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P40337

- VHL_HUMAN

UniProt

P40337 - VHL_HUMAN

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
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    • History
      Entry version 173 (01 Oct 2014)
      Sequence version 2 (15 Dec 1998)
      Previous versions | rss
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    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 ligase activity Source: ParkinsonsUK-UCL
    5. 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

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

    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

    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.3 Publications
    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).18 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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. 3 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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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 CARD9.16 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CUL2Q136179EBI-301246,EBI-456179
    DGKIO759123EBI-301270,EBI-1765520
    FN1P027512EBI-301246,EBI-1220319
    FZR1Q9UM112EBI-301270,EBI-724997
    GLI1P081512EBI-3504450,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. 37 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.
    ModBaseiSearch...
    MobiDBiSearch...

    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 – 1161