SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P40337

- VHL_HUMAN

UniProt

P40337 - VHL_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Von Hippel-Lindau disease tumor suppressor

Gene
VHL
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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, ADRB2.3 Publications

Pathwayi

GO - Molecular functioni

  1. enzyme binding Source: UniProtKB
  2. protein binding Source: IntAct
  3. transcription factor binding Source: UniProtKB
  4. ubiquitin-protein transferase activity Source: Reactome

GO - Biological processi

  1. cell morphogenesis Source: UniProtKB
  2. cellular response to hypoxia Source: Reactome
  3. negative regulation of apoptotic process Source: UniProtKB
  4. negative regulation of cell proliferation Source: ProtInc
  5. negative regulation of transcription from RNA polymerase II promoter Source: ProtInc
  6. negative regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: UniProtKB
  7. positive regulation of cell differentiation Source: UniProtKB
  8. positive regulation of transcription, DNA-templated Source: UniProtKB
  9. protein stabilization Source: UniProtKB
  10. protein ubiquitination Source: UniProtKB
  11. proteolysis Source: ProtInc
  12. regulation of transcription, DNA-templated Source: BHF-UCL
  13. regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: Reactome
  14. response to stress Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiREACT_120916. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Von Hippel-Lindau disease tumor suppressor
Alternative name(s):
Protein G7
pVHL
Gene namesi
Name:VHL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:12687. VHL.

Subcellular locationi

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.2 Publications
Isoform 3 : Cytoplasm. Nucleus
Note: Equally distributed between the nucleus and the cytoplasm but not membrane-associated.2 Publications

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. endoplasmic reticulum Source: UniProtKB
  3. intermediate filament cytoskeleton Source: HPA
  4. membrane Source: UniProtKB-SubCell
  5. mitochondrion Source: UniProtKB
  6. nucleoplasm Source: Reactome
  7. nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.18 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti38 – 381S → P in VHLD; type II. 1 Publication
VAR_005670
Natural varianti52 – 521E → K in VHLD; type I. 1 Publication
VAR_005671
Natural varianti65 – 651S → L in VHLD; type I. 2 Publications
VAR_005672
Natural varianti65 – 651S → W in VHLD; type I. 2 Publications
VAR_005673
Natural varianti66 – 738Missing in VHLD; type I.
VAR_005674
Natural varianti68 – 681S → W in pheochromocytoma and VHLD; type II. 2 Publications
VAR_005675
Natural varianti70 – 701E → K in VHLD; type I. 1 Publication
VAR_005676
Natural varianti74 – 741V → G in VHLD; type I-II. 1 Publication
Corresponds to variant rs5030803 [ dbSNP | Ensembl ].
VAR_005677
Natural varianti75 – 751Missing in VHLD. 1 Publication
VAR_034990
Natural varianti76 – 761F → I in VHLD; type I. 1 Publication
VAR_005679
Natural varianti76 – 761F → L in VHLD; type I. 1 Publication
VAR_005680
Natural varianti76 – 761F → S in VHLD; type I. 1 Publication
VAR_005681
Natural varianti76 – 761Missing in VHLD; type I; common mutation. 1 Publication
VAR_005678
Natural varianti78 – 781N → H in VHLD; type I. 1 Publication
VAR_005682
Natural varianti78 – 781N → S in VHLD; type I; common mutation. 1 Publication
Corresponds to variant rs5030804 [ dbSNP | Ensembl ].
VAR_005683
Natural varianti78 – 781N → T in VHLD; type I. 1 Publication
VAR_005684
Natural varianti79 – 791R → P in VHLD.
VAR_005685
Natural varianti80 – 801S → I in VHLD; type I. 1 Publication
VAR_005686
Natural varianti80 – 801S → N in pheochromocytoma and VHLD; type I. 3 Publications
Corresponds to variant rs5030805 [ dbSNP | Ensembl ].
VAR_005688
Natural varianti80 – 801S → R in VHLD; type I. 2 Publications
VAR_005687
Natural varianti81 – 811P → S in VHLD; type I. 2 Publications
Corresponds to variant rs5030806 [ dbSNP | Ensembl ].
VAR_005689
Natural varianti82 – 843Missing in VHLD.
VAR_005691
Natural varianti82 – 821R → P in VHLD; type I.
VAR_005690
Natural varianti84 – 841V → L in VHLD; type II and type 2C. 2 Publications
Corresponds to variant rs5030827 [ dbSNP | Ensembl ].
VAR_005692
Natural varianti86 – 861P → A in VHLD; type I. 1 Publication
VAR_005693
Natural varianti86 – 861P → H in VHLD.
VAR_008097
Natural varianti86 – 861P → L in VHLD; type I. 1 Publication
VAR_005694
Natural varianti86 – 861P → R in VHLD; type I. 1 Publication
VAR_005695
Natural varianti86 – 861P → S in VHLD. 2 Publications
VAR_005696
Natural varianti88 – 881W → R in VHLD; type I. 2 Publications
VAR_005697
Natural varianti88 – 881W → S in VHLD; type I. 2 Publications
VAR_005698
Natural varianti89 – 891L → P in VHLD; type I. 1 Publication
Corresponds to variant rs5030807 [ dbSNP | Ensembl ].
VAR_005700
Natural varianti92 – 976Missing in VHLD; type I.
VAR_005702
Natural varianti93 – 931G → C in pheochromocytoma and VHLD; type II. 2 Publications
Corresponds to variant rs5030808 [ dbSNP | Ensembl ].
VAR_005703
Natural varianti93 – 931G → D in VHLD.
VAR_005704
Natural varianti93 – 931G → S in pheochromocytoma and VHLD; type II. 1 Publication
Corresponds to variant rs5030808 [ dbSNP | Ensembl ].
VAR_005705
Natural varianti96 – 961Q → P in VHLD; type I. 1 Publication
VAR_005706
Natural varianti98 – 981Y → H in pheochromocytoma and VHLD; type II. 1 Publication
Corresponds to variant rs5030809 [ dbSNP | Ensembl ].
VAR_005707
Natural varianti101 – 1011L → G in VHLD; type I; requires 2 nucleotide substitutions. 1 Publication
VAR_005708
Natural varianti101 – 1011L → R in VHLD; type I. 1 Publication
VAR_005709
Natural varianti105 – 1051T → P in VHLD; type I. 1 Publication
VAR_005711
Natural varianti107 – 1071R → P in VHLD; type I. 1 Publication
VAR_005713
Natural varianti111 – 1111S → C in VHLD; type II.
VAR_005714
Natural varianti111 – 1111S → N in VHLD; type I. 2 Publications
VAR_005715
Natural varianti111 – 1111S → R in VHLD; type I. 1 Publication
VAR_005716
Natural varianti112 – 1121Y → H in VHLD; type IIA.
VAR_005717
Natural varianti112 – 1121Y → N in VHLD. 1 Publication
VAR_034992
Natural varianti114 – 1141G → C in VHLD; type II. 1 Publication
VAR_005718
Natural varianti114 – 1141G → R in VHLD; type I-II.
VAR_005719
Natural varianti114 – 1141G → S in VHLD; type II. 1 Publication
VAR_005720
Natural varianti115 – 1151H → Q in VHLD; type II. 1 Publication
VAR_005723
Natural varianti115 – 1151H → R in VHLD; type II.
Corresponds to variant rs5030812 [ dbSNP | Ensembl ].
VAR_008098
Natural varianti115 – 1151H → Y in VHLD; type I. 1 Publication
Corresponds to variant rs5030811 [ dbSNP | Ensembl ].
VAR_005722
Natural varianti116 – 1161L → V in VHLD. 1 Publication
VAR_005724
Natural varianti117 – 1171W → C in VHLD; type I. 3 Publications
VAR_005725
Natural varianti118 – 1181L → P in VHLD; type I. 2 Publications
Corresponds to variant rs5030830 [ dbSNP | Ensembl ].
VAR_005726
Natural varianti118 – 1181L → R in VHLD. 1 Publication
VAR_005727
Natural varianti119 – 1191F → L in pheochromocytoma and VHLD; type II. 1 Publication
VAR_005728
Natural varianti119 – 1191F → S in VHLD; type II. 1 Publication
VAR_005729
Natural varianti121 – 1211D → G in VHLD; type I. 1 Publication
Corresponds to variant rs5030832 [ dbSNP | Ensembl ].
VAR_005730
Natural varianti128 – 1281L → F in VHLD; type II.
VAR_005731
Natural varianti129 – 1291L → LE in VHLD.
VAR_005732
Natural varianti130 – 1301V → L in ECYT2 and VHLD; type I. 3 Publications
VAR_005733
Natural varianti131 – 1311N → K in VHLD; type I. 1 Publication
VAR_005734
Natural varianti131 – 1311N → T in VHLD; type I. 1 Publication
VAR_005735
Natural varianti136 – 1361F → C in pheochromocytoma and VHLD; type II. 1 Publication
Corresponds to variant rs5030833 [ dbSNP | Ensembl ].
VAR_005737
Natural varianti136 – 1361F → S in VHLD. 1 Publication
VAR_005736
Natural varianti136 – 1361F → Y in VHLD.
VAR_008099
Natural varianti143 – 1431D → E in VHLD; type II. 1 Publication
VAR_005738
Natural varianti145 – 1451Q → H in VHLD.
VAR_008100
Natural varianti148 – 1481Missing in VHLD; type I.
VAR_005739
Natural varianti149 – 1491A → T in VHLD; type II. 1 Publication
VAR_005740
Natural varianti154 – 1541P → L in VHLD; type II.
VAR_005741
Natural varianti155 – 1551V → G in VHLD; type II. 1 Publication
VAR_005742
Natural varianti155 – 1551V → M in VHLD; with RCC.
VAR_008101
Natural varianti156 – 1561Y → C in pheochromocytoma and VHLD; type I. 3 Publications
VAR_005743
Natural varianti156 – 1561Y → D in VHLD; type I. 1 Publication
VAR_005744
Natural varianti157 – 1571T → I in VHLD; type II. 2 Publications
VAR_005746
Natural varianti157 – 1571T → TF in VHLD; type I.
VAR_005747
Natural varianti158 – 1581L → P in VHLD; type I-II; abolishes release from chaperonin complex and the interaction with Elongin BC complex. 3 Publications
VAR_005748
Natural varianti158 – 1581L → V in VHLD; type I. 1 Publication
VAR_005749
Natural varianti159 – 1591K → E in VHLD; type II.
VAR_005750
Natural varianti161 – 1611R → G in VHLD; type II.
Corresponds to variant rs5030818 [ dbSNP | Ensembl ].
VAR_005753
Natural varianti161 – 1611R → P in pheochromocytoma and VHLD; type I. 2 Publications
VAR_005752
Natural varianti161 – 1611R → Q in pheochromocytoma and VHLD; type II. 2 Publications
VAR_005751
Natural varianti162 – 1621C → F in VHLD; type I; No effect on interaction with HIF1A nor on HIF1A degradation. 4 Publications
VAR_005754
Natural varianti162 – 1621C → R in VHLD; type I. 1 Publication
VAR_005755
Natural varianti162 – 1621C → W in VHLD; type I-II. 2 Publications
Corresponds to variant rs5030622 [ dbSNP | Ensembl ].
VAR_005756
Natural varianti162 – 1621C → Y in VHLD; type I. 1 Publication
VAR_005757
Natural varianti164 – 1641Q → H in VHLD.
VAR_008102
Natural varianti164 – 1641Q → R in VHLD; type II. 2 Publications
VAR_005758
Natural varianti166 – 1661V → D in VHLD; with RCC.
VAR_008103
Natural varianti166 – 1661V → F in VHLD; type IIA. 2 Publications
VAR_005759
Natural varianti167 – 1671R → G in VHLD; type I-II. 1 Publication
VAR_005760
Natural varianti167 – 1671R → Q in pheochromocytoma and VHLD; type II; common mutation. 3 Publications
Corresponds to variant rs5030821 [ dbSNP | Ensembl ].
VAR_005761
Natural varianti167 – 1671R → W in pheochromocytoma and VHLD; type II; common mutation. 4 Publications
Corresponds to variant rs5030820 [ dbSNP | Ensembl ].
VAR_005762
Natural varianti170 – 1701V → D in VHLD; type II. 1 Publication
VAR_005763
Natural varianti170 – 1701V → F in VHLD; type II.
VAR_005764
Natural varianti170 – 1701V → G in VHLD; type I. 2 Publications
VAR_005765
Natural varianti175 – 1751Y → D in VHLD; type I. 1 Publication
VAR_005766
Natural varianti176 – 1761R → W in VHLD.
VAR_008104
Natural varianti177 – 1771R → RLRVKPE in VHLD; type I.
VAR_005767
Natural varianti178 – 1781L → P in VHLD; type I-II; common mutation. 1 Publication
VAR_005768
Natural varianti178 – 1781L → Q in VHLD; type II.
Corresponds to variant rs5030822 [ dbSNP | Ensembl ].
VAR_005769
Natural varianti180 – 1801I → V in VHLD; type I. 1 Publication
VAR_005770
Natural varianti184 – 1841L → P in VHLD; type I. 2 Publications
VAR_005772
Natural varianti184 – 1841L → R in VHLD; type I. 1 Publication
VAR_005771
Natural varianti186 – 1861E → K in VHLD; type I. 2 Publications
VAR_005773
Natural varianti186 – 1861Missing in VHLD. 1 Publication
VAR_005774
Natural varianti188 – 1881L → P in VHLD; type I-II. 1 Publication
VAR_005775
Natural varianti188 – 1881L → Q in VHLD; type I. 1 Publication
VAR_005776
Natural varianti188 – 1881L → V in ECYT2, pheochromocytoma and VHLD; type IIA. 2 Publications
Corresponds to variant rs5030824 [ dbSNP | Ensembl ].
VAR_005777
Natural varianti198 – 1981L → R in ECY2 and VHLD; type II.
VAR_005778
Natural varianti200 – 2001R → W in ECYT2 and VHLD; type I. 4 Publications
Corresponds to variant rs28940298 [ dbSNP | Ensembl ].
VAR_005779
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.2 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti126 – 1261D → Y in ECYT2. 1 Publication
VAR_034994
Natural varianti130 – 1301V → L in ECYT2 and VHLD; type I. 3 Publications
VAR_005733
Natural varianti188 – 1881L → V in ECYT2, pheochromocytoma and VHLD; type IIA. 2 Publications
Corresponds to variant rs5030824 [ dbSNP | Ensembl ].
VAR_005777
Natural varianti191 – 1911H → D in ECYT2. 1 Publication
Corresponds to variant rs28940301 [ dbSNP | Ensembl ].
VAR_034999
Natural varianti192 – 1921P → S in ECYT2. 1 Publication
Corresponds to variant rs28940300 [ dbSNP | Ensembl ].
VAR_035000
Natural varianti200 – 2001R → W in ECYT2 and VHLD; type I. 4 Publications
Corresponds to variant rs28940298 [ dbSNP | Ensembl ].
VAR_005779
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.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti155 – 1551V → M in VHLD; with RCC.
VAR_008101
Natural varianti163 – 1631L → P in RCC; with paraneoplastic erythrocytosis; inhibits binding to HIF1AN. 2 Publications
Corresponds to variant rs28940297 [ dbSNP | Ensembl ].
VAR_034998
Natural varianti166 – 1661V → D in VHLD; with RCC.
VAR_008103

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi98 – 981Y → N: No interaction with HIF1A. No HIF1A degradation. 1 Publication

Keywords - Diseasei

Congenital erythrocytosis, Disease mutation, Tumor suppressor

Organism-specific databases

MIMi144700. phenotype.
171300. phenotype.
193300. phenotype.
263400. phenotype.
Orphaneti238557. Chuvash erythrocytosis.
892. Von Hippel-Lindau disease.
PharmGKBiPA37307.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 213213Von Hippel-Lindau disease tumor suppressorPRO_0000065809Add
BLAST

Proteomic databases

MaxQBiP40337.
PRIDEiP40337.

PTM databases

PhosphoSiteiP40337.

Expressioni

Tissue specificityi

Expressed in the adult and fetal brain and kidney.

Developmental stagei

At 4-10 weeks pc, strong expression in the developing central nervous system, kidneys, testis and lung. Differentially expressed within renal tubules.1 Publication

Gene expression databases

ArrayExpressiP40337.
BgeeiP40337.
CleanExiHS_VHL.
GenevestigatoriP40337.

Organism-specific databases

HPAiCAB005430.
HPA031631.
HPA031632.

Interactioni

Subunit structurei

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 CARD9.12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CUL2Q136179EBI-301246,EBI-456179
DGKIO759123EBI-301270,EBI-1765520
FN1P027512EBI-301246,EBI-1220319
FZR1Q9UM112EBI-3504450,EBI-724997
GLI1P081512EBI-301270,EBI-308084
GNB2L1P632449EBI-301246,EBI-296739
HIF1AQ1666517EBI-301246,EBI-447269
Hif1aQ612212EBI-301246,EBI-298954From a different organism.
PRKCZQ055133EBI-301246,EBI-295351
PRMT1Q998732EBI-301246,EBI-78738
RNF139Q8WU172EBI-301246,EBI-1551681
TGM2P2198010EBI-301246,EBI-727668

Protein-protein interaction databases

BioGridi113269. 280 interactions.
DIPiDIP-32585N.
IntActiP40337. 36 interactions.
MINTiMINT-133223.
STRINGi9606.ENSP00000256474.

Structurei

Secondary structure

1
213
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi71 – 788
Beta strandi80 – 823
Beta strandi84 – 896
Beta strandi91 – 933
Beta strandi95 – 973
Beta strandi105 – 1128
Beta strandi116 – 1216
Turni122 – 1243
Beta strandi127 – 1304
Beta strandi142 – 1443
Beta strandi147 – 1526
Helixi158 – 16912
Helixi172 – 1776
Beta strandi178 – 1803
Helixi183 – 1897
Helixi194 – 20613

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
DisProtiDP00287.
ProteinModelPortaliP40337.
SMRiP40337. Positions 60-207.

Miscellaneous databases

EvolutionaryTraceiP40337.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati14 – 1851
Repeati19 – 2352
Repeati24 – 2853
Repeati29 – 3354
Repeati34 – 3855
Repeati39 – 4356
Repeati44 – 4857
Repeati49 – 5358

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni14 – 53408 X 5 AA tandem repeats of G-[PAVG]-E-E-[DAYSLE]Add
BLAST
Regioni100 – 15556Involved in binding to CCT complexAdd
BLAST
Regioni157 – 16610Interaction with Elongin BC complex

Domaini

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG327868.
HOGENOMiHOG000030904.
HOVERGENiHBG044781.
InParanoidiP40337.
KOiK03871.
OMAiNTREPSQ.
OrthoDBiEOG7VMP7B.
PhylomeDBiP40337.
TreeFamiTF318985.

Family and domain databases

Gene3Di1.10.750.10. 1 hit.
2.60.40.780. 1 hit.
InterProiIPR002714. Tumour_suppress_VHL.
IPR024048. VHL_alpha_dom.
IPR024053. VHL_beta_dom.
IPR022772. VHL_tumour_suppress_b/a_dom.
[Graphical view]
PANTHERiPTHR15160:SF0. PTHR15160:SF0. 1 hit.
PfamiPF01847. VHL. 1 hit.
[Graphical view]
SUPFAMiSSF49468. SSF49468. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing and alternative initiation. Align

Isoform 1 (identifier: P40337-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MPRRAENWDE AEVGAEEAGV EEYGPEEDGG EESGAEESGP EESGPEELGA    50
EEEMEAGRPR PVLRSVNSRE PSQVIFCNRS PRVVLPVWLN FDGEPQPYPT 100
LPPGTGRRIH SYRGHLWLFR DAGTHDGLLV NQTELFVPSL NVDGQPIFAN 150
ITLPVYTLKE RCLQVVRSLV KPENYRRLDI VRSLYEDLED HPNVQKDLER 200
LTQERIAHQR MGD 213

Note: Major isoform.

Length:213
Mass (Da):24,153
Last modified:December 15, 1998 - v2
Checksum:iBA5D6765FBC16EA7
GO
Isoform 2 (identifier: P40337-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     114-154: Missing.

Show »
Length:172
Mass (Da):19,654
Checksum:i46E2C22E8C98393D
GO
Isoform 3 (identifier: P40337-3) [UniParc]FASTAAdd to Basket

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.

Show »
Length:160
Mass (Da):18,532
Checksum:i2644C3B8C3A87D64
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti25 – 251P → L in pheochromocytoma. 3 Publications
Corresponds to variant rs35460768 [ dbSNP | Ensembl ].
VAR_034562
Natural varianti38 – 381S → P in VHLD; type II. 1 Publication
VAR_005670
Natural varianti52 – 521E → K in VHLD; type I. 1 Publication
VAR_005671
Natural varianti63 – 631L → P in pheochromocytoma. 1 Publication
VAR_034987
Natural varianti64 – 641R → P in pheochromocytoma. 1 Publication
VAR_034988
Natural varianti65 – 651S → A in pheochromocytoma. 1 Publication
VAR_034989
Natural varianti65 – 651S → L in VHLD; type I. 2 Publications
VAR_005672
Natural varianti65 – 651S → W in VHLD; type I. 2 Publications
VAR_005673
Natural varianti66 – 738Missing in VHLD; type I.
VAR_005674
Natural varianti68 – 681S → W in pheochromocytoma and VHLD; type II. 2 Publications
VAR_005675
Natural varianti70 – 701E → K in VHLD; type I. 1 Publication
VAR_005676
Natural varianti74 – 741V → G in VHLD; type I-II. 1 Publication
Corresponds to variant rs5030803 [ dbSNP | Ensembl ].
VAR_005677
Natural varianti75 – 751Missing in VHLD. 1 Publication
VAR_034990
Natural varianti76 – 761F → I in VHLD; type I. 1 Publication
VAR_005679
Natural varianti76 – 761F → L in VHLD; type I. 1 Publication
VAR_005680
Natural varianti76 – 761F → S in VHLD; type I. 1 Publication
VAR_005681
Natural varianti76 – 761Missing in VHLD; type I; common mutation. 1 Publication
VAR_005678
Natural varianti78 – 781N → H in VHLD; type I. 1 Publication
VAR_005682
Natural varianti78 – 781N → S in VHLD; type I; common mutation. 1 Publication
Corresponds to variant rs5030804 [ dbSNP | Ensembl ].
VAR_005683
Natural varianti78 – 781N → T in VHLD; type I. 1 Publication
VAR_005684
Natural varianti79 – 791R → P in VHLD.
VAR_005685
Natural varianti80 – 801S → I in VHLD; type I. 1 Publication
VAR_005686
Natural varianti80 – 801S → N in pheochromocytoma and VHLD; type I. 3 Publications
Corresponds to variant rs5030805 [ dbSNP | Ensembl ].
VAR_005688
Natural varianti80 – 801S → R in VHLD; type I. 2 Publications
VAR_005687
Natural varianti81 – 811P → S in VHLD; type I. 2 Publications
Corresponds to variant rs5030806 [ dbSNP | Ensembl ].
VAR_005689
Natural varianti82 – 843Missing in VHLD.
VAR_005691
Natural varianti82 – 821R → P in VHLD; type I.
VAR_005690
Natural varianti84 – 841V → L in VHLD; type II and type 2C. 2 Publications
Corresponds to variant rs5030827 [ dbSNP | Ensembl ].
VAR_005692
Natural varianti86 – 861P → A in VHLD; type I. 1 Publication
VAR_005693
Natural varianti86 – 861P → H in VHLD.
VAR_008097
Natural varianti86 – 861P → L in VHLD; type I. 1 Publication
VAR_005694
Natural varianti86 – 861P → R in VHLD; type I. 1 Publication
VAR_005695
Natural varianti86 – 861P → S in VHLD. 2 Publications
VAR_005696
Natural varianti88 – 881W → R in VHLD; type I. 2 Publications
VAR_005697
Natural varianti88 – 881W → S in VHLD; type I. 2 Publications
VAR_005698
Natural varianti89 – 891L → H in lung cancer.
VAR_005699
Natural varianti89 – 891L → P in VHLD; type I. 1 Publication
Corresponds to variant rs5030807 [ dbSNP | Ensembl ].
VAR_005700
Natural varianti91 – 911F → L in cerebellar hemangioblastoma. 1 Publication
VAR_005701
Natural varianti92 – 976Missing in VHLD; type I.
VAR_005702
Natural varianti93 – 931G → C in pheochromocytoma and VHLD; type II. 2 Publications
Corresponds to variant rs5030808 [ dbSNP | Ensembl ].
VAR_005703
Natural varianti93 – 931G → D in VHLD.
VAR_005704
Natural varianti93 – 931G → S in pheochromocytoma and VHLD; type II. 1 Publication
Corresponds to variant rs5030808 [ dbSNP | Ensembl ].
VAR_005705
Natural varianti96 – 961Q → P in VHLD; type I. 1 Publication
VAR_005706
Natural varianti98 – 981Y → H in pheochromocytoma and VHLD; type II. 1 Publication
Corresponds to variant rs5030809 [ dbSNP | Ensembl ].
VAR_005707
Natural varianti101 – 1011L → G in VHLD; type I; requires 2 nucleotide substitutions. 1 Publication
VAR_005708
Natural varianti101 – 1011L → R in VHLD; type I. 1 Publication
VAR_005709
Natural varianti104 – 1041G → A in cerebellar hemangioblastoma. 1 Publication
VAR_005710
Natural varianti105 – 1051T → P in VHLD; type I. 1 Publication
VAR_005711
Natural varianti106 – 1061G → D in lung cancer.
VAR_005712
Natural varianti107 – 1071R → G in pheochromocytoma. 1 Publication
VAR_034991
Natural varianti107 – 1071R → P in VHLD; type I. 1 Publication
VAR_005713
Natural varianti110 – 1101H → Y.1 Publication
Corresponds to variant rs17855706 [ dbSNP | Ensembl ].
VAR_055087
Natural varianti111 – 1111S → C in VHLD; type II.
VAR_005714
Natural varianti111 – 1111S → N in VHLD; type I. 2 Publications
VAR_005715
Natural varianti111 – 1111S → R in VHLD; type I. 1 Publication
VAR_005716
Natural varianti112 – 1121Y → H in VHLD; type IIA.
VAR_005717
Natural varianti112 – 1121Y → N in VHLD. 1 Publication
VAR_034992
Natural varianti114 – 1141G → C in VHLD; type II. 1 Publication
VAR_005718
Natural varianti114 – 1141G → R in VHLD; type I-II.
VAR_005719
Natural varianti114 – 1141G → S in VHLD; type II. 1 Publication
VAR_005720
Natural varianti115 – 1151H → Q in VHLD; type II. 1 Publication
VAR_005723
Natural varianti115 – 1151H → R in VHLD; type II.
Corresponds to variant rs5030812 [ dbSNP | Ensembl ].
VAR_008098
Natural varianti115 – 1151H → Y in VHLD; type I. 1 Publication
Corresponds to variant rs5030811 [ dbSNP | Ensembl ].
VAR_005722
Natural varianti116 – 1161L → V in VHLD. 1 Publication
VAR_005724
Natural varianti117 – 1171W → C in VHLD; type I. 3 Publications
VAR_005725
Natural varianti118 – 1181L → P in VHLD; type I. 2 Publications
Corresponds to variant rs5030830 [ dbSNP | Ensembl ].
VAR_005726
Natural varianti118 – 1181L → R in VHLD. 1 Publication
VAR_005727
Natural varianti119 – 1191F → L in pheochromocytoma and VHLD; type II. 1 Publication
VAR_005728
Natural varianti119 – 1191F → S in VHLD; type II. 1 Publication
VAR_005729
Natural varianti121 – 1211D → G in VHLD; type I. 1 Publication
Corresponds to variant rs5030832 [ dbSNP | Ensembl ].
VAR_005730
Natural varianti122 – 1221A → I in pheochromocytoma; requires 2 nucleotide substitutions. 1 Publication
VAR_034993
Natural varianti126 – 1261D → Y in ECYT2. 1 Publication