P40337 (VHL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Von Hippel-Lindau disease tumor suppressor

Alternative name(s):
Protein G7
pVHL

Gene names

Name:

VHL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	213 AA.
Sequence status	Complete.
Protein existence	Evidence 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 PHF17. 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. 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 Familial erythrocytosis 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 process	Ubl conjugation pathway
Cellular component	Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative initiation Alternative splicing Polymorphism
Disease	Congenital erythrocytosis Disease mutation Tumor suppressor
Domain	Repeat
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell morphogenesis Non-traceable author statement Ref.17. Source: UniProtKB 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 transcription from RNA polymerase II promoter in response to hypoxia Inferred from direct assay Ref.15. Source: UniProtKB positive regulation of cell differentiation Non-traceable author statement Ref.17. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from mutant phenotype PubMed 17973242. Source: UniProtKB protein stabilization Non-traceable author statement Ref.17. Source: UniProtKB proteolysis Traceable author statement PubMed 10353251. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome endoplasmic reticulum Non-traceable author statement Ref.17. Source: UniProtKB membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Non-traceable author statement Ref.17. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	transcription factor binding Traceable author statement PubMed 7660122. Source: ProtInc ubiquitin-protein ligase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DGKI	O75912	3	EBI-301270,EBI-1765520
FZR1	Q9UM11	2	EBI-301246,EBI-724997
GNB2L1	P63244	9	EBI-301246,EBI-296739
HIF1A	Q16665	6	EBI-301246,EBI-447269
RNF139	Q8WU17	2	EBI-301246,EBI-1551681
TGM2	P21980	10	EBI-301246,EBI-727668

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 213

213

Von Hippel-Lindau disease tumor suppressor

PRO_0000065809

Regions

Repeat

14 – 18

5

1

Repeat

19 – 23

5

2

Repeat

24 – 28

5

3

Repeat

29 – 33

5

4

Repeat

34 – 38

5

5

Repeat

39 – 43

5

6

Repeat

44 – 48

5

7

Repeat

49 – 53

5

8

Region

14 – 53

40

8 X 5 AA tandem repeats of G-[PAVG]-E-E-[DAYSLE]

Region

100 – 155

56

Involved in binding to CCT complex

Region

157 – 166

10

Interaction with Elongin BC complex

Natural variations

Alternative sequence

1 – 53

53

Missing in isoform 3.

VSP_007740

Alternative sequence

114 – 154

41

Missing in isoform 2.

VSP_004488

Natural variant

25

1

P → L in pheochromocytoma. Ref.39 Ref.46 Ref.50
Corresponds to variant rs35460768 [ dbSNP | Ensembl ].

VAR_034562

Natural variant

38

1

S → P in VHLD; type II. Ref.34

VAR_005670

Natural variant

52

1

E → K in VHLD; type I. Ref.38

VAR_005671

Natural variant

63

1

L → P in pheochromocytoma. Ref.39

VAR_034987

Natural variant

64

1

R → P in pheochromocytoma. Ref.39

VAR_034988

Natural variant

65

1

S → A in pheochromocytoma. Ref.44

VAR_034989

Natural variant

65

1

S → L in VHLD; type I. Ref.33 Ref.38

VAR_005672

Natural variant

65

1

S → W in VHLD; type I. Ref.33 Ref.37

VAR_005673

Natural variant

66 – 73

8

Missing in VHLD; type I.

VAR_005674

Natural variant

68

1

S → W in pheochromocytoma and VHLD; type II. Ref.36 Ref.44

VAR_005675

Natural variant

70

1

E → K in VHLD; type I. Ref.38

VAR_005676

Natural variant

74

1

V → G in VHLD; type I-II. Ref.33
Corresponds to variant rs5030803 [ dbSNP | Ensembl ].

VAR_005677

Natural variant

75

1

Missing in VHLD. Ref.1

VAR_034990

Natural variant

76

1

F → I in VHLD; type I. Ref.33

VAR_005679

Natural variant

76

1

F → L in VHLD; type I. Ref.34

VAR_005680

Natural variant

76

1

F → S in VHLD; type I. Ref.37

VAR_005681

Natural variant

76

1

Missing in VHLD; type I; common mutation. Ref.33

VAR_005678

Natural variant

78

1

N → H in VHLD; type I. Ref.33

VAR_005682

Natural variant

78

1

N → S in VHLD; type I; common mutation. Ref.33
Corresponds to variant rs5030804 [ dbSNP | Ensembl ].

VAR_005683

Natural variant

78

1

N → T in VHLD; type I. Ref.33

VAR_005684

Natural variant

79

1

R → P in VHLD.

VAR_005685

Natural variant

80

1

S → I in VHLD; type I. Ref.33

VAR_005686

Natural variant

80

1

S → N in pheochromocytoma and VHLD; type I. Ref.33 Ref.38 Ref.44
Corresponds to variant rs5030805 [ dbSNP | Ensembl ].

VAR_005688

Natural variant

80

1

S → R in VHLD; type I. Ref.33 Ref.38

VAR_005687

Natural variant

81

1

P → S in VHLD; type I. Ref.33 Ref.37
Corresponds to variant rs5030806 [ dbSNP | Ensembl ].

VAR_005689

Natural variant

82 – 84

3

Missing in VHLD.

VAR_005691

Natural variant

82

1

R → P in VHLD; type I.

VAR_005690

Natural variant

84

1

V → L in VHLD; type II and type 2C. Ref.30 Ref.49
Corresponds to variant rs5030827 [ dbSNP | Ensembl ].

VAR_005692

Natural variant

86

1

P → A in VHLD; type I. Ref.33

VAR_005693

Natural variant

86

1

P → H in VHLD.

VAR_008097

Natural variant

86

1

P → L in VHLD; type I. Ref.33

VAR_005694

Natural variant

86

1

P → R in VHLD; type I. Ref.37

VAR_005695

Natural variant

86

1

P → S in VHLD. Ref.38 Ref.50

VAR_005696

Natural variant

88

1

W → R in VHLD; type I. Ref.33 Ref.37

VAR_005697

Natural variant

88

1

W → S in VHLD; type I. Ref.33 Ref.38

VAR_005698

Natural variant

89

1

L → H in lung cancer.

VAR_005699

Natural variant

89

1

L → P in VHLD; type I. Ref.33
Corresponds to variant rs5030807 [ dbSNP | Ensembl ].

VAR_005700

Natural variant

91

1

F → L in cerebellar hemangioblastoma. Ref.38

VAR_005701

Natural variant

92 – 97

6

Missing in VHLD; type I.

VAR_005702

Natural variant

93

1

G → C in pheochromocytoma and VHLD; type II. Ref.40 Ref.44
Corresponds to variant rs5030808 [ dbSNP | Ensembl ].

VAR_005703

Natural variant

93

1

G → D in VHLD.

VAR_005704

Natural variant

93

1

G → S in pheochromocytoma and VHLD; type II. Ref.44
Corresponds to variant rs5030808 [ dbSNP | Ensembl ].

VAR_005705

Natural variant

96

1

Q → P in VHLD; type I. Ref.32

VAR_005706

Natural variant

98

1

Y → H in pheochromocytoma and VHLD; type II. Ref.44
Corresponds to variant rs5030809 [ dbSNP | Ensembl ].

VAR_005707

Natural variant

101

1

L → G in VHLD; type I; requires 2 nucleotide substitutions. Ref.37

VAR_005708

Natural variant

101

1

L → R in VHLD; type I. Ref.33

VAR_005709

Natural variant

104

1

G → A in cerebellar hemangioblastoma. Ref.38

VAR_005710

Natural variant

105

1

T → P in VHLD; type I. Ref.38

VAR_005711

Natural variant

106

1

G → D in lung cancer.

VAR_005712

Natural variant

107

1

R → G in pheochromocytoma. Ref.44

VAR_034991

Natural variant

107

1

R → P in VHLD; type I. Ref.37

VAR_005713

Natural variant

110

1

H → Y. Ref.5
Corresponds to variant rs17855706 [ dbSNP | Ensembl ].

VAR_055087

Natural variant

111

1

S → C in VHLD; type II.

VAR_005714

Natural variant

111

1

S → N in VHLD; type I. Ref.33 Ref.37

VAR_005715

Natural variant

111

1

S → R in VHLD; type I. Ref.33

VAR_005716

Natural variant

112

1

Y → H in VHLD; type IIA.

VAR_005717

Natural variant

112

1

Y → N in VHLD. Ref.41

VAR_034992

Natural variant

114

1

G → C in VHLD; type II. Ref.33

VAR_005718

Natural variant

114

1

G → R in VHLD; type I-II.

VAR_005719

Natural variant

114

1

G → S in VHLD; type II. Ref.31

VAR_005720

Natural variant

115

1

H → Q in VHLD; type II. Ref.38

VAR_005723

Natural variant

115

1

H → R in VHLD; type II.
Corresponds to variant rs5030812 [ dbSNP | Ensembl ].

VAR_008098

Natural variant

115

1

H → Y in VHLD; type I. Ref.33
Corresponds to variant rs5030811 [ dbSNP | Ensembl ].

VAR_005722

Natural variant

116

1

L → V in VHLD. Ref.32

VAR_005724

Natural variant

117

1

W → C in VHLD; type I. Ref.33 Ref.37 Ref.38

VAR_005725

Natural variant

118

1

L → P in VHLD; type I. Ref.33 Ref.38
Corresponds to variant rs5030830 [ dbSNP | Ensembl ].

VAR_005726

Natural variant

118

1

L → R in VHLD. Ref.32

VAR_005727

Natural variant

119

1

F → L in pheochromocytoma and VHLD; type II. Ref.44

VAR_005728

Natural variant

119

1

F → S in VHLD; type II. Ref.31

VAR_005729

Natural variant

121

1

D → G in VHLD; type I. Ref.33
Corresponds to variant rs5030832 [ dbSNP | Ensembl ].

VAR_005730

Natural variant

122

1

A → I in pheochromocytoma; requires 2 nucleotide substitutions. Ref.44

VAR_034993

Natural variant

126

1

D → Y in ECYT2. Ref.48

VAR_034994

Natural variant

128

1

L → F in VHLD; type II.

VAR_005731

Natural variant

129

1

L → LE in VHLD.

VAR_005732

Natural variant

130

1

V → L in ECYT2 and VHLD; type I. Ref.33 Ref.38 Ref.48

VAR_005733

Natural variant

131

1

N → K in VHLD; type I. Ref.38

VAR_005734

Natural variant

131

1

N → T in VHLD; type I. Ref.37

VAR_005735

Natural variant

135

1

L → F in hemangioblastoma. Ref.25

VAR_034995

Natural variant

136

1

F → C in pheochromocytoma and VHLD; type II. Ref.44
Corresponds to variant rs5030833 [ dbSNP | Ensembl ].

VAR_005737

Natural variant

136

1

F → S in VHLD. Ref.38

VAR_005736

Natural variant

136

1

F → Y in VHLD.

VAR_008099

Natural variant

143

1

D → E in VHLD; type II. Ref.31

VAR_005738

Natural variant

145

1

Q → H in VHLD.

VAR_008100

Natural variant

147

1

I → T in pheochromocytoma. Ref.39

VAR_034996

Natural variant

148

1

Missing in VHLD; type I.

VAR_005739

Natural variant

149

1

A → T in VHLD; type II. Ref.35

VAR_005740

Natural variant

154

1

P → L in VHLD; type II.

VAR_005741

Natural variant

155

1

V → G in VHLD; type II. Ref.40

VAR_005742

Natural variant

155

1

V → M in VHLD; with RCC.

VAR_008101

Natural variant

156

1

Y → C in pheochromocytoma and VHLD; type I. Ref.38 Ref.44 Ref.46

VAR_005743

Natural variant

156

1

Y → D in VHLD; type I. Ref.38

VAR_005744

Natural variant

156

1

Y → N in pheochromocytoma. Ref.44

VAR_034997

Natural variant

157

1

T → I in VHLD; type II. Ref.38 Ref.40

VAR_005746

Natural variant

157

1

T → TF in VHLD; type I.

VAR_005747

Natural variant

158

1

L → 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 variant

158

1

L → V in VHLD; type I. Ref.33

VAR_005749

Natural variant

159

1

K → E in VHLD; type II.

VAR_005750

Natural variant

161

1

R → G in VHLD; type II.
Corresponds to variant rs5030818 [ dbSNP | Ensembl ].

VAR_005753

Natural variant

161

1

R → P in pheochromocytoma and VHLD; type I. Ref.33 Ref.44

VAR_005752

Natural variant

161

1

R → Q in pheochromocytoma and VHLD; type II. Ref.38 Ref.44

VAR_005751

Natural variant

162

1

C → 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 variant

162

1

C → R in VHLD; type I. Ref.33

VAR_005755

Natural variant

162

1

C → W in VHLD; type I-II. Ref.33 Ref.38
Corresponds to variant rs5030622 [ dbSNP | Ensembl ].

VAR_005756

Natural variant

162

1

C → Y in VHLD; type I. Ref.33

VAR_005757

Natural variant

163

1

L → P in RCC; with paraneoplastic erythrocytosis; inhibits binding to HIF1AN. Ref.6 Ref.43
Corresponds to variant rs28940297 [ dbSNP | Ensembl ].

VAR_034998

Natural variant

164

1

Q → H in VHLD.

VAR_008102

Natural variant

164

1

Q → R in VHLD; type II. Ref.31 Ref.33

VAR_005758

Natural variant

166

1

V → D in VHLD; with RCC.

VAR_008103

Natural variant

166

1

V → F in VHLD; type IIA. Ref.32 Ref.38

VAR_005759

Natural variant

167

1

R → G in VHLD; type I-II. Ref.37

VAR_005760

Natural variant

167

1

R → Q in pheochromocytoma and VHLD; type II; common mutation. Ref.33 Ref.38 Ref.44
Corresponds to variant rs5030821 [ dbSNP | Ensembl ].

VAR_005761

Natural variant

167

1

R → 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 variant

170

1

V → D in VHLD; type II. Ref.32

VAR_005763

Natural variant

170

1

V → F in VHLD; type II.

VAR_005764

Natural variant

170

1

V → G in VHLD; type I. Ref.33 Ref.38

VAR_005765

Natural variant

175

1

Y → D in VHLD; type I. Ref.37

VAR_005766

Natural variant

176

1

R → W in VHLD.

VAR_008104

Natural variant

177

1

R → RLRVKPE in VHLD; type I.

VAR_005767

Natural variant

178

1

L → P in VHLD; type I-II; common mutation. Ref.33

VAR_005768

Natural variant

178

1

L → Q in VHLD; type II.
Corresponds to variant rs5030822 [ dbSNP | Ensembl ].

VAR_005769

Natural variant

180

1

I → V in VHLD; type I. Ref.33

VAR_005770

Natural variant

184

1

L → P in VHLD; type I. Ref.33 Ref.37

VAR_005772

Natural variant

184

1

L → R in VHLD; type I. Ref.33

VAR_005771

Natural variant

186

1

E → K in VHLD; type I. Ref.33 Ref.37

VAR_005773

Natural variant

186

1

Missing in VHLD. Ref.32

VAR_005774

Natural variant

188

1

L → P in VHLD; type I-II. Ref.38

VAR_005775

Natural variant

188

1

L → Q in VHLD; type I. Ref.33

VAR_005776

Natural variant

188

1

L → V in ECYT2, pheochromocytoma and VHLD; type IIA. Ref.44 Ref.45
Corresponds to variant rs5030824 [ dbSNP | Ensembl ].

VAR_005777

Natural variant

191

1

H → D in ECYT2. Ref.45
Corresponds to variant rs28940301 [ dbSNP | Ensembl ].

VAR_034999

Natural variant

192

1

P → S in ECYT2. Ref.45
Corresponds to variant rs28940300 [ dbSNP | Ensembl ].

VAR_035000

Natural variant

198

1

L → Q in pheochromocytoma. Ref.44

VAR_035001

Natural variant

198

1

L → R in ECY2 and VHLD; type II.

VAR_005778

Natural variant

200

1

R → 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

Mutagenesis

98

1

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

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

213

Helix Strand Turn

Details...

Beta strand

71 – 78

8

Beta strand

80 – 82

3

Beta strand

84 – 89

6

Beta strand

91 – 93

3

Beta strand

95 – 97

3

Beta strand

105 – 112

8

Beta strand

116 – 121

6

Turn

122 – 124

3

Beta strand

127 – 130

4

Beta strand

142 – 144

3

Beta strand

147 – 152

6

Helix

158 – 169

12

Helix

172 – 177

6

Beta strand

178 – 180

3

Helix

183 – 189

7

Helix

194 – 206

13

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (VHL30) (VHLp24(MPR)) [UniParc]. Last modified December 15, 1998. Version 2. Checksum: BA5D6765FBC16EA7	FASTA	213	24,153
	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
	Isoform 2 [UniParc]. Checksum: 46E2C22E8C98393D	FASTA	172	19,654
	10 20 30 40 50 60 MPRRAENWDE AEVGAEEAGV EEYGPEEDGG EESGAEESGP EESGPEELGA EEEMEAGRPR 70 80 90 100 110 120 PVLRSVNSRE PSQVIFCNRS PRVVLPVWLN FDGEPQPYPT LPPGTGRRIH SYRVYTLKER 130 140 150 160 170 CLQVVRSLVK PENYRRLDIV RSLYEDLEDH PNVQKDLERL TQERIAHQRM GD
	Isoform 3 (VHL19) (VHLp18(MEA)) [UniParc]. Checksum: 2644C3B8C3A87D64	FASTA	160	18,532
	10 20 30 40 50 60 MEAGRPRPVL RSVNSREPSQ VIFCNRSPRV VLPVWLNFDG EPQPYPTLPP GTGRRIHSYR 70 80 90 100 110 120 GHLWLFRDAG THDGLLVNQT ELFVPSLNVD GQPIFANITL PVYTLKERCL QVVRSLVKPE 130 140 150 160 NYRRLDIVRS LYEDLEDHPN VQKDLERLTQ ERIAHQRMGD

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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 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 PHF17.
[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. , 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. , 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. , 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. , 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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

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.

IPI

IPI00027969.
IPI00336024.
IPI00939404.

PIR

I38926.

RefSeq

NP_000542.1. NM_000551.3.
NP_937799.1. NM_198156.2.

UniGene

Hs.517792.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LM8	X-ray	1.85	V	54-213	[»]
1LQB	X-ray	2.00	C	54-213	[»]
1VCB	X-ray	2.70	C/F/I/L	54-213	[»]
3ZRC	X-ray	2.90	C/F/I/L	54-213	[»]
3ZRF	X-ray	2.80	C/F/I/L	54-213	[»]
3ZTC	X-ray	2.65	C/F/I/L	54-213	[»]
3ZTD	X-ray	2.79	C/F/I/L	54-213	[»]
3ZUN	X-ray	2.50	C/F/I/L	54-213	[»]
4AJY	X-ray	1.73	V	54-213	[»]
4AWJ	X-ray	2.50	C/F/I/L	54-213	[»]
4B95	X-ray	2.80	C/F/I/L	54-213	[»]
4B9K	X-ray	2.00	C/F/I/L	54-213	[»]

DisProt

DP00287.

ProteinModelPortal

P40337.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-32585N.

IntAct

P40337. 26 interactions.

MINT

MINT-133223.

STRING

9606.ENSP00000256474.

PTM databases

PhosphoSite

P40337.

Polymorphism databases

DMDM

4033778.

Proteomic databases

PRIDE

P40337.

Protocols and materials databases

DNASU

7428.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000256474; ENSP00000256474; ENSG00000134086.
ENST00000345392; ENSP00000344757; ENSG00000134086.

GeneID

7428.

KEGG

hsa:7428.

UCSC

uc003bvc.3. human.
uc003bvd.3. human.

Organism-specific databases

CTD

7428.

GeneCards

GC03P010185.

HGNC

HGNC:12687. VHL.

HPA

CAB005430.

MIM

144700. phenotype.
171300. phenotype.
193300. phenotype.
263400. phenotype.
608537. gene.

neXtProt

NX_P40337.

Orphanet

238557. Chuvash erythrocytosis.
892. Von Hippel-Lindau disease.

PharmGKB

PA37307.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG327868.

HOGENOM

HOG000030904.

HOVERGEN

HBG044781.

InParanoid

P40337.

KO

K03871.

OMA

NTREPSQ.

OrthoDB

EOG4J119K.

PhylomeDB

P40337.

Enzyme and pathway databases

Pathway_Interaction_DB

hif1apathway. Hypoxic and oxygen homeostasis regulation of HIF-1-alpha.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.

Reactome

REACT_120956. Cellular responses to stress.
REACT_6900. Immune System.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

P40337.

Bgee

P40337.

CleanEx

HS_VHL.

Genevestigator

P40337.

GermOnline

ENSG00000134086. Homo sapiens.

Family and domain databases

Gene3D

1.10.750.10. 1 hit.
2.60.40.780. 1 hit.

InterPro

IPR002714. Tumour_suppress_VHL-disease.
IPR024048. VHL_alpha_dom.
IPR024053. VHL_beta_dom.
IPR022772. VHL_tumour_suppress_b/a_dom.
[Graphical view]

PANTHER

PTHR15160. PTHR15160. 1 hit.

Pfam

PF01847. VHL. 1 hit.
[Graphical view]

SUPFAM

SSF49468. SSF49468. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P40337.

GenomeRNAi

7428.

NextBio

29090.

SOURCE

Search...

Entry information

Entry name

VHL_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 157 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.