(Pt 13):2132-42. [PMID: 21652636]
[4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[6] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[7] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]

Functional Description

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.

REPEAT 14 18 1.
REPEAT 19 23 2.
REPEAT 24 28 3.
REPEAT 29 33 4.
REPEAT 34 38 5.
REPEAT 39 43 6.
REPEAT 44 48 7.
REPEAT 49 53 8.
REGION 14 53 8 X 5 AA tandem repeats of G-[PAVG]-E-E-
REGION 100 155 Involved in binding to CCT complex.
REGION 157 166 Interaction with Elongin BC complex.

3D-structure; Alternative initiation; Alternative splicing; Complete proteome; Congenital erythrocytosis; Cytoplasm; Disease mutation; Membrane; Nucleus; Polymorphism; Reference proteome; Repeat; Tumor suppressor; Ubl conjugation pathway.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; TAS:Reactome.
GO:0005783; C:endoplasmic reticulum; NAS:UniProtKB.
GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
GO:0005739; C:mitochondrion; NAS:UniProtKB.
GO:0005654; C:nucleoplasm; TAS:Reactome.
GO:0008134; F:transcription factor binding; TAS:ProtInc.
GO:0004842; F:ubiquitin-protein ligase activity; TAS:Reactome.
GO:0000902; P:cell morphogenesis; NAS:UniProtKB.
GO:0043066; P:negative regulation of apoptotic process; NAS:UniProtKB.
GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc.
GO:0061428; P:negative regulation of transcription from RNA polymerase II promoter in response to hypoxia; IDA:UniProtKB.
GO:0045597; P:positive regulation of cell differentiation; NAS:UniProtKB.
GO:0045893; P:positive regulation of transcription, DNA-dependent; IMP:UniProtKB.
GO:0050821; P:protein stabilization; NAS:UniProtKB.
GO:0006508; P:proteolysis; TAS:ProtInc.

IPR002714; Tumour_suppress_VHL-disease.
IPR024048; VHL_alpha_dom.
IPR024053; VHL_beta_dom.
IPR022772; VHL_tumour_suppress_b/a_dom.