Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P40337 (VHL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 168. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Von Hippel-Lindau disease tumor suppressor
Alternative name(s):
Protein G7
pVHL
Gene names
Name:VHL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length213 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.11 Ref.13 Ref.20

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 AND CUL2. Isoform 1 and isoform 3 interact with LIMD1 (via LIM zinc-binding 2), AJUBA (via LIM domains) and WTIP (via LIM domains). Interacts with EPAS1. Interacts with CARD9. Ref.8 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21

Subcellular location

Isoform 1: Cytoplasm. Membrane; Peripheral membrane protein. Nucleus. Note: Found predominantly in the cytoplasm and with less amounts nuclear or membrane-associated. Colocalizes with ADRB2 at the cell membrane. Ref.11 Ref.20

Isoform 3: Cytoplasm. Nucleus. Note: Equally distributed between the nucleus and the cytoplasm but not membrane-associated. Ref.11 Ref.20

Tissue specificity

Expressed in the adult and fetal brain and kidney.

Developmental stage

At 4-10 weeks pc, strong expression in the developing central nervous system, kidneys, testis and lung. Differentially expressed within renal tubules. Ref.7

Domain

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

Involvement in disease

Pheochromocytoma (PCC) [MIM:171300]: A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

von Hippel-Lindau disease (VHLD) [MIM:193300]: VHLD is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign neoplasms, most frequently retinal, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma, and pancreatic tumors. VHL type 1 is without pheochromocytoma, type 2 is with pheochromocytoma. VHL type 2 is further subdivided into types 2A (pheochromocytoma, retinal angioma, and hemangioblastomas without renal cell carcinoma and pancreatic cyst) and 2B (pheochromocytoma, retinal angioma, and hemangioblastomas with renal cell carcinoma and pancreatic cyst).
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.12 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Ref.40 Ref.41 Ref.42 Ref.49

Erythrocytosis, familial, 2 (ECYT2) [MIM:263400]: An autosomal recessive disorder characterized by an increase in serum red blood cell mass, hypersensitivity of erythroid progenitors to erythropoietin, increased erythropoietin serum levels, and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.45 Ref.48

Renal cell carcinoma (RCC) [MIM:144700]: Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.43

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentCytoplasm
Membrane
Nucleus
   Coding sequence diversityAlternative initiation
Alternative splicing
Polymorphism
   DiseaseCongenital erythrocytosis
Disease mutation
Tumor suppressor
   DomainRepeat
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: Ensembl

blood vessel endothelial cell migration

Inferred from electronic annotation. Source: Ensembl

cell morphogenesis

Non-traceable author statement Ref.17. Source: UniProtKB

cellular response to hypoxia

Traceable author statement. Source: Reactome

extracellular matrix organization

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Non-traceable author statement Ref.17. Source: UniProtKB

negative regulation of cell proliferation

Traceable author statement Ref.10. Source: ProtInc

negative regulation of thymocyte apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Traceable author statement PubMed 7660122. Source: ProtInc

negative regulation of transcription from RNA polymerase II promoter in response to hypoxia

Inferred from direct assay Ref.15. Source: UniProtKB

neuron differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell differentiation

Non-traceable author statement Ref.17. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 17973242. Source: UniProtKB

proteasomal protein catabolic process

Inferred from electronic annotation. Source: Ensembl

protein heterooligomerization

Inferred from electronic annotation. Source: Ensembl

protein stabilization

Non-traceable author statement Ref.17. Source: UniProtKB

protein ubiquitination

Inferred from mutant phenotype Ref.17. Source: UniProtKB

proteolysis

Traceable author statement PubMed 10353251. Source: ProtInc

regulation of apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

regulation of catecholamine metabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of transcription from RNA polymerase II promoter in response to hypoxia

Traceable author statement. Source: Reactome

regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 15824735. Source: BHF-UCL

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to stress

Non-traceable author statement Ref.17. Source: UniProtKB

   Cellular_componentVCB complex

Inferred from electronic annotation. Source: Ensembl

cytosol

Traceable author statement. Source: Reactome

endoplasmic reticulum

Non-traceable author statement Ref.17. Source: UniProtKB

intermediate filament cytoskeleton

Inferred from direct assay. Source: HPA

membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Non-traceable author statement Ref.17. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionenzyme binding

Inferred from physical interaction Ref.15. Source: UniProtKB

transcription factor binding

Inferred from physical interaction Ref.15. Source: UniProtKB

ubiquitin-protein ligase activity

Traceable author statement. Source: Reactome

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]
Isoform 1 (identifier: P40337-1)

Also known as: VHL30; VHLp24(MPR);

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: Major isoform.
Isoform 2 (identifier: P40337-2)

The sequence of this isoform differs from the canonical sequence as follows:
     114-154: Missing.
Isoform 3 (identifier: P40337-3)

Also known as: VHL19; VHLp18(MEA);

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: Missing.
Note: Produced by alternative initiation at Met-54 of isoform 1.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 213213Von Hippel-Lindau disease tumor suppressor
PRO_0000065809

Regions

Repeat14 – 1851
Repeat19 – 2352
Repeat24 – 2853
Repeat29 – 3354
Repeat34 – 3855
Repeat39 – 4356
Repeat44 – 4857
Repeat49 – 5358
Region14 – 53408 X 5 AA tandem repeats of G-[PAVG]-E-E-[DAYSLE]
Region100 – 15556Involved in binding to CCT complex
Region157 – 16610Interaction with Elongin BC complex

Natural variations

Alternative sequence1 – 5353Missing in isoform 3.
VSP_007740
Alternative sequence114 – 15441Missing in isoform 2.
VSP_004488
Natural variant251P → L in pheochromocytoma. Ref.39 Ref.46 Ref.50
Corresponds to variant rs35460768 [ dbSNP | Ensembl ].
VAR_034562
Natural variant381S → P in VHLD; type II. Ref.34
VAR_005670
Natural variant521E → K in VHLD; type I. Ref.38
VAR_005671
Natural variant631L → P in pheochromocytoma. Ref.39
VAR_034987
Natural variant641R → P in pheochromocytoma. Ref.39
VAR_034988
Natural variant651S → A in pheochromocytoma. Ref.44
VAR_034989
Natural variant651S → L in VHLD; type I. Ref.33 Ref.38
VAR_005672
Natural variant651S → W in VHLD; type I. Ref.33 Ref.37
VAR_005673
Natural variant66 – 738Missing in VHLD; type I.
VAR_005674
Natural variant681S → W in pheochromocytoma and VHLD; type II. Ref.36 Ref.44
VAR_005675
Natural variant701E → K in VHLD; type I. Ref.38
VAR_005676
Natural variant741V → G in VHLD; type I-II. Ref.33
Corresponds to variant rs5030803 [ dbSNP | Ensembl ].
VAR_005677
Natural variant751Missing in VHLD. Ref.1
VAR_034990
Natural variant761F → I in VHLD; type I. Ref.33
VAR_005679
Natural variant761F → L in VHLD; type I. Ref.34
VAR_005680
Natural variant761F → S in VHLD; type I. Ref.37
VAR_005681
Natural variant761Missing in VHLD; type I; common mutation. Ref.33
VAR_005678
Natural variant781N → H in VHLD; type I. Ref.33
VAR_005682
Natural variant781N → S in VHLD; type I; common mutation. Ref.33
Corresponds to variant rs5030804 [ dbSNP | Ensembl ].
VAR_005683
Natural variant781N → T in VHLD; type I. Ref.33
VAR_005684
Natural variant791R → P in VHLD.
VAR_005685
Natural variant801S → I in VHLD; type I. Ref.33
VAR_005686
Natural variant801S → N in pheochromocytoma and VHLD; type I. Ref.33 Ref.38 Ref.44
Corresponds to variant rs5030805 [ dbSNP | Ensembl ].
VAR_005688
Natural variant801S → R in VHLD; type I. Ref.33 Ref.38
VAR_005687
Natural variant811P → S in VHLD; type I. Ref.33 Ref.37
Corresponds to variant rs5030806 [ dbSNP | Ensembl ].
VAR_005689
Natural variant82 – 843Missing in VHLD.
VAR_005691
Natural variant821R → P in VHLD; type I.
VAR_005690
Natural variant841V → L in VHLD; type II and type 2C. Ref.30 Ref.49
Corresponds to variant rs5030827 [ dbSNP | Ensembl ].
VAR_005692
Natural variant861P → A in VHLD; type I. Ref.33
VAR_005693
Natural variant861P → H in VHLD.
VAR_008097
Natural variant861P → L in VHLD; type I. Ref.33
VAR_005694
Natural variant861P → R in VHLD; type I. Ref.37
VAR_005695
Natural variant861P → S in VHLD. Ref.38 Ref.50
VAR_005696
Natural variant881W → R in VHLD; type I. Ref.33 Ref.37
VAR_005697
Natural variant881W → S in VHLD; type I. Ref.33 Ref.38
VAR_005698
Natural variant891L → H in lung cancer.
VAR_005699
Natural variant891L → P in VHLD; type I. Ref.33
Corresponds to variant rs5030807 [ dbSNP | Ensembl ].
VAR_005700
Natural variant911F → L in cerebellar hemangioblastoma. Ref.38
VAR_005701
Natural variant92 – 976Missing in VHLD; type I.
VAR_005702
Natural variant931G → C in pheochromocytoma and VHLD; type II. Ref.40 Ref.44
Corresponds to variant rs5030808 [ dbSNP | Ensembl ].
VAR_005703
Natural variant931G → D in VHLD.
VAR_005704
Natural variant931G → S in pheochromocytoma and VHLD; type II. Ref.44
Corresponds to variant rs5030808 [ dbSNP | Ensembl ].
VAR_005705
Natural variant961Q → P in VHLD; type I. Ref.32
VAR_005706
Natural variant981Y → H in pheochromocytoma and VHLD; type II. Ref.44
Corresponds to variant rs5030809 [ dbSNP | Ensembl ].
VAR_005707
Natural variant1011L → G in VHLD; type I; requires 2 nucleotide substitutions. Ref.37
VAR_005708
Natural variant1011L → R in VHLD; type I. Ref.33
VAR_005709
Natural variant1041G → A in cerebellar hemangioblastoma. Ref.38
VAR_005710
Natural variant1051T → P in VHLD; type I. Ref.38
VAR_005711
Natural variant1061G → D in lung cancer.
VAR_005712
Natural variant1071R → G in pheochromocytoma. Ref.44
VAR_034991
Natural variant1071R → P in VHLD; type I. Ref.37
VAR_005713
Natural variant1101H → Y. Ref.5
Corresponds to variant rs17855706 [ dbSNP | Ensembl ].
VAR_055087
Natural variant1111S → C in VHLD; type II.
VAR_005714
Natural variant1111S → N in VHLD; type I. Ref.33 Ref.37
VAR_005715
Natural variant1111S → R in VHLD; type I. Ref.33
VAR_005716
Natural variant1121Y → H in VHLD; type IIA.
VAR_005717
Natural variant1121Y → N in VHLD. Ref.41
VAR_034992
Natural variant1141G → C in VHLD; type II. Ref.33
VAR_005718
Natural variant1141G → R in VHLD; type I-II.
VAR_005719
Natural variant1141G → S in VHLD; type II. Ref.31
VAR_005720
Natural variant1151H → Q in VHLD; type II. Ref.38
VAR_005723
Natural variant1151H → R in VHLD; type II.
Corresponds to variant rs5030812 [ dbSNP | Ensembl ].
VAR_008098
Natural variant1151H → Y in VHLD; type I. Ref.33
Corresponds to variant rs5030811 [ dbSNP | Ensembl ].
VAR_005722
Natural variant1161L → V in VHLD. Ref.32
VAR_005724
Natural variant1171W → C in VHLD; type I. Ref.33 Ref.37 Ref.38
VAR_005725
Natural variant1181L → P in VHLD; type I. Ref.33 Ref.38
Corresponds to variant rs5030830 [ dbSNP | Ensembl ].
VAR_005726
Natural variant1181L → R in VHLD. Ref.32
VAR_005727
Natural variant1191F → L in pheochromocytoma and VHLD; type II. Ref.44
VAR_005728
Natural variant1191F → S in VHLD; type II. Ref.31
VAR_005729
Natural variant1211D → G in VHLD; type I. Ref.33
Corresponds to variant rs5030832 [ dbSNP | Ensembl ].
VAR_005730
Natural variant1221A → I in pheochromocytoma; requires 2 nucleotide substitutions. Ref.44
VAR_034993
Natural variant1261D → Y in ECYT2. Ref.48
VAR_034994
Natural variant1281L → F in VHLD; type II.
VAR_005731
Natural variant1291L → LE in VHLD.
VAR_005732
Natural variant1301V → L in ECYT2 and VHLD; type I. Ref.33 Ref.38 Ref.48
VAR_005733
Natural variant1311N → K in VHLD; type I. Ref.38
VAR_005734
Natural variant1311N → T in VHLD; type I. Ref.37
VAR_005735
Natural variant1351L → F in hemangioblastoma. Ref.25
VAR_034995
Natural variant1361F → C in pheochromocytoma and VHLD; type II. Ref.44
Corresponds to variant rs5030833 [ dbSNP | Ensembl ].
VAR_005737
Natural variant1361F → S in VHLD. Ref.38
VAR_005736
Natural variant1361F → Y in VHLD.
VAR_008099
Natural variant1431D → E in VHLD; type II. Ref.31
VAR_005738
Natural variant1451Q → H in VHLD.
VAR_008100
Natural variant1471I → T in pheochromocytoma. Ref.39
VAR_034996
Natural variant1481Missing in VHLD; type I.
VAR_005739
Natural variant1491A → T in VHLD; type II. Ref.35
VAR_005740
Natural variant1541P → L in VHLD; type II.
VAR_005741
Natural variant1551V → G in VHLD; type II. Ref.40
VAR_005742
Natural variant1551V → M in VHLD; with RCC.
VAR_008101
Natural variant1561Y → C in pheochromocytoma and VHLD; type I. Ref.38 Ref.44 Ref.46
VAR_005743
Natural variant1561Y → D in VHLD; type I. Ref.38
VAR_005744
Natural variant1561Y → N in pheochromocytoma. Ref.44
VAR_034997
Natural variant1571T → I in VHLD; type II. Ref.38 Ref.40
VAR_005746
Natural variant1571T → TF in VHLD; type I.
VAR_005747
Natural variant1581L → P in VHLD; type I-II; abolishes release from chaperonin complex and the interaction with Elongin BC complex. Ref.12 Ref.33 Ref.38
VAR_005748
Natural variant1581L → V in VHLD; type I. Ref.33
VAR_005749
Natural variant1591K → E in VHLD; type II.
VAR_005750
Natural variant1611R → G in VHLD; type II.
Corresponds to variant rs5030818 [ dbSNP | Ensembl ].
VAR_005753
Natural variant1611R → P in pheochromocytoma and VHLD; type I. Ref.33 Ref.44
VAR_005752
Natural variant1611R → Q in pheochromocytoma and VHLD; type II. Ref.38 Ref.44
VAR_005751
Natural variant1621C → F in VHLD; type I; No effect on interaction with HIF1A nor on HIF1A degradation. Ref.13 Ref.33 Ref.34 Ref.37
VAR_005754
Natural variant1621C → R in VHLD; type I. Ref.33
VAR_005755
Natural variant1621C → W in VHLD; type I-II. Ref.33 Ref.38
Corresponds to variant rs5030622 [ dbSNP | Ensembl ].
VAR_005756
Natural variant1621C → Y in VHLD; type I. Ref.33
VAR_005757
Natural variant1631L → P in RCC; with paraneoplastic erythrocytosis; inhibits binding to HIF1AN. Ref.6 Ref.43
Corresponds to variant rs28940297 [ dbSNP | Ensembl ].
VAR_034998
Natural variant1641Q → H in VHLD.
VAR_008102
Natural variant1641Q → R in VHLD; type II. Ref.31 Ref.33
VAR_005758
Natural variant1661V → D in VHLD; with RCC.
VAR_008103
Natural variant1661V → F in VHLD; type IIA. Ref.32 Ref.38
VAR_005759
Natural variant1671R → G in VHLD; type I-II. Ref.37
VAR_005760
Natural variant1671R → Q in pheochromocytoma and VHLD; type II; common mutation. Ref.33 Ref.38 Ref.44
Corresponds to variant rs5030821 [ dbSNP | Ensembl ].
VAR_005761
Natural variant1671R → W in pheochromocytoma and VHLD; type II; common mutation. Ref.30 Ref.33 Ref.38 Ref.44
Corresponds to variant rs5030820 [ dbSNP | Ensembl ].
VAR_005762
Natural variant1701V → D in VHLD; type II. Ref.32
VAR_005763
Natural variant1701V → F in VHLD; type II.
VAR_005764
Natural variant1701V → G in VHLD; type I. Ref.33 Ref.38
VAR_005765
Natural variant1751Y → D in VHLD; type I. Ref.37
VAR_005766
Natural variant1761R → W in VHLD.
VAR_008104
Natural variant1771R → RLRVKPE in VHLD; type I.
VAR_005767
Natural variant1781L → P in VHLD; type I-II; common mutation. Ref.33
VAR_005768
Natural variant1781L → Q in VHLD; type II.
Corresponds to variant rs5030822 [ dbSNP | Ensembl ].
VAR_005769
Natural variant1801I → V in VHLD; type I. Ref.33
VAR_005770
Natural variant1841L → P in VHLD; type I. Ref.33 Ref.37
VAR_005772
Natural variant1841L → R in VHLD; type I. Ref.33
VAR_005771
Natural variant1861E → K in VHLD; type I. Ref.33 Ref.37
VAR_005773
Natural variant1861Missing in VHLD. Ref.32
VAR_005774
Natural variant1881L → P in VHLD; type I-II. Ref.38
VAR_005775
Natural variant1881L → Q in VHLD; type I. Ref.33
VAR_005776
Natural variant1881L → V in ECYT2, pheochromocytoma and VHLD; type IIA. Ref.44 Ref.45
Corresponds to variant rs5030824 [ dbSNP | Ensembl ].
VAR_005777
Natural variant1911H → D in ECYT2. Ref.45
Corresponds to variant rs28940301 [ dbSNP | Ensembl ].
VAR_034999
Natural variant1921P → S in ECYT2. Ref.45
Corresponds to variant rs28940300 [ dbSNP | Ensembl ].
VAR_035000
Natural variant1981L → Q in pheochromocytoma. Ref.44
VAR_035001
Natural variant1981L → R in ECY2 and VHLD; type II.
VAR_005778
Natural variant2001R → W in ECYT2 and VHLD; type I. Ref.33 Ref.38 Ref.45 Ref.48
Corresponds to variant rs28940298 [ dbSNP | Ensembl ].
VAR_005779

Experimental info

Mutagenesis981Y → N: No interaction with HIF1A. No HIF1A degradation. Ref.13

Secondary structure

............................... 213
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (VHL30) (VHLp24(MPR)) [UniParc].

Last modified December 15, 1998. Version 2.
Checksum: BA5D6765FBC16EA7

FASTA21324,153
        10         20         30         40         50         60 
MPRRAENWDE AEVGAEEAGV EEYGPEEDGG EESGAEESGP EESGPEELGA EEEMEAGRPR 

        70         80         90        100        110        120 
PVLRSVNSRE PSQVIFCNRS PRVVLPVWLN FDGEPQPYPT LPPGTGRRIH SYRGHLWLFR 

       130        140        150        160        170        180 
DAGTHDGLLV NQTELFVPSL NVDGQPIFAN ITLPVYTLKE RCLQVVRSLV KPENYRRLDI 

       190        200        210 
VRSLYEDLED HPNVQKDLER LTQERIAHQR MGD 

« Hide

Isoform 2 [UniParc].

Checksum: 46E2C22E8C98393D
Show »

FASTA17219,654
Isoform 3 (VHL19) (VHLp18(MEA)) [UniParc].

Checksum: 2644C3B8C3A87D64
Show »

FASTA16018,532

References

« Hide 'large scale' references
[1]"Identification of the von Hippel-Lindau disease tumor suppressor gene."
Latif F., Tory K., Gnarra J., Yao M., Duh F.-M., Orcutt M.L., Stackhouse T., Kuzmin I., Modi W., Geil L., Schmidt L., Zhou F., Li H., Wei M.H., Chen F., Glenn G., Choyke P., Walther M.M. expand/collapse author list , Weng Y., Duan D.-S.R., Dean M., Glavac D., Richards F.M., Crossey P.A., Ferguson-Smith M.A., le Paslier D., Chumakov I., Cohen D., Chinault A.C., Maher E.R., Linehan W.M., Zbar B., Lerman M.I.
Science 260:1317-1320(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANTS VHLD ILE-75 DEL AND ARG-82--84-VAL DEL, ALTERNATIVE SPLICING (ISOFORM 2).
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] (ISOFORM 2), VARIANT TYR-110.
[6]Wenzel M.
Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 33-67 AND 156-213, VARIANT PRO-163.
Tissue: Renal cell carcinoma.
[7]"Expression of the von Hippel-Lindau disease tumour suppressor gene during human embryogenesis."
Richards F.M., Schofield P.N., Fleming S., Maher E.R.
Hum. Mol. Genet. 5:639-644(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
[8]"The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins."
Pause A., Lee S., Worrel R., Chen D.Y.T., Burgess W.H., Linehan W.M., Klausner R.D.
Proc. Natl. Acad. Sci. U.S.A. 94:2156-2161(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CUL2.
[9]"A second major native von Hippel-Lindau gene product, initiated from an internal translation start site, functions as a tumor suppressor."
Schoenfeld A., Davidowitz E.J., Burk R.D.
Proc. Natl. Acad. Sci. U.S.A. 95:8817-8822(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 3).
[10]"Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C."
Kibel A., Iliopoulos O., DeCaprio J.A., Kaelin W.G. Jr.
Science 269:1444-1446(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ELONGIN BC COMPLEX.
[11]"pVHL19 is a biologically active product of the von Hippel-Lindau gene arising from internal translation initiation."
Iliopoulos O., Ohh M., Kaelin W.G. Jr.
Proc. Natl. Acad. Sci. U.S.A. 95:11661-11666(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION (ISOFORM 3), SUBCELLULAR LOCATION.
[12]"Formation of the VHL-elongin BC tumor suppressor complex is mediated by the chaperonin TRiC."
Feldman D.E., Thulasiraman V., Ferreyra R.G., Frydman J.
Mol. Cell 4:1051-1061(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CHAPERONES, VARIANT VHLD PRO-158.
[13]"Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von Hippel-Lindau tumor suppressor protein."
Tanimoto K., Makino Y., Pereira T., Poellinger L.
EMBO J. 19:4298-4309(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIF1A, FUNCTION, CHARACTERIZATION OF VARIANT PHE-162, MUTAGENESIS OF TYR-98.
[14]"Muf1, a novel elongin BC-interacting leucine-rich repeat protein that can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase."
Kamura T., Burian D., Yan Q., Schmidt S.L., Lane W.S., Querido E., Branton P.E., Shilatifard A., Conaway R.C., Conaway J.W.
J. Biol. Chem. 276:29748-29753(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN E3 UBIQUITIN-PROTEIN LIGASE COMPLEXES.
[15]"FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity."
Mahon P.C., Hirota K., Semenza G.L.
Genes Dev. 15:2675-2686(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIF1AN; HIF1A AND HISTONE DEACETYLASES.
Tissue: Brain.
[16]"Ubiquitination of a novel deubiquitinating enzyme requires direct binding to von Hippel-Lindau tumor suppressor protein."
Li Z., Na X., Wang D., Schoen S.R., Messing E.M., Wu G.
J. Biol. Chem. 277:4656-4662(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH USP33.
[17]"The von Hippel-Lindau tumor suppressor stabilizes novel plant homeodomain protein Jade-1."
Zhou M.I., Wang H., Ross J.J., Kuzmin I., Xu C., Cohen H.T.
J. Biol. Chem. 277:39887-39898(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH JADE1.
[18]"The TRC8 hereditary kidney cancer gene suppresses growth and functions with VHL in a common pathway."
Gemmill R.M., Bemis L.T., Lee J.P., Sozen M.A., Baron A., Zeng C., Erickson P.F., Hooper J.E., Drabkin H.A.
Oncogene 21:3507-3516(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RNF139.
[19]"Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role for residues C-terminal to the hydroxylacceptor proline."
Furlow P.W., Percy M.J., Sutherland S., Bierl C., McMullin M.F., Master S.R., Lappin T.R., Lee F.S.
J. Biol. Chem. 284:9050-9058(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EPAS1.
[20]"Oxygen-regulated beta(2)-adrenergic receptor hydroxylation by EGLN3 and ubiquitylation by pVHL."
Xie L., Xiao K., Whalen E.J., Forrester M.T., Freeman R.S., Fong G., Gygi S.P., Lefkowitz R.J., Stamler J.S.
Sci. Signal. 2:RA33-RA33(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ADRB2, SUBCELLULAR LOCATION, FUNCTION.
[21]"The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity."
Foxler D.E., Bridge K.S., James V., Webb T.M., Mee M., Wong S.C., Feng Y., Constantin-Teodosiu D., Petursdottir T.E., Bjornsson J., Ingvarsson S., Ratcliffe P.J., Longmore G.D., Sharp T.V.
Nat. Cell Biol. 14:201-208(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LIMD1; AJUBA AND WTIP, IDENTIFICATION IN A COMPLEX WITH LIMD1; EGLN1/PHD2; TCEB2 AND CUL2.
[22]"Structure of an HIF-1alpha-pVHL complex: hydroxyproline recognition in signaling."
Min J.-H., Yang H., Ivan M., Gertler F., Kaelin W.G. Jr., Pavletich N.P.
Science 296:1886-1889(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 54-213 IN COMPLEX WITH 556-575 OF HIF1A; TCEB1 AND TCEB2.
[23]"Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL."
Hon W.-C., Wilson M.I., Harlos K., Claridge T.D.W., Schofield C.J., Pugh C.W., Maxwell P.H., Ratcliffe P.J., Stuart D.I., Jones E.Y.
Nature 417:975-978(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 52-213 IN COMPLEX WITH 549-582 OF HIF1A; 17-112 OF TCEB1 AND TCEB2.
[24]"Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor suppressor function."
Stebbins C.E., Kaelin W.G. Jr., Pavletich N.P.
Science 284:455-461(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 54-213 IN COMPLEX WITH 17-112 OF TCEB1 AND TCEB2.
[25]"Somatic mutations of the von Hippel-Lindau tumor suppressor gene in sporadic central nervous system hemangioblastomas."
Kanno H., Kondo K., Ito S., Yamamoto I., Fujii S., Torigoe S., Sakai N., Hosaka M., Shuin T., Yao M.
Cancer Res. 54:4845-4847(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HEMANGIOBLASTOMA PHE-135.
[26]"Molecular analysis of the von Hippel-Lindau disease tumor suppressor gene in human lung cancer cell lines."
Sekido Y., Bader S., Latif F., Gnarra J.R., Gazdar A.F., Linehan W.M., Zbar B., Lerman M.I., Minna J.D.
Oncogene 9:1599-1604(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS IN LUNG CANCER.
[27]"Identification of intragenic mutations in the von Hippel-Lindau disease tumour suppressor gene and correlation with disease phenotype."
Crossey P.A., Richards F.M., Foster K., Green J.S., Prowse A., Latif F., Lerman M.I., Zbar B., Affara N.A., Ferguson-Smith M.A., Maher E.R.
Hum. Mol. Genet. 3:1303-1308(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VHLD.
[28]"Germline mutations in the von Hippel-Lindau disease tumor suppressor gene: correlations with phenotype."
Chen F., Kishida T., Yao M., Hustad T., Glavac D., Dean M., Gnarra J.R., Orcutt M.L., Duh F.-M., Glenn G., Green J.S., Hsia Y.E., Lamiell J., Li H., Wei M.H., Schmidt L., Tory K., Kuzmin I. expand/collapse author list , Stackhouse T., Latif F., Linehan W.M., Lerman M.I., Zbar B.
Hum. Mutat. 5:66-75(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VHLD.
[29]"Germline mutations in the von Hippel-Lindau disease (VHL) gene in Japanese VHL. Clinical Research Group for VHL in Japan."
Kondo K., Sakai N., Kaneko S., Kobayashi K., Hosaka M., Ito S., Fujii S., Yamamoto I., Kim I., Miyagami M., Shidara N., Shinohara N., Koyanagi T., Kato N., Yamanaka H., Kuratu J., Fujioka M., Nakatsu H. expand/collapse author list , Shimazaki J., Yoshida J., Sugita K., Hirao Y., Okajima E., Tanigawa T., Sato S., Fujino H., Nagata M., Kanayama H., Kagawa S., Yamashima T., Furuta T., Saito Y., Kanno H., Yao M., Shuin T.
Hum. Mol. Genet. 4:2233-2237(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VHLD.
[30]"Molecular genetic diagnosis of von Hippel-Lindau disease in familial phaeochromocytoma."
Crossey P.A., Eng C., Ginalska-Malinowska M., Lennard T.W.J., Wheeler D.C., Ponder B.A.J., Maher E.R.
J. Med. Genet. 32:885-886(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VHLD LEU-84 AND TRP-167.
[31]"Mutations in the RET proto-oncogene and the von Hippel-Lindau disease tumour suppressor gene in sporadic and syndromic phaeochromocytomas."
Eng C., Crossey P.A., Mulligan L.M., Healey C.S., Houghton C., Prowse A., Chew S.L., Dahia P.L.M., O'Riordan J.L.H., Toledo S.P.A., Smith D.P., Maher E.R., Ponder B.A.J.
J. Med. Genet. 32:934-937(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VHLD SER-114; SER-119; GLU-143 AND ARG-164.
[32]"Phenotypic expression in von Hippel-Lindau disease: correlations with germline VHL gene mutations."
Maher E.R., Webster A.R., Richards F.M., Green J.S., Crossey P.A., Payne S.J., Moore A.T.
J. Med. Genet. 33:328-332(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VHLD PRO-96; VAL-116; ARG-118; PHE-166; ASP-170 AND GLU-186 DEL.
[33]"Germline mutations in the von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan."
Zbar B., Kishida T., Chen F., Schmidt L., Maher E.R., Richards F.M., Crossey P.A., Webster A.R., Affara N.A., Ferguson-Smith M.A., Brauch H., Glavac D., Neumann H.P.H., Tisherman S., Mulvihill J.J., Gross D.J., Shuin T., Whaley J. expand/collapse author list , Seizinger B., Kley N., Olschwang S., Boisson C., Richard S., Lips C.H.M., Linehan W.M., Lerman M.I.
Hum. Mutat. 8:348-357(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VHLD LEU-65; TRP-65; GLY-74; PHE-76 DEL; ILE-76; HIS-78; SER-78; THR-78; ARG-80; ASN-80; ILE-80; SER-81; ALA-86; LEU-86; ARG-88; SER-88; PRO-89; ARG-101; ARG-111; ASN-111; CYS-114; TYR-115; CYS-117; PRO-118; GLY-121; LEU-130; PRO-158; VAL-158; PRO-161; ARG-162; PHE-162; TYR-162; TRP-162; ARG-164; GLN-167; TRP-167; GLY-170; PRO-178; VAL-180; ARG-184; PRO-184; LYS-186; GLN-188 AND TRP-200.
[34]"Germline mutations detected in the von Hippel-Lindau disease tumor suppressor gene by Southern blot and direct genomic DNA sequencing."
Li C., Weber G., Ekman P., Lagercrantz J., Norlen B.J., Aakerstroem G., Nordenskjoeld M., Bergerheim U.S.R.
Hum. Mutat. Suppl. 1:S31-S33(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VHLD PRO-38; LEU-76 AND PHE-162.
[35]"Three novel mutations in the von Hippel-Lindau tumour suppressor gene in Italian patients."
Mandich P., Montera M., Bellone E., Trojani A., Daniele S., Ajmar F.
Hum. Mutat. Suppl. 1:S268-S270(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VHLD THR-149.
[36]"Variable penetrance of familial pheochromocytoma associated with the von Hippel-Lindau gene mutation, S68W."
Martin R., Hockey A., Walpole I., Goldblatt J.
Hum. Mutat. 12:71-71(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VHLD TRP-68.
[37]"Improved detection of germline mutations in the von Hippel-Lindau disease tumor suppressor gene."
Stolle C., Glenn G., Zbar B., Humphrey J.S., Choyke P., Walther M., Pack S., Hurley K., Andrey C., Klausner R., Linehan W.M.
Hum. Mutat. 12:417-423(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VHLD TRP-65; SER-76; SER-81; ARG-86; ARG-88; GLY-101; PRO-107; ASN-111; CYS-117; THR-131; PHE-162; GLY-167; ASP-175; PRO-184 AND LYS-186.
[38]"Germline mutation profile of the VHL gene in von Hippel-Lindau disease and in sporadic hemangioblastoma."
Olschwang S., Richard S., Boisson C., Giraud S., Laurent-Puig P., Resche F., Thomas G.
Hum. Mutat. 12:424-430(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VHLD LYS-52; LEU-65; LYS-70; ASN-80; ARG-80; SER-86; SER-88; LEU-91; ALA-104; PRO-105; GLN-115; CYS-117; PRO-118; LEU-130; LYS-131; SER-136; ASP-156; CYS-156; ILE-157; PRO-158; GLN-161; TRP-162; PHE-166; GLN-167; TRP-167; GLY-170; PRO-188 AND TRP-200.
[39]"Germline mutations in the vhl gene in patients presenting with phaeochromocytomas."
van der Harst E., de Krijger R.R., Dinjens W.N.M., Weeks L.E., Bonjer H.J., Bruining H.A., Lamberts S.W.J., Koper J.W.
Int. J. Cancer 77:337-340(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PHEOCHROMOCYTOMA LEU-25; PRO-63; PRO-64 AND THR-147.
[40]Murigia M.
Unpublished observations (MAY-1999)
Cited for: VARIANTS VHLD CYS-93; GLY-155 AND ILE-157.
[41]"Two distinct phenotypes caused by two different missense mutations in the same codon of the VHL gene."
Bradley J.F., Collins D.L., Schimke R.N., Parrott H.N., Rothberg P.G.
Am. J. Med. Genet. 87:163-167(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VHLD ASN-112.
[42]"Mutations of the VHL gene in sporadic renal cell carcinoma: definition of a risk factor for VHL patients to develop an RCC."
Gallou C., Joly D., Mejean A., Staroz F., Martin N., Tarlet G., Orfanelli M.T., Bouvier R., Droz D., Chretien Y., Marechal J.M., Richard S., Junien C., Beroud C.
Hum. Mutat. 13:464-475(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VHLD.
[43]"Paraneoplastic erythrocytosis associated with an inactivating point mutation of the von Hippel-Lindau gene in a renal cell carcinoma."
Wiesener M.S., Seyfarth M., Warnecke C., Juergensen J.S., Rosenberger C., Morgan N.V., Maher E.R., Frei U., Eckardt K.-U.
Blood 99:3562-3565(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT RCC PRO-163, CHARACTERIZATION OF VARIANT RCC PRO-163.
[44]"Germ-line mutations in nonsyndromic pheochromocytoma."
The Freiburg-Warsaw-Columbus pheochromocytoma study group
Neumann H.P.H., Bausch B., McWhinney S.R., Bender B.U., Gimm O., Franke G., Schipper J., Klisch J., Altehoefer C., Zerres K., Januszewicz A., Smith W.M., Munk R., Manz T., Glaesker S., Apel T.W., Treier M., Reineke M. expand/collapse author list , Walz M.K., Hoang-Vu C., Brauckhoff M., Klein-Franke A., Klose P., Schmidt H., Maier-Woelfle M., Peczkowska M., Szmigielski C., Eng C.
N. Engl. J. Med. 346:1459-1466(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PHEOCHROMOCYTOMA ALA-65; TRP-68; ASN-80; SER-93; CYS-93; HIS-98; GLY-107; LEU-119; ILE-122; CYS-136; ASN-156; CYS-156; GLN-161; PRO-161; TRP-167; GLN-167; VAL-188 AND GLN-198.
[45]"Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia."
Pastore Y.D., Jedlickova K., Guan Y., Liu E., Fahner J., Hasle H., Prchal J.F., Prchal J.T.
Am. J. Hum. Genet. 73:412-419(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ECYT2 VAL-188; ASP-191; SER-192 AND TRP-200.
[46]"Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas."
Gimenez-Roqueplo A.-P., Favier J., Rustin P., Rieubland C., Crespin M., Nau V., Khau Van Kien P., Corvol P., Plouin P.-F., Jeunemaitre X.
Cancer Res. 63:5615-5621(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PHEOCHROMOCYTOMA LEU-25 AND CYS-156.
[47]Erratum
Pastore Y.D., Jedlickova K., Guan Y., Liu E., Fahner J., Hasle H., Prchal J.F., Prchal J.T.
Am. J. Hum. Genet. 74:598-598(2004)
[48]"Mutations in the VHL gene in sporadic apparently congenital polycythemia."
Pastore Y.D., Jelinek J., Ang S., Guan Y., Liu E., Jedlickova K., Krishnamurti L., Prchal J.T.
Blood 101:1591-1595(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ECYT2 TYR-126; LEU-130 AND TRP-200.
[49]"The von Hippel-Lindau (VHL) germline mutation V84L manifests as early-onset bilateral pheochromocytoma."
Abbott M.-A., Nathanson K.L., Nightingale S., Maher E.R., Greenstein R.M.
Am. J. Med. Genet. A 140:685-690(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VHLD LEU-84.
[50]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-25 AND SER-86.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF010238 Genomic DNA. Translation: AAB64200.1.
L15409 mRNA. No translation available.
AK315799 mRNA. Translation: BAG38142.1.
AC034193 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW64064.1.
BC058831 mRNA. Translation: AAH58831.1.
U54612 Genomic DNA. Translation: AAA98614.1.
X96489 Genomic DNA. Translation: CAA65343.1.
PIRI38926.
RefSeqNP_000542.1. NM_000551.3.
NP_937799.1. NM_198156.2.
UniGeneHs.517792.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LM8X-ray1.85V54-213[»]
1LQBX-ray2.00C54-213[»]
1VCBX-ray2.70C/F/I/L54-213[»]
3ZRCX-ray2.90C/F/I/L54-213[»]
3ZRFX-ray2.80C/F/I/L54-213[»]
3ZTCX-ray2.65C/F/I/L54-213[»]
3ZTDX-ray2.79C/F/I/L54-213[»]
3ZUNX-ray2.50C/F/I/L54-213[»]
4AJYX-ray1.73V54-213[»]
4AWJX-ray2.50C/F/I/L54-213[»]
4B95X-ray2.80C/F/I/L54-213[»]
4B9KX-ray2.00C/F/I/L54-213[»]
4BKSX-ray2.20C/F/I/L54-213[»]
4BKTX-ray2.35C/F/I/L54-213[»]
DisProtDP00287.
ProteinModelPortalP40337.
SMRP40337. Positions 60-207.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113269. 278 interactions.
DIPDIP-32585N.
IntActP40337. 35 interactions.
MINTMINT-133223.
STRING9606.ENSP00000256474.

PTM databases

PhosphoSiteP40337.

Polymorphism databases

DMDM4033778.

Proteomic databases

PRIDEP40337.

Protocols and materials databases

DNASU7428.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000256474; ENSP00000256474; ENSG00000134086. [P40337-1]
ENST00000345392; ENSP00000344757; ENSG00000134086. [P40337-2]
GeneID7428.
KEGGhsa:7428.
UCSCuc003bvc.3. human. [P40337-1]
uc003bvd.3. human. [P40337-2]

Organism-specific databases

CTD7428.
GeneCardsGC03P010185.
HGNCHGNC:12687. VHL.
HPACAB005430.
HPA031631.
HPA031632.
MIM144700. phenotype.
171300. phenotype.
193300. phenotype.
263400. phenotype.
608537. gene.
neXtProtNX_P40337.
Orphanet238557. Chuvash erythrocytosis.
892. Von Hippel-Lindau disease.
PharmGKBPA37307.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG327868.
HOGENOMHOG000030904.
HOVERGENHBG044781.
InParanoidP40337.
KOK03871.
OMANTREPSQ.
OrthoDBEOG7VMP7B.
PhylomeDBP40337.
TreeFamTF318985.

Enzyme and pathway databases

ReactomeREACT_120956. Cellular responses to stress.
REACT_6900. Immune System.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressP40337.
BgeeP40337.
CleanExHS_VHL.
GenevestigatorP40337.

Family and domain databases

Gene3D1.10.750.10. 1 hit.
2.60.40.780. 1 hit.
InterProIPR002714. Tumour_suppress_VHL-disease.
IPR024048. VHL_alpha_dom.
IPR024053. VHL_beta_dom.
IPR022772. VHL_tumour_suppress_b/a_dom.
[Graphical view]
PANTHERPTHR15160. PTHR15160. 1 hit.
PfamPF01847. VHL. 1 hit.
[Graphical view]
SUPFAMSSF49468. SSF49468. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP40337.
GeneWikiVon_Hippel%E2%80%93Lindau_tumor_suppressor.
GenomeRNAi7428.
NextBio29090.
PROP40337.
SOURCESearch...

Entry information

Entry nameVHL_HUMAN
AccessionPrimary (citable) accession number: P40337
Secondary accession number(s): B2RE45, Q13599, Q6PDA9
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: December 15, 1998
Last modified: April 16, 2014
This is version 168 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM